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Fetal androgen exposure may be associated with autism spectrum disorder (ASD). We studied 1777 mother-child pairs in the prospective Odense Child Cohort. Prenatal androgen exposure was assessed by maternal 3rd trimester testosterone concentrations, maternal polycystic ovary syndrome (PCOS), and 3 months offspring anogenital distance. ASD traits were assessed at age 3 years with the ASD-symptom scale of the Child Behavior Checklist for ages 1 1/2-5 years. Maternal testosterone was positively associated with traits of ASD in boys (p < 0.05). Maternal PCOS was associated with increased offspring ASD traits (p = 0.046), but became non-significant after excluding parental psychiatric diagnosis. Offspring anogenital distance was not linked to ASD traits. Higher prevalence of ASD in boys could be linked to higher susceptibility to fetal androgen exposure.

Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P = 3.2 × 10-8, odds ratio (OR) = 1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF = 6.4%, P = 1.3 × 10-8, OR = 1.7; rs143445068, MAF = 0.8%, P = 5.2 × 10-9, OR = 3.4; rs183453668, MAF = 0.5%, P = 2.8 × 10-8, OR = 3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.

BackgroundRapid human papillomavirus (HPV) DNA testing is an emerging cervical cancer screening strategy in resource-limited countries, yet it requires follow-up of women who test HPV positive. ObjectiveThis study aimed to determine if one-way text messages improved attendance to a 14-month follow-up cervical cancer screening among HPV-positive women. MethodsThis multicenter, parallel-group randomized controlled trial was conducted at 3 hospitals in Tanzania. Eligible participants were aged between 25 and 60 years, had tested positive to a rapid HPV test during a patient-initiated screening, had been informed of their HPV result, and had a private mobile phone with a valid number. Participants were randomly assigned in a 1:1 ratio to the intervention or control group through an incorporated algorithm in the text message system. The intervention group received one-way text messages, and the control group received no text messages. The primary outcome was attendance at a 14-month health provider-initiated follow-up screening. Participants were not blinded, but outcome assessors were. The analysis was based on intention to treat. ResultsBetween August 2015 and July 2017, 4080 women were screened for cervical cancer, of which 705 were included in this trial—358 women were allocated to the intervention group, and 347 women were allocated to the control group. Moreover, 16 women were excluded before the analysis because they developed cervical cancer or died (8 from each group). In the intervention group, 24.0% (84/350) women attended their follow-up screening, and in the control group, 23.8% (80/335) women attended their follow-up screening (risk ratio 1.02, 95% CI 0.79-1.33). ConclusionsAttendance to a health provider-initiated follow-up cervical cancer screening among HPV-positive women was strikingly low, and one-way text messages did not improve the attendance rate. Implementation of rapid HPV testing as a primary screening method at the clinic level entails the challenge of ensuring a proper follow-up of women. Trial RegistrationClinicalTrials.gov NCT02509702; https://clinicaltrials.gov/ct2/show/NCT02509702. International Registered Report Identifier (IRRID)RR2-10.2196/10.2196/15863

Objective: To investigate associations between maternal testosterone status and offspring birth anthropometrics. Design: Population‐based prospective cohort study. Setting: University Hospital. Population: 1486 mother–child dyads from Odense Child Cohort. Methods: Maternal blood samples were collected at gestational weeks 27–30 and free testosterone (FT) levels were calculated using the Vermeulen equation from total testosterone (TT) analysed by mass spectrometry and sex hormone binding globulin. Associations between FT or TT levels and birth anthropometrics were analysed with multiple linear regression models according to offspring sex with adjustment for maternal age, parity, smoking and educational level. Analyses were repeated with polycystic ovary syndrome as exposure for offspring birth anthropometrics. Main outcome measures: Offspring birth weight (BW), birth length, abdominal and head circumferences. Results: Maternal mean (SD) age was 30.2 (4.5) years and pre‐pregnancy body mass index was 23.5 (5.3) kg/m2. In boys (n = 787), higher FT was associated with lower birth weight (adjusted doubling constant = −65.53, P = 0.010), shorter birth length (adjusted doubling constant = −0.43, P < 0.001), and lower abdominal circumference (adjusted doubling constant = −0.39, P < 0.001); Higher TT was associated with lower abdominal circumference (adjusted doubling constant = −0.25, P = 0.028). In girls, no associations were found between maternal FT or TT and offspring anthropometrics. Conclusions: Higher maternal free testosterone exposure was linked to reduced birth weight, length and abdominal circumference in boys, whereas girls were not susceptible to maternal testosterone exposure. [ABSTRACT FROM AUTHOR]

