Influence of exercise mode on pregnancy outcomes: ENHANCED by Mom project.

BACKGROUND: The extent of the benefits of exercise training during pregnancy on maternal, fetal, and neonatal health outcomes has not been sufficiently addressed. While aerobic exercise training has been determined as safe and efficacious throughout pregnancy, the effects of other training modes on fetal health and development as well as any continued benefits for the neonate, especially with regards to cardiovascular development and function, is largely unknown. In the ENHANCED by Mom study we aim to determine the effects of different modes of exercise training (aerobic, circuit, and resistance) throughout pregnancy on childhood health by controlling individual exercise programs and assessing the effects of each on fetal and neonatal health adaptations. METHODS/DESIGN: ENHANCED by mom is a cross sectional comparison study utilizing 3 intervention groups in comparison to a control group. Participants will complete three 5 min warmup + 45 min sessions weekly from 16 weeks to 36 weeks gestation of aerobic, resistance, or circuit training, in comparison to non-exercising controls. Maternal physical measurements will occur every 4 weeks throughout the intervention period. Fetal morphometric and heart measurements will occur at 34 weeks gestation. Neonatal measurements will be acquired at birth and at 1 month, 6 months, and 12 months. DISCUSSION: A better understanding on the effects of exercise training during pregnancy on fetal and neonatal health could have a profound impact on the prevention and development of chronic diseases such as obesity, hypertension, and diabetes.

Analysis of the safety and reliability of a hydrothermal ablation system: a multicenter, prospective postmarket study.

OBJECTIVE: To obtain information on practitioner experience in the use of the Genesys HydroThermAblator (HTA) System under normal clinical conditions through documentation of the system's acute safety features, in terms of burn rates, and its technical reliability. STUDY DESIGN: This was a prospective, observational, multicenter, postmarket interventional clinical trial with outcome measures of acute (within 21 days post-procedure) safety, serious adverse device effects, and technical malfunctions in a population of premenopausal women > or = 18 years of age. RESULTS: A total of 992 women (mean age, 41.7 +/- 6.8 years; range, 22-65 years) were enrolled in 18 clinical sites throughout the United States. The Genesys HTA System provided low burn rates in the intent-to-treat (n = 992 [0.4%] [95% CI 0.1-1.0%]) and evaluable (n = 931 [0.2%] [95% CI 0.1-0.8%]) subject populations. Only 1 burn was clinically significant and was defined as a serious adverse device effect (1/992 [0.10%] [95% CI 0.0-0.6%]). Fifty-three (5.1%) technical malfunctions occurred in 44 procedures, and 27 (27/44 [61.4%]) patients completed their procedures after 31 (31/ 53 [58.5%]) technical problems were addressed and resolved. CONCLUSION: The Genesys HTA System delivers a safe and reliable treatment option for premenopausal women with heavy menstrual bleeding.

Persistent cloaca: a 10-year review of prenatal diagnosis.

OBJECTIVE: The purpose of this study was to review antenatal sonographic findings in children born with persistent cloaca. METHODS: Infants (n =145) with persistent cloaca followed at a center for colorectal congenital anomalies were identified by a retrospective chart review. Fifty female infants with a persistent cloaca met inclusion criteria and had prenatal records and imaging studies available for review. Sonographic data were retrospectively abstracted from charts. RESULTS: Anomalies were detected in 27 of 50 cases (54%). A correct antenatal diagnosis of persistent cloaca occurred in 3 of 50 (6%). Common findings misinterpreted on antenatal sonography include urinary tract anomalies, dilated bowel, and a cystic pelvic mass (representing hydrocolpos). CONCLUSIONS: Antenatal diagnosis of persistent cloaca is difficult. Persistent cloaca should be considered in the differential diagnosis if urinary tract malformations, dilated bowel loops, or cystic pelvic masses are visualized by prenatal diagnosis.

Assessment of neonatal adrenal size using high resolution 2D ultrasound and its correlation with birth demographics and clinical outcomes.

