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Case reviews of maternal death have revealed a concerning pattern of delay in recognition of hemorrhage, hypertensive crisis, sepsis, venous thromboembolism, and heart failure. Early-warning systems have been proposed to facilitate timely recognition, diagnosis, and treatment for women developing critical illness. A multidisciplinary working group convened by the National Partnership for Maternal Safety used a consensus-based approach to define The Maternal Early Warning Criteria, a list of abnormal parameters that indicate the need for urgent bedside evaluation by a clinician with the capacity to escalate care as necessary in order to pursue diagnostic and therapeutic interventions. This commentary reviews the evidence supporting the use of early-warning systems, describes The Maternal Early Warning Criteria, and provides considerations for local implementation., (© 2014 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.)

Objective: To compare composite maternal and neonatal morbidities (CMM, CNM) among nulliparous women with primary indications for caesarean section (CS) as acute clinical emergency (group I; ACE), non-reassuring fetal heart rate (group II) and arrest disorder (group III)., Design: A multicentre prospective study., Setting: Nineteen academic centres in the USA, with deliveries in 1999-2002., Population: Nulliparous women (n = 9829) that had CS., Methods: Nulliparous women undergoing CS for three categories of indications were compared using logistic regression model, adjusted for five variables., Main Outcome Measures: CMM was defined as the presence of any of the following: intrapartum or postpartum transfusion, uterine rupture, hysterectomy, cystotomy, ureteral or bowel injury or death; CNM was defined as the presence of any of the following: umbilical arterial pH <7.00, neonatal seizure, cardiac, hepatic, renal dysfunction, hypoxic ischaemic encephalopathy or neonatal death., Results: The primary reasons for CS were ACE in 1% (group I, n = 114) non-reassuring FHR in 29% (group II; n = 2822) and failed induction/dystocia in the remaining 70% (group III; n = 6893). The overall risks of CMM and CNM were 2.5% (95% confidence intervals, CI, 2.2-2.8%) and 1.9% (95% CI 1.7-2.2), respectively. The risk of CMM was higher in group I than in group II (RR 4.1, 95% CI 3.1, 5.3), and group III (RR 3.2, 95% CI 2.7, 3.7). The risk of CNM was also higher in group I than in group II (RR 2.8, 95% CI 2.3, 3.4) and group III (RR 14.1, 95% CI 10.7, 18.7)., Conclusions: Nulliparous women who have acute clinically emergent caesarean sections are at the highest risks of both composite maternal and neonatal morbidity and mortality., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Advancing biomedical knowledge is crucial to the understanding of disease pathophysiology, diagnosis, treatment, and the maintenance of health. Whereas collaborative pursuits among basic and translational scientists, clinical researchers, and clinicians should advance biomedical progress and its translation to better medicine. The field of obstetrics and gynecology and its subspecialties has not escaped this problem. Obstetrics and gynecology specialists and subspecialists have limited opportunities to interact with translational or basic investigators, and cross-fertilization and collaborations are further challenged by the current healthcare and funding climate. This opinion manuscript focuses on the field of maternal-fetal medicine, serving as an example that illustrates the risks and opportunities that might exist within our obstetrics and gynecology academic community. A Pregnancy Task Force recently sought to identify ways to overcome hurdles related to research training, and ensure a sufficient pool of physician-scientists pursuing pertinent questions in the field. The group discussed strategies to promote a culture of intellectual curiosity and research excellence, securing additional resources for trainees, and attracting current and next generation basic, translational, and clinical scholars to our field. Recommendations encompassed activities within annual academic meetings, training initiatives, and additional funding opportunities. Inferences from these discussions can be made to all obstetrics and gynecology subspecialty areas., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: Perioperative antibiotics are recommended during cesarean delivery to reduce the risk of postoperative infections and resulting maternal morbidity. We examined the patterns of use and predictors of receipt of antibiotics in women undergoing cesarean delivery., Methods: We identified a national cohort of women who underwent a cesarean delivery between 2003 and 2010 using a commercial hospitalization database. Women who received antibiotics on the day of cesarean delivery were classified as having received perioperative antibiotics. Multivariable regression models were developed to account for patient, obstetric, physician, and hospital factors on receipt of antibiotics. Between-hospital variation was calculated using generalized linear mixed models., Results: Among 1,137,804 women who underwent cesarean delivery, 59.5% received perioperative antibiotics. The proportion of patients receiving antibiotics increased over time from 52.5% in 2003 to 63.1% in 2010 (P<.001) and varied significantly by geographic region. Women who did not labor were more likely to receive antibiotics than those who had a cesarean delivery after labor (66% compared with 44%, P<.001). Age, race, and insurance status were not major determinants of the use of perioperative antibiotics., Conclusion: Among women undergoing cesarean delivery, compliance with the recommendation for universal perioperative antibiotic prophylaxis is poor. Coordinated efforts are needed to enhance use of guideline-based perioperative antibiotic prophylaxis for women undergoing cesarean delivery., Level of Evidence: III.

Context: Lower birth weight has been reported in conjunction with high maternal free T4 (FT4) in euthyroid pregnancies, raising concerns for suboptimal outcomes., Objective: The objective of the study was to explore the relationships between high maternal FT4 and pregnancy complications in euthyroid women and to further examine the relationships among maternal size, FT4, and birth weight., Design: This was an observational multicenter cohort study., Setting: The study was conducted at prenatal clinics., Study Subjects: A total of 9209 euthyroid women with singleton pregnancies participated in the study., Interventions: There were no interventions., Main Outcome Measures: Relationships between second-trimester high maternal FT4 and pregnancy/delivery complications and, among FT4, maternal weight and birth weight were measured., Results: Women in the highest FT4 quintile are younger and weigh less than women in quintiles 1-4; gestational diabetes and preeclampsia occur less often (P = < .001, P < .001, P < .001, and P = .05, respectively). Lowest median birth weight occurs among women in the highest FT4 quintile (P = < .001), but deliveries less than 37 weeks' gestation are not increased. Labor/delivery complications do not differ by FT4 quintile. Restricting analyses to maternal weight-adjusted small-for-gestational-age deliveries yields similar results, except for preeclampsia. In the highest maternal weight decile, adjusted median birth weight is 266 g higher (8.3%) than in the lowest weight decile; adjusted median FT4 is 0.91 pmol/L lower (6.8%). Among women in the highest FT4 decile, adjusted median birth weight is 46 g lower (1.3%) than in the lowest FT4 decile. All three relationships are statistically significant (P < .001, P < .001, and P = .004, respectively)., Conclusions: Lower median birth weight among euthyroid women with high FT4 is not associated with adverse pregnancy outcomes. Further investigation is indicated to determine how the variations in thyroid hormone concentration influence birth weight.

