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Objective: To compare stillbirth rates per week of expectant management stratified by birth weight in pregnancies complicated by gestational diabetes mellitus (GDM) or pregestational diabetes mellitus., Methods: A national population-based retrospective cohort study of singleton, nonanomalous pregnancies complicated by pregestational diabetes or GDM was performed using national birth and death certificate data from 2014 to 2017. Stillbirth rates per 10,000 patients (stillbirth incidence at gestational age week/ongoing pregnancies-[0.5×live births at gestational age week]) were determined for each week of pregnancy from 34 to 39 completed weeks of gestation. Pregnancies were stratified by birth weight, categorized as having small-for-gestational-age (SGA), appropriate-for-gestational-age (AGA), or large-for-gestational-age (LGA) fetuses, assigned by sex-based Fenton criteria. Relative risk (RR) and 95% CI for stillbirth were calculated for each gestational age week compared with the GDM-related AGA group., Results: We included 834,631 pregnancies complicated by either GDM (86.9%) or pregestational diabetes (13.1%) in the analysis, with a total of 3,033 stillbirths. Stillbirth rates increased with advancing gestational age for pregnancies complicated by both GDM and pregestational diabetes regardless of birth weight. Compared with pregnancies with AGA fetuses, those with both SGA and LGA fetuses were significantly associated with an increased risk of stillbirth at all gestational ages. Ongoing pregnancies at 37 weeks of gestation complicated by pregestational diabetes with LGA or SGA fetuses had respective stillbirth rates of 64.9 and 40.1 per 10,000 patients. Pregnancies complicated by pregestational diabetes had an RR of stillbirth of 21.8 (95% CI 17.4-27.2) for LGA fetuses and 13.5 (95% CI 8.5-21.2) for SGA fetuses compared with GDM-related AGA at 37 weeks of gestation. The greatest absolute risk of stillbirth was in pregnancies complicated by pregestational diabetes at 39 weeks of gestation with LGA fetuses (97/10,000)., Conclusion: Pregnancies complicated by both GDM and pregestational diabetes affected by pathologic fetal growth have an increased risk of stillbirth with advancing gestational age. This risk is significantly higher with pregestational diabetes, especially pregestational diabetes with LGA fetuses., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

This was a retrospective cohort study of patients who delivered singleton, small-for-gestational-age (SGA) neonates between April and June 2019, before the coronavirus disease 2019 (COVID-19) pandemic (pre-COVID-19), and between April and July 2020, during the pandemic (COVID-19 epoch). The primary outcome was the rate of undetected antenatal fetal growth restriction (FGR) in the two periods. A total of 268 patients met inclusion criteria. Patients who delivered small-for-gestational-age neonates during the COVID-19 epoch were significantly more likely to have undetected FGR compared with those who delivered pre-COVID-19 (70.1% vs 58.1%, P =.04). Patients who delivered SGA neonates during the COVID-19 epoch had more telehealth visits but fewer in-person prenatal visits, recorded fundal height measurements, and growth ultrasonograms. As telemedicine continues to be incorporated into prenatal care, these data may lend further support toward self-assessment of fundal height or routine third-trimester growth ultrasonograms to identify fetal growth abnormalities., Competing Interests: Financial Disclosure Sindhu K. Srinivas received payment from Huff Powell Bailey, Goodell Devries Leech and Dann, LLP, and Sinai Hospital. Nadav Schwartz is a paid consultant for Nuvo Group, LTD. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies., Data Sources: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded., Methods of Study Selection: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs., Tabulation, Integration, and Results: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward., Conclusion: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone., Systematic Review Registration: PROSPERO, CRD42018090866., Competing Interests: Financial Disclosure Elena Carreras is a member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA (EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516). One included research project was supported, in part, by the Division of Population Health, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and, in part, with federal funds for the NICHD Fetal Growth Studies – Dichorionic Twins under Contract Numbers: HHSN275200800013C; HHSN275200800002I; HHSN27500006; HHSN275200800003IC; HHSN275200800014C; HHSN275200800012C; HHSN275200800028C; and HHSN275201000009C. Katherine L. Grantz has contributed to this work as part of her official duties as an employee of the United States federal government. Wessel Ganzevoort reports government funding (ZonMW 843002825) and free-of-charge test kits from Roche Diagnostics. Sanne J. Gordijn disclosed that money was paid to their institution from ZonMW, Roche (in-kind kits unrestricted and shipping and handling of material), and SCEM (conference payment to research fund). They also received funding from Dublin Maternity Hospital (payment for travels for Charter Day lecture). In addition, they report holding government funding (ZonMW 852002034) and free-of-charge test kits from Roche Diagnostics. R. Katie Morris disclosed money was paid to her through a consultancy to a company that designs neonatal vital signs monitors (SUREPULSE), and money was paid to her institution from the NIHR. Ben W. Mol is supported by a NHMRC Investigator grant (GNT1176437), and reports consultancy for ObsEva and research funding from Ferring and Merck. The PREDICT study received funding from The Danish Medical Research Council, The Fetal Medicine Foundation, The Copenhagen University Hospital's Research Fund, The Aase and Ejnar Danielsens Fund, The Augustinus Fund, The Ivan Nielsen Fund, The Doctor Sofus Carl Emil Friis, and wife Olga Doris Friis' Fund, The Simon Fougner Hartmanns Family Fund, The Danish Medical Society in Copenhagen, and The A.P. Moeller Foundation. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate outcomes of the first pregnancy after fertility-sparing surgery in patients with early-stage cervical cancer., Methods: We performed a population-based study of women aged 18-45 years with a history of stage I cervical cancer reported to the 2000-2012 California Cancer Registry. Data were linked to the OSHPD (California Office of Statewide Health Planning and Development) birth and discharge data sets. We included patients with cervical cancer who conceived at least 3 months after a fertility-sparing surgery, which included cervical conization or loop electrosurgical excision procedure. Those undergoing trachelectomy were excluded. The primary outcome was preterm birth. Secondary outcomes included growth restriction, neonatal morbidity, stillbirth, cesarean delivery, and severe maternal morbidity. We used propensity scores to match similar women from two groups in a 1:2 ratio of case group participants to control group participants: population individuals without cancer and individuals with cervical cancer (women who delivered before their cervical cancer diagnosis). Wald statistics and logistic regressions were used to evaluate outcomes., Results: Of 4,087 patients with cervical cancer, 118 (2.9%) conceived after fertility-sparing surgery, and 107 met inclusion criteria and were matched to control group participants. Squamous cell carcinoma was the most common histology (63.2%), followed by adenocarcinoma (30.8%). Patients in the case group had higher odds of preterm birth before 37 weeks of gestation compared with both control groups (21.5% vs 9.3%, odds ratio [OR] 2.7, 95% CI 1.4-5.1; 21.5% vs 12.7%, OR 1.9, 95% CI 1.0-3.6), but not preterm birth before 32 weeks. Neonatal morbidity was more common among the patients in the case group relative to those in the cervical cancer control group (15.9% vs 6.9%, OR 2.5, 95% CI 1.2-5.5). There were no differences in rates of growth restriction, stillbirth, cesarean delivery, and maternal morbidity., Conclusion: In a population-based cohort, patients who conceived after surgery for cervical cancer had higher odds of preterm delivery compared with control groups., Competing Interests: Financial Disclosure Mark A. Clapp reports that money was paid to him from the American Association of Obstetricians and Gynecologists Foundation. Larissa A. Meyer reports that money was paid to her institution from AstraZeneca, and money was paid to her from GlaxoSmithKline. The other authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Obstetrician-gynecologists are the leading experts in the health care of women, and obesity is the most common medical condition in women of reproductive age. Obesity in women is such a common condition that the implications relative to pregnancy often are unrecognized, overlooked, or ignored because of the lack of specific evidence-based treatment options. The management of obesity requires long-term approaches ranging from population-based public health and economic initiatives to individual nutritional, behavioral, or surgical interventions. Therefore, an understanding of the management of obesity during pregnancy is essential, and management should begin before pregnancy and continue through the postpartum period. Although the care of the obese woman during pregnancy requires the involvement of the obstetrician or other obstetric care professional, additional health care professionals, such as nutritionists, can offer specific expertise related to management depending on the comfort level of the obstetric care professional. The purpose of this Practice Bulletin is to offer an integrated approach to the management of obesity in women of reproductive age who are planning a pregnancy., Competing Interests: All ACOG committee members and authors have submitted a conflict of interest disclosure statement related to this published product. Any potential conflicts have been considered and managed in accordance with ACOG’s Conflict of Interest Disclosure Policy. The ACOG policies can be found on acog.org. For products jointly developed with other organizations, conflict of interest disclosures by representatives of the other organizations are addressed by those organizations. The American College of Obstetricians and Gynecologists has neither solicited nor accepted any commercial involvement in the development of the content of this published product., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The Royal College of Obstetricians and Gynaecologists (RCOG) defines fetal growth restriction as ultrasound-estimated fetal weight less than the 10th percentile or abdominal circumference less than the 10th percentile; the American College of Obstetricians and Gynecologists (ACOG) defines fetal growth restriction as estimated fetal weight less than the 10th percentile alone. We compared each method's ability to predict small for gestational age (SGA) at birth., Methods: For this retrospective study of diagnostic accuracy, we reviewed deliveries at the University of New Mexico Hospital from January 1, 2013, to March 31, 2017. We included mothers with singleton, well-dated pregnancies and nonanomalous fetuses undergoing indicated fetal growth restriction surveillance with an ultrasound-estimated fetal weight within 30 days of delivery. Estimated fetal weights and percentiles were calculated using the Hadlock intrauterine growth curve. Small for gestational age was defined as birth weight less than the 10th percentile based on a recent, sex-specific curve. We calculated the area under the curve, sensitivity, specificity, and positive and negative likelihood ratios for various approaches using abdominal circumference and estimated fetal weight to diagnose fetal growth restriction, including the definitions endorsed by ACOG and RCOG., Results: We included 1,704 pregnancies with a mean ultrasonography-to-delivery interval of 14.0 days (±8.6). There were 235 SGA neonates (13.8%). The rate of fetal growth restriction was 13.6% when using ACOG's criteria and 16.9% according to RCOG's criteria (P=.007). The area under the curve of RCOG's diagnostic approach was 0.78 (95% CI 0.76-0.80), which was higher than ACOG's (0.76, 95% CI 0.74-0.78, P=.01). Sensitivities and specificities of the various methods were similar. Adopting estimated fetal weight or abdominal circumference less than the 10th percentile instead of estimated fetal weight alone to predict SGA at birth would correctly identify one additional case of SGA for each 14 patients assessed., Conclusion: The diagnostic approach endorsed by RCOG is a marginally better predictor of SGA at birth compared with the method endorsed by ACOG. Future research should consider the potential benefits and harms of the different methods in different populations.

