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  • 1.
    Kullinger, Merit
    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), Obstetrics and Reproductive Health Research. Region Vastmanland – Uppsala University, Center for Clinical Research, Hospital of Vastmanland Västerås, Sweden.
    Discrepancy between pregnancy dating methods – correlates and outcomes2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    With the introduction of obstetric ultrasound there has been a shift from last menstrual period-based to ultrasound-based estimation of gestational age. The choice of the method and timing of pregnancy dating is important because it can affect dating precision and perinatal outcomes.

    First, when comparing two large population-based cohorts from the Medical Birth Register, from before and after the introduction of ultrasound-based pregnancy dating, male infants on the edge of prematurity did not benefit from progress in medical care as much as female infants in terms of prematurity-related outcomes. This might reflect a bias introduced by the ultrasound-based pregnancy dating method, because of a tendency to overestimate gestational age in pregnancies with a male fetus.

    Second, in a large population-based cross-sectional study, the associations of discrepancies between last menstrual period-based and ultrasound-based estimates with variables such as fetal sex and maternal height, indicated that ultrasound-based pregnancy dating introduced systematic errors presumably related to the method’s use of fetal size as a proxy for gestational age. The largest effect estimates were found for maternal obesity in cases of large negative discrepancies.

    Third, in a large population-based cohort study, discrepancies between last menstrual period-based and ultrasound-based estimates were associated with several adverse pregnancy, delivery, and neonatal outcomes. Most importantly, a large negative discrepancy was associated with higher odds for neonatal and intrauterine fetal death, as well as for an infant being small for gestational age.

    Fourth, in a survey study there was overall good adherence to national guidelines, except for early pregnancy dating. However, the management of discrepancies between methods for pregnancy dating varied widely in clinical practice, which may be due to the lack of national guidelines.

    In summary, ultrasound-based dating can be biased by maternal or fetal characteristics. Discrepancies between methods for pregnancy dating may indicate a need for closer monitoring to optimize perinatal care during pregnancy and childbirth.

    List of papers
    1. Maternal and fetal characteristics affect discrepancies between pregnancy-dating methods: a population-based cross-sectional register study
    Open this publication in new window or tab >>Maternal and fetal characteristics affect discrepancies between pregnancy-dating methods: a population-based cross-sectional register study
    2017 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 96, no 1, p. 86-95Article in journal (Refereed) Published
    Abstract [en]

    IntroductionGestational age is estimated by ultrasound using fetal size as a proxy for age, although variance in early growth affects reliability. The aim of this study was to identify characteristics associated with discrepancies between last menstrual period-based (EDD-LMP) and ultrasound-based (EDD-US) estimated delivery dates. Material and methodsWe identified all singleton births (n=1201679) recorded in the Swedish Medical Birth Register in 1995-2010, to assess the association between maternal/fetal characteristics and large negative and large positive discrepancies (EDD-LMP earlier than EDD-US and 10th percentile in the discrepancy distribution vs. EDD-LMP later than EDD-US and 90th percentile). Analyses were adjusted for age, parity, height, body mass index, smoking, and employment status. ResultsWomen with a body mass index >40kg/m(2) had the highest odds for large negative discrepancies (-9 to -20days) [odds ratio (OR) 2.16, 95% CI 2.01-2.33]. Other factors associated with large negative discrepancies were: diabetes, young maternal age, multiparity, body mass index between 30 and 39.9kg/m(2) or <18.5kg/m(2), a history of gestational diabetes, female fetus, shorter stature (<-1SD), a history of preeclampsia, smoking or snuff use, and unemployment. Large positive discrepancies (+4 to +20days) were associated with male fetus (OR 1.80, 95% CI 1.77-1.83), age 30years, multiparity, not living with a partner, taller stature (>+1 SD), and unemployment. ConclusionsSeveral maternal and fetal characteristics were associated with discrepancies between dating methods. Systematic associations of discrepancies with maternal height, fetal sex, and partly obesity, may reflect an influence on the precision of the ultrasound estimate due to variance in early growth.

