Melissa L. Wilson

A transient placental source of serotonin for the fetal forebrain

Serotonin (5-hydroxytryptamine or 5-HT) is thought to regulate neurodevelopmental processes through maternal–fetal interactions that have long-term mental health implications. It is thought that beyond fetal 5-HT neurons there are significant maternal contributions to fetal 5-HT during pregnancy but this has not been tested empirically. To examine putative central and peripheral sources of embryonic brain 5-HT, we used Pet1−/− (also called Fev) mice in which most dorsal raphe neurons lack 5-HT. We detected previously unknown differences in accumulation of 5-HT between the forebrain and hindbrain during early and late fetal stages, through an exogenous source of 5-HT which is not of maternal origin. Using additional genetic strategies, a new technology for studying placental biology ex vivo and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source. We uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor in both mice and humans. This study reveals a new, direct role for placental metabolic pathways in modulating fetal brain development and indicates that maternal–placental–fetal interactions could underlie the pronounced impact of 5-HT on long-lasting mental health outcomes.

Strategy for Standardization of Preeclampsia Research Study Design

Preeclampsia remains a major problem worldwide for mothers and babies. Despite intensive study, we have not been able to improve the management or early recognition of preeclampsia. At least part of this is because of failure to standardize the approach to studying this complex syndrome. It is possible that within the syndrome there may be different phenotypes with pathogenic pathways that differ between the subtypes. The capacity to recognize and to exploit different subtypes is of obvious importance for prediction, prevention, and treatment. We present a strategy for research to study preeclampsia, which will allow discrimination of such possible subtypes and also allow comparison and perhaps combinations of findings in different studies by standardized data and biosample collection. To make studies relevant to current clinical practice, the definition of preeclampsia can be that currently used and accepted. However, more importantly, sufficient data should be collected to allow other diagnostic criteria to be used and applied retrospectively. To that end, we present what we consider to be the minimum requirements for a data set in a study of preeclampsia that will facilitate comparisons. We also present a comprehensive or optimal data set for in-depth investigation of pathophysiology. As we approach the definition of phenotypes of preeclampsia by clinical and biochemical criteria, adherence to standardized protocols will hasten our understanding of the causes of preeclampsia and development of targeted treatment strategies

Molecular epidemiology of preeclampsia.

Numerous articles have been published that address the possible genetic influences on the development of preeclampsia (PE). However, to our knowledge, a complete review of the results has not yet been completed. We undertook a MEDLINE search to identify English-language articles published after January 1, 1990 that examined the possible role of specific genes in the etiology of PE. After a brief introduction and a concise review of the prevailing etiologic hypotheses, we have categorized the candidate genes into six categories, based on their hypothesized role in PE etiology. The purpose of this paper is to review the literature, comment on its quality, and provide a reference for researchers interested in the molecular epidemiology of preeclampsia. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to list the prevailing etiologic hypotheses of preeclampsia, to outline the published data on possible genetic influence on the development of preeclampsia, and to clearly state the definition of preeclampsia.

Pregnancy outcomes during an era of aggressive management for intrahepatic cholestasis of pregnancy.

Our objective was to examine whether delivery at 37 weeks of gestation alters adverse pregnancy outcomes in Latina patients with intrahepatic cholestasis of pregnancy (ICP). We conducted a retrospective chart review of Latina patients who delivered at our institution coded with ICP between 2000 and 2007. During this time period it was our practice to offer delivery to patients with ICP at 37 weeks of gestation. Subjects were classified into three groups according to total bile acid (TBA) concentration: < 20 micromol/L (mild ICP), > or = 20 micromol/L and < 40 micromol/L (moderate ICP), and > or = 40 micromol/L (severe ICP). Meconium passage was observed in no births in patients with mild IC, but was found in 18% of deliveries with moderate/severe ICP. The risk of meconium passage increased linearly, with a 19.7% increased risk for each 10 mumol/L increase in TBA concentration ( P = 0.001). There was no association with higher TBA concentration and other adverse outcomes. There was no difference in adverse outcomes between moderate and severe ICP. We concluded that in our Latina population with ICP, an association existed between meconium passage and moderate/severe ICP. Delivering at 37 weeks was associated with a low risk of adverse outcomes due to ICP among all patients, including those with higher TBA concentrations.