Objective: To estimate the risk of adverse perinatal outcomes among women with isolated fetal growth restriction from 17 to 22 weeks of gestation., Methods: This was a retrospective cohort study of all singleton, nonanomalous pregnancies undergoing ultrasonography to assess fetal anatomy between 17 and 22 weeks of gestation at a single center from 2010 to 2014. After excluding patients with fetal structural malformations, chromosomal abnormalities, or identified infectious etiologies, we compared perinatal outcomes between pregnancies with and without fetal growth restriction, defined as estimated fetal weight less than the 10th percentile for gestational age. Our primary outcome was small for gestational age (SGA) at birth, defined as birth weight less than the 10th percentile. Secondary outcomes included preterm delivery at less than 37 and less than 28 weeks of gestation, preeclampsia, abruption, stillbirth, neonatal death, neonatal intensive care unit admission, intraventricular hemorrhage, need for respiratory support, and necrotizing enterocolitis., Results: Of 12,783 eligible patients, 355 (2.8%) had early second-trimester fetal growth restriction. Risk factors for growth restriction were African American race and tobacco use. Early second-trimester growth restriction was associated with a more than fivefold increase in risk of SGA at birth (36.9% compared with 9.1%, adjusted odds ratio [OR] 5.5, 95% CI 4.3-7.0), stillbirth (2.5% compared with 0.4%, OR 6.2, 95% CI 2.7-12.8), and neonatal death (1.4% compared with 0.3%, OR 5.2, 95% CI 1.6-13.5). Rates of indicated preterm birth at less than 37 weeks of gestation (7.3% compared with 3.3%, OR 2.3, 95% CI 1.5-3.5) and less than 28 weeks of gestation (2.5% compared with 0.2%, OR 10.8, 95% CI 4.5-23.4), neonatal need for respiratory support (16.9% compared with 7.8%, adjusted OR 1.6, 95% CI 1.1-2.2), and necrotizing enterocolitis (1.4% compared with 0.2%, OR 7.7, 95% CI 2.3-20.9) were also significantly higher for those with growth restriction. Rates of preeclampsia, abruption, and other neonatal outcomes were not significantly different., Conclusion: Although fetal growth restriction in the early second trimester occurred in less than 3% of our cohort and most of those with isolated growth restriction did not have adverse outcomes, it is a strong risk factor for SGA, stillbirth, neonatal death, and indicated preterm birth.

Objective: To explore the hypothesis that selective placental pathology affecting the nonpresenting twin is a significant contributory factor mediating the smaller size at birth of nonpresenting dichorionic twins., Methods: We conducted a retrospective cohort study of all dichorionic twin deliveries in a single tertiary center between 2002 and 2015 where by departmental policy, all placentas from multifetal gestations are routinely sent for pathologic examination. Maternal charts, neonatal charts, and pathology reports were reviewed. Placental abnormalities were classified into lesions associated with maternal vascular malperfusion, fetal vascular malperfusion, placental hemorrhage, and chronic villitis. Comparison of neonatal outcomes and placental abnormalities was made between all nonpresenting and all presenting twins as well as within twin pairs., Results: A total of 1,322 women with dichorionic twins were studied. Nonpresenting twins were smaller at birth compared with the presenting cotwin starting at 32 weeks of gestation (birth weight [±standard deviation] 2,224±666 g compared with 2,278±675 g, P=.036). Nonpresenting twins had smaller placentas (361±108 g compared with 492±129 g, P<.001) as early as 24 weeks of gestation. Nonpresenting twins had higher odds for any placental abnormality (adjusted odds ratio [OR] 1.91, 95% confidence interval [95% CI] 1.63-2.23), small placenta (adjusted OR 4.69, 95% CI 3.75-5.88), and maternal vascular malperfusion (OR 2.75, 95% CI 2.32-3.27) compared with their presenting cotwins. In nonpresenting twins, the presence of maternal vascular malperfusion pathology was associated with lower birth weight compared with their presenting cotwin during the third trimester., Conclusion: The lower birth weight of nonpresenting fetuses in dichorionic twin pregnancies is correlated with a higher rate of placental maternal vascular malperfusion pathology.

Objective: To investigate the association of the cause of preterm birth on in-hospital mortality of preterm neonates born from 24 to 34 weeks of gestation., Methods: L'Etude épidémiologique sur les petits âges gestationnels (EPIPAGE)-2 is a prospective, nationwide, population-based cohort of very preterm births. After dividing causes of preterm birth into six mutually exclusive groups, we analyzed the association of each cause with in-hospital deaths of preterm neonates born alive with adjustment for organizational, maternal, and obstetric factors., Results: The analysis included 3,138 singleton live births from 24 to 34 weeks of gestation with a newborn in-hospital mortality rate of 5.0% (95% confidence interval 4.5-5.7). Preterm labor was the most frequent cause of preterm birth (n=1,293 [43.5%]) followed by preterm premature rupture of membranes (n=765 [23.9%]), hypertensive disorders without suspected fetal growth restriction (n=397 [12.7%]), hypertensive disorders with suspected fetal growth restriction (n=408 [10.9%]), placental abruption after an uncomplicated pregnancy (n=92 [3.0%]), and suspected fetal growth restriction without hypertensive disorders (n=183 [5.9%]). Neonates born because of suspected fetal growth restriction with or without hypertensive disorders (adjusted odds ratio [OR] 3.0 [1.9-4.7] and adjusted OR 2.3 [1.1-4.6], respectively) had higher adjusted risks of in-hospital death than those born after preterm labor. Risks of in-hospital mortality for preterm births caused by preterm premature rupture of membranes (adjusted OR 1.3 [0.9-1.9]), hypertensive disorders without fetal growth restriction (adjusted OR 0.7 [0.4-1.4]), or placental abruption (adjusted OR 1.6 [0.7-3.7]) were similar to those born after preterm labor., Conclusion: Among neonates born alive before 34 weeks of gestation, only those born because of suspected fetal growth restriction have a higher mortality risk than those born after preterm labor.

Objective: To assess the association of reported smoking cessation at various time points during pregnancy with fetal growth restriction., Methods: This was a population-based retrospective cohort study of singleton nonanomalous live births using Ohio birth certificates, 2006-2012. Outcomes of women who reported smoking only in the 3 months before conception and women who reported smoking through the first, second, or third trimester were compared with a referent group of nonsmokers. Multivariate logistic regression assessed the association between smoking cessation at various times in pregnancy and fetal growth restriction less than the 10th and 5th percentiles., Results: Of 927,424 births analyzed, 75% of mothers did not smoke. Of smokers, 24% smoked preconception only, 10% quit after the first trimester, 4% quit after the second trimester, and 59% smoked throughout pregnancy. The rate of fetal growth restriction less than the 10th and 5th percentiles among nonsmokers was 8.1% and 3.6%, respectively. Although smoking only in the preconception period did not significantly increase fetal growth restriction risk, smoking in any trimester did. The adjusted odds ratio (95% confidence interval) for fetal growth restriction less than the 10th and 5th percentiles, respectively, of cessation after the first trimester was 1.19 (1.13-1.24) and 1.25 (1.17-1.33) and 1.67 (1.57-1.78) and 1.83 (1.68, 1.99) for cessation after the second trimester. Women who reported smoking throughout pregnancy had the highest risks of fetal growth restriction, 2.26 (2.22-2.31) and 2.44 (2.37-2.51), after accounting for the influence of race, low socioeconomic status, and medical comorbidities., Conclusion: Smoking of any duration during pregnancy is associated with an increased risk of fetal growth restriction with decreasing risk the earlier that cessation occurs. Smoking cessation programs should focus on the benefit of quitting as early in pregnancy as possible., Level of Evidence: II.

