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.

Rate of wound complications with enoxaparin use among women at high risk for postpartum thrombosis.

Objective: To estimate the rate of wound complications associated with protocol-driven postcesarean enoxaparin thromboprophylaxis.

Methods: After implementing an Institutional Clinical Practice Guideline for postoperative cesarean delivery thromboprophylaxis among at-risk gravid women (older than 35 years of age, body mass index greater than 30 kg/m2, or both), data on all cesarean deliveries over the first 23 months of guideline implementation were extracted and analyzed. Primary (wound hematoma, separation, or dehiscence) and secondary (venous thromboembolism) outcomes were compared in stratified and multivariable models controlling for potential confounders.

Role of second-trimester genetic sonography after Down syndrome screening.

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

Methods: The First and Second Trimester Evaluation of Risk (FASTER) aneuploidy screening trial participants were studied from 13 centers where a 15- to 23-week genetic sonogram was performed in the same center. Midtrimester Down syndrome risks were estimated for five screening test policies: first-trimester combined, second-trimester quadruple, and testing sequentially by integrated, stepwise, or contingent protocols.

Influence of maternal BMI on genetic sonography in the FaSTER trial.

Objective: We sought to evaluate the influence of maternal body mass index (BMI) on sonographic detection employing data from the FaSTER trial.

Method: Unselected singleton pregnancies underwent detailed genetic sonogram to evaluate for structural fetal anomalies and soft markers for aneuploidy. BMI (kg/m(2)) were calculated from reported initial visit values.

Loss of Erk3 function in mice leads to intrauterine growth restriction, pulmonary immaturity, and neonatal lethality.

Extracellular signal-regulated kinase 3 (Erk3) is an atypical member of the mitogen-activated protein (MAP) kinase family. No function has yet been ascribed to this MAP kinase. Here we show that targeted disruption of the Mapk6 gene (encoding Erk3) leads to intrauterine growth restriction, associated with marked pulmonary hypoplasia, and early neonatal death during the first day of life.

Pheochromocytoma and Von Hippel-Lindau in pregnancy.

Pheochromocytoma is an infrequent but well-acknowledged primary cause of malignant hypertension in pregnancy. Although the majority of pheochromocytomas are sporadic, those that present as bilateral or multifocal tumors may be a manifestation of a rare cancer susceptibility syndrome, such as Von Hippel-Lindau (VHL). Gravidae with unrecognized pheochromocytoma are at risk for recurrent paroxysmal hypertensive crises with ensuant maternal and fetal risks.

A maternal high-fat diet is accompanied by alterations in the fetal primate metabolome.

Objective: To characterize the serum metabolome of a primate model of in utero high-fat exposure.

Study Design: Serum from maternal and fetal (e130) macaque monkeys exposed to either a high-fat or control diet were analyzed by gas chromatography-mass spectrometry. Multivariate data analysis was performed to reduce the generated data set.

Environmental influences on epigenetic profiles.

Studies of environmental challenges, such as hazardous air pollutants, nonmutagenic toxins, diet choice, and maternal behavioral patterns, reveal changes in gene expression patterns, DNA methylation, and histone modifications that are in causal association with exogenous exposures. In this article we summarize some of the recent advances in the field of environmental epigenetics and highlight seminal studies that implicate in utero exposures as causative agents in altering not only the epigenome of the exposed gestation, but that of subsequent generations. Current studies of the effects of maternal behavior, exposure to environmental toxins, and exposure to maternal diet and an altered gestational milieu are summarized.

Animal models of epigenetic inheritance.

Although genomic DNA is the template of our heredity, it is the coordination and regulation of its expression that results in the wide complexity and diversity seen among organisms. In recent years, an emerging body of evidence has focused on the role of epigenetics as one mechanism by which gene expression can be maintained and modulated throughout the lifetime of an individual. Epigenetics refers to heritable alterations in gene expression that are not mediated by changes in primary DNA sequence and includes mitotic and/or meiotic events.

Group A streptococcal puerperal sepsis: initial characterization of virulence factors in association with clinical parameters.

