Medical Birth Registry Of Norway Research Articles

P-447 Gestational weight gain in relation to time-to-pregnancy and conception by assisted reproductive technology

Abstract Study question Does the gestational weight gain trajectory differ across levels of time-to-pregnancy (TTP) for spontaneously conceived pregnancies and pregnancies conceived by assisted reproductive technology (ART)? Summary answer Women with ART pregnancies had lower weekly weight gain during the third trimester compared with women with spontaneous conceptions with TTP ≤3. What is known already Studies suggest that both prolonged TTP and conception by ART may increase the risk of pregnancy complications and affect perinatal outcomes such as birthweight. Suboptimal gestational weight gain might further increase the risk of adverse pregnancy outcomes. However, it remains unclear whether there may be differences in gestational weight gain according to TTP and ART, which contribute to the subsequent risk of adverse pregnancy outcomes. Study design, size, duration We studied 69,121 singleton planned pregnancies contributed by 60,847 women participating in the Norwegian Mother, Father and Child Cohort Study. Participants completed questionnaires at 15 weeks’ gestation (study entry), 30 weeks’ gestation, and six months postpartum on sociodemographic, reproductive, and behavioral factors. Participants reported their TTP, and up to four weight measurements and corresponding gestational age from preconception through delivery. We identified use of ART in the Medical Birth Registry of Norway. Participants/materials, setting, methods We fitted gestational weight gain trajectories using mixed-effects linear regression models and included an interaction term between time (gestational weeks) and the exposure groups, TTP ≤3 (reference); TTP 4-6; TTP 7-11, TTP ≥12 months, and ART, to assess differences across levels of TTP and conception by ART. The analyses were adjusted for maternal age at start of pregnancy, pre-pregnancy height, educational attainment, pre-pregnancy smoking, parity, and gestational age at birth. Main results and the role of chance The adjusted average weekly weight gain was -15g (95% CI: −19; −12) during the first trimester, 620g (95% CI: 615; 624) during the second trimester, and 491g (95% CI: 489; 494) during the third trimester. When we compared differences in average weekly weight change during the first trimester, we observed little difference between the exposure groups. During the second trimester, compared with TTP≤3 months women with TTP 4-6 months, TTP 7-11 months or TTP ≥12 months gained on average 7g (95% CI: −18; 3), 19g (95% CI: −33; −5) and 15g (95% CI: −29; −1) less per week, respectively, whereas women with ART pregnancies gained 11g more per week (95% CI: −13; 34). However, the results for TTP 4-6 and ART pregnancies were imprecise. During the third trimester, average weekly weight gain did not differ according to TTP for spontaneous conceptions, while women who conceived after ART gained 35g (95% CI: −49; −22) less than women with TTP≤3 each week. Limitations, reasons for caution Because TTP and gestational weight gain were self-reported, non-differential misclassification may have influenced our results. Wider implications of the findings Decelerated weight gain during the third trimester in ART pregnancies compared with women who conceived spontaneously within 3 months might be associated with adverse pregnancy outcomes. Although our findings are imprecise and need to be replicated, monitoring gestational weight gain trajectories might support identification of pregnancies at increased risk. Trial registration number Not applicable

No impact of prenatal paracetamol and folic acid exposure on cord blood DNA methylation in children with attention-deficit/hyperactivity disorder.

Pharmacoepigenetic studies are important to understand the mechanisms through which medications influence the developing fetus. For instance, we and others have reported associations between prenatal paracetamol exposure and offspring DNA methylation (DNAm). Additionally, folic acid (FA) intake during pregnancy has been associated with DNAm in genes linked to developmental abnormalities. In this study, we aimed to: (i) expand on our previous findings showing differential DNAm associated with long-term prenatal paracetamol exposure in offspring with attention-deficit/hyperactivity disorder (ADHD), and (ii) examine if there is an interaction effect of FA and paracetamol on DNAm in children with ADHD. We used data from the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN). We did not identify any impact of paracetamol or any interaction effect of paracetamol and FA on cord blood DNAm in children with ADHD. Our results contribute to the growing literature on prenatal pharmacoepigenetics, but should be replicated in other cohorts. Replication of pharmacoepigenetic studies is essential to ensure robust findings and to increase the clinical relevance of such studies.

