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Background: Low plasma folate concentrations in pregnancy are associated with preterm birth. Here we show an association between preconceptional folate supplementation and the risk of spontaneous preterm birth. Methods and Findings: In a cohort of 34,480 low-risk singleton pregnancies enrolled in a study of aneuploidy risk, preconceptional folate supplementation was prospectively recorded in the first trimester of pregnancy. Duration of pregnancy was estimated based on first trimester ultrasound examination. Natural length of pregnancy was defined as gestational age at delivery in pregnancies with no medical or obstetrical complications that may have constituted an indication for delivery. Spontaneous preterm birth was defined as duration of pregnancy between 20 and 37 wk without those complications. The association between preconceptional folate supplementation and the risk of spontaneous preterm birth was evaluated using survival analysis. Comparing to no supplementation, preconceptional folate supplementation for 1 y or longer was associated with a 70% decrease in the risk of spontaneous preterm delivery between 20 and 28 wk (41 [0.27%] versus 4 [0.04%] spontaneous preterm births, respectively; HR 0.22, 95% confidence interval [CI] 0.08-0.61, p = 0.004) and a 50% decrease in the risk of spontaneous preterm delivery between 28 and 32 wk (58 [0.38%] versus 12 [0.18%] preterm birth, respectively; HR 0.45, 95% CI 0.24-0.83, p = 0.010). Adjustment for maternal characteristics age, race, body mass index, education, marital status, smoking, parity, and history of prior preterm birth did not have a material effect on the association between folate supplementation for 1 y or longer and spontaneous preterm birth between 20 and 28, and 28 to 32 wk (adjusted HR 0.31, 95% CI 0.11-0.90, p = 0.031 and 0.53, 0.28-0.99, p = 0.046, respectively). Preconceptional folate supplementation was not significantly associated with the risk of spontaneous preterm birth beyond 32 wk. The association between shorter duration (,1 y) of preconceptional folate supplementation and the risk of spontaneous preterm birth was not significant after adjustment for maternal characteristics. However, the risk of spontaneous preterm birth decreased with the duration of preconceptional folate supplementation (test for trend of survivor functions, p = 0.01) and was the lowest in women who used folate supplementation for 1 y or longer. There was also no significant association with other complications of pregnancy studied after adjustment for maternal characteristics. Conclusions: Preconceptional folate supplementation is associated with a 50%-70% reduction in the incidence of early spontaneous preterm birth. The risk of early spontaneous preterm birth is inversely proportional to the duration of preconceptional folate supplementation. Preconceptional folate supplementation was specifically related to early spontaneous preterm birth and not associated with other complications of pregnancy. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the relationship between low maternal body mass index (BMI) as calculated in the first trimester and the risk of preeclampsia and gestational hypertension. Methods. Patients enrolled in the First And Second Trimester Evaluation of Risk for aneuploidy (FASTER) trial were grouped into three weight categories: low BMI (BMI <19.8 kg/m2), normal BMI (BMI 19.8 - 26 kg/m2), and overweight BMI (26.1 - 29 kg/m2). The incidences of gestational hypertension and preeclampsia were ascertained for each group. Tests for differences in crude incidence proportions were performed using Chi-square tests. Multiple logistic regression was used to adjust for maternal age, race, parity, obesity, use of assisted reproductive technology (ART), in vitro fertilization (IVF), gestational diabetes, pre-gestational diabetes, cocaine use, and smoking. Results. The proportion of patients having gestational hypertension in the low BMI group was 2.0% compared to 3.2% for normal BMI and 6.0% for overweight BMI (p < 0.0001). Women with low BMI were also less likely to develop preeclampsia, 1.1% vs. 1.9% for normal BMI and 2.8% for overweight BMI (p < 0.0001). Conclusions. We found that women with low BMI in the first trimester were significantly less likely to develop gestational hypertension or preeclampsia than women with a normal BMI. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine whether maternal serum levels of pregnancy-associated plasma protein A, free-beta subunit human chorionic gonadotropin, or nuchal translucency size are associated with obstetric complications. Study design: Data were obtained from the First and Second Trimester Evaluation of Risk trial. Pregnancy-associated plasma protein A and free-beta subunit human chorionic gonadotropin levels were analyzed, and nuchal translucency was measured between 10 weeks 3 days and 13 weeks 6 days of gestation in 34,271 pregnancies. Results: Women with pregnancy-associated plasma protein A of ≤5th percentile were significantly more likely to experience spontaneous fetal loss at ≤24 weeks of gestation, low birth weight, preeclampsia, gestational hypertension, preterm birth (P < .001) and stillbirth, preterm premature rupture of membranes, and placental abruption (P < .02). Nuchal translucency at ≥99th percentile and free-beta subunit human chorionic gonadotropin at ≤1st percentile were associated with an increased risk of spontaneous loss at ≤24 weeks of gestation (adjusted odds ratios, 3.90, 3.62, respectively; P < .001). Conclusion: Low pregnancy-associated plasma protein A levels in the first trimester were associated strongly with a number of adverse pregnancy outcomes. Low free-beta subunit human chorionic gonadotropin levels and large nuchal translucency were both associated with early fetal loss. [ABSTRACT FROM AUTHOR]

