Large-for-gestational age and stillbirth: is there a role for antenatal testing?

OBJECTIVE: To investigate the association between large-for-gestational-age (LGA) pregnancy and stillbirth to determine if the LGA fetus may benefit from antenatal testing with non-stress test or biophysical profile. METHODS: This was a retrospective cohort study of singleton pregnancies that were ongoing at 24 weeks' gestation and that had undergone routine second-trimester anatomy ultrasound examination, during the period 1990 to 2009. Pregnancies complicated by fetal anomaly or aneuploidy, those with missing birth weight information and those that were small-for-gestational age were excluded. Appropriate-for-gestational age (AGA) and LGA were defined as birth weight between the 10th and 90th percentiles and > 90th percentile, respectively, according to the Alexander growth standard. The incidence of stillbirth was calculated as the number of stillbirths per 10 000 ongoing pregnancies. Adjusted odds ratios (aOR) with 95% CI for stillbirth in LGA compared with AGA pregnancies were estimated using logistic regression analysis, controlling for pre-existing and gestational diabetes. The incidence and aOR for stillbirth were estimated at 4-week intervals from ≥ 24 to ≥ 40 weeks' gestation. RESULTS: Of 52 749 pregnancies ongoing at 24 weeks, 46 205 (87.6%) were AGA and 6544 (12.4%) were LGA at delivery. The incidence of stillbirth in LGA pregnancies was significantly higher than that in AGA pregnancies from 36 weeks' gestation (26/10 000 vs 7/10 000; aOR, 3.10; 95% CI, 1.68-5.70). When women with diabetes were excluded in stratified analysis, pregnancies complicated by LGA continued to be at increased risk for stillbirth ≥ 36 weeks (18/10 000 vs 7/10 000; OR, 2.63; 95% CI, 1.27-5.43). CONCLUSION: Pregnancies complicated by LGA are at significantly increased risk for stillbirth at or beyond 36 weeks, independent of maternal diabetes status, and may benefit from antenatal testing. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Early versus 6-12 week postpartum glucose tolerance testing for women with gestational diabetes.

OBJECTIVE: The objective of this study is to estimate the accuracy of early oral glucose tolerance testing (GTT), to predict impaired glucose tolerance. STUDY DESIGN: This was a prospective cohort study. Women received an early 75 g 2 h GTT between postpartum days 2-4 and again 6-12 weeks postpartum. The ability of the early GTT to accurately detect impaired glucose tolerance and diabetes was assessed by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPVs). The routine 6-12-week postpartum GTT was considered the gold standard. RESULTS: The early GTT was completed by 100% of subjects, whereas only 31 of 58 (53%) women returned to complete the 6-12-week postpartum GTT. The early GTT had modest sensitivity for impaired glucose tolerance (62.5%) and overt diabetes (50%). However, it had excellent specificity (100%), PPV (100%) and NPV (96.7%) for diabetes. The NPV for impaired glucose tolerance with the early GTT was 80%. CONCLUSION: Rates of 6-12 week postpartum GTT completion among patients with gestational diabetes is poor. Appropriate postpartum management may improve by using the early GTT as a screening test.

Group versus traditional prenatal care in low-risk women delivering at term: a retrospective cohort study.