Birth size after embryo cryopreservation: larger by all measures?

Are the changes in birthweight after frozen and fresh embryo transfer associated with corresponding changes in other measures of foetal growth and placental efficiency? Although placental efficiency was reduced for both frozen and fresh embryo transfer, children born after frozen embryo transfer (frozen-ET) had symmetrically increased size at birth, whereas children born after fresh embryo transfer (fresh-ET) were asymmetrically smaller at birth, compared to naturally conceived children. In pregnancies following frozen-ET, the risk of being born large, as measured by birthweight, is higher than after natural and fresh-ET conceptions. It is not known whether this is a result of symmetrically increased growth and increased placental efficiency. A Norwegian nationwide registry-based cohort study of 3093 singletons born after frozen-ET, 15 510 singletons born after fresh-ET and 1 125 366 singletons born after natural conception from 1988 to 2015 was performed. We identified 6334 sibships with at least two different conception methods. Data were collected from the Medical Birth Registry of Norway and the Norwegian National Education Database. Main outcome measures were birth length, birthweight, head circumference, ponderal index (birthweight relative to birth length in kg/m3), placental weight, birthweight:placental weight ratio, gestational age, and birthweight z-score. We estimated mean differences between children born after frozen-ET and fresh-ET compared to natural conception, at the population level and within sibships. Adjustments were made for birth year, maternal age, parity, and education. Estimates at the population level and within sibships were consistent for all outcomes, for both fresh and frozen-ET compared to natural conception. Within sibships, children born after frozen-ET had longer mean length (Δ = 0.42 cm, 95% CI 0.29 to 0.55) and head circumference (Δ = 0.32 cm, 95% CI 0.23 to 0.41) at birth, but a similar ponderal index (Δ = 0.11 kg/m3, 95% CI -0.04 to 0.26), compared to naturally conceived. Children born after fresh-ET had a shorter length (Δ = -0.22 cm, 95% CI -0.29 to -0.15) and head circumference (Δ = -0.15 cm, 95% CI -0.19 to -0.10), and lower ponderal index (Δ = -0.15 kg/m3, 95% CI -0.23 to -0.07) at birth compared to natural conception within sibships. Furthermore, mean placental weight was larger after both frozen-ET (Δ = 37 g, 95% CI 28 to 45) and fresh-ET (Δ = 7 g, 95% CI 2 to 13) compared to natural conception within sibships, whereas mean birthweight:placental weight ratio was reduced for both frozen-ET (Δ = -0.11, 95% CI -0.17 to -0.05) and fresh-ET (Δ = -0.13, 95% CI -0.16 to -0.09). A range of sensitivity analyses all gave similar conclusions as the main models, including restriction to full siblings, restriction to single embryo transfer, and adjustment for maternal BMI, height, and smoking. Additional adjustment for maternal BMI, height, and smoking was possible only for a small sample of the study population (15%). Data on causes and duration of infertility, as well as treatment details, were limited. The increased birthweight observed in singletons after frozen-ET is associated with a symmetrically increased birth size and large placentas, also after controlling for maternal factors through sibship analyses. Identifying the responsible treatment factors and the long-term health outcomes are particularly important considering the increase in elective freezing of all embryos. This work was partly supported by the Central Norway Regional Health Authorities (project number 46045000), the Norwegian University of Science and Technology (project number 81850092) and the Research Council of Norway through its Centres of Excellence funding scheme (project number 262700). The authors have no conflicts of interest to declare. N/A.

Effects of prenatal exposure to (es)citalopram and maternal depression during pregnancy on DNA methylation and child neurodevelopment