Objective: To compare the composite neonatal morbidity of pregnancies with fetal growth restriction (estimated fetal weight less than the 10th percentile) and normal compared with elevated umbilical artery systolic-to-diastolic ratios., Methods: This was a retrospective cohort study of all pregnancies complicated by fetal growth restriction with normal compared with elevated umbilical artery systolic-to-diastolic ratios from January 2008 to July 2012 at a single center. Exclusions were multiple gestation, prenatally diagnosed fetal anomalies, delivery at outside institution, and absent or reversed end diastolic flow. Maternal characteristics and perinatal outcomes including composite neonatal morbidity were compared between groups., Results: Of 11,785 pregnancies evaluated, 789 (7%) were diagnosed with fetal growth restriction. Among 512 that met inclusion criteria, 394 (77%) had normal and 118 (23%) had elevated umbilical artery systolic-to-diastolic ratios. When fetal growth-restricted pregnancies with elevated umbilical artery systolic-to-diastolic ratios were delivered at 37 weeks of gestation were compared with those with normal umbilical artery systolic-to-diastolic ratios delivered at 39 weeks of gestation, there was no difference in the rate of neonatal intensive care unit admission (101 [25.7%] compared with 51 [43.2%]; crude odds ratio [OR] 2.5, 95% confidence interval 1.5-4.0; adjusted OR 1.37, 95% CI 0.69-2.71) or composite neonatal morbidity (60 [15.2%] compared with 24 [20.3%]; crude OR 1.42, 95% CI 0.84-2.40; adjusted OR 0.91, 95% CI 0.45-1.84)., Conclusion: Composite neonatal morbidity is comparable in fetal growth-restricted pregnancies with elevated compared with normal umbilical artery systolic-to-diastolic ratios when delivered at 37 and 39 weeks of gestation, respectively. Planning delivery of pregnancies with fetal growth restriction and elevated systolic-to-diastolic ratios and without other complications at 37 weeks of gestation results in good outcomes.

Objective: To evaluate whether use of the B-Lynch suture is associated with subsequent adverse pregnancy outcomes., Methods: This is a cohort study of women who experienced postpartum hemorrhage between January 2000 and June 2010 and had a subsequent pregnancy at a single university hospital. Women who had postpartum hemorrhage and B-Lynch suture were compared with those complicated by postpartum hemorrhage but no B-Lynch suture placement. The primary outcome was a composite adverse outcome related to placentation abnormalities and included placenta previa, placenta accreta, preeclampsia, preterm birth, or a small-for-gestational-age neonate. The study was powered to detect a twofold difference in the frequency of the composite outcome., Results: Two hundred fifty-two patients met inclusion criteria, 63 of whom had a prior B-Lynch suture. Women with a prior B-Lynch had a higher mean estimated blood loss (1,800 mL compared with 1,200 mL, P<.001) and were more likely to have received a blood transfusion (29.2% compared with 13.3%, P=.01) in the index pregnancy. The composite outcome was not different between the groups (14.3% compared with 13.8%, P=.92). A logistic regression controlling for potential confounding factors did not show any association between exposure to a B-Lynch suture and adverse pregnancy outcome in a subsequent pregnancy (adjusted odds ratio 0.88, 95% confidence interval 0.34-2.28., Conclusion: Placement of a B-Lynch suture is not associated with an increased risk of future adverse pregnancy outcomes related to abnormal placentation., Level of Evidence: II.

Objective: To estimate the risk of stillbirth among pregnancies complicated by a major isolated congenital anomaly detected by antenatal ultrasonography and the influence of incidental growth restriction., Methods: A retrospective cohort study of all consecutive singleton pregnancies undergoing routine anatomic survey between 1990 and 2009 was performed. Stillbirth rates among fetuses with an ultrasound-detected isolated major congenital anomaly were compared with fetuses without major anomalies. Stillbirth rates were calculated per 1,000 ongoing pregnancies. Exclusion criteria included delivery before 24 weeks of gestation, multiple fetal anomalies, minor anomalies, and chromosomal abnormalities. Analyses were stratified by gestational age at delivery (before 32 weeks compared with 32 weeks of gestation or after) and birth weight less than the 10th percentile. We adjusted for confounders using logistic regression., Results: Among 65,308 singleton pregnancies delivered at 24 weeks of gestation or after, 873 pregnancies with an isolated major congenital anomaly (1.3%) were identified. The overall stillbirth rate among fetuses with a major anomaly was 55 per 1,000 compared with 4 per 1,000 in nonanomalous fetuses (adjusted odds ratio [OR] 15.17, 95% confidence interval [CI] 11.03-20.86). Stillbirth risk in anomalous fetuses was similar before 32 weeks of gestation (26/1,000) and 32 weeks of gestation or after (31/1,000). Among growth-restricted fetuses, the stillbirth rate increased among anomalous (127/1,000) and nonanomalous fetuses (18/1,000), and congenital anomalies remained associated with higher rates of stillbirth (adjusted OR 8.20, 95% CI 5.27-12.74)., Conclusion: The stillbirth rate is increased in anomalous fetuses regardless of incidental growth restriction. These risks can assist practitioners in designing care plans for anomalous fetuses who have elevated and competing risks of stillbirth and neonatal death., Level of Evidence: II.

Antiphospholipid syndrome (APS) is an autoimmune disorder defined by the presence of characteristic clinical features and specified levels of circulating antiphospholipid antibodies (Box 1 and Box 2). Diagnosis requires that at least one clinical and one laboratory criterion are met. Because approximately 70% of individuals with APS are female (1), it is reasonably prevalent among women of reproductive age. Antiphospholipid antibodies are a diverse group of antibodies with specificity for binding to negatively charged phospholipids on cell surfaces. Despite the prevalence and clinical significance of APS, there is controversy about the indications for and types of antiphospholipid tests that should be performed in order to diagnose the condition. Much of the debate results from a lack of well-designed and controlled studies on the diagnosis and management of APS. The purpose of this document is to evaluate the data for diagnosis and treatment of APS.

Objective: To estimate epidemiologic risk factors for cerebral palsy., Methods: Data were collected by linkage to state-based perinatal repositories and cerebral palsy registers and using a maternal questionnaire. The cohort included 587 individuals with cerebral palsy and 1,154 non-cerebral palsy controls., Results: The following factors were associated with cerebral palsy: recorded maternal infection during pregnancy (41.4% patients compared with 31.3% controls; odds ratio [OR] 1.55, 95% confidence interval 1.26-1.91), small for gestational age ([birth weight less than third customized centile] 43.9% patients compared with 6.3% controls; OR 11.75, 6.25-22.08), gestational age less than 32 weeks (29.3% patients compared with 0.7% controls; OR 59.20, 28.87-121.38), multiple birth (OR 6.62, 4.00-10.95), a relative with cerebral palsy (OR 1.61, 1.12-2.32), breech position (13.7% patients compared with 6.0% controls; OR 2.48, 1.76-3.49), bleeding at any time in pregnancy (29.3% patients compared with 16.9% controls; OR 2.04, 1.61-2.58), male sex (58.8% patients compared with 45.8% controls; OR 1.68, 1.38-2.06), multiple miscarriage (7.7% patients compared with 3.5% controls; OR 2.30, 1.38-3.82), smoking (14.0% patients compared with 10.6% controls; OR 1.37, 1.02-1.85), and illicit drug use (3.3% patients compared with 1.5% controls; OR 2.22, 1.14-4.30). Factors not associated with cerebral palsy were "disappearing twin," diabetes, maternal body mass index, hypertension, alcohol consumption, anemia, maternal hypothyroidism, forceps or vacuum delivery, and maternal age., Conclusion: Preterm birth, intrauterine growth restriction, perinatal infection, and multiple birth present the largest risks for a cerebral palsy outcome. Reassuringly, upper respiratory tract and gastrointestinal infections during pregnancy were not associated with cerebral palsy., Level of Evidence: II.

Objective: To estimate the comparative efficiency of first-trimester fetal growth restriction, second-trimester fetal growth restriction, and first-to-second-trimester growth lag for predicting adverse perinatal outcomes., Methods: This is a retrospective cohort study of pregnancies with reliable dating based on last menstrual periods and first-trimester ultrasound examinations. Pregnancies with multiple fetuses, aneuploidy, and major structural anomalies were excluded. Fetal crown-rump lengths at 10-14 weeks, estimated fetal weights based on fetal biometry at 18-22 weeks, and interval growth were measured and converted to gestational age-adjusted Z-scores. The primary outcome was small for gestational age (SGA) at delivery. Secondary outcomes were low birth weight, preterm delivery, stillbirth, and preeclampsia. Receiver-operating characteristics curves were used to identify the optimal definitions of early fetal growth restriction associated with SGA and to compare screening efficiencies. Multivariable logistic regression was used to adjust for confounders., Results: Among 8,978 pregnancies meeting inclusion criteria, 551 (6.5%) neonates were SGA. Crown-rump length Z-score less than -1.0, estimated fetal weights Z-score less than -1.0, and growth Z-score less than -1.0 were identified as the optimal definitions of early fetal growth restriction associated with SGA (adjusted odds ratio 1.41 [95% confidence interval (CI) 1.13-1.74], 3.44 [95% CI 2.85-4.15] and 2.61 [95% CI 2.09-3.25], respectively). The sensitivity and specificity of first- and second-trimester fetal growth restriction for predicting SGA were 21.4% and 83.4%, and 37.2% and 85.5%, respectively. The area under the receiver-operating characteristics curve for second-trimester fetal growth restriction was greater than that for first-trimester fetal growth restriction and first-to-second-trimester growth lag (0.70 compared with 0.59 and 0.66, P<.001)., Conclusion: Second-trimester fetal growth restriction is superior to first-trimester fetal growth restriction and first-to-second-trimester growth lag for predicting SGA.

