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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.

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 Preeclampsia in a first pregnancy is a strong risk factor for preeclampsia in a second pregnancy. Whether chronic hypertension developed after a first pregnancy (interpregnancy hypertension) affects the recurrence risk of preeclampsia is unknown. METHODS This is a population-based cohort study of 391,645 women with their first and second singleton births between 2006 and 2017. Exposure groups were women with preeclampsia in their first pregnancy, interpregnancy hypertension, or both risk factors. Women with neither risk factor were used as a reference group. We calculated the adjusted relative risk (aRR) with 95% confidence intervals (CIs) for overall preeclampsia in the second pregnancy as well as preterm (<37 gestational weeks) and term (>= 37 gestational weeks) subgroups of the disease. RESULTS Women with preeclampsia in their first pregnancy who did or did not develop interpregnancy hypertension had rates of preeclampsia in their second pregnancy of 21.5% and 13.6%, respectively. In the same population, the corresponding rates of preterm preeclampsia were 5.5% and 2.6%, respectively. After adjusting for maternal factors, women with preeclampsia in their first pregnancy who developed interpregnancy hypertension and those who did not have almost the same risk of overall preeclampsia in their second pregnancy (aRRs with 95% CIs: 14.51; 11.77-17.89 and 12.83; 12.09-13.62, respectively). However, preeclampsia in the first pregnancy and interpregnancy hypertension had a synergistic interaction on the outcome of preterm preeclampsia (aRR with 95% CI 26.66; 17.44-40.80). CONCLUSIONS Women with previous preeclampsia who developed interpregnancy hypertension had a very high rate of preterm preeclampsia in a second pregnancy, and the two risk factors had a synergistic interaction.

Objective: To investigate fetal growth trajectories and risks of small and large for gestational age (SGA and LGA), and macrosomia in pregnancies after fresh and frozen embryo transfer (ET), and natural conception (NC).

Design: Longitudinal population-based cohort study.

Setting: Swedish national registers.

Population: A total of 196 008 singleton pregnancies between 2013 and 2017.

Methods: Of all singleton pregnancies resulting in live births in the Swedish Pregnancy Register, 10 970 fresh ET, 6520 frozen ET, and 178 518 NC pregnancies with ultrasound data were included. A general least squares model was used to examine the effect of fresh or frozen ET on fetal growth while adjusting for confounders.

Main Outcome: MeasuresFetal growth velocity. SGA, LGA and macrosomia.

Results: At 120 days, fetal weights were lower in fresh ET pregnancies compared with NC pregnancies. Thereafter fresh ET as well as FET fetuses had higher fetal weights than NC fetuses, with no differences between themselves until the second trimester. From 210 days, FET fetuses were heavier than fresh ET fetuses, whereas fresh ET fetuses had lower fetal weights than NC fetuses from 245 days. After fresh ET, SGA was more frequent, whereas LGA and macrosomia were less frequent, than after FET.

Conclusions: This study gives new insights into the differences in fetal growth dynamics between fresh and frozen ET and NC pregnancies. Clinically relevant differences in proportions of SGA, LGA and macrosomia were observed.

Objective Preterm birth (PTB, birth before 37 gestational weeks) is the leading cause of neonatal death and a major challenge for obstetric and neonatal care. About two-thirds of PTBs are spontaneous PTB (sPTB), of which approximately 30% start with preterm premature rupture of membranes (PPROM). The aim of the study was to investigate risk factors and maternal and perinatal outcomes in sPTB with and without PPROM.

Study Design This is a national population-based cohort study including all singleton pregnancies in nulliparous women with spontaneous onset of labor and vaginal births (n = 266,968) registered in the Swedish Medical Birth Register 2005 to 2014. sPTB with PPROM (sPTB-PPROM) and sPTB without PPROM were compared regarding risk factors and maternal and perinatal outcomes. Logistic regression was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Adjustments were made for maternal age, body mass index, country of birth, smoking, chronic hypertension, pregestational and gestational diabetes, and gestational length.