OBJECTIVE: Group prenatal care (GC) models are receiving increasing attention as a means of preventing preterm birth; yet, there are limited data on whether group care improves perinatal outcomes in women who deliver at term. The purpose of this study was to evaluate our institutional experience with GC over the past decade and test the hypothesis that GC, compared with traditional individual care (TC), improves perinatal outcomes in women who deliver at term. STUDY DESIGN: We performed a retrospective cohort study of women delivering at term who participated in GC compared with TC. A group of 207 GC patients who delivered at term from 2004 to 2014 were matched in a 1:2 ratio to 414 patients with term singleton pregnancies who delivered at our institution during the same period by delivery year, maternal age, race and insurance status. The primary outcome was low birth weight (<2500 g). Secondary outcomes included early term birth (37.0 to 38 6/7 weeks), 5 min APGAR score <7, special care nursery admission, neonatal intensive care unit (NICU) admission, neonatal demise, cesarean section and number of prenatal visits. Outcomes were compared between the two groups using univariable statistics. RESULTS: Baseline characteristics were similar between the two matched groups. GC was associated with a significant reduction in low birth weight infants compared with TC (11.1% vs 19.6%; relative risk (RR) 0.57; 95% confidence interval (CI) 0.37 to 0.87). Patients in GC were significantly less likely than controls to require cesarean delivery, have low 5 min APGAR scores and need higher-level neonatal care (NICU: 1.5% vs 6.5%; RR 0.22; 95% CI 0.07 to 0.72). There were no significant differences in rates of early term birth and neonatal demise. CONCLUSIONS: Low-risk women participating in GC and delivering at term had a lower risk of low birth weight and other adverse perinatal outcomes compared with women in TC. This suggests GC is a promising alternative to individual prenatal care to improve perinatal outcomes in addition to preterm birth.

Prenatal visit utilization and outcomes in pregnant women with type II and gestational diabetes.

OBJECTIVE: To investigate the association between the number of prenatal visits (PNVs) and pregnancy outcomes in women with gestational diabetes (GDM) and Type 2 diabetes mellitus (DM). STUDY DESIGN: A 4-year prospective cohort study of women with GDM and DM and was conducted. Patients ⩾75th percentile for number of PNVs were compared with those ⩽25th percentile. The primary outcomes were large for gestational age (LGA) with birth weight >90% and neonatal intensive care unit (NICU) admission for >24 h. Secondary neonatal outcomes included severe LGA (>95%), shoulder dystocia, hyperbilirubinemia requiring phototherapy, neonatal hypoglycemia, low 5 min APGAR score (<7) and preterm birth (prior to 37 weeks). Secondary maternal outcomes included mean third trimester fasting blood glucose, hemoglobin A1c (Hgb A1c) in labor, preeclampsia, gestational weight gain over Institute of Medicine recommendations, mode of delivery and maternal readmission within 30 days. Logistic regression was used to adjust for maternal race, nulliparity and body mass index. RESULTS: Of the 305 women, 4 were excluded for unknown number of PNVs. Among the 301 included, the average number of visits was 12. Rates of LGA were similar between the high (28%) compared with low (18%) utilization groups (adjusted odds ratio (aOR) 1.69; 95% confidence interval (CI) 0.81-3.54). The high utilization group was 85% less likely to deliver an infant requiring NICU admission (aOR 0.15; 95% CI 0.04-0.53) and 59% less likely to have a preterm birth (aOR 0.41; 95% CI 0.21-0.80). A time-to-event analysis to account for the fact that patients who delivered earlier had fewer weeks to experience PNVs showed that the risk for NICU admission was still significantly lower in the high PNV utilization group (hazard ratio 0.15; 95% CI 0.04-0.51) after adjusting for confounders in a Cox proportional hazard model. The mean Hgb A1c at the time of delivery was significantly better in the high (6.4%) compared with low (6.9%) utilization groups (P=0.01). There were no differences in other maternal outcomes based on prenatal care utilization. CONCLUSIONS: Diabetic women with high PNV utilization have better glycemic control in the 3 months prior to delivery and are significantly less likely to deliver preterm infants or infants requiring NICU admission. There may be innovative ways to provide prenatal care for GDM and DM to optimize maternal and neonatal outcomes.

Diagnostic ability of elevated 1-h glucose challenge test.

