Safety of low weight gain or weight loss in pregnancies with class 1, 2, and 3 obesity: a population-based cohort study.

BACKGROUND: There are concerns that current gestational weight gain recommendations for women with obesity are too high and that guidelines should differ on the basis of severity of obesity. In this study we investigated the safety of gestational weight gain below current recommendations or weight loss in pregnancies with obesity, and evaluated whether separate guidelines are needed for different obesity classes. METHODS: In this population-based cohort study, we used electronic medical records from the Stockholm-Gotland Perinatal Cohort study to identify pregnancies with obesity (early pregnancy BMI before 14 weeks' gestation ≥30 kg/m2) among singleton pregnancies that delivered between Jan 1, 2008, and Dec 31, 2015. The pregnancy records were linked with Swedish national health-care register data up to Dec 31, 2019. Gestational weight gain was calculated as the last measured weight before or at delivery minus early pregnancy weight (at <14 weeks' gestation), and standardised for gestational age into z-scores. We used Poisson regression to assess the association of gestational weight gain z-score with a composite outcome of: stillbirth, infant death, large for gestational age and small for gestational age at birth, preterm birth, unplanned caesarean delivery, gestational diabetes, pre-eclampsia, excess postpartum weight retention, and new-onset longer-term maternal cardiometabolic disease after pregnancy, weighted to account for event severity. We calculated rate ratios (RRs) for our composite adverse outcome along the weight gain z-score continuum, compared with a reference of the current lower limit for gestational weight gain recommended by the US Institute of Medicine (IOM; 5 kg at term). RRs were adjusted for confounding factors (maternal age, height, parity, early pregnancy BMI, early pregnancy smoking status, prepregnancy cardiovascular disease or diabetes, education, cohabitation status, and Nordic country of birth). FINDINGS: Our cohort comprised 15 760 pregnancies with obesity, followed up for a median of 7·9 years (IQR 5·8-9·4). 11 667 (74·0%) pregnancies had class 1 obesity, 3160 (20·1%) had class 2 obesity, and 933 (5·9%) had class 3 obesity. Among these pregnancies, 1623 (13·9%), 786 (24·9%), and 310 (33·2%), respectively, had weight gain during pregnancy below the lower limit of the IOM recommendation (5 kg). In pregnancies with class 1 or 2 obesity, gestational weight gain values below the lower limit of the IOM recommendation or weight loss did not increase risk of the adverse composite outcome (eg, at weight gain z-score -2·4, corresponding to 0 kg at 40 weeks: adjusted RR 0·97 [95% CI 0·89-1·06] in obesity class 1 and 0·96 [0·86-1·08] in obesity class 2). In pregnancies with class 3 obesity, weight gain values below the IOM limit or weight loss were associated with reduced risk of the adverse composite outcome (eg, adjusted RR 0·81 [0·71-0·89] at weight gain z-score -2·4, or 0 kg). INTERPRETATION: Our findings support calls to lower or remove the lower limit of current IOM recommendations for pregnant women with obesity, and suggest that separate guidelines for class 3 obesity might be warranted. FUNDING: Karolinska Institutet and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Histologic Remission in Inflammatory Bowel Disease and Female Fertility: A Nationwide Study.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is linked to reduced female fertility, but it is unclear how fertility rates vary by histologic disease activity. METHODS: Nationwide IBD cohort of Swedish women aged 15 to 44 years. We examined fertility rates during periods with vs without histologic inflammation (n = 21,046; follow-up, 1990-2016) and during periods with vs without clinical activity (IBD-related hospitalization, surgery, or treatment escalation) (n = 24,995; follow-up, 2006-2020). Accounting for sociodemographics and comorbidities, we used Poisson regression to estimate adjusted fertility rate ratios (aFRRs) for live births conceived during 12-month periods of histologic inflammation (vs histologic remission) and 3-month periods of clinically active IBD (vs quiescent IBD). RESULTS: During periods with vs without histologic inflammation, there were 6.35 (95% confidence interval [CI], 5.98-6.73) and 7.09 (95% CI, 6.48-7.70) live births conceived per 100 person-years of follow-up, respectively, or 1 fewer child per 14 women with 10 years of histologic inflammation (aFRR, 0.90; 95% CI, 0.81-1.00). In women with histologic inflammation, fertility was similarly reduced in ulcerative colitis (UC) (aFRR, 0.89 [95% CI, 0.78-1.02]) and Crohn's disease (CD) (aFRR, 0.86 [95% CI, 0.72-1.04]). Clinical IBD activity was associated with an aFRR of 0.76 (95% CI, 0.72-0.79) or 1 fewer child per 6 women with 10 years of clinical activity. Fertility was reduced in clinically active UC (aFRR, 0.75 [95% CI, 0.70-0.81]) and CD (aFRR, 0.76 [95% CI, 0.70-0.82]). Finally, among women with clinically quiescent IBD, histologic inflammation (vs histologic remission) was associated with reduced fertility (aFRR, 0.85 [95% CI, 0.73-0.98]). CONCLUSIONS: An association between histologic and clinical activity and reduced female fertility in CD and UC was found. Notably, histologic inflammation was also linked to reduced fertility in women with clinically quiescent IBD.