Results sPTB-PPROM (n = 5,037), compared with sPTB without PPROM (n = 8,426), was more common in women with previous spontaneous abortions, prepregnancy urinary tract infections, chronic hypertension, and gestational diabetes and had a higher risk of postpartum endometritis (aOR: 2.78, 95% CI: 1.55–5.00). Infants born to women with sPTB-PPROM had a lower risk of birth asphyxia (aOR: 0.60, 95% CI: 0.43–0.83), respiratory distress syndrome (aOR: 0.86, 95% CI: 0.70–1.00), retinopathy of prematurity (aOR: 0.93, 95% CI: 0.92–0.94), necrotizing enterocolitis (aOR: 0.95, 95% CI: 0.94–0.96), and higher risk of hypoglycemia (aOR: 1.14, 95% CI: 1.01–1.28), and hyperbilirubinemia (aOR: 1.28, 95% CI: 1.19–1.38) compared with infants born to sPTB without PPROM.

Conclusion Our findings of risk factors and distinct differences in adverse outcomes after sPTB-PPROM compared with sPTB without PPROM are of vital importance and might serve as a basis when elaborating programs for the prevention and management of PPROM.

IntroductionChildhood obesity is associated with maternal obesity, but the link to gestational weight gain (GWG) is not fully elucidated. We examined the relationship between early pregnancy maternal body mass index (BMI) and GWG on early childhood growth.Material and MethodsData from 30 197 mother-child pairs from Uppsala County Mother and Child Cohort were divided into 15 groups according to maternal BMI and GWG, based on World Health Organization classification and Institute of Medicine guidelines, respectively. Postnatal growth patterns were analyzed with linear mixed regression models within maternal BMI groups. Odds ratios of overweight and obesity at 4 years of age were assessed with logistic regression analyses. We treated children of mothers with normal weight and adequate GWG as the reference group, and all analyses were adjusted for potential confounders.ResultsGWG was associated with infant BMI z-score at birth, independent of potential confounding factors. Independent of GWG, we observed an overall decrease in BMI z-score from 18 months to 5 years in children of mothers who were underweight, while an increase in BMI z-score was seen in children of mothers who were overweight or obese. In children of normal- and overweight mothers, the risk of childhood overweight and obesity was associated with excessive compared to adequate GWG (adjusted odds ratio [aOR] 1.17, 95% confidence interval [CI] 1.01-1.36 for normal-weight mothers, and aOR 1.25, 95% CI 1.04-1.51 for overweight mothers, respectively). Children of mothers with obesity and excessive GWG had the highest risk of being overweight or obese at 4 years (aOR 2.88, 95% CI 2.40-3.44, and 4.38, 95% CI 3.37-5.67, respectively). Associations did not differ between children of mothers with obesity class 1 and 2-3 when comparing excessive and adequate GWG (aOR 1.33, 95% CI 0.96-1.85, and 1.12, 95% CI 0.74-1.70, respectively).ConclusionsMaternal GWG affects infant birth size and growth until 18 months, although maternal BMI is more crucial for childhood growth beyond 18 months. Further, children of mothers who are normal- or overweight and experience excessive GWG have an increased risk of obesity at 4 years. Maternal gestational weight gain (GWG) affects growth patterns in early childhood. Excessive GWG increases the risk of overweight and obesity in children of mothers with normal weight and overweight, while children of mothers with obesity are at increased risk of childhood overweight and obesity independent of GWG.image

Introduction: Fetal growth assessment by ultrasound is an essential part of modern obstetric care. The formula by Persson and Weldner for estimated fetal weight (EFW), used in Sweden since decades, has not yet been evaluated. The objective of this study was to evaluate accuracy and precision of the formula by Persson and Weldner, and to compare it to two other formulae using biparietal diameter instead of head circumference.

Material and methods: The study population consisted of 31 521 singleton pregnancies delivered at 22+0 gestational weeks or later, with an ultrasound EFW performed within 2 days before delivery, registered in the Swedish Pregnancy Register between 2014 and 2021. Fetal biometric ultrasound measurements were used to calculate EFW according to the formulae by Persson and Weldner, Hadlock 2 and Shepard. Bland–Altman analysis, systematic error (mean percentage error), random error (standard deviation [SD] of mean percentage error), proportion of weight estimates within ±10% of birthweight, and proportion with underestimated and overestimated weight was calculated. Moreover, calculations were made after stratification into small, appropriate, and large for gestational age (SGA, AGA and LGA), respectively, and gestational age at examination.