    Keywords
    Pregnancy dating, pregnancy, gestational age, ultrasonography, prenatal, menstruation, female, humans
    National Category
    Obstetrics, Gynecology and Reproductive Medicine
    Identifiers
    urn:nbn:se:uu:diva-315826 (URN)10.1111/aogs.13034 (DOI)000391980100011 ()27696340 (PubMedID)
    Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2018-03-15Bibliographically approved
    2. Effects of ultrasound pregnancy dating on neonatal morbidity in late preterm and early term male infants: a register-based cohort study
    Open this publication in new window or tab >>Effects of ultrasound pregnancy dating on neonatal morbidity in late preterm and early term male infants: a register-based cohort study
    2016 (English)In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 16, article id 335Article in journal (Refereed) Published
    Abstract [en]

    Background: Assessing gestational age by ultrasound can introduce a systematic bias due to sex differences in early growth. Methods: This cohort study included data on 1,314,602 births recorded in the Swedish Medical Birth Register. We compared rates of prematurity-related adverse outcomes in male infants born early term (gestational week 37-38) or late preterm (gestational week 35-36), in relation to female infants, between a time period when pregnancy dating was based on the last menstrual period (1973-1978), and a time period when ultrasound was used for pregnancy dating (1995-2010), in order to assess the method's influence on outcome by fetal sex. Results: As expected, adverse outcomes were lower in the later time period, but the reduction in prematurity-related morbidity was less marked for male than for female infants. After changing the pregnancy dating method, male infants born early term had, in relation to female infants, higher odds for pneumothorax (Cohort ratio [CR] 2. 05; 95 % confidence interval [CI] 1.33-3.16), respiratory distress syndrome of the newborn (CR 1.99; 95 % CI 1.33-2. 98), low Apgar score (CR 1.26; 5 % CI 1.08-1.47), and hyperbilirubinemia (CR 1.12; 95 % CI 1.06-1.19), when outcome was compared between the two time periods. A similar trend was seen for late preterm male infants. Conclusion: Misclassification of gestational age by ultrasound, due to size differences, can partially explain currently reported sex differences in early term and late preterm infants' adverse neonatal outcomes, and should be taken into account in clinical decisions and when interpreting study results related to fetal sex.

    Keywords
    Pregnancy dating, Ultrasound, Gestational age, Antenatal, Infant, Morbidity
    National Category
    Obstetrics, Gynecology and Reproductive Medicine
    Identifiers
    urn:nbn:se:uu:diva-308914 (URN)10.1186/s12884-016-1129-z (DOI)000386858200001 ()27799069 (PubMedID)
    Funder
    The Karolinska Institutet's Research Foundation
    Available from: 2016-12-01 Created: 2016-12-01 Last updated: 2018-03-15Bibliographically approved
    3. Adherence to Swedish national pregnancy dating guidelines and management of discrepancies between pregnancy dating methods: a survey study
    Open this publication in new window or tab >>Adherence to Swedish national pregnancy dating guidelines and management of discrepancies between pregnancy dating methods: a survey study
    2019 (English)In: Reproductive Health, ISSN 1742-4755, E-ISSN 1742-4755, Vol. 16, article id 95Article in journal (Refereed) Published
    Abstract [en]

    Background. Swedish national guidelines for pregnancy dating were published in 2010. Follow-up is needed to assess adherence and to identify whether any clinical topics are not covered in the guidelines.

    Methods. All units in Sweden that performed ultrasound-based pregnancy dating were asked to complete a web-based questionnaire comprising multiple-response questions and commentary fields. Information was collected regarding baseline information, current and previous clinical practice, and management of discrepancies between last-menstrual-period- and ultrasound-based methods for pregnancy dating.

    Results. The response rate was 88% (38/43 units). Half of the units offered first-trimester ultrasound to all pregnant women. However, contrary to the guidelines, the crown–rump length was not used for ultrasound-based pregnancy dating in most units. Ultrasound-based pregnancy dating was performed only if the biparietal diameter was between 21 and 55 mm. The methods for management of discrepancies between methods for pregnancy dating varied widely.

