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  • 1.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Domellof, Magnus
    Andersson, Dan
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Effect of Delayed vs Early Umbilical Cord Clamping on Iron Status and Neurodevelopment at Age 12 Months A Randomized Clinical Trial2014In: JAMA PEDIATR, ISSN 2168-6203, Vol. 168, no 6, p. 547-554Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Prevention of iron deficiency in infancy may promote neurodevelopment. Delayed cord clamping (DCC) can prevent iron deficiency during the first 6 months of life. However, no data are available on long-term effects on infant outcomes in relation to time for umbilical cord clamping. OBJECTIVE To investigate effects of DCC, as compared with early cord clamping (ECC), on infant iron status and neurodevelopment at age 12 months in a European setting. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 382 full-term infants born after a low-risk pregnancy at a Swedish county hospital. Follow-up at 12 months included evaluation of iron status (ferritin level, transferrin saturation, transferrin receptor level, reticulocyte hemoglobin level, and mean cell volume) and parental assessment of neurodevelopment by the Ages and Stages Questionnaire, second edition (ASQ). INTERVENTIONS Infants were randomized to DCC (>= 180 seconds after delivery) or ECC (<= 10 seconds after delivery). MAIN OUTCOMES AND MEASURES The main outcome was iron status at age 12 months; the secondary outcome was ASQ score. RESULTS In total, 347 of 382 infants (90.8%) were assessed. The DCC and ECC groups did not differ in iron status (mean ferritin level, 35.4 vs 33.6 ng/mL, respectively; P =.40) or neurodevelopment (mean ASQ total score, 229.6 vs 233.1, respectively; P =.42) at age 12 months. Predictors of ferritin levels were infant sex and ferritin in umbilical cord blood. Predictors of ASQ score were infant sex and breastfeeding within 1 hour after birth. For both outcomes, being a boy was associated with lower results. Interaction analysis showed that DCC was associated with an ASQ score 5 points higher among boys (mean [SD] score, 229 [43] for DCC vs 224 [39] for ECC) but 12 points lower among girls (mean [SD] score, 230 [39] for DCC vs 242 [36] for ECC), out of a maximum of 300 points (P =.04 for the interaction term). CONCLUSIONS AND RELEVANCE Delayed cord clamping did not affect iron status or neurodevelopment at age 12 months in a selected population of healthy term-born infants. However, it may not be possible to demonstrate minor effects on neurodevelopment with the size of the study population and the chosen method for assessment. The current data indicate that sex may influence the effects on infant development after DCC in different directions. The magnitude and biological reason for this finding remain to be investigated.

  • 2.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Domellöf, Magnus
    Andersson, Dan
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Effects of delayed cord clamping on neurodevelopment and infection at four months of age: a randomised trial2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 5, p. 525-531Article in journal (Refereed)
    Abstract [en]

    AIM:

    To investigate the effect that delayed and early umbilical cord clamping have on neurodevelopment, immunoglobulin G (IgG) and symptoms of infection during the first 4 months of life.

    METHODS:

    Full-term infants (n = 382) were randomised to delayed (≥180 sec) or early cord clamping (≤10 sec). The Ages and Stages Questionnaire (ASQ) was used to assess neurodevelopment at 4 months. Immunoglobulin G was measured at birth, 2-3 days and 4 months. Parents recorded any symptoms indicating infection during the first 4 months of life.

    RESULTS:

    The total scores from the ASQ did not differ between groups. However, the delayed cord clamping (DCC) group had a higher mean (SD) score in the problem-solving domain [55.3 (7.2) vs. 53.5 (8.2), p = 0.03] at 4 months and a lower mean (SD) score in the personal-social domain [49.5 (9.3) vs. 51.8 (8.1), p = 0.01]. The IgG level was higher in the DCC group at 2-3 days (11.7 vs. 11.0 g/L, p = 0.004), but did not differ between the groups at 4 months. Symptoms of infection were comparable between the groups.

    CONCLUSION:

    Delayed cord clamping did not affect overall neurodevelopment or symptoms of infection up to 4 months of age, but may have an impact on specific neurodevelopmental domains.

  • 3.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Andersson, Dan
    Clausen, Jesper
    Domellöf, Magnus
    Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial2013In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 5, p. 567-574Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate the effect of delayed cord clamping (DCC) compared with early cord clamping (ECC) on maternal postpartum hemorrhage (PPH) and umbilical cord blood gas sampling.

    Design

    Secondary analysis of a parallel-group, single-center, randomized controlled trial.

    Setting

    Swedish county hospital.

    Population

    382 term deliveries after a low-risk pregnancy.

    Methods

    Deliveries were randomized to DCC (≥180 seconds, n = 193) or ECC (≤10 seconds, n = 189). Maternal blood loss was estimated by the midwife. Samples for blood gas analysis were taken from one umbilical artery and the umbilical vein, from the pulsating unclamped cord in the DCC group and from the double-clamped cord in the ECC group. Samples were classified as valid when the arterial-venous difference was -0.02 or less for pH and 0.5 kPa or more for pCO2.

    Main outcome measures

    PPH and proportion of valid blood gas samples.

    Results

    The differences between the DCC and ECC groups with regard to PPH (1.2%, p = 0.8) and severe PPH (-2.7%, p = 0.3) were small and non-significant. The proportion of valid blood gas samples was similar between the DCC (67%, n = 130) and ECC (74%, n = 139) groups, with 6% (95% confidence interval: -4%-16%, p = 0.2) fewer valid samples after DCC.

    Conclusions

    Delayed cord clamping, compared with early, did not have a significant effect on maternal postpartum hemorrhage or on the proportion of valid blood gas samples. We conclude that delayed cord clamping is a feasible method from an obstetric perspective.

  • 4.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Andersson, Dan
    Domellöf, Magnus
    Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial2011In: The BMJ, E-ISSN 1756-1833, Vol. 343, p. d7157-Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on infant iron status at 4 months of age in a European setting.

    Design: Randomised controlled trial.

    Setting: Swedish county hospital.

    Participants: 400 full term infants born after a low risk pregnancy.

    Intervention: Infants were randomised to delayed umbilical cord clamping (>= 180 seconds after delivery) or early clamping (<= 10 seconds after delivery).

    Main outcome measures: Haemoglobin and iron status at 4 months of age with the power estimate based on serum ferritin levels. Secondary outcomes included neonatal anaemia, early respiratory symptoms, polycythaemia, and need for phototherapy.

    Results: At 4 months of age, infants showed no significant differences in haemoglobin concentration between the groups, but infants subjected to delayed cord clamping had 45% (95% confidence interval 23% to 71%) higher mean ferritin concentration (117 mu g/L v 81 mu g/L, P<0.001) and a lower prevalence of iron deficiency (1 (0.6%) v 10 (5.7%), P=0.01, relative risk reduction 0.90; number needed to treat=20 (17 to 67)). As for secondary outcomes, the delayed cord clamping group had lower prevalence of neonatal anaemia at 2 days of age (2 (1.2%) v 10 (6.3%), P=0.02, relative risk reduction 0.80, number needed to treat 20 (15 to 111)). There were no significant differences between groups in postnatal respiratory symptoms, polycythaemia, or hyperbilirubinaemia requiring phototherapy.

    Conclusions: Delayed cord clamping, compared with early clamping, resulted in improved iron status and reduced prevalence of iron deficiency at 4 months of age, and reduced prevalence of neonatal anaemia, without demonstrable adverse effects. As iron deficiency in infants even without anaemia has been associated with impaired development, delayed cord clamping seems to benefit full term infants even in regions with a relatively low prevalence of iron deficiency anaemia.

  • 5.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH). Department of Research and Development, Region Halland, Sweden.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Domellöf, Magnus
    Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
    Elective caesarean: does delay in cord clamping for 30 s ensure sufficient iron stores at 4 months of age? A historical cohort control study2016In: BMJ Open, E-ISSN 2044-6055, Vol. 6, no 11, article id e012995Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare iron stores in infants born after elective caesarean section (CS) and a 30 s delay of umbilical cord clamping with those born vaginally after early (≤10 s) or delayed (≥180 s) cord clamping.

    DESIGN: Prospective observational study with historical control.

    SETTING: Swedish county hospital.

    POPULATION: 64 infants born after elective CS were compared with a historical control of 166 early clamped and 168 delayed clamped after vaginal birth.

    METHODS: Blood and iron status were measured in blood samples collected at birth, 48-96 hours after birth, 4 and 12 months of age.

    PRIMARY AND SECONDARY OUTCOME MEASURES: Ferritin at 4 months of age was the primary outcome, second outcome measures were other indicators of iron status, and haemoglobin, at 4 and 12 months of age, as well as respiratory distress at 1 and 6 hours after birth.

    RESULTS: At 4 months infants born by elective CS had better iron status than those born vaginally subjected to early cord clamping, shown by higher adjusted mean difference of ferritin concentration (39 µg/L (95% CI 10 to 60)) and mean cell volume (1.8 fL (95% CI 0.6 to 3.0)); and lower levels of transferrin receptors (-0.39 mg/L (95% CI -0.69 to -0.08)). No differences were seen between infants born after elective CS and delayed clamped vaginally born infants at 4 months. No differences were found between groups at 12 months of age.

    CONCLUSIONS: Waiting to clamp the umbilical cord for 30 s after elective CS results in higher iron stores at 4 months of age compared with early cord clamping after vaginal birth, and seems to ensure iron status comparable with those achieved after 180 s delayed cord clamping after vaginal birth.

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  • 6.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lindquist, Barbro
    Hosp Halland, Habilitat Ctr, Halmstad, Sweden..
    Lindgren, Magnus
    Lund Univ, Dept Psychol, Lund, Sweden..
    Stjernqvist, Karin
    Lund Univ, Dept Psychol, Lund, Sweden..
    Domellof, Magnus
    Umea Univ, Dept Clin Sci, Pediat Unit, Umea, Sweden..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Effect of Delayed Cord Clamping on Neurodevelopment at 4 Years of Age A Randomized Clinical Trial2015In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 169, no 7, p. 631-638Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Prevention of iron deficiency in infancy may promote neurodevelopment. Delayuci umbilical cord clamping (CC) prevents iron deficiency at 4 to 6 months of age, but long-term effects after 12 months of age have not been reported. OBJECTIVE To investigate the effects of delayed CC compared with early CC on neurodevelopment at 4 years of age. DESIGN, SETTING, AND PARTICIPANTS Follow-up of a randomized clinical trial conducted from April 16, 2008, through May 21, 2010, at a Swedish county hospital. Children who were included in the original study (n = 382) as full-term infants born after a low-risk pregnancy were invited to return for follow-up at 4 years of age. Wechsler Preschool and Primary Scale of Intelligence (WPPSI-111) and Movement Assessment Battery for Children (Movement ABC) scores (collected between April 18, 2012, and July 5, 2013) were assessed by a blinded psychologist. Between April 11, 2012, and August 13, 2013, parents recorded their child's development using the Ages and Stages Questionnaire, Third Edition (ASQ) and behavior using the Strengths and Difficulties Questionnaire. All data were analyzed by intention to treat. INTERVENTIONS Randomization to delayed CC (>= 180 seconds after delivery) or early CC (<= 10 seconds after delivery). MAIN OUTCOMES AND MEASURES The main outcome was full-scale IQ as assessed by the were development as assessed by the scales from the WPPSI-III and Movement ABC, development as recorded using the ASQ, and behavior using the Strengths and Difficulties Questionnaire. RESULTS We assessed 263 children (68.8%). No differences were found in WPPSI-III scores between groups. Delayed CC improved the adjusted mean differences (AMDs) in the ASQ personal-social (AMD, 2.8; 95% Cl, 0.8-4.7) and fine-motor (AMD, 2.1; 95% Cl, 0.2-4.0) domains and the Strengths and Difficulties Questionnaire prosocial subscale (AMD, 0.5; 95% Cl, >0.0-0.9). Fewer children in the delayed-CC group had results below the cutoff in the ASQ fine-motor domain (11.0% vs 3.7%; P =.02) and the Movement ABC bicycle-trail task (12.9% vs 3.8%; P =.02). Boys who received delayed CC had significantly higher AMDs in the WPPSI-III processing-speed quotient (AMD, 4.2; 95% Cl, 0.8-7.6; P =.02), Movement ABC bicycle-trail task (AMD, 0.8; 95% Cl, 0.1-1.5; P =.03), and fine-motor (AMD, 4.7; 95% Cl, 1.0-8.4; P =.01) and personal-social (AMD, 4.9; 95% Cl, 1.6-8.3; P =.004) domains of the ASQ. CONCLUSIONS AND RELEVANCE Delayed CC compared with early CC improved scores in the fine-motor at 4 years of age, especially in boys, indicating that optimizing the time to CC may affect neurodevelopment in a low-risk population of children born in a high-income country.