Objective: To estimate the effect of maternal heart disease on fetal growth and neonatal outcomes., Methods: A retrospective cohort study of all women with congenital and acquired heart disease admitted at Chelsea and Westminster Hospital between 1994 and 2010 was performed. The women who delivered immediately before and immediately after each index pregnancy were used as controls. Data were obtained from medical and obstetric notes. Birth weight percentiles were calculated using a customized birth weight percentile program, and neonatal complications (preterm birth, perinatal mortality, and recurrence of congenital heart disease) were noted., Results: Median birth weight percentile was significantly lower in the heart disease group (31) compared with the control group (49;P.001 Mann-Whitney U test [corrected].The rate of neonatal complications was significantly higher in the heart disease group (34% compared with 15%). Preterm birth occurred in 42 (13%) pregnancies, of which 67% were iatrogenic. Eighty-one (25%) newborns in the heart disease group were small for gestational age, and there were four stillbirths and four neonatal deaths (perinatal mortality rate 20 per 1,000)., Conclusion: This cohort study suggests a significant reduction in fetal growth rates associated with maternal heart disease, which is also associated with preterm delivery and reduced birth weight. The presence of maternal cyanosis and a reduced cardiac output are the most significant predictors., Level of Evidence: II.

Objective: To estimate the effect of low-dose aspirin started in early pregnancy on the incidence of preeclampsia and intrauterine growth restriction (IUGR)., Data Sources: A systematic review and meta-analysis were performed through electronic database searches (PubMed, Cochrane, Embase)., Methods of Study Selection: Randomized controlled trials of pregnant women at risk of preeclampsia who were assigned to receive aspirin or placebo (or no treatment) were reviewed. Secondary outcomes included IUGR, severe preeclampsia and preterm birth. The effect of aspirin was analyzed as a function of gestational age at initiation of the intervention (16 weeks of gestation or less, 16 weeks of gestation or more)., Tabulation, Integration, and Results: Thirty-four randomized controlled trials met the inclusion criteria, including 27 studies (11,348 women) with follow-up for the outcome of preeclampsia. Low-dose aspirin started at 16 weeks or earlier was associated with a significant reduction in preeclampsia (relative risk [RR] 0.47, 95% confidence interval [CI] 0.34-0.65, prevalence in 9.3% treated compared with 21.3% control) and IUGR (RR 0.44, 95% CI 0.30-0.65, 7% treated compared with 16.3% control), whereas aspirin started after 16 weeks was not (preeclampsia: RR 0.81, 95% CI 0.63-1.03, prevalence in 7.3% treated compared with 8.1% control; IUGR: RR 0.98, 95% CI 0.87-1.10, 10.3% treated compared with 10.5% control). Low-dose aspirin started at 16 weeks or earlier also was associated with a reduction in severe preeclampsia (RR 0.09, 95% CI 0.02-0.37, 0.7% treated compared with 15.0% control), gestational hypertension (RR 0.62, 95% CI 0.45-0.84, 16.7% treated compared with 29.7% control), and preterm birth (RR 0.22, 95% CI 0.10-0.49, 3.5% treated compared with 16.9% control). Of note, all studies for which aspirin had been started at 16 weeks or earlier included women identified to be at moderate or high risk for preeclampsia., Conclusion: Low-dose aspirin initiated in early pregnancy is an efficient method of reducing the incidence of preeclampsia and IUGR.

Objective: To estimate whether the presence of a single umbilical artery is associated with intrauterine growth restriction (IUGR), fetal demise, or major congenital anomalies., Methods: We performed a retrospective cohort study of all consecutive singleton pregnancies undergoing routine anatomic survey between 1990 and 2007 at a major tertiary medical center. Two dedicated research nurses obtained complete pregnancy outcome data in an ongoing manner. Pregnancies with a diagnosis of single umbilical artery were compared with those with two umbilical arteries. The primary outcomes were IUGR (less than 10th percentile), renal, and cardiac anomalies. Multivariable logistic regression was used to refine the risk association between single umbilical artery and adverse pregnancy outcomes while adjusting for confounding effects., Results: Of 72,373 pregnancies, 64,047 (88.5%) had pregnancy follow-up information and were available for this analysis. There were 392 cases of single umbilical artery (0.61%) diagnosed at anatomic survey; slightly lower than previously reported. Single umbilical artery as compared with double umbilical artery was associated with increased risk of renal anomalies (adjusted odds ratio [OR] 3.0, 95% confidence interval [CI] 1.9-4.9, P<.01) and cardiac anomalies (adjusted OR 20.3, 95% CI 13.5-30.4, P<.01). Single umbilical artery was also associated with an increased risk of IUGR (adjusted OR 2.1, 95% CI 1.6-2.7, P<.01), even after excluding all fetuses with known anomalies., Conclusion: Our data suggest an increased risk of IUGR when the diagnosis of single umbilical artery is made, making a clinical recommendation for serial growth assessments in the setting of single umbilical artery reasonable.

Objective: To estimate the association between five commonly inherited thrombophilia polymorphisms and adverse pregnancy outcomes in women who had no prior history of adverse pregnancy outcomes or personal or family history of venous thromboembolism., Methods: Healthy nulliparous women (n=2,034) were recruited to this prospective cohort study before 22 weeks of gestation. Genotyping for factor V Leiden, prothrombin gene mutation, methylenetetrahydrofolate reductase enzyme (MTHFR) C677T, MTHFR A1298C, and thrombomodulin polymorphism was performed. Clinicians caring for women were blinded to the results of thrombophilia tests. The primary composite outcome was the development of severe preeclampsia, fetal growth restriction, placental abruption, stillbirth, or neonatal death., Results: Complete molecular results and pregnancy outcome data were available in 1,707 women. These complications were experienced by 136 women (8.0%). Multivariable logistic regression demonstrated two statistically significant findings. Women who carried the prothrombin gene mutation had an odds ratio of 3.58 (95% confidence interval [CI] 1.20-10.61, P=.02) for the development of the composite primary outcome. Homozygous carriers of the MTHFR 1298 polymorphism had an odds ratio of 0.26 (95% CI 0.08-0.86, P=.03). None of the other polymorphisms studied showed a significant association with the development of the primary outcome in this cohort of women., Conclusion: Prothrombin gene mutation confers an increased risk for the development of adverse pregnancy outcomes in otherwise asymptomatic, nulliparous women, whereas homozygosity for MTHFR 1298 may protect against these complications. The majority of asymptomatic women who carry an inherited thrombophilia polymorphism have a successful pregnancy outcome., Level of Evidence: II.

Objective: To estimate whether women with a recent history of a placental syndrome and concomitant metabolic syndrome have reduced cardiac diastolic function., Methods: In this cohort study, women with a history of a placental syndrome were included. We assessed body mass index, blood pressure, fasting serum lipids, glucose and insulin levels, and 24-hour urinary protein and albumin output after an interval of at least 6 months postpartum. Cardiac diastolic function was assessed by echocardiography., Results: Metabolic syndrome was found in 22% of the women evaluated. Diastolic dysfunction was seen in 24% of the women with the metabolic syndrome compared with 6.3% in those without (odds ratio 4.77, 95% confidence interval 2.18-10.41; adjusted odds ratio 6.09, 95% confidence interval 2.64-14.04). Univariable analysis showed that all the constituents of the metabolic syndrome related to diastolic dysfunction., Conclusion: In women with a history of placental syndrome complicating pregnancy, the presence of metabolic syndrome increases the risk of cardiac diastolic dysfunction fourfold., Level of Evidence: II.

Objective: To compare the accuracy of fetal weight estimations between normal and growth-restricted twin and singleton pregnancies in a single tertiary center., Methods: The computerized ultrasound database of a tertiary center was searched for all fetal weight estimations made in twin pregnancies from 2001 to 2006, which were performed up to 3 days before delivery. Accuracy was compared with a control group of singleton pregnancies at a 3:1 ratio. Estimated fetal weight was calculated by the Hadlock formula. Analyses were performed for the whole group and for pregnancies associated with fetal growth restriction and discordancy., Results: The study groups included 278 twins and 834 singleton pregnancies. The twins group was characterized by a higher mean absolute percentage error compared with the singleton group (8.9% compared with 6.8%). Accuracy was lower for the second twins than for the first twins. When comparing the subgroup of fetal growth restriction, differences in sensitivity and specificity were small for singleton compared with overall twins (47.5% compared with 48.9% and 97.7% compared with 95.7%, respectively). Overall accuracy was better in the singleton group (95% compared with 88%), mainly due to relatively low accuracy in the second twin (86%). For detection of discordancy, estimated fetal weight had a sensitivity of 52%, specificity of 88%, and overall accuracy of 81%., Conclusion: The accuracy of the ultrasonographic estimated fetal weight seems to be lower for twin gestations than for singleton gestations, especially for second twins. These data should be considered by clinicians when making decisions based on ultrasonographic characteristics.