Maternal intrahepatic cholestasis of pregnancy and neurodevelopmental conditions in offspring: A population-based cohort study of 2 million Swedish children.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is the most common obstetric liver disorder and is associated with an increased risk of iatrogenic preterm birth and adverse infant outcomes. Hence, there are several plausible pathways through which ICP could affect offspring neurodevelopment. However, to the best of our knowledge, no studies have investigated these associations. Thus, we aimed to determine whether ICP is associated with offspring neurodevelopmental conditions. METHODS AND FINDINGS: In this Swedish register-based cohort study, we included singleton non-adopted children born in Sweden between the 1st of January 1987 and the 31st of December 2010, who were resident in Sweden >5 years, with no missing covariate information, which we followed until the 31st of December 2016. Maternal ICP diagnosis and the date of the initial diagnosis during pregnancy were obtained from the National Patient Register. Offspring diagnoses of attention deficit/hyperactivity disorder (ADHD), autism, or intellectual disability were obtained from the National Patient Register, and the dispensation of ADHD medications were obtained from the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression while controlling for observed confounders and unobserved confounders shared among full siblings and maternal full cousins. A total of 2,375,856 children were included in the study; 81.6% of them were of Nordic origin, and 51.4% were male. Of these, 10,378 (0.44%) were exposed to ICP. During a median of 18 years follow-up (interquartile range 11 to 24), 143,746 (6.05%) of children were diagnosed with a neurodevelopmental condition. After adjusting for child's sex, birth year, birth month, maternal age, highest parental education level, maternal birth country, birth order, maternal psychiatric history, ICP was associated with increased odds of offspring neurodevelopmental conditions (OR 1.22, 95% CI 1.13 to 1.31), particularly among those exposed to early-onset ICP (OR 2.38, 95% CI 1.71 to 3.30) as compared to ICP diagnosed after reaching term (≥37 weeks of gestation) (OR 1.08, 95% CI 0.97 to 1.20). The findings of early-onset ICP were consistent in family-based analyses. Within-family comparisons of full maternal cousins yielded an OR of 2.99 (95% CI 1.48 to 6.04), and comparisons of full siblings showed an OR of 1.92 (95% CI 0.92 to 4.02), though the latter was less precise. The findings were consistent across specific neurodevelopmental conditions and different analytical approaches. The primary limitations of this study included its observational design, the absence of data on ICP therapeutics, and the lack of bile acid measures. CONCLUSIONS: In this study, we observed that exposure to ICP during gestation is associated with an increased likelihood of neurodevelopmental conditions in offspring, particularly in cases of early-onset ICP. Further studies are warranted to better understand the role of early-ICP in offspring neurodevelopment.

Duration of the active first stage of labour and severe perineal lacerations and maternal postpartum complications: a population-based cohort study.

OBJECTIVE: The impact of first stage labour duration on maternal outcomes is sparsely investigated. We aimed to study the association between a longer active first stage and maternal complications in the early postpartum period. DESIGN: A population-based cohort study. SETTING: Regions of Stockholm and Gotland, Sweden, 2008-2020. POPULATION: A cohort of 159 459 term, singleton, vertex pregnancies, stratified by parity groups. METHODS: The exposure was active first stage duration, categorised in percentiles. Poisson regression analysis was performed to estimate the adjusted relative risk (aRR) and the 95% confidence interval (95% CI). To investigate the effect of second stage duration on the outcome, mediation analysis was performed. MAIN OUTCOME MEASURES: Severe perineal lacerations (third or fourth degree), postpartum infection, urinary retention and haematoma in the birth canal or ruptured sutures. RESULTS: The risks of severe perineal laceration, postpartum infection and urinary retention increased with a longer active first stage, both overall and stratified by parity group. The aRR increased with a longer active first stage, using duration of <50th percentile as the reference. In the ≥90th percentile category, the aRR for postpartum infection was 1.64 (95% CI 1.46-1.84) in primiparous women, 2.43 (95% CI 1.98-2.98) in parous women with no previous caesarean delivery (CD) and 2.33 (95% CI 1.65-3.28) in parous women with a previous CD. The proportion mediated by second stage duration was 33.4% to 36.9% for the different outcomes in primiparous women. The risk of haematoma or ruptured sutures did not increased with a longer active first stage. CONCLUSIONS: Increasing active first stage duration is associated with maternal complications in the early postpartum period.

Acetaminophen Use During Pregnancy and Children's Risk of Autism, ADHD, and Intellectual Disability.

