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Background: Monitoring labor and childbirth, early recognition, and treatment of complications are critical for preventing adverse birth outcomes. However excessive use of interventions during labor has not been demonstrated to enhance subsequent birth outcomes and may, in fact, pose a risk of harm. The World Health Organization has recently synthesized research from the last decade concerning labor progress and patient-centered care into a new recommendation: the Labour Care Guide (LCG). No trial has, however, compared the LCG with standard care regarding adverse neonatal outcomes or the degree of safety associated with implementing this recommendation within a high-resource setting, and its potential to enhance birth outcomes remains undetermined.

Aim and hypothesis: This trial aims to evaluate the impacts of using two different guidelines for monitoring labor with respect to neonatal and maternal outcomes, the LCG and the currently used standard care guideline. The hypothesis is that use of the LCG will reduce the number of adverse neonatal outcomes and decrease the rate of intrapartum cesarean sections, as compared with standard care.

Materials and methods: A national, multicenter, stepped-wedge cluster randomized controlled trial that includes 24 Swedish maternity wards randomized to six clusters. The trial is planned to run during a 22 month period in 2023-2025 and the intervention LCG will be implemented in the six clusters, with three months intervals. The recruited wards will together have approximatively 100,000 births during the study period. Outcome data will be extracted from the Swedish national pregnancy, neonatal, and patient registers. Two safety analyses will be performed at one-third and two-thirds of the way through the trial.

Discussion The LCG offers a promising new approach, but its effectiveness and safety in high resource settings remain unexplored and must be studied further before LCG can be fully implemented in settings with similar health care.Trial registration The trial has been registered at www.clinicaltrials.gov: NCT05560802.

Importance  Gestational hypertension, preeclampsia, and eclampsia are established risk factors for stroke and dementia later in life. Whether these pregnancy complications are associated with an increased risk of new-onset neurological disorders within months to years after giving birth is not known.

Objective  To explore whether gestational hypertension, preeclampsia, and eclampsia are associated with new-onset migraine, headache, epilepsy, sleep disorder, or mental fatigue within months to years after giving birth.

Design, Setting, and Participants  In this register-based cohort study, exposures were identified in the Swedish Medical Birth Register from 2005 to 2018. Follow-up was conducted using the National Patient Register, containing diagnoses from specialized inpatient and outpatient care. Follow-up started 42 days after delivery and continued until the first event, death, emigration, or the end of the follow-up period (2019). The risk was calculated with Cox regression analysis and expressed as adjusted hazard ratio (aHR) with a 95% CI. Through the Swedish Medical Birth Register, 659 188 primiparous women with singleton pregnancies between 2005 and 2018 were identified. Women with a diagnosis of chronic hypertension (n = 4271) or a prepregnancy neurological disorder (n = 6532) were excluded. The final study population included 648 385 women. Data analyses were conducted in 2023.

Exposures  Gestational hypertension, preeclampsia, and eclampsia.

Main outcome  The primary outcome was a composite neurological outcome of migraine, headache, epilepsy, sleep disorder, or mental fatigue.

Results  The study included 648 385 women with a mean age of 28.5 (SD, 5.0) years at the time of their first pregnancy. Women with gestational hypertension (n = 11 133), preeclampsia (n = 26 797), and eclampsia (n = 625) all had an association with increased risk for a new-onset neurological disorder compared with women with normotensive pregnancies. The aHR for gestational hypertension was 1.27 (95% CI, 1.12-1.45), 1.32 (95% CI, 1.22-1.42) for preeclampsia, and 1.70 (95% CI, 1.16-2.50) for eclampsia. When exploring individual outcomes, women with eclampsia were associated with more than a 5 times increased risk of epilepsy (aHR, 5.31; 95% CI, 2.85-9.89).

Conclusion and Relevance  In this study, gestational hypertension, preeclampsia, and eclampsia were associated with an increased risk of new-onset migraine, headache, epilepsy, sleep disorder, or mental fatigue within months to years after giving birth. Guidelines recommend follow-up after delivery for women with gestational hypertension and preeclampsia for their increased risk of cardiovascular disease. At these visits, caregivers should also pay attention to persisting or new-onset of neurological symptoms, since this group of women appears to be vulnerable to developing or experiencing neurological disorders.

Introduction: It is well known that both women with polycystic ovary syndrome (PCOS) and women with gestational diabetes mellitus (GDM) have increased risks of adverse pregnancy outcomes, but little is known whether the combination of these two conditions exacerbate the risk estimates. We explored risk estimates for adverse pregnancy outcomes in women with either PCOS or GDM and the combination of both PCOS and GDM.

