Urinary Incontinence in Midlife According to Weight Changes Across and After Childbearing Years.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate how weight change across and after the childbearing years was associated with urinary incontinence (UI) in midlife. METHODS: Data were obtained from 35,645 women responding to the Maternal Follow-up questionnaire in the Danish National Birth Cohort in 2013-2014. Outcome was self-reported UI and its subtypes. Exposures were changes in body mass index (BMI) across and after the childbearing years. Adjusted odds ratios were estimated using logistic regression. RESULTS: At follow-up, the mean age was 44 years and 32% experienced UI. Compared with stable weight, weight gain across the childbearing years of > 1 to 3, > 3 to 5 or > 5 BMI units increased the odds of any UI by 15%, 27%, and 41% respectively. For mixed UI, the odds increased by 23%, 41%, and 68% in these groups. Weight gain after childbearing showed the same pattern, but with a higher increase in the odds of mixed UI (25%, 60%, and 95% in the respective groups). Women with any weight loss during this period had 9% lower odds of any UI than women with a stable weight. CONCLUSIONS: Weight gain across and after childbearing increased the risk of UI in midlife, especially the subtype mixed UI. Weight loss after childbearing decreased the risk.

Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes.

BACKGROUND: Higher maternal pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and perinatal outcomes. However, whether these associations are causal remains unclear. METHODS: We explored the relation of maternal pre-/early-pregnancy BMI with 20 pregnancy and perinatal outcomes by integrating evidence from three different approaches (i.e. multivariable regression, Mendelian randomisation, and paternal negative control analyses), including data from over 400,000 women. RESULTS: All three analytical approaches supported associations of higher maternal BMI with lower odds of maternal anaemia, delivering a small-for-gestational-age baby and initiating breastfeeding, but higher odds of hypertensive disorders of pregnancy, gestational hypertension, preeclampsia, gestational diabetes, pre-labour membrane rupture, induction of labour, caesarean section, large-for-gestational age, high birthweight, low Apgar score at 1 min, and neonatal intensive care unit admission. For example, higher maternal BMI was associated with higher risk of gestational hypertension in multivariable regression (OR = 1.67; 95% CI = 1.63, 1.70 per standard unit in BMI) and Mendelian randomisation (OR = 1.59; 95% CI = 1.38, 1.83), which was not seen for paternal BMI (OR = 1.01; 95% CI = 0.98, 1.04). Findings did not support a relation between maternal BMI and perinatal depression. For other outcomes, evidence was inconclusive due to inconsistencies across the applied approaches or substantial imprecision in effect estimates from Mendelian randomisation. CONCLUSIONS: Our findings support a causal role for maternal pre-/early-pregnancy BMI on 14 out of 20 adverse pregnancy and perinatal outcomes. Pre-conception interventions to support women maintaining a healthy BMI may reduce the burden of obstetric and neonatal complications. FUNDING: Medical Research Council, British Heart Foundation, European Research Council, National Institutes of Health, National Institute for Health Research, Research Council of Norway, Wellcome Trust.

Parity, mode of birth, and long-term gynecological health: A follow-up study of parous and nonparous women in the Australian Longitudinal Study on Women's Health cohort.

BACKGROUND: Although gynecological health issues are common and cause considerable distress, little is known about their causes. We examined how birth history is associated with urinary incontinence (UI), severe period pain, heavy periods, and endometriosis. METHODS: We studied 7700 women in the Australian Longitudinal Study on Women's Health with an average follow-up of 10.9 years after their last birth. Surveys every third year provided information about birth history and gynecological health. Logistic regression was used to estimate how parity, mode of birth, and vaginal tears were associated with gynecological health issues. Presented results are adjusted odds ratios (OR) with 95% confidence intervals. RESULTS: UI was reported by 16%, heavy periods by 31%, severe period pain by 28%, and endometriosis by 4%. Compared with women with two children, nonparous women had less UI (OR 0.35 [0.26-0.47]) but tended to have more endometriosis (OR 1.70 [0.97-2.96]). Also, women with only one child had less UI (OR 0.77 [0.61-0.98]), but more severe period pain (OR 1.24 [1.01-1.51]). Women with 4+ children had more heavy periods (OR 1.42 [1.07-1.88]). Compared with women with vaginal birth(s) only, women with only cesarean sections or vaginal birth after cesarean section had less UI (ORs 0.44 [0.34-0.58] and 0.55 [0.40-0.76]), but more endometriosis (ORs 1.91 [1.16-3.16] and 2.31 [1.25-4.28]) and heavy periods (ORs 1.21 [1.00-1.46] and 1.35 [1.06-1.72]). Vaginal tear(s) did not increase UI after accounting for parity and birth mode. CONCLUSION: While women with vaginal childbirth(s) reported more urinary incontinence, they had less menstrual complaints and endometriosis.

Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.

Prayer and meditation practices in the early COVID-19 pandemic: A nationwide survey among Danish pregnant women. The COVIDPregDK study.

BACKGROUND: The emergence of the COVID-19 pandemic and the derived changes in maternity care have created stress and anxiety among pregnant women in different parts of the world. In times of stress and crisis, spirituality, including spiritual and religious practices, may increase. OBJECTIVE: To describe if the COVID-19 pandemic influenced pregnant women's considerations and practises of existential meaning-making and to investigate such considerations and practices during the early pandemic in a large nationwide sample. METHODS: We used survey data from a nationwide cross-sectional study sent to all registered pregnant women in Denmark during April and May 2020. We used questions from four core items on prayer and meditation practices. RESULTS: A total of 30,995 women were invited, of whom 16,380 participated (53%). Among respondents, we found that 44% considered themselves believers, 29% confirmed a specific form of prayer, and 18% confirmed a specific form of meditation. In addition, most respondents (88%) reported that the COVID-19 pandemic had not influenced their responses. CONCLUSION: In a nationwide Danish cohort of pregnant women, existential meaning-making considerations and practices were not changed due to the COVID-19 pandemic. Nearly one in two study participants described themselves as believers, and many practised prayer and/or meditation.

Genetic effects on the timing of parturition and links to fetal birth weight.

The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal-fetal relationship between gestational duration and birth weight.

Body mass index, waist circumference, and urinary incontinence in midlife: A follow-up of mothers in the Danish National Birth Cohort.

BACKGROUND: Obesity is a modifiable risk factor for urinary incontinence, yet few studies have investigated how waist circumference as compared to body mass index (BMI) influences the risk of urinary incontinence. OBJECTIVE: To estimate how BMI and waist circumference associates with risk of urinary incontinence in midlife and determine which of the two is the strongest predictor of urinary incontinence. METHODS: Cohort study among mothers in the Danish National Birth Cohort. Weight and waist circumference were self-reported 7 years after cohort entry. Symptoms of urinary incontinence in midlife were self-reported using the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and analyzed continuously and as presence or absence of any, stress (SUI), urgency (UUI), and mixed (MUI) urinary incontinence. Linear and log binomial regressions were used to calculate mean differences and risk ratios (RR) with 95% confidence intervals (CI). Restricted cubic splines were generated to explore nonlinear relationships. RESULTS: Among 27 254 women at a mean age of 44.2 years, any urinary incontinence was reported by 32.1%, SUI by 20.9%, UUI by 2.4%, and MUI by 8.6%. For all outcomes, increases in risk were similar with higher BMI and waist circumference. The estimates of association were strongest for MUI (RR 1.10, 95% CI 1.08;1.12 and RR 1.12, 95% CI 1.10;1.14 for half a standard deviation increase in BMI and waist circumference, respectively). While increases in risk of the other outcomes were seen across the entire range of BMI and waist circumference, the risk of SUI rose until BMI 28 kg/m2 (waist circumference 95 cm), and then fell slightly. CONCLUSIONS: Symptoms of urinary incontinence and prevalence of any urinary incontinence, SUI, UUI, and MUI increased with higher BMI and waist circumference. Self-reported BMI and waist circumference were equally predictive of urinary incontinence.

Parity and mode of birth and their relationships with quality of life: A longitudinal study.