Importance: Several studies suggest that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children. If true, this would have substantial implications for management of pain and fever during pregnancy. Objective: To examine the associations of acetaminophen use during pregnancy with children's risk of autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. Design, Setting, and Participants: This nationwide cohort study with sibling control analysis included a population-based sample of 2 480 797 children born in 1995 to 2019 in Sweden, with follow-up through December 31, 2021. Exposure: Use of acetaminophen during pregnancy prospectively recorded from antenatal and prescription records. Main Outcomes and Measures: Autism, ADHD, and intellectual disability based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes in health registers. Results: In total, 185 909 children (7.49%) were exposed to acetaminophen during pregnancy. Crude absolute risks at 10 years of age for those not exposed vs those exposed to acetaminophen were 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability. In models without sibling control, ever-use vs no use of acetaminophen during pregnancy was associated with marginally increased risk of autism (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]; risk difference [RD] at 10 years of age, 0.09% [95% CI, -0.01% to 0.20%]), ADHD (HR, 1.07 [95% CI, 1.05-1.10]; RD, 0.21% [95% CI, 0.08%-0.34%]), and intellectual disability (HR, 1.05 [95% CI, 1.00-1.10]; RD, 0.04% [95% CI, -0.04% to 0.12%]). To address unobserved confounding, matched full sibling pairs were also analyzed. Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, -0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, -0.02% [95% CI, -0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, -0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively. Conclusions and Relevance: Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding.

Neonatal Outcomes After COVID-19 Vaccination in Pregnancy.

Importance: Better knowledge about neonatal adverse events after COVID-19 vaccination during pregnancy could help address concerns about vaccine safety. Objective: To evaluate the risks of neonatal adverse events after exposure to COVID-19 vaccination during pregnancy. Design, Setting, and Participants: Population-based cohort study including all infants in Sweden and Norway born from June 2021 to January 2023. Unique personal identity numbers were used to link individual information from different national registers. Exposure: Administration of any mRNA vaccine against COVID-19 during pregnancy, irrespective of previous vaccination, number of doses during pregnancy, or vaccine manufacturer. Main Outcomes and Measures: Outcomes were neonatal conditions with bleeding/thrombosis or inflammation/infection; disorders of the central nervous system; circulatory, respiratory, or gastrointestinal problems; and neonatal mortality. Statistical methods included logistic regression adjusted for characteristics of the pregnant individuals, with additional restricted and stratified analyses. Results: Of 196 470 newborn infants included (51.3% male, 93.8% born at term, 62.5% born in Sweden), 94 303 (48.0%) were exposed to COVID-19 vaccination during pregnancy. Exposed infants exhibited no increased odds of adverse neonatal outcomes, and they exhibited lower odds for neonatal nontraumatic intracranial hemorrhage (event rate, 1.7 vs 3.2/1000; adjusted odds ratio [aOR], 0.78 [95% CI, 0.61-0.99]), hypoxic-ischemic encephalopathy (1.8 vs 2.7/1000; aOR, 0.73 [95% CI, 0.55-0.96]), and neonatal mortality (0.9 vs 1.8/1000; aOR, 0.68 [95% CI, 0.50-0.91]). Subgroup analyses found a similar association between vaccination during pregnancy and lower neonatal mortality; subgroups were restricted to infants delivered by individuals unvaccinated before pregnancy, individuals vaccinated before pregnancy, individuals vaccinated after a general recommendation of vaccination during pregnancy was issued, and individuals without COVID-19 infection during pregnancy. Analyses restricted to term infants, singleton births, or infants without birth defects yielded similar results. Stratifying the analysis by vaccine manufacturer did not attenuate the association between vaccination and low neonatal mortality. Conclusions and Relevance: In this large population-based study, vaccination of pregnant individuals with mRNA COVID-19 vaccines was not associated with increased risks of neonatal adverse events in their infants.

Pregnancy Outcomes in Women With Autoimmune Hepatitis - A Nationwide Population-based Cohort Study With Histopathology.

BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is a chronic inflammatory liver condition that predominantly affects women. However, pregnancy risks remain unclear. METHODS: A nationwide population-based cohort study (ESPRESSO) in Sweden from 1992 to 2016 including 309 singleton births in women with AIH and 1532 matched births in women from the general population was performed. AIH was diagnosed as a combination of administrative coding from medical diagnosis of AIH and liver biopsy data from Sweden's 28 pathology departments. Using conditional logistic regression, odds ratios (ORs) for adverse pregnancy outcomes were determined. RESULTS: Among 306 live births to women with AIH, 51 (16.7%) were preterm, compared with 70 of 1524 (4.6%) reference births. This corresponded to an OR of 5.10 for preterm birth (95% confidence interval [CI], 3.29-7.92), with similar odds using sibling comparators. Women with AIH with and without cirrhosis had similar odds for preterm birth. The AIH association was particularly strong with medically indicated preterm birth (OR, 13.01; 95% CI, 5.50-30.79). AIH was associated with low birth weight (OR, 5.31; 95% CI, 2.82-9.99) and low 5-minute Apgar score (OR, 3.46; 95% CI, 1.14-10.49) offspring, but we found no association with congenital malformations (OR, 1.14; 95% CI, 0.68-1.91), small for gestational age (OR, 1.04; 95% CI, 0.38-2.85), stillbirth (OR, 0.59; 95% CI, 0.02-18.88), or neonatal death (OR, 7.42; 95% CI, 0.65-84.25). Maternal AIH was linked to an increased odds of cesarean section (OR, 1.44; 95% CI, 1.04-2.00) and preeclampsia (OR, 3.65; 95% CI, 2.01-6.64), but not to gestational diabetes. CONCLUSIONS: Maternal AIH was associated with a 5-fold higher odds of preterm birth, and cirrhosis at diagnosis did not add to the impact of AIH on preterm birth. Future studies are needed to understand how to reduce this risk.

