Eugene Y. Chang

Costs and clinical outcomes of noninvasive fetal RhD typing for targeted prophylaxis.

OBJECTIVE: To examine the cost and clinical outcomes of noninvasive RhD typing with cell-free fetal DNA to selectively deliver antenatal and postnatal prophylaxis with anti-D immune globulin for prevention of alloimmunization in RhD-negative women. METHODS: We developed a decision tree to compare the costs and clinical outcomes of three strategies in an RhD-negative nonalloimmunized population as follows: 1) routine antenatal anti-D immune globulin prophylaxis and postpartum prophylaxis guided by cord blood typing (the current approach in most of the United States); 2) noninvasive fetal RhD typing with prophylaxis guided by test results; and 3) no screening or prophylaxis. Costs were estimated for testing and treatment algorithms using hospital billing records and information from the manufacturer of the fetal RhD genotyping test. Probability estimates were derived from published literature. The decision tree and sensitivity analyses were constructed and performed with Microsoft Excel. RESULTS: We estimated the cost of the current approach to prevention of alloimmunization to be

N-acetylcysteine attenuates the maternal and fetal proinflammatory response to intrauterine LPS injection in an animal model for preterm birth and brain injury

351 per pregnancy, and we estimated the cost of noninvasive determination of fetal RhD status to be

N-acetylcysteine prevents preterm birth by attenuating the LPS-induced expression of contractile associated proteins in an animal model

682. Assuming essentially perfect test performance, threshold analysis found the cost must decrease to

The use of blunt needles does not reduce glove perforations during obstetrical laceration repair

119 to break even. The gap widened in favor of routine prophylaxis in most other circumstances (increased false-negative test rate and decreasing prevalence of RhD negativity). CONCLUSION: Unless the cost of noninvasive fetal RhD typing is reduced substantially, routine antenatal anti-D immune globulin prophylaxis with postpartum prophylaxis guided by cord blood typing is less costly than noninvasive determination of fetal RhD status.

Examining the effect of maternal obesity on outcome of labor induction in patients with preeclampsia.

Objective. Maternal immune activation (MIA) is associated with preterm birth (PTB) and abnormal neurologic outcome. We hypothesized that N-acetylcysteine (NAC) would decrease PTB and neonatal brain injury acting as an anti-inflammatory. Methods. Pregnant CD-1 mice received intrauterine LPS or saline on day 15/20. They received NAC or saline and were monitored until delivery. Pups were followed and sacrificed on postnatal days 1/30 and brains were collected. Immunostaining for heavy-chain neurofilament protein (NF-H), myelin basic protein (MBP), and proteolipid protein (PLP) was performed. In another group, animals were sacrificed 6 h after treatment, and fetal brain, placenta, and myometrium were collected. Il-6, Il-1β, Il-10, and tumor necrosis factor (TNF)-α mRNA expression was determined. Nonparametric analysis was used for analysis, and pairwise comparisons were performed when appropriate. Results. Lipopolysaccharide (LPS) caused PTB (79 vs. 0%, p < 0.005), and this was reduced by NAC [0.45 (95% CI: 0.26–0.83), p < 0.008]. LPS increased IL-6 expression in myometrium and placenta. This was attenuated by NAC in myometrium. IL-1β, IL-6, and TNF-α expression increased in the fetal brain with LPS. LPS produced altered NF-H, MBP, and PLP staining, and these effects were attenuated by NAC. Conclusion. NAC attenuates inflammation in this MIA model and reduces PTB and white matter injury. It is an interesting candidate for study for prevention of PTB and neurologic injury.