    Conclusions. The units reported high adherence to national guidelines, except for early pregnancy dating, for which many units followed unwritten or informal guidelines. The management of discrepancies between last-menstrual-period-based and ultrasound-based estimated day of delivery varied widely. These findings emphasize the need for regular updating of national written guidelines and efforts to improve their implementation in all units.

    National Category
    Obstetrics, Gynecology and Reproductive Medicine
    Identifiers
    urn:nbn:se:uu:diva-345956 (URN)10.1186/s12978-019-0760-3 (DOI)000474617600001 ()31272510 (PubMedID)
    Projects
    Discrepancy between pregnancy dating methods – correlates and outcomes
    Available from: 2018-03-13 Created: 2018-03-13 Last updated: 2019-08-21Bibliographically approved
    4. Discrepancy between pregnancy dating methods affects obstetric and neonatal outcomes: a population-based register cohort study
    Open this publication in new window or tab >>Discrepancy between pregnancy dating methods affects obstetric and neonatal outcomes: a population-based register cohort study
    2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 6936Article in journal (Refereed) Published
    Abstract [en]

    To assess associations between discrepancy of pregnancy dating methods and adverse pregnancy, delivery, and neonatal outcomes, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for discrepancy categories among all singleton births from the Medical Birth Register (1995–2010) with estimated date of delivery (EDD) by last menstrual period (LMP) minus EDD by ultrasound (US) -20 to +20 days. Negative/positive discrepancy was a fetus smaller/larger than expected when dated by US (EDD postponed/changed to an earlier date). Large discrepancy was <10th or >90th percentile. Reference was median discrepancy ± 2 days. Odds for diabetes and preeclampsia were higher in pregnancies with negative discrepancy, and for most delivery outcomes in case of large positive discrepancy (+9 to +20 days): shoulder dystocia [OR 1.16 (95% CI 1.01–1.33)] and sphincter injuries [OR 1.13 (95% CI 1.09–1.17)]. Odds for adverse neonatal outcomes were higher in large negative discrepancy (–4 to –20 days): low Apgar score [OR 1.18 (95% CI 1.09–1.27)], asphyxia [OR 1.18 (95% CI 1.11–1.25)], fetal death [OR 1.47 (95% CI 1.32–1.64)], and neonatal death [OR 2.19 (95% CI 1.91–2.50)]. In conclusion, especially, large negative discrepancy was associated with increased risks of adverse perinatal outcomes. 

    National Category
    Obstetrics, Gynecology and Reproductive Medicine
    Identifiers
    urn:nbn:se:uu:diva-345955 (URN)10.1038/s41598-018-24894-y (DOI)000431204500016 ()29720591 (PubMedID)
    Projects
    Discrepancy between pregnancy dating methods – correlates and outcomes
    Available from: 2018-03-13 Created: 2018-03-13 Last updated: 2018-07-25Bibliographically approved
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  • 2.
    Kullinger, Merit
    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), Obstetrics and Reproductive Health Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Granfors, Michaela
    Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Kieler, Helle
    Department of Medicine, Solna; Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden.
    Skalkidou, Alkistis
    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), Obstetrics and Reproductive Health Research.
    Adherence to Swedish national pregnancy dating guidelines and management of discrepancies between pregnancy dating methods: a survey study2019In: Reproductive Health, ISSN 1742-4755, E-ISSN 1742-4755, Vol. 16, article id 95Article in journal (Refereed)
    Abstract [en]

    Background. Swedish national guidelines for pregnancy dating were published in 2010. Follow-up is needed to assess adherence and to identify whether any clinical topics are not covered in the guidelines.

    Methods. All units in Sweden that performed ultrasound-based pregnancy dating were asked to complete a web-based questionnaire comprising multiple-response questions and commentary fields. Information was collected regarding baseline information, current and previous clinical practice, and management of discrepancies between last-menstrual-period- and ultrasound-based methods for pregnancy dating.

    Results. The response rate was 88% (38/43 units). Half of the units offered first-trimester ultrasound to all pregnant women. However, contrary to the guidelines, the crown–rump length was not used for ultrasound-based pregnancy dating in most units. Ultrasound-based pregnancy dating was performed only if the biparietal diameter was between 21 and 55 mm. The methods for management of discrepancies between methods for pregnancy dating varied widely.