Studies assessing associations between prenatal exposure to antidepressants, maternal depression, and offspring DNA methylation (DNAm) have been inconsistent. Here, we investigated whether prenatal exposure to citalopram or escitalopram ((es)citalopram) and maternal depression is associated with differences in DNAm. Then, we examined if there is an interaction effect of (es)citalopram exposure and DNAm on offspring neurodevelopmental outcomes. Finally, we investigated whether DNAm at birth correlates with neurodevelopmental trajectories in childhood. We analyzed DNAm in cord blood from the Norwegian Mother, Father and Child Cohort Study (MoBa) biobank. MoBa contains questionnaire data on maternal (es)citalopram use and depression during pregnancy and information about child neurodevelopmental outcomes assessed by internationally recognized psychometric tests. In addition, we retrieved ADHD diagnoses from the Norwegian Patient Registry and information on pregnancies from the Medical Birth Registry of Norway. In total, 958 newborn cord blood samples were divided into three groups: (1) prenatal (es)citalopram exposed (n = 306), (2) prenatal maternal depression exposed (n = 308), and (3) propensity score-selected controls (n = 344). Among children exposed to (es)citalopram, there were more ADHD diagnoses and symptoms and delayed communication and psychomotor development. We did not identify differential DNAm associated with (es)citalopram or depression, nor any interaction effects on neurodevelopmental outcomes throughout childhood. Trajectory modeling identified subgroups of children following similar developmental patterns. Some of these subgroups were enriched for children exposed to maternal depression, and some subgroups were associated with differences in DNAm at birth. Interestingly, several of the differentially methylated genes are involved in neuronal processes and development. These results suggest DNAm as a potential predictive molecular marker of later abnormal neurodevelopmental outcomes, but we cannot conclude whether DNAm links prenatal (es)citalopram exposure or maternal depression with child neurodevelopmental outcomes.

Adverse childhood experiences and pre-pregnancy body mass index in the HUNT study: A population-based cohort study.

Investigate the association between adverse childhood experiences and pre-pregnancy body mass index (BMI) in a population-based cohort in Trøndelag county, Norway. We linked data from the third (2006-2008) or fourth (2017-2019) survey of the Trøndelag Health Study (HUNT) and the Medical Birth Registry of Norway for 6679 women. Multiple logistic regression models were used to examine the association between adverse childhood experiences and pre-pregnancy BMI. Adverse childhood experiences were self-reported in adulthood and included perceiving childhood as difficult, parental divorce, parental death, dysfunctional family environment, bad childhood memories and lack of support from a trusted adult. Pre-pregnancy BMI was derived from the Medical Birth Registry of Norway or BMI measurement from the HUNT survey conducted within 2 years prior to the woman's pregnancy. Perceiving childhood as difficult was associated with higher odds of pre-pregnancy underweight (OR 1.78, 95%CI 0.99-3.22) and obesity (OR 1.58, 95%CI 1.14-2.2). A difficult childhood was positively associated with obesity with an adjusted OR of 1.19, 95%CI 0.79-1.81 (class I obesity), 2.32, 95%CI 1.35-4.01 (class II obesity) and 4.62, 95%CI 2.0-10.65 (class III obesity). Parental divorce was positively associated obesity (OR 1.34, 95%CI 1.10-1.63). Bad childhood memories were associated with both overweight (OR 1.34, 95%CI 1.01-1.79) and obesity (OR 1.63, 95%CI 1.13-2.34). Parental death was not associated with pre-pregnancy BMI. Childhood adversities were associated with pre-pregnancy BMI. Our results suggest that the positive associations between childhood adversities and pre-pregnancy obesity increased with increasing obesity level.

Association between SARS-CoV-2 infection and newly diagnosed hypertension during pregnancy: prospective, population based cohort study

ObjectiveTo study the association between SARS-CoV-2 infection and newly diagnosed hypertension during pregnancy.DesignProspective, population based cohort study.SettingAll singleton pregnancies after 22 completed gestational weeks registered in the Swedish Pregnancy Register...

A population-based study of caesarean section in women with juvenile idiopathic arthritis.

The literature on delivery methods in women with JIA is limited. Active inflammation is a risk factor for caesarean section (CS) in other arthritic diseases. A CS entails a higher risk for complications than vaginal delivery and restricted physical activity in the first weeks after birth. Our objective was to explore a possible association of inflammatory active disease and the proportion of CS in women with JIA. Data from the Norwegian nationwide observational register RevNatus were linked with data from the Medical Birth Registry of Norway (MBRN). Cases comprised singleton births in women with JIA (n = 196) included in RevNatus from 2010 to 2019. Singleton births registered in the MBRN during the same period of time, excluding births in mothers with rheumatic inflammatory diseases, served as population controls (n = 575 798). CS was more frequent in women with JIA (20.4%) and in the subgroup of women with inflammatory active JIA (30.0%) than in population controls (15.6%). Women with active JIA had a risk for elective CS similar to population controls [risk difference 2.3% (95% CI -2.5, 12.9)] and a higher risk for emergency CS [risk difference 14.0% (95% CI 4.3, 27.4)] compared with population controls. Women with active JIA had a higher risk for emergency CS, but not elective CS, compared with population controls.