For women with end-stage organ failure, transplantation is an established therapeutic option. Pregnancy after solid organ transplantation is no longer uncommon, especially with the recent advances in transplantation surgery and the availability of newer immunosuppressants. This article will review preconceptional counseling, common pregnancy complications, prenatal and intrapartum considerations, outcome by organ, immunosuppressant therapies, and neonatal outcomes based on data available from case series and voluntary registries. Some recommendations are provided to assist in the management of pregnancies after solid organ transplantation.

Objective: To estimate the effect of chorionicity on the risk of stillbirth in twins., Methods: A retrospective cohort analysis was performed of all twin deliveries of at least 24 weeks of gestation at a single tertiary care center from December 2000 to May 2007. The risk of fetal death with advancing gestation was calculated for monochorionic-diamniotic twins and for dichorionic-diamniotic twins. Overall in utero survival was compared by using Kaplan-Meier analysis and a hazards ratio with 95% confidence intervals estimated to assess the degree of difference. Pregnancies affected by growth abnormalities, anomalies, or twin-twin transfusion syndrome were subsequently excluded and survival by chorionicity similarly compared within these "apparently normal" gestations., Results: Data from 1,000 consecutive twin pairs (196 monochorionic-diamniotic twins and 804 dichorionic-diamniotic twins) were analyzed. Stillbirths occurred in seven (3.6%) monochorionic-diamniotic and nine (1.1%) dichorionic-diamniotic twin pairs. Monochorionic-diamniotic twins had a higher risk of stillbirth compared with dichorionic-diamniotic twins, both overall (log-rank P=.004) and at each gestational age after 24 weeks, with this risk persisting in the subset of 771 (130 monochorionic-diamniotic twins and 641 dichorionic-diamniotic twins) "apparently normal" twins (log-rank P=.039)., Conclusion: Monochorionicity has a negative effect on the in utero survival of twins, even among monochorionic-diamniotic twins without abnormalities., Level of Evidence: II.

Objective: To examine the association between infertility, with or without treatment, and fetal growth, as well as perinatal and infant mortality., Methods: From the Danish National Birth Cohort (1997-2003), we identified 51,041 singletons born of fertile couples (time to pregnancy 12 months or less), 5,787 born of infertile couples conceiving naturally (time to pregnancy more than 12 months), and 4,317 born after treatment. We defined small for gestational age (SGA) as the lowest 5% of birth weight by sex and gestational age., Results: Crude estimates suggested an increased risk of perinatal mortality and SGA among infertile couples (treated and untreated), but the odds ratios (ORs) of perinatal mortality among infertile couples were attenuated after adjustment for maternal age and body mass index (1.32, 95% confidence interval [CI] 0.95-1.84 among untreated and 1.26, 95% CI 0.86-1.85 among treated couples). The elevated risk of SGA among infertile couples persisted after adjustment for maternal age, parity, and smoking (OR 1.24, 95% CI 1.10-1.40 among untreated, and OR 1.40, 95% CI 1.23-1.60 among treated). The risk of SGA increased with time to pregnancy, and a longer time to pregnancy was associated with a small reduction in birth weight across the whole distribution., Conclusion: The increased risk of SGA observed among infertile couples with or without infertility treatment suggests that infertility may be a risk factor for intrauterine growth restriction. Treatment per se may have little effect on fetal growth. A small-to-moderate increased risk of perinatal mortality in infertile couples cannot be ruled out due to the small number of cases., Level of Evidence: II.

Objective: To describe pregnancy outcomes with fetal gastroschisis, including the associations of prenatal ultrasound findings with neonatal surgical complications and other morbidities., Methods: This was a review of pregnancies complicated by fetal gastroschisis and delivered from January 1998 through June 2006. The last ultrasonogram before delivery was reviewed to determine stomach dilatation, bowel dilatation, or abnormalities of amniotic fluid volume. Neonatal records were reviewed to determine type of closure and any bowel complications., Results: There were 66 pregnancies with gastroschisis, 1 per 2,000 deliveries. There were three stillbirths and three neonatal deaths. Delayed closure was necessary in 49% who underwent surgery. Birth weight below the third percentile, which occurred in 38%, was associated with need for delayed closure, 64% compared with 25% without growth restriction, P<.001, but was not associated with longer hospital stay or neonatal death. Fetal gastroschisis was diagnosed by prenatal ultrasonography in 58 cases. Bowel complications requiring surgery were more frequent when ultrasonography had demonstrated stomach dilatation (five cases), 60% compared with 10%, P=.002. Fetuses with defects so large that no normal ventral wall could be visualized ultrasonographically (three cases) were at increased risk for neonatal death, 100% compared with 0%, P<.001., Conclusion: Ultrasound findings associated with adverse outcome in fetal gastroschisis included stomach dilatation and a defect so large that no normal ventral wall could be visualized. Fetal growth restriction was common, and such infants were more likely to require delayed gastroschisis closure. Despite more than 90% survival, morbidity with gastroschisis remains high., Level of Evidence: II.

Objective: To estimate the relationship between maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in early pregnancy with the risk of subsequent adverse outcome., Methods: A nested, case-control study was performed within a prospective cohort study of Down syndrome screening. Maternal serum levels of sFlt-1 and PlGF at 10-14 weeks of gestation were compared between 939 women with complicated pregnancies and 937 controls. Associations were quantified as the odds ratio for a one decile increase in the corrected level of the analyte., Results: Higher levels of sFlt-1 were not associated with the risk of preeclampsia but were associated with a reduced risk of delivery of a small for gestational age infant (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.88-0.96), extreme (24-32 weeks) spontaneous preterm birth (OR 0.90, 95% CI 0.83-0.99), moderate (33-36 weeks) spontaneous preterm birth (OR 0.93, 95% CI 0.88-0.98), and stillbirth associated with abruption or growth restriction (OR 0.77, 95% CI 0.61-0.95). Higher levels of PlGF were associated with a reduced risk of preeclampsia (OR 0.95, 95% CI 0.90-0.99) and delivery of a small for gestational age infant (OR 0.95, 95% CI 0.91-0.99). Associations were minimally affected by adjustment for maternal characteristics., Conclusion: Higher early pregnancy levels of sFlt-1 and PlGF were associated with a decreased risk of adverse perinatal outcome.

Objective: We sought to assess whether small for gestational age is a risk factor for stillbirth of a subsequent sibling., Methods: The Missouri maternally linked cohort data set, containing data on births from 1978 through 1997, was used. We identified the study group (women who delivered a SGA infant in the first pregnancy) and a comparison group (women who delivered a non-SGA infant in their first pregnancy) and compared the outcome (stillbirth) in the second pregnancy between both groups., Results: We analyzed information on the first and second pregnancies of 402,015 women (43,549 [10.8%] in the study arm and 358,466 [89.2%] in the comparison arm). Of the 1,883 cases of stillbirth in the second pregnancy, 314 cases occurred in mothers with a history of SGA (stillbirth rate 7.2/1,000) and 1,569 in the comparison group (stillbirth rate 4.4/1,000), P < .001. The adjusted risk of stillbirth was 60% higher in women with a prior SGA (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.4-1.8). The risk for stillbirth in the second pregnancy increased with decreasing gestational age at birth of the SGA infant in the first pregnancy (term: OR 1.4, 95% CI 1.2-1.6; preterm: OR 2.8, 95% CI 2.0-3.8; and very preterm: OR 4.2, 95% CI 2.4-7.3), P for trend < .001., Conclusion: Small for gestational age is a marker for subsequent stillbirth, and the risk rises with decreasing gestational age of the SGA birth. This information is potentially useful for counseling parents of SGA infants., Level of Evidence: II-2.

Objective: We investigated the association between high parity and fetal morbidity outcomes., Methods: We analyzed 22,463,141 singleton deliveries at 20 weeks or more of gestation in the United States from 1989 through 2000. Adjusted odds ratios generated from logistic regression models were used to approximate relative risk for neonatal morbidity in women with 1-4 (moderate parity or type I; referent group), 5-9 (high parity or type II), 10-14 (very high parity or type III) and 15 or more (extremely high parity or type IV) prior live births. Main outcome measures included low and very low birth weight, preterm and very preterm birth, and small and large for gestational age delivery., Results: The overall crude rates for low birth weight, very low birth weight, preterm birth, very preterm birth, and small and large for gestational age were 55, 11, 97, 19, 83, and 129 per 1,000 live births, respectively. The adjusted odds ratios for low birth weight, very low birth weight, preterm, and very preterm delivery increased consistently and in a dose-effect fashion with ascending parity (P for trend < .001). In the case of large for gestational age delivery, the adjusted odds ratio showed an inverted-U pattern, being highest among women in the type III parity cluster. The findings with respect to small for gestational age were inconclusive., Conclusion: High parity is a risk factor for adverse fetal outcomes. However, the impact of heightened parity is more manifest as shortened gestation rather than physical size restriction. These findings could prove beneficial for counseling women of high parity.