Group A beta-hemolytic streptococcus (GAS) is an uncommon but potentially fatal source of postpartum infection. Pathogenesis in invasive GAS infections has been linked to bacterial virulence factors. In this study, we sought to provide an initial description of potential virulence factors in association with puerperal morbidity by virtue of specific M-protein type antigens.

Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome.

Chromatin structure is epigenetically altered via covalent modifications of histones to allow for heritable gene regulation without altering the nucleotide sequence. Multiple lines of evidence from rodents have established a role for epigenetic remodeling in regulating gene transcription in response to an altered gestational milieu. However, to date, it is unknown whether variations in the intrauterine environment in primates similarly induce changes in key determinants of hepatic chromatin structure.

In utero tobacco exposure is associated with modified effects of maternal factors on fetal growth.

Objective: The objective of the study was to evaluate whether maternal tobacco use is associated with an attenuation in fetal birthweight among women with nutritional and uteroplacental constraints.

Study Design: A population-based retrospective analysis of term (37 weeks or longer) singleton pregnancies delivered in Utah from 1991 to 2001. Birthweight (BW) and percent small for gestational age (SGA) (less than 10% for gestational age) among self-identified smokers and nonsmokers were compared.

Hyperemesis in pregnancy: an evaluation of treatment strategies with maternal and neonatal outcomes.

Objective: The objective of the study was to evaluate the use of interventions such as a peripherally inserted central catheters (PICC) line or nasogastric (NG)/nasoduodenal (ND) tube with the use of medications alone in the management of pregnancies with hyperemesis.

Study Design: Subjects were identified with confirmed intrauterine pregnancy, admitted with hyperemesis gravidarum (HEG) between 1998 and 2004. Medical records were then abstracted for information with regard to therapy.

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.

Beckwith-Wiedemann syndrome presenting with an elevated triple screen in the second trimester of pregnancy.

Background: Beckwith-Wiedemann syndrome (BWS) is a distinct clinical syndrome with unique features, generally diagnosed postnatally.

Case: A 26-year-old patient, gravida 4, para 3-0-0-3, was noted to have an abnormal maternal serum screen. Amniocentesis with imaging studies were remarkable only for a two-vessel umbilical cord and prominent maternal ovaries.

Preeclampsia and subsequent risk of cancer in Utah.

Objective: The purpose of this study was to determine if preeclampsia is associated with a reduced risk of cancer later in life.

Study Design: We performed a cohort study where women with preeclampsia over the interval 1947 to 1999 were identified from the Utah Population Database. Preeclamptics (n = 17,432) were matched 1:3 with nonpreeclamptics (n = 52,296) on maternal age and birth year.

Immunology of normal pregnancy.

Since Medawar's initial contemplations in 1953 on the mechanisms of immune evasion allowing for the survival of the allogeneic conceptus in an immunologically competent mother, physicians and immunologists alike have struggled to understand the immunological paradox of pregnancy. Ultimately, our attempts to define the immunology of normal pregnancy have broadened our appreciation of the myriad mechanisms at play that enable the promotion of implantation and maintenance of pregnancy. In this review, we summarise what is known regarding the immunology of normal pregnancy, with special emphasis on the relation to common disorders of pregnancy.

Factors associated with nonanomalous stillbirths: the Utah Stillbirth Database 1992-2002.

Objective: This study was undertaken to characterize risk factors associated with nonanomalous stillborn (SB) infants and to ascribe the probability of fetal survival by gestational age among high-risk pregnancies.

Study Design: We compiled a database of all SB infants and an equivalent number of controls using information obtained from Utah Birth and Fetal Death Certificates during the years 1992 through 2002. Adjusted and unadjusted odds ratios for risk factors associated with SB were generated.

Preterm premature rupture of membranes: perspectives surrounding controversies in management.

Preterm premature rupture of the membranes (PPROM) occurs in approximately 3% of all pregnancies, and accounts for one third of all preterm births. Despite its prevalence, optimal management of PPROM remains largely undefined and lacks conformity. In this article, we review the pathophysiology of PPROM, and summarize the available literature describing various management strategies in an effort to define current controversies in the management of PPROM.