  • 7.
    Askelöf, Ulrica
    et al.
    Karolinska Inst, Div Obstet & Gynecol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Sahlgrens Univ Hosp, Swedish Natl Umbil Cord Blood Bank, Gothenburg, Sweden..
    Andersson, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Domellöf, Magnus
    Umea Univ, Dept Clin Sci, Unit Pediat, Umea, Sweden..
    Fasth, Anders
    Sahlgrens Univ Hosp, Swedish Natl Umbil Cord Blood Bank, Gothenburg, Sweden.;Univ Gothenburg, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden..
    Hallberg, Boubou
    Karolinska Inst, CLINTEC, Dept Neonatol, Stockholm, Sweden.;Univ Hosp, Stockholm, Sweden..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Pettersson, Karin
    Karolinska Inst, Div Obstet & Gynecol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Sahlgrens Univ Hosp, Swedish Natl Umbil Cord Blood Bank, Gothenburg, Sweden..
    Westgren, Magnus
    Karolinska Inst, Div Obstet & Gynecol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Sahlgrens Univ Hosp, Swedish Natl Umbil Cord Blood Bank, Gothenburg, Sweden..
    Wiklund, Ingela E.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Gotherstrom, Cecilia
    Karolinska Inst, Div Obstet & Gynecol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Sahlgrens Univ Hosp, Swedish Natl Umbil Cord Blood Bank, Gothenburg, Sweden.;Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden..
    Wait a minute?: An observational cohort study comparing iron stores in healthy Swedish infants at 4 months of age after 10-, 60-and 180-second umbilical cord clamping2017In: BMJ Open, E-ISSN 2044-6055, Vol. 7, no 12, article id e017215Article in journal (Refereed)
    Abstract [en]

    Background and objective: Umbilical cord blood (UCB) is a valuable stem cell source used for transplantation. Immediate umbilical cord (UC) clamping is widely practised, but delayed UC clamping is increasingly advocated to reduce possible infant anaemia. The aim of this study was to investigate an intermediate UC clamping time point and to evaluate iron status at the age of 4 months in infants who had the UC clamped after 60 s and compare the results with immediate and late UC clamping.

    Design: Prospective observational study with two historical controls.

    Setting: A university hospital in Stockholm, Sweden, and a county hospital in Halland, Sweden.

    Methods: Iron status was assessed at 4 months in 200 prospectively recruited term infants whose UC was clamped 60 s after birth. The newborn baby was held below the uterine level for the first 30 s before placing the infant on the mother’s abdomen for additional 30 s. The results were compared with data from a previously conducted randomised controlled trial including infants subjected to UC clamping at ≤10 s (n=200) or ≥180 s (n=200) after delivery.

    Results: After adjustment for age differences at the time of follow-up, serum ferritin concentrations were 77, 103 and 114 µg/L in the 10, 60 and 180 s groups, respectively. The adjusted ferritin concentration was significantly higher in the 60 s group compared with the 10 s group (P=0.002), while the difference between the 60 and 180 s groups was not significant (P=0.29).

    Conclusion: In this study of healthy term infants, 60 s UC clamping with 30 s lowering of the baby below the uterine level resulted in higher serum ferritin concentrations at 4 months compared with 10 s UC clamping. The results suggest that delaying the UC clamping for 60 s reduces the risk for iron deficiency.

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  • 8.
    Austeng, Dordi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Blennow, Mats
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Fellman, Vineta
    Fritz, Thomas
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellström, Ann
    Holmgren, Per Ake
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Jakobsson, Peter
    Jeppsson, Annika
    Johansson, Kent
    Kallen, Karin
    Lagercrantz, Hugo
    Laurini, Ricardo
    Lindberg, Eva
    Lundqvist, Anita
    Marsal, Karel
    Nilstun, Tore
    Nordén Lindeberg, Solveig
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Norman, Mikael
    Olhager, Elisabeth
    Oestlund, Ingrid
    Serenius, Fredrik
    Simic, Marija
    Sjörs, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Stigson, Lennart
    Stjernqvist, Karin
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Tornqvist, Kristina
    Wennergren, Margareta
    Wallin, Agneta
    Westgren, Magnus
    Incidence of and risk factors for neonatal morbidity after active perinatal care: extremely preterm infants study in Sweden (EXPRESS)2010In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 99, no 7, p. 978-992Article in journal (Refereed)
    Abstract [en]

    Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.

  • 9.
    Bengtsson, Jörgen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Ederoth, P
    Ley, D
    Hansson, S
    Amer-Wåhlin, I
    Hellström-Westas, Lena
    Marsál, K
    Nordström, C-H
    Hammarlund-Udenaes, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    The influence of age on the distribution of morphine and morphine-3-glucuronide across the blood-brain barrier in sheep2009In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 157, no 6, p. 1085-1096Article in journal (Refereed)
    Abstract [en]

    Background and purpose

     The effect of age on the distribution of morphine and morphine-3-glucuronide (M3G) across the blood-brain barrier (BBB) was studied in a sheep model utilizing intracerebral microdialysis. The effect of neonatal asphyxia on brain drug distribution was also studied.

    Experimental approach

     Microdialysis probes were inserted into the cortex, striatum and blood of 11 lambs (127 gestation days) and six ewes. Morphine, 1 mg.kg(-1), was intravenously administered as a 10 min constant infusion. Microdialysis and blood samples were collected for up to 360 min and analysed using liquid chromatography-tandem mass spectrometry. The half-life, clearance, volume of distribution, unbound drug brain : blood distribution ratio (K(p,uu)) and unbound drug volume of distribution in brain (V(u,brain)) were estimated.

     Key results

     Morphine K(p,uu) was 1.19 and 1.89 for the sheep and premature lambs, respectively, indicating that active influx into the brain decreases with age. Induced asphyxia did not affect transport of morphine or M3G across the BBB. Morphine V(u,brain) measurements were higher in sheep than in premature lambs. The M3G K(p,uu) values were 0.27 and 0.17 in sheep and premature lambs, indicating a net efflux from the brain in both groups.

    Conclusions and implications

     The morphine K(p,uu) was above unity, indicating active transport into the brain; influx was significantly higher in premature lambs than in adult sheep. These results in sheep differ from those in humans, rats, mice and pigs where a net efflux of morphine from the brain is observed.

  • 10.
    Berg, Jenny
    et al.
    Swedish Agcy Hlth Technol Assessment & Assessment, Box 6183, SE-10233 Stockholm, Sweden..
    Kallen, Karin
    Lund Univ, Inst Clin Sci, Dept Obstet & Gynaecol, Unit Reprod Epidemiol,Tornblad Inst, Lund, Sweden..
    Andolf, Ellika
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Div Obstet & Gynaecol, Stockholm, Sweden..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ekéus, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Alvan, Jonatan
    Swedish Agcy Hlth Technol Assessment & Assessment, Box 6183, SE-10233 Stockholm, Sweden..
    Vitols, Sigurd
    Swedish Agcy Hlth Technol Assessment & Assessment, Box 6183, SE-10233 Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Economic Evaluation of Elective Cesarean Section on Maternal Request Compared With Planned Vaginal Birth-Application to Swedish Setting Using National Registry Data2023In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 26, no 5, p. 639-648Article in journal (Refereed)
    Abstract [en]

    Objectives: There is a lack of consensus around the definition of delivery by cesarean section (CS) on maternal request, and clinical practice varies across and within countries. Previous economic evaluations have focused on specific populations and selected complications. Our aim was to evaluate the cost-effectiveness of CS on maternal request compared with planned vaginal birth in a Swedish context, based on a systematic review of benefits and drawbacks and national registry data on costs.

    Methods: We used the results from a systematic literature review of somatic risks for long-and short-term complications for mother and child, in which certainty was rated low, moderate, or high using the Grading of Recommendations Assessment, Development and Evaluation. Swedish national registry data were used for healthcare costs of delivery and complications. Utilities for long-term complications were based on a focused literature review. We constructed a decision tree and conducted separate analyses for primi-and multiparous women. Costs and effects were discounted by 3% and the time horizon was varied between 1 and 20 years.

    Results: Planned vaginal birth leads to lower healthcare costs and somatic health gains compared with elective CS without medical indication over up to 20 years. Although there is uncertainty around, for example, quality-of-life effects, results remain stable across sensitivity analyses.

    Conclusions: CS on maternal request leads to increased hospitalization costs in a Swedish setting, taking into account short -and long-term consequences for both mother and child. Future research needs to study the psychological consequences related to different delivery methods, costs in outpatient care, and productivity losses.

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  • 11.
    Berggren, Sara
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Paediat, Vitaminvagen 21,Plan 2, S-41650 Gothenburg, Sweden.;Halland Hosp Halmstad, Dept Paediat, Halmstad, Sweden.;Hlth Ctr Halland, Hlth Ctr Hyltebruk, Halmstad, Sweden..
    Andersson, Ola
    Lund Univ, Dept Clin Sci Lund, Pediat Neonatol, Lund, Sweden..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Dahlgren, Jovanna
    Univ Gothenburg, Sahlgrenska Acad, Dept Paediat, Vitaminvagen 21,Plan 2, S-41650 Gothenburg, Sweden..
    Roswall, Josefine
    Univ Gothenburg, Sahlgrenska Acad, Dept Paediat, Vitaminvagen 21,Plan 2, S-41650 Gothenburg, Sweden.;Halland Hosp Halmstad, Dept Paediat, Halmstad, Sweden..
    Serum osteocalcin levels at 4 months of age were associated with neurodevelopment at 4 years of age in term-born children2022In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 111, no 2, p. 338-345Article in journal (Refereed)
    Abstract [en]

    Aim: The hormone osteocalcin influenced neurodevelopment and cognition in mice models; this human study explored potential associations between total serum levels in human infants and neurodevelopment at 4 years of age.

    Methods: The data were based on two Swedish birth cohorts from 2008 to 2009. We followed 158 healthy full-term vaginal births (51% girls) by measuring serum osteocalcin in cord blood and at 4, 12 and 36 months. The values were compared with neurodevelopment tests at 4 years of age.

    Results: There was an association between osteocalcin at 4 months and later full-scale intelligence quotient (IQ; r(2) 0.031, p < 0.05). Children with osteocalcin levels in the highest quartile scored 5.6 (95% confidence interval [1.3, 9.9]) points higher than those in the lowest quartile, with mean scores of 118.8 +/- 8.8 and 113.2 +/- 9.2 (p < 0.05). They also scored higher on gross motor skills (p < 0.05) and showed greater ability during the drawing trail test (p < 0.005). Cord levels of osteocalcin were negatively associated with processing speed and fine motor development at 4 years, but levels at 12 and 36 months were not associated with later neurodevelopment.

    Conclusion: Osteocalcin levels in infancy appeared to be associated with later IQ and motor development, but more research is needed.