Objective: To evaluate interval fetal growth and compare the incidence of small-for-gestational age (SGA) newborns between fetuses with an isolated single umbilical artery and those with a 3-vessel umbilical cord., Methods: A retrospective, case-controlled study in which 84 singleton pregnancies with an isolated single umbilical artery were compared with 3-vessel umbilical cord fetuses as the control group., Results: There was no statistical difference between the groups in maternal demographic data, except for ethnicity and neonatal outcomes, respectively. The mean newborn birth weight was similar between the isolated single umbilical artery and the control groups, 3,268 +/- 596 g and 3,274 +/- 627 g, respectively. The prevalence of SGA newborns was 7.1% (6 of 84) in the isolated single umbilical artery group and 4.8% (4 of 84) in the control group. An ultrasound examination demonstrated fetal growth restriction in 50% of cases (3 of 6) in the isolated single umbilical artery group and in 25% of subjects (1 of 4) in the control group, respectively., Conclusion: Fetuses with an isolated single umbilical artery are at similar risk for SGA compared with fetuses with 3-vessel umbilical cords. It appears that antepartum serial ultrasound examination does not provide more information for interval fetal growth assessment in fetuses with an isolated single umbilical artery.

Objective: To evaluate the outcome of pregnancies complicated by first-trimester intrauterine hematoma., Methods: An analysis was performed on 248 cases. The pregnancy outcome was correlated with hematoma volume, gestational age (weeks), and maternal age (years)., Results: One hundred eighty-two cases were eligible for the study. Clinical complications occurred in 38.5% of the cases (adverse outcome group). Spontaneous abortion (14.3%), fetal growth restriction (7.7%), and preterm delivery (6.6%) were the most frequent clinical conditions observed. Considering the hematoma variables in adverse and favorable outcome groups, we found a significant difference only for gestational age at diagnosis. The median gestational age was significantly lower (P < .02) in the adverse outcome group (7.27, I and III quartiles 6.22-8.78) than in the favorable outcome cases (8.62, I and III quartiles 6.70-9.98). Among clinical conditions, the median gestational age was significantly lower (P = .02) in pregnancies complicated by spontaneous abortion (6.60, I and III quartiles 5.95-8.36) than in cases not ending in a miscarriage (8.50, I and III quartiles 6.70-9.91). The overall risk of adverse outcome was 2.4 times higher when the hematoma was diagnosed before 9 weeks (odds ratio 2.37, 95% confidence interval 1.20-4.70). In particular, intrauterine hematoma observed before 9 weeks significantly increases the risk of spontaneous abortion (odds ratio 14.79, 95% confidence interval 1.95-112.09), Conclusion: Intrauterine hematoma can affect the outcome of pregnancy. The risk of spontaneous abortion is related to gestational age and is significantly increased if diagnosed before 9 weeks., Level of Evidence: III.

Objective: To assess associations between vitamin-dependent homocysteine metabolism and vascular-related pregnancy complications by considering interval between delivery and postpartum investigation and maternal age., Methods: Case-control study performed at the University Medical Center Nijmegen in the Netherlands. Patients had experienced pregnancy-induced hypertension (n = 37), preeclampsia (n = 144), hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 104), recurrent early pregnancy loss (n = 544), abruptio placentae (n = 135), intrauterine growth restriction (n = 144), or intrauterine fetal death (n = 104). Controls comprised 176 women with uncomplicated obstetric histories. Oral methionine loading tests and fasting vitamin profiles were performed more than 6 weeks after delivery. Odds ratios and 95% confidence intervals were calculated after logistic regression analysis., Results: Hyperhomocysteinemia was associated with an approximately 2-fold to 3-fold increased risk for pregnancy-induced hypertension, abruptio placentae, and intrauterine growth restriction. Cobalamin deficiency was associated with HELLP syndrome, abruptio placentae, intrauterine growth restriction, and intrauterine fetal death. Pyridoxal 5-phosphate deficiency increased the risk for pregnancy-induced hypertension 4-fold. These associations lost their significance after adjustment for time interval and maternal age. High red cell folate was associated with a decreased risk for abruptio placentae and intrauterine growth restriction. An increased creatinine concentration was associated with pregnancy-induced hypertension, preeclampsia, HELLP syndrome, and abruptio placentae., Conclusion: Hyperhomocysteinemia and vitamin deficiencies are largely determined by the interval between delivery and postpartum investigation and by maternal age. Time interval and maternal age should be considered in the risk estimation for vascular-related pregnancy complications.

Objective: To estimate whether maternal weight changes between pregnancies influence the risk for small for gestational age (SGA) births., Methods: SGA cases (n = 8,062) below the tenth percentile birth weight for gestational age were selected from liveborn singletons born of Missouri residents during 1989-1997. Normal weight controls (n = 8,062) were selected according to birth year. The risk of SGA from interpregnancy body mass index (BMI) change and other maternal factors was estimated using logistic regression analysis., Results: An increase in BMI between pregnancies decreased SGA risk (adjusted odds ratio = 0.8; 95% confidence interval 0.7, 1.0). Other risk factors were prior SGA (4.4; 4.0, 4.8), preeclampsia/eclampsia (2.6; 2.1, 3.2), maternal cardiac disease (1.8; 1.1, 2.9), inadequate weight gain (1.9; 1.8, 2.2), and cigarette smoking (1.9; 1.7, 2.3 for 1-9 cigarettes per day; 2.5; 2.2, 2.8 for 10-19/d; and 2.8; 2.5, 3.3 for 20/d or more)., Conclusion: Increase in interpregnancy BMI lowers SGA risk, but adequate weight gain during pregnancy is more effective.

Objective: To determine whether maternal rheumatologic disease is associated with an increased risk of adverse obstetric or neonatal outcomes., Methods: Using an institutional database, we identified all women with diagnosed rheumatologic disease (n = 114) who delivered a baby at our institution during a 33-month period. We compared the incidence of adverse obstetric and neonatal outcomes among these women with the incidence among women without rheumatologic diseases (n = 18,534)., Results: Women with rheumatologic diseases were more likely to have preeclampsia than women without rheumatologic disease (8.8% versus 2.3%, P <.001) Women with rheumatologic diseases were also at increased risk of preterm delivery (15.2% versus 7.8%, P =.002) and small-for-gestational-age infants (8.0% versus 3.1%, P =.001) compared with women without rheumatologic disease., Conclusion: The finding that women with rheumatologic diseases are at increased risk of adverse obstetric outcomes suggests a need for heightened clinical vigilance and further research into the common pathophysiologic correlates., Level of Evidence: II-2

Objective: To assess, in a randomized trial, the safety and accuracy of amniocentesis and transabdominal chorionic villus sampling (CVS) performed at 11-14 weeks of gestation, given that this time frame is increasingly relevant to early trisomy screening., Methods: We compared amniocentesis with CVS from 77 to 104 days of gestation in a randomized trial in a predominantly advanced maternal age population. Before randomization, the feasibility of both procedures was confirmed by ultrasonography, and experienced operators performed sampling under ultrasound guidance; conventional cytogenetic analysis was employed. The primary outcome measure was a composite of fetal loss plus preterm delivery before 28 weeks of gestation in cytogenetically normal pregnancies., Results: We randomized 3,775 women into 2 groups (1,914 to CVS; 1,861 to amniocentesis), which were comparable at baseline. More than 99.6% had the assigned procedure, and 99.9% were followed through delivery. In contrast to previous thinking, in the cytogenetically normal cohort (n = 3,698), no difference in primary study outcome was observed: 2.1% (95% confidence interval 1.5, 2.8) for CVS and 2.3% (95% confidence interval, 1.7, 3.1) for amniocentesis. However, spontaneous losses before 20 weeks and procedure-related, indicated terminations combined were increased in the amniocentesis group (P =.07, relative risk 1.74). We found a 4-fold increase in the rate of talipes equinovarus after amniocentesis (P =.02) overall and in week 13 (P =.03, relative risk = 4.65), but data were insufficient to determine this risk in week 14., Conclusion: Amniocentesis at 13 weeks carries a significantly increased risk of talipes equinovarus compared with CVS and also suggests an increase in early, unintended pregnancy loss., Level of Evidence: I

Objective: To evaluate the prognostic values of fetal size before birth and fetal growth during the latency period in patients with preterm premature rupture of the membranes (PROM)., Methods: A prospective cohort study of 69 singleton pregnancies complicated by prolonged (14 days or more) PROM (24 to 31 weeks of gestation). Measures of fetal size and growth were compared with corresponding expected values from our reference curves. The correlations between deviations from expected measures of fetal size and growth, short-term neonatal complications, and infant neurodevelopmental outcome at 2 years were studied by univariate methods and logistic regression., Results: The mean gestational ages and standard deviations at membrane rupture and at birth were 27.9 +/- 2.4 and 31.5 +/- 2.1 weeks. At a corrected age of 2 years, of the 65 (94.2%) survivors, 3 infants (4.6%) had cerebral palsy, 13 (20%) had minor neurodevelopmental impairment, and 49 (75.4%) were judged to have had normal development. Compared with surviving infants without a major handicap, the group of infants who died and those with cerebral palsy had lower proportions of expected birth weight (0.766 +/- 0.1 as compared with 0.859 +/- 0.13, P =.029), head (0.869 +/- 0.07 as compared with 0.950 +/- 0.07, P =.05), and abdominal (0.793 +/- 0.04 as compared with 0.888 +/- 0.1, P =.001) circumference growth during latency period. In logistic regression analysis, lower-than-expected ultrasound measures of fetal abdominal circumference before birth (odds ratio 1.09; 95% confidence interval 1.01, 1.18) or of abdominal circumference growth during the latency period (odds ratio 1.1; 95% confidence interval 1.01, 1.2) were significantly associated with an increased likelihood of an infant neurodevelopmental abnormality at 2-year follow-up., Conclusion: In pregnancies complicated by preterm PROM, lower-than-expected measures of fetal size and fetal growth were associated with an increased rate of infant neurodevelopmental outcome at 2-year follow-up., Level of Evidence: II-2