Placental Nkx2-5 and target gene expression in early-onset and severe preeclampsia

Objective: Intrauterine infection is associated with maternal immune activation (MIA) leading to preterm birth through upregulation of contractile associated proteins (CAPs). We hypothesized that N-acetylcysteine would decrease NF-κB activation and CAP expression in a MIA model for preterm birth. Methods: Pregnant CD-1 mice were given intrauterine LPS or saline on day 15/20. They received NAC or saline prior to injection and were monitored until delivery. The rate of preterm birth in the control, LPS, and LPS + NAC animals was determined. In another group, animals were sacrificed 6 h after treatment and myometrium was collected. COX-2, connexin 43, and oxytocin receptor expression was determined. Results: LPS administration resulted in preterm birth and this effect was attenuated by NAC. LPS increased COX-2, connexin 43, and oxytocin receptor expression. NAC significantly decreased COX-2 expression. LPS increased NF-κB activation; this was attenuated by NAC. Conclusion: NAC may be beneficial in prevention of MIA-related preterm birth through attenuation of NF-κB activation and COX-2 upregulation.

Impact of dosing schedule on uptake of neuroprotective magnesium sulfate

OBJECTIVE The objective of the study was to compare the rate of glove perforation for blunt and sharp needles used during obstetrical laceration repair. A secondary aim was to assess physician satisfaction with blunt needles. STUDY DESIGN This was an institutional review board-approved, randomized, prospective trial. Patients with obstetric lacerations were randomized to repair with either blunt or sharp needles. Patient demographics, operator experience, and other clinical variables were collected. Physicians reported any percutaneous injuries and were surveyed regarding satisfaction with the assigned needles. Glove perforation was determined using a validated water test method. RESULTS There were 438 patients enrolled in the trial: 221 in the control group and 217 in the study group. There was no statistical difference between groups in patient demographics, clinical variables, severity of laceration, or experience level of the surgeon. There was no difference in the glove perforation rate between blunt and sharp needles (risk ratio, 0.79; 95% confidence interval, 0.2-2.95). There was poor correlation between reported perforations and those detected by water test (R(2) = 0.33). The physicians reported that blunt needles were more difficult to use than sharp needles (P = .0001). CONCLUSION There was no difference in the rate of surgical glove perforation for blunt, compared with sharp, needles used during vaginal laceration repair. Physicians also reported increased difficulty performing the repair with blunt needles.

Evaluation of placenta growth factor and soluble Fms-like tyrosine kinase 1 receptor levels in mild and severe preeclampsia

Objective The objective of this investigation was to evaluate the effect of maternal obesity, as measured by prepregnancy body mass index (BMI), on the mode of delivery in women undergoing indicated induction of labor for preeclampsia. Study Design Following Institutional Review Board (IRB) approval, patients with preeclampsia who underwent an induction of labor from 1997 to 2007 were identified from a perinatal information database, which included historical and clinical information. Data analysis included bivariable and multivariable analyses of predictor variables by mode of delivery. An artificial neural network was trained and externally validated to independently examine predictors of mode of delivery among women with preeclampsia. Results Six hundred and eight women met eligibility criteria and were included in this investigation. Based on multivariable logistic regression (MLR) modeling, a 5-unit increase in BMI yields a 16% increase in the odds of cesarean delivery. An artificial neural network trained and externally validated confirmed the importance of obesity in the prediction of mode of delivery among women undergoing labor induction for preeclampsia. Conclusion Among patients who are affected by preeclampsia, obesity complicates labor induction. The risk of cesarean delivery is enhanced by obesity, even with small increases in BMI. Prediction of mode of delivery by an artificial neural network performs similar to MLR among patients undergoing labor induction for preeclampsia.