Material and methods: Retrospective nationwide register-based cohort study in Sweden including women who gave birth to singleton infants during 1997–2015 (N=281 806).The risk of adverse pregnancy outcomes were estimated for women exposed for PCOS-only (n = 40 272), GDM-only (n = 2236), both PCOS and GDM (n = 1036) using multivariate logistic regression analyses. Risks were expressed as odds ratios with 95% confidence intervals (CIs) and adjusted for maternal characteristics, including maternal BMI. Women with neither PCOS nor GDM served as control group.

Main Outcome Measures: Maternal outcomes were gestational hypertension, preeclampsia, postpartum haemorrhage, and obstetric anal sphincter injury. Neonatal outcomes were preterm birth, stillbirth, shoulder dystocia, born small or large for gestational age, macrosomia, low Apgar score, infant birth trauma, cerebral impact of the infant, neonatal hypoglycaemia, meconium aspiration syndrome and respiratory distress.

Results: Women with both PCOS and GDM have a tendency for higher odds than women with either PCOS or GDM for developing preeclampsia, preterm birth, stillbirth, infant born large for gestational age and infant birth trauma. The adjusted odds ratio for preterm birth in women with PCOS-only were 1.34 (95% CI 1.28–1.41) and GDM-only 1.64 (95% CI 1.39–1.93) and for women with PCOS and GDM 2.08 (95% CI 1.67–2.58).

Conclusions: The combination of PCOS and GDM appears to exacerbate the risk of adverse pregnancy outcomes for both mother and infant compared with women with either PCOS or GDM.

Importance It is unclear whether a higher dose (150-160 mg) or a lower dose (75 mg) of aspirin should be used to prevent preeclampsia. Objectives To compare the risk of preeclampsia and bleeding complications between women using 150 to 160 mg of aspirin and those using 75 mg of aspirin for preeclampsia prevention. Design, Setting, and ParticipantsThis nationwide cohort study included 13 828 women giving birth at 22 weeks' gestation or later in Sweden between January 2017 and December 2020 who used low dose aspirin (75-160 mg) during pregnancy. Data were analyzed from October to November 2023. Exposure The use of 150 to 160 mg or 75 mg of aspirin in pregnancy. Main Outcome and MeasuresThe main outcome was a preeclampsia diagnosis recorded in the maternal birth record at the time of hospital discharge. The main safety outcome was postpartum hemorrhage, defined as bleeding more than 1000 mL after delivery. Relative risks (RRs) and 95% CIs were estimated using a doubly robust inverse probability-weighted regression adjustment model controlling for background characteristics. Results In the total cohort of 13 828 women, the mean (SD) age was 33.0 (5.5) years and 3003 women (21.7%) were nulliparous. Of the women, 4687 (33.9%) were prescribed 150 to 160 mg of aspirin, and 9141 (66.1%) were prescribed 75 mg of aspirin. A total of 10 635 women (76.9%) had at least 2 dispensed prescriptions of low-dose aspirin. Among women using 150 to 160 mg of aspirin, 443 (9.5%) developed preeclampsia compared with 812 (8.9%) of those using 75 mg of aspirin (adjusted RR [aRR], 1.07; 95% CI, 0.93-1.24). Additionally, the risk of postpartum hemorrhage between the groups was similar, with 326 women (6.9%) using 150 to 160 mg of aspirin experiencing a postpartum hemorrhage compared with 581 (6.4%) in the 75-mg group (aRR, 1.08; 95% CI, 0.90-1.30). Conclusions and Relevance In this cohort study of 13 828 women, no difference was found in preeclampsia incidence or bleeding complications between those using 150 to 160 mg of aspirin vs 75 mg of aspirin during pregnancy for preeclampsia prevention. These findings suggest that either dose may be a reasonable choice when using aspirin to prevent preeclampsia. However, large randomized trials investigating aspirin dose in pregnancy are still needed.

Objective: The primary aim of this study was to determine the appropriate gestational age for planned births by elective cesarean section (ECS) or induction of labor (IOL) in relation to no excess risk of neonatal respiratory distress.

Study design: Register-based Swedish cohort study including 575,817 singleton live births at 36 weeks or later. Births not eligible for vaginal delivery, preterm premature rupture of membranes and infants with congenital anomalies were excluded. The primary outcome was respiratory distress, and a secondary outcome was Apgar score <7 at five minutes. The risk of outcomes according to onset of birth was calculated for each day from gestational week 36 to 41 and compared with expectant management (EM), defined as births at least one day later.

