Kent D. Heyborne

Does 17-alpha hydroxyprogesterone caproate prevent recurrent preterm birth in obese women?

OBJECTIVE We sought to determine if maternal weight or body mass index (BMI) modifies the effectiveness of 17-alpha hydroxyprogesterone caproate (17OHP-C). STUDY DESIGN We performed a secondary analysis of the Maternal-Fetal Medicine Units Network Trial for the Prevention of Recurrent Preterm Delivery by 17-Alpha Hydroxyprogesterone Caproate. Binomial regression models were estimated to determine the relative risk (RR) of preterm birth (PTB) in women randomized to 17OHP-C vs placebo according to BMI category and maternal weight. Adjusted models considered inclusion of potential confounders. RESULTS In all, 443 women with complete data were included. 17OHP-C is effective in preventing PTB <37 weeks only in women with prepregnancy BMI <30 kg/m(2) (RR, 0.54; 95% confidence interval, 0.43-0.68). Above this BMI threshold there is a nonsignificant trend toward an increased risk of PTB (RR, 1.55; 95% confidence interval, 0.83-2.89) with 17OHP-C treatment. When analyzing by maternal weight, a similar threshold is observed at 165 lb, above which 17OHP-C is no longer effective. CONCLUSION The effectiveness of 17OHP-C is modified by maternal weight and BMI, and treatment does not appear to reduce the rate of PTB in women who are obese or have a weight >165 lb. This finding may be due to subtherapeutic serum levels in women with increased BMI or weight. Studies of adjusted-dose 17OHP-C in women who are obese or who weigh >165 lb are warranted, and current recommendations regarding the uniform use of 17OHP-C regardless of maternal BMI and weight may deserve reassessment.

Preeclampsia in high risk women is characterized by risk group-specific abnormalities in serum biomarkers

OBJECTIVE To determine if early pregnancy serum biomarkers in high-risk women who develop preeclampsia vary according to risk factor. STUDY DESIGN We performed a secondary analysis of the Maternal-Fetal Medicine Units Network randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in high-risk women. Serum biomarker levels at enrollment (before initiation of aspirin or placebo) were compared between women who did and did not develop preeclampsia, both for the group as a whole and within each of 4 high-risk groups (insulin-dependent diabetes, hypertension, multiple gestation, and previous preeclampsia) using a regression model adjusting for gestational age at collection and prepregnancy body mass index. RESULTS 1258 women were included (233 with insulin-dependent diabetes, 387 with chronic hypertension, 315 with a multiple gestation, 323 with previous preeclampsia). Multiple early pregnancy serum biomarkers differed between women who did and did not develop preeclampsia. Each high-risk group had a unique and largely nonoverlapping pattern of biomarker abnormality. Differences between those who did and did not develop preeclampsia were noted in vascular cell adhesion molecule in the diabetes group; human chorionic gonadotropin, soluble tumor necrosis factor receptor-2, tumor necrosis factor-alpha, selectin and angiogenin in the chronic hypertension group; interleukin-6, placental growth factor, soluble fms-like tyrosine kinase plus endoglin to placental growth factor ratio in the multiple gestation group; and angiogenin in the previous preeclampsia group. CONCLUSION Patterns of serum biomarkers vary by high-risk group. These data support the hypothesis that multiple pathogenic pathways lead to the disease recognized clinically as preeclampsia.

Smoking, 17 Alpha-Hydroxyprogesterone Caproate, and Preterm Birth.

Objective The objective of this study was to determine if maternal smoking modifies the effectiveness of 17 α-hydroxyprogesterone caproate (17OHP-C). Study Design Secondary analysis of the Maternal-Fetal Medicine Units Network trial of 17OHP-C. The prevalence of preterm birth (PTB) by smoking status and treatment group was compared by chi-squared analysis and analysis of variance was used to compare gestational age (GA) at birth. Multivariable modeling was used to estimate the effect of smoking on 17OHP-C treatment. Results In this study, 459 women were included. Maternal smoking significantly modified the effectiveness of 17OHP-C treatment. In smokers, 17OHP-C significantly reduced the prevalence of multiple outcomes (PTB < 37 and < 35 weeks, spontaneous PTB < 37 and < 35 weeks), while in nonsmokers, only PTB < 37 weeks was reduced. Delivery GA was later in 17OHP-C versus placebo treated smokers (36.4 vs. 34.3 weeks, p = 0.041) but not nonsmokers (36.3 vs. 35.5 weeks, p = nonsignificant). In multivariable modeling, 17OHP-C was more effective in smokers than nonsmokers as measured by multiple outcomes (PTB < 37 weeks [p = 0.041] and < 35 weeks [p = 0.036] and spontaneous PTB < 37 weeks [p = 0.029]). Conclusion In this cohort of women with a prior PTB, maternal smoking status significantly modified the effectiveness of 17OHP-C treatment.

Managing Monoamniotic Twin Pregnancies

Monoamniotic twins comprise a rare but important subset of twins at risk of unique and serious complications, placing them at the highest risk of perinatal mortality of all twin gestations. In addition to risks faced by all twins (prematurity, selective growth restriction), all monochorionic twins (twin-twin transfusion syndrome), and all monozygotic twins (congenital anomalies), monoamniotic twins face the unique risk of cord entanglement. Accordingly, early diagnosis, screening for fetal anomalies, surveillance for twin-twin transfusion syndrome, decisions related to monitoring after viability, and timing and route of delivery are all critical. Herein, we present recommendations for optimal management.

A Systematic Review of Intrapartum Fetal Head Compression: What Is the Impact on the Fetal Brain?