OBJECTIVE: To determine whether a threshold of a 1-h glucose challenge test (GCT) eliminates the need for a 3-h glucose tolerance test (GTT). STUDY DESIGN: A retrospective cohort of patients undergoing GTT after GCT was ⩾140 mg dl(-1). Gestational diabetes mellitus (GDM) was diagnosed using National Diabetes Data Group (NDDG) and Carpenter-Coustan (CC) criteria. Sensitivity, specificity and predictive values were calculated for 1-h GCT values of 160 to 220 mg dl(-1). RESULT: Of 6218 patients, 988 (15.9%) had an elevated GCT and 753 (12.1%) underwent a GTT. In all, 165 (2.7%) were diagnosed with GDM using NDDG criteria, and 250 (4.0%) by CC criteria. The positive predictive value of a 1-h of GCT ⩾200 mg dl(-1) for GDM was 68.6% by NDDG and 80.0% for GDM by CC criteria. CONCLUSION: Although the predictive value of an elevated 1-h ⩽200 mg dl(-1) for GDM was high, 1 in 3 to 1 in 5 women would be overdiagnosed with GDM if the 3-h GTT was omitted.

Number of prenatal visits and pregnancy outcomes in low-risk women.

OBJECTIVE: We investigated the association between number of prenatal visits (PNV) and pregnancy outcomes. STUDY DESIGN: A retrospective cohort of 12 092 consecutive, uncomplicated term births was included. Exclusion criteria included unknown or third trimester pregnancy dating, pre-existing medical conditions and common pregnancy complications. Patients with ⩽10 PNV were compared with those with >10. The primary outcome was a neonatal composite including neonatal intensive-care unit admission, low APGAR score (<7), low umbilical cord pH (<7.10) and neonatal demise. Secondary outcomes included components of the composite as well as vaginal delivery, induction and cesarean delivery. Logistic regression was used to adjust for potential confounders. RESULT: Of 7256 patients in the cohort meeting inclusion criteria, 30% (N=2163) had >10 PNV and the remaining 70% (N=5093) had ⩽10, respectively. There was no difference in the neonatal composite between the two groups. However, women with>10 PNV were more likely to undergo induction of labor and cesarean delivery. CONCLUSION: Low-risk women with ⩾10 PNV had higher rates of pregnancy interventions without improvement in neonatal outcomes.

Pregnancy outcomes in women with sickle-cell disease in low and high income countries: a systematic review and meta-analysis.

BACKGROUND: Pregnancy in women with sickle-cell disease (SCD) is associated with increased adverse outcomes. Findings on the association between SCD and adverse pregnancy outcomes are conflicting, and the results do not address whether these associations are similar in both low- and high-income countries. OBJECTIVES: We conducted a systematic review and meta-analysis to evaluate pregnancy outcomes associated with SCD. SEARCH STRATEGY: The MEDLINE database was searched using medical subject headings (MeSH) and keywords for articles on pregnancy outcomes in women with SCD. SELECTION CRITERIA: We used full research articles published in English that compared women with SCD with women who did not have SCD, as controls. DATA COLLECTION AND ANALYSIS: Data were abstracted and analysed using comprehensive Meta-analysis 2.2. The primary outcomes were intrauterine growth restriction and perinatal mortality. Secondary outcomes were rates of caesarean sections, pre-eclampsia, eclampsia, postpartum haemorrhage, maternal mortality, prematurity, and low birthweight. Random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs). MAIN RESULTS: Sixteen studies met all of the selection criteria and were included in the analysis. SCD was associated with intrauterine growth restriction (pooled OR 2.79, 95% CI 1.85-4.21), perinatal mortality (pooled OR 3.76, 95% CI 2.34-6.06), and low birthweight (pooled OR 2.00, 95% CI 1.42-2.83). SCD was also associated with an increased risk of pre-eclampsia (pooled OR 2.05, 95% CI 1.47-2.85), maternal mortality (pooled OR 10.91, 95% CI 1.83-65.11, P = 0.009), and eclampsia (pooled OR 3.02, 95% CI 1.20-7.58). CONCLUSION: Pregnancy in women with SCD is associated with increased risks of adverse perinatal and maternal outcomes in both low- and high-income countries. TWEETABLE ABSTRACT: This meta-analysis showed worse pregnancy outcomes in women with sickle-cell disease compared with controls.

Early prediction and aspirin for prevention of pre-eclampsia (EPAPP) study: a randomized controlled trial.