Recognition of the need to reduce maternal mortality and morbidity in the United States has led to the creation of the National Partnership for Maternal Safety. This collaborative, broad-based initiative will begin with three priority bundles for the most common preventable causes of maternal death and severe morbidity: obstetric hemorrhage, severe hypertension in pregnancy, and peripartum venous thromboembolism. In addition, three unit-improvement bundles for obstetric services were identified: a structured approach for the recognition of early warning signs and symptoms, structured internal case reviews to identify systems improvement opportunities, and support tools for patients, families, and staff that experience an adverse outcome. This article details the formation of the National Partnership for Maternal Safety and introduces the initial priorities.

The Perinatal Quality Foundation has created an examination containing both knowledge-based and judgment questions relating to the interpretation of electronic fetal heart rate monitoring for credentialing all medical and nursing personnel working on a labor and delivery floor. A description of the examination and the rationale for its use throughout the United States is presented., (Copyright © 2014. Published by Mosby, Inc.)

In 2004, leaders in first-trimester aneuploidy screening and a multidisciplinary group of experts established the Nuchal Translucency Quality Review Program, a national program to standardize education, credentialing, and quality monitoring of nuchal translucency. Since its inception, the program has credentialed more than 6,600 physician and ultrasonographer participants and collected more than 2.4 million nuchal translucency measurements. Ongoing quality monitoring is conducted through statistical analysis comparing the distribution and standard deviation of participants' nuchal translucency measurements against those obtained from a standard referent curve. Results of these analyses are distributed to participants quarterly and are used to track each participant's performance and to trigger performance improvement activities or mandatory remediation. This program could serve as a template for future education and credentialing programs that include partnerships with academic leaders, national professional organizations, and industry.

Objective: To characterize contemporary practice patterns for postcesarean thromboembolism prophylaxis and determine whether opportunities to substantially decrease maternal mortality and morbidity in this clinical setting are being missed., Methods: A commercial hospitalization database that includes procedure and diagnosis codes, health care provider and hospital information, and patient demographic data were used to analyze use of venous thromboembolism prophylaxis after cesarean delivery in the United States between 2003 and 2010. The analysis evaluated whether patients received pharmacologic prophylaxis, mechanical prophylaxis, combined prophylaxis, or no prophylaxis. Hospital-level factors and patient characteristics were included in multivariable regression models evaluating prophylaxis administration., Results: We identified 1,263,205 women who underwent cesarean delivery. Within the cohort, 75.7% (n=955,787) received no thromboembolism prophylaxis, 22.1% (n=278,669) received mechanical prophylaxis alone, 1.3% (n=16,639) received pharmacologic prophylaxis, and 1.0% (n=12,110) received combination prophylaxis. The rate of prophylaxis increased from 8.4% in 2003 to 41.6% in 2010. Prophylaxis rates varied significantly by geographic region. Medical risk factors for thromboembolism were associated with only modest increases in prophylaxis., Conclusion: Although our findings demonstrated increased adoption of postcesarean venous thromboembolism prophylaxis, fewer than half of patients received recommended care as of 2010, and significant variation was present. Thromboembolism prophylaxis is underused and represents a major opportunity to reduce maternal morbidity and mortality. Risk assessment tools and thromboprophylaxis guidelines are needed to assure high-quality, uniform care., Level of Evidence: : III.

Objective: We surveyed obstetricians to determine their knowledge, patterns of care and treatment preferences for women with placenta accreta., Methods: A 27-item survey was mailed to fellows of the American College of Obstetricians and Gynecologists. The survey included demographics, questions regarding knowledge and items to examine practice patterns., Results: Among 994 surveyed practitioners 508 responded including 338 who practiced obstetrics. Among generalists, 23.8% of respondents referred patients with placenta accreta to a sub-specialist. Overall, 20.4% referred women to the nearest tertiary center, and 7.1% referred to a regional center. Delivery was recommended at 34-36 weeks by 41.2%. Adjuvant interventions including ureteral stents (26.3%), iliac artery embolization catheters (28.1%), and balloon occlusion catheters (20.1%) were used infrequently. Six or more units of blood were crossed for delivery by only 29.0% of practitioners., Conclusion: There is widespread variation in the care of women with or at risk for placenta accreta.

Objective: To determine the clinical outcomes and risk factors for persistence of ovarian cysts in pregnant women. With the increased use of ultrasound in pregnancy, the identification of incidental ovarian masses is becoming more common., Study Design: An observational study of women with ovarian masses identified before 24 weeks of pregnancy was performed. Only women who underwent follow-up imaging or surgery were included. Factors associated with persistence and outcomes of women who underwent surgery were analyzed., Results: Of the 803 women with available follow-up, the cysts resolved in 707 (88.1%) patients. Fifty (6.2%) women underwent surgical intervention. Women with persistent cysts were younger, more often Hispanic, detected at a later gestational age, had larger cysts, and more often had complex or solid components (p < 0.05 for all). Overall, 1 (0.1%) malignancy was diagnosed (a patient with a B-cell lymphoma), while 3 (0.4%) women had borderline epithelial ovarian tumors., Conclusion: Ovarian masses identified during pregnancy have a low risk of malignancy. The majority of women can be serially monitored without intervention.

Objective: Accurate amniocentesis-related pregnancy loss (ARL) rates for twin gestations remains elusive because of varying ARL definitions in the literature. We examined how OB/GYNs define/counsel women carrying twins about ARL., Methods: A random sample of 1000 American College of OB/GYN (ACOG) fellows and ACOG Collaborative Ambulatory Research Network (CARN) members were mailed surveys about their opinions/practice patterns regarding amniocentesis in twins. There were 208/400 (52%) CARN members and 166/600 (27%) ACOG fellows who returned the survey (37% response rate)., Results: Of respondents, 80.8% practiced general OB/GYN, and 9.1% practiced maternal fetal medicine. Of respondents, 72% discussed amniocentesis for prenatal diagnosis. Of these, 91.7% discuss the risk of ARL; however, 47.4% do not quote an ARL rate. Of those who discuss ARL rates, 65% quote a rate greater than for singletons. Regarding monochorionic-diamniotic twins, 12.1% of respondents said the ARL rate was less, 39.6% said equal to, and 38.9% said greater than for dichorionic twins. Table 1 lists the most common clinical definitions/time intervals used to describe ARL., Conclusion: Various definitions/ARL rates are used when counseling about ARL in twins. Further studies using a widely accepted definition of ARL are necessary to improve the counseling of women considering amniocentesis for prenatal diagnosis in twins., (© 2013 John Wiley & Sons, Ltd.)

