Derivation and assessment of a sex-specific fetal growth standard.

PURPOSE: To derive a prescriptive sex-specific fetal growth standard and assess clinical management and outcomes according to sex-specific growth status. MATERIALS AND METHODS: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a prospective observational study of 10,038 nulliparas from eight U.S. centers who underwent ultrasounds at 14-20 and 22-29 weeks with outcomes ascertained after delivery. From these, we selected a nested cohort of lower risk participants (excluded those with chronic hypertension, pre-gestational diabetes, suspected aneuploidy, and preterm delivery) to derive a sex-specific equation for expected fetal growth using fetal weights by ultrasound and at birth. We compared the male-female discrepancy in the rate of weight <10th (small for gestational age [SGA]) and >90th (large for gestational age [LGA]) percentiles between the sex-specific and sex-neutral (Hadlock) standards. Using the full unselected cohort, we then assessed outcomes and clinical management according to sex-specific SGA and LGA status. RESULTS: Overall, 7280 infants in the lower risk nested cohort were used to derive a sex-specific equation with fetal sex included as an equation intercept. The sex-neutral standard diagnosed SGA more often in female newborns (21% vs. 13%, p < .001) and LGA more often in male newborns (5% vs. 3%, p < .001). The sex-specific standard resolved these disparities (SGA: 9% vs. 10%, p = .23; LGA: 13% vs. 13%, p = .58). To approximate an unselected population, 1059 participants initially excluded for risk factors for abnormal growth were then included for our secondary objective (N = 8339). In this unselected cohort, 39% (95% CI 37.0-42.0%) of the 1498 newborns classified as SGA by the sex-neutral standard were reclassified as appropriate for gestational age (AGA) by the sex-specific standard. These reclassified newborns were more likely to be delivered for growth restriction despite having lower risk of morbidity (females) or comparable risk of morbidity (males) compared to newborns considered AGA by both methods. Of the 6485 newborns considered AGA by the sex-neutral standard, 737 (11.4%, 95% CI 10.6-12.2%) were reclassified as LGA by the sex-specific standard. These reclassified newborns had higher rates of cesarean for arrest of descent, cesarean for arrest of dilation, and shoulder dystocia than newborns considered AGA by both methods. None were reclassified from LGA to AGA by the sex-specific standard. CONCLUSION: The Hadlock sex-neutral standard generates sex disparities in SGA and LGA at birth. Our sex-specific standard resolves these disparities and has the potential to improve accuracy of growth pathology risk stratification.

Hypertension and patterns of induced labor at term.

OBJECTIVE: To study patterns of induced labor at term in hypertensive women. STUDY DESIGN: We performed a retrospective cohort study using the Consortium on Safe Labor database; a multicenter study of labor and delivery practices from electronic medical records in 19 hospitals. 55,572 women were studied: 28,254 nulliparas and 27,318 multiparas, undergoing induction of labor at term without a prior cesarean with a singleton vertex live born fetus. Four hypertensive groups were defined: chronic hypertension (n=1164), gestational hypertension (n=1861), preeclampsia (n=1513) and superimposed preeclampsia (n=655), compared to controls (no hypertension, n=50,379). Labor characteristics and patterns were compared among the groups, stratified by parity. MAIN OUTCOME MEASURES: Interval-censored regression analysis estimated median and 95th% duration of labor, stratified by centimeter-by-centimeter dilation. Repeated-measures analysis established mean labor curves. RESULTS: Time to progress from 4 to 10 cm was 7.5, 6.4, 4.9 and 4.6h in nulliparous women with superimposed preeclampsia, chronic hypertension, preeclampsia and gestational hypertension respectively, which differed from controls (4.9h; p<0.05 for chronic hypertension and superimposed preeclampsia). Multiparous women required 3.8, 3.9, 3.2 and 3.3h, respectively, compared to controls (3.2h, p<0.05 except preeclampsia p=0.1) to progress from 4 to 10cm. Second stage of labor without epidural was longer for all nulliparous groups compared to controls except for women with chronic hypertension, but second stage did not differ in multiparas. CONCLUSION: Regardless of parity, women with chronic disease, chronic hypertension and superimposed preeclampsia, labor longer whereas those with relatively acute disease, gestational hypertension and preeclampsia, progress more rapidly.

Low Soluble Syndecan-1 Precedes Preeclampsia.

INTRODUCTION: Syndecan-1 (Sdc1; CD138) is a major transmembrane heparan sulfate proteoglycan expressed on the extracellular, luminal surface of epithelial cells and syncytiotrophoblast, thus comprising a major component of the glycocalyx of these cells. The "soluble" (shed) form of Sdc1 has paracrine and autocrine functions and is normally produced in a regulated fashion. We compared plasma soluble Sdc1 concentrations, in relation to placental Sdc1 expression, in uncomplicated (control) and preeclamptic pregnancies. METHODS: We evaluated soluble Sdc1 across uncomplicated pregnancy, and between preeclamptic, gestational hypertensive and control patients at mid-pregnancy (20 weeks) and 3rd trimester by ELISA. Placental expression level of Sdc1 was compared between groups in relation to pre-delivery plasma soluble Sdc1. Participants were recruited from Magee-Womens Hospital. RESULTS: In uncomplicated pregnancy, plasma soluble Sdc1 rose significantly in the 1st trimester, and reached an approximate 50-fold increase at term compared to post pregnancy levels. Soluble Sdc1 was lower at mid-pregnancy in women who later developed preeclampsia (P<0.05), but not gestational hypertension, compared to controls, and remained lower at late pregnancy in preeclampsia (P<0.01) compared to controls. Sdc1 was prominently expressed on syncytiotrophoblast of microvilli. Syncytiotrophoblast Sdc1 immunostaining intensities, and mRNA content in villous homogenates, were lower in preeclampsia vs. controls (P<0.05). Soluble Sdc1 and Sdc1 immunostaining scores were inversely associated with systolic blood pressures, and positively correlated with infant birth weight percentile. CONCLUSION: Soluble Sdc1 is significantly lower before the clinical onset of preeclampsia, with reduced expression of Sdc1 in the delivered placenta, suggesting a role for glycocalyx disturbance in preeclampsia pathophysiology.