OBJECTIVE: To examine how (a) parity and (b) mode of birth were associated with later Quality of Life (QOL) in young adult women, with a mean follow-up of 11.0 years. DESIGN: Prospective cohort study. SETTING: Australia. R SAMPLE: A total of 7770 women participating in the 1973-1978 cohort of the Longitudinal Study of Women's Health. METHODS: Linear regression models were used to estimate (1) prospective associations between parity and mode of birth with eight subscale and two summary scores of the SF36, assessed after a mean follow-up of 11 years., and (2) differences between SF36 scores at follow up for women in different parity and mode of birth categories. MAIN OUTCOME MEASURE: Quality of Life as measured by the SF36. RESULTS: Women experiencing no births (parity 0) and one birth (parity 1) had lower scores on all the physical health measures, and on some mental health measures, than women who had 2 births (parity 2) (all p<0.05). CONCLUSIONS: Parity and mode of birth may have long-term implications for women's physical and mental health. Both childless and women with only one child had poorer physical and mental health than their peers with two children. Women with only caesarean section(s) also had poorer health than women who had vaginal birth/s.

Use of pudendal nerve block among midwives in Norway: A national cross-sectional study.

INTRODUCTION: Pudendal nerve block (PNB) is an effective analgesic during the second stage of labor and for suturing. With the introduction of epidural and spinal analgesia, PNB use decreased considerably. Most midwives receive some teaching on PNB during their midwifery education. The aim of this study was to examine the use of PNB by midwives in Norway. METHODS: This was a cross-sectional study, in January 2020, using an electronic questionnaire which was distributed to approximately 1500 midwives. RESULTS: A total of 527 midwives responded to the questionnaire (35%). Less than half (44.6%) of the midwives used PNB, of whom only half (123/235) used it frequently (at least once a month). The use of PNB was most common at specialized obstetric units with ≥1500 births per year. Midwives who reported good theoretical knowledge and practical skills of PNB used it significantly more often than midwives not reporting these (p<0.001). Reasons for not using PNB were: the lack of practice and experience (72.6%), and never having been taught (42.8%). Midwives reported needing training (83%) and clinical support to start using PNB (43%). CONCLUSIONS: Few midwives use PNB regularly. To increase the use of PNB, midwifery education needs to include both theoretical and practical skills teaching. Midwives with insufficient knowledge and skills require the same teaching and training. In the clinical area, midwives require clinical support and supervision to practice and gain experience. Women are not offered PNB as long as midwives are not confident in providing this method of pain relief.

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

BACKGROUND: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. METHODS: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268). RESULTS: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10-7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10-6) in older children and had methylation differences in the same direction. CONCLUSIONS: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.

The COVIDPregDK Study: A national survey on pregnancy during the early COVID-19 pandemic in Denmark.

AIM: We aimed to describe the aim, data collection and content from a survey completed among pregnant women during the first peak of the COVID-19 pandemic in Denmark. METHODS: The declaration of the COVID-19 pandemic in early 2020 challenged pregnant women's mental well-being due to a concern for their unborn child and their need for healthcare services through pregnancy and birth. To explore how the COVID-19 pandemic and the intensified measures such as the lockdown of Denmark impacted pregnant women's well-being and mental health, we conducted a questionnaire survey in the spring of 2020 when the COVID-19 pandemic was at its first peak, and the consequences for pregnant women and the unborn child were very uncertain. All women residing in Denmark and registered with an ongoing pregnancy on 24 April 2020 were invited to participate. The questionnaire included background information, variables on COVID-19 symptoms and validated batteries of questions on loneliness, anxiety, stress, quality of life, meditation and prayers. Additional questions were included to examine concerns related to pregnancy and childbirth during the pandemic. COHORT CHARACTERISTICS: Almost 18,000 women answered the questionnaire, which represents 60% of all invited women who experienced a national lockdown for the first time. Their median age was 30 years, and they were more likely to be multiparous. CONCLUSIONS: Data from the COVIDPregDK Study will enable us to gain valuable knowledge on how the pandemic, the intensified measures from the health authorities and the national lockdown affected pregnant women's mental health and their concerns during the COVID-19 pandemic.