OBJECTIVE: Assessment of adrenal function in a sick neonate remains a challenge in spite of major advances in neonatal care. We used 2D ultrasound of adrenal glands to assess maturity of adrenal glands in extremely preterm infants and sick term and near term infants. STUDY DESIGN: We collected demographics details of 99 mother-infants pairs (24-41 weeks) and obtained 2D ultrasound scans of adrenal glands in first week of life to measure adrenal volume, fetal zone size, and adrenal to kidney ratios. Relationship between adrenal measurements, antenatal factors, and postnatal outcomes were studied. RESULTS: We reported normative adrenal gland volume data during gestation from 80 appropriate for gestational age (AGA) infants. In a binary analysis, adrenal size was significantly related to gender, race, intrauterine growth restriction (IUGR), maternal chorioamnionitis, and maternal hypertension. Linear regression analysis showed that fetal zone is significantly related to not only gestational age but also chorioamnionitis and later development of intraventricular hemorrhage (IVH). Adrenal volume likewise is also related to gestational age, preeclampsia, and IVH. CONCLUSIONS: Antenatal maternal factors and uterine environment affects adrenal growth and development thus postnatal high resolution 2D US scan of adrenal glands can provide useful information to predict outcomes. This information can complement hormone and adrenocorticotrophic hormone (ACTH) stimulation assays.

The outcome of twin-twin transfusion syndrome complicated with placental insufficiency.

OBJECTIVE: The aim was to evaluate the incidence and perinatal outcomes of TTTS complicated with placental insufficiency (PI/TTTS). STUDY DESIGN: This was a retrospective study of all TTTS with PI. PI is defined as estimated fetal weight < 10% with elevated head circumference/abdominal circumference ratio and weight discordance > 20%. RESULTS: Fifty-two out of 270 (19%) pregnancies met criteria. Forty-nine (94.2%) donor twins were diagnosed with PI/TTTS. Fifteen were treated with amnioreduction, 26 with selective fetoscopic laser photocoagulation, 4 with donor intrafetal radiofrequency ablation (RFA), and 7 had expectant management. There was a high incidence of abnormal Dopplers and abnormal placental cord insertion in the donor twin (58% marginal, 35% membranous) with a mean estimated fetoscopic donor placental share of 26.1 +/- 14.3%. There was a significant decrease in the overall donor survival rate of 61% (4 RFA selected donors were excluded) as compared to overall recipient survival rate of 85%, respectively (P = .009). There was no significant difference in donor or recipient survival rate among the treatment groups (P = .058). CONCLUSION: Placental insufficiency impacts the survival of the affected twins in the setting of TTTS. Studies are needed for appropriate treatment in TTTS with placental insufficiency.

Acute effects of selective fetoscopic laser photocoagulation on recipient cardiac function in twin-twin transfusion syndrome.

OBJECTIVE: This study evaluated the acute effects of selective fetoscopic laser photocoagulation (SFLP) on recipient cardiovascular function in a twin-twin transfusion syndrome (TTTS) pregnancy. STUDY DESIGN: This was a retrospective chart review of echocardiographic data in TTTS including right (RV) and left (LV) ventricular Doppler myocardial performance index (MPI); LV and RV end diastolic wall thickness; and umbilical artery (UA), vein (UV), and ductus venosus (DV) Dopplers. The primary outcome measures were improved MPI defined as greater than 10% interval decrease in left and/or right MPI. Data were analyzed by Student t test and Fisher's exact test. RESULTS: Sixty-five patients met inclusion criteria. SFLP results in a significant improvement in UV and DV Doppler and an increase in both RV and LV wall thickness. A 10% or greater improvement in recipient LV MPI after SFLP is associated with improved recipient survival as compared with unimproved LV MPI (100% vs 86.1%, P = .05). CONCLUSION: Improved recipient myocardial performance index after SFLP is associated with improvement in recipient survival.

Influence of maternal exercise on fetal heart response during labor and delivery.