Venous thromboembolism remains in the top three leading causes of maternal death in the US, representing 10.2% of pregnancy-related deaths. Risk of developing a pulmonary embolus appears to increase throughout pregnancy, with a peak in incidence in the early postpartum period. Overall the incidence of VTE is 0.6-1.8 VTEs per 1000 deliveries. Diagnosis and management of pulmonary embolus can prove challenging, but the aim should be to optimize maternal outcome while minimizing hemorrhagic complications. Low-molecular-weight heparin is a safe and effective treatment for the majority of cases of pregnancy-related pulmonary embolus., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Although maternal death remains rare in the United States, the rate has not decreased for 3 decades. The rate of severe maternal morbidity, a more prevalent problem, is also rising. Rise in maternal age, in rates of obesity, and in cesarean deliveries as well as more pregnant women with chronic medical conditions all contribute to maternal mortality and morbidity in the United States. We believe it is the responsibility of maternal-fetal medicine (MFM) subspecialists to lead a national effort to decrease maternal mortality and morbidity. In doing so, we hope to reestablish the vital role of MFM subspecialists to take the lead in the performance and coordination of care in complicated obstetrical cases. This article will summarize our initial recommendations to enhance MFM education and training, to establish national standards to improve maternal care and management, and to address critical research gaps in maternal medicine., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To examine trends in electronic fetal monitoring (EFM) use and quantify the extent to which such trends are associated with changes in rates of primary cesarean delivery and neonatal morbidity and mortality., Methods: We carried out a retrospective study of more than 55 million nonanomalous singleton live births (24-44 weeks of gestation) delivered in the United States between 1990 and 2004. Changes in the risks of neonatal mortality, cesarean delivery, and operative vaginal delivery for fetal distress, 5-minute Apgar score lower than 4, and neonatal seizures (at 34 weeks of gestation or after) were examined in relation to changes in EFM use., Results: Electronic fetal monitoring use increased from 73.4% in 1990 to 85.7% in 2004, a relative increase of 17% (95% confidence interval 16-18%). This increase was associated with an additional 5% and 2% decline in early and late neonatal deaths, respectively, at 24-33 weeks of gestation as well as a 4-7% additional decline in the 5-minute Apgar score lower than 4 at 24-33, 34-36, and 37-44 weeks of gestation. Increasing EFM use was associated with a 2-4% incremental increased rate of both cesarean delivery and operative vaginal delivery for fetal distress at 24-33, 34-36, and 37-44 weeks of gestation. Increasing EFM was not associated with any temporal changes in the rate of neonatal seizures., Conclusions: The temporal increase in EFM use in the United States appears to be modestly associated with the recent declines in neonatal mortality, especially at preterm gestations., Level of Evidence: II.

Street drug use during pregnancy is detrimental to fetal development. Although the prevalence of wheeze is high in offspring of substance-abusing mothers, nothing is known about the role of street drug use during pregnancy in its development. We investigated the impact of maternal street drug use and distress during pregnancy on the development of wheeze and allergy in preschool children. Questionnaire data were accessed from the Community Perinatal Care trial of 791 mother-child pairs in Calgary, Alberta. Using logistic regression, the association between maternal substance use and distress during pregnancy, and wheeze and allergy at age 3 years was determined in boys and girls. After adjusting for alcohol use during pregnancy, pre- and postnatal tobacco use, preterm birth, duration of exclusive breastfeeding, daycare attendance and maternal socioeconomic status, maternal street drug use during pregnancy [odds ratio (OR): 5.02, 95% confidence interval (CI): 1.30-19.4] and severe maternal distress during pregnancy (OR: 5.79, 95% CI: 1.25-26.8) were associated with wheeze in girls. In boys, an independent association was found between severe distress during pregnancy (OR: 3.85, 95% CI: 1.11-13.3) and allergies, but there was no association with maternal street drug use. In conclusion, we found an association between maternal street drug use and wheeze in preschool girls that could not be accounted for by maternal distress, smoking or alcohol use during pregnancy. Prenatal programming effects of street drugs may explain this association.

Background: Among euthyroid pregnant women in a large clinical trial, free thyroxine (FT4) measurements below the 2.5th centile were associated with a 17 lb higher weight (2.9 kg/m(2)) than in the overall study population. We explore this relationship further., Methods: Among 9351 women with second trimester thyrotropin (TSH) measurements between 1st and 98th centiles, we examine: (i) the weight/FT4 relationship; (ii) percentages of women in three weight categories at each FT4 decile; (iii) FT4 concentrations in three weight categories at each TSH decile; and (iv) impact of adjusting FT4 for weight--in the reference group and in 190 additional women with elevated TSH measurements., Results: FT4 values decrease steadily as weight increases (p<0.0001 by ANOVA) among women in the reference group (TSH 0.05-3.8 IU/L). TSH follows no consistent pattern with weight. When stratified into weight tertiles, 48% of women at the lowest FT4 decile are heavy; the percentage decreases steadily to 22% at the highest FT4 decile. Median FT4 is lowest in heaviest women regardless of the TSH level. In the reference group, weight adjustment reduces overall variance by 2.9%. Fewer FT4 measurements are at either extreme (below the 5th FT4 centile: 4.8% before adjustment, 4.7% after adjustment; above the 95th FT4 centile: 5.0% and 4.7%, respectively). Adjustment places more light weight women and fewer heavy women below the 5th FT4 centile; the converse above the 95th centile. Between TSH 3.8 and 5 IU/L, the FT4 percentage below the 5th FT4 centile is not elevated (3.8% before adjustment, 3.1% after adjustment). Percentage of FT4 values above the 95th centile, however, is lower (1.5% before adjustment, 0.8% after adjustment). Above TSH 5 IU/L, 25% of women have FT4 values below the 5th FT4 centile; weight adjustment raises this to 30%; no FT4 values remain above the 95th FT4 centile., Conclusions: During early pregnancy, TSH values are not associated with weight, unlike nonpregnant adults. Lower average FT4 values among heavy women at all TSH deciles partially explain interindividual differences in FT4 reference ranges. The continuous reciprocal relationship between weight and FT4 explains lower FT4 with higher weight. Weight adjustment refines FT4 interpretation.

