Alexandria J. Hill

The role of NADPH oxidase in a mouse model of fetal alcohol syndrome

OBJECTIVE Fetal alcohol syndrome (FAS) is the most common cause of nongenetic mental retardation. Oxidative stress is one of the purported mechanisms. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is an enzyme involved in the production of reactive oxygen species. Our objective was to evaluate NOX in the fetal brain of a well-validated mouse model of FAS. STUDY DESIGN Timed, pregnant C57BL/6J mice were injected intraperitoneally with 0.03 mL/g of either 25% ethyl alcohol or saline. Fetal brain, liver, and placenta were harvested on gestational day 18. The unit of analysis was the litter; tissue from 6-8 litters in the alcohol and control group was isolated. Evaluation of messenger ribonucleic acid (mRNA) expression of NOX subunits (DUOX1, DUOX2, NOX1, NOX2, NOX3, NOX4, NOXA1, NOXO1, RAC1, p22phox, and p67phox) was performed using quantitative real-time polymerase chain reaction; alcohol vs placebo groups were compared using a Student t test or a Mann-Whitney test (P < .05). RESULTS Alcohol exposed fetal brains showed significant up-regulation in subunits DUOX2 (1.61 ± 0.28 vs 0.84 ± 0.09; P = .03), NOXA1 (1.75 ± 0.27 vs 1.09 ± 0.06; P = .04), and NOXO1 (1.59 ± 0.10 vs 1.28 ± 0.05; P = .02). Differences in mRNA expression in the placenta were not significant; p67phox was significantly up-regulated in alcohol-exposed livers. CONCLUSION Various NOX subunits are up-regulated in fetal brains exposed to alcohol. This effect was not observed in the fetal liver or placenta. Given the available evidence, the NOX system may be involved in the causation of FAS through the generation of reactive oxygen species and may be a potential target for preventative treatment in FAS.

Umbilical artery aneurysm.

BACKGROUND: Umbilical artery aneurysm is a rare condition associated with increased risk for aneuploidy and fetal demise. CASE: We report a case of umbilical artery aneurysm discovered at 27 weeks of gestation in one fetus of a dichorionic, diamniotic twin pregnancy. The patient was hospitalized to monitor for expansion of the aneurysm. Corticosteroids were administered, and, after genetic amniocentesis revealed a normal karyotype, cesarean delivery was performed at 28 2/7 weeks of gestation. Pathologic examination confirmed an umbilical artery aneurysm in the cord of the affected fetus. CONCLUSION: Given the high incidence of aneuploidy associated with umbilical artery aneurysm, it is important to consider karyotype analysis of the affected fetus. If a normal karyotype is identified, early delivery may be warranted to decrease the risk of fetal demise.

Familial hypertriglyceridemia in pregnancy.