Introduction Perfluoroalkyl acids (PFAA) are persistent chemicals used as surface repellants in fabrics and food packaging due to water-, stain-, and grease-resistant properties (ATSDR 2018). Prevalent routes of PFAA exposure [...], Background: Perfluoroalkyl acids (PFAA) are repellants that cross the placental barrier, enabling interference with fetal programming. Maternal PFAA concentrations have been associated with offspring obesity and dyslipidemia in childhood and adulthood, but this association has not been studied in infancy. Objectives: We investigated associations between maternal PFAA concentrations and repeated markers of adiposity and lipid metabolism in infancy. Methods: In the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAA: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 649 women. Offspring were examined at birth (n = 613) and at 3 months (n = 602) and 18 months (n = 503) of age. Total cholesterol, LDL, HDL, and triglyceride were evaluated at 3 months (n = 262) and 18 months (n = 198) of age. Mixed effects linear regression models estimated associations between PFAA and standardized (SDS) body mass index (BMI), ponderal index, and waist circumference. Associations between PFAA and body fat% (BF%) and plasma lipids SDS at 3 months and 18 months of age were investigated with linear regression models. Results: PFNA and PFDA were associated with higher BMI SDS [adjusted [beta] = 0.26; 95% confidence interval (CI): 0.03, 0.49 and [beta] = 0.58; 95% CI: -0.03, 1.19, respectively, for 1-ng/mL increases] and ponderal index SDS ([beta] = 0.36; 95% CI: 0.13, 0.59 and [beta] = 1.02; 95% CI: 0.40, 1.64, respectively) at 3 and 18 months of age (pooled) in girls. Corresponding estimates for boys were closer to the null but not significantly different from estimates for girls. In boys and girls (combined), PFNA and PFDA were associated with BF% at age 3 months (for 1-ng/mL PFDA, [beta] = 0.40; 95% CI: 0.04, 0.75), and PFDA was associated with total cholesterol SDS at 18 months ([beta] = 1.06; 95% CI: 0.08, 2.03) (n = 83). Discussion: Prenatal PFAA were positively associated with longitudinal markers of adiposity and higher total cholesterol in infancy. These findings deserve attention in light of rising rates of childhood overweight conditions and dyslipidemia. https://doi.org/10.1289/EHP5184

BACKGROUND: Perfluoroalkyl acids (PFAA) are repellants that cross the placental barrier, enabling interference with fetal programming. Maternal PFAA concentrations have been associated with offspring obesity and dyslipidemia in childhood and adulthood, but this association has not been studied in infancy. OBJECTIVES: We investigated associations between maternal PFAA concentrations and repeated markers of adiposity and lipid metabolism in infancy. METHODS: In the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAA: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 649 women. Offspring were examined at birth (n=613) and at 3 months (n=602) and 18 months (n=503) of age. Total cholesterol, LDL, HDL, and triglyceride were evaluated at 3 months (n=262) and 18 months (n=198) of age. Mixed effects linear regression models estimated associations between PFAA and standardized (SDS) body mass index (BMI), ponderal index, and waist circumference. Associations between PFAA and body fat% (BF%) and plasma lipids SDS at 3 months and 18 months of age were investigated with linear regression models. RESULTS: PFNA and PFDA were associated with higher BMI SDS [adjusted β=0.26; 95% confidence interval (CI): 0.03, 0.49 and β=0.58; 95% CI: -0.03, 1.19, respectively, for 1-ng/mL increases] and ponderal index SDS (β=0.36; 95% CI: 0.13, 0.59 and β=1.02; 95% CI: 0.40, 1.64, respectively) at 3 and 18 months of age (pooled) in girls. Corresponding estimates for boys were closer to the null but not significantly different from estimates for girls. In boys and girls (combined), PFNA and PFDA were associated with BF% at age 3 months (for 1-ng/mL PFDA, β=0.40; 95% CI: 0.04, 0.75), and PFDA was associated with total cholesterol SDS at 18 months (β=1.06; 95% CI: 0.08, 2.03) (n=83). DISCUSSION: Prenatal PFAA were positively associated with longitudinal markers of adiposity and higher total cholesterol in infancy. These findings deserve attention in light of rising rates of childhood overweight conditions and dyslipidemia. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D deficiency is common in pregnancy, especially in obese women. Lifestyle intervention could potentially result in higher levels of vitamin D. We therefore aimed to study the effect of lifestyle intervention during pregnancy on serum levels of 25-hydroxyvitamin D (25(OH)D).Material and Methods: A total of 360 obese women were randomized before gestational age 14 weeks to lifestyle intervention (diet and exercise) or routine clinical follow up (controls). Clinical outcomes and levels of 25(OH)D were determined three times: At gestational age 12-15 weeks (baseline), gestational age 28-30 weeks and 6 months postpartum.Results: A total of 304 (84%) women completed the intervention study and 238 (66%) attended postpartum follow up. Vitamin D levels were similar in the two groups at baseline. At gestational age 28-30 weeks and 6 months postpartum, 25(OH)D levels were significantly higher in the intervention group than in controls (75.6 vs 66.8 nmol/L, P = 0.009) and (54.8 vs 43.1 nmol/L, P = 0.013), respectively. Concurrently, vitamin D deficiency (25-hydroxyvitamin D <50 nmol/L) was less frequent in the intervention group than in controls: 15 vs 25% (P = 0.038) at gestational age 28-30 and 45 vs 63% (P = 0.011) 6 months postpartum, respectively.Conclusions: Lifestyle intervention during pregnancy was associated with significantly increased vitamin D levels in late pregnancy and postpartum compared with controls. [ABSTRACT FROM AUTHOR]