OBJECTIVE: To estimate the effect of early administration of aspirin on the prevention of pre-eclampsia in high-risk women. METHODS: This was planned as a randomized, double-blind, placebo-controlled trial of aspirin for women with risk factors for pre-eclampsia. Participants were randomized to start either aspirin (81 mg/day) or placebo at 11 + 0 to 13 + 6 weeks of gestation. The primary outcome was pre-eclampsia and secondary outcomes included gestational hypertension and small-for-gestational age at birth. RESULTS: The trial suffered from slow recruitment, leading to a protocol change to broaden the inclusion criteria (from a minimum score of multiple risk factors to at least one risk factor for pre-eclampsia). The trial was then terminated prematurely due to continuing slow recruitment and a lack of equipoise given a change in national guidelines to administer aspirin to high-risk women. From the 53 women who were randomized, 30 were included in the final analysis. There was no evidence that the primary outcome of pre-eclampsia was prevented by low-dose aspirin (relative risk (RR) 0.88, 95% CI 0.21-3.66). Gestational hypertension was seen in two women, both in the aspirin group. There was no evidence that the occurrence of small-for-gestational age was reduced by aspirin (RR 0.88, 95% CI 0.06-12.72). CONCLUSIONS: Although this study was underpowered to show effectiveness of aspirin compared to placebo due to the premature termination and difficulties encountered, it highlights practical issues to inform future studies.

Stillbirth and the small fetus: use of a sex-specific versus a non-sex-specific growth standard.

OBJECTIVE: To determine if the use of a sex-specific standard to define small-for-gestational age (SGA) will improve prediction of stillbirth. STUDY DESIGN: We performed a retrospective cohort study of singleton pregnancies excluding anomalies, aneuploidy, undocumented fetal sex or birthweight. SGA was defined as birthweight <10th percentile by the non-sex-specific and sex-specific Alexander standards. The association between SGA and stillbirth using these standards was assessed using logistic regression. RESULT: Among 57,170 pregnancies meeting inclusion criteria, 319 (0.6%) pregnancies were complicated by stillbirth. The area under the receiver operating characteristic curve for the prediction of stillbirth was greater for the sex-specific compared to the non-sex-specific standard (0.83 vs 0.72, P<0.001). CONCLUSION: Our findings suggest adoption of a sex-specific standard for diagnosis of SGA as it is more discriminative in identifying the SGA fetus at risk for stillbirth.

Loop electrosurgical excision procedure and risk of vaginal infections during pregnancy: an observational study.

OBJECTIVE: To investigate the risk for preterm birth associated with vaginal infections in pregnancies after a loop electrosurgical excision procedure (LEEP), compared with women with no prior LEEP. DESIGN: Multicentre retrospective cohort study. SETTING: USA. POPULATION: Women with LEEP between 1996 and 2006 were compared with two unexposed groups who had cervical biopsy or Pap test, without any other cervical procedure, in the same calendar year. METHODS: The first pregnancy progressing beyond 20 weeks of gestation in women with prior LEEP was compared with pregnancy in women without LEEP. Stratified analysis according to the presence or the absence of vaginal infection during pregnancy was used to investigate whether the risk for preterm birth differed according to the presence or the absence of infection. The interaction between LEEP and vaginal infection was investigated using multivariable logistic regression with interaction terms, as well as the Mantel-Haenszel test for homogeneity. MAIN OUTCOME MEASURES: Spontaneous preterm birth (<37 and <34 weeks of gestation). RESULTS: Of 1727 patients who met the inclusion criteria, 34.4% (n = 598) underwent LEEP prior to an index pregnancy. There was no increased risk for vaginal infections among women with LEEP compared with women without LEEP. Chlamydia infection and LEEP demonstrated significant interaction, suggesting that the presence of chlamydia infection in women with a history of LEEP augments the risk for preterm birth, compared with women with no history of LEEP. CONCLUSIONS: Vaginal infections during pregnancy in women with a history of LEEP may be associated with an increased risk for preterm birth, compared with women with no history of LEEP.