Twin gestations face an increased risk of structural abnormalities compared with singleton gestations, as well as an increased risk of aneuploidy. Accordingly, there is a need for accurate prenatal diagnosis of fetal genetic disorders and structural anomalies in twin gestations. Given the increased risk of congenital anomalies, a detailed sonographic survey of fetal anatomy is recommended in the early second trimester of twin gestations. In addition, fetal echocardiography should be considered in monochorionic twin gestations and in dichorionic twin pregnancies conceived using assisted reproductive technologies given the increased risk of congenital heart disease in these populations. Although first- and second-trimester aneuploidy screening in twin gestations is available, screening is less accurate than in singleton gestations. Invasive prenatal diagnosis in twin pregnancies is associated with a risk of pregnancy loss that is higher than the baseline risk of loss among twin gestations. Precise procedure-related loss rates in twin gestations undergoing chorionic villus sampling or amniocentesis, however, remain unclear because of methodological differences between published studies investigating diagnostic procedures in twins., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Using published data, we sought to determine the amniocentesis-related loss rate in twin gestations., Methods: We searched the PUBMED database using keywords "amniocentesis", "twin" and "twins" to identify articles evaluating genetic amniocentesis in twin gestations published from January 1970 to December 2010. Random effects models were used to pool procedure-related loss rates from included studies., Results: The definition of "loss" varied across the 17 studies identified (Table 1). The pooled procedure-related loss rate at < 24 weeks was 3.5% (95% confidence interval [CI] 2.6-4.7) (Figure 2). Pooled loss rates at < 28 weeks (Figure 4) and to term (Figure 5) could not be calculated due to unacceptable heterogeneity of available data. Seven studies included a control (no amniocentesis) group and reported a pooled odds ratio for total pregnancy loss among cases of 1.8 (95% CI 1.2-2.7) (Figure 3). Only 1 study reported procedure-related loss rates by chorionicity (7.7% among monochorionics vs 1.4% among controls; p 0.02)., Conclusion: Analysis of published data demonstrated a pooled amniocentesis-related loss rate of 3.5% in twin gestations < 24 weeks. Pooled loss rates within other post-amniocentesis intervals or other gestational age windows and the impact of chorionicity on procedure-related loss rates cannot be determined from published data., (© 2011 John Wiley & Sons, Ltd.)

Background: Previous studies have shown that woman's risk of breast cancer in later life is associated with her infants birth weights. The objective of this study was to determine if this association is independent of breast cancer risk factors, mother's own birth weight and to evaluate association between infants birth weight and hormonal environment during pregnancy. Independent association would have implications for understanding the mechanism, but also for prediction and prevention of breast cancer., Methods and Findings: Risk of breast cancer in relation to a first infant's birth weight, mother's own birth weight and breast cancer risk factors were evaluated in a prospective cohort of 410 women in the Framingham Study. Serum concentrations of estriol (E3), anti-estrogen alpha-fetoprotein (AFP), and pregnancy-associated plasma protein-A (PAPP-A) were measured in 23,824 pregnant women from a separate prospective cohort, the FASTER trial. During follow-up (median, 14 years) 31 women (7.6%) were diagnosed with breast cancer. Women with large birth weight infants (in the top quintile) had a higher breast cancer risk compared to other women (hazard ratio (HR), 2.5; 95% confidence interval (CI), 1.2-5.2; P = 0.012). The finding was not affected by adjustment for birth weight of the mother and traditional breast cancer risk factors (adjusted HR, 2.5; 95% CI, 1.2-5.6; P = 0.021). An infant's birth weight had a strong positive relationship with the mother's serum E3/AFP ratio and PAPP-A concentration during pregnancy. Adjustment for breast cancer risk factors did not have a material effect on these relationships., Conclusions: Giving birth to an infant with high birth weight was associated with increased breast cancer risk in later life, independently of mother's own birth weight and breast cancer risk factors and was also associated with a hormonal environment during pregnancy favoring future breast cancer development and progression.

Objective: We examined predictors of massive blood loss for women with placenta accreta who had undergone hysterectomy., Study Design: A retrospective review of women who underwent peripartum hysterectomy for pathologically confirmed placenta accreta was performed. Characteristics that are associated with massive blood loss (≥ 5000 mL) and large-volume transfusion (≥ 10 units packed red cells) were examined., Results: A total of 77 patients were identified. The median blood loss was 3000 mL, with a median of 5 units of red cells transfused. There was no association among maternal age, gravidity, number of previous deliveries, number of previous cesarean deliveries, degree of placental invasion, or antenatal bleeding and massive blood loss or large-volume transfusion (P > .05). Among women with a known diagnosis of placenta accreta, 41.7% had an estimated blood loss of ≥ 5000 mL, compared with 12.0% of those who did not receive the diagnosis antenatally with ultrasound scanning (P = .01)., Conclusion: There are few reliable predictors of massive blood loss in women with placenta accreta., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Prenatal repair of myelomeningocele, the most common form of spina bifida, may result in better neurologic function than repair deferred until after delivery. We compared outcomes of in utero repair with standard postnatal repair., Methods: We randomly assigned eligible women to undergo either prenatal surgery before 26 weeks of gestation or standard postnatal repair. One primary outcome was a composite of fetal or neonatal death or the need for placement of a cerebrospinal fluid shunt by the age of 12 months. Another primary outcome at 30 months was a composite of mental development and motor function., Results: The trial was stopped for efficacy of prenatal surgery after the recruitment of 183 of a planned 200 patients. This report is based on results in 158 patients whose children were evaluated at 12 months. The first primary outcome occurred in 68% of the infants in the prenatal-surgery group and in 98% of those in the postnatal-surgery group (relative risk, 0.70; 97.7% confidence interval [CI], 0.58 to 0.84; P<0.001). Actual rates of shunt placement were 40% in the prenatal-surgery group and 82% in the postnatal-surgery group (relative risk, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001). Prenatal surgery also resulted in improvement in the composite score for mental development and motor function at 30 months (P=0.007) and in improvement in several secondary outcomes, including hindbrain herniation by 12 months and ambulation by 30 months. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at delivery., Conclusions: Prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00060606.).

Objective: To estimate the relationship between thyroid antibodies and placental abruption., Methods: This cohort study assesses thyroperoxidase and thyroglobulin antibodies in relation to placental abruption among 10,062 women with singleton viable pregnancies (from the First and Second Trimester Risk of Aneuploidy [FaSTER] trial). A thyroperoxidase antibody cutoff of 50 international units/mL is used for comparison with published data from another cohort., Results: Women with elevated thyroperoxidase antibody levels in the first and second trimesters have a higher rate of placental abruption than antibody-negative women. This relationship is less strong in the first trimester (1.51% compared with 0.83%; odds ratio [OR], 1.83; 95% confidence interval [CI], 0.99-3.37) than in the second trimester (1.78% compared with 0.82%; OR, 2.20; 95% CI, 1.21-3.99). A similar, but weaker, relationship is present for thyroglobulin antibodies. Sixty-four of 782 thyroperoxidase antibody-positive pregnancies without abruption become negative by the second trimester; one pregnancy with abruption becomes antibody-positive. Odds ratios for pregnancies with both thyroperoxidase and thyroglobulin antibody elevations are also higher (first trimester: OR, 2.10; 95% CI, 0.91-4.86; second trimester: OR, 2.73; 95% CI, 1.17-6.33)., Conclusion: The present data confirm an association between thyroid antibody elevations and placental abruption described in a recent report. These findings, however, do not provide support for recommending routine testing for thyroid antibodies during pregnancy., Level of Evidence: II.