Objective: To investigate pregnancy outcome of patients with beta-thalassemia minor., Methods: A population-based study comparing all pregnancies of women with and without beta-thalassemia minor was conducted. Deliveries occurred during the years 1988-2002 at Soroka University Medical Center. A multivariate logistic regression model, with backward elimination, was constructed to find independent risk factors associated with maternal beta-thalassemia minor., Results: During the study period there were 159,195 deliveries, of which 261 (0.2%) occurred in patients with beta-thalassemia minor. The following conditions were significantly associated with beta-thalassemia minor: oligohydramnios (odds ratio [OR] 2.1; 95% confidence interval [CI] 1.2%, 3.7%), intrauterine growth restriction (IUGR; OR 2.4; 95% CI 1.4%, 4.2%), Jewish ethnicity (OR 1.5; 95% CI 1.2%, 1.9%), and previous cesarean delivery (OR 1.4; 95% CI 1.1%, 2.0%). No significant differences were noted between the groups regarding perinatal outcomes such as birth weight, low Apgar scores, congenital malformations, or perinatal mortality. Patients with beta-thalassemia minor were more likely to have cesarean deliveries than were the nonthalassemic parturients (16.9% and 12.2%, respectively; P =.021). However, while controlling for possible confounders such as IUGR, oligohydramnios, and previous cesarean delivery, with another multivariate analysis with cesarean delivery as the outcome variable, beta-thalassemia minor was not found as an independent risk factor for cesarean delivery (OR 1.3; 95% CI 0.9%, 1.9%)., Conclusion: The course of pregnancy of patients with thalassemia minor, including perinatal outcomes, is favorable. Because higher rates of IUGR were found, we recommend ultrasound surveillance of fetal weight for early detection of IUGR., Level of Evidence: II-2

Objective: To examine the impact of group versus individual prenatal care on birth weight and gestational age., Methods: This prospective, matched cohort study included pregnant women (N = 458) entering prenatal care at 24 or less weeks' gestation; one half received group prenatal care with women of the same gestational age. Women were matched by clinic, age, race, parity, and infant birth date. Women were predominantly black and Hispanic of low socioeconomic status, served by one of three public clinics in Atlanta, Georgia or New Haven, Connecticut., Results: Birth weight was greater for infants of women in group versus individual prenatal care (P < .01). Among those born preterm, infants of group patients were significantly larger than infants of individual-care patients (mean, 2398 versus 1990 g, P < .05). Although not statistically significant, infants of group patients were less likely than those of individual-care patients to be low birth weight (less than 2500 g; 16 versus 23 infants); very low birth weight (less than 1500 g; three versus six infants); early preterm (less than 33 weeks; two versus seven infants); or to experience neonatal loss (none versus three infants). There were no differences in number of prenatal visits or other risk characteristics (patient age, race, prior preterm birth)., Conclusions: Group prenatal care results in higher birth weight, especially for infants delivered preterm. Group prenatal care provides a structural innovation, permitting more time for provider-patient interaction and therefore the opportunity to address clinical as well as psychological, social, and behavioral factors to promote healthy pregnancy. Results have implications for design of sustainable prenatal services that might contribute to reduction of racial disparities in adverse perinatal outcomes.

Objective: To ascertain whether fetal growth restriction is associated with alterations of leptin concentrations in umbilical cord blood and maternal serum., Methods: Maternal serum and umbilical cord blood leptin concentrations were determined by immunoradiometric assay at term in 43 women with uncomplicated singleton pregnancies (group A) and in 27 women with singleton pregnancies complicated by fetal growth restriction (group B), all with normal pregravid body mass index (BMI)., Results: Maternal serum leptin concentrations were significantly higher in group B compared with group A (45.0 ng/mL [range 34.2-54.9] versus 29.0 ng/mL [range 24.7-33.3]; P<.01). Umbilical cord blood leptin levels were significantly lower in group B compared with group A (8.4 ng/mL [range 3.6-13.2] versus 13.1 ng/mL [9.7-16.5]; P<.01). Maternal serum leptin levels were not significantly correlated with maternal BMI or with neonatal birth weight in either group. Umbilical cord blood leptin concentrations were significantly correlated with neonatal birth weight in both groups., Conclusion: Growth restricted fetuses at term show umbilical cord blood leptin concentrations significantly lower than those in normal fetuses, suggesting that fetal adipose tissue is a major source of leptin. Maternal serum leptin concentrations are higher in the presence of a growth restricted fetus. This increase might be due to an intrinsic placental mechanism, by which small placentas produce more leptin as a compensatory mechanism, or to early hypoxia.

Objective: To evaluate the effect of introducing two biophysical ultrasound examinations in a low-risk antenatal population. Scans were performed at 30-32 weeks' gestation and 36-37 weeks' gestation., Methods: Scans assessed placental maturity, amniotic fluid volume, and estimated fetal weight. One thousand nine hundred ninety-eight low-risk patients were randomized at 30 weeks' gestation to a control group receiving standard antenatal care, or to the study group who also received an ultrasound scan. Outcome measures were frequency of small for dates (less than 10th percentile at birth), intervention rates, and admissions to neonatal intensive care., Results: The proportion of infants assessed as small for dates at birth in the study group was 6.9% (69 of 994) compared with 10.4% (104 of 999) in the control group (P =.008). The rates of intervention in the study and control groups were 31.3% (313 of 999) and 16.9% (169 of 999), respectively (P <.001). Twenty-eight (2.8%) neonates in the study group were admitted to the neonatal unit compared with 34 (3.4%) in the control group (P =.532)., Conclusion: Introduction of an ultrasound scan at 30-32 weeks' and 36-37 weeks' gestation may reduce the risk of a growth-restricted infant and increases antenatal interventions. Rates of admission to a neonatal unit are not significantly affected.

Objective: To evaluate the effects of early- and late-onset preeclampsia on fetal growth and body proportion., Methods: This was a population-based study based on records of 672,130 pregnancies from the Medical Birth Registry of Norway during 1967-1998. Women with a prior birth, multiple births, those without valid data on the last menstrual period or newborn's crown-heel length, and chronic maternal disease were excluded., Results: In newborns of women with preeclampsia, mean birth weight, crown-heel length, and ponderal index were 4.4%, 0.8%, and 2.6% lower than in births without preeclampsia, respectively. In preterm births, mean differences in birth weight ranged from -11% to -23% against near-equal birth weights in term births. Mean differences in crown-heel length and ponderal index ranged from -1% to -5% and from -5% to -10% before term, respectively. In late preeclampsia, rates of birth weight and crown-heel length above the 90th and 97.5th percentiles and ponderal index above the 97.5th percentile were slightly but significantly higher than in term births without preeclampsia (odds ratios = 1.1-1.5). However, infants born to mothers with preterm preeclampsia were less likely to be heavy, long, or with high ponderal index for gestational age (odds ratios = 0.4-0.6)., Conclusion: Our results support the hypothesis that preeclampsia is an etiologically heterogeneous disorder that occurs in at least two subsets, one with normal or enhanced placental function, and another involving placental dysfunction and fetal growth restriction, often with asymmetric fetal body proportion, reduced fetal length, and preterm delivery. In future studies, distinguishing between the two subtypes may be important.

Objective: To estimate the association between birth weight discordance and neonatal mortality controlling for the effects of fetal growth, and to understand the differences in the incidence of mortality between larger and smaller infants., Methods: This analysis is based on the National Center for Health Statistics matched multiple birth data set file containing all twin births in the United States from 1995 through 1997. Birth weight discordance was grouped into four levels (15-19%, 20-24%, 25-29%, and 30% or more). Generalized estimating equations were used to obtain adjusted odds ratios and 95% confidence intervals to estimate the mortality risk associated with discordance after adjusting for fetal growth., Results: Mortality was 11 times higher among highly discordant smaller twins (30% or more) compared with nondiscordant smaller twins (43.4 and 3.8 per 1000, respectively). Risk estimates ranged from 1.08 (95% confidence interval 0.85, 1.38) among 15-19% discordant twins to 2.05 (95% confidence interval 1.66, 2.51) among 30% or more discordant twins. Larger twins had similar risk estimates. After accounting for the association between fetal growth and discordance, mortality risk was substantially higher among smaller and larger twins who were highly discordant (30% or more). In addition, there was little difference in the magnitude of risk estimates between highly discordant smaller and larger twins., Conclusion: After controlling for fetal growth, smaller and larger twins affected by higher levels of birth weight discordance (25% or more) remain at disproportionate risk for neonatal mortality when compared with other smaller or larger twins. Additionally, smaller twins do not have an elevated risk compared with larger twins after adjusting for their different fetal growth distributions.

