Preterm Premature Rupture of Membranes in Human Immunodeficiency Virus-Infected Women: A Novel Case Series

Objective. To evaluate the management and outcomes of a series of human immunodeficiency virus-(HIV-) infected women whose pregnancies were complicated by preterm premature rupture of membranes (PPROM). Study design. We conducted a retrospective chart review of all women with confirmed HIV infection who had a pregnancy complicated by PPROM remote from term. PPROM remote from term was defined as rupture of membranes prior to 32-week gestation. Collective cases from two centers (Hennepin County Medical Center and The University of Alabama at Birmingham) were reviewed and data on management and outcomes were abstracted. Results. Of the HIV-positive women, we identified 291 pregnancies having occurred in the study interval from two institutions. Of these pregnancies, 7 (2.4%) developed PPROM remote from term with subsequent delivery from 25- to 32-week gestation. Vertical HIV transmission was noted in 2 of 6 children whose long-term followup status was confirmed (33%) of these cases. However, both of these cases occurred in women with either no antepartum/intrapartum antiviral therapy or where only zidovudine monotherapy was used. Importantly, in spite of expectant management, no cases of vertical HIV transmission occurred in women who were receiving either multidrug or highly active antiviral therapy (HAART) at the time of PPROM and who had a cesarean delivery in cases where the predelivery viral load > 1000 copies/mL. Conclusion. Our limited observations raise the question as to whether in the current era of multidrug therapy immediate delivery should be undertaken in HIV+ pregnancies complicated by PPROM at an early gestational age. This case series further suggests that in those pregnancies that lend themselves to expectant management, such a strategy may be considered appropriate

Role of Second-Trimester Genetic Sonography After Down Syndrome Screening

To estimate the effectiveness of second-trimester genetic sonography in modifying Down syndrome screening test results

Maternal tobacco use modestly alters correlated epigenome-wide placental DNA methylation and gene expression

Several studies linking alterations in differential placental methylation with pregnancy disorders have implicated (de) regulation of the placental epigenome with fetal programming and later-in-life disease. We have previously demonstrated that maternal tobacco use is associated with alterations in promoter methylation of placental CYP1A1 and that these changes are correlated with CYP1A1 gene expression and fetal growth restriction. In this study we sought to expand our analysis of promoter methylation by correlating it to gene expression on a genome-wide scale. Employing side-by-side IlluminaHG-12 gene transcription with Infinium27K methylation arrays, we interrogated correlative changes in placental gene expression and DNA methylation associated with maternal tobacco smoke exposure at an epigenome-wide level and in consideration of signature gene pathways. We observed that the expression of 623 genes and the methylation of 1,024 CpG dinucleotides are significantly altered among smokers, with only 38 CpGs showing significant differential methylation (differing by a methylation level of ≥10%). We identified a significant Pearson correlation (≥0.7 or ≤-0.7) between placental transcriptional regulation and differential CpG methylation in only 25 genes among non-smokers but in 438 genes among smokers (18-fold increase, p < 0.0001), with a dominant effect among oxidative stress pathways. Differential methylation at as few as 6 sites was attributed to maternal smoking-mediated birth weight reduction in linear regression models with Bonferroni correction (p < 1.8 × 10−6). These studies suggest that a common perinatal exposure (such as maternal smoking) deregulates placental methylation in a CpG site-specific manner that correlates with meaningful alterations in gene expression along signature pathways