Results: No excess risk of respiratory distress was found for ECS from 40 weeks and for IOL from 38 weeks compared with EM. At 37 weeks, the absolute risk of respiratory distress was 12.4 % for ECS (aRR:5.7; 95 % CI:4.8; 6.5) and 4.0% for IOL (aRR:1.7; 95 %CI:1.5; 2.0). At 39 weeks, the absolute risk of respiratory distress for ECS was 3.2 % (aRR:1.6; 95 %CI:1.3; 1.8) whereas the risk was reduced for IOL. ECS <38 weeks increased the risk of Apgar <7 compared with EM.

Conclusion: Regarding neonatal respiratory distress, IOL was safe from 38 weeks and ECS from 40 weeks. At earlier gestational ages, the risk of respiratory distress was significantly higher, which highlights the importance of clear health policies regarding appropriate timing and indications for planned births by ECS and IOL.

Background: Pregnant women often experience subjective sleep disturbances shown to be associated with maternal and fetal outcomes. However, subjectively experienced sleep often deviates from objective measurements. Therefore, the aim of this study was to explore the relationship between objectively measured sleep in early to mid-pregnancy and maternal and fetal outcomes and inflammatory biomarkers.

Methodology: A total of 1,610 pregnant women aged 18 or older from the Safe Physical Activity in Pregnancy (SPAP) study were recruited during early (week 10-14) to mid-pregnancy (week 16-19). Blood samples were taken and sleep was monitored using an Actiwatch, tracking total sleep time, sleep efficiency, wake after sleep onset, and sleep onset latency for 7 days in early to mid-pregnancy. A combined sleep categorisation was created using total sleep time and sleep efficiency to categorise participants into three sleep quality groups: Good, Intermediate, and Poor. Maternal and fetal outcomes were collected via questionnaires, medical records, and plasma samples were analysed using the Olink cardiovascular paneI Il (n = 407).

Results: A total of 1,444 participants were included. The women were categorized as good sleepers (50.4%), intermediate (32.6%), or poor sleepers (17.0%) based on the distribution of the participant's sleep parameters. Poor sleep was more common in women born outside Europe, those with higher pre-gestational BMI, and those with pre-pregnancy diabetes. Sleep groups did not differ in metabolic factors. Poor sleep was associated with an increased likelihood of requiring an emergency caesarean section (AOR = 1.86, 95% CI 1.13-3.05). No significant associations were found for other outcomes such as pre-eclampsia, premature birth, small for gestational age etc. Nine inflammatory biomarkers were significantly lower in poor sleepers, while one marker was higher.

Conclusion: Poor sleep in early to mid-pregnancy was more common in pregnant women with pre-pregnancy diabetes, obesity, and those born outside of Europe. Poor sleep was associated with a higher likelihood of emergency caesarean section, but no other maternal or fetal outcomes. An overall trend was observed towards lower levels of inflammatory markers in women that slept poorly; however, additional studies are needed to better understand the immune system's role in the relationship between sleep, maternal health, and maternal and fetal outcomes. Possible mechanisms underlying these associations warrant further research.

Introduction

Physical activity during pregnancy is beneficial for the woman and the fetus. However, non-objective methods are often used to measure physical activity levels during pregnancy. This study aimed to evaluate objectively measured maternal early to mid-pregnancy sedentary behavior and physical activity in relation to infant well-being.

Material and Methods

This cohort study included 1153 pregnant women and was performed at Uppsala University Hospital, Uppsala, Sweden, between 2016 and 2023. Sedentary behavior and physical activity levels were measured by accelerometers during 4–7 days in early to mid-pregnancy. Outcome measures were infant birthweight standard deviation score, small-for-gestational-age, large-for-gestational-age, preterm birth (<37 weeks' gestation), spontaneous preterm birth, iatrogenic preterm birth, Apgar <7 at 5 min of age, umbilical artery pH ≤7.05, and admission to the neonatal intensive care unit (NICU).

Results

There were no associations of sedentary behavior and physical activity levels with infant birthweight standard deviation score, small-for-gestational-age, or large-for-gestational-age. After adjustment for BMI, age, smoking, parity, maternal country of birth, and a composite of pre-pregnancy disease, the most sedentary women had higher odds of preterm birth (adjusted odds ratio (AOR) 2.47, 95% confidence interval (CI) 1.17–5.24, p = 0.018), and NICU admission (AOR 1.93, CI 1.11–3.37, p = 0.021) than the least sedentary women. The most physically active women had lower adjusted odds for NICU admission (AOR 0.45, CI 0.26–0.80, p = 0.006) than the least physically active women.

Conclusions

Objectively measured levels of sedentary behavior and physical activity in early to mid-pregnancy were not associated with standardized infant birth size. Sedentary behavior was associated with an increased likelihood of preterm birth and NICU admission, while high level of physical activity was associated with a decreased likelihood of admission to NICU.

