Epigenome Wide Association and Stochastic Epigenetic Mutation Analysis on Cord Blood of Preterm Birth.

Preterm birth (PTB) can be defined as the endpoint of a complex process that could be influenced by maternal and environmental factors. Epigenetics recently emerged as an interesting field of investigation since it represents an important mechanism of regulation. This study evaluates epigenetic impact of preterm birth on DNA methylation. Genome-wide DNAm was measured using the Illumina 450K array in cord blood samples obtained from 72 full term and 18 preterm newborns. Lymphocyte composition was calculated based on specific epigenetic markers that are present on the 450k array. Differential methylation analysis was performed both at site and region level; moreover, stochastic epigenetic mutations (SEMs) were also evaluated. The study showed significant differences in blood cell composition between the two groups. Moreover, after multiple testing correction, statistically significant differences in DNA methylation levels emerged between the two groups both at site and region levels. Results obtained were compared to those reported by previous EWAS, leading to a list of more consistent genes associated with PTB. Finally, the SEMs analysis revealed that the burden of SEMs resulted significantly higher in the preterm group. In conclusion, PTB resulted associated to specific epigenetic signatures that involve immune system. Moreover, SEMs analysis revealed an increased epigenetic drift at birth in the preterm group.

Fetal intra-abdominal calcifications from meconium peritonitis: sonographic predictors of postnatal surgery.

OBJECTIVE: To study the relationship between prenatal ultrasound features and postnatal course of meconium peritonitis. STUDY DESIGN: We reviewed our cohort of cases of meconium peritonitis (MP) (n = 13/37, 225 pregnancies or 0.3/1000) as well as those published in the English literature with prenatal ultrasonographic findings and postnatal follow-up (n = 56). The total number of cases (n = 69) was divided into 4 grades of progressive severity based on the number of pertinent sonographic findings: grade 0, isolated intra-abdominal calcifications (n = 18); grade 1, intra-abdominal calcifications and ascites (n = 17) or pseudocyst (n = 2) or bowel dilatation (n = 6); grade 2, two associated findings (n = 20); and grade 3, all sonographic features (n = 6). Presence of polyhydramnios was also recorded. Prenatal predictors of need for neonatal surgery and risk of neonatal death were identified using Chi-square and Fisher exact test, with P < 0.05 considered significant. RESULTS: Neonatal surgical intervention was required in 0% (0/18) of newborns with grade 0 MP; in 52% (13/25) of those with grade 1; in 80% (16/20) with grade 2; and in 100% (6/6) with grade 3 MP (P < 0.001, Chi-square for trend). Moreover, neonatal surgery was more frequent in the presence than absence of polyhydramnios [69% (18/26) vs 37% (16/43); P = 0.007]. Neonatal mortality was 6% (4/69; 3 after surgery and 1 for premature delivery) and it was confined to the subgroup with polyhydramnios (4/26, 15%). CONCLUSIONS: Prenatal sonographic features are related to postnatal outcome. Persistently isolated intra-abdominal calcifications have an excellent outcome. Delivery in a tertiary care center is recommended when calcifications are associated with other sonographic findings.

Predictors of adverse perinatal outcome in twins delivered at < 37 weeks.

OBJECTIVE: Multiple gestations are at increased risk for prematurity as well as perinatal mortality and morbidity. The aim of this study was to identify the independent risk factors for adverse perinatal outcome in a large uniform population of twins delivered preterm. METHODS: We accessed a cohort of twin gestations for the period 1990-2000 delivered at < 37.0 weeks gestation. Chorionicity was established by ultrasound assessment of the dividing membrane, neonatal gender and histologic examination of the placenta at birth. Adverse perinatal outcome was defined as stillbirth, neonatal death, or major neonatal complications. Statistical analysis used contingency tables, Student's t test, one-way ANOVA and logistic regression, with a two-tailed p < 0.05 considered significant. RESULTS: A total of 356 twin gestations (712 twins) were included in the database, and 183 twins (25.7%) had adverse perinatal outcome. Logistic regression analysis demonstrated that gestational age at delivery (p < 0.001), premature rupture of membranes (PROM) (p = 0.004), birth weight discordance (p = 0.009), and 5-min Apgar scores (p = 0.001) were significant and independent predictors of adverse perinatal outcome, whereas monochorionicity and twin-twin transfusion syndrome were not. CONCLUSIONS: Gestational age at delivery and birth weight discordance are the most important independent predictors of perinatal mortality or morbidity among preterm twins.