Increasing evidence suggests the importance of pregnancy and early life factors in the etiology of asthma and allergy in childhood. We and others in the Epidemiology Branch have established a collaboration with the Norwegian Mother and Child Cohort (called MoBa), a population based cohort of approximately 100,000 pregnant women in Norway who are being followed until their children reach adulthood. I established a collaboration with the asthma group in Norway around early life factors and epigenetics. I have been working on analyses of early childhood outcomes with the MoBa investigators and pre and postdoctoral trainees from NIEHS and Norway. Our finding that children of mothers with higher levels of folate had slightly higher risk of asthma phenotypes in early childhood is of potential public health importance. Norway is an ideal place to examine this association because food is not fortified with folate. Using the seven year follow-up of MoBa funded by NIEHS, we recently published our findings through age seven years and find that the association with maternal folate status persists for school age asthma (PMID: 27518161). We also published an analysis of maternal folate levels and epigenome wide methylation in newborns and identified many novel signals not previously implicated in biologic response to folate (PMID: 26861414 ) A major focus of this project is to examine effects of in utero exposures on the epigenome of newborns. For this purposes we measured DNA methylation in cord blood on approximately 1700 newborns from the Norwegian Mother and Child pregnancy cohort using the Illumina450K methylation bead chip. In the first paper to examine the effects of any in utero exposure using this platform we identified and replicated associations of maternal smoking with DNA methylation in a number of genes (PMID: 22851337). We have followed up this finding in several ways. This appears to be an in utero effect that requires sustained exposure during pregnancy (PMID: 24740201). These methylation signals enabled development biomarker in the newborn of sustained exposure to maternal smoking during pregnancy (PMID: 27323799). We also followed up this association with much larger sample size in an international consortium that we created called Pregnancy and Childhood Epigenetics (PACE). We identified over 6000 signals in newborns related to maternal smoking, about half in novel loci and found strong persistence into later childhood (PMID: 27040690). PACE continues to grow with over 26 birth and child cohorts participating. We recently published the second PACE paper examining traffic related air pollution exposure during pregnancy (PMID: 27448387). We have PACE projects underway on maternal BMI, child BMI, birthweight, asthma, atopy, pulmonary function, maternal alcohol intake, gestational age and complications of pregnancy.
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