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  • 12.
    Biskop, Emilia
    et al.
    Univ Hosp, Neonatal Intens Care Unit, Uppsala, Sweden.
    Paulsdotter, Therese
    Univ Hosp, Neonatal Intens Care Unit, Uppsala, Sweden.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research. Univ Hosp, Neonatal Intens Care Unit, Uppsala, Sweden.
    Ågren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research. Univ Hosp, Neonatal Intens Care Unit, Uppsala, Sweden.
    Thernström Blomqvist, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research. Univ Hosp, Neonatal Intens Care Unit, Uppsala, Sweden.
    Parental participation during therapeutic hypothermia for neonatal hypoxicischemic encephalopathy2019In: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 20, p. 77-80Article in journal (Refereed)
    Abstract [en]

    Objectives: To examine parental participation in the care of newborn infants receiving therapeutic hypothermia, and to explore the possible impact of in-born vs out-born status, and location of hospital accommodation. Study design: Retrospective, quantitative and descriptive design. Main outcome measures: Infants medical charts were reviewed for defined aspects of parental participation (infant holding, tube feeding, and diaper change), and related to their in-born vs out-born status, and whether the parents were accommodated in the NICU or elsewhere. All infants have been cared for at the University Hospital Neonatal Intensive Care Unit, serving as a regional referral center for hypothermia treatment. This study is a part of a population-based regional cohort of asphyxiated newborn infants (n = 112) that received therapeutic hypothermia in 2007-2015. Results: Parents engaged in holding (60/112, 54%) or tube feeding (59/112, 53%) their infant. Parents of inborn infants (24/112, 21%) were more likely to check the placement of the feeding tube (11/24, 46% vs 15/88, 17%; p < 0.01) and change diapers (9/24, 38% vs 14/88, 16%; p < 0.05) than parents of out-born infants (88/112, 79%). A similar pattern of more extensive involvement was observed for both mothers and fathers who stayed at the neonatal intensive care compared to those accommodated elsewhere (p < 0.05). Conclusions: Active parental participation is feasible at the NICU even during therapeutic hypothermia. Timely postnatal transfer of parents of out-born/transported infants, and the provision of on-site accommodation may influence the quality of parental involvement.

  • 13.
    Bolk, J.
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Kaul, Ylva Fredriksson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Stjernqvist, K.
    Lund Univ, Dept Psychol, Lund, Sweden..
    Padilla, N.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Serenius, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellgren, K.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Aden, U.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Visual-Motor Integration In Extremely Preterm Born Children In Sweden2016In: European Journal of Pediatrics, ISSN 0340-6199, E-ISSN 1432-1076, Vol. 175, no 11, p. 1530-1530Article in journal (Refereed)
  • 14.
    Bolk, Jenny
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Sachs Children & Youth Hosp, Stockholm, Sweden.
    Kaul, Ylva Fredriksson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Stjernqvist, Karin
    Lund Univ, Dept Psychol, Div Dev Psychol, Lund, Sweden.
    Padilla, Nelly
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Serenius, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research. Univ Umeå, Pediat, Inst Clin Sci, Umeå, Sweden.
    Hellgren, Kerstin
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Åden, Ulrika
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    National population-based cohort study found that visual-motor integration was commonly affected in extremely preterm born children at six-and-a-half years2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 5, p. 831-837Article in journal (Refereed)
    Abstract [en]

    Aim: This study aimed to explain the relationship between visual‐motor integration (VMI) abilities and extremely preterm (EPT) birth, by exploring the influence of perinatal variables, cognition, manual dexterity and ophthalmological outcomes.

    Methods: This was part of the population‐based national Extremely Preterm Infant Study in Sweden (EXPRESS) study. We studied 355 children, born at a gestational age of <27 weeks from April 2004 to March 2007, and 364 term‐born controls. At six‐and‐a‐half years of age, we assessed VMI, cognitive function, motor skills and vision. VMI impairment was classified as <−1 standard deviation (SD).

    Results: The mean (SD) VMI score was 87 (±12) in preterm children compared to 98 (±11) in controls (p < 0.001). VMI impairment was present in 55% of preterm infants and in 78% of children born at 22–23 weeks. Male sex and postnatal steroids showed a weak association with poorer visual‐motor performance, whereas low manual dexterity and cognitive function showed a stronger association.

    Conclusion: Poor VMI performance was common in this EXPRESS cohort of children born EPT. Its strong association to cognition and manual dexterity confirms that all of these factors need to be taken into account when evaluating risks in preterm born children.

  • 15.
    Bäcke, Pyrola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Univ Childrens Hosp, Neonatal Intens Care Unit, Uppsala, Sweden.;Uppsala Univ, Dept Womens & Childrens Hlth, S-75185 Uppsala, Sweden..
    Hjelte, Beatrice
    Univ Childrens Hosp, Neonatal Intens Care Unit, Uppsala, Sweden..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research. Univ Childrens Hosp, Neonatal Intens Care Unit, Uppsala, Sweden.;Uppsala Univ, Dept Womens & Childrens Hlth, S-75185 Uppsala, Sweden..
    Ågren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research. Univ Childrens Hosp, Neonatal Intens Care Unit, Uppsala, Sweden.;Uppsala Univ, Dept Womens & Childrens Hlth, S-75185 Uppsala, Sweden..
    Thernström Blomqvist, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research. Univ Childrens Hosp, Neonatal Intens Care Unit, Uppsala, Sweden.;Uppsala Univ, Dept Womens & Childrens Hlth, S-75185 Uppsala, Sweden..
    When all I wanted was to hold my baby-The experiences of parents of infants who received therapeutic hypothermia2021In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 110, no 2, p. 480-486Article in journal (Refereed)
    Abstract [en]

    Aim The knowledge is limited about how parents experience the time when their infant is receiving therapeutic hypothermia (TH) after severe perinatal asphyxia. The aim of this study was to explore parents' experience of closeness and involvement in their infant's care while in the neonatal intensive care unit (NICU) with their newborn undergoing TH. Methods Face-to-face, semi-structured interviews were conducted with parents (n = 11) whose infants (n = 8, aged 3-5 years at the time of the study) underwent TH at a level III Swedish NICU during 2013-2016. The interviews were analysed using qualitative content analysis. Results All the parents shared the trauma of being both physically and psychologically separated from their infant. They all described a need for information and emotional support, and reported that the NICU staff had influenced the extent to which they as parents had been able to be near and actively participate in the care. Parents described the wish to be closer to their infant and to be more actively involved in their infant's care. Conclusion Strategies to enable parent-infant closeness and active guidance from staff might help alleviate the emotional stress of parents and promote their participation during TH.

  • 16.
    Chalak, L.
    et al.
    Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Bonifacio, S.
    Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA..
    Tsuchida, T.
    George Washington Univ, Childrens Natl Hosp, Sch Med & Hlth Sci, Dept Neurol & Pediat,Div Neurophysiol Epilepsy &, 111 Michigan Ave NW,West Wing,4th Floor, Washington, DC 20010 USA..
    Chock, V
    Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA..
    El-Dib, M.
    Harvard Med Sch, Brigham & Womens Hosp, Dept Pediat Newborn Med, 75 Francis St,CWN 418, Boston, MA 02115 USA..
    Massaro, An N.
    George Washington Univ, Sch Med, Dept Pediat, Washington, DC USA.;Childrens Natl Hosp, Div Neonatol, Washington, DC USA..
    Garcia-Alix, A.
    Hosp St Joan Deu, Inst Recerca St Joan Deu, Barcelona, Spain.;Univ Barcelona, Barcelona, Spain.;NeNe Fdn, Madrid, Spain.;Passeig St Joan Deu 2, Barcelona 08950, Spain..
    Bedside and laboratory neuromonitoring in neonatal encephalopathy2021In: Seminars in Fetal & Neonatal Medicine, ISSN 1744-165X, E-ISSN 1878-0946, Vol. 26, no 5, article id 101273Article, review/survey (Refereed)
    Abstract [en]

    Several bedside and laboratory neuromonitoring tools are currently used in neonatal encephalopathy (NE) to assess 1) brain function [amplitude-integrated electroencephalogram (aEEG) and EEG], 2) cerebral oxygenation delivery and consumption [near-infrared spectroscopy (NIRS)] and 3) blood and cerebrospinal fluid biomarkers. The aim of the review is to provide the role of neuromonitoring in understanding the development of brain injury in these newborns and better predict their long-term outcome. Simultaneous use of these monitoring modalities may improve our ability to provide meaningful prognostic information regarding ongoing treatments. Evidence will be summarized in this review for each of these modalities, by describing (1) the methods, (2) the clinical evidence in context of NE both before and with hypothermia, and (3) the research and future directions.

  • 17.
    Challis, Pontus
    et al.
    Umeå Univ, Dept Clin Sci, Pediat, Umeå, Sweden.;Umeå Univ Klin Vetenskap, Pediat, S-90185 Umeå, Sweden..
    Kallen, Karin
    Lund Univ, Fac Med, Dept Clin Sci Obstet & Gynecol, Lund, Sweden..
    Bjorklund, Lars
    Lund Univ, Dept Clin Sci, Paediat, Lund, Sweden..
    Elfvin, Anders
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Pediat, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Pediat, Gothenburg, Sweden..
    Farooqi, Aijaz
    Umeå Univ, Dept Clin Sci, Pediat, Umeå, Sweden..
    Hakansson, Stellan
    Umeå Univ, Dept Clin Sci, Pediat, Umeå, Sweden..
    Ley, David
    Lund Univ, Dept Clin Sci, Paediat, Lund, Sweden..
    Norman, Mikael
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Pediat, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neonatal Med, Stockholm, Sweden..
    Normann, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Serenius, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research. Umeå Univ, Dept Clin Sci, Pediat, Umeå, Sweden..
    Savman, Karin
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Pediat, Gothenburg, Sweden..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Um-Bergstrom, Petra
    Karolinska Inst, Sodersjukhuset, Dept Pediat, Stockholm, Sweden.;Karolinska Inst, Sodersjukhuset, Clin Sci & Educ, Stockholm, Sweden..
    Aden, Ulrika
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Pediat, Stockholm, Sweden.;Linköping Univ, Dept Biomed & Clin Sci & Pediat, Linköping, Sweden..
    Abrahamsson, Thomas
    Linköping Univ, Dept Biomed & Clin Sci & Pediat, Linköping, Sweden.;Linköping Univ Hosp, Dept Pediat, Linköping, Sweden..
    Domellof, Magnus
    Umeå Univ, Dept Clin Sci, Pediat, Umeå, Sweden..
    Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004-2007 vs 2014-2016)2024In: Archives of Disease in Childhood: Fetal and Neonatal Edition, ISSN 1359-2998, E-ISSN 1468-2052, Vol. 109, no 1, p. 87-93Article in journal (Refereed)
    Abstract [en]

    Objective To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants.Design Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage >= II) were validated against hospital records.Patients All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden.Main outcome measures NEC incidence.Results The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047).Conclusions The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.