    Conclusions. The units reported high adherence to national guidelines, except for early pregnancy dating, for which many units followed unwritten or informal guidelines. The management of discrepancies between last-menstrual-period-based and ultrasound-based estimated day of delivery varied widely. These findings emphasize the need for regular updating of national written guidelines and efforts to improve their implementation in all units.

    Download full text (pdf)
    fulltext
  • 3.
    Kullinger, Merit
    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). Region Västmanland – Uppsala University, Center for Clinical Research, Hospital of Västmanland Västerås, Sweden.
    Granfors, Michaela
    Department of Clinical Science, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Kieler, Helle
    Skalkidou, Alkistis
    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), Obstetrics and Reproductive Health Research.
    Discrepancy between pregnancy dating methods affects obstetric and neonatal outcomes: a population-based register cohort study2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 6936Article in journal (Refereed)
    Abstract [en]

    To assess associations between discrepancy of pregnancy dating methods and adverse pregnancy, delivery, and neonatal outcomes, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for discrepancy categories among all singleton births from the Medical Birth Register (1995–2010) with estimated date of delivery (EDD) by last menstrual period (LMP) minus EDD by ultrasound (US) -20 to +20 days. Negative/positive discrepancy was a fetus smaller/larger than expected when dated by US (EDD postponed/changed to an earlier date). Large discrepancy was <10th or >90th percentile. Reference was median discrepancy ± 2 days. Odds for diabetes and preeclampsia were higher in pregnancies with negative discrepancy, and for most delivery outcomes in case of large positive discrepancy (+9 to +20 days): shoulder dystocia [OR 1.16 (95% CI 1.01–1.33)] and sphincter injuries [OR 1.13 (95% CI 1.09–1.17)]. Odds for adverse neonatal outcomes were higher in large negative discrepancy (–4 to –20 days): low Apgar score [OR 1.18 (95% CI 1.09–1.27)], asphyxia [OR 1.18 (95% CI 1.11–1.25)], fetal death [OR 1.47 (95% CI 1.32–1.64)], and neonatal death [OR 2.19 (95% CI 1.91–2.50)]. In conclusion, especially, large negative discrepancy was associated with increased risks of adverse perinatal outcomes. 

    Download full text (pdf)
    fulltext
  • 4.
    Kullinger, Merit
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Vastmanland Cty Hosp, Clin Res Ctr, Vasteras, Sweden.;Vastmanland Cty Hosp, Dept Obstet & Gynecol, Vasteras, Sweden..
    Haglund, Bengt
    Karolinska Inst, Ctr Pharmacoepidemiol CPE, Dept Med, Stockholm, Sweden..
    Kieler, Helle
    Karolinska Inst, Ctr Pharmacoepidemiol CPE, Dept Med, Stockholm, Sweden..
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Effects of ultrasound pregnancy dating on neonatal morbidity in late preterm and early term male infants: a register-based cohort study2016In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 16, article id 335Article in journal (Refereed)
    Abstract [en]

    Background: Assessing gestational age by ultrasound can introduce a systematic bias due to sex differences in early growth. Methods: This cohort study included data on 1,314,602 births recorded in the Swedish Medical Birth Register. We compared rates of prematurity-related adverse outcomes in male infants born early term (gestational week 37-38) or late preterm (gestational week 35-36), in relation to female infants, between a time period when pregnancy dating was based on the last menstrual period (1973-1978), and a time period when ultrasound was used for pregnancy dating (1995-2010), in order to assess the method's influence on outcome by fetal sex. Results: As expected, adverse outcomes were lower in the later time period, but the reduction in prematurity-related morbidity was less marked for male than for female infants. After changing the pregnancy dating method, male infants born early term had, in relation to female infants, higher odds for pneumothorax (Cohort ratio [CR] 2. 05; 95 % confidence interval [CI] 1.33-3.16), respiratory distress syndrome of the newborn (CR 1.99; 95 % CI 1.33-2. 98), low Apgar score (CR 1.26; 5 % CI 1.08-1.47), and hyperbilirubinemia (CR 1.12; 95 % CI 1.06-1.19), when outcome was compared between the two time periods. A similar trend was seen for late preterm male infants. Conclusion: Misclassification of gestational age by ultrasound, due to size differences, can partially explain currently reported sex differences in early term and late preterm infants' adverse neonatal outcomes, and should be taken into account in clinical decisions and when interpreting study results related to fetal sex.