OBJECTIVES: The purpose of this study was to determine if prenatal exercise alters the maternal and fetal heart responses during labor and delivery. We hypothesized that fetuses of exercising mothers would exhibit a lower baseline heart rate (HR), increased HR variability (HRV), and no differences in fetal heart accelerations and decelerations. DESIGN: This study employed a cross-sectional design. METHODS: The Modifiable Physical Activity Questionnaire was used for group classification. Exercising women were those participating in 30 minutes of moderate-to-vigorous exercise at least 3×/week throughout the entire pregnancy. Women achieving a lower dose of exercise were classified as non-exercisers. Cardiotocography recordings during the first hour of labor and delivery assessed fetal baseline HR, HRV, accelerations, decelerations, and contractions. ANCOVA analyses were performed to assess group differences in these outcomes and were adjusted for maternal body mass index. RESULTS: Thirty-one women were included in the analyses. No group mean differences were found for maternal and fetal characteristics, except for maternal age (EX: mean (SD) 28.5 (±4.6y) vs NON-EX: 24.1 (±1.2y)). After controlling for body mass index, no statistical differences in maternal HR response (ß = 3.9, SE = 5.0, 95%CI -6.4-14.2) or fetal HR response (ß = 3.9, SE = 2.5, 95%CI -1.2-9.11), accelerations and decelerations (ß= -0.03, SE = 0.4, 95%CI -0.9-0.8; ß= -0.10, SE = 0.4, 95%CI -0.8-0.9, respectively), or HRV (ß = 0.6, SE = 1.7, 95%CI -2.8-4.0) were observed. CONCLUSIONS: Based on the findings of this study, we found no evidence that maternal exercise during pregnancy was associated with maternal or fetal HR response during labor and delivery. These data suggest maternal exercise may not elicit positive or negative effects on maternal and fetal cardiovascular responses to the physiological stress of labor and delivery.

Mirror syndrome: a novel approach to therapy with fetal peritoneal-amniotic shunt.

BACKGROUND: Mirror syndrome is a rare entity characterized by maternal disease mimicking fetal hydrops. In mirror syndrome, there is maternal hypertension, edema, and often proteinuria in association with fetal hydrops. The causal link between mirror syndrome and hydrops fetalis remains elusive. CASE: This is a case report of a pregnant woman who developed mirror syndrome associated with fetal hydrops. A fetal pelvic mass resulted in bladder outlet obstruction, subsequent bladder rupture, and massive urinary ascites. The resultant massive ascites caused thoracic and cardiac compression and subsequent hydrops fetalis. Placement of a peritoneal-amniotic shunt resolved the fetal hydrops and maternal mirror syndrome. CONCLUSION: In utero treatment of hydropic fetus can result in the cure of maternal mirror syndrome.

Intrafetal radiofrequency ablation for twin reversed arterial perfusion (TRAP): a single-center experience.

OBJECTIVE: The objective of the study was to review perinatal outcomes in pregnancies treated with intrafetal radiofrequency ablation (RFA) for twin reversed arterial perfusion (TRAP) sequence. STUDY DESIGN: Perinatal outcome data from a quaternary care referral center were abstracted from a chart review of pregnancies with TRAP sequence treated in the midtrimester with umbilical cord RFA of the perfused twin. RESULTS: Twenty-one pregnancies with TRAP sequence were evaluated. Two women had a pump twin demise prior to therapy, 1 with trisomy 21 declined treatment. Four of 20 were treated successfully with RFA but remain undelivered, and 1 was treated with fetoscopic cord coagulation. Twelve of 13 pump twins treated with RFA (94%) survived to 30 days of life. Mean preoperative cardiac combined cardiac output was 588 mL/kg and pump/twin ratio was 0.7 (range 0.4 to 1.1). The effect of RFA on postoperative cardiac output was variable (6-85%). The average gestational age at birth was 37 weeks (range 26-39 weeks). CONCLUSION: Primary therapy with RFA is a successful modality for pregnancies complicated by TRAP sequence.

A prospective, randomized, multicenter trial of amnioreduction vs selective fetoscopic laser photocoagulation for the treatment of severe twin-twin transfusion syndrome.