No Increased Risk of Cardiac Birth Defects in Infants of Mothers With Celiac Disease: A Population and Sibling Comparison.

INTRODUCTION: Several earlier studies have indicated an increased risk of cardiac birth defects among infants born to mothers with celiac disease (CeD). Through linking nationwide Swedish health care registries, we aimed to investigate maternal CeD and risk of any or cardiac birth defects in their offspring. METHODS: We performed a retrospective cohort study of infants born between 2002 and 2016 to women with biopsy-proven CeD (villous atrophy, Marsh III) matched to infants born to nonceliac women from the general population. Conditional logistic regression with odds ratios (OR) and their 95% confidence intervals (CI) was used to determine the association between maternal CeD and birth defects. To minimize the impact of intrafamilial confounding, we also compared infants born to mothers with CeD with infants born to their nonaffected sisters. RESULTS: A total of 6,990 infants were born to mothers with diagnosed CeD compared with 34,643 infants born to reference mothers. Any birth defect was seen in 234 (33 per 1,000 infants) and 1,244 (36/1,000) reference infants corresponding to an OR of 0.93 (95% CI 0.81-1.08). Cardiac birth defects were seen in 113 (16/1,000) vs 569 (16/1,000) infants (OR 0.98, 95% CI 0.80-1.20). Similar OR for any and cardiac birth defects were also seen in sibling comparisons. DISCUSSION: We found no statistically significant risk of any or cardiac birth defects in infants born to mothers with diagnosed CeD compared with the general population and to their nonaffected sisters.

Maternal suicide attempts and deaths in the first year after cesarean delivery.

BACKGROUND: Cesarean delivery (CD) has been associated with postpartum psychiatric disorders, but less is known about the risk of suicidal behaviors. We estimated the incidence and risk of suicide attempts and deaths during the first postpartum year in mothers who delivered via CD v. vaginally. METHOD: All deliveries in Sweden between 1973 and 2012 were identified. The mothers were followed since delivery for 12 months or until the date of one of the outcomes (i.e. suicide attempt or death by suicide), death by other causes or emigration. Associations were estimated using Cox proportional hazards regression models. RESULTS: Of 4 016 789 identified deliveries, 514 113 (12.8%) were CDs and 3 502 676 (87.2%) were vaginal deliveries. During the 12-month follow-up, 504 (0.098%) suicide attempts were observed in the CD group and 2240 (0.064%) in the vaginal delivery group (risk difference: 0.034%), while 11 (0.0037%) deaths by suicide were registered in the CD group and 109 (0.0029%) in the vaginal delivery group (risk difference: 0.008%). Compared to vaginal delivery, CD was associated with an increased risk of suicide attempts [hazard ratio (HR) 1.46; 95% CI 1.32-1.60], but not of deaths by suicide (HR 1.44; 95% CI 0.88-2.36). CONCLUSIONS: Maternal suicidal behaviors during the first postpartum year were uncommon in Sweden. Compared to vaginal delivery, CD was associated with a small increased risk of suicide attempts, but not death by suicide. Improved understanding of the association between CD and maternal suicidal behaviors may promote more appropriate measures to improve maternal mental well-being and further reduce suicidal risks.

Maternal and fetal outcomes in acute hepatic porphyria: A Swedish National Cohort Study.

Current knowledge of pregnancy and perinatal outcomes in women with acute hepatic porphyria (AHP) is largely based on biochemical disease models, case reports, and case series. We performed a nationwide, registered-based cohort study to investigate the association between maternal AHP and the risk of adverse pregnancy and perinatal outcomes. All women in the Swedish Porphyria Register with confirmed AHP aged 18 years or older between 1987 and 2015 and matched general population comparators, with at least one registered delivery in the Swedish Medical Birth Register were included. Risk ratios (RRs) of pregnancy complications, delivery mode and perinatal outcomes were estimated and adjusted for maternal age at delivery, area of residency, birth year and parity. Women with acute intermittent porphyria (AIP), the most common form of AHP, were further categorized according to maximal lifetime urinary porphobilinogen (U-PBG) levels. The study included 214 women with AHP and 2174 matched comparators. Women with AHP presented with a higher risk for pregnancy-induced hypertensive disorder (aRR 1.73, 95% CI 1.12-2.68), gestational diabetes (aRR 3.41, 95% CI 1.69-6.89), and small-for-gestational-age birth (aRR 2.08, 95% CI 1.26-3.45). In general, RRs were higher among women with AIP who had high lifetime U-PBG levels. Our study shows an increased risk for pregnancy induced hypertensive disease, gestational diabetes, and small for gestational age births for AHP women, with higher relative risks for women with biochemically active AIP. No increased risk for perinatal death or malformations was observed.