Objective During labor the fetal head is subjected to pressure related to uterine contractions and maternal pushing. Here we systematically review what is known about fetal head compression and its effects on fetal intracranial pressure, oxygenation, blood flow and cerebral function, and the plausibility that it might cause isolated fetal brain injury. Study Design Systematic review of intrapartum fetal head compression and fetal brain injury in accordance with the MOOSE methodology. The PubMed database was searched using a combination of the terms “fetal,” “head,” “cranial,” “extracranial,” “pressure,” and “compression.” Additional references were obtained using multiple strategies. Results were evaluated, and relevant studies encompassing animal and human data using several approaches are summarized in this review. Results Studies support a significant increase in fetal extracranial pressure with contractions and pushing. However, available data do not support a concomitant significant relative increase in intracranial pressure, a reduction in cerebral circulation or oxygenation, or an impact on cerebral function. Conclusion A review of the literature indicates that fetal intracranial pressure is well protected from extracranial forces. Available data do not support intrapartum fetal extracranial pressure as a cause of fetal brain injury. Precis The fetal brain is relatively unaffected by intrapartum fetal head compression.

Impact of aspirin on fetal growth in diabetic pregnancies according to White classification

BACKGROUND: Current US Preventive Services Task Force and other guidelines recommend low‐dose aspirin for all pregnant women with pregestational diabetes mellitus to prevent preeclampsia and small‐for‐gestational‐age birth. The Maternal‐Fetal Medicine Units High‐Risk Aspirin trial did not show a reduction in either preeclampsia or small‐for‐gestational‐age birth in diabetic women. OBJECTIVE: Our objective was to reassess the impact of aspirin on fetal growth in diabetic pregnancies overall and according to White classification. We hypothesized that aspirin improves fetal growth in pregnancies with vascular complications of diabetes at highest risk for poor fetal growth. STUDY DESIGN: We conducted secondary analysis of the cohort of diabetic women enrolled in the Maternal‐Fetal Medicine Units High‐Risk Aspirin trial. The impact of aspirin prophylaxis on birthweight was assessed in the overall cohort and in 2 groups categorized according to White classification as nonvascular (White class B, C, D) or vascular (White class R, F, RF). Birthweight was converted to Z‐score normalized for gestational age at delivery and neonatal sex. Difference in birthweight Z‐score between aspirin and placebo was tested with a 2‐sample t test. The effect of vascular group, aspirin vs placebo randomization, and the interaction of the 2 on normalized birthweight percentile was estimated with linear regression with a multivariable model including covariates body mass index, tobacco use, race, and parity. The percentage of small and large‐for‐gestational‐age newborns born to aspirin‐ vs placebo‐treated women was compared between groups using Pearson exact χ2 analysis, and an adjusted model was estimated by logistic regression. RESULTS: All 444 women with pregestational diabetes and complete outcome data were included (53 vascular, 391 nonvascular). Aspirin was significantly associated with a higher birthweight Z‐score (0.283; 95% confidence interval, 0.023–0.544) in the overall cohort (P = .03). In the adjusted model, the association of aspirin with higher birthweight Z‐score was confined to neonates of women with nonvascular diabetes (0.341; 95% confidence interval, 0.677–0.006; P = .044). An opposite but nonsignificant effect was observed among neonates from women with vascular diabetes (–0.416; 95% confidence interval, –1.335 to 0.503; P = .6). This difference in the relationship of aspirin and birthweight Z‐score by vascular group was significant at P = .046. Aspirin‐randomized women with nonvascular diabetes had more large‐for‐gestational‐age births than those treated with placebo (40.2 vs 26.6%; P = .005). Small‐for‐gestational‐age births occurred at the same frequency with aspirin vs placebo randomization in the overall cohort (8% in each group) and in each vascular group. CONCLUSION: Inconsistent with our hypothesis, aspirin did not reduce small‐for‐gestational‐age births in the overall cohort or either group. The increased incidence of large‐for‐gestational‐age infants in aspirin‐treated diabetic gestations is of potential concern given the known increased maternal and neonatal morbidity associated with macrosomia.

Historical and clinical factors associated with positive urine toxicology screening on labor and delivery

OBJECTIVE Illicit drug use in pregnancy may lead to adverse outcomes. Although the American College of Obstetricians and Gynecologists recommends that all pregnant women be screened for substance use by questionnaire or conversation, it remains unclear how well these methods identify women with illicit drug use. Drug use may also be suspected based on clinical complications, such as fetal demise or placental abruption. There are currently no formal recommendations to guide targeted laboratory testing in women perceived to be at risk based on historical or clinical factors. Our objective was to determine which historical and clinical factors are associated with positive urine toxicology screens in women admitted to labor and delivery. STUDY DESIGN Historical cohort study of all women admitted to labor and delivery at our county hospital over a 5-year period (2010-2014). All patients underwent historical and clinical risk assessment and women perceived to be at increased risk of illicit drug use and who consented to testing had urine toxicology performed. We conducted a detailed chart review on all women with a positive test during this 5-year period and compared them to all women with a negative test in 2014, reporting values significant at a p-value of ≤0.05. RESULTS Amongst the 19,604 admissions during this period, 850 women underwent urine toxicology testing, accounting for 4.8% of all admissions. We compared the 83 women who tested positive for illicit drugs (9.8% of all women tested) to the 179 women who tested negative in 2014. Historical drug use was the factor most strongly associated with a positive test. Other historical and demographic factors associated with a positive test included single relationship status, lack of employment, lack of high school education, nulliparity and history of a prior sexually-transmitted or blood-borne infection. Regarding clinical risk factors, maternal medical complications were not associated with a positive test, and obstetrical complications, like preterm labor, were associated with a negative test. CONCLUSIONS A positive urine toxicology test was most strongly associated with maternal historical factors, especially known drug use. No clinical risk factor was associated with a positive test. The implications of our findings in guiding targeted laboratory testing are discussed.