Is there a safe limit of delay for emergency caesarean section in Ghana? Results of analysis of early perinatal outcome.

OBJECTIVE: To determine the limits of delaying caesarean section in a busy obstetric unit in a developing country setting that is not associated with neonatal survival. METHODS: Retrospective cohort study of emergency cesarean sections. Indications were sub-divided into imminent threat and no imminent threat to fetal wellbeing. The primary outcomes was a composite measure of adverse perinatal outcome including stillbirth, 5-minute Apgar score < 7 and neonatal intensive care unit admission. Effect of decision-to-delivery interval on perinatal outcomes was evaluated using Kaplan-Meier survival analysis. RESULTS: 495 women met inclusion criteria (142 'imminent threat' group, 353 'no imminent threat' group). The median decision-to-delivery interval was significantly shorter in the 'imminent threat' group (2.25 [95% CI 1.38 - 5.83] versus 3.42 [95% CI 1.83 - 5.85] hours, p <0.001). Only 1.7% and 12.7% sections were performed within 30 minutes and 1 hour, respectively. Risk of the composite outcome was significantly higher in the 'imminent threat group (46.5% versus 31.2%, RR=1.49 [95% CI 1.18 - 1.89], p=0.001). A 95% probability of 'live intact' survival occurred at 1 hr and 2 hrs respectively, for the imminent threat and the no imminent threat groups. CONCLUSION: Increasing decision-to-delivery interval is associated with higher risk of adverse perinatal outcomes, but a 95% live intact survival can be achieved if the delivery occurs within 2 hours.

Sonographic predictors of postnatal bowel atresia in fetal gastroschisis.

OBJECTIVES: To estimate the association between antenatal bowel dilation and postnatal small-bowel atresia in fetal gastroschisis and to establish a threshold at which the risk of adverse neonatal outcome increases. METHODS: This was a retrospective cohort study of singleton gestations with an antenatal diagnosis of gastroschisis seen in our ultrasound unit from 2001 to 2010. We reviewed stored images from the last ultrasound examination before delivery, blinded to postnatal diagnoses and outcomes. Fetal intra- and extra-abdominal bowel dilation (IABD and EABD, respectively) and bowel-wall thickness were measured. Previously published definitions of bowel dilation, including > 6, > 10, > 14 and > 18 mm, were evaluated for association with the primary outcome of bowel atresia. The optimal threshold to define fetal bowel dilation was determined by evaluating the significance of association as well as test performance characteristics. RESULTS: Of 109 consecutive patients with fetal gastroschisis, there were four cases of intrauterine fetal demise and three neonatal deaths. Of the 94 live births with complete outcome data, 39 (41.5%) had measurable IABD. There were 14 (14.9%) cases of bowel atresia. Using a threshold of > 14 mm, IABD was significantly associated with an increased risk for bowel atresia (relative risk, 3.1 (95% CI, 1.2-8.2)) with a sensitivity of 57.1%, specificity of 75.0%, positive predictive value of 28.6% and negative predictive value of 90.9%. IABD > 14 mm was also associated with a significantly longer stay in neonatal intensive care unit. There was no significant association between EABD and bowel atresia at any of the thresholds evaluated. CONCLUSION: IABD > 14 mm is associated with an increased risk for postnatal bowel atresia in fetal gastroschisis. This finding may be useful in counseling patients regarding the anticipated postnatal course for their neonate.

IVF outcomes in obese donor oocyte recipients: a systematic review and meta-analysis.

