sFlt-1 Levels as a Predicting Tool in Placental Dysfunction Complications in Multiple Pregnancies.

BACKGROUND: several studies have demonstrated that angiogenic markers can improve the clinical management of hypertensive disorders (HDs) and fetal growth restriction (FGR) in singleton pregnancies, but few studies have evaluated the performance of these tests in multiple pregnancies. Our aim was to investigate the role of soluble fms-like tyrosine kinase 1 (sFlt-1) in predicting adverse obstetric outcomes in hospitalized multiple pregnancies with HD (preeclampsia/gestational hypertension/uncontrolled chronic hypertension) and/or FGR in one or more fetuses. METHODS: A retrospective analysis of multiple pregnancies with HD/FGR occurring after the 20th gestational week. Pregnant women were divided into two groups: women with high levels of sFlt-1 and those with low levels of sFlt-1. A value of sFlt-1 greater than or equal to 15,802 pg/mL was considered arbitrarily high, as it is equivalent to two times the 90th percentile expected in an uncomplicated full-term singleton pregnancy based on data from a prospective multicenter study (7901 pg/mL). RESULTS: The cohort included 39 multiple pregnancies. There were no cases of birth <34 weeks, HELLP syndrome, ICU admission, and urgent cesarean sections for HD/FGR complications reported among women with low levels of sFlt-1. CONCLUSIONS: A cut-off value of sFlt-1 ≥ 15,802 pg/mL could represent a valuable tool for predicting adverse obstetric outcomes in multiple pregnancies hospitalized for HD/FGR disorders, regardless of gestational age and chorionicity.

Impact of excessive pre-pregnancy body mass index and abnormal gestational weight gain on pregnancy outcomes in women with chronic hypertension.

OBJECTIVES: To investigate the effects of excessive pre-pregnancy body mass index (BMI) and abnormal gestational weight gain on adverse outcomes in women with chronic hypertension (CH). STUDY DESIGN: A retrospective cohort study of CH women with singleton pregnancy delivered at our Institution in 2002-2013. Women were categorized as normal, overweight, and obese, according to their pre-pregnancy BMI. Further stratification was based on gestational weight gain (insufficient, adequate, and excessive) as defined by 2009 IOM guidelines. MAIN OUTCOMES MEASURES: Gestational diabetes, hypothyroidism, superimposed preeclampsia, preterm birth <37 weeks, cesarean section, and delivery of a small or large for gestational age neonate. RESULTS: 309 women met inclusion criteria. Obese women had increased odds of gestational diabetes (aOR, 3.18; 95% CI, 1.46-6.90), hypothyroidism (aOR, 2.41; 95% CI, 1.15-5.54), and superimposed preeclampsia (aOR, 2.36; 95% CI, 1.20-4.65), compared to normal BMI. Overweight women also displayed higher risk of diabetes (aOR 2.19; 95% CI, 1.05-5.03). Insufficient weight gain increased odds of small for gestational age neonate in normal BMI women (aOR, 1.82; 95% CI 1.31-2.07), whereas excessive gain was associated with superimposed preeclampsia in normal BMI patients (aOR, 3.51; 95% CI, 1.16-7.89) and with cesarean delivery in obese women (aOR, 2.96; 95% CI, 1.09-5.81). CONCLUSIONS: Excessive pre-conception BMI and abnormal gestational weight gain increase odds of pregnancy complications in CH women. Our results stress the importance of pre-conception counseling for weight normalization in CH women, and support IOM recommendations for adequate weight gain during CH pregnancies.

PlGF in a clinical setting of pregnancies at risk of preeclampsia and/or intrauterine growth restriction.