High Prevalence of Severe Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum among Relatives of Affected Individuals

OBJECTIVE The goal of this study was to determine the prevalence of severe nausea and vomiting of pregnancy/hyperemesis gravidarum among relatives of affected individuals. STUDY DESIGN Family history data were obtained on 1224 self-reported cases of hyperemesis gravidarum. Cases completed an online survey administered by the Hyperemesis Education and Research Foundation between 2003 and 2006. RESULTS Approximately 28% of cases reported their mother had severe nausea and vomiting or hyperemesis gravidarum while pregnant with them. Of the 721 sisters with a pregnancy history, 137 (19%) had hyperemesis gravidarum. Among the most severe cases, those requiring total parenteral nutrition or nasogastric feeding tube, the proportion of affected sisters was even higher, 49/198 (25%). Nine percent of cases reported having at least two affected relatives including sister(s), mother, grandmother, daughters, aunt(s), and cousin(s). CONCLUSION There is a high prevalence of severe nausea and vomiting of pregnancy/hyperemesis gravidarum among relatives of hyperemesis gravidarum cases in this study population. Because the incidence of hyperemesis gravidarum is most commonly reported to be 0.5%, this study provides strong but preliminary evidence for a genetic component to extreme nausea and vomiting of pregnancy.

Effects of Polymer-coated Urea on Nitrate Leaching and Nitrogen Uptake by Potato

Increasing groundwater nitrate concentrations in potato (Solanum tuberosum L.) production regions have prompted the need to identify alternative nitrogen management practices. A new type of polymer-coated urea (PCU) called Environmentally Smart Nitrogen (Agrium, Inc., Calgary, AB) is significantly lower in cost than comparable PCUs, but its potential to reduce nitrate leaching and improve fertilizer recovery has not been extensively studied in potato. In 2006 and 2007, four rates of PCU applied at emergence were compared with equivalent rates of soluble N split-applied at emergence and post-hilling. Additional treatments included a 0 N control, two PCU timing treatments (applied at preplant or planting), and a soluble N fertigation simulation. Nitrate leaching, fertilizer N recovery, N use efficiency (NUE), and residual soil inorganic N were measured. Both 2006 and 2007 were low leaching years. Nitrate leaching with PCU (21.3 kg NO(3)-N ha(-1) averaged over N rates) was significantly lower than with split-applied soluble N (26.9 kg NO(3)-N ha(-1)). The soluble N fertigation treatment resulted in similar leaching as PCU at equivalent N rates. Apparent fertilizer N recovery with PCU (65% averaged over four rates) tended to be higher than split-applied soluble N (55%) at equivalent rates (p = 0.059). Residual soil N and NUE were not significantly affected by N source. Under the conditions of this study, PCU significantly reduced leaching and tended to improved N recovery over soluble N applied in two applications and resulted in similar N recovery and nitrate leaching as soluble N applied in six applications.

Perinatal Depressive Symptoms in HIV-Infected Versus HIV-Uninfected Women: A Prospective Study from Preconception to Postpartum

OBJECTIVE Depression is common among HIV-infected women, predicts treatment nonadherence, and consequently may impact vertical transmission of HIV. We report findings from a study evaluating preconception, pregnancy, and postpartum depressive symptoms in HIV-infected vs. at-risk, HIV-uninfected women. METHODS We examined the prevalence and predictors of elevated perinatal (i.e., pregnancy and/or postpartum) depressive symptoms using a Center for Epidemiological Studies-Depression (CES-D) scale score of ≥16 in 139 HIV-infected and 105 HIV-uninfected women (62% African American) from the Womens Interagency HIV Study (WIHS). RESULTS The prevalence of elevated perinatal depressive symptoms did not differ by HIV serostatus (HIV-infected 44%, HIV-uninfected 50%, p=0.44). Among HIV-infected women, the strongest predictor of elevated symptoms was preconception depression (odds ratio [OR] 5.71, 95% confidence interval [CI] 2.67-12.19, p<0.001); crack, cocaine, and/or heroin use during preconception was marginally significant (OR 3.10, 95% CI 0.96-10.01, p=0.06). In the overall sample, additional significant predictors of perinatal depression included having multiple sex partners preconception (OR 2.20, 95% CI 1.12-4.32, p=0.02), use of preconception mental health services (OR 2.51, 95% CI 1.03-6.13, p=0.04), and not graduating from high school (OR 1.92, 95% CI 1.06-3.46, p=0.03). CONCLUSIONS Elevated perinatal depressive symptoms are common among HIV-infected and at-risk HIV-uninfected women. Depressive symptoms before pregnancy were the strongest predictor of perinatal symptoms. Findings underscore the importance of early and ongoing assessment and treatment to ensure low vertical transmission rates and improving postpregnancy outcomes for mothers and children.