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  • 18.
    Dickmark, Malin
    et al.
    Uppsala Univ Hosp, Dept Obstet & Gynecol, Uppsala, Sweden..
    Ågren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Jonsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Risk factors for seizures in the vigorous term neonate: A population-based register study of singleton births in Sweden2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 2, article id e0264117Article in journal (Refereed)
    Abstract [en]

    Background Neonatal seizures have been associated with increased mortality and impaired neurodevelopment and, knowledge about risk factors may be useful for prevention. Clear associations have been established between labor-related risk factors and seizures in asphyxiated neonates. However, there is limited information about why some vigorous term-born infants experience seizures. Objectives Our aim was to assess antepartum and intrapartum risk factors for seizures in vigorous term-born neonates. Methods This was a national cohort study of singleton infants born at term in Sweden from 2009-2015. Vigorous was defined as an Apgar score of at least 7 at 5 and 10 minutes. Data on the mothers and infants were obtained from the Swedish Medical Birth Register and the Swedish Neonatal Quality Register. A diagnosis of neonatal seizures was the main outcome measure and the exposures were pregnancy and labor variables. Logistic regression analysis was used and the results are expressed as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results The incidence of neonatal seizures was 0.81/1,000 for 656 088 births. Seizures were strongly associated with obstetric emergencies (aOR 4.0, 95% CI 2.2-7.4), intrapartum fever and/or chorioamnionitis (aOR 3.4, 95% CI 2.1-5.3), and intrapartum fetal distress (aOR 3.0, 95% CI 2.4-3.7). Other associated intrapartum factors were: labor dystocia, occiput posterior position, operative vaginal delivery, and Cesarean delivery. Some maternal factors more than doubled the risk: a body mass of more than 40 (aOR 2.6, 95% CI 1.4-4.8), hypertensive disorders (aOR 2.3, 95% CI 1.7-3.1) and diabetes mellitus (aOR 2.6, 95% CI 1.7-4.1). Conclusion A number of intrapartum factors were associated with an increased risk of seizures in vigorous term-born neonates. Obstetric emergencies, intrapartum fever and/or chorioamnionitis and fetal distress were the strongest associated risks. The presence of such factors, despite a reassuring Apgar score could prompt close surveillance.

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  • 19.
    El-Dib, Mohamed
    et al.
    Harvard Med Sch, Dept Pediat Newborn Med, Brigham & Womens Hosp, Boston, MA 02115 USA..
    Abend, Nicholas S.
    Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.;Univ Penn, Philadelphia, PA 19104 USA..
    Austin, Topun
    Univ Cambridge, Dept Paediat, Cambridge, England..
    Boylan, Geraldine
    Univ Coll Cork, INFANT Res Ctr & Dept Paediat & Child Hlth, Cork, Ireland..
    Chock, Valerie
    Stanford Univ, Sch Med, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA..
    Cilio, M. Roberta
    Catholic Univ Louvain, Dept Pediat, Div Pediat Neurol, Clin Univ St Luc, Brussels, Belgium..
    Greisen, Gorm
    Univ Copenhagen, Copenhagen Univ Hosp, Rigshosp, Dept Neonatol, Copenhagen, Denmark.;Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research. Uppsala Univ Hosp, Div Neonatol, Uppsala, Sweden..
    Lemmers, Petra
    Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Neonatol, Utrecht, Netherlands..
    Pellicer, Adelina
    La Paz Univ Hosp, Dept Neonatol, Madrid, Spain.;IdiPAZ, Neonatol Grp, Madrid, Spain..
    Pressler, Ronit M.
    Great Ormond St Hosp Sick Children, Dept Clin Neurophysiol, London, England.;UCL Great Ormond St Inst Child Hlth, Clin Neurosci, London, England..
    Sansevere, Arnold
    George Washington Univ, Dept Neurol & Pediat, Sch Med & Hlth Sci, Washington, DC USA.;Childrens Natl Hosp, Div Neurophysiol Epilepsy & Crit Care, Washington, DC USA..
    Szakmar, Eniko
    Semmelweis Univ, Dept Pediat 1, Div Neonatol, Budapest, Hungary..
    Tsuchida, Tammy
    George Washington Univ, Dept Neurol & Pediat, Sch Med & Hlth Sci, Washington, DC USA.;Childrens Natl Hosp, Div Neurophysiol Epilepsy & Crit Care, Washington, DC USA..
    Vanhatalo, Sampsa
    Helsinki Univ Hosp, Childrens Hosp, Dept Clin Neurophysiol, BABA Ctr,Neurosci Ctr HILIFE, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland..
    Wusthoff, Courtney J.
    Stanford Univ, Div Child Neurol, Palo Alto, CA 94304 USA..
    Neuromonitoring in neonatal critical care part II: extremely premature infants and critically ill neonates2023In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 94, no 1, p. 55-63Article, review/survey (Refereed)
    Abstract [en]

    Neonatal intensive care has expanded from cardiorespiratory care to a holistic approach emphasizing brain health. To best understand and monitor brain function and physiology in the neonatal intensive care unit (NICU), the most commonly used tools are amplitude-integrated EEG, full multichannel continuous EEG, and near-infrared spectroscopy. Each of these modalities has unique characteristics and functions. While some of these tools have been the subject of expert consensus statements or guidelines, there is no overarching agreement on the optimal approach to neuromonitoring in the NICU. This work reviews current evidence to assist decision making for the best utilization of these neuromonitoring tools to promote neuroprotective care in extremely premature infants and in critically ill neonates. Neuromonitoring approaches in neonatal encephalopathy and neonates with possible seizures are discussed separately in the companion paper. Impact For extremely premature infants, NIRS monitoring has a potential role in individualized brain-oriented care, and selective use of aEEG and cEEG can assist in seizure detection and prognostication. For critically ill neonates, NIRS can monitor cerebral perfusion, oxygen delivery, and extraction associated with disease processes as well as respiratory and hypodynamic management. Selective use of aEEG and cEEG is important in those with a high risk of seizures and brain injury. Continuous multimodal monitoring as well as monitoring of sleep, sleep-wake cycling, and autonomic nervous system have a promising role in neonatal neurocritical care.

  • 20.
    El-Dib, Mohamed
    et al.
    Harvard Med Sch, Brigham & Womens Hosp, Dept Pediat Newborn Med, Boston, MA 02115 USA.;Stanford Univ, Neonatol, Pediat, Sch Med, Palo Alto, CA USA..
    Abend, Nicholas S. J.
    Univ Penn, Childrens Hosp Philadelphia, Dept Neurol & Pediat, Philadelphia, PA USA..
    Austin, Topun
    Univ Cambridge, Dept Paediat, Cambridge, England..
    Boylan, Geraldine
    Univ Coll Cork, INFANT Res Ctr & Dept Paediat & Child Hlth, Cork, Ireland..
    Chock, Valerie
    Stanford Univ, Div Neonatal & Dev Med, Sch Med, Palo Alto, CA USA..
    Cilio, M. Roberta
    Department of Pediatrics, Division of Pediatric Neurology, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
    Greisen, Gorm
    Department of Neonatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research. Uppsala Univ Hosp, Div Neonatol, Uppsala, Sweden..
    Lemmers, Petra
    Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Neonatol, Utrecht, Netherlands..
    Pellicer, Adelina
    Department of Neonatology, La Paz University Hospital, Madrid, Spain;Neonatology Group, IdiPAZ, Madrid, Spain.
    Pressler, Ronit
    Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Trust,London, UK;Clinical Neuroscience, UCL- Great Ormond Street Institute of Child Health, London, UK.
    Sansevere, Arnold
    Department of Neurology and Pediatrics, George Washington University School of Medicine and Health Sciences, Washinton DC, USA;Children’s National Hospital Division of Neurophysiology, Epilepsy and Critical Care, Washington, DC, USA.
    Tsuchida, Tammy
    Department of Neurology and Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA;Children’s National Hospital Division of Neurophysiology, Epilepsy and Critical Care, Washington, DC, USA.
    Vanhatalo, Sampsa
    Department of Clinical Neurophysiology, Children’s Hospital, BABA Center, Neuroscience Center/HILIFE, Helsinki University Hospital, Helsinki, Finland;University of Helsinki, Helsinki, Finland.
    Wusthoff, Courtney J.
    Stanford Univ, Div Child Neurol, Palo Alto, CA USA..
    Neuromonitoring in neonatal critical care part I: neonatal encephalopathy and neonates with possible seizures2023In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 94, no 1, p. 64-73Article, review/survey (Refereed)
    Abstract [en]

    The blooming of neonatal neurocritical care over the last decade reflects substantial advances in neuromonitoring and neuroprotection. The most commonly used brain monitoring tools in the neonatal intensive care unit (NICU) are amplitude integrated EEG (aEEG), full multichannel continuous EEG (cEEG), and near-infrared spectroscopy (NIRS). While some published guidelines address individual tools, there is no consensus on consistent, efficient, and beneficial use of these modalities in common NICU scenarios. This work reviews current evidence to assist decision making for best utilization of neuromonitoring modalities in neonates with encephalopathy or with possible seizures. Neuromonitoring approaches in extremely premature and critically ill neonates are discussed separately in the companion paper. Impact:center dot Neuromonitoring techniques hold promise for improving neonatal care. center dot For neonatal encephalopathy, aEEG can assist in screening for eligibility for therapeutic hypothermia, though should not be used to exclude otherwise eligible neonates. Continuous cEEG, aEEG and NIRS through rewarming can assist in prognostication. center dot For neonates with possible seizures, cEEG is the gold standard for detection and diagnosis. If not available, aEEG as a screening tool is superior to clinical assessment alone. The use of seizure detection algorithms can help with timely seizures detection at the bedside.

  • 21.
    Ericson, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Eriksson, Mats
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hagberg, Lars
    Hoddinott, Pat
    Flacking, Renée
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    The effectiveness of proactive telephone support provided to breastfeeding mothers of preterm infants: study protocol for a randomized controlled trial2013In: BMC Pediatrics, E-ISSN 1471-2431, Vol. 13, p. 73-Article in journal (Refereed)
    Abstract [en]

    Background: Although breast milk has numerous benefits for infants' development, with greater effects in those born preterm (at < 37 gestational weeks), mothers of preterm infants have shorter breastfeeding duration than mothers of term infants. One of the explanations proposed is the difficulties in the transition from a Neonatal Intensive Care Unit (NICU) to the home environment. A person-centred proactive telephone support intervention after discharge from NICU is expected to promote mothers' sense of trust in their own capacity and thereby facilitate breastfeeding. Methods/design: A multicentre randomized controlled trial has been designed to evaluate the effectiveness and cost-effectiveness of person-centred proactive telephone support on breastfeeding outcomes for mothers of preterm infants. Participating mothers will be randomized to either an intervention group or control group. In the intervention group person-centred proactive telephone support will be provided, in which the support team phones the mother daily for up to 14 days after hospital discharge. In the control group, mothers are offered a person-centred reactive support where mothers can phone the breastfeeding support team up to day 14 after hospital discharge. The intervention group will also be offered the same reactive telephone support as the control group. A stratified block randomization will be used; group allocation will be by high or low socioeconomic status and by NICU. Recruitment will be performed continuously until 1116 mothers (I: 558 C: 558) have been included. Primary outcome: proportion of mothers exclusively breastfeeding at eight weeks after discharge. Secondary outcomes: proportion of breastfeeding (exclusive, partial, none and method of feeding), mothers satisfaction with breastfeeding, attachment, stress and quality of life in mothers/partners at eight weeks after hospital discharge and at six months postnatal age. Data will be collected by researchers blind to group allocation for the primary outcome. A qualitative evaluation of experiences of receiving/providing the intervention will also be undertaken with mothers and staff. Discussion: This paper presents the rationale, study design and protocol for a RCT providing person-centred proactive telephone support to mothers of preterm infants. Furthermore, with a health economic evaluation, the cost-effectiveness of the intervention will be assessed. Trial registration: NCT01806480

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  • 22.
    Ericson, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Eriksson, Mats
    Örebro Universitet.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Hoddinott, Pat
    University of Stirling, Stirling, Scotland.
    Flacking, Renée
    Högskolan Dalarna.
    Proactive telephone support provided to breastfeeding mothers of preterm infants after discharge: a randomised controlled trial2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 5, p. 791-798Article in journal (Refereed)
    Abstract [en]

    Aim: The aim was to evaluate the effectiveness of proactive telephone support provided to breastfeeding mothers of preterm infants after discharge from neonatal intensive care units (NICU).

    Methods: Between March 2013 and December 2015, a randomised controlled trial was conducted at six NICUs across Sweden. At each NICU, a breastfeeding support team recruited, randomised and delivered the support to participating mothers. The intervention group received a daily proactive telephone call up to 14 days after discharge from the support team. The control group could initiate telephone contact themselves. Primary outcome was exclusive breastfeeding eight weeks after discharge. Secondary outcomes were maternal satisfaction with breastfeeding, attachment, quality of life and parental stress.