Results: For the formula by Persson and Weldner, MPE was −2.7 (SD 8.9) and the proportion of EFW within ±10% from actual birthweight was 76.0%. MPE was largest for fetuses estimated as severe SGA (<3rd percentile, −5.4) and for the most preterm fetuses (<24 weeks, −5.4). For Hadlock 2 and Shepard's formulae, MPE were 3.9 (SD 8.9) and 3.4 (SD 9.7), respectively, and the proportions of EFW within ±10% from actual birthweight were 69.4% and 67.1%, respectively. MPE was largest for fetuses estimated as severe LGA (>97th percentile), 7.6 and 9.4, respectively.

Conclusions: The recommended Swedish formula by Persson and Weldner is generally accurate for fetal weight estimation. The systematic underestimation of EFW and random error is largest in extreme preterm and estimated SGA-fetuses, which is of importance in clinical decision making. The accuracy of EFW with the formula by Persson and Weldner is as good as or better than Hadlock 2 and Shepard's formulae.

Objective: To explore whether the association between polycystic ovary syndrome (PCOS) and pre-eclampsia depends on treated clinical hyperandrogenism and whether PCOS is associated with different subtypes of pre-eclampsia.

Design: Nationwide register-based cohort study.

Setting: Sweden.

Population: Nulliparous women with PCOS (n = 22 947) and non-PCOS controls (n = 115 272) giving singleton birth at ≥22 gestational weeks during 1997-2015. Treated clinical hyperandrogenism was defined as filled prescriptions of anti-androgenic drugs during 2005-2017 (n = 2301 among PCOS women).

Methods: The risk of pre-eclampsia was estimated with conditional logistic regression, expressed as adjusted odds ratio (OR) with 95% confidence interval (CI). Adjustments were performed individually for confounders and predictors.

Main outcome measures: Overall pre-eclampsia. Early/late (delivery <34/≥34 weeks) pre-eclampsia. Pre-eclampsia with or without a small-for-gestational-age (SGA) infant.

Results: Compared with controls, women with PCOS had a 29% increased risk of pre-eclampsia (predictor adjusted OR 1.29, 95% CI 1.20-1.39), with similar risk estimates for PCOS women with and without treated clinical hyperandrogenism. The association between PCOS and early pre-eclampsia seemed stronger than its association with late pre-eclampsia (predictor adjusted OR 1.64 (95% CI 1.33-2.02) and 1.26 (95% CI 1.17-1.37). Additionally, the association seemed slightly stronger between PCOS and pre-eclampsia in women with an SGA infant than without.

Conclusions: Women with PCOS face an increased risk for pre-eclampsia, especially early pre-eclampsia and pre-eclampsia with an SGA infant. We were unable to determine on the basis of available data, whether hyperandrogenism is associated with pre-eclampsia.

The objective of this study was to evaluate the relationship between random capillary glucose levels in healthy pregnant women and infant size at birth and childhood growth to the age of five years. This population-based cohort study comprised 10,937 healthy mother-child dyads. Data on highest maternal random capillary glucose level during pregnancy and sequential anthropometric data on their children during the first five years of life were gathered from the Uppsala County Mother and Child Cohort. Statistical analyses were performed with linear regression and linear mixed effect regression models. We found that higher glucose level during pregnancy was associated with higher weight z-score (beta 0.10, 95% confidence interval (CI) 0.08-0.11), length z-score (beta 0.05, 95% CI 0.03-0.07) and BMI z-score (beta 0.09, 95% CI 0.07-0.12) at birth, adjusted for maternal BMI and country of birth, smoking during pregnancy and parity. The association did not remain at 11/2, 3, 4 and 5 years of age. There was a positive relationship between higher glucose level during pregnancy and a decrease in weight z-score, height z-score and BMI z-score from birth to 5 years of age. In conclusion, higher random capillary glucose levels in pregnant healthy women were associated with greater infant size at birth, as well as decreased growth velocity in early childhood.