STUDY QUESTION: Does obesity influence the chance of pregnancy after IVF in donor oocyte recipients? SUMMARY ANSWER: The chance of pregnancy after IVF is no different in obese donor oocyte recipients versus those in the normal BMI range. WHAT IS KNOWN ALREADY: Obesity is associated with decreased chances of pregnancy in women undergoing IVF with autologous oocytes. Prior studies have investigated the impact of obesity on IVF outcomes in donor oocyte recipients, with disparate results. This is the first systematic review and meta-analysis to address this topic. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of published literature identified in Medline, EMBASE and Scopus through December of 2011 were performed to address the association between BMI and outcomes for donor oocyte recipients. The primary outcome of this study was implantation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two authors conducted the searches independently, selected the studies and abstracted the data. Studies in English of first donor oocyte cycles with reported recipient BMI were included. Primary data collected from the IVF program at Washington University were also included as one study (n = 123 donor oocyte recipients). Studies limited to frozen embryo transfer were excluded. Data were synthesized using DerSimonian-Laird random effects models for implantation, clinical pregnancy, miscarriage and live birth. MAIN RESULTS AND THE ROLE OF CHANCE: Of 475 screened articles, 7 were reviewed and 5 were included together with primary data from Washington University, giving a total of 4758 women who were included for the assessment of the primary outcome. No associations between obesity (BMI ≥ 30 kg/m(2)) and chance of pregnancy after IVF were noted in women using donor oocytes [risk ratio (RR): 0.98, 95% confidence intervals (CI): 0.83-1.15, I(2): 61.6%]. Additional analyses assessing associations between recipient obesity and embryo implantation (RR: 0.93, 95% CI: 0.80-1.07, I(2): 0%), miscarriage (RR: 1.12, 95% CI: 0.83-1.50, I(2): 0%) and live birth (RR: 0.91, 95% CI: 0.65-1.27, I(2) 47.9%) also failed to show a negative effect. LIMITATIONS, REASONS FOR CAUTION: Included studies were small and they were performed in a variety of locations and practice settings where stimulation and laboratory protocols may differ, and extremes of BMI may also differ. Furthermore, included studies had different inclusion and exclusion criteria. These factors could not be controlled for in this meta-analysis and statistical heterogeneity was noted for some outcomes. WIDER IMPLICATIONS OF THE FINDINGS: These data suggest obesity does not affect IVF outcomes in women using donor oocytes. Oocyte quality rather than endometrial receptivity may be the overriding factor influencing IVF outcomes in obese women using autologous oocytes. STUDY FUNDING/COMPETING INTEREST(S): E.S.J. and M.G.T receive support from the Women's Reproductive Health Research Program sponsored by the National Institutes of Health (K12 HD063086). The authors do not have any competing interests. TRIAL REGISTRATION NUMBER: N/A.

First-trimester serum soluble fms-like tyrosine kinase-1, free vascular endothelial growth factor, placental growth factor and uterine artery Doppler in preeclampsia.

OBJECTIVE: To compare the first-trimester serum concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), free vascular endothelial growth factor (free-VEGF), placental growth factor (PlGF), and uterine artery pulsatility index (PI) in women who later developed preeclampsia (PE). STUDY DESIGN: Prospectively collected maternal serum samples were evaluated for sFlt-1, free VEGF, and PlGF levels in 63 cases who later developed PE compared with 252 unaffected controls. Serum levels of these angiogenic factors were measured using Quantikine immunoassays. Both univariate and multivariate analyses were used to evaluate the association between angiogenic factors and PE. The relationship between the angiogenic factors and mean maternal uterine artery PI was also evaluated. RESULT: Maternal serum sFlt-1 levels were not significantly different between the cases and controls. Mean free-VEGF levels were significantly higher in women destined to develop PE compared with the controls (P=0.04), and mean PlGF levels were significantly lower in women who later developed PE (P=0.01). There was no significant correlation between maternal mean uterine artery PI and angiogenic factors evaluated. Receiver-operating characteristic curves revealed that none of the factors were clinically useful for prediction in the first trimester of PE. CONCLUSION: Despite some significant differences in the first-trimester serum levels of angiogenic factors, our models suggest that these factors are not clinically useful for prediction in women who later developed PE.

Customized growth charts for twin gestations to optimize identification of small-for-gestational age fetuses at risk of intrauterine fetal death.