Objective: To further evaluate the relationship between thyroid antibodies and preterm births., Methods: This is a prospective study of pregnancy outcome and demographic data combined with retrospective measurement of thyroperoxidase and thyroglobulin antibodies. Sera were obtained at 11-13 and 15-18 weeks of gestation from 10,062 women with singleton viable pregnancies (a subset from the First- and Second-Trimester Risk of Aneuploidy [FaSTER] trial)., Results: Women with elevated levels of thyroperoxidase, thyroglobulin antibodies, or both in the first trimester have a higher rate of preterm delivery before 37 weeks of gestation than antibody-negative women (7.5% compared with 6.4%, odds ratio [OR] 1.18; 95% confidence interval [CI] 0.95-1.46). This is also the case for very preterm delivery before 32 weeks of gestation (1.2% compared with 0.7%, OR 1.70; 95% CI 0.98-2.94). Preterm premature rupture of membranes is also increased (2.0% compared with 1.2%, OR 1.67; 95% CI 1.05-2.44). These associations are less strong for second-trimester antibody measurements., Conclusion: The present data do not confirm strong associations between thyroid antibody elevations and preterm birth found in three of five previously published reports. Preterm premature rupture of membranes appears to contribute to the thyroid antibody-associated early deliveries, possibly as a result of inflammation., Level of Evidence: II.

Objective: To perform a population-based analysis to examine the morbidity and mortality of peripartum hysterectomy in comparison with nonobstetric hysterectomy., Methods: Data from the Nationwide Inpatient Sample were used to compare peripartum and nonobstetric hysterectomy in women younger than 50 years of age. Intraoperative, perioperative, and postoperative medical complications were examined. The outcomes of peripartum and nonobstetric hysterectomy were compared using chi square. Odds ratios were calculated using multivariable logistic regression models for each individual complication., Results: A total of 4,967 women who underwent peripartum hysterectomy and 578,179 patients who had a nonobstetric hysterectomy were identified. Bladder (9% compared with 1%) and ureteral (0.7% compared with 0.1%) injuries were more common for peripartum hysterectomy (P<.001). There were no differences in the rates of intestinal or vascular injuries between peripartum and nonobstetric hysterectomy. Rates of reoperation (4% compared with 0.5%), postoperative hemorrhage (5% compared with 2%), wound complications (10% compared with 3%), and venous thromboembolism (1% compared with 0.7%) were all higher in women who underwent peripartum hysterectomy. In multivariable analysis, the odds ratio for death for peripartum compared to nonobstetric hysterectomy was 14.4 (95% confidence interval 9.84-20.98)., Conclusion: Peripartum hysterectomy is accompanied by substantial morbidity and mortality. Compared with nonobstetric hysterectomy, the procedure is associated with increased rates of both intraoperative and postoperative complications. The mortality of peripartum hysterectomy is more than 25 times that of hysterectomy performed outside of pregnancy., Level of Evidence: II.

Objective: To examine factors that influence the morbidity and mortality of peripartum hysterectomy and analyze the effect of hospital volume on maternal mortality., Methods: We examined women who underwent peripartum hysterectomy at the time of cesarean delivery in a quality and resource utilization database. Procedure-associated intraoperative, perioperative, and postoperative medical complications, length of stay, intensive care unit use, and maternal mortality were analyzed. Hospitals were stratified into tertiles based on procedure volume and complications and compared using adjusted generalized estimating equations. Results are reported as odds ratios., Results: Maternal mortality among the 2,209 women who underwent peripartum hysterectomy was 1.2%. After adjusting for other clinical and demographic factors, perioperative mortality was 71% (odds ratio 0.29, 95% confidence interval 0.10-0.88) lower in women who underwent operation at high-volume hospitals compared with those treated at low-volume facilities. Hospital volume had no effect on the rates of intraoperative injuries, medical complications, length of stay, or transfusion. In contrast, compared with women treated at low-volume centers, patients who underwent operation at high-volume hospitals had a lower incidence of perioperative surgical complications (odds ratio 0.66, 95% confidence interval 0.47-0.93) and a lower rate of intensive care unit usage (odds ratio 0.53, 95% confidence interval 0.34-0.83)., Conclusion: Peripartum hysterectomy is associated with substantial morbidity and mortality. Maternal mortality is lower when the procedure is performed in high-volume hospital settings., Level of Evidence: II.

Objective: We sought to evaluate the influence of maternal body mass index (BMI) on sonographic detection employing data from the FaSTER trial., Method: Unselected singleton pregnancies underwent detailed genetic sonogram to evaluate for structural fetal anomalies and soft markers for aneuploidy. BMI (kg/m(2)) were calculated from reported initial visit values. Sensitivity, specificity, false positive and false negative rates (FPR and FNR), likelihood ratio, detection rates, and a missed diagnosis rate (MDR: FNR + marker recorded as 'missing'/N) were calculated., Results: Eight thousand five hundred and fifty-five patients with complete BMI information had detailed genetic sonography. A lower sensitivity with an elevated FNR and MDR was observed in obese women for multiple aneuploid markers (e.g. > or =2 markers 32% sensitivity with 68% FNR among BMI <25 vs 22% and 78% among BMI >30). Similarly, the detection rate for cardiac anomalies among women at BMI <25 was higher (21.6%) at a significantly lower FPR (78.4%; 95% CI 77.3-79.5%) in comparison to obese women (8.3% with FPR 91.7%; 95% CI 90.1-93.2%). In a logistic regression model, maternal obesity significantly decreased the likelihood of sonographic detection of common anomalies (adjusted OR 0.7; 95% CI 0.6-0.9; p = 0.001)., Conclusion: The performance of second trimester genetic sonography is influenced by obesity, with a significantly higher MDR for multiple minor markers and lower likelihood for detecting common anomalies., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