Prevalence, birth, and clinical characteristics of dyskinetic cerebral palsy compared with spastic cerebral palsy subtypes: A Norwegian register-based study.

To study the prevalence, birth, and clinical characteristics of children with dyskinetic cerebral palsy (CP) in Norway compared with spastic quadriplegic CP and other spastic CP subtypes. Data on children born from 1996 to 2015 were collected from the Norwegian Quality and Surveillance Registry for Cerebral Palsy and the Medical Birth Registry of Norway. One hundred and seventy (6.8%) children had dyskinetic CP. The birth prevalence decreased during 1996 to 2015 from 0.21 to 0.07 per 1000 livebirths (p < 0.001). Dyskinetic CP was more often associated with term/post-term birth, and motor and associated impairments were more severe compared with spastic bilateral and unilateral CP, but less severe than spastic quadriplegic CP. On neuroimaging, grey matter injuries were most prevalent in dyskinetic CP (mainly basal ganglia/thalamus) and spastic quadriplegic CP (mainly cortico-subcortical), white matter injuries in spastic bilateral, and white and grey matter injuries were equally common in spastic unilateral CP. Normal neuroimaging and brain maldevelopment were present in 25% of children with dyskinetic CP. The decrease in birth prevalence of dyskinetic CP was probably due to improved antenatal and perinatal care. Potential sentinel events at term were more common in dyskinetic CP than other spastic CP subtypes. However, probable antenatal aetiologies were most prevalent. Motor and associated impairments were less severe in children with dyskinetic CP compared with spastic quadriplegic CP. Birth prevalence of those with dyskinetic and spastic bilateral cerebral palsy (CP) in Norway decreased between 1996 and 2015. Potential sentinel events at term were more common in dyskinetic CP. Nonetheless, probable antenatal aetiologies were most prevalent in dyskinetic CP. Basal ganglia/thalamus lesions were more common in dyskinetic than spastic quadriplegic CP. Motor and associated impairments were milder in dyskinetic than spastic quadriplegic CP.

Seasonal variation in gestational diabetes mellitus among women in Norway: a national population-based study

ObjectivesPrevious research on seasonal variation in the incidence of gestational diabetes mellitus (GDM) has shown inconclusive results. Furthermore, little is known about whether a seasonal variation in GDM might be...

Caesarean section in women with axial spondyloarthritis and psoriatic arthritis: a population-based study

BackgroundThere is sparse documentation on pregnancy outcomes in women with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Data on disease activity are often lacking, preventing the direct investigation of the...

Risk of Subsequent Preeclampsia by Maternal Country of Birth: A Norwegian Population-Based Study

In this nationwide population-based study, we investigated the associations of preeclampsia in the first pregnancy with the risk of preeclampsia in the second pregnancy, by maternal country of birth using data from the Medical Birth Registry of Norway and Statistics Norway (1990-2016). The study population included 101,066 immigrant and 544,071 non-immigrant women. Maternal country of birth was categorized according to the seven super-regions of the Global Burden of Disease study (GBD). The associations between preeclampsia in the first pregnancy with preeclampsia in the second pregnancy were estimated using log-binomial regression models, using no preeclampsia in the first pregnancy as the reference. The associations were reported as adjusted risk ratios (RR) with 95% confidence intervals (CI), adjusted for chronic hypertension, year of first childbirth, and maternal age at first birth. Compared to those without preeclampsia in the first pregnancy, women with preeclampsia in the first pregnancy were associated with a considerably increased risk of preeclampsia in the second pregnancy in both immigrant (n = 250; 13.4% vs. 1.0%; adjusted RR 12.9 [95% CI: 11.2, 14.9]) and non-immigrant women (n = 2876; 14.6% vs. 1.5%; adjusted RR 9.5 [95% CI: 9.1, 10.0]). Immigrant women from Latin America and the Caribbean appeared to have the highest adjusted RR, followed by immigrant women from North Africa and the Middle East. A likelihood ratio test showed that the variation in adjusted RR across all immigrant and non-immigrant groups was statistically significant (p = 0.006). Our results suggest that the association between preeclampsia in the first pregnancy and preeclampsia in the second pregnancy might be increased in some groups of immigrant women compared with non-immigrant women in Norway.