OBJECTIVE: Customized growth charts developed for singleton pregnancies have been shown to be more effective than population-based ones at identifying small-for-gestational age (SGA) fetuses at risk for intrauterine fetal death (IUFD). We sought to compare the association between SGA and IUFD in twins using customized growth charts designed for twin gestations compared to those designed for singletons. METHODS: This was a retrospective cohort study using a database including singleton and twin pregnancies undergoing ultrasound examination between 16 and 20 weeks' gestation. After excluding preterm births < 34 weeks, congenital anomalies and stillbirths, we identified 51, 150 singleton births. Coefficients for significant physiological and pathological variables affecting birth weight for singletons were derived using backward stepwise multiple regression. The same process was repeated for twin births (1608 pairs), also adjusting for chorionicity. Customized growth charts for each pregnancy were derived using these two regression models for optimal birth weight at term and a proportionality equation. The association between SGA < 10(th) percentile, defined using the twin and singleton-customized charts, and IUFD were compared. Statistical analysis, including calculation of adjusted odds ratios (OR) for IUFD and screening accuracy using each chart, was performed. RESULTS: The derived coefficients for optimal birth weight for twins were different from those for singletons, with lower constants and root mean square error (3422 and 288.9, respectively, in twins vs 3543 and 416 in singletons). Among 3786 twin infants, IUFD was seen in 123 (3.2%). The numbers of fetuses identified as SGA were 575 (15.2%) and 504 (13.3%) by the singleton and twin charts, respectively. Fetuses classified as SGA by the twin-specific customized charts were at a significantly increased risk for IUFD (adjusted OR, 2.3 (95% CI, 1.4-3.5)), whereas those classified as SGA by the singleton-customized charts were not (adjusted OR, 1.2 (95% CI, 0.7-2.0)). CONCLUSION: Customized charts designed specifically for twins are more effective at identifying twin pregnancies at risk for IUFD than are those derived using singleton birth data.

Screening for fetal growth disorders by clinical exam in the era of obesity.

OBJECTIVE: To evaluate the performance of clinical estimation of fetal weight as a screening test for fetal growth disorders and then to estimate the effect of maternal body mass index (BMI) on its screening efficiency. STUDY DESIGN: This was a retrospective cohort study of patients referred for third trimester ultrasound for the indication of 'size unequal to dates'. Patients with medical co-morbidities that may alter their a priori risk for fetal growth disorders were excluded. The incidence of fetal growth disorders as well as amniotic fluid disturbances was determined for each group and then compared across maternal BMI categories of <25 kg m(-2), 25-30 kg m(-2), ≥ 30 kg m(-2) and ≥ 40 kg m(-2). To evaluate the accuracy of clinical estimation of fetal weight in predicting fetal growth disorders, the sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios, as well as number needed to scan (NNS) was calculated and compared across BMI categories. RESULT: Of 51366 patients, 1623 were referred for the indication of size>dates and 1543 for the indication of size90th percentile and 13.5 and 96.7% for predicting BW<10th percentile. The NNS to detect one neonate with a BW<10th percentile ranged from 5 to 19, whereas the NNS to detect one neonate with a BW>90th percentile ranged from 6 to 13 across BMI categories. CONCLUSION: Overall, clinical estimation of fetal weight yields a low detection rate of fetal growth abnormalities; however, its screening efficiency is not adversely impacted by maternal BMI.

First trimester serum analytes, maternal characteristics and ultrasound markers to predict pregnancies at risk for preterm birth.