Objective: To estimate the effectiveness of second-trimester genetic sonography in modifying Down syndrome screening test results., Methods: The First and Second Trimester Evaluation of Risk (FASTER) aneuploidy screening trial participants were studied from 13 centers where a 15- to 23-week genetic sonogram was performed in the same center. Midtrimester Down syndrome risks were estimated for five screening test policies: first-trimester combined, second-trimester quadruple, and testing sequentially by integrated, stepwise, or contingent protocols. The maternal age-specific risk and the screening test risk were modified using likelihood ratios derived from the ultrasound findings. Separate likelihood ratios were obtained for the presence or absence of at least one major fetal structural malformation and for each "soft" sonographic marker statistically significant at the P<.005 level. Detection and false-positive rate were calculated for the genetic sonogram alone and for each test before and after risk modification., Results: A total of 7,842 pregnancies were studied, including 59 with Down syndrome. Major malformations and 8 of the 18 soft markers evaluated were highly significant. The detection rate for a 5% false-positive rate for the genetic sonogram alone was 69%; the detection rate increased from 81% to 90% with the combined test, from 81% to 90% with the quadruple test, from 93% to 98% with the integrated test, from 97% to 98% with the stepwise test, and from 95% to 97% with the contingent test. The stepwise and contingent use of the genetic sonogram after first-trimester screening both yielded a 90% detection rate., Conclusion: Genetic sonography can increase detection rates substantially for combined and quadruple tests and more modestly for sequential protocols. Substituting sonography for quadruple markers in sequential screening was not useful., Level of Evidence: II.

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.

Objective: To evaluate nuchal translucency measurement quality assurance techniques in a large-scale study., Methods: From 1999 to 2001, unselected patients with singleton gestations between 10 + 3 weeks and 13 + 6 weeks were recruited from 15 centers. Sonographic nuchal translucency measurement was performed by trained technicians. Four levels of quality assurance were employed: (1) a standardized protocol utilized by each sonographer; (2) local-image review by a second sonographer; (3) central-image scoring by a single physician; and (4) epidemiological monitoring of all accepted nuchal translucency measurements cross-sectionally and over time., Results: Detailed quality assessment was available for 37 018 patients. Nuchal translucency measurement was successful in 96.3% of women. Local reviewers rejected 0.8% of images, and the single central physician reviewer rejected a further 2.9%. Multivariate analysis indicated that higher body mass index, earlier gestational age and transvaginal probe use were predictors of failure of nuchal translucency measurement and central image rejection (P = 0.001). Epidemiological monitoring identified a drift in measurements over time., Conclusion: Despite initial training and continuous image review, changes in nuchal translucency measurements occur over time. To maintain screening accuracy, ongoing quality assessment is needed.

Mothers should be counseled that the most concerning risks related to maternal request cesarean delivery are neonatal respiratory morbidity and those that may affect the mother's future reproductive health, including life-threatening conditions, such as placenta accreta. The literature suggests that overall risks of maternal complications with cesarean delivery on maternal request are slightly lower than a trial of vaginal delivery and are primarily driven by the avoidance of unplanned or emergent cesarean deliveries and their associated increased rate of complications. When addressing risks and benefits with patients, there are three areas of importance. First, the risks for neonatal respiratory morbidity and abnormal placentation with future pregnancies should be emphasized. Secondly, there are many areas on which studies are lacking. Finally, numerous factors can alter the risks and benefits--such as culture, maternal obesity, and provider background--and should be acknowledged.

Objective: To develop and evaluate a method of estimating patient-specific risk for fetal loss by combining maternal characteristics with serum markers., Study Design: Data were obtained on 36,014 women from the FaSTER trial. Separate likelihood ratios were estimated for significant maternal characteristics and serum markers. Patient-specific risk was calculated by multiplying the incidence of fetal loss by the likelihood ratios for each maternal characteristic and for different serum marker combinations., Results: Three hundred eighteen women had fetal loss < 24 weeks (early) and 103 > 24 weeks (late). Clinical characteristics evaluated included maternal age, body mass index, race, parity, threatened abortion, previous preterm delivery, and previous early loss. Serum markers studied as possible predictors of early loss included first-trimester pregnancy-associated plasma protein A and second-trimester alpha-fetoprotein, and unconjugated estriol. A risk assessment for early loss based on all of these factors yielded a 46% detection rate, for a fixed 10% false-positive rate, 39% for 5% and 28% for 1%. The only significant marker for late loss was inhibin A. The detection rate was 27% for a fixed 10% false-positive rate and only increased slightly when clinical characteristics were added to the model., Conclusion: Patient-specific risk assessment for early fetal loss using serum markers, with or without maternal characteristics, has a moderately high detection. Patient-specific risk assessment for late fetal loss has low detection rates.

Objective: The objective of the study was to further explore relationships between human chorionic gonadotropin (hCG), TSH, and free T4 in pregnant women at 11 through 18 wk gestation., Study Design: The design of the study was to analyze hCG in comparison with TSH and free T4, in paired first- and second-trimester sera from 9562 women in the First and Second Trimester Evaluation of Risk for Fetal Aneuploidy trial study., Results: hCG is strongly correlated with body mass index, smoking, and gravidity. Correlations with selected maternal covariates also exist for TSH and free T4. As hCG deciles increase, body mass index and percent of women who smoke both decrease, whereas the percent of primigravid women increases (P < 0.0001). hCG/TSH correlations are weak in both trimesters (r2 = 0.03 and r2 = 0.02). TSH concentrations at the 25th and fifth centiles become sharply lower at higher hCG levels, whereas 50th centile and above TSH concentrations are only slightly lower. hCG/free T4 correlations are weak in both trimesters (r2 = 0.06 and r2 = 0.003). At 11-13 wk gestation, free T4 concentrations rise uniformly at all centiles, as hCG increases (test for trend, P < 0.0001), but not at 15-18 wk gestation. Multivariate analyses with TSH and free T4 as dependent variables and selected maternal covariates and hCG as independent variables do not alter these observations., Conclusions: In early pregnancy, a woman's centile TSH level appears to determine susceptibility to the TSH being suppressed at any given hCG level, suggesting that hCG itself may be the primary analyte responsible for stimulating the thyroid gland. hCG affects lower centile TSH values disproportionately.

Objective: The purpose of this study was to examine how closely hypothyroidism management in the general pregnancy population satisfies recently issued guidelines and to determine whether improvements are indicated., Study Design: This was an observational study in which women at 5 recruitment centers in the first- and second-trimester evaluation of risk for aneuploidy trial allowed the use of sequentially obtained first- and second-trimester sera for additional research. Three hundred eighty-nine women had hypothyroidism by self-report. Thyroid-related measurements were performed on all samples between July 2004 and May 2005., Results: Forty-three percent of the thyroid-stimulating hormone (TSH) values are at or above recently recommended guidelines in the first trimester (2.5 mU/L), as opposed to 33% of the values in the second trimester (3.0 mU/L). Twenty percent of the TSH values are at or above a less restrictive 98th percentile of normal in the first trimester, as opposed to 23% of the values in the second trimester. Mean TSH levels are higher in women with antibodies. Free thyroxine values are unremarkable., Conclusion: Future strategies should focus on more effectively treating women with hypothyroidism who have persistently elevated TSH values.