Second-trimester angiogenic factors as biomarkers for future-onset preeclampsia

Objective: Preeclampsia (PE) affects 2–8% of pregnancies worldwide and is a significant source of maternal and neonatal morbidity and mortality. However, the mechanisms underlying PE are poorly understood and major questions regarding etiology and risk factors remain to be addressed. Our objective was to examine whether abnormal expression of the cardiovascular developmental transcription factor, Nkx2-5, was associated with early onset and severe preeclampsia (EOSPE). Methods: Using qPCR and immunohistochemical assay, we examined expression of Nkx2-5 and target gene expression in EOSPE and control placental tissue. We tested resulting mechanistic hypotheses in cultured cells using shRNA knockdown, qPCR, and western blot. Results: Nkx2-5 is highly expressed in racially disparate fashion (Caucasians > African Americans) in a subset of early EOSPE placentae. Nkx2-5 mRNA expression is highly correlated (Caucasians > African Americans) to mRNA expression of the preeclampsia marker sFlt-1, and of the Nkx2-5 target and RNA splicing factor, Sam68. Knockdown of Sam68 expression in cultured cells significantly impacts sFlt-1 mRNA isoform generation in vitro, supporting a mechanistic hypothesis that Nkx2-5 impacts EOSPE severity in a subset of patients via upregulation of Sam68 to increase sFlt-1 expression. Expression of additional Nkx2-5 targets potentially regulating metabolic stress response is also elevated in a racially disparate fashion in EOSPE. Conclusions: Expression of Nkx2-5 and its target genes may directly influence the genesis and racially disparate severity, and define a mechanistically distinct subclass of EOSPE.

The association between hyaline membrane disease and preeclampsia

Abstract Background: Preterm delivery <32-week gestation is associated with significant neurodevelopmental morbidity ranging from mild delay to profound disability. Several randomized trials have shown that magnesium sulfate (MgSO4) is an effective neuroprotectant, demonstrating reduced rates of cerebral palsy, death, and gross motor dysfunction for the neonate or infant. Dosing was not consistent among the major trials and the onus was placed on institutions by ACOG to develop and implement protocols with respect to MgSO4 as a neuroprotectant. A recent study demonstrated that MgSO4 exposure <12 h prior to delivery was associated with a decrease in CP compared to more remote exposure. Objective: To assess impact of dosing schedule on uptake of neuroprotective MgSO4 in patients delivering <32 weeks gestational age. Study design: A retrospective cohort study of all deliveries occurring <32 weeks’ gestation at a single academic center between March–December 2014 and March–December 2015 was conducted. Institutional policy shifted in 2015 from MgSO4 bolus with continuous infusion based on the BEAM trial to a single bolus dose based on the PREMAG trial. Patients with preeclampsia, known fetal anomalies, and/or stillbirth were excluded from this analysis. Patients were identified through query of the Medical University of South Carolina Perinatal Information System (PINS) database with respect to whether or not they had received MgSO4 within 12 h of delivery. Chi-squared analysis was performed to compare the overall rate of MgSO4 exposure and MgSO4 exposure <12 h prior to delivery between groups. Fisher’s exact test was used to evaluate maternal, obstetric, and neonatal variables among those receiving MgSO4 within 12 h of delivery in each cohort. Binary logistic regression analysis was performed to control for co-linear or potential confounding variables. Results: A total of 224 patients were identified, 115 delivered between March–December 2014 and 109 delivered between March–December 2015. With respect to MgSO4 exposure prior to delivery, 27 (23.5%) received MgSO4 in the 2014 cohort compared to 44 (40.4%) in the 2015 cohort (OR: 2.2, p < .01). Of those being exposed within 12 h of delivery, there were 16 (13.9%) maternal exposures in the 2014 cohort versus 28 (26.7%) in the 2015 cohort (OR: 2.15, p = .02). Of the 18 neonates delivered in 2014 there were four cases of grade III or IV intraventricular hemorrhage versus one case among the 36 neonates (2.7%) born in 2015 (0.04). This finding holds after controlling for race, preterm labor, gestational age, corticosteroid, birthweight, and indomethacin exposure. Conclusions: Dosing of neuroprotective MgSO4 according to PREMAG trial specifications was associated with a significantly greater percentage of patients having received neuroprotective magnesium at any point prior to delivery or within the 12 h prior to delivery when compared to dosing according to BEAM trial specifications.