INTRODUCTION: Markers of placental dysfunction are used for risk prediction of adverse obstetric outcomes including preeclampsia and growth restriction. Although medically indicated preterm birth is often distinguished from spontaneous preterm birth, we hypothesize that similar placental dysfunction may underlay all preterm birth. We aimed to investigate whether first trimester placental protein 13 (PP-13), pregnancy associated plasma protein A (PAPP-A) and uterine artery pulsatility index, with maternal characteristics could be used to predict all preterm birth. METHODS: Prospective cohort study of singleton gestations between 11 and 14 weeks who underwent serum measurement of PP-13, PAPP-A, and measurement of uterine artery Doppler pulsatility index. Primary outcomes were preterm birth (PTB) at less than 37 and 33 weeks. Analysis performed both including and excluding preeclampsia to assess the utility of the predictors for all types of preterm birth. Predictive models assembled using logistic regression with each predictor alone and in combination, along with maternal characteristics. Predictive utility of models was assessed using receiver operating curve (ROC) analysis and sensitivities for fixed false positive values. RESULTS: Of 471 women, PTB occurred in 12.5% and early PTB (<33 weeks) occurred in 4.7%. PP-13 was decreased in PTB <37 weeks. PAPP-A was decreased in a dose-response pattern for PTB at <37 weeks and <33 weeks. Uterine artery pulsatility index was increased in early PTB. All patterns of predictors remained the same whether patients with preeclampsia were excluded or included suggesting predictive utility for all causes of PTB. Predictive models all demonstrated good predictive ability with ROC ≥ 0.90. CONCLUSIONS: PP-13, PAPP-A, and uterine artery Doppler pulsatility index obtained in the first trimester are good predictors of all types of preterm birth, both indicated and spontaneous. Models including first trimester markers combined with maternal characteristics demonstrated good predictive ability and could be investigated for application of targeted prophylactic strategies.

Placental volume and vascular flow assessed by 3D power Doppler and adverse pregnancy outcomes.

OBJECTIVE: To estimate the utility of first-trimester 3D-placental volume and vascular flow indices in the prediction of adverse pregnancy outcomes. METHODS: A prospective cohort study including women with singleton pregnancies seen between 11 and 14 weeks as part of a screening program for aneuploidy. Placental volume and vascularization indices were obtained using 3D power Doppler imaging and the VOCAL technique. Placental volume (PV), Vascularization Index (VI), Flow Index (FI) and Vascularization Flow Index (VFI) were calculated. The adverse pregnancy outcomes investigated include preeclampsia (PE), gestational hypertension (GH) and small for gestational age (SGA). The predictive ability of each variable was evaluated using receiver-operating characteristic (ROC) curves. RESULTS: Of 388 women included, PE was seen in 30 (7.7%), GH in 37 (9.0%) and SGA in 31 (8.0%). Placental volume was not significantly different between the pregnancies with adverse outcomes and those without. The mean values of the VI and VFI were significantly lower in the pregnancies that developed PE but not in GH or SGA. The area under the ROC curve for the prediction of PE was 0.71, 0.69 and 0.70 for VI, FI and VFI, respectively. CONCLUSION: The study confirms lower 3D power Doppler vascular flow indices in pregnancies that develop PE. The discriminatory ability of using these indices alone for predicting PE appears modest.

Review: Oxygen and trophoblast biology--a source of controversy.

Oxygen is necessary for life yet too much or too little oxygen is toxic to cells. The oxygen tension in the maternal plasma bathing placental villi is <20 mm Hg until 10-12 weeks' gestation, rising to 40-80 mm Hg and remaining in this range throughout the second and third trimesters. Maldevelopment of the maternal spiral arteries in the first trimester predisposes to placental dysfunction and sub-optimal pregnancy outcomes in the second half of pregnancy. Although low oxygen at the site of early placental development is the norm, controversy is intense when investigators interpret how defective transformation of spiral arteries leads to placental dysfunction during the second and third trimesters. Moreover, debate rages as to what oxygen concentrations should be considered normal and abnormal for use in vitro to model villous responses in vivo. The placenta may be injured in the second half of pregnancy by hypoxia, but recent evidence shows that ischemia with reoxygenation and mechanical damage due to high flow contributes to the placental dysfunction of diverse pregnancy disorders. We overview normal and pathologic development of the placenta, consider variables that influence experiments in vitro, and discuss the hotly debated question of what in vitro oxygen percentage reflects the normal and abnormal oxygen concentrations that occur in vivo. We then describe our studies that show cultured villous trophoblasts undergo apoptosis and autophagy with phenotype-related differences in response to hypoxia.