Objective: To estimate whether maternal thyroid hypofunction is associated with complications., Methods: A total of 10,990 patients had first- and second-trimester serum assayed for thyroid-stimulating hormone (TSH), free thyroxine (freeT4), and antithyroglobulin and antithyroid peroxidase antibodies. Thyroid hypofunction was defined as 1) subclinical hypothyroidism: TSH levels above the 97.5th percentile and free T4 between the 2.5th and 97.5th percentiles or 2) hypothyroxinemia: TSH between the 2.5th and 97.5th percentiles and free T4 below the 2.5th percentile. Adverse outcomes were evaluated. Patients with thyroid hypofunction were compared with euthyroid patients (TSH and free T4 between the 2.5th and 97.5th percentiles). Patients with and without antibodies were compared. Multivariable logistic regression analysis adjusted for confounders was used., Results: Subclinical hypothyroidism was documented in 2.2% (240 of 10,990) in the first and 2.2% (243 of 10,990) in the second trimester. Hypothyroxinemia was documented in 2.1% (232 of 10,990) in the first and 2.3% (247 of 10,990) in the second trimester. Subclinical hypothyroidism was not associated with adverse outcomes. In the first trimester, hypothyroxinemia was associated with preterm labor (adjusted odds ratio [aOR] 1.62; 95% confidence interval [CI] 1.00-2.62) and macrosomia (aOR 1.97; 95% CI 1.37-2.83). In the second trimester, it was associated with gestational diabetes (aOR 1.7; 95% CI 1.02-2.84). Fifteen percent (1,585 of 10,990) in the first and 14% (1,491 of 10,990) in the second trimester had antithyroid antibodies. When both antibodies were positive in either trimester, there was an increased risk for preterm premature rupture of membranes (P=.002 and P<.001, respectively)., Conclusion: Maternal thyroid hypofunction is not associated with a consistent pattern of adverse outcomes., Level of Evidence: II.

Objective: The purpose of this study was to calculate first and second trimester reference ranges and within-woman correlations for TSH, free T4, and thyroid antibodies., Study Design: TSH, free T4, and thyroid antibodies were measured in paired sera from 9562 women in the FaSTER trial of Down syndrome screening., Results: The median first trimester TSH (1.05 mIU/L) is lower than the second (1.23 mIU/L); and 98th centile is higher (4.15 vs 3.77 mIU/L). Within-woman paired TSH correlations are moderately strong (r(2) = 0.64). Among women with first trimester TSH values above the 98th centile, second trimester values are over the 95th centile in 68%. Median first trimester free T4 values (1.10 ng/dL) are higher than second (1.01 ng/dL). Paired free T4 measurements correlate weakly (r(2) = 0.23). Among women with first trimester free T4 values below the 2nd centile, second trimester values are below the 5th centile in 32%. Antibody measurements correlate strongly between trimesters (thyroperoxidase r(2) = 0.79, thyroglobulin r(2) = 0.83)., Conclusion: TSH and free T4 measurements require gestation-specific reference ranges.

Growth abnormalities which include intrauterine growth restriction and weight discordance between twins are common in pregnancies complicated by multiple gestations and may be associated with poor perinatal outcomes. Knowledge of chorionicity is paramount when managing a multiple pregnancy. Monochorionic twins are at greater risk than dichorionic twins for growth issues, which may result in long-term complications including adverse neurological sequelae for the offspring. The purpose of the following article is to define normal and abnormal growth in multiples. In addition, the management of growth abnormalities in relationship to chorionicity will be discussed.

Objective: To demonstrate that individualized optimal fetal growth norms, accounting for physiologic and pathologic determinants of fetal growth, better identify normal and abnormal outcomes of pregnancy than existing methods., Methods: In a prospective cohort of 38,033 singleton pregnancies, we identified 9,818 women with a completely normal outcome of pregnancy and characterized the physiologic factors affecting birth weight using multivariable regression. We used those physiologic factors to individually predict optimal growth trajectory and its variation, growth potential, for each fetus in the entire cohort. By comparing actual birth weight with growth potential, population, ultrasound, and customized norms, we calculated for each fetus achieved percentiles, by each norm. We then compared proportions of pregnancies classified as normally grown, between 10th and 90th percentile, or aberrantly grown, outside this interval, by growth potential and traditional norms, in 14,229 complicated pregnancies, 1,518 pregnancies with diabetes or hypertensive disorders, and 1,347 pregnancies with neonatal complications., Results: Nineteen physiologic factors, associated with maternal characteristics and early placental function, were identified. Growth potential norms correctly classified significantly more pregnancies than population, ultrasound, or customized norms in complicated pregnancies (26.4% compared with 18.3%, 18.7%, 22.8%, respectively, all P<.05), pregnancies with diabetes or hypertensive disorders (37.3% compared with 23.0%, 28.0%, 34.0%, respectively, all P<.05) and neonatal complications (33.3% compared with 19.7%, 24.9%, 29.8%, respectively, all P<.05)., Conclusion: Growth potential norms based on the physiologic determinants of birth weight are a better discriminator of aberrations of fetal growth than traditional norms., Level of Evidence: II.

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.

Objective: To determine if first trimester fetal growth is associated with birth weight, duration of pregnancy, and the risk of delivering a small for gestational age infant., Design: Prospective cohort study of 38 033 pregnancies between 1999 and 2003., Setting: 15 centres representing major regions of the United States., Participants: 976 women from the original cohort who conceived as the result of assisted reproductive technology, had a first trimester ultrasound measurement of fetal crown-rump length, and delivered live singleton infants without evidence of chromosomal or congenital abnormalities. First trimester growth was expressed as the difference between the observed and expected size of the fetus, expressed as equivalence to days of gestational age., Main Outcome Measures: Birth weight, duration of pregnancy, and risk of delivering a small for gestational age infant., Results: For each one day increase in the observed size of the fetus, birth weight increased by 28.2 (95% confidence interval 14.6 to 41.2) g. The association was substantially attenuated by adjustment for duration of pregnancy (adjusted coefficient 17.1 (6.6 to 27.5) g). Further adjustments for maternal characteristics and complications of pregnancy did not have a significant effect. The risk of delivering a small for gestational age infant decreased with increasing size in the first trimester (odds ratio for a one day increase 0.87, 0.81 to 0.94). The association was not materially affected by adjustment for maternal characteristics or complications of pregnancy., Conclusion: Variation in birth weight may be determined, at least in part, by fetal growth in the first 12 weeks after conception through effects on timing of delivery and fetal growth velocity.