Associations between Ambient Air Pollution and Hypertensive Disorders of Pregnancy

BACKGROUND Exposure to ambient air pollution is linked to adverse pregnancy outcomes. Previous reports examining the relationship between ambient air pollution and Hypertensive Disorders of Pregnancy have been inconsistent. OBJECTIVES We evaluated the effects of ambient air pollution on the odds of Hypertensive Disorder of Pregnancy and whether these associations varied by body mass index (BMI). METHODS We conducted a retrospective, case-control study among 298 predominantly Hispanic women (136 clinically confirmed cases) who attended the Los Angeles County+University of Southern California Womens and Childrens Hospital during 1996-2008. Trimester-specific carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and particulate matter with aerodynamic diameter <10 μm and <2.5 μm (PM10, PM2.5) exposure were estimated based on 24-hour exposure level at residential address. Logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for two standard deviation increase in exposure levels. RESULTS Exposures to CO and PM2.5 in the 1st trimester were significantly associated with Hypertensive Disorders of Pregnancy, and these associations were modified by BMI. In non-obese women (BMI <30), 1st trimester exposures to PM2.5 and CO were significantly associated with increased odds of Hypertensive Disorder of Pregnancy (ORs per 2-standard deviation increase in PM2.5 (7 μg/m(3)) and CO (1 ppm) exposures were 9.10 [95% CI: 3.33-24.6] and 4.96 [95% CI: 1.85-13.31], respectively). Additionally, there was a significantly positive association between exposure to O3 in the 2nd trimester and Hypertensive Disorder of Pregnancy (OR per 15 ppb=2.05; 95% CI: 1.22-3.46). CONCLUSION Among non-obese women, 1st trimester exposure to PM2.5 and carbon monoxide are associated with increased odds of Hypertensive Disorder of Pregnancy.

The brain study: Cognition, quality of life and social functioning following preeclampsia; An observational study

OBJECTIVES Previously preeclamptic women may express cognitive difficulties, which have largely been unappreciated or attributed to stresses of a complicated pregnancy. This study aimed to explore the scope of perceived neurocognitive and psychosocial problems as well as quality of life following preeclampsia. STUDY DESIGN Observational study. Through website promotion and e-mail, registrants of the USA-based Preeclampsia Foundation who experienced preeclampsia in the past 20years were invited to complete a web-based survey. Participants were requested to ask an acquaintance that had a normotensive pregnancy to also complete the survey (controls). MAIN OUTCOME MEASURES The Cognitive Failures Questionnaire (CFQ), abbreviated WHO Quality Of Life questionnaire (WHOQOL-BREF), Social Functioning Questionnaire (SFQ) and Breslau Short Screening Scale for DSM-IV Posttraumatic Stress Disorder were used in the survey. Analysis was performed using Mann-Whitney U tests and linear regression. RESULTS 966 cases and 342 controls completed the survey (median age 34, median time since first pregnancy 4 vs. 5years). Cases scored significantly worse on CFQ (median 35 vs. 27), WHOQOL-BREF domains physical health (15 vs. 17), psychological (13 vs. 15), social relationships (13 vs. 15) and environment (15 vs. 16), and SFQ (8 vs. 7). All p<0.001. Multivariable analysis showed an independent significant effect of eclampsia on CFQ and of migraine on all questionnaires and the effect of preeclampsia was still present after adjustment for confounders. Posttraumatic stress symptoms accounted for part of the relationships. CONCLUSIONS Previously preeclamptic women appear to perceive more cognitive and social problems, and report poorer quality of life compared to a group of women with normotensive pregnancies. Research relating to the origin and management of these issues is needed.

Follicular development in a 7-day versus 4-day hormone-free interval with an oral contraceptive containing 20 mcg ethinyl estradiol and 1 mg norethindrone acetate

BACKGROUND Combined oral contraceptive (COC) formulations with 20 mcg ethinyl estradiol (EE) have a greater incidence of ovarian hormone production and follicular development, which can be managed by shortening the number of hormone-free days per COC cycle. This study evaluates differences in follicular development during a 7-day versus 4-day hormone-free interval in a COC regimen with 20 mcg EE and 1 mg norethindrone acetate. STUDY DESIGN Forty-one healthy women were randomized in an open-label fashion to this formulation in either a 24/4 or a 21/7 day regimen for three cycles. Estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone and inhibin B were measured daily from Cycle 2, Day 21 to Cycle 3, Day 3 and on Day 7 of Cycle 3. Follicular diameter and Hoogland score were calculated on Cycle 2, Days 21, 24 and 28 and Cycle 3, Days 3 and 7. RESULTS Sixty-six percent of subjects in the 21/7 group and 70% of the subjects in the 24/4 group developed a follicle greater than 10 mm diameter. Ovarian steroid hormone levels, Hoogland scores and bleeding patterns were not statistically significant between the groups. CONCLUSION In contrast to prior studies, this analysis suggests no difference in follicle development or bleeding patterns among women receiving a 21/7 or 24/4 regimen of a 20-mcg EE/1-mg norethindrone acetate COC.