Pregnancies in Women with a Previous Complete Uterine Rupture.

To study the outcomes of new pregnancies after a previous complete uterine rupture. Descriptive study based on population data from the Medical Birth Registry of Norway, the Patient Administration System, and the medical records. Sample. Maternities with a previous complete uterine rupture in Norway during the period 1967-2011 (N = 72), extracted from 2 455 797 maternities. We measured the rate of new complete ruptures and partial ruptures, as well as the maternal and perinatal outcomes of these pregnancies. The characteristics of both previous ruptures and new ruptures were described. Among 72 maternities, there were thirty-seven with previous ruptures in the lower segment (LS) and 35 outside the LS. We found three new complete ruptures and six uneventful partial ruptures, resulting in a rate of 4.2% and 8.3%, respectively. All three complete ruptures occurred preterm in scars outside the LS. The rate of the new complete rupture was 0% in those with previous ruptures in the LS and 8.6% in those with previous ruptures outside the LS. The corrected perinatal mortality was 1.3%, and prematurity (<37 weeks) was high (36.1%); this was noticed even in the absence of new ruptures and was mostly iatrogenic. Two hysterectomies were performed in the absence of rupture and two cases had abnormal invasive placenta. The prognosis for pregnancies after a previous complete uterine rupture is favorable. Prematurity is a problem caused by both obstetrician and mother's anxiety; therefore, the timing of delivery is the most challenging. Management should include careful counseling, vigilance for symptoms, and immediate delivery when a rupture is suspected.

Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study

BackgroundNumerous intrauterine factors may affect the offspring’s growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent.MethodsThis parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age).ResultsHigher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ Pinteraction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ Pinteraction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ Pinteraction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ Pinteraction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ Pinteraction ≤ 0.99).ConclusionsMaternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.

Association of placental and umbilical cord characteristics with cerebral palsy: national cohort study.

Cerebral palsy (CP) is a group of movement disorders usually diagnosed in childhood. A substantial proportion are thought to be caused by antenatal events. Abnormalities of the umbilical cord and placenta are associated with an increased risk of adverse neonatal outcomes, but it is unclear whether these conditions also carry an increased risk of CP. We aimed to determine whether abnormalities of the umbilical cord or placenta are associated with CP and assess if these associations differ by sex of the child or gestational age at birth. We performed a national cohort study by linking data from The Medical Birth Registry of Norway with other national registries. All liveborn singletons born between 1999 and 2017 (n = 1 087 486) were included and followed up until the end of 2019. Diagnoses of CP were provided by the Norwegian National Insurance Scheme and the Norwegian Patient Register. We used generalized estimating equations and multilevel log binomial regression to calculate relative risks (RR), adjusted for year of birth, and stratified analyses were carried out based on sex and gestational age at birth. Exposures were abnormal umbilical cord (velamentous or marginal insertion, single umbilical artery (SUA), knots and entanglement), and placental abnormalities (retained placenta, placental abruption and previa). A total of 2443 cases with CP (59.8% males) were identified. Velamentous cord insertion (adjusted RR (aRR), 2.11 (95% CI, 1.65-2.60)), cord knots (aRR, 1.53 (95% CI, 1.15-2.04)) and placental abnormalities (placenta previa (aRR, 3.03 (95% CI, 2.00-4.61)), placental abruption (aRR, 10.63 (95% CI, 8.57-13.18)) and retained placenta (aRR, 1.71 (95% CI, 1.32-2.22))) carried an increased risk of CP. Velamentous cord insertion was associated with CP regardless of gestational age or sex. A retained placenta was associated with a 2-fold increased risk for CP in males, while the associations of SUA and cord knot with CP were significant only among females. The detection of placental and umbilical cord abnormalities may help identify children at increased risk of CP. The associations between placental or umbilical cord abnormalities and the risk of CP do not vary substantially with gestational age at birth or sex of the child. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Diet in Early Life Is Related to Child Mental Health and Personality at 8 Years: Findings from the Norwegian Mother, Father and Child Cohort Study (MoBa).