Sexual health in parous women with a history of polycystic ovary syndrome: A national cross-sectional study in Denmark.

OBJECTIVE: To examine associations between polycystic ovary syndrome (PCOS) and sexual health in midlife. METHODS: We included 31 645 mothers from the Danish National Birth Cohort who participated in a Maternal Follow up in 2013-14. A lifetime PCOS diagnosis was self-reported. Sexual health was assessed by specific sexual problems including reduced sexual desire, insufficient lubrication, difficulty in obtaining orgasm, vaginismus and pain during intercourse within the past year. We also generated a combined outcome which was positive if the women reported one or more sexual problems. Logistic regression was used to estimate adjusted odds ratios (aOR) for sexual problems with 95% confidence intervals (CI). RESULTS: Participants were on average 44 years old, and 920 women (2.9%) had ever had PCOS. One or more sexual problems were more often reported in women with PCOS compared with other women (42.6% versus 36.3%, aOR 1.29, 95% CI 1.13-1.48). Especially reduced sexual desire (25.6% versus 21.0%, aOR 1.29, 95% CI 1.10-1.50) and dyspareunia (11.4% versus 8.7%, aOR 1.34, 95% CI 1.09-1.66) were more frequent in women with PCOS. These associations were slightly weakened when further adjusting for mental and somatic health problems. CONCLUSION: Our data suggest that PCOS is linked to long-term impaired sexual health, especially reduced sexual desire and dyspareunia.

Associations of maternal birth weight, childhood height, BMI, and change in height and BMI from childhood to pregnancy with risks of preterm delivery.

BACKGROUND: It remains unknown whether maternal early life body size and changes in height and BMI from childhood to pregnancy are associated with risks of having a preterm delivery. OBJECTIVES: We investigated whether a woman's birth weight, childhood height, BMI, and changes in height and BMI from childhood to pregnancy were associated with preterm delivery. METHODS: We studied 47,947 nulliparous women born from 1940 to 1996 who were included in the Copenhagen School Health Records Register with information on birth weight and childhood heights and weights at ages 7 and/or 13 years. Gestational age was obtained from the Danish Birth Register, as was prepregnancy BMI, for 13,114 women. Deliveries were classified as very (22 to <32 weeks) or moderately (32 to <37 weeks) preterm. Risk ratios (RRs) and 95% CIs were estimated using binomial regression. RESULTS: A woman's birth weight and childhood height were inversely associated with having very and moderately preterm delivery. Childhood BMI had a U-shaped association with having a very preterm delivery; at age 7 years, compared to a BMI z score of 0, the RRs were 1.31 (95% CI, 1.11-1.54) for a z score of -1 and 1.18 (95% CI, 1.01-1.38) for a z score of +1. Short stature in childhood and adulthood was associated with higher risks of very and moderately preterm delivery. Changing from a BMI at the 85th percentile at 7 years (US CDC reference) to a prepregnancy BMI of 22.5 kg/m2 was associated with RRs of 1.12 (95% CI, 0.91-1.37) and 0.88 (95% CI, 0.78-0.99) for very and moderately preterm delivery, respectively, compared to a reference woman at the 50th percentile at 7 years (22.5 kg/m2 prepregnancy BMI). CONCLUSIONS: Maternal birth weight, childhood height, and BMI are associated with very and moderately preterm delivery, although in different patterns. Consistent short stature is associated with very and moderately preterm delivery, whereas normalizing BMI from childhood to pregnancy may reduce risks of having a very preterm delivery.

Menstrual pain and sexual health in mothers-A cross-sectional study in the Danish National Birth Cohort.

