Maternal Fiber Intake During Pregnancy and Development of Attention-Deficit/Hyperactivity Disorder Symptoms Across Childhood: The Norwegian Mother, Father, and Child Cohort Study.

BACKGROUND: Epidemiological studies suggest that maternal diet quality during pregnancy may influence the risk of neurodevelopmental disorders in offspring. Here, we investigated associations between maternal intake of dietary fiber and attention-deficit/hyperactivity disorder (ADHD) symptoms in early childhood. METHODS: We used longitudinal data of up to 21,852 mother-father-child trios (49.2% female offspring) from MoBa (the Norwegian Mother, Father, and Child Cohort Study). The relationships between maternal fiber intake during pregnancy and offspring ADHD symptoms at ages 3, 5, and 8 years were examined using 1) multivariate regression (overall levels of ADHD symptoms), 2) latent class analysis (subclasses of ADHD symptoms by sex at each age), and 3) latent growth curves (longitudinal change in offspring ADHD symptoms). Covariates were ADHD polygenic scores in child and parents, total energy intake and energy-adjusted sugar intake, parental ages at birth of the child, and sociodemographic factors. RESULTS: Higher maternal prenatal fiber intake was associated with lower offspring ADHD symptom scores at all ages (Bage3 = -0.14 [95% CI, -0.18 to -0.10]; Bage5 = -0.14 [95% CI, -0.19 to -0.09]; Bage8 = -0.14 [95% CI, -0.20 to -0.09]). Of the derived low/middle/high subclasses of ADHD symptoms, fiber was associated with lower risk of belonging to the middle subclass for boys and girls and to the high subclass for girls only (middle: odds ratioboys 0.91 [95% CI, 0.86 to 0.97]/odds ratiogirls 0.86 [95% CI, 0.81 to 0.91]; high: odds ratiogirls 0.82 [95% CI, 0.72 to 0.94]). Maternal fiber intake and rate of change in child ADHD symptoms across ages were not associated. CONCLUSIONS: Low prenatal maternal fiber intake may increase symptom levels of ADHD in offspring during childhood, independently of genetic predisposition to ADHD, unhealthy dietary exposures, and sociodemographic factors.

Anxiety and depression in expectant parents: ART versus spontaneous conception.

STUDY QUESTION: Do expectant parents experience increased anxiety and depression during pregnancies conceived through ART compared to spontaneous conception? SUMMARY ANSWER: Among all expectant parents in the sample, those who conceived through ART reported overall lower levels of anxiety and depression in pregnancy compared to expectant parents who conceived spontaneously, while in the subsample of parents who conceived both through ART and spontaneous conception, expectant mothers experienced increased anxiety and depression in early pregnancy following ART compared to spontaneous conception. WHAT IS KNOWN ALREADY: Previous research on expectant parents' psychosocial adjustment in response to ART has found mixed results, with some studies suggesting ART is associated with increased anxiety and depression, and other studies suggesting improved mental health or no relationship. Mixed findings may relate to the use of cross-sectional designs that do not account for confounding differences between groups, or variability in the timing of assessment. STUDY DESIGN, SIZE, DURATION: This prospective cohort study used data from the Norwegian Mother, Father and Child Cohort Study (MoBa), which includes 2960 pregnant women who underwent ART and 108 183 women who conceived spontaneously. Of these, a subsample of expectant parents had two consecutive pregnancies with one pregnancy resulting from ART and one conceived spontaneously (n = 286 women, n = 211 partners). Women self-reported their composite symptoms of anxiety and depression at two timepoints during each pregnancy (gestational weeks 17 and 30). Their partners self-reported composite symptoms of anxiety and depression at 17 weeks gestation during each pregnancy. Couples reported their relationship satisfaction at 17 weeks gestation. MAIN RESULTS AND THE ROLE OF CHANGE: Using a conventional full-cohort analysis we found that ART was associated with less total anxiety and depression and greater relationship satisfaction, compared to spontaneous conception among both women and men. However, in the subsample of parents who experienced both ART and spontaneous pregnancies, ART was associated with increased levels of maternal anxiety and depression at gestational age 17 weeks (M = 1.19), compared to spontaneous pregnancies (M = 1.15), 95% CI of the mean difference 0.006, 0.074. At 30 weeks gestation, anxiety and depression were similar across both types of pregnancies. Expectant fathers reported similar levels of anxiety and depression at 17 weeks gestation during both pregnancies. Among women relationship satisfaction was higher following ART conception than spontaneous conception. LIMITATIONS, REASONS FOR CAUTION: There is potential for selection effects in the sample, as women who have conceived through both ART and spontaneous conception in their first two pregnancies are rare. In addition, several factors that may be important predictors of mental health in this context, such as previous miscarriages and long-term infertility, were not assessed in the current study. WIDER IMPLICATIONS OF THE FINDINGS: Our findings indicate that previous discrepancies in the literature may be related to inherent differences between the groups of parents receiving reproductive treatment and those who do not. This study addresses that limitation by prospectively comparing different types of pregnancies within the same expectant parents. Earlier inconsistencies may also relate to variations in gestational age when anxiety and depression were assessed. By examining symptoms at two timepoints in each pregnancy, we were able to examine the relation between gestational age and symptoms of anxiety and depression. STUDY FUNDING/COMPETING INTEREST(S): The MoBa is supported by the Norwegian Ministry of Health and the Norwegian Research Council/FUGE (grant number 151918/S10). This work was also supported by the Research Council of Norway grant number 288083 and 301004. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Population prevalence and inheritance pattern of recurrent CNVs associated with neurodevelopmental disorders in 12,252 newborns and their parents.