There is rising concern about population mental health. Personality and mental health traits manifest early. Sufficient nutrition is fundamental to early development. However, little is known about early life dietary impact on later mental health. The aim of this study was to investigate associations of exposure to a healthy and sustainable antenatal and early childhood diet with personality traits and symptoms of depression and anxiety measured at 8 years of age. This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa) and uses data from the Medical Birth Registry of Norway (MBRN) including 40,566 participants. Mental health measures and personality traits were assessed at 8 years. Dietary data from pregnancy, child age 6 and 18 months and 3 and 7 years were used. With few exceptions, inverse associations were observed between healthier diet at all time points and depression and anxiety symptom scores at age 8. We found positive associations between diet scores at almost all time points and extraversion, benevolence, conscientiousness and imagination. Inverse associations were observed between diet scores and neuroticism. Combined, these findings underpin a probable impact of both maternal pregnancy diet and early childhood diet on several aspects of child mental health.

Body mass index and childhood symptoms of depression, anxiety, and attention-deficit hyperactivity disorder: A within-family Mendelian randomization study.

Higher BMI in childhood is associated with emotional and behavioural problems, but these associations may not be causal. Results of previous genetic studies imply causal effects but may reflect influence of demography and the family environment. This study used data on 40,949 8-year-old children and their parents from the Norwegian Mother, Father and Child Cohort Study (MoBa) and Medical Birth Registry of Norway (MBRN). We investigated the impact of BMI on symptoms of depression, anxiety, and attention-deficit hyperactivity disorder (ADHD) at age 8. We applied within-family Mendelian randomization, which accounts for familial effects by controlling for parental genotype. Within-family Mendelian randomization estimates using genetic variants associated with BMI in adults suggested that a child's own BMI increased their depressive symptoms (per 5 kg/m2 increase in BMI, beta = 0.26 S.D., CI = -0.01,0.52, p=0.06) and ADHD symptoms (beta = 0.38 S.D., CI = 0.09,0.63, p=0.009). These estimates also suggested maternal BMI, or related factors, may independently affect a child's depressive symptoms (per 5 kg/m2 increase in maternal BMI, beta = 0.11 S.D., CI:0.02,0.09, p=0.01). However, within-family Mendelian randomization using genetic variants associated with retrospectively-reported childhood body size did not support an impact of BMI on these outcomes. There was little evidence from any estimate that the parents' BMI affected the child's ADHD symptoms, or that the child's or parents' BMI affected the child's anxiety symptoms. We found inconsistent evidence that a child's BMI affected their depressive and ADHD symptoms, and little evidence that a child's BMI affected their anxiety symptoms. There was limited evidence of an influence of parents' BMI. Genetic studies in samples of unrelated individuals, or using genetic variants associated with adult BMI, may have overestimated the causal effects of a child's own BMI. This research was funded by the Health Foundation. It is part of the HARVEST collaboration, supported by the Research Council of Norway. Individual co-author funding: the European Research Council, the South-Eastern Norway Regional Health Authority, the Research Council of Norway, Helse Vest, the Novo Nordisk Foundation, the University of Bergen, the South-Eastern Norway Regional Health Authority, the Trond Mohn Foundation, the Western Norway Regional Health Authority, the Norwegian Diabetes Association, the UK Medical Research Council. The Medical Research Council (MRC) and the University of Bristol support the MRC Integrative Epidemiology Unit.