    Results: In total, 493 mothers were randomised, 231 to intervention group and 262 to control group. There were no differences between the groups for exclusive breastfeeding, odds ratio 0.96, 95% CI 0.66–1.38, nor for maternal satisfaction with breastfeeding, attachment or quality of life. The intervention group reported significantly less parental stress than the controls, t = 2.44, 95% CI 0.03–0.23, effect size d = 0.26.

    Conclusion: In this trial, proactive telephone support was not associated with increased exclusive breastfeeding prevalence eight weeks following discharge. However, intervention group mothers showed significantly lower parental stress.

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  • 23.
    Ericson, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Falun Hospital; Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Eriksson, Mats
    Orebro Univ, Fac Med & Hlth, Sch Hlth Sci, Orebro, Sweden.
    Hoddinott, Pat
    Univ Stirling, Nursing Midwifery & Allied Hlth Profess Res Unit, Stirling, Scotland.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research. U.
    Flacking, Renee
    Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Breastfeeding and risk for ceasing in mothers of preterm infants-Long-term follow-up2018In: Maternal and Child Nutrition, ISSN 1740-8695, E-ISSN 1740-8709, Vol. 14, no 4, article id e12618Article in journal (Refereed)
    Abstract [en]

    Breastfeeding is challenging for mothers of preterm infants. The aim of this paper is to describe risk factors for ceasing breastfeeding and methods of feeding until 12 months postnatal age in mothers who breastfed their preterm infants at discharge from neonatal intensive care units (NICUs). The data come from a randomised controlled trial, which evaluated the effectiveness on exclusive breastfeeding at 8 weeks of proactive telephone support compared with reactive support offered to mothers of preterm infants following discharge from NICU. Six NICUs across Sweden randomised a total of 493 mothers. We used regression and survival analyses to assess the risk factors for ceasing breastfeeding and the long-term outcomes of the intervention. The results showed that 305 (64%) of the infants were breastfed at 6 months and 49 (21%) at 12 months. Partial breastfeeding at discharge, low maternal educational level, and longer length of stay in the NICU increased the risk for ceasing breastfeeding during the first 12 months. Furthermore, the Kaplan-Meier analysis showed that the proportion of mothers who ceased breastfeeding did not differ between the intervention (n = 231) and controls (n = 262) during the first 12 months (log-rank test p = .68). No difference was found between groups on method of feeding. More than 85% of the infants were fed directly at the breast. These findings provide important insights for health professionals who are supporting mothers of preterm infants to breastfeed long term.

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  • 24.
    Ericson, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Ctr Clin Res Dalarna, Falun, Sweden.;Falun Cent Hosp, Dept Pediat, Falun, Sweden..
    Flacking, Renee
    Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Eriksson, Mats
    Univ Orebro, Sch Hlth Sci, Fac Med & Hlth, Orebro, Sweden..
    Changes in the prevalence of breast feeding in preterm infants discharged from neonatal units: a register study over 10 years2016In: BMJ Open, E-ISSN 2044-6055, Vol. 6, no 12, article id e012900Article in journal (Refereed)
    Abstract [en]

    Objective: There are indications that the prevalence of exclusively breastfed preterm infants is decreasing in Sweden. The objective was to investigate trends in exclusive breast feeding at discharge from Swedish neonatal units and associated factors in preterm infants. Design, setting and participants: This is a register study with data from the Swedish Neonatal Quality Register. Data from 29 445 preterm infants (gestational age (GA) < 37 weeks) who were born during the period 2004-2013 were retrieved. Data included maternal, perinatal and neonatal characteristics. Data were analysed for the whole population as well as for 3 GA groups. Results: From 2004 to 2013, the prevalence of exclusive breast feeding decreased, in extremely preterm (GA 22-27 weeks) from 55% to 16%, in very preterm (GA 28-31 weeks) from 41% to 34% and in moderately preterm infants (GA 32-36 weeks) from 64% to 49%. The decline was statistically significant (p<0.001) in all 3 GA groups. This decline remained significant when adjustments were made for factors negatively associated with exclusive breast feeding and which became more prevalent during the study period, that is, small for GA (all groups) and maternal mental illness (very preterm and moderately preterm infants). Conclusions: In the past 10 years, Sweden has experienced a lower rate of exclusive breast feeding in preterm infants, especially in extremely preterm infants. The factors analysed in this study explain only a small proportion of this decline. The decline in exclusive breast feeding at discharge from neonatal units raises concern and present challenges to the units to support and promote breast feeding.

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  • 25.
    Farooqi, Aijaz
    et al.
    Umeå Univ, Dept Clin Sci, Pediat, Umeå, Sweden..
    Hakansson, Stellan
    Umeå Univ, Dept Clin Sci, Pediat, Umeå, Sweden.;Umeå Univ, Pediat, Swedish Neonatal Qual Register, Umeå, Sweden..
    Serenius, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kallen, Karin
    Lund Univ, Dept Reprod Epidemiol, Lund, Sweden..
    Bjorklund, Lars
    Skane Univ Hosp Lund, Dept Clin Sci, Lund, Sweden.;Skane Univ Hosp Lund, Dept Pediat, Lund, Sweden..
    Normann, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Domellof, Magnus
    Umeå Univ, Dept Clin Sci Pediat, Med Fak, Umeå, Sweden..
    Aden, Ulrika
    Karolinska Inst, Woman & Child Hlth, Stockholm, Sweden..
    Abrahamsson, Thomas
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden.;Linköping Univ, Dept Pediat, Linköping, Sweden..
    Elfvin, Anders
    Univ Gothenburg, Inst Clin Sci, Dept Pediat, Sahlgrenska Acad, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Pediat, Gothenburg, Sweden..
    Savman, Karin
    Sahlgrens Univ Hosp, Dept Pediat, Gothenburg, Sweden..
    Bergstrom, Petra Um
    Karolinska Inst, Clin Sci & Educ Sodersjukhuset, Stockholm, Sweden..
    Stephansson, Olof
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Inst, Dept Clin Epidemiol, Stockholm, Sweden..
    Ley, David
    Lund Univ, Dept Clin Sci, Pediat, Lund, Sweden..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Norman, Mikael
    Karolinska Inst, Karolinska Univ Hosp, Neonatal Med, Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    One-year survival and outcomes of infants born at 22 and 23 weeks of gestation in Sweden 2004-2007, 2014-2016 and 2017-20192024In: Archives of Disease in Childhood: Fetal and Neonatal Edition, ISSN 1359-2998, E-ISSN 1468-2052, Vol. 109, no 1, p. 10-17Article in journal (Refereed)
    Abstract [en]

    Objective: To explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden.

    Design/Setting: Data on all births at 22 and 23 weeks' gestational age (GA) were prospectively collected in 2004-2007 (T1) or obtained from national registers in 2014-2016 (T2) and 2017-2019 (T3). Infants were assigned perinatal activity scores based on 3 key obstetric and 4 neonatal interventions.

    Main outcome: One-year survival and survival without major neonatal morbidities (MNM): intraventricular haemorrhage grade 3-4, cystic periventricular leucomalacia, surgical necrotising enterocolitis, retinopathy of prematurity stage 3-5 or severe bronchopulmonary dysplasia. The association of GA-specific perinatal activity score and 1-year survival was also determined.

    Results: 977 infants (567 live births and 410 stillbirths) were included: 323 born in T1, 347 in T2 and 307 in T3. Among live-born infants, survival at 22 weeks was 5/49 (10%) in T1 and rose significantly to 29/74 (39%) in T2 and 31/80 (39%) in T3. Survival was not significantly different between epochs at 23 weeks (53%, 61% and 67%). Among survivors, the proportions without MNM in T1, T2 and T3 were 20%, 17% and 19% for 22 weeks and 17%, 25% and 25% for 23 weeks' infants (p>0.05 for all comparisons). Each 5-point increment in GA-specific perinatal activity score increased the odds for survival in first 12 hours of life (adjusted OR (aOR) 1.4; 95% CI 1.3 to 1.6) in addition to 1-year survival (aOR 1.2; 95% CI 1.1 to 1.3), and among live-born infants it was associated with increased survival without MNM (aOR 1.3; 95% CI 1.1 to 1.4).

    Conclusion: Increased perinatal activity was associated with reduced mortality and increased chances of survival without MNM in infants born at 22 and 23 weeks of GA.

  • 26.
    Fredriksson Kaul, Ylva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rosander, Kerstin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    von Hofsten, Claes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Strand Brodd, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research Sörmland.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Visual tracking at 4 months in preterm infants predicts 6.5-year cognition and attention2022In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 92, no 4, p. 1082-1089Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Visual tracking of moving objects requires sustained attention and prediction of the object’s trajectory. We tested the hypothesis that measures of eye-head tracking of moving objects are associated to long-term neurodevelopment in very preterm infants.METHODS: Visual tracking performance was assessed at 4 month’s corrected age in 57 infants with gestational age <32 weeks. An object moved in front of the infant with sinusoidal or triangular (i.e. abrupt) turns of the direction. Gaze gain, smooth pursuit gain, and timing of gaze to object motion were analyzed. At 6.5 years the Wechsler Intelligence Scale for Children (WISC-IV), the Brown Attention Deficit Disorder (Brown ADD), and visual examination were performed. 

    RESULTS: Gaze gain and smooth pursuit gain at 4 months were strongly related to all WISC-IV parameters at 6.5 years. Gaze gain for the triangular and sinusoidal motion patterns related similarly to the cognitive scores. For the sinusoidal motion pattern, timing related to most Brown ADD parameters. There were no statistically significant differences in associations dependent on motion pattern. Visual function did not influence the results. 

    CONCLUSION: The ability to attend to and smoothly track a moving object in infancy is an early marker of cognition and attention at 6.5 years. 

  • 27. Griesmaier, Elke
    et al.
    Enot, David Pierre
    Bachmann, Miriam
    Neubauer, Vera
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kiechl-Kohlendorfer, Ursula
    Keller, Matthias
    Systematic characterization of amplitude-integrated EEG signals for monitoring the preterm brain2013In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 73, no 2, p. 226-235Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In preterm infants, the amplitude-integrated electroencephalogram (aEEG) is not established in clinical routine. The aim of this study was to derive normative data on aEEG parameters by means of longitudinal characterization and to evaluate the impact of gestational age (GA), postnatal age (PNA), postmenstrual age, sedation, and patent ductus arteriosus (PDA). METHODS: Recordings from 61 infants with GA 28-31 weeks were obtained during the first 72 h, then weekly until the age of 4 wk. Infants were divided into three groups: (i) no sedation, no PDA, (ii) sedation, no PDA, and (iii) sedation, PDA. Assessed parameters included background activity, cycling, amplitude, and log ratio of the maximum/minimum amplitude. RESULTS: GA and PNA had a significant impact within 72h. Sedation modified aEEG, and presence of PDA was associated with reduced aEEG scores within 72 h. The log ratio of the amplitude correlated with GA but was unaffected by sedation and PDA. CONCLUSION: Evaluation of electrocortical background activity within the first postnatal hours and longitudinally over days and weeks is important to better understand the postnatal factors impacting cerebral function in preterm infants. There is a need to agree on definitions and a standardized reporting system in order to permit comparisons between studies and establish aEEG as a method for routine monitoring of preterm infants.

