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Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.

In this study based on registry data, women with a history of bariatric surgery who were matched with women without this history had a reduced risk of gestational diabetes and excessive fetal growth, a shorter gestation, and an increased risk of small-for-gestational-age infants. In 2008, an estimated 300 million women worldwide were obese (body-mass index [BMI; the weight in kilograms divided by the square of the height in meters], ≥30). 1 In 2011–2012 in the United States, 36% of adult women were obese, 2 and the majority of women in early pregnancy were either overweight or obese (BMI, ≥25). 3 Maternal obesity is a risk factor for gestational diabetes, with attendant increased risks of macrosomia, delivery complications, obesity in the offspring, and later development of type 2 diabetes in the mother. 4 – 6 Maternal obesity is also associated with an increased risk of stillbirth, 7 preterm birth, 8 and . . .

Objective To assess whether use of specific selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in early pregnancy is associated with an increased risk of birth defects, with emphasis on cardiovascular birth defects even when accounting for lifestyle or other familial confounding.Design Multicountry population based cohort study, including sibling controlled design.Setting Nordic population (Denmark, Finland, Iceland, Norway, and Sweden) identified from nationwide health registers at different periods in 1996-2010.Population The full study cohort included women giving birth to 2.3 million live singletons. The sibling cohort included 2288 singleton live births. The sibling controlled analyses included sibling pairs who were discordant for exposure to SSRIs or venlafaxine and birth defects.Main outcome measure Prevalence of birth defects, including subtypes of cardiac defects. Odds ratio of birth defects from logistic and conditional logistic regression.Results Among 36 772 infants exposed to any SSRI in early pregnancy, 3.7% (n=1357) had a birth defect compared with 3.1% of 2 266 875 unexposed infants, yielding a covariate adjusted odds ratio of 1.13 (95% confidence interval 1.06 to 1.20). In the sibling controlled analysis the adjusted odds ratio decreased to 1.06 (0.91 to 1.24). The odds ratios for any cardiac birth defect with use of any SSRI or venlafaxine were 1.15 (95% confidence interval 1.05 to 1.26) in the covariate adjusted analysis and 0.92 (0.72 to 1.17) in the sibling controlled analysis. For atrial and ventricular septal defects the covariate adjusted odds ratio was 1.17 (1.05 to 1.31). Exposure to any SSRI or venlafaxine increased the prevalence of right ventricular outflow tract obstruction defects, with a covariate adjusted odds ratio of 1.48 (1.15 to 1.89). In the sibling controlled analysis the adjusted odds ratio decreased to 0.56 (0.21 to 1.49) for any exposure to SSRIs or venlafaxine and right ventricular outflow tract obstruction defects.Conclusions In this large Nordic study no substantial increase was found in prevalence of overall cardiac birth defects among infants exposed to SSRIs or venlafaxine in utero. Although the prevalence of septal defects and right ventricular outflow tract defects was higher in exposed infants, the lack of an association in the sibling controlled analyses points against a teratogenic effect of these drugs.