The Stockholm-Gotland perinatal cohort-A population-based cohort including longitudinal data throughout pregnancy and the postpartum period.

BACKGROUND: Register-based reproductive and perinatal databases rarely contain detailed information from medical records or repeated measurements throughout pregnancy and delivery. This lack of enriched pregnancy and birth data led to the initiation of the Swedish Stockholm-Gotland Perinatal Cohort (SGPC). OBJECTIVES: To describe the strengths of the SGPC, as well as the unique research questions that can be addressed using this cohort. POPULATION: The SGPC is a prospectively collected, population-based cohort that includes all births (from 22 completed gestational weeks onwards) between 1 January 2008 and 15 June 2020 in the Stockholm and Gotland regions of Sweden (335,153 singleton and 11,025 multiple pregnancies). DESIGN: Descriptive study. METHODS: The SGPC is based on the electronic medical records of women and their infants. The medical record system is used for all antenatal clinic visits and admissions, delivery and neonatal admissions, as well as postpartum clinical visits. SGPC has been further enriched with data linkages to 10 Swedish National Health Care and Quality Registers. PRELIMINARY RESULTS: In contrast to other reproductive and perinatal databases available in Sweden, including the Medical Birth Register and the Pregnancy Register, SGPC contains highly detailed medical record data, including time-varying serial measurements for physiological parameters throughout pregnancy, delivery, and postpartum, for both mother and infant. These strengths have enabled studies that were previously inconceivable; the effects of serial measurements of pregnancy weight gain, changes in haemoglobin counts and blood pressure during pregnancy, fetal weight estimations by ultrasound, duration of stages and phases of labour, cervical dilatation and oxytocin use during delivery, and constructing reference curves for umbilical cord pH. CONCLUSIONS: The SGPC-with its rich content, repeated measurements and linkages to numerous health care and quality registers-is a unique cohort that enables high-quality perinatal studies that would otherwise not be possible.

The Swedish medical birth register during five decades: documentation of the content and quality of the register.

Pregnancy-related factors are important for short- and long-term health in mothers and offspring. The nationwide population-based Swedish Medical Birth Register (MBR) was established in 1973. The present study describes the content and quality of the MBR, using original MBR data, Swedish-language and international publications based on the MBR.The MBR includes around 98% of all births in Sweden. From 1982 onwards, the MBR is based on prospectively recorded information in standardized antenatal, obstetric, and neonatal records. When the mother and infant are discharged from hospital, this information is forwarded to the MBR, which is updated annually. Maternal data include information from first antenatal visit on self-reported obstetric history, infertility, diseases, medication use, cohabitation status, smoking and snuff use, self-reported height and measured weight, allowing calculation of body mass index. Birth and neonatal data include date and time of birth, mode of delivery, singleton or multiple birth, gestational age, stillbirth, birth weight, birth length, head circumference, infant sex, Apgar scores, and maternal and infant diagnoses/procedures, including neonatal care. The overall quality of the MBR is very high, owing to the semi-automated data extraction from the standardized regional electronic health records, Sweden's universal access to antenatal care, and the possibility to compare mothers and offspring to the Total Population Register in order to identify missing records. Through the unique personal identity numbers of mothers and live-born offspring, the MBR can be linked to other health registers. The Swedish MBR contains high-quality pregnancy-related information on more than 5 million births during five decades.

The association between episiotomy or OASIS at vacuum extraction in nulliparous women and subsequent prelabor cesarean delivery: A nationwide observational study.

INTRODUCTION: Severe perineal injuries at childbirth affect women's postnatal health, including future childbirths. First births with vacuum extraction carry an increased risk of obstetric anal sphincter injuries (OASIS). Lateral or mediolateral episiotomy at vacuum extraction may decrease the risk of OASIS. Our aim was to assess whether lateral or mediolateral episiotomy, or OASIS, at vacuum extraction in nulliparous women is associated with prelabor cesarean delivery in the subsequent childbirth. MATERIAL AND METHODS: This is a nationwide observational study using data from the Swedish Medical Birth Register, including women having a first birth with vacuum extraction and a second birth in 2000-2014. Both births were live, single, cephalic, ≥34 gestational weeks without malformations. The association between episiotomy or OASIS in the first birth and prelabor cesarean delivery in the second birth was examined using univariate and multivariate logistic regression with inverse probability of treatment weighting, and interaction analysis. Main outcome measure was prelabor cesarean delivery in the second birth. RESULTS: In total, 44 656 women with vacuum extraction at their first birth were included. The rate of prelabor cesarean delivery in the second birth was 5.9% (824 of 13 950) in women with episiotomy, compared with 6.0% (1830 of 30 706) in women without episiotomy. Thus, women with episiotomy did not have an increased risk of prelabor cesarean delivery (adjusted odds ratio [aOR] 1.00, 95% confidence interval [95% CI] 0.83-1.20) compared with women without episiotomy. For comparison, the rate of prelabor cesarean delivery in the second birth was 20.6% (1275 of 6176) in women with OASIS, compared with 3.6% (1379 of 38 480) in women without OASIS (aOR 6.57, 95% CI 5.97-7.23). There was no interaction between episiotomy and OASIS. CONCLUSIONS: Lateral or mediolateral episiotomy at vacuum extraction in nulliparous women did not increase the risk of prelabor cesarean delivery in the subsequent childbirth. OASIS increased the odds of prelabor cesarean delivery more than sixfold.