Placental growth factor (PlGF) is an angiogenic molecule produced by the placenta and implicated in the pathogenesis of preeclampsia (PE) and intrauterine growth restriction (IUGR). We have evaluated utility and applicability of the PlGF test in a clinical setting of pregnancies at risk of PE or complicated by IUGR in order to assess its relationship with pregnancy outcomes. Seventy-three pregnancies were enrolled between 19 and 35 weeks: 57 pregnancies at risk of PE and 16 at diagnosis of IUGR. Maternal circulating PlGF levels were measured by the Triage PlGF test (Alere, San Diego, CA). Pregnancy outcomes were evaluated in relation to three categories of plasma PlGF levels: very low (<12 pg/ml), low (12-100 pg/ml) and normal (≥100 pg/ml). Uterine artery Doppler velocimetry (UADV) pulsatility index (PI) was measured in the same patients on the day of maternal sampling. Pregnancies at risk with very low plasma PlGF levels had significantly lower gestational age at delivery than patients with low or normal PlGF. The rate of emergency C-section was significantly higher in the group with PlGF <12 pg/ml. IUGR pregnancies with very low and low PlGF delivered earlier than patients with normal PlGF. All IUGR with very low and low PlGF had UADV PI > 95th percentile. Our data indicate that PlGF may provide useful information to identify fetuses requiring increased surveillance and possibly urgent delivery in pregnancies at risk of adverse outcomes. Furthermore, in IUGR, PlGF can predict adverse pregnancy outcomes that may be secondary to placental insufficiency.

Stillbirths in singletons, dichorionic and monochorionic twins: a comparison of risks and causes.

OBJECTIVES: To estimate the risk of stillbirth in dichorionic and monochorionic twins compared with singletons, and to evaluate the relevant causes of stillbirth in each group. STUDY DESIGN: A retrospective cohort analysis of all pregnancies ≥22 weeks of gestation was performed at a tertiary care center from January 1995 to June 2011. The overall fetal survival and the prospective risk of stillbirth were compared in monochorionic diamniotic (MCDA) twins, dichorionic diamniotic (DCDA) twins, and singletons. Causes of stillbirth were classified using the ReCoDe classification and were compared among the three study groups. RESULTS: A total of 46,200 singletons, 462 MCDA twins and 1108 DCDA twins were included in the study. Both Kaplan-Meier analysis and prospective risk calculation showed that MCDA twins had the highest risk of stillbirth (OR ranging between 13.5 95% CI 8.7-20.7 at 22.0-24.6 weeks and 4.0 95% CI 1.1-13.1 at 31.0-33.6 weeks, compared to singletons), while singletons had the lowest. Main causes of stillbirth were major congenital malformations in singletons (25.1%) and in DCDA twins (75%), and twin-twin transfusion syndrome in MCDA twins (81.5%). When excluding fetuses affected by major congenital anomalies, MCDA twins (p<0.001) but not DCDA twins (p=0.2) remained at increased risk for stillbirth compared with singletons. CONCLUSION: The risk of stillbirth is significantly higher both in MCDA and DCDA twins compared with singletons. Stillbirths are mainly due to twin-twin transfusion syndrome in MCDA twins and major congenital anomalies in DCDA twins. When major congenital anomalies are excluded, DCDA twins have a similar in utero mortality to singletons.

Seasonal impact in the frequency of isolated spina bifida.

OBJECTIVES: To evaluate whether a relationship exists between season at conception and occurrence of isolated spina bifida (ISB). STUDY DESIGN: All fetuses with prenatal diagnosis of ISB were analyzed according to date of conception. We compared the seasonal rates of conception between ISB fetuses and a control group consisting of a cohort of fetuses delivered during the same period from 1992 to 2009. RESULTS: In the control group, conceptions were equally distributed among the four seasons. Chi-square analysis showed a significantly higher rate of ISB conceptions in the fall compared with the control group (16/36, 44% vs. 12467/50533, 25%, Odds Ratio (OR) 2.44, 95% confidence interval 1.21-4.92). Not a single woman with a fetus affected by ISB took preconceptional supplement of folic acid. CONCLUSIONS: Seasonality affects the frequency of ISB. We hypothesize that the seasonal differences may reflect dietary and climate changes with reduced intake of folic acid in the fall.