  • 28. Hansen Pupp, Ingrid
    et al.
    Hövel, Holger
    Hellström, Ann
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Löfqvist, Chatarina
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lazeyras, Francois
    Fellman, Vineta
    Hüppi, Petra S.
    Ley, David
    Postnatal decrease in circulating insulin-like growth factor-I and low brain volumes in very preterm infants2011In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 96, no 4, p. 1129-1135Article in journal (Refereed)
    Abstract [en]

    Context: IGF-I and IGF binding protein-3 (IGFBP-3) are essential for growth and maturation of the developing brain. Objective: The aim of this study was to evaluate the association between postnatal serum concentrations of IGF-I and IGFBP-3 and brain volumes at term in very preterm infants. Design: Fifty-one infants with a mean (sd) gestational age (GA) of 26.4 (1.9) wk and birth weight (BW) of 888 (288) g were studied, with weekly blood sampling of IGF-I and IGFBP-3 from birth until 35 gestational weeks (GW) and daily calculation of protein and caloric intake. Magnetic resonance images obtained at 40 GW were segmented into total brain, cerebellar, cerebrospinal fluid, gray matter, and unmyelinated white matter volumes. Main Outcome Measures: We evaluated brain growth by measuring brain volumes using magnetic resonance imaging. Results: Mean IGF-I concentrations from birth to 35 GW correlated with total brain volume, unmyelinated white matter volume, gray matter volume, and cerebellar volume [r = 0.55 (P < 0.001); r = 0.55 (P < 0.001); r = 0.44 (P = 0.002); and r = 0.58 (P < 0.001), respectively]. Similar correlations were observed for IGFBP-3 concentrations. Correlations remained after adjustment for GA, mean protein and caloric intakes, gender, severe brain damage, and steroid treatment. Protein and caloric intakes were not related to brain volumes. Infants with BW small for GA had lower mean concentrations of IGF-I (P = 0.006) and smaller brain volumes (P = 0.001-0.013) than infants with BW appropriate for GA. Conclusion: Postnatal IGF-I and IGFBP-3 concentrations are positively associated with brain volumes at 40 GW in very preterm infants. Normalization of the IGF-I axis, directly or indirectly, may support normal brain development in very preterm infants.

  • 29. Hansen-Pupp, Ingrid
    et al.
    Hovel, Holger
    Lofqvist, Chatarina
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Fellman, Vineta
    Huppi, Petra S.
    Hellstrom, Ann
    Ley, David
    Circulatory insulin-like growth factor-I and brain volumes in relation to neurodevelopmental outcome in very preterm infants2013In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 74, no 5, p. 564-569Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To evaluate the relationships between postnatal change in circulatory insulin-like growth factor-I (IGF-I) concentrations, brain volumes, and developmental outcome at 2 y of age in very preterm infants. METHODS: IGF-I was measured weekly, and nutritional intake was calculated daily from birth until a postmenstrual age (PMA) of 35 wk. Individual beta coefficients for IGF-I, IGF-I(B), representing the rate of increase in IGF-I from birth until a PMA of 35 wk were calculated. Brain magnetic resonance imaging was performed at term age, with segmentation into total brain, cerebellar, gray matter, and unmyelinated white matter volume (UWMV). Developmental outcome was evaluated using Bayley Scales of Infant Development-II. RESULTS: Forty-nine infants, with mean gestational age (GA) of 26.0 wk, were evaluated at mean 24.6 mo corrected age. Higher IGF-I(B), UWMV, and cerebellar volume were associated with a decreased risk for a Mental Developmental Index (MDI) <85 (odds ratio (95% confidence interval): 0.6 (0.4-0.9), 0.96 (0.94-0.99), and 0.78 (0.6-0.96), respectively). In multivariate analysis, higher IGF-I(B) and higher UWMV combined with female gender constituted the two models with the highest predictive value for MDI > 85. CONCLUSION: A higher rate of increase in circulating IGF-I is associated with a decreased risk for subnormal MDI at 2 y of corrected age. This relationship is in part dependent on brain volume at term age.

  • 30. Heinemann, Ann-Britt
    et al.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Nyqvist, Kerstin Hedberg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Factors affecting parents' presence with their extremely preterm infants in a neonatal intensive care room2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 7, p. 695-702Article in journal (Refereed)
    Abstract [en]

    Aim To describe parents' experiences of factors that influenced their stay with their extremely preterm infants in a neonatal intensive care unit (NICU). Methods This study has a qualitative descriptive design based on semistructured interviews conducted with seven mothers and six fathers. Results Opportunities to stay overnight together with their infant facilitated parental presence, and opportunities for taking over their infant's care empowered the parents in their parental role and increased their motivation to stay. Kangaroo mother care helped them to feel in control and feel needed, which increased their presence. High levels of illumination and noise rendered it difficult for parents to sleep and stay overnight with the infant. Low staffing levels limited their use of kangaroo mother care when they had to wait for assistance to transfer the infant from the incubator. Several participants perceived the performance of painful procedures on their child as stressful and as an obstacle to their presence. Conclusion Kangaroo mother care and active involvement in the infant's care gave parents a sense of control and strengthened their motivation to be with their infant. High levels of noise and illumination and a dismissive staff attitude were obstacles to parents' presence.

  • 31.
    Hellstrom, Ann
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Sahlgrenska Ctr Pediat Ophthalmol Res,Dept Clin N, Gothenburg, Sweden..
    Jacobson, Lena
    Karolinska Inst, Dept Clin Neurosci, Sect Eye & Vis, Stockholm, Sweden.;Karolinska Univ Sjukhuset, Astrid Lindgren Childrens Hosp, Neuropediat Dept, Stockholm, Sweden..
    Al-Hawasi, Abbas
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rakow, Alexander
    Karolinska Inst, Dept Woman & Child Hlth, Stockholm, Sweden..
    Johnson, Mats
    Univ Gothenburg, Sahlgrenska Acad, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden..
    Savman, Karin
    Sahlgrens Univ Hosp, Queen Silvia Childrens Hosp, Dept Neonatol, Reg Vastra Gotland, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden..
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Ophthalmic Biophsics.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Ophthalmic Biophsics.
    Granse, Lotta
    Skane Univ Hosp Lund, Dept Clin Sci, Ophthalmol, Lund, Sweden..
    Saric, Marie
    Umeå Univ, Med Fak, Dept Clin Sci, Ophthalmol, Umeå, Sweden..
    Sunnqvist, Birgitta
    Lanssjukhuset Ryhov, Dept Ophthalmol, Jönköping, Sweden..
    Smith, Lois
    Harvard Med Sch, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA..
    Hard, Anna-Lena
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Sahlgrenska Ctr Pediat Ophthalmol Res,Dept Clin N, Gothenburg, Sweden..
    Morsing, Eva
    Skane Univ Hosp Lund, Dept Pediat, Clin Sci, Lund, Sweden..
    Lundgren, Pia
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Sahlgrenska Ctr Pediat Ophthalmol Res,Dept Clin N, Gothenburg, Sweden..
    Retrospective evaluation of ophthalmological and neurological outcomes for infants born before 24 weeks gestational age in a Swedish cohort2022In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 8, article id e055567Article in journal (Refereed)
    Abstract [en]

    Objectives To retrospectively evaluate ophthalmological and neurological outcomes in a Swedish cohort of infants born before 24 weeks gestational age (GA) and explore risk factors for visual impairment. Setting Eye and paediatric clinics in Sweden. Participants Infants screened for retinopathy of prematurity (ROP) (n=399), born before 24 weeks GA, 2007-2018. Cases were excluded if ophthalmological follow-up records could not be traced. Primary and secondary outcome measures Primary outcomes were ophthalmological, including visual acuity (VA), refractive error, strabismus, nystagmus and cerebral visual impairment (CVI). Secondary outcomes comprised neonatal and neurological morbidities. Data were retrospectively retrieved from medical records. Results The 355 assessed children had a median GA of 23 weeks and 2 days and a median birth weight of 565 g. At the last available ophthalmological examination, the median age was 4.8 years (range 0.5-13.2 years). Nystagmus was recorded in 21.1%, strabismus in 34.8%, and 51.0% wore spectacles. Seventy-three of 333 (21.9%) were visually impaired, defined as being referred to a low vision clinic and/or having a VA less than 20/60 at 3.5 years of age or older. ROP treatment was a significant risk factor for visual impairment (OR 2.244, p=0.003). Visually impaired children, compared with children without visual impairment, more often had neurological deficits such as intellectual disability 63.8% versus 33.3% (p<0.001), epilepsy 21.1% versus 7.5% (p=0.001) and autism spectrum disorders 32.8% versus 20.9% (p=0.043). Nine of the 355 children had been diagnosed with CVI. Conclusions Children born before 24 weeks GA frequently had visual impairment in association with neurological deficits. CVI was rarely diagnosed. A multidisciplinary approach for the evaluation and habilitation of these vulnerable infants is warranted. National follow-up guidelines need to be developed and implemented.

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  • 32.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Amplitude-integrated electroencephalography for seizure detection in newborn infants2018In: Seminars in Fetal & Neonatal Medicine, ISSN 1744-165X, E-ISSN 1878-0946, Vol. 23, no 3, p. 175-182Article in journal (Refereed)
    Abstract [en]

    The amplitude-integrated electroencephalogram (aEEG) is a filtered and compressed EEG trend that can be used for long-term monitoring of brain function in patients of all ages. aEEG is increasingly used in neonatal intensive care units since several studies have shown its utility in high-risk newborn infants. Main indications for aEEG monitoring include early evaluation of brain function after perinatal asphyxia and seizure detection. The aEEG is usually recorded from one or two channels derived from parietal, central, or frontal leads. Although the aEEG is very useful for identifying high-risk infants and infants with seizures, the compressed trend has limitations with regards to detection of individual seizures. However, modern monitors also display the corresponding EEG (aEEG/EEG), which increases the probability of detecting single brief seizures. For improved evaluation of electrocortical brain activity the aEEG/EEG should be assessed together with repeated conventional EEGs or multi-channel EEG monitoring in a multi-disciplinary team. (C) 2018 Elsevier Ltd. All rights reserved.

  • 33.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Monitoring brain function with aEEG in term asphyxiated infants before and during cooling2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 7, p. 678-679Article in journal (Refereed)
  • 34.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    The need for more research on seizures in preterm infants.2010In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 157, no 5, p. 700-1Article in journal (Refereed)
  • 35.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Using magnetic resonance imaging to diagnose neonatal seizures2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 8, p. 792-793Article in journal (Other academic)
  • 36.
    Hellström-Westas, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Boylan, Geraldine
    Department of Paediatrics & Child Health, University College Cork, Cork, Ireland.
    Ågren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Systematic review of neonatal seizure management strategies provides guidance on anti-epileptic treatment2015In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, no 2Article, review/survey (Refereed)
    Abstract [en]

    There is a lack of scientific evidence to support the best management of neonatal seizures. Current strategies for neonatal seizure management were investigated by analysis of all surveys published during the time period 2000-2012. Methods for seizure diagnosis and availability of electroencephalogram (EEG), including monitoring, varied. Phenobarbital was the drug of first choice, and the use of off-label drugs and treatment times varied. We conclude that there is an urgent need for more evidence-based studies to guide neonatal seizure management.

  • 37. Hovel, Holger
    et al.
    Partanen, Eino
    Tideman, Eva
    Stjernqvist, Karin
    Hellström-Westass, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Huotilainen, Minna
    Fellman, Vineta
    Auditory event-related potentials are related to cognition at preschool age after very preterm birth2015In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 77, no 4, p. 570-578Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Auditory event-related potentials (AERP) are neurophysiological correlates of sound perception and cognitive processes. Our aim was to study in very preterm born children at preschool age if AERP correlate with cognitive outcome. METHODS: Seventy children (mean +/- SD gestational age 27.4 +/- 1.9 wk, birth weight 996 +/- 288 g) were investigated at age 4.3-5.3 y with psychological testing (WPPSI-R, four subtests of NEPSY), Electroencephalogram was recorded while they listened to a repeated standard tone, randomly replaced by one of three deviants. Latencies and amplitudes for AERP components and mean amplitudes in successive 50-ms AERP time windows were measured. RESULTS: Better cognitive test results and higher gestational age correlated with shorter P1 latencies and more positive mean amplitudes 150-500 ms after stimulus change onset. Neonatal brain damage was associated with a negative displacement of AERP curves. Neonatal morbidity had an impact on earlier time windows while gestational age and brain damage on both early and later time windows. CONCLUSION: AERP measures were associated with cognitive outcome. Neonatal morbidity mainly affects early cortical auditory encoding, while immaturity and brain damage additionally influence higher cortical functions of auditory perception and distraction. Perinatal auditory environment might play a role in development of auditory processing.