Introduction: Low socioeconomic status (SES) may be associated with increased risk of polycystic ovary syndrome (PCOS) and vice versa. Possible associations between SES, obesity and ethnicity in PCOS are undetermined.Material and Methods: National register-based study including women with PCOS aged 25 years or above (PCOS Denmark and an embedded cohort; PCOS Odense University Hospital [OUH]) and one control population. PCOS Denmark (n = 13 891) included women with PCOS in the Danish National Patient Register. Women in PCOS OUH underwent clinical examination (n = 814). Three age-matched controls were included per patient (n = 41 584). The main outcome measure was SES (personal income, occupational status and education).Results: The median (Q1; Q3) age of women in PCOS Denmark and controls was 33 (29; 39) years. Women with personal income in the lower tertile had a higher probability of a PCOS diagnosis than women in the high-income tertile (adjusted odds ratio [aOR] 1.5, 95% confidence interval [CI] 1.4-1.6). Women who were unemployed or on welfare payment (aOR 1.5, 95% CI 1.4-1.6), or who retired early (OR 1.8, 95% CI 1.7-2.0) had a higher probability of a PCOS diagnosis than women affiliated to the labor market. Women originating from the Middle East more often had PCOS (aOR 3.2, 95% CI 2.8-3.7) compared with women originating from Europe. In PCOS OUH, SES was lower in obese than in normal weight women.Conclusions: A diagnosis of PCOS was associated with lower SES. In PCOS, women of foreign origin and women with obesity more often had low SES. [ABSTRACT FROM AUTHOR]

Objective: To study effects of lifestyle intervention on metabolic and clinical outcomes in obese women fulfilling the World Health Organization (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) in early gestation.Research Design and Methods: Secondary analysis of data from the Lifestyle in Pregnancy (LiP) study, a lifestyle randomized controlled trial in 304 pregnant women with BMI ≥30 kg/m2. Early GDM (week 12-15) was diagnosed according to modified WHO 2013 GDM criteria: fasting venous plasma glucose ≥5.1 mmol/L and/or 2-h capillary blood glucose (CBG) ≥8.5 mmol/L (75-g oral glucose tolerance test [OGTT]). Women with treated GDM fulfilling local Danish GDM criteria (2-h CBG ≥9.0 mmol/L) (n = 16) and women with normal OGTT (n = 198) were excluded.Results: Of 90 women with early GDM, 36 received lifestyle intervention and 54 standard care. All were Caucasian, and median age was 29 years (interquartile range 27-33) and BMI 34.5 kg/m2 (32.3-38.1). All baseline characteristics were similar in the lifestyle intervention and standard care groups. At gestational week 28-30, the women in the lifestyle intervention group had significantly higher fasting total cholesterol and fasting LDL. All other metabolic parameters including measurements of glucose, insulin, and HOMA of insulin resistance were similar. There were more planned cesarean sections in the lifestyle intervention group (22.2 vs. 5.6%), but all other obstetric outcomes were similar.Conclusions: Lifestyle intervention in obese women fulfilling WHO 2013 GDM criteria in early pregnancy was not effective in improving obstetric or metabolic outcomes. Future studies should focus on interventions starting prepregnancy. [ABSTRACT FROM AUTHOR]