Association of Prenatal Exposure to Benzodiazepines and Z-Hypnotics With Risk of Attention-Deficit/Hyperactivity Disorder in Childhood

Evidence is limited regarding the safety of prenatal benzodiazepine and z-hypnotic exposure and its association with long-term neurodevelopment in childhood. To quantify the associations of the timing and number of intervals of prenatal exposure to benzodiazepines and/or z-hypnotics with the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood. This cohort study used data from the 1999 to 2008 population-based Norwegian Mother, Father and Child Cohort Study, which are linked to the Medical Birth Registry of Norway, Norwegian Patient Registry, and Norwegian Prescription Database. Two populations of participants were created: a full sample and a mental health sample. The full sample included mothers and their live-born singletons, whereas the mental health sample was restricted to offspring of mothers who reported anxiety, depression, or sleeping problems during pregnancy or 6 months before pregnancy. Data were analyzed from September 2021 to February 2022. Maternal self-report of benzodiazepine and/or z-hypnotic use during pregnancy was grouped into early pregnancy exposure and middle and/or late pregnancy exposure for analysis of the association with timing of exposure, and number of 4-week intervals of exposure was classified (single [1] vs multiple [≥2]) for analysis of the association with number of exposed intervals. The outcome was ADHD, defined as time to ADHD diagnosis or filled prescription for ADHD medication. To control for confounding, inverse probability of treatment-weighted Cox proportional hazards regression models were used. Hazard ratios and 95% CIs were estimated. The weights were derived from propensity score modeling of the probability of benzodiazepine and/or z-hypnotic exposure as a function of potential confounders between the exposure and the outcome, including maternal symptoms of depression and anxiety. The full sample comprised 82 201 pregnancies, and the mental health sample included 19 585 pregnancies. In total, 681 offspring (0.8%) in the full sample and 468 offspring (2.4%) in the mental health sample were prenatally exposed to benzodiazepines and/or z-hypnotics. After weighting, exposure in early (hazard ratio, 0.74; 95% CI, 0.39-1.94) and middle and/or late (hazard ratio, 0.76; 95% CI, 0.35-1.61) pregnancy was not associated with increased risk of childhood ADHD. There was no evidence of substantial association between the number of exposed intervals during pregnancy and childhood ADHD. Results of this study suggest that there may be no increased risk of childhood ADHD associated with prenatal exposure to benzodiazepines and/or z-hypnotics, regardless of timing of exposure and number of exposed intervals. However, these findings should be interpreted with caution due to low study power.

Is the increasing prevalence of labor induction accompanied by changes in pregnancy outcomes? An observational study of all singleton births at gestational weeks 37-42 in Norway during 1999-2019.

Induction of labor is often performed to prevent adverse perinatal and maternal outcomes, and has become increasingly common. We studied whether changes in prevalence of labor induction in gestational weeks 37-42 weeks were accompanied by changes in adverse pregnancy outcomes or mode of delivery. We used data from the Medical Birth Registry of Norway, and included all singleton births in gestational weeks 37-42 in Norway, 1999-2019 (n=1127 945). We calculated the prevalence of labor induction and outcome measures according to year of birth. We repeated these calculations for each gestational week at birth. The prevalence of labor induction increased from 9.7% to 25.9%, and the increase was particularly high in gestational week 41. A modest decline in fetal deaths was observed in all gestational weeks, except gestational week 41. The overall decline was from 0.18% in 1999-2004 to 0.13% during 2015-2019. There were no overall changes in other perinatal outcomes. The prevalence of postpartum hemorrhage ≥500 ml increased from 11.4% in 1999 to 30.1% in 2019, and operative deliveries increased slightly. The prevalence of acute cesarean section increased from 6.5% to 9.3%, whereas vacuum and/or forceps assisted deliveries increased from 7.8% to 10.4%. A high increase in labor inductions was accompanied by a modest decline in fetal deaths, but no decline in other adverse perinatal outcomes. In settings where the prevalence of adverse perinatal outcomes is low, the beneficial effect of increased use of labor induction may not outweigh the side effects or the costs.