  • 38.
    Hreinsdottir, Jonina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kaul, Ylva Fredriksson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Rosander, Kerstin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    von Hofsten, Claes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Impaired cognitive ability at 2.5 years predicts later visual and ophthalmological problems in children born very preterm2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 5, p. 822-830Article in journal (Refereed)
    Abstract [en]

    Aim: To identify possible predictive factors for visual problems at 6.5 years in children born very preterm.

    Methods: During 2004–2007, all very preterm infants (gestational age [GA] <32 weeks) in Uppsala County, Sweden were screened for retinopathy of prematurity (ROP) neonatally; at four months, visual tracking was tested; at 2.5 years, visuospatial and cognitive tests were carried out. At 6.5 years, 84 preterm children and a reference group of 64 full‐term children underwent ophthalmological testing.

    Results: Mean visual acuity (VA) did not differ between the groups, but subnormal VA (≤0.8) was more common in the preterm group (31% vs 14%; p < 0.05). More often than full‐term children, preterm children had impaired contrast sensitivity (<0.5) (36% vs 19%; p < 0.05) and strabismus (8% vs 0%; p < 0.05). Low GA, ROP, intraventricular haemorrhage 3‐4/periventricular leukomalacia and cognitive disability at 2.5 years predicted ophthalmological and visual problems at 6.5 years. Visual tracking ability at four months was not predictive of ophthalmological outcome.

    Conclusion: Children born preterm had more ophthalmological problems at 6.5 years of age, including subtle dysfunctions. ROP, early brain injury and impaired cognitive function around 2.5 years predicted later ophthalmological dysfunctions.

  • 39. Hyttel-Sorensen, Simon
    et al.
    Austin, Topun
    van Bel, Frank
    Benders, Manon
    Claris, Olivier
    Dempsey, Eugene
    Fumagalli, Monica
    Greisen, Gorm
    Grevstad, Berit
    Hagmann, Cornelia
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lemmers, Petra
    Lindschou, Jane
    Naulaers, Gunnar
    van Oeveren, Wim
    Pellicer, Adelina
    Pichler, Gerhard
    Roll, Claudia
    Skoog, Maria
    Winkel, Per
    Wolf, Martin
    Gluud, Christian
    A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial2013In: Trials, E-ISSN 1745-6215, Vol. 14, p. 120-Article in journal (Refereed)
    Abstract [en]

    Background: Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO(2). Methods/Design: SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO(2) values outside the target ranges of 55% to 85%, that is, the 'burden of hypoxia and hyperoxia' expressed in '%hours'. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events. Discussion: Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia.

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  • 40. Hyttel-Sorensen, Simon
    et al.
    Austin, Topun
    van Bel, Frank
    Benders, Manon
    Claris, Olivier
    Dempsey, Eugene M.
    Fumagalli, Monica
    Gluud, Christian
    Hagmann, Cornelia
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lemmers, Petra
    Naulaers, Gunnar
    van Oeveren, Wim
    Pellicer, Adelina
    Pichler, Gerhard
    Roll, Claudia
    Stoy, Lina Saem
    Wolf, Martin
    Greisen, Gorm
    Clinical use of cerebral oximetry in extremely preterm infants is feasible2013In: Danish Medical Journal, E-ISSN 2245-1919, Vol. 60, no 1, p. A4533-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The research programme Safeguarding the Brains of our smallest Children (SafeBoosC) aims to test the benefits and harms of cerebral near-infrared spectroscopy (NIRS) oximetry in infants born before 28 weeks of gestation. In a phase II trial, infants will be randomised to visible cerebral NIRS oximetry with pre-specified treatment guidelines compared to standard care with blinded NIRS-monitoring. The primary outcome is duration multiplied with the extent outside the normal range of regional tissue oxygen saturation of haemoglobin (rStO(2)) of 55 to 85% in percentage hours (burden). This study was a pilot of the Visible Oximetry Group. MATERIAL AND METHODS: This was an observational study including ten infants. RESULTS: The median gestational age was 26 weeks + three days, and the median start-up time was 133 minutes after delivery. The median recording time was 69.7 hours, mean rStO(2) was 64.2 +/- 4.5%, median burden of hyper- and hypoxia was 30.3% hours (range 2.8-112.3). Clinical staff responded to an out of range value 29 times - only once to values above 85%. In comparison, there were 83 periods of more than ten minutes with an rStO(2) below 55% and four episodes with an rStO(2) above 85%. These periods accounted for 72% of the total hypoxia burden. A total of 18 of the 29 interventions were adjustments of FiO(2) which in 13 of the 18 times resulted in an out-of-range SpO(2). Two infants suffered second-degree burns from the sensor. Five infants died. In all cases, this was unrelated to NIRS monitoring and treatment. CONCLUSION: The intervention of early cerebral NIRS monitoring proved feasible, but prolonged periods of hypoxia went untreated. Thus, a revision of the treatment guideline and an alarm system is required.

  • 41. Isacson, Manuela
    et al.
    Thies-Lagergren, Li
    Oras, Paola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Anderssson, Ola
    Umbilical cord clamping and management of the third stage of labor: A telephone-survey describing Swedish midwives’ clinical practice2022In: European Journal of Midwifery, E-ISSN 2585-2906, Vol. 6, p. 1-7, article id 6Article in journal (Refereed)
    Abstract [en]

    Introduction:The timing of cord clamping impacts children’s short- and longterm well-being. When making clinical decisions, midwives incorporate their tacit and professional knowledge, experience and current evidence. There appears to be a lack of knowledge regarding Swedish midwives’ management of the third stage of labor and cord clamping practice. The aim of this study was to explore Swedish midwives’ clinical practice concerning umbilical cord clamping and the third stage of labor in spontaneous vaginal births.

    Methods:The study was designed as a cross-sectional telephone survey including 13 questions. Midwives were randomly selected from 48 births units in Sweden. Two midwives from each unit were interviewed. The primary outcome was timing of umbilical cord clamping practice in full-term infants. Secondary outcomes were the management of the third stage of labor including prophylactic use of synthetic oxytocin, the timing of cord clamping in preterm infants, controlled cord traction, uterine massage, and cord milking.

    Results:Altogether, 95 midwives were interviewed. In full-term infants, all midwives preferred late cord clamping. Considerable heterogeneity was seen regarding the practices of synthetic oxytocin administration postpartum, controlled cord traction, uterine massage or cord milking, and cord clamping in preterm infants.

    Conclusions:Midwives in Sweden modify recommendations regarding delayed cord clamping in a way they might perceive as more natural and practical in their daily, clinical work. The study revealed a reluctance toward the administration of prophylactic oxytocin due to fear that the drug could pass to the infant. An overall large variation of the management of the third stage of labor was seen.

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  • 42.
    Iyer, Kartik K.
    et al.
    QIMR Berghofer Med Res Inst, Syst Neurosci Grp, Brisbane, Qld, Australia.;Univ Queensland, Fac Med & Biomed Sci, Sch Med, Brisbane, Qld 4072, Australia..
    Roberts, James A.
    QIMR Berghofer Med Res Inst, Syst Neurosci Grp, Brisbane, Qld, Australia..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Wikstrom, Sverre
    Karlstad Cent Hosp, Dept Pediat, Karlstad, Sweden..
    Pupp, Ingrid Hansen
    Lund Univ, Inst Clin Sci, Dept Pediat, Lund, Sweden..
    Ley, David
    Lund Univ, Inst Clin Sci, Dept Pediat, Lund, Sweden..
    Breakspear, Michael
    QIMR Berghofer Med Res Inst, Syst Neurosci Grp, Brisbane, Qld, Australia.;Metro North Mental Hlth Serv, Brisbane, Qld, Australia..
    Vanhatalo, Sampsa
    Univ Helsinki, Cent Hosp, HUS Med Imaging Ctr, Dept Childrens Clin Neurophysiol, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland.;Univ Cent Hosp, Childrens Hosp, Dept Pediat, Helsinki, Finland..
    Early Detection of Preterm Intraventricular Hemorrhage From Clinical Electroencephalography2015In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 10, p. 2219-2227Article in journal (Refereed)
    Abstract [en]

    Objectives: Intraventricular hemorrhage is a common neurologic complication of extremely preterm birth and leads to lifelong neurodevelopmental disabilities. Early bedside detection of intraventricular hemorrhage is crucial to enabling timely interventions. We sought to detect early markers of brain activity that preempt the occurrence of intraventricular hemorrhage in extremely preterm infants during the first postnatal days. Design: Cross-sectional study. Setting: Level III neonatal ICU. Patients: Twenty-five extremely preterm infants (22-28 wk gestational age). Measurements and Main Results: We quantitatively assessed electroencephalography in the first 72 hours of postnatal life, focusing on the electrical burst activity of the preterm. Cranial ultrasound was performed on day 1 (0-24 hr) and day 3 (48-72 hr). Outcomes were categorized into three classes: 1) no intraventricular hemorrhage (grade 0); 2) mild-moderate intraventricular hemorrhage (grades 1-2, i.e., germinal matrix hemorrhages or intraventricular hemorrhage without ventricular dilatation, respectively); and 3) severe intraventricular hemorrhage (grades 3-4, i.e., intraventricular hemorrhage with ventricular dilatation or intraparenchymal involvement). Quantitative assessment of electroencephalography burst shapes was used to preempt the occurrence and severity of intraventricular hemorrhage as detected by ultrasound. The shapes of electroencephalography bursts found in the intraventricular hemorrhage infants were significantly sharper (F = 13.78; p < 0.0001) and less symmetric (F = 6.91; p < 0.015) than in preterm infants without intraventricular hemorrhage. Diagnostic discrimination of intraventricular hemorrhage infants using measures of burst symmetry and sharpness yielded high true-positive rates (82% and 88%, respectively) and low false-positive rates (19% and 8%). Conventional electroencephalography measures of interburst intervals and burst counts were not significantly associated with intraventricular hemorrhage. Conclusions: Detection of intraventricular hemorrhage during the first postnatal days is possible from bedside measures of brain activity prior to ultrasound confirmation of intraventricular hemorrhage. Significantly, our novel automated assessment of electroencephalography preempts the occurrence of intraventricular hemorrhage in the extremely preterm. Early bedside detection of intraventricular hemorrhage holds promise for advancing individual care, targeted therapeutic trials, and understanding mechanisms of brain injury in neonates.

  • 43. Iyer, Kartik K.
    et al.
    Roberts, James A.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Wikstrom, Sverre
    Pupp, Ingrid Hansen
    Ley, David
    Vanhatalo, Sampsa
    Breakspear, Michael
    y Cortical burst dynamics predict clinical outcome early in extremely preterm infants2015In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 138, p. 2206-2218Article in journal (Refereed)
    Abstract [en]

    Predicting long-term outcomes in extremely preterm infants is challenging. Iyer <italic toggle="yes">et al. show that the average shapes of EEG bursts in the first 72 hours after birth predict neurodevelopmental outcome at age 2 years, and that poorer outcomes are associated with sharper, more asymmetric complexes.See Luhmann <italic toggle="yes">et al. (doi:<related-article ext-link-type="doi" id="RA3" related-article-type="companion" xlink:href="10.1093/brain/awv147">10.1093/brain/awv147</related-article>) for a scientific commentary on this article. Predicting long-term outcomes in extremely preterm infants is challenging. Iyer <italic toggle="yes">et al. show that the average shapes of EEG bursts in the first 72 hours after birth predict neurodevelopmental outcome at age 2 years, and that poorer outcomes are associated with sharper, more asymmetric complexes.See Luhmann <italic toggle="yes">et al. (doi:<related-article ext-link-type="doi" id="RA4" related-article-type="companion" xlink:href="10.1093/brain/awv147">10.1093/awv147</related-article>) for a scientific commentary on this article.