by the University of California San Francisco, San Francisco, USA, and University TeachingHospital, Lusaka, Zambia; allwomen gave informed consent. Study participants presented with hypovolemic shock secondary to obstetric hemorrhage at 3 tertiary care facilities in Zambia. Trial inclusion criteria included at least 2 of the following indicators of hemodynamic instability: systolic blood pressure below 100 mm Hg; pulse higher than 100 beats per minute; and estimated blood loss (EBL) of at least 1000 mL. Owing to the composite nature of the eligibility criteria, it was possible for women to be included in the study with an EBL of less than 1000 mL. Data on demographic characteristics, level of consciousness, EBL at study entry, obstetric history, and HIV status were retrospectively reviewed. The primary outcome—severe hemorrhage—was defined as an EBL of at least 1000 mL. We estimated multivariable logistic regression models to evaluate the relationship between HIV infection and severe hemorrhage, adjusting for age, parity, and study site. Data were analyzed using Stata version 12.1 (StataCorp, College Station, TX, USA). Differences were considered statistically significant at P b 0.05. HIV status was missing for 28 (8%) of the 349 women, leaving 321 women in the present analysis. There were no significant differences across HIV status with regard to age, duration of pregnancy, level of consciousness, or study site. HIV-negative women had marginally higher parity than HIV-positive women (2.82 vs 2.19; P= 0.05) (Table 1). HIVpositive women in hypovolemic shock had nearly double the odds of severe hemorrhage compared with HIV-negative women in hypovolemic shock, after controlling for age, parity, and study site (odds ratio 1.92; 95% confidence interval, 1.05–3.50; P = 0.03). Sensitivity analysis confirmed no difference in results when women for whom HIV status was missing were assigned to either HIV-positive or HIV-negative status. The results of the present study indicate that HIV might affect hemorrhage-related maternal mortality by increasing blood loss. While an underlying mechanism of this association could not be investigated in the present analysis, it is possible that the observed association could be attributable to iron-deficiency anemia, which can be exacerbated in HIV-positive patients [5]. These results are an important step toward elucidating the impact of HIV on hemorrhage-related maternal mortality; however, there were limitations to the present study. Because the parent study was not designed to explore this association,wewere unable to investigate any potential underlying mechanisms; furthermore, HIV status might have been underreported owing to missing HIV data. Another limitation was the overlap between inclusion criteria and the characterization of EBL (mild, 500–999 mL vs severe, ≥1000 mL) across HIV status. The composite nature of the inclusion criteria added a degree of complexity to the analysis. Despite the limitations, the present analysis adds to a growing body of literature characterizing the impact of HIV on maternal health and has generated an interesting and testable hypothesis. An association between these 2 conditions has direct clinical implications for the care of HIV-positive pregnant women. Furthermore, it would highlight dual gains that could be achieved through integrating HIV and maternal healthcare services.

Association of group B streptococcus colonization with early term births.

Abstract Objective: The objective of this study was to reproduce and validate the association of group B streptococcus (GBS) colonization resulting in early-term birth (370/7–386/7 weeks’ gestation) and lower birth weight, reported in African-American and Caucasian populations, in a Hispanic cohort. Methods: GBS status of women 18–40 years of age with uncomplicated pregnancies who experienced spontaneous labor and vaginal delivery between 370/7 and 420/7 weeks’ gestation over 5 years were identified. Bivariate analysis was conducted on stratified data (GBS+ vs. GBS–) to assess relationship to early versus late-term delivery. Chi-square, Fisher’s exact, and Student’s t-tests were used for analysis. Results: Our cohort was 86% Hispanic, with a GBS+ rate of 10%. No difference for mean gestational age at delivery for GBS+ (275.9 days±6.8) vs. GBS– (275.6 days±6.9) was seen (P-value=0.61). Birth weight for GBS+ and GBS– groups were similar (3388.5 g±388.6 vs. 3395.1 g±401.7, P-value=0.86). Conclusions: In specific evaluation of Hispanic women experiencing spontaneous, term, vaginal delivery, GBS colonization does not result in early-term delivery. This is not consistent with prior data in the African-American and Caucasian population suggesting racial disparity in outcomes related to GBS colonization.

Multiple embolizations of pulmonary arteriovenous malformations during pregnancy

Abstract Pulmonary arteriovenous malformations in a pregnant patient are rare and can cause deleterious, life-threatening complications. We report a patient with multiple pulmonary arteriovenous malformations, with the subsequent diagnosis of hereditary hemorrhagic telangiectasia, requiring multiple embolizations during pregnancy. Pulmonary arteriovenous malformations can carry a high risk of morbidity in the pregnant woman; however, they can be safely treated in pregnancy.

A New Method for Creating the Bladder Flap

Background Bladder flaps are commonly created during routine cesarean deliveries and often require multiple steps that increase operating time and expose the surgeon to inadvertent injury. Objective We report a simple method of creating a bladder flap that eliminates the need for multiple instrument handoffs and repositioning. Conclusion The simplicity of this method allows the surgeon decreased operative entry time while decreasing exposure to injuries from multiple instrument handoffs during bladder flap development.