OBJECTIVE: The objective of the study was to examine the effect of selective fetoscopic laser photocoagulation (SFLP) vs serial amnioreduction (AR) on perinatal mortality in severe twin-twin transfusion syndrome (TTTS). STUDY DESIGN: This was a 5 year multicenter, prospective, randomized controlled trial. The primary outcome variable was 30 day postnatal survival of donors and recipients. RESULTS: There was no statistically significant difference in 30-day postnatal survival between SFLP or AR treatment for donors at 55% (11 of 20) vs 55% (11 of 20) (P = 1.0, odds ratio [OR] 1, 95% confidence interval [CI] 0.242 to 4.14) or recipients at 30% (6 of 20) vs 45% (9 of 20) (P = .51, OR 1.88, 95% CI 0.44 to 8.64). There was no difference in 30 day survival of 1 or both twins on a per-pregnancy basis between AR at 75% (15 of 20) and SFLP at 65% (13 of 20) (P = .73, OR 1.62, 95% CI 0.34 to 8.09). Overall survival (newborns divided by the number of fetuses treated) was not statistically significant for AR at 60% (24 of 40) vs SFLP 45% (18 of 40) (P = .18, OR 2.01, 95% CI 0.76 to 5.44). There was a statistically significant increase in fetal recipient mortality in the SFLP arm at 70% (14 of 20) vs the AR arm at 35% (7 of 20) (P = .25, OR 5.31, 95% CI 1.19 to 27.6). This was offset by increased recipient neonatal mortality of 30% (6 of 20) in the AR arm. Echocardiographic abnormality in recipient twin Cardiovascular Profile Score is the most significant predictor of recipient mortality (P = .055, OR 3.025/point) by logistic regression analysis. CONCLUSION: The outcome of the trial did not conclusively determine whether AR or SFLP is a superior treatment modality. TTTS cardiomyopathy appears to be an important factor in recipient survival in TTTS.

Second-trimester asynchronous multifetal delivery results in poor perinatal outcome.

OBJECTIVE: The purpose of this study is to estimate the maternal and fetal morbidities associated with asynchronous delivery. METHODS: A review of maternal and fetal medical records was performed at 2 tertiary care centers over 12 years. Charts were identified by the International Classification of Diseases, 9th Revision, Clinical Modification codes for twin and triplet gestations. Asynchronous delivery was defined as an active attempt (tocolysis and/or emergent cerclage placement) to increase latency between delivery of the first fetus and subsequent fetuses. RESULTS: Fourteen cases of asynchronous delivery were identified out of 96922 deliveries including 1352 pregnancies complicated by multifetal gestation. The occurrence rate of asynchronous delivery was 0.14 per 1000 births. The etiology of preterm birth of the first fetus in 12 (86%) of 14 cases was second-trimester rupture of membranes. The mean gestational age for delivery of the first fetus was 21.+/- 2.0 weeks. All women received tocolysis and intravenous antibiotics. Two of 3 attempts at cerclage placement were successful. Median latency obtained was 2 days (range less than 1-70 days). There was 1 survival of a first born. There were 19 retained fetuses, 2 died in utero, 10 died between birth and day 57 of life, and 7 survived (37%; 95% confidence interval 16%, 62%) until hospital discharge. Six of 7 survivors had major sequelae from prematurity. One of 19 fetuses was discharged without major sequelae (5%; 95% confidence interval 0%, 25%). Maternal morbidity included 2 placental abruptions and 8 cases of infectious morbidity including 1 case of septic shock. CONCLUSION: Attempts at asynchronous deliveries are uncommon and are associated with a high rate of perinatal death. Most fetal survivors have significant damage from preterm birth.

Magnesium sulfate in women with mild preeclampsia: a randomized controlled trial.