  • 44.
    Johansson, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Fredriksson Kaul, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Montgomery, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Ophthalmic Biophsics.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Kochukhova, Olga
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Different aspects of visual perception are important for 12-year social functioning depending on gestational age2023In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 112, no 7, p. 1537-1547Article in journal (Refereed)
    Abstract [en]

    Aim

    Perceptual mechanisms in social functioning might promote interventions. We investigated relations between visual perception and social functioning, in preterm children.

    Methods

    A prospective preterm cohort born in Uppsala County, Sweden, in 2004–2007 and 49 full-term controls were examined at 12 years. Aspects of visual perception, including static shapes, emotions and time to detect biological motion, were related to social functioning and visual acuity.

    Results

    The preterm group comprised 25 extremely preterm children, EPT, born below 28 gestational weeks and 53 children born between 28 and 31 weeks. Preterm children had difficulties in perception of static shapes (p = 0.004) and biological motion (p < 0.001), but not in emotion perception, compared to controls. In the EPT children, poorer shape perception and lower scores on emotion perception were associated with more social problems (p = 0.008) and lower visual acuity (p = 0.004). Shape perception explained more variance in social functioning than emotion perception. In controls, fewer social problems were linked to faster biological motion perception (p = 0.04).

    Conclusion

    Static shape and biological motion perception was affected in the preterm groups. Biological motion perception was relevant for social functioning in full-term children. In EPT children, only shape perception was linked to social functioning, suggesting differential visual perception mechanisms for social deficits.

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  • 45.
    Kaplan-Sturk, Rebecka
    et al.
    Department of Clinical Science and Education, Section of Obstetrics and Gynecology, Karolinska Institute, Soder Hospital, Stockholm, Sweden.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Volgsten, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Wiberg-Itzel, Eva
    Department of Clinical Science and Education, Section of Obstetrics and Gynecology, Karolinska Institute, Soder Hospital, Stockholm, Sweden.
    Outcome of deliveries in healthy but obese women: obesity and delivery outcome2013In: BMC Research Notes, E-ISSN 1756-0500, Vol. 6, p. 50-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Obesity among fertile women is a global problem. 25% of pregnant Swedish women are overweight at admission to the antenatal clinic and 12% of them are considered as obese. Previous studies have shown an increased risk of delivery complications with an elevated maternal BMI. The aim of this study was to evaluate delivery outcomes in relation to maternal BMI on admission to the antenatal clinic.

    A healthy group of 787 women with full-term pregnancies and spontaneous onset of labor were included in the study. Delivery outcome was assessed in relation to maternal BMI when attending the antenatal clinic.

    RESULTS:

    The results indicated that in deliveries where the maternal BMI was >30 a high frequency of abnormal CTG trace during the last 30 minutes of labor was shown. A blood sample for evaluation of risk of fetal hypoxia was performed in only eight percent of these deliveries. A spontaneous vaginal delivery without intervention was noted in 85.7%, and 12% of neonates were delivered with an adverse fetal outcome compared to 2.8% in the group with a maternal BMI<30 (p<0.001).

    CONCLUSION:

    These results indicate an increased risk at delivery for healthy, but obese women in labor. Furthermore, the delivery management may not always be optimal in these deliveries.

  • 46.
    Karimi, Annette
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Radiology Department, Uppsala University Hospital, Uppsala, Sweden.
    Setänen, Sirkku
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Ophthalmic Biophsics.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Ophthalmic Biophsics.
    Fredriksson Kaul, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Kochukhova, Olga
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Johansson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Montgomery, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Brain MRI findings and their association with visual impairment in young adolescents born very preterm2024In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 66, no 1, p. 145-154Article in journal (Refereed)
    Abstract [en]

    Purpose

    Very preterm birth increases risk for neonatal white matter injury, but there is limited data on to what extent this persists into adolescence and how this relates to ophthalmological outcomes. The aim of this study was to assess brain MRI findings in 12-year-old children born very preterm compared to controls and their association with concurrent ophthalmological outcomes.

    Methods

    We included 47 children born very preterm and 22 full-term controls (gestational age <32 and >37 weeks, respectively). Brain MRI findings were studied in association with concurrent ophthalmological outcomes at 12-year follow-up.

    Results

    Evans index (0.27 vs 0.25, p<0.001) and a proposed “posterior ventricle index” (0.47 vs 0.45, p=0.018) were increased in children born very preterm. Higher gestational age associated with larger corpus callosum area (β=10.7, 95%CI 0.59–20.8). Focal white matter lesions were observed in 15 (32%) of very preterm children and in 1 (5%) of full-term controls. Increased posterior ventricle index increased risk for visual acuity ≤1.0 (OR=1.07×1011, 95%CI=7.78–1.48×1021) and contrast sensitivity <0.5 (OR=2.6×1027, 95%CI=1.9×108–3.5×1046). Decreased peritrigonal white matter thickness associated with impaired visual acuity (β=0.04, 95%CI 0.002–0.07).

    Conclusion

    More white matter lesions and evidence of lower white matter volume were found in children born very preterm compared with full-term controls at 12-year follow-up. The association between larger posterior ventricle index and reduced visual acuity and contrast sensitivity suggests disturbances of the posterior visual pathway due to diffuse white matter lesions.

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  • 47.
    Karlsson, Victoria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Univ Hosp, Unit Pediat Anesthesia, Uppsala, Sweden.;Univ Childrens Hosp, Div Neonatol, Uppsala, Sweden..
    Sporre, Bengt
    Univ Hosp, Unit Pediat Anesthesia, Uppsala, Sweden..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research. Univ Childrens Hosp, Div Neonatol, Uppsala, Sweden..
    Ågren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research. Univ Childrens Hosp, Div Neonatol, Uppsala, Sweden..
    Poor performance of main-stream capnography in newborn infants during general anesthesia2017In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 27, no 12, p. 1235-1240Article in journal (Refereed)
    Abstract [en]

    Background

    Endtidal (ET) measurement of carbon dioxide is well established for intraoperative respiratory monitoring of adults and children, but the method's accuracy for intraoperative use in small newborn infants has been less extensively investigated.

    Aims

    The aim of this study was to compare carbon dioxide from ET measurements with arterialized capillary blood samples in newborn infants during general anesthesia and surgery.

    Methods

    Endtidal carbon dioxide was continuously measured during anesthesia and surgery and compared with simultaneous blood gas analyses obtained from capillary blood samples. Fifty-nine sample sets of ET to blood gas carbon dioxide were obtained from 23 prospectively enrolled infants with a gestational age of 23-41 weeks and a birth weight of 670-4110 g.

    Results

    Endtidal levels of carbon dioxide were considerably lower in all sample sets and only 4/23 individual ET-blood gas sample pairs differed <7.5 mm Hg (1 kPa). Bland-Altman analysis indicated a poor agreement with a bias of -13 7 mm Hg and a precision of +/- 14 mm Hg. The performance of ET measurements was particularly poor in infants weighing below 2.5 kg, in infants in need of respiratory support prior to anesthesia, and when the true (blood gas) carbon dioxide level was high, above 45 mm Hg.

    Conclusion

    Main-stream capnography during anesthesia and surgery correlated poorly to blood gas values in small and/or respiratory compromised infants. We conclude that caution should be exercised when relying solely on ET measurements to guide mechanical ventilation in the OR.

  • 48.
    Kaul, Ylva F.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Naseh, Nima
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Strand Brodd, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research Sörmland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Böhm, Birgitta
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Average 2.5-year neurodevelopmental test results in children born very preterm did not rule out cognitive deficits at 6.5 years of age2021In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 110, no 3, p. 846-854Article in journal (Refereed)
    Abstract [en]

    Aim

    The aim of the study was to investigate cognitive outcomes at 6.5 years in children born very preterm, in relation to neonatal characteristics and 2.5-year neurodevelopment.

    Methods

    A prospective cohort, with gestational age 22.3-31.9 weeks, born 2004-2007, were examined at 2.5 years with the Bayley Scales of Infant and Toddler Development (Bayley-III) (n = 100) and at 6.5 years with the Wechsler Intelligence Scales (n = 91).

    Results

    Neonatal factors independently related to 6.5-year outcome were gestational age, retinopathy of prematurity and treated persistent ductus arteriosus. The Bayley-III cognitive scores explained only 44% of the Full-Scale Intelligence Quotient result at 6.5 years, and 22% of the children had Wechsler index results below −1 SD, indicating cognitive impairment, after average test results at 2.5 years. The relative risk to score below −1 SD on the Full-Scale IQ was 2.83 (95% CI 1.45-5.53) in children with gestational age below 28 weeks and 2.22 (95% CI 1.18-4.17) at gestational age 28-31 weeks.

    Conclusion

    Very preterm infants born in the 2000s had increased risks for impaired cognition at 6.5 years, but individual predictions based on neonatal risks and 2.5-year test results were not enough to identify all high-risk children.

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  • 49.
    Kaul, Ylva Fredriksson
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Rosander, Kerstin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Grönqvist, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Brodd, Katarina Strand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    von Hofsten, Claes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Reaching skills of infants born very preterm predict neurodevelopment at 2.5 years2019In: Infant Behavior and Development, ISSN 0163-6383, E-ISSN 1879-0453, Vol. 57, article id 101333Article in journal (Refereed)
    Abstract [en]

    The purpose was to investigate associations between quality of reaching for moving objects at 8 months corrected age and neurodevelopment at 2.5 years in children born very preterm (gestational age (GA), 24–31 weeks). Thirtysix infants were assessed while reaching for moving objects. The movements were recorded by a 3D motion capture system. Reaching parameters included aiming, relative length of the reach, number of movement units, proportion of bimanual coupled reaches and number of hits. Neurodevelopment was assessed at 2.5 years by the Bayley Scales of Infant Development III. There were strong associations between infant reaching kinematics and neurodevelopment of cognition and language but the patterns differed: in children born extremely preterm (GA < 28 weeks), planning and control of reaching was strongly related to outcome, while in children born very preterm (GA 28–31 weeks) number of hits and bimanual strategies were of greater relevance. In conclusion, for extremely preterm infants, basic problems on how motion information is incorporated with action planning prevail, while in very preterm infants the coordination of bimanual reaches is more at the focus. We conclude that the results reflect GA related differences in neural vulnerability and that early motor coordination deficits have a cascading effect on neurodevelopment.

  • 50.
    Kaul, Ylva Fredriksson
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Rosander, Kerstin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Hofsten, von, Claes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Brodd, Katarina Strand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research Sörmland.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kaul, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Bohm, Birgitta
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Visual tracking in very preterm infants at 4 mo predicts neurodevelopment at 3 y of age2016In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 80, no 1, p. 35-42Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Typically developing infants track moving objects with eye and head movements in a smooth and predictive way at 4 mo of age, but this ability is delayed in very preterm infants. We hypothesized that visual tracking ability in very preterm infants predicts later neurodevelopment. METHOD: In 67 very preterm infants (gestational age<32wk), eye and head movements were assessed at 4 mo corrected age while the infant tracked a moving object. Gaze gain, smooth pursuit, head movements, and timing of gaze relative the object were analyzed off line. Results of the five subscales included in the Bayley Scales of Infant Development (BSID-III) at 3 y of age were evaluated in relation to the visual tracking data and to perinatal risk factors. RESULTS: Significant correlations were obtained between gaze gain and cognition, receptive and expressive language, and fine motor function, respectively, also after controlling for gestational age, severe brain damage, retinopathy of prematurity, and bronchopulmonary dysplasia. CONCLUSION: This is the first study demonstrating that the basic ability to visually track a moving object at 4 mo robustly predicts neurodevelopment at 3 y of age in children born very preterm.

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