Recurrent copy number variations (CNVs) are common causes of neurodevelopmental disorders (NDDs) and associated with a range of psychiatric traits. These CNVs occur at defined genomic regions that are particularly prone to recurrent deletions and duplications and often exhibit variable expressivity and incomplete penetrance. Robust estimates of the population prevalence and inheritance pattern of recurrent CNVs associated with neurodevelopmental disorders (NDD CNVs) are lacking. Here we perform array-based CNV calling in 12,252 mother-father-child trios from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and analyse the inheritance pattern of 26 recurrent NDD CNVs in 13 genomic regions. We estimate the total prevalence of recurrent NDD CNVs (duplications and deletions) in live-born children to 0.48% (95% C.I.: 0.37-0.62%), i.e., ~1 in 200 newborns has either a deletion or duplication in these NDDs associated regions. Approximately a third of the newborn recurrent NDD CNVs (34%, N = 20/59) are de novo variants. We provide prevalence estimates and inheritance information for each of the 26 NDD CNVs and find higher prevalence than previously reported for 1q21.1 deletions (~1:2000), 15q11.2 duplications (~1:4000), 15q13.3 microdeletions (~1:2500), 16p11.2 proximal microdeletions (~1:2000) and 17q12 deletions (~1:4000) and lower than previously reported prevalence for the 22q11.2 deletion (~1:12,000). In conclusion, our analysis of an unselected and representative population of newborns and their parents provides a clearer picture of the rate of recurrent microdeletions/duplications implicated in neurodevelopmental delay. These results will provide an important resource for genetic diagnostics and counseling.

Moderating effect of mode of delivery on the genetics of intelligence: Explorative genome-wide analyses in ALSPAC.

INTRODUCTION: Intelligence is a core construct of individual differences in cognitive abilities and a strong predictor of important life outcomes. Within recent years, rates of cesarean section have substantially increased globally, though little is known about its effect on neurodevelopmental trajectories. Thus, we aimed to investigate the influence of delivery by cesarean section on the genetics of intelligence in children. METHODS: Participants were recruited through the Avon Longitudinal Study of Parents and Children (ALSPAC). Intelligence was measured by the Wechsler Intelligence Scale for Children (WISC). Genotyping was performed using the Illumina Human Hap 550 quad genome-wide SNP genotyping platform and was followed by imputation using MACH software. Genome-wide interaction analyses were conducted using linear regression. RESULTS: A total of 2,421 children and 2,141,747 SNPs were subjected to the genome-wide interaction analyses. No variant reached genome-wide significance. The strongest interaction was observed at rs17800861 in the GRIN2A gene (ß = -3.43, 95% CI = -4.74 to -2.12, p = 2.98E-07). This variant is predicted to be located within active chromatin compartments in the hippocampus and may influence binding of the NF-kappaB transcription factor. CONCLUSIONS: Our results may indicate that mode of delivery might have a moderating effect on genetic disposition of intelligence in children. Studies of considerable sizes (>10,000) are likely required to more robustly detect variants governing such interaction. In summary, the presented findings prompt the need for further studies aimed at increasing our understanding of effects various modes of delivery may have on health outcomes in children.