INTRODUCTION: Prevalence and consequences of menstrual pain have mainly been studied in younger women. We aimed to describe the prevalence of menstrual pain in mothers and its association with sexual problems. MATERIAL AND METHODS: A cross-sectional study using questionnaire data from the Maternal Follow Up (2013-2014) in the Danish National Birth Cohort (1996-2002). Of 82 569 eligible mothers, 43 639 (53%) completed the follow up. Of these, 24 000 women had a partner, and answered the questions on menstrual pain. Log binomial regression was used to calculate prevalence proportion ratios (PPR) with 95% CI for the association between menstrual pain and specific sexual problems. RESULTS: Menstrual pain was reported by 16 464 women (69%), and severe menstrual pain by 19%. Treatment had previously been requested by 19% of women with menstrual pain. The most common treatment was oral contraceptives, but for 18% of women seeking treatment, no treatment was given. Women with menstrual pain were more likely to report reduced sexual desire (PPR 1.22, 95% CI 1.15-1.29), vaginismus (PPR 1.31, 95% CI 0.96-1.78), and dyspareunia (PPR 1.63, 95% CI 1.47-1.81), in particular deep dyspareunia (PPR 1.92, 95% CI 1.67-2.20). CONCLUSIONS: A majority of Danish mothers in mid-life experienced menstrual pain, and these women more often reported reduced sexual desire, vaginismus, and deep dyspareunia. Few women sought and received treatment for menstrual pain. Healthcare practitioners should be aware that menstrual pain can affect parous women and co-occurs with sexual problems. Future studies should identify barriers to seeking and receiving adequate treatment for menstrual pain.

Do genetic risk scores for childhood adiposity operate independent of BMI of their mothers?

OBJECTIVES: Genetic predisposition and maternal body mass index (BMI) are risk factors for childhood adiposity, defined by either BMI or overweight. We aimed to investigate whether childhood-specific genetic risk scores (GRSs) for adiposity-related traits are associated with childhood adiposity independent of maternal BMI, or whether the associations are modified by maternal BMI. METHODS: We constructed a weighted 26-SNP child BMI-GRS and a weighted 17-SNP child obesity-GRS in overall 1674 genotyped children within the Danish National Birth Cohort. We applied a case-cohort (N = 1261) and exposure-based cohort (N = 912) sampling design. Using logistic regression models we estimated associations of the GRSs and child overweight at age 7 years and examined if the GRSs influence child adiposity independent of maternal BMI (per standard deviation units). RESULTS: In the case-cohort design analysis, maternal BMI and the child GRSs were associated with increased odds for childhood overweight [OR for maternal BMI: 2.01 (95% CI: 1.86; 2.17), OR for child BMI-GRS: 1.56 (95% CI: 1.47; 1.66), and OR for child obesity-GRS 1.46 (95% CI: 1.37; 1.54)]. Adjustment for maternal BMI did not change the results, and there were no significant interactions between the GRSs and maternal BMI. However, in the exposure-based cohort design analysis, significant interactions between the child GRSs and maternal BMI on child overweight were observed, suggesting 0.85-0.87-fold attenuation on ORs of child overweight at higher values of maternal BMI and child GRS. CONCLUSION: GRSs for childhood adiposity are strongly associated with childhood adiposity even when adjusted for maternal BMI, suggesting that the child-specific GRSs and maternal BMI contribute to childhood overweight independent of each other. However, high maternal BMI may attenuate the effects of child GRSs in children.

Maternal weight change from prepregnancy to 18 months postpartum and subsequent risk of hypertension and cardiovascular disease in Danish women: A cohort study.

