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The pregnancies and deliveries of buprenorphine-using women were uneventful, but severe NAS and need for morphine replacement therapy was seen in 57% of the buprenorphine-exposed newborns. A high number of sudden infant deaths occurred.

There is a substantial risk of children born to mothers with significant alcohol and/or substance abuse related problems for out-of-home care during early childhood. Factors identified during the pre- and perinatal period are associated with this risk.

Study Question Does prenatal alcohol exposure (PAE) affect regulation of the insulin-like growth factor 2 (IGF2)/H19 locus in placenta and the growth-restricted phenotype of newborns? Summary Answer PAE results in genotype-specific trends in both placental DNA methylation at the IGF2/H19 locus and head circumference (HC) of newborns. What is Known Already PAE can disturb development of the nervous system and lead to restricted growth of the head, even microcephaly. To clarify the etiology of alcohol-induced growth restriction, we focused on the imprinted IGF2/H19 locus known to be important for normal placental and embryonic growth. The expression of IGF2 and a negative growth controller H19 are regulated by the H19 imprinting control region ( H19 ICR) with seven-binding sites for the methylation-sensitive zinc-finger regulatory protein CTCF. A single nucleotide polymorphism rs10732516 G/A in the sixth-binding site has shown to associate with genotype-specific DNA methylation profiles at the H19 ICR. Study Design, Size, Duration By grouping 39 alcohol-exposed and 100 control samples according to rs10732516 polymorphism we explored alcohol-induced, genotype-specific changes in DNA methylation at the H19 ICR and the promoter region of H19 ( H19 differentially methylated region). Also, IGF2 and H19 mRNA expression level in placenta as well as the phenotypes of newborns were examined. Participants/Materials, Setting, Methods We explored alcohol-induced, genotype-specific changes in placental DNA methylation by MassARRAY EpiTYPER and allele-specific changes by bisulphite sequencing. IGF2 and H19 expression in placenta were analyzed by quantitative PCR and the HC, birthweight and birth length of newborns were examined using national growth charts. Main Results and the Role of Chance We observed a consistent trend in genotype-specific changes in DNA methylation at H19 ICR in alcohol-exposed placentas. DNA methylation level in the normally highly methylated paternal allele of rs10732516 paternal A/maternal G genotype was decreased in alcohol-exposed placentas. In addition to decreased IGF2 mRNA expression in alcohol-exposed placentas of this specific genotype ( P = 0.03), we observed significantly increased expression of H19 in relation to IGF2 when comparing all alcohol-exposed placentas to unexposed controls ( ...