    Download full text (pdf)
    fulltext
  • 5.
    Kullinger, Merit
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Vastmanland Cty Hosp, Clin Res Ctr, Vasteras, Sweden..
    Wesström, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Ctr Clin Res Dalarna, Falun, Sweden..
    Kieler, Helle
    Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Maternal and fetal characteristics affect discrepancies between pregnancy-dating methods: a population-based cross-sectional register study2017In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 96, no 1, p. 86-95Article in journal (Refereed)
    Abstract [en]

    IntroductionGestational age is estimated by ultrasound using fetal size as a proxy for age, although variance in early growth affects reliability. The aim of this study was to identify characteristics associated with discrepancies between last menstrual period-based (EDD-LMP) and ultrasound-based (EDD-US) estimated delivery dates. Material and methodsWe identified all singleton births (n=1201679) recorded in the Swedish Medical Birth Register in 1995-2010, to assess the association between maternal/fetal characteristics and large negative and large positive discrepancies (EDD-LMP earlier than EDD-US and 10th percentile in the discrepancy distribution vs. EDD-LMP later than EDD-US and 90th percentile). Analyses were adjusted for age, parity, height, body mass index, smoking, and employment status. ResultsWomen with a body mass index >40kg/m(2) had the highest odds for large negative discrepancies (-9 to -20days) [odds ratio (OR) 2.16, 95% CI 2.01-2.33]. Other factors associated with large negative discrepancies were: diabetes, young maternal age, multiparity, body mass index between 30 and 39.9kg/m(2) or <18.5kg/m(2), a history of gestational diabetes, female fetus, shorter stature (<-1SD), a history of preeclampsia, smoking or snuff use, and unemployment. Large positive discrepancies (+4 to +20days) were associated with male fetus (OR 1.80, 95% CI 1.77-1.83), age 30years, multiparity, not living with a partner, taller stature (>+1 SD), and unemployment. ConclusionsSeveral maternal and fetal characteristics were associated with discrepancies between dating methods. Systematic associations of discrepancies with maternal height, fetal sex, and partly obesity, may reflect an influence on the precision of the ultrasound estimate due to variance in early growth.

    Download full text (pdf)
    fulltext
  • 6.
    Skalkidou, Alkistis
    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), Obstetrics and Reproductive Health Research.
    Kullinger, Merit
    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), Obstetrics and Reproductive Health Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Georgakis, Marios K.
    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), Obstetrics and Reproductive Health Research.
    Kieler, Helle
    Karolinska Inst, Ctr Pharmacoepidemiol, Dept Med, Solna, Sweden.
    Kesmodel, Ulrik S.
    Univ Copenhagen, Herlev Univ Hosp, Dept Obstet & Gynecol, Herlev, Denmark.
    Systematic misclassification of gestational age by ultrasound biometry: implications for clinical practice and research methodology in the Nordic countries2018In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 97, no 4, p. 440-444Article in journal (Other academic)
    Abstract [en]

    Historically, pregnancy dating has been based on self-reported information on the first day of the last menstrual period. In the 1970s, ultrasound biometry was introduced as an alternative for pregnancy dating and is now the leading method in Nordic countries. The use of ultrasound led to a reduction of post-term births and fewer inductions, and is considered more precise than last menstrual period-based methods for pregnancy dating. Nevertheless, differences in early growth and specific situations, such as maternal obesity, can render its estimates less precise, leading to gestational age misclassification. Clinical implications of ultrasound dating include effect on timely induction in case of post-term pregnancies, treatment with corticosteroids in cases of anticipated preterm delivery and decision on viability in cases of extreme prematurity. Furthermore, gestational age misclassification may influence the numbers and the magnitude of some adverse perinatal outcomes, closely related to gestational age, which are recorded in the Nordic birth registers.

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