Down syndrome (DS) is the most prevalent chromosomal disorder, accounting for significant morbidity and mortality. Definitive diagnosis requires invasive amniocentesis, and current maternal serum-based testing requires a false-positive rate of about 5% to detect 85% of affected pregnancies. We have performed a comprehensive proteomic analysis to identify potential serum biomarkers to detect DS. First- and second-trimester maternal serum samples of DS and gestational age-matched controls were analyzed using multiple, complementary proteomic approaches, including fluorescence 2-dimensional gel electrophoresis (2D-DIGE), 2-dimensional liquid chromatography-chromatofocusing (2D-CF), multidimensional protein identification technology (MudPIT; LC/LC-MS/MS), and MALDI-TOF-MS peptide profiling. In total, 28 and 26 proteins were differentially present in first- and second-trimester samples, respectively. Of these, 19 were specific for the first trimester and 16 for the second trimester, and 10 were differentially present in both trimesters. Analysis of MALDI-TOF-MS peptide profiles with pattern-recognition software also discriminated between DS and controls in both trimesters, with an average recognition capability approaching 96%. A majority of the biomarkers identified are serum glycoproteins that may play a role in cellular differentiation and growth of fetus. Further characterization and quantification of these markers in a larger cohort of subjects may provide the basis for new tests for improved DS screening.

Multiple pregnancies currently account for 3% of all births in the United States but are disproportionately responsible for larger rates of prematurity and significant neonatal morbidity. The mean birth age for most multi-fetal pregnancies occurs during the late preterm period when both spontaneous preterm labor and iatrogenic premature birth because of obstetrical or maternal complications are common. Multiples pose numerous unique challenges, emphasizing the significant impact of plurality on late preterm births.

Objective: The purpose of this study was to evaluate whether there is a nuchal translucency (NT) measurement, independent of gestational age, above which immediate diagnostic testing should be offered without waiting for first trimester serum markers., Study Design: Thirty-six thousand one hundred twenty patients had successful measurement of simple NT at 10 3/7 to 13 6/7 weeks and had first trimester serum screening. No risks were reported until second trimester serum screening was completed., Results: Thirty-two patients (0.09%) had NT > or = 4.0 mm; the lowest combined first trimester trisomy 21 risk assessment in euploid cases was 1 in 8 and among aneuploidy cases was 7 in 8. One hundred twenty-eight patients (0.3%) had simple NT > or = 3.0 mm: the lowest combined first trimester trisomy 21 risk assessment of any patient in this group was 1 in 1479 and the lowest risk assessment among aneuploid cases was 1 in 2. Ten patients (8%) had first trimester trisomy 21 risk assessments lowered to less that 1:200 and none of these 10 cases had an abnormal outcome., Conclusion: During first trimester Down syndrome screening, whenever an NT measurement of 3.0 mm or greater is obtained there is minimal benefit in waiting for serum screening results, and no benefit for NT of 4.0 mm or greater. Differentiation between cystic hygroma and enlarged simple NT (> or = 3.0 mm) is now a moot point as both are sufficiently high risk situations to warrant immediate CVS.

Objective: To determine whether first- and second-trimester Down syndrome screening markers and screen-positive rates are altered in pregnancies conceived using assisted reproductive technologies (ARTs)., Methods: ART pregnancies in the multicenter FASTER trial were identified. Marker levels were evaluated for five types of ART: in vitro fertilization with ovulation induction (IVF-OI), IVF with OI and egg donation (IVF-OI-ED), IVF with ED (IVF-ED), and intrauterine insemination with OI (IUI-OI) or without OI (IUI). Each group was compared to non-ART controls using Mann-Whitney U analysis., Results: First-trimester marker levels were not significantly different between ART and control pregnancies, with the exception of reduced PAPP-A levels in the IUI-OI group. In contrast, second-trimester inhibin A levels were increased in all ART pregnancies, estriol was reduced and human chorionic gonadotropin (hCG) was increased in IVF and IUI pregnancies without ED, and alpha-fetoprotein (AFP) was increased in ED pregnancies. Second-trimester screen-positive rates were significantly higher than expected for ART pregnancies, except when ED was used., Conclusions: These data show that ART significantly impacts second-, but not first-, trimester markers and screen-positive rates. The type of adjustment needed in second-trimester screening depends on the particular type of ART used.

Multiple gestations present unique challenges to the modern obstetrician. Many twin and high-order multiple pregnancies are delivered between 34 and 37 weeks' gestation either secondary to preterm labor or obstetrical complications necessitating intervention. Recognizing the increasing prevalence of multiple gestations and the impact of late preterm deliveries in modern practice, this review analyzes the impact of multiple pregnancies on perinatal outcomes, reviews the strategies to prevent preterm labor, and summarizes potential indications for late preterm delivery. In this paper, "late preterm" has been used instead of "near-term," as the former was considered more appropriate to reflect this subgroup of preterm infants in a workshop on this topic held in July 2005, organized by the National Institute of Child Health and Human Development.

Screening for the risk of fetal aneuploidy can be effectively performed in either the first or second trimester. When obtained independently, the interpretation of those data is straightforward. However, the effectiveness of screening can be enhanced by combining studies performed in each trimester in a variety of ways. In this commentary we will define and discuss both the advantages and disadvantages of using integrated, stepwise, sequential or contingency screening for risk assessment of fetal aneuploidy.

Objective: The purpose of this study was to examine the levels of first- and second-trimester maternal serum markers used in Down syndrome screening in relation to the time between sample collection and arrival at the laboratory., Methods: The FASTER trial, designed to compare first- and second-trimester screening tests for aneuploidy, has recently been completed, having recruited more than 38,000 patients. According to the trial protocol, all blood samples were drawn in serum separator tubes, centrifuged within 30 min and stored at 4 degrees C until shipment by air express. To examine the effect of delayed shipment, serum marker levels (expressed as multiple of the median--MoM) were evaluated in the first- and second-trimester samples and stratified by the number of days between serum collection and laboratory receipt., Results: Under specified collection and shipment conditions, first and second-trimester screening marker mean levels and degrees of variance were stable for up to 9 days, with the exception of unconjugated estriol, which was stable for up to 6 days., Conclusion: The levels of first- and second-trimester Down syndrome screening markers can be measured reliably when the sample is centrifuged, refrigerated until shipment and received in the laboratory within a week of being drawn. A conservative approach would be to restrict testing to within 6 days of draw, with the intent to keep shipping delays to a minimum., (2006 John Wiley & Sons, Ltd.)