Severe COVID-19 during pregnancy in Sweden, Norway, and Denmark.

INTRODUCTION: Pregnancy is a risk factor for severe coronavirus disease 2019 (COVID-19) and adverse pregnancy outcomes. We aimed to explore maternal characteristics, pregnancy outcomes, vaccination status, and virus variants among pregnant women admitted to intensive care units (ICU) with severe COVID-19. MATERIAL AND METHODS: We identified pregnant women admitted to ICU in Sweden (n = 96), Norway (n = 31), and Denmark (n = 16) because of severe COVID-19, from national registers and clinical databases between March 2020 and February 2022 (Denmark), August 2022 (Sweden), or December 2022 (Norway). Their background characteristics, pregnancy outcome, and vaccination status were compared with all birthing women and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test-positive pregnant women during the same time period. We calculated the number admitted to ICU per 10 000 birthing and per 1000 SARS-CoV-2 test-positive women during the Index, Alpha, Delta, and Omicron periods. RESULTS: Women admitted to ICU had a higher mean body mass index, were more often of non-Scandinavian origin, had on average lower education and income levels, had a higher proportion of chronic and pregnancy-related conditions, delivered preterm, had neonates with low Apgar scores, and had more infants admitted to neonatal care, compared with all birthing and test-positive pregnant women. Of those admitted to ICU, only 7% had been vaccinated before admission. Overall, the highest proportion of women admitted to ICU per birthing was during the Delta period (4.1 per 10 000 birthing women). In Norway, the highest proportion admitted to ICU per test-positive pregnant women was during the Delta period (17.8 per 1000 test-positive), whereas the highest proportion of admitted per test-positive in Sweden and Denmark was seen during the Index period (15.4 and 8.9 per 1000 test-positive, respectively). CONCLUSIONS: Admission to ICU because of COVID-19 in pregnancy was a rare event in the Scandinavian countries, but women who were unvaccinated, of non-Scandinavian origin, and with lower socio-economic status were at higher risk of admission to ICU. In addition, women admitted to ICU for COVID-19 had higher risk of adverse pregnancy outcomes.

Crude and adjusted comparisons of cesarean delivery rates using the Robson classification: A population-based cohort study in Canada and Sweden, 2004 to 2016.

BACKGROUND: The Robson classification has become a global standard for comparing and monitoring cesarean delivery (CD) rates across populations and over time; however, this classification does not account for differences in important maternal, fetal, and obstetric practice factors known to impact CD rates. The objectives of our study were to identify subgroups of women contributing to differences in the CD rate in Sweden and British Columbia (BC), Canada using the Robson classification and to estimate the contribution of maternal, fetal/infant, and obstetric practice factors to differences in CD rates between countries and over time. METHODS AND FINDINGS: We conducted a population-based cohort study of deliveries in Sweden (January 1, 2004 to December 31, 2016; n = 1,392,779) and BC (March 1, 2004 to April 31, 2017; n = 559,205). Deliveries were stratified into Robson categories and the CD rate, relative size of each group and its contribution to the overall CD rate were compared between the Swedish and the Canadian cohorts. Poisson and log-binomial regression were used to assess the contribution of maternal, fetal, and obstetric practice factors to spatiotemporal differences in Robson group-specific CD rates between Sweden and BC. Nulliparous women comprised 44.8% of the study population, while women of advanced maternal age (≥35 years) and women with overweight/obesity (≥25 kg/m2) constituted 23.5% and 32.4% of the study population, respectively. The CD rate in Sweden was stable at approximately 17.0% from 2004 to 2016 (p for trend = 0.10), while the CD rate increased in BC from 29.4% to 33.9% (p for trend < 0.001). Differences in CD rates between Sweden and BC varied by Robson group, for example, in Group 1 (nullipara with a term, single, cephalic fetus with spontaneous labor), the CD rate was 8.1% in Sweden and 20.4% in BC (rate ratio [RR] for BC versus Sweden = 2.52, 95% confidence interval [CI] 2.49 to 2.56, p < 0.001) and in Group 2 (nullipara, single, cephalic fetus, term gestation with induction of labor or prelabor CD), the rate of CD was 37.3% in Sweden and 45.9% in BC (RR = 1.23, 95% CI 1.22 to 1.25, p < 0.001). The effect of adjustment for maternal characteristics (e.g., age, body mass index), maternal comorbidity (e.g., preeclampsia), fetal characteristics (e.g., head position), and obstetric practice factors (e.g., epidural) ranged from no effect (e.g., among breech deliveries; Groups 6 and 7) to explaining up to 5.2% of the absolute difference in the CD rate (Group 2: adjusted CD rate in BC 40.7%, adjusted RR = 1.09, 95% CI 1.08 to 1.12, p < 0.001). Adjustment also explained a substantial fraction of the temporal change in CD rates among some Robson groups in BC. Limitations of the study include a lack of information on intrapartum details, such as labor duration as well as maternal and perinatal outcomes associated with the observed differences in CD rates. CONCLUSIONS: In this study, we found that several factors not included in the Robson classification explain a significant proportion of the spatiotemporal difference in CD rates in some Robson groups. These findings suggest that incorporating these factors into explanatory models using the Robson classification may be useful for ensuring that public health initiatives regarding CD rates are evidence informed.