Objective: Intrauterine growth restriction has been associated with failed maternal physiologic changes such as abnormal spiral artery remodeling and reduced maternal blood volume. A polymorphism of angiotensinogen Thr235 has been considered a risk factor for preeclampsia. We genotyped maternal and fetal deoxyribonucleic acid (DNA) for angiotensinogen Thr235 to estimate whether the polymorphism is also a risk factor for intrauterine growth restriction., Methods: We examined maternal blood DNA in 174 patients with intrauterine growth restriction and 60 patients with both preeclampsia and intrauterine growth restriction. The control group comprised 400 consecutive cases of women with term pregnancies and infants with birth weight between the fifth and 95th percentiles. We also examined 162 DNA samples from fetal blood with intrauterine growth restriction for the Thr235 polymorphism, and 240 normal fetuses were used as the control group. The angiotensinogen genotype was determined using mutagenically separated polymerase chain reaction. The products were size fractionated on an agarose gel. Angiotensinogen genotypes were divided into three groups: MM (homozygous for angiotensinogen Met235 allele), TT (homozygous for angiotensinogen Thr235 allele), and MT (heterozygous)., Results: Maternal genotyping revealed a significantly higher Thr235 allele frequency in intrauterine growth restriction (.60) and preeclampsia/intrauterine growth restriction (.63) than in the control group (.36) (P <.001). Fetal genotyping revealed a Thr235 allele frequency of.59 in intrauterine growth restriction fetuses, as compared with the control group (.38) (P <.001)., Conclusion: Maternal and fetal angiotensinogen Thr235 genotypes are associated with an increased risk of intrauterine growth restriction in our study population. The angiotensinogen Thr235 allele may predispose women to deliver growth-restricted fetuses.

Objective: To examine the association of intrapair birth weight discordance with fetal and neonatal mortality., Methods: We used the United States (1995-1997) Matched Multiple Birth File (n = 297,155)., Results: Among twin live births and stillborn fetuses, 29.9% had less than 5% birth weight discordance, 24.2% had 5-9%, 29.6% had 10-19%, 11.1% had 20-29%, 3.4% had 30-39%, and 1.8% had 40% or more. The stillborn fetus rate increased progressively with increasing birth weight discordance for smaller and larger twins of the same sex. Compared with the less than 5% birth weight discordance category, the adjusted odds ratios (OR) (95% confidence intervals [CIs]) for stillborn fetus associated with 5-9%, 10-19%, 20-29%, 30-39%, and 40% or more birth weight discordance, respectively, were 0.81 (95% CI 0.58, 1.11), 1.41 (95% CI 1.07, 1.84), 1.74 (95% CI 1.28, 2.35), 3.06 (95% CI 2.21, 4.24), and 4.29 (95% CI 3.05, 6.04) for smaller twins. The corresponding ORs (95% CIs) for larger twins were 0.78 (95% CI 0.57, 1.08), 1.26 (95% CI 0.96, 1.66), 1.77 (95% CI 1.27, 2.46), 3.38 (95% CI 2.33, 4.92), and 2.91 (95% CI 1.89, 4.47). Similar associations were observed among smaller but not larger twins of opposite sex. Among larger but not smaller twins of the same sex, increasing birth weight discordance was associated with overall neonatal deaths. This association was not apparent among smaller and larger twins of opposite sex. However, increasing birth weight discordance was associated with neonatal deaths related to congenital malformations among smaller and larger twins., Conclusion: The results provide evidence that increased twin birth weight discordance was associated with increased risk of intrauterine death and malformation-related neonatal deaths.

Objective: To evaluate the effect of antenatal corticosteroids on mortality, morbidity, and disability or handicap rate in early preterm, growth-restricted infants., Methods: This case-control study in two tertiary care centers included all live-born singleton infants with growth-restriction due to placental insufficiency, who were delivered by cesarean because of cardiotocographic signs of fetal distress before the beginning of labor at a gestational age of 26-32 weeks during the years 1984-1991. Infants who had been treated antenatally with corticosteroids more than 24 hours and less than 7 days before birth were matched by birth weight, sex, and year of birth with infants whose mothers had been admitted more than 24 hours before delivery but were not treated antenatally with steroids. The main outcome measure was survival without disability or handicap at 2 years corrected age. A sample of 60 case-control pairs would give 81% power to demonstrate 50% increase of this outcome [odds ratio (OR) 3.0] by corticosteroid treatment. Behavior and physical growth were evaluated at school age by questionnaire., Results: The study group and control group consisted of 62 infants each. Survival without disability or handicap at 2 years' corrected age was more frequent in the corticosteroid group [OR 3.2, confidence interval (CI) 1.1, 11.2]. In the long-term follow-up at school age there was a statistically significant negative effect on physical growth (OR 5.1, CI 1.4, 23.8), but no differences in behavior were detected., Conclusion: Benefits from antenatal corticosteroids for early preterm, growth-restricted infants appear to outweigh possible adverse effects.

Objective: To evaluate the effect of low birth weight adjusted for gestational age in first pregnancies on preeclampsia in second pregnancies and to estimate the proportion of preeclampsia in second pregnancies attributable to histories of LBW for gestational age., Methods: We conducted a cohort study based on linked data from the Medical Birth Registry of Norway, which covered all births in 1967-1992., Results: Women who delivered infants under the third percentile birth weight were three times more likely to have initial or recurrent preeclampsia in second pregnancies than those who delivered infants at or above the tenth percentile. After adjusting for maternal age, year of birth, interpregnancy interval, education, chronic hypertension, diabetes mellitus, and change of partner, the increased risk persisted. Birth weight below the tenth percentile in the first delivery accounted for 10% of the total cases of preeclampsia in the second pregnancy and 30% of recurrent cases., Conclusion: A history of low birth weight adjusted for gestational age is associated significantly with subsequent occurrence as well as recurrence of preeclampsia. These findings are consistent with the hypothesis of a shared etiologic factor or recurrent pathophysiologic mechanism for preeclampsia and fetal growth restriction. A history of fetal smallness for gestational age is found in a substantial proportion of all cases of preeclampsia and thus seems to be important in the etiology of preeclampsia.

Objective: To examine the association of maternal hemoglobin during pregnancy with preterm birth and small for gestational age (SGA)., Methods: We performed a retrospective cohort analysis of hemoglobin and birth outcome among 173,031 pregnant women who attended publicly funded health programs in ten states and delivered a liveborn infant at 26-42 weeks' gestation. We defined preterm as less than 37 weeks' gestation and SGA as less than the tenth percentile of a US fetal growth reference., Results: Risk of preterm birth was increased in women with low hemoglobin level in the first and second trimester. The odds ratio (OR) for preterm birth with moderate-to-severe anemia during the first trimester (more than three standard deviations [SD] below reference median hemoglobin, equivalent to less than 95 g/L at 12 weeks' gestation) was 1.68 (95% confidence interval [CI] 1.29, 2. 21). Anemia was not associated with SGA. High hemoglobin level during the first and second trimester was associated with SGA but not preterm birth. The ORs for SGA in women with very high hemoglobin level during the first and second trimester (more than three SDs above reference median hemoglobin, equivalent to greater than 149 g/L at 12 weeks' gestation and greater than 144 g/L at 18 weeks') were 1.27 (95% CI 1.02, 1.58) and 1.79 (95% CI 1.49, 2.15), respectively., Conclusion: These data highlight the importance of considering anemia and high hemoglobin level as indicators for adverse pregnancy outcome. An elevated hemoglobin level (greater than 144 g/L) is an indicator for possible pregnancy complications associated with poor plasma volume expansion, and should not be mistaken for good iron status.

Objective: To calculate the frequencies of very low birth weight (VLBW) neonates among twins in a large population database., Methods: The database comprised 12,567 live-born twin pairs delivered from 1993 to 1998 in Israel. Low birth weight (LBW) and VLBW were defined as less than 2500 and 1500 g, respectively. We counted the number of pairs with VLBW neonates in three combinations: VLBW-VLBW, VLBW-LBW, and VLBW-over 2500 g. We compared the subsets of nulliparas and multiparas and the frequency of like- versus unlike-sex twins., Results: The frequency of at least one VLBW twin was significantly higher among nulliparas than multiparas (odds ratio [OR] 2.3; 95% confidence interval [CI] 2.1, 2.6; P <.001). For pairs with VLBW-VLBW and VLBW-LBW combinations, a significantly higher frequency was found among nulliparas than multiparas (OR 2.0; 95% CI 1.7, 2.8; P <.001 and OR 2.6; 95% CI 2.2, 3.1; P <.001, respectively). The risk seemed to be accentuated in like-sex twins. Overall, the risk of having at least one VLBW infant was 1:5 among nulliparas and 1:12 among multiparas. The risk of having two VLBW twins among nulliparas (1:11) was double that of multiparas (1:22)., Conclusion: Nulliparas are at significantly increased risk of delivering one or two VLBW twins.