Objective: Severe twin-to-twin transfusion syndrome (TTTS) is usually classified according to a staging system (I-V) based on ultrasonographic findings of polyhydramnios in the recipient, oligohydramnios in the donor, the presence or absence of the donor's bladder, Doppler waveform changes and (impending) hydrops. Stage correlates with the severity of disease, and it is assumed that, without intervention, severe TTTS will evolve in succession from stage I to stage V (fetal demise). However, this progression has not been validated in longitudinal studies. Herein, we report on the natural progression of severe TTTS in a cohort of patients from a regional Fetal Treatment Program. Methods: Eighteen patients with severe TTTS, diagnosed between 15 and 25 weeks of gestation, were managed over a 28-month period. Data were collected until delivery, endoscopic surgical intervention or dual fetal demise. Patients were evaluated at least once a week. Stage, estimated fetal weight, percent recipient/donor body weight discordance and survival were recorded. Results: The present study represents a total follow-up of 108 patient-weeks. Of 90 week-to-week evaluations, 65 showed no change in stage; 11 showed downstaging (by more than 1 stage in 3, or 27%), and 13 showed upstaging (by more than 1 stage in 8, or 62%). Nine patients (all stage II or above) underwent endoscopic laser ablation. Overall survival was 67%, and survival of at least 1 twin occurred in 78% of pregnancies. Weight discordance between the donor and recipient did not predict outcome. Conclusion: The current staging system for severe TTTS may not be helpful in predicting the direction, degree or speed of progression of the condition. Indications for intervention should remain stage-related, and not based on projected progression. [ABSTRACT FROM AUTHOR]

The article reports on the results of a study of individualized norms of optimal fetal growth. A description of the study methods is presented. The study concluded that growth potential norms based on the physiologic determinants of birth weight are a better discriminator of aberrations of fetal growth than traditional norms.

Objective: To estimate the effect of second-trimester levels of maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), unconjugated estriol (uE3), and inhibin A (the quad screen) on obstetric complications by using a large, prospectively collected database (the FASTER database). Methods: The FASTER trial was a multicenter study that evaluated first- and second-trimester screening programs for aneuploidy in women with singleton pregnancies. As part of this trial, patients had a quad screen drawn at 15–18 6/7 weeks. We analyzed the data to identify associations between the quad screen markers and preterm birth, intrauterine growth restriction, preeclampsia, and fetal loss. Our analysis was performed by evaluating the performance characteristics of quad screen markers individually and in combination. Crude and adjusted effects were estimated by multivariable logistic regression analysis. Patients with fetal anomalies were excluded from the analysis. Results: We analyzed data from 33,145 pregnancies. We identified numerous associations between the markers and the adverse outcomes. There was a relatively low, but often significant, risk of having an adverse pregnancy complication if a patient had a single abnormal marker. However, the risk of having an adverse outcome increased significantly if a patient had 2 or more abnormal markers. The sensitivity and positive predictive values using combinations of markers is relatively low, although superior to using individual markers. Conclusion: These data suggest that components of the quad screen may prove useful in predicting adverse obstetric outcomes. We also showed that the total number and specific combinations of abnormal markers are most useful in predicting the risk of adverse perinatal outcome. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the role of fetal nasal bone imaging at 10 3/7 to 13 6/7 weeks as a screening tool for aneuploidy, in a prospective multicenter trial. METHODS: Unselected patients from the general population with viable singleton pregnancies at 10 3/7 to 13 6/7 weeks were recruited at 15 U.S. centers. All had screening with nuchal translucency (NT) ultrasound by specially trained sonographers. In the last 8 months of this trial, first trimester nasal bone evaluation was added to the screening protocol. Nasal bones were described as present, absent, or unable to determine. [ABSTRACT FROM AUTHOR]