Preterm birth after the introduction of COVID-19 mitigation measures in Norway, Sweden, and Denmark: a registry-based difference-in-differences study.

BACKGROUND: Although some studies have reported a decrease in preterm birth following the start of the COVID-19 pandemic, the findings are inconsistent. OBJECTIVE: This study aimed to compare the incidences of preterm birth before and after the introduction of COVID-19 mitigation measures in Scandinavian countries using robust population-based registry data. STUDY DESIGN: This was a registry-based difference-in-differences study using births from January 2014 through December 2020 in Norway, Sweden, and Denmark. The changes in the preterm birth (<37 weeks) rates before and after the introduction of COVID-19 mitigation measures (set to March 12, 2020) were compared with the changes in preterm birth before and after March 12 from 2014 to 2019. The differences per 1000 births were calculated for 2-, 4-, 8-, 12-, and 16-week intervals before and after March 12. The secondary analyses included medically indicated preterm birth, spontaneous preterm birth, and very preterm (<32 weeks) birth. RESULTS: A total of 1,519,521 births were included in this study. During the study period, 5.6% of the births were preterm in Norway and Sweden, and 5.7% were preterm in Denmark. There was a seasonal variation in the incidence of preterm birth, with the highest incidence during winter. In all the 3 countries, there was a slight overall decline in preterm births from 2014 to 2020. There was no consistent evidence of a change in the preterm birth rates following the introduction of COVID-19 mitigation measures, with difference-in-differences estimates ranging from 3.7 per 1000 births (95% confidence interval, -3.8 to 11.1) for the first 2 weeks after March 12, 2020, to -1.8 per 1000 births (95% confidence interval, -4.6 to 1.1) in the 16 weeks after March 12, 2020. Similarly, there was no evidence of an impact on medically indicated preterm birth, spontaneous preterm birth, or very preterm birth. CONCLUSION: Using high-quality national data on births in 3 Scandinavian countries, each of which implemented different approaches to address the pandemic, there was no evidence of a decline in preterm births following the introduction of COVID-19 mitigation measures.

Association between first and second stage of labour duration and mode of delivery: A population-based cohort study.

BACKGROUND: Active first stage of labour duration can widely vary between women. However, the nature of the relationship between the active first stage and second stage of labour duration is sparsely studied. OBJECTIVES: To determine whether active first stage of labour duration (i) influences second stage of labour duration; and (ii) is associated with mode of delivery. METHODS: A population-based cohort study of 13,379 women primiparous women, with spontaneous start in Stockholm-Gotland Region, Sweden, between 2008 and 2014. Duration of the active first stage of labour was examined in relation to second-stage duration using univariate and multivariable quantile regressions, with the first quartile (first stage duration) as the reference. Nonlinearity of associations was tested by restricted cubic splines. Association between active first-stage duration with mode of delivery was estimated using a multinomial logistic regression based on adjusted odds ratios. RESULTS: Longer active first stage of labour duration was linearly associated with longer second stage of labour duration until approximately 12 h of active first stage of labour duration. After 12 h, a non-linear trend is seen, demonstrated by a plateau in the second-stage duration. In addition, longer active first stage of labour duration was associated with increased occurrence of operative vaginal delivery (adjusted odds ratio 3.36, 95% confidence interval [CI] 2.89, 3.89) and caesarean delivery (adjusted odds ratio 4.75, 95% CI 3.85, 5.80). CONCLUSIONS: Among primiparous women with spontaneous onset of labour, longer active first stage of labour duration was associated with both longer second stage of labour duration and higher odds of operative delivery. This study contributes with findings, which may inform future discussions regarding how to properly account for second-stage duration, with applications in obstetric and perinatal epidemiology.

Time of delivery among low-risk women at 37-42 weeks of gestation and risks of stillbirth and infant mortality, and long-term neurological morbidity.