Obesity increases the risk of adverse delivery outcomes. Whether weight loss induced by bariatric surgery influences these risks remains to be determined. The objective was to investigate the risk of adverse delivery outcomes among post-surgery women compared with women without bariatric surgery history but with similar characteristics. We identified 801,443 singleton live-born term births (≥37 gestational weeks) in the Swedish Medical Birth Register between 1 January 2006 and 31 December 2013, of which 1,929 were in women with a history of bariatric surgery and a pre-surgery weight available from the Scandinavian Obesity Surgery Registry. For each post-surgery delivery, up to 5 control deliveries were matched by maternal pre-surgery BMI (early-pregnancy BMI used for controls), age, parity, smoking, education, height, country of birth, and delivery year (N post-surgery deliveries:matched controls = 1,431:4,476). The main outcome measures were mode of delivery, induction of labor, post-term pregnancy (≥42 + 0 gestational weeks), epidural analgesia, fetal distress, labor dystocia, peripartum infection, obstetric anal sphincter injury (perineal tear grade III-IV), and postpartum hemorrhage. Among the women with a history of bariatric surgery, the mean pre-surgery BMI was 42.6 kg/m2, the median surgery-to-conception interval was 1.4 years, and the mean BMI loss between surgery and early pregnancy was 13.5 kg/m2 (38 kg). Compared to matched control women, post-surgery women were less likely to have cesarean delivery (18.2% versus 25.0%, risk ratio [RR] 0.70, 95% CI 0.60-0.80), especially emergency cesarean (6.8% versus 15.1%, RR 0.40, 95% CI 0.31-0.51). Post-surgery women also had lower risks of instrumental delivery (5.0% versus 6.5%, RR 0.73, 95% CI 0.53-0.98), induction of labor (23.4% versus 34.0%, RR 0.68, 95% CI 0.59-0.78), post-term pregnancy (4.2% versus 10.3%, RR 0.40, 95% CI 0.30-0.53), obstetric anal sphincter injury (1.5% versus 2.9%, RR 0.46, 95% CI 0.25-0.81), and postpartum hemorrhage (4.6% versus 8.0%, RR 0.58, 95% CI 0.44-0.76). Since this study was not randomized, a limitation is the possibility of selection bias, despite our efforts using careful matching. Bariatric-surgery-induced weight loss was associated with lower risks for adverse delivery outcomes in term births.

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. 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). 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). 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. Karolinska Institutet and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Objective To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs.Design Population based cohort study using data from the national health registers.Setting Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007.Participants More than 1.6 million infants born after gestational week 33.Main outcome measures Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs.Results Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000); adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0).Conclusions The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect.

ObjectivesReports on pregnancy outcomes among women with juvenile onset arthritis (JIA) have been few and small. The aim of this study was to assess pregnancy outcomes in a large and contemporary cohort of women diagnosed with JIA.MethodsIn a nationwide Swedish population-based cohort study between 1992 and 2011, we identified 1807 births among women with JIA and 1 949 202 control births. Since JIA is a heterogenic condition, births to women with JIA was divided into JIA paediatric only (n=1169) and JIA persisting into adulthood (n=638). ORs and 95% CIs were estimated with generalised estimating equations.ResultsWomen with JIA were at increased risk of preterm birth, especially medically indicated, in both subgroups: adjusted OR (aOR) 1.74 (1.35–2.67) for JIA paediatric and aOR 4.12 (2.76–6.15) for JIA persisting into adulthood. JIA persisting into adulthood was associated with very preterm birth (aOR 3.14, 1.58–6.24), spontaneous preterm birth (aOR 1.63, 1.11–2.39), small for gestational age birth (aOR 1.84, 1.19–2.85), early-onset pre-eclampsia (aOR 6.28, 2.68–13.81) and late-onset pre-eclampsia (aOR 1.96, 1.31–2.91). Women with JIA paediatric only were at increased risk of delivery by caesarean section (aOR 1.42, 1.66–1.73) and induction of labour (aOR 1.45, 1.18–1.77).ConclusionsWe found increased risks of both maternal and infant complications among women with JIA confined to childhood and in women with JIA persistent into adulthood as compared with population controls. Pregnancies in women with JIA should thus be subject to increased surveillance during pregnancy and delivery.

This Swedish registry study showed that women who had undergone bariatric surgery had a higher risk of preterm birth than did women in a control group matched for presurgery body-mass index. To the Editor: Bariatric surgery, the most effective method of achieving sustained weight loss, is increasingly performed in women of reproductive age. 1 Some studies have shown that women who have undergone bariatric surgery have a higher risk of preterm birth than women who have the same body-mass index (BMI) and have not undergone bariatric surgery. 1 – 3 We previously reported outcomes of pregnancy in 590 women with a history of bariatric surgery who gave birth between 2006 and 2011, as compared with women matched for presurgery BMI, and we found no significant association with preterm birth. 4 We now report the risk . . .