BACKGROUND: One-fourth of women experience substantially higher weight years after childbirth. We examined weight change from prepregnancy to 18 months postpartum according to subsequent maternal risk of hypertension and cardiovascular disease (CVD). METHODS AND FINDINGS: We conducted a cohort study of 47,966 women with a live-born singleton within the Danish National Birth Cohort (DNBC; 1997-2002). Interviews during pregnancy and 6 and 18 months postpartum provided information on height, gestational weight gain (GWG), postpartum weights, and maternal characteristics. Information on pregnancy complications, incident hypertension, and CVD was obtained from the National Patient Register. Using Cox regression, we estimated adjusted hazard ratios (HRs; 95% confidence interval [CI]) for hypertension and CVD through 16 years of follow-up. During this period, 2,011 women were diagnosed at the hospital with hypertension and 1,321 with CVD. The women were on average 32.3 years old (range 18.0-49.2) at start of follow-up, 73% had a prepregnancy BMI <25, and 27% a prepregnancy BMI ≥25. Compared with a stable weight (±1 BMI unit), weight gains from prepregnancy to 18 months postpartum of >1-2 and >2 BMI units were associated with 25% (10%-42%), P = 0.001 and 31% (14%-52%), P < 0.001 higher risks of hypertension, respectively. These risks were similar whether weight gain presented postpartum weight retention or a new gain from 6 months to 18 months postpartum and whether GWG was below, within, or above the recommendations. For CVD, findings differed according to prepregnancy BMI. In women with normal-/underweight, weight gain >2 BMI units and weight loss >1 BMI unit were associated with 48% (17%-87%), P = 0.001 and 28% (6%-55%), P = 0.01 higher risks of CVD, respectively. Further, weight loss >1 BMI unit combined with a GWG below recommended was associated with a 70% (24%-135%), P = 0.001 higher risk of CVD. No such increased risks were observed among women with overweight/obesity (interaction by prepregnancy BMI, P = 0.01, 0.03, and 0.03, respectively). The limitations of this observational study include potential confounding by prepregnancy metabolic health and self-reported maternal weights, which may lead to some misclassification. CONCLUSIONS: Postpartum weight retention/new gain in all mothers and postpartum weight loss in mothers with normal-/underweight may be associated with later adverse cardiovascular health.

Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation.

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.

Associations between work environment, health status and sick leave among pregnant employees.

Aims: To study the associations between and timing of psychosocial and physical work factors and health status on sick leave among Danish pregnant employees. Methods: A total of 910 pregnant women completed a questionnaire in gestational weeks 12 (baseline) and 27 (follow-up). Information about psychosocial and physical work factors and health status was obtained at baseline. Associations with sick leave ⩾14 days were estimated using logistic regression. Further, the impact of timing and duration of exposure on sick leave were examined. Results: A total of 133 women (14.6%) reported ⩾14 days of sick leave at follow-up (27 weeks of gestation). Work-related risk factors for sick leave were high work pace, low influence, low recognition, low job satisfaction, conflict in work-family balance, standing/walking, heavy lifting, and shift work/night shift. Health-related risk factors were burnout, stress, possibility of depression, low work ability, previous sick leave, and poor self-rated health. Being exposed to work-related risk factors during the first 27 weeks of pregnancy or at follow-up increased the risk of sick leave compared with those not exposed at any time or only exposed at baseline. Poor health status increased the risk if women were exposed in the first 27 weeks of pregnancy; however, high possibility of depression was also a risk factor when experienced in early pregnancy. Conclusions: Psychosocial and physical work-related risk factors and poor health status were associated with more sick leave in pregnant employees. Early adjustment of work-related risk factors at the workplace is needed to reduce sick leave.

Risk of gestational diabetes mellitus in nulliparous women - Associations with early life body size and change in body mass index from childhood to adulthood.

AIMS: We examined whether a woman's birthweight, childhood height, body mass index (BMI), and BMI changes from childhood to pregnancy were associated with risks of gestational diabetes mellitus (GDM). METHODS: We studied 13,031 women from the Copenhagen School Health Records Register born 1959-1996 with birthweight and measured anthropometric information at ages 7 and/or 13. The diagnosis of GDM (n = 255) was obtained from a national health register. Risk ratios (RR) were estimated using log-linear binomial regression. RESULTS: Own birthweight and childhood height were inversely associated with GDM. Girls with overweight at age 7 had a higher risk of GDM than girls with normal-weight (RR: 1.79, 95% CI: 1.31, 2.47). Compared to women with normal-weight in childhood and adulthood, risks of GDM were higher in women who developed overweight from age 7 to pregnancy (RR: 4.62; 3.48, 6.14) or had overweight at both times (RR: 4.71; 3.24, 6.85). In women whose BMI normalized from age 7 to pregnancy the RR for GDM was 1.08 (0.47, 2.46). CONCLUSIONS: Lower birthweight, shorter childhood height, and higher childhood BMI are associated with increased risks of GDM. Efforts to help girls maintain a normal BMI before pregnancy may be warranted to minimize risks of GDM.