BACKGROUND: The most important knowledge gap in connection with obstetric management for time of delivery in term low-risk pregnancies relates to the absence of information on long-term neurodevelopmental outcomes. OBJECTIVES: We examined risks of stillbirth, infant mortality, cerebral palsy (CP) and epilepsy among low-risk pregnancies. METHODS: In this population-based Swedish study, we identified, from 1998 to 2019, 1,773,269 singleton infants born between 37 and 42 completed weeks in women with low-risk pregnancies. Poisson log-linear regression models were used to examine the association between gestational age at delivery and stillbirth, infant mortality, CP and epilepsy. Adjusted rate ratios (RR) and 95% confidence intervals expressing the effect of birth at a particular gestational week compared with birth at a later gestational week were estimated. RESULTS: Compared with those born at a later gestation, RRs for stillbirth and infant mortality were higher among births at 37 weeks' and 38 weeks' gestation. The RRs for infant mortality were approximately 20% and 25% lower among births at 40 or 41 weeks compared with those born at later gestation, respectively. Infants born at 37 and 38 weeks also had higher RRs for CP (vs infants born at ≥38 and ≥39 weeks, respectively), while those born at 39 gestation had similar RRs (vs infants born at ≥40 weeks); infants born at 40 and 41 weeks had lower RRs of CP (vs those born at ≥41 and 42 weeks, respectively). The RRs for epilepsy were higher in those born at 37 and 38 weeks compared with those born at later gestation. CONCLUSIONS: Among low-risk pregnancies, birth at 37 or 38 completed weeks' gestation is associated with increased risks of stillbirth, infant mortality and neurological morbidity, while birth at 39-40 completed weeks is associated with reduced risks compared with births at later gestation.

Associations between ambient temperature and risk of preterm birth in Sweden: A comparison of analytical approaches.

BACKGROUND: Evidence indicates that high temperatures are a risk factor for preterm birth. Increasing heat exposures due to climate change are therefore a concern for pregnant women. However, the large heterogeneity of study designs and statistical methods across previous studies complicate interpretation and comparisons. We investigated associations of short-term exposure to high ambient temperature with preterm birth in Sweden, applying three complementary analytical approaches. METHODS: We included 560,615 singleton live births between 2014 and 2019, identified in the Swedish Pregnancy Register. We estimated weekly mean temperatures at 1-km2 spatial resolution using a spatiotemporal machine learning methodology, and assigned them at the residential addresses of the study participants. The main outcomes of the study were gestational age in weeks and subcategories of preterm birth (<37 weeks): extremely preterm birth (<28 weeks), very preterm birth (from week 28 to <32), and moderately preterm birth (from week 32 to<37). Case-crossover, quantile regression and time-to-event analyses were applied to estimate the effects of short-term exposure to increased ambient temperature during the week before birth on preterm births. Furthermore, distributed lag nonlinear models (DLNM) were applied to identify susceptibility windows of exposures throughout pregnancy in relation to preterm birth. RESULTS: A total of 1924 births were extremely preterm (0.4%), 2636 very preterm (0.5%), and 23,664 moderately preterm (4.2%). Consistent across all three analytical approaches (case-crossover, quantile regression and time-to-event analyses), higher ambient temperature (95th vs 50th percentile) demonstrated increased risk of extremely preterm birth, but associations did not reach statistical significance. In DLNM models, we observed no evidence to suggest an increased effect of high temperature on preterm birth risk. Even so, a suggested trend was observed in both the quantile regression and time-to-event analyses of a higher risk of extremely preterm birth with higher temperature during the last week before birth. CONCLUSIONS: In Sweden, with high quality data on exposure and outcome, a temperate climate and good quality ante-natal health care, we did not find an association between high ambient temperatures and preterm births. Results were consistent across three complementary analytical approaches.

Risk of gestational diabetes mellitus in relation to early pregnancy and gestational weight gain before diagnosis: A population-based cohort study.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common pregnancy complication associated with adverse consequences for the mother and offspring in both short and long term. The aim of this study was to investigate associations between risk of GDM and gestational weight gain in early pregnancy and before diagnosis. MATERIAL AND METHODS: Our population-based cohort study included 131 164 singleton pregnancies in the Stockholm-Gotland region in Sweden from 2008 through 2013. The exposures were weight gain in early pregnancy (<22 weeks) and weight gain before diagnosis, standardized into gestational age-specific z scores. The outcome was GDM. We used logistic regression models with a generalized estimating equations method to estimate odds ratios with 95% confidence intervals for GDM, stratified by early-pregnancy body mass index (BMI) category. RESULTS: Above average weight gain before diagnosis (z score >0) was associated with increased risk of GDM among all BMI groups except for obese III. Early gestational weight gain above average was associated with increased risk for GDM in overweight women. Below average weight gain before diagnosis (z score <0) was only associated with decreased risk of GDM in obese III. Early gestational weight gain below average was associated with reduced risks of GDM in obese class I, II, and III women. CONCLUSIONS: The risk of GDM increased with higher weight gain before diagnosis in all BMI groups except obese class III, whereas the risk was reduced with lower weight gain before diagnosis in obese III women only. The risk of GDM increased with higher early gestational weight gain in overweight women, while the risk was reduced with lower early gestational weight gain among obese women. Obese women may benefit from lower weight gain, especially in early pregnancy.