These data suggest that an increment of 25 mg choline/d to meet the demands of pregnancy is insufficient and show that a higher maternal choline intake increases the use of choline as a methyl donor in both maternal and fetal compartments. This trial was registered at clinicaltrials.gov as NCT01127022.

The in utero availability of methyl donors, such as choline, may modify fetal epigenetic marks and lead to sustainable functional alterations throughout the life course. The hypothalamic-pituitary-adrenal (HPA) axis regulates cortisol production and is sensitive to perinatal epigenetic programming. As an extension of a 12-wk dose-response choline feeding study conducted in third-trimester pregnant women, we investigated the effect of maternal choline intake (930 vs. 480 mg/d) on the epigenetic state of cortisol-regulating genes, and their expression, in placenta and cord venous blood. The higher maternal choline intake yielded higher placental promoter methylation of the cortisol-regulating genes, corticotropin releasing hormone (CRH; P=0.05) and glucocorticoid receptor (NR3C1; P=0.002); lower placental CRH transcript abundance (P=0.04); lower cord blood leukocyte promoter methylation of CRH (P=0.05) and NR3C1 (P=0.04); and 33% lower (P=0.07) cord plasma cortisol. In addition, placental global DNA methylation and dimethylated histone H3 at lysine 9 (H3K9me2) were higher (P=0.02) in the 930 mg choline/d group, as was the expression of select placental methyltransferases. These data collectively suggest that maternal choline intake in humans modulates the epigenetic state of genes that regulate fetal HPA axis reactivity as well as the epigenomic status of fetal derived tissues.

The authors investigated the association between maternal psychological and fetal neurobehavioral functioning. Data were provided by 52 maternal-fetal pairs at 24, 30, and 36 weeks gestation. The relations between maternal measures and fetal heart rate, variability, and motor activity were statistically modeled. Fetuses of women who were more affectively intense, appraised their lives as more stressful, and reported more frequent pregnancy-specific hassles were more active across gestation. Fetuses of women who perceived their pregnancy to be more intensely and frequently uplifting and had positive emotional valence toward pregnancy were less active. Associations with fetal heart-rate measures were detected at 36 weeks gestation. These data provide evidence for proximal effects of maternal psychological functioning on fetal neurobehavior.

This study evaluated whether motor activity prior to birth is predictive of motor behavior and temperament in neonates, infants, and toddlers. Three measures of fetal motor activity (activity level, amplitude, and number of movements) were collected at 24, 30, and 36 weeks of gestation in 52 healthy fetuses using Doppler-based actography. Postnatal data collection included a neurobehavioral assessment at 2-weeks postpartum (n = 41), and laboratory-based behavioral observations at 1 and 2 years of age (ns = 35). Individual stability in motor activity was present during gestation. Predictive relations between fetal movement and neonatal behavior were inconsistent; significant but small positive associations were detected between motor behavior at 36 weeks and neonatal irritability and motor development. Fetal activity level at 36 weeks was positively associated with observed 1-year activity level for boys (but inversely related for girls) and maternal report of activity level at 2 years. Fetal movement was consistently and negatively predictive of distress to limitations at 1 year and behavioral inhibition at 2 years, accounting for 21 to 43% of the variance in these measures. Intrafetal variability in motor behavior makes this a relatively unstable metric for prediction to neonatal maturational outcomes, which are relatively constrained, but fetal motor activity appears to predict temperament attributes related to regulatory behaviors in early childhood.

Alteration in the HPA axis is a robust biomarker of anxiety and depression in adults, but questions remain about this association in pregnancy. We examined the longitudinal links between diurnal cortisol and mood symptoms from self-report questionnaire and diagnostic interview in an ethnically diverse, psychosocially at-risk sample of 101 women at mid-pregnancy and early third trimester. There were modest but significant associations between depression and elevated cortisol, indexed by a decreased morning level and diminished diurnal decline; the effects were strongest for diagnostic data from clinical interview. These effects were independent of socio-demographic factors and sleep disturbance. Associations with anxiety and trauma were generally non-significant. These findings extend prior work by showing that significant mood symptoms in pregnancy are associated with altered diurnal cortisol in pregnancy, which may have implications for maternal and child health.