INTRODUCTION: Women with spontaneous preterm birth have an increased risk of cardiovascular disease later in life. Studies suggest potential pathophysiological mechanisms in common, but whether these could be identified by measurement of soluble circulating protein biomarkers in women with spontaneous preterm birth is unknown. The aim of this study was to determine if protein biomarkers associated with cardiovascular disease distinguish women with spontaneous preterm birth from healthy controls, both at pregnancy and at follow up.

MATERIAL AND METHODS: Study participants were identified in the population-based Uppsala biobank of pregnant women in Sweden, where plasma samples were collected in mid-pregnancy. In a first screening phase, we identified participants who subsequently experienced spontaneous preterm birth (<37 weeks) in the index pregnancy (N = 13) and controls (N = 6). In these samples, differences in protein expression were examined by comparative mass spectrometry. In a second validation phase, we invited 100 cases with previous spontaneous preterm birth in the index pregnancy and 100 controls (matched for age, body mass index, and year of delivery) from the same source population, to a follow-up visit 4-15 years after pregnancy. At follow up, we collected plasma samples and data on cardiovascular risk factors. We measured concentrations of selected biomarkers identified in the screening phase, as well as lipid profiles in samples both from pregnancy (biobank) and follow up.

CLINICALTRIALS: gov registration NCT05693285.

RESULTS: In the screening phase, fibrinogen, cadherin-5, complement C5, factor XII, plasma kallikrein, apolipoprotein M, and vitamin D-binding protein differed significantly at pregnancy. In the validation phase, 65 women agreed to participate (35 cases and 30 controls), with a median follow-up time of 11.8 years since pregnancy. The concentration of fibrinogen (p = 0.02) and triglycerides (p = 0.03) were slightly higher in cases compared with matched controls at follow up.

CONCLUSIONS: Compared with women without preterm birth, those with spontaneous preterm birth had slightly higher concentrations of fibrinogen, both at mid-pregnancy and a decade after pregnancy. Additionally, we found slightly higher concentration of triglycerides at follow up in women with previous spontaneous preterm birth. The relevance of this finding is uncertain but might indicate potential pathophysiological mechanisms in common between spontaneous preterm birth and cardiovascular disease.

Background

The number of pregnant women with congenital heart disease (CHD) is rising, and the disease poses increased risks of cardiovascular and obstetric complications during pregnancy, potentially impacting breastfeeding success. This study aimed to investigate breastfeeding in primiparous women with CHD compared to primiparous women without CHD, and to examine potential hindering factors for breastfeeding in women with CHD.

Methods

The data were gathered between 2014 and 2019 and obtained by merging the Swedish Congenital Heart Disease Register (SWEDCON) with the Swedish Pregnancy Register. Primiparous women ≥ 18 years of age with CHD (n = 578) were matched by age and municipality to 3049 women without CHD, giving birth after 22 gestational weeks. Multivariable logistic regression analysis was used to identify factors associated with non-breastfeeding in women with CHD.

Results

Fewer women with CHD breastfed than women without CHD two days (94% vs. 97%, p = 0.001) and four weeks after birth (84% vs. 89%, p = 0.006). When all women were analysed, having CHD was associated with non-breastfeeding at both two days and four weeks after birth. For women with CHD, body mass index (BMI) ≥ 30 (OR 3.1; 95% CI 1.4, 7.3), preterm birth (OR 6.4; 95% CI 2.1, 19.0), self-reported history of psychiatric illness (OR 2.4; 95% CI 1.2, 5.1), small for gestational age (OR 4.2; 95% CI 1.4, 12.2), and New York Heart Association Stages of Heart Failure class II − III (OR 6.0; 95% CI 1.4, 26.7) were associated with non-breastfeeding two days after birth. Four weeks after birth, factors associated with non-breastfeeding were BMI ≥ 30 (OR 4.3; 95% CI 2.1, 9.0), self-reported history of psychiatric illness (OR 2.2; 95% CI 1.2, 4.2), and preterm birth (OR 8.9; 95% CI 2.8, 27.9).

Conclusions

The study shows that most women with CHD breastfeed, however, at a slightly lower proportion compared to women without CHD. In addition, factors related to the heart disease were not associated with non-breastfeeding four weeks after birth. Since preterm birth, BMI ≥ 30, and psychiatric illness are associated with non-breastfeeding, healthcare professionals should provide greater support to women with CHD having these conditions.

Background

The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes.

Methods and findings

A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis.

After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables.

In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26).

In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations.

Conclusions

In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women's and children's health in the short and long term.

Trial registration

The trial is registered with ISRCTN (41918550).