Faculty Bibliography

BACKGROUND:Preterm Premature Rupture of Membranes (PPROM) precedes many deliveries and experts agree with expectant management until 34 weeks gestation. However, there is controversy regarding the gestational age (GA) for administration of corticosteroids. STUDY DESIGN/METHODS:We performed a retrospective cohort study in the University of California Fetal Consortium (UCfC). We searched available charts of singleton pregnancies with PPROM between 32 and 33 6/7 weeks GA. Outcomes from the groups were analyzed. RESULTS:Of 191 women with PPROM at 32 to 33 6/7 weeks, 150 received corticosteroids. The median GA at admission was earlier for the exposed versus unexposed group (32 4/7 versus 33 0/7 weeks, respectively, p = 0.001). The mean GA at delivery in the exposed was 33 2/7 (32 0/7 to 35 0/7) weeks versus 33 5/7 (32 0/7 to 36 1/7) weeks in the unexposed (p = 0.001). There was no difference in chorioamnionitis or RDS. CONCLUSION/CONCLUSIONS:In women with PPROM at 32 to 33 6/7 weeks, our data suggests that corticosteroids are associated with similar outcomes despite earlier GA at delivery and no differences in major morbidities. A larger prospective study is needed to determine if the benefit of corticosteroids outweighs the potential risks in PPROM.

Endogenous hydrogen sulfide (H2S) synthesized via metabolizing L-cysteine by cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) is a potent vasodilator and angiogenic factor. The objectives of this study were to determine if human uterine artery (UA) H2S production increases with augmented expression and/or activity of CBS and/or CSE during the menstrual cycle and pregnancy and whether exogenous H2S dilates UA. Uterine arteries from nonpregnant (NP) premenopausal proliferative (pPRM) and secretory (sPRM) phases of the menstrual cycle and pregnant (P) women were studied. H2S production was measured by the methylene blue assay. CBS and CSE mRNAs were assessed by quantitative real-time PCR, and proteins were assessed by immunoblotting and semiquantitative immunofluorescence microscopy. Effects of H2S on rat UA relaxation were determined by wire myography ex vivo. H2S production was greater in NP pPRM and P than NP sPRM UAs and inhibited by the specific CBS but not CSE inhibitor. CBS but not CSE mRNA and protein were greater in NP pPRM and P than NP sPRM UAs. CBS protein was localized to endothelium and smooth muscle and its levels were in a quantitative order of P >NP UAs of pPRM>sPRM. CSE protein was localized in UA endothelium and smooth muscle with no difference among groups. A H2S donor relaxed P > NP UAs but not mesentery artery. Thus, human UA H2S production is augmented with endothelium and smooth muscle CBS upregulation, contributing to UA vasodilation in the estrogen-dominant physiological states in the proliferative phase of the menstrual cycle and pregnancy.

Estrogens dramatically dilate numerous vascular beds with the greatest response in the uterus. Endogenous hydrogen sulfide (H2S) is a potent vasodilator and proangiogenic second messenger, which is synthesized from L-cysteine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). We hypothesized that estrogen replacement therapy (ERT) selectively stimulates H2S biosynthesis in uterine artery (UA) and other systemic arteries. Intact and endothelium-denuded UA, mesenteric artery (MA), and carotid artery (CA) were obtained from ovariectomized nonpregnant ewes (n = 5/group) receiving vehicle or estradiol-17β replacement therapy (ERT). Total RNA and protein were extracted for measuring CBS and CSE, and H2S production was determined by the methylene blue assay. Paraffin-embedded UA rings were used to localize CBS and CSE proteins by immunofluorescence microscopy. ERT significantly stimulated CBS mRNA and protein without altering CSE mRNA or protein in intact and denuded UA. Quantitative immunofluorescence microscopic analyses showed CBS and CSE protein localization in endothelium and smooth muscle and confirmed that ERT stimulated CBS but not CSE protein expression in UA endothelium and smooth muscle. ERT also stimulated CBS, but not CSE, mRNA and protein expression in intact and denuded MA but not CA in ovariectomized ewes. Concomitantly, ERT stimulated UA and MA but not CA H2S production. ERT-stimulated UA H2S production was completely blocked by a specific CBS but not CSE inhibitor. Thus, ERT selectively stimulates UA and MA but not CA H2S biosynthesis by specifically up-regulating CBS expression, implicating a role of H2S in estrogen-induced vasodilation and postmenopausal women's health.

INTRODUCTION/BACKGROUND:Induction of labor remains one of the most commonly performed procedures in the US and in other developed countries around the world. Various agents for cervical ripening are used prior to induction; the most commonly used are prostaglandins and oxytocin. The ideal agent is one that decreases time to vaginal delivery without compromising maternal and/or fetal safety. AREAS COVERED/METHODS:This article reviews the current pharmacologic methods available for induction of labor. Although these agents have been extensively studied and their safety and efficacy profile are well accepted, there is still ongoing research to determine the safest and most effective method. The article discusses the impact of pharmacogenomics as it relates to the most common induction agents. The dosing, route of administration, and side effects of these agents are reviewed. EXPERT OPINION/CONCLUSIONS:Prostaglandins and oxytocin have been proven to be safe and effective methods of induction. However, the optimal medication for induction is yet to be determined. Although there are currently no pharmacogenomic findings that affect dosing of either prostaglandins or oxytocin, this is a growing area of research. In the near future, it may become clear that there is no 'one regimen for all' when selecting an induction or cervical ripening agent, or any other pharmaceutical altogether.

Intrahepatic cholestasis (ICP) of pregnancy is a disease that is likely multifactorial in etiology and has a prevalence that varies by geography and ethnicity. The diagnosis is made when patients have a combination of pruritus and abnormal liver-function tests. It is associated with a high risk for adverse perinatal outcome, including preterm birth, meconium passage, and fetal death. As of yet, the cause for fetal death is unknown. Because fetal deaths caused by ICP appear to occur predominantly after 37 weeks, it is suggested to offer delivery at approximately 37 weeks. Ursodeoxycholic acid appears to be the most effective medication to improve maternal pruritus and liver-function tests; however, there is no medication to date that has been shown to reduce the risk for fetal death.