Up to 13% of women may experience symptoms of depression during pregnancy or in the postpartum period. Depression during pregnancy has been associated with an increased risk of adverse neurodevelopmental outcomes in the child and epigenetic mechanisms could be one of the biological pathways to explain this association. In 844 mother–child pairs from the Avon Longitudinal Study of Parents and Children, we carried out an epigenome-wide association study (EWAS) to investigate associations between prospectively collected data on maternal depression ascertained by the Edinburgh Postnatal Depression Scale in pregnancy and DNA methylation in the cord blood of newborn offspring. In individual site analysis, we identified two CpG sites associated with maternal depression in the middle part of pregnancy. In our regional analysis, we identified 39 differentially methylated regions (DMRs). Seven DMRs were associated with depression at any time point during pregnancy, 7 associated with depression in mid-pregnancy, 23 were associated with depression in late pregnancy, and 2 DMRs were associated with depression throughout pregnancy. Several of these map to genes associated with psychiatric disease and brain development. We attempted replication in The Generation R Study and could not replicate our results. Although our findings in ALSPAC suggest that maternal depression could be associated with cord blood DNA methylation the results should be viewed as preliminary and hypothesis generating until further replicated in a larger sample.

IntroductionEpigenetic mechanisms are important for the regulation of gene expression and differentiation in the fetus and the newborn child. Symptoms of maternal depression and antidepressant use affects up to 20 % of pregnant women, and may lead to epigenetic changes with life-long impact on child health. The aim of this review is to investigate whether there is an association between exposure to maternal antidepressants during pregnancy and epigenetic changes in the newborn.Material and methodsSystematic literature searches were performed in MEDLINE and EMBASE combining MeSH terms covering epigenetic changes, use of antidepressant medication, pregnancy and newborns. A keyword search was also performed. We included studies on pregnant women and their children where there was a history of maternal depressed mood or anxiety, a reported use of antidepressant medication, and measurements of epigenetic changes in umbilical cord blood. Studies using genome-wide or candidate-based epigenetic analyses were included. Citations and references from the included articles were investigated to locate further relevant articles. The completeness of reporting as well as the risk of bias and confounding was assessed.ResultsSix studies were included. They all investigated methylation changes. Genome-wide methylation changes were examined in 184 children and methylation status in specific genes was examined in 96 children exposed to antidepressant medication. Three of the studies found an association between use of antidepressant medication during pregnancy and methylation status at various CpG sites measured in cord blood of the newborn. One of these studies found an association in African-Americans, but not Caucasians.The remaining three studies found associations between maternal mood and epigenetic changes in umbilical cord blood but no association between epigenetic changes and maternal use of antidepressant medication.ConclusionThe included studies have not established a clear association between use of antidepressant medication during pregnancy and epigenetic changes in the cord blood. Future studies using newer, more wide-ranging epigenetic methods could discover possible new differentially methylated sites. Larger sample sizes and good validity of exposures are warranted in order to adjust for level of maternal depression, other maternal illness, maternal use of other types of medication, and maternal ethnicity.PROSPERO registration number: CRD42015026575.

Background. Early diagnosis of cerebral palsy (CP) is important to enable intervention at a time when neuroplasticity is at its highest. Current mean age at diagnosis is 13 months in Denmark. Recent research has documented that an early-diagnosis set-up can lower diagnostic age in high-risk infants. The aim of the current study is to lower diagnostic age of CP regardless of neonatal risk factors. Additionally, we want to investigate if an early intervention program added to standard care is superior to standard care alone. Methods The current multicentre study CP-EDIT (Early Diagnosis and Intervention Trial) with the GO-PLAY intervention included (Goal Oriented ParentaL supported home ActivitY program), aims at testing the feasibility of an early diagnosis set-up and the GO-PLAY early intervention. CP-EDIT is a prospective cohort study, consecutively assessing approximately 500 infants at risk of CP. We will systematically collect data at inclusion (age 3-11 months) and follow a subset of participants (n=300) with CP or at high risk of CP until the age of two years. The GO-PLAY early intervention will be tested in 80 infants with CP or high risk of CP. Focus is on eight areas related to implementation and perspectives of the families: early cerebral magnetic resonance imaging (MRI), early genetic testing, implementation of the General Movements Assessment method, analysis of the GO-PLAY early intervention, parental perspective of early intervention and early diagnosis, early prediction of CP, and comparative analysis of the Hand Assessment for Infants, Hammersmith Infant Neurological Examination, MRI, and the General Movements method. Discussion Early screening for CP is increasingly possible and an interim diagnosis of “high risk of CP” is recommended but not currently used in clinical care in Denmark. Additionally, there is a need to accelerate identification in mild or ambiguous cases to facilitate appropriate therapy early. Most studies on early diagnosis focus on identifying CP in infants below five months corrected age. Little is known about early diagnosis in the 50% of all CP cases that are discernible later in infancy. The current study aims at improving care of patients with CP even before they have an established diagnosis. Trial registration ClinicalTrials.gov ID 22013292 (reg. date 31/MAR/2023) for the CP-EDIT cohort and ID 22041835 (reg. date 31/MAR/2023) for the GO-PLAY trial.

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