S124 Antibiotic Exposure Before 2 Years of Age is Associated With Increased Risk of Pediatric IBD in a Norwegian Nation-Wide Study

Background: The incidence of pediatric IBD (PIBD) rises. This development is likely related to environmental factors that cause disturbances in the gut microbiota. The infant’s microbiome is shaped among other factors by exposure to the maternal microbiome and reaches adult diversity around 3 years age. Antibiotics impact the developing microbiome. Earlier studies have shown an association between PIBD and postnatal antibiotic exposure but lack information on prenatal antibiotic exposure and potential confounders. Thus, the primary aim of this study was to determine whether prenatal antibiotic exposure and antibiotics the first 2 years of life are independently associated with subsequent PIBD, before a mature and stabilized gut microbiome is established. Methods: We conducted a nationwide register-based cohort study using data from the Norwegian Patient Registry to identify children with pediatric IBD <18 years born from 2004 to 2012. Dispensed antibiotics were retrieved from the Norwegian Prescription Database, and the Medical Birth Registry of Norway and Statistics Norway contributed with potential confounding factors. The unique personal ID number given to all new-born in Norway was used to connect the registers. All children were followed until December 31, 2020. We analyzed whether use of pre- and postnatal antibiotics until 2 years of age were associated with subsequent IBD by logistic regression adjusted for potential confounders. Results: The study-population included 536,821 children; 758 were classified as PIBD cases distributed as: 403 (53%) Crohn`s Disease, 243 (32%) Ulcerative Colitis and 112 (15%). IBD Unclassified. The IBD cases included 423 boys and 335 girls with a male predominance among the CD cases (2.2: 1). In the main analysis, sex-adjusted odds ratio (aOR) for developing IBD when exposed to antibiotics before 2 years of age compared to no exposure was 1.40 (95% CI: 1.21-1.61). After adjustment for prenatal antibiotic exposure the aOR was 1.39 (95% 1.20-1.59). Further adjustments for potential confounders as mode of delivery, preeclampsia, birthweight and gestational age, season of birth and maternal age, education, smoking, and parity did not change the OR estimates more than +/- 0.01. We found the strongest association for ≥2 courses of antibiotic exposures (aOR 2.14 (95% 1.34-3.43) and for broad-spectrum AB (aOR 2.36 95%CI: 1.45-3.83) compared to no exposure. This association was driven by the CD cases (aOR 1.59 with 95%CI: 1.31-1.94 P<0.01) while no significant association to antibiotic exposure was observed for the UC cases (aOR 1.12 95%CI: 0.87-1.44 P=0.89). Antibiotic exposure during the last trimester was associated with offspring PIBD (aOR 1.23 95%CI: 1.01-1.51), but this association was borderline significant after adjustment for postnatal antibiotic exposure (P = 0.07). Conclusion(s): In a nation-wide, register-based study from Norway, children exposed to antibiotics before 2 years of age were 1.4 -fold more likely to develop IBD before the age 18 years than controls. This association was found for CD only and was robust to adjustments for prenatal antibiotic exposures and other potential confounders.

Different pathways for preterm birth between singleton and twin pregnancies: a population-based registry study of 481 176 nulliparous women.

To explore the contribution of pregnancy-related complications on the prevalence of extremely, very and late preterm births in singleton and twin pregnancies. To study the risk of spontaneous preterm birth in twin pregnancies compared with singleton pregnancies. Population-based registry study. Medical birth registry of Norway and Statistics Norway. Nulliparous women with singleton (n=472 449) or twin (n=8727) births during 1999-2018. Prevalence rates of pregnancy-related complications for extremely, very and late preterm birth in twin and singleton pregnancies were calculated with 95% confidence intervals. Multivariable logistic regression was applied to assess odds ratios for preterm birth, adjusted for obstetric and socio-economic factors. Extremely preterm (<28+0 weeks of gestation), very preterm (28+0 -33+6 weeks of gestation) and late preterm (34+0 -36+6 weeks of geatation) birth. Preterm birth was significantly more prevalent in twin pregnancies than in singleton pregnancies in all categories: all preterm (54.7% vs 6.1%), extremely preterm (3.6% vs 0.4%), very preterm (18.2% vs 1.4%) and late preterm (33.0% vs 4.3%) births. Stillbirth, congenital malformation and pre-eclampsia were more prevalent in twin pregnancies than in singleton pregnancies, but the prevalence of complications differed in the three categories of preterm birth. Pre-eclampsia was more prevalent in singleton than in twin pregnancies ending in extremely and very preterm birth. The adjusted odds of spontaneous preterm live birth were between 19- and 54-fold greater in twin pregnancies than in singleton pregnancies. Singleton and twin pregnancies seem to have different pathways leading to extremely, very and late preterm birth.