OBJECTIVE: To determine whether magnesium sulfate prevents disease progression in women with mild preeclampsia. METHODS: A total of 222 women with mild preeclampsia were randomized to receive intravenous magnesium sulfate (n = 109) or matched placebo (n = 113). Mild preeclampsia was defined as blood pressure of at least 140/90 mm Hg taken on two occasions in the presence of new-onset proteinuria. Patients with chronic hypertension or severe preeclampsia were excluded. Patients were considered to have disease progression if they developed signs or symptoms of severe preeclampsia, eclampsia, or laboratory abnormalities of full or partial HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. RESULTS: The groups were similar with respect to maternal age, ethnicity, gestational age, parity, and maternal weight at enrollment. Fourteen women (12.8%) in the magnesium group and 19 (16.8%) in the placebo group developed severe preeclampsia after randomization (relative risk = 0.8, 95% confidence interval 0.4, 1.5, P =.41). None in either group developed eclampsia or thrombocytopenia. Women assigned magnesium had similar rates of cesarean delivery (30% versus 25%), chorioamnionitis (3% versus 2.7%), endometritis (5.3% versus 4.3%), and postpartum hemorrhage (1% versus 0.9%), compared to those assigned placebo. Neonates born to women assigned magnesium had similar mean Apgar scores at 1 and 5 minutes as those born to women assigned placebo (7.7 +/- 1.5 versus 7.8 +/- 1.6 and 8.7 +/- 0.7 versus 8.8 +/- 0.6, respectively). CONCLUSION: Magnesium sulfate does not have a major impact on disease progression in women with mild preeclampsia. Magnesium use does not seem to increase rates of cesarean delivery, infectious morbidity, obstetric hemorrhage, or neonatal depression.

Heat shock protein 70 is not increased in women with severe preeclampsia.

OBJECTIVE: The purpose of this study is to determine if heat shock protein 70 (Hsp 70), a marker of cellular stress, is elevated in pregnancies complicated by severe preeclampsia. METHODS: Maternal blood was collected from women with severe preeclampsia (n=47) matched for delivery gestational age to normotensive pregnant controls (n=51). Hsp 70 concentrations were measured by standard ELISA techniques. Data were analyzed with the Student's t-test and chi-square test. MAIN OUTCOME MEASURES: The primary outcome measured was Hsp 70 concentrations. Our hypothesis prior to data collection was that HSP 70 would be increased in women with severe preeclampsia. RESULTS: Compared with normotensive women, those with severe preeclampsia had similar maternal age, parity, delivery gestational age, maternal weight, and ethnicity. There was no difference in mean concentrations of Hsp 70 between women with severe preeclampsia and controls (35.4 +/- 96.7 vs. 30.1 +/- 11.5, p=0.80). Similar numbers of women with severe preeclampsia (n=28) and controls (n=30) had Hsp 70 concentrations below the 0.02 ng/dL level of detection (chi-square value=0.024, p=0.88). CONCLUSION: Hsp 70 concentrations are not elevated in women with severe preeclampsia.

Concentrations of estrogens in patients with preeclampsia.

The role of estrogens in the pathophysiology of preeclampsia remains to be determined. The aim of our study was to compare serum concentrations of 17 beta-estradiol and estriol in women with preeclampsia to normotensive pregnant controls. Serum concentrations of estrogens were measured in women with mild (n = 24) and severe (n = 24) preeclampsia as well as is normotensive pregnant controls (n = 24). Patients were matched for gestational age. Pregnancies complicated by early onset severe preeclampsia are associated with increased rates of maternal and fetal morbidity. Subsequently, we created further subgroups before and after 34 weeks of gestation (34 + 0). Serum estrogen concentrations were determined by standard ELISA technique. Compared to normotensive controls, the differences between the overall median serum concentrations of 17 beta-estradiol in women with mild (3811 v. 3730 pg/ml, P = 0.9) and severe (3811 v. 3630 pg/ml, P = 0.1) preeclampsia were statistically not significant. The differences between the overall median serum concentrations of estroil in controls and in patients with mild (121 v. 76 ng/ml, P = 0.6) and severe (121 v. 79 ng/ml, P = 0.4) preeclampsia were similar. The differences between the median concentrations of 17 beta-estradiol in patient with early onset severe preeclampsia compared to patients with mild preeclampsia (3061 v. 3715 pg/ml, P = 0.004) and controls (3061 v. 3807 pg/ml, P = 0.006) were statistically significant. In addition, the differences between the median concentrations of estriol in women with early onset severe preeclampsia compared to controls were statistically significant (20 v. 92 ng/ml, P = 0.02). The differences between the median concentrations of estrogens in those with late onset severe preeclampsia compared to women with mild preeclampsia were not significant. We found significantly lower concentrations of estrogens in women with early onset severe preeclampsia.

Higher maternal doses of methadone does not increase neonatal abstinence syndrome.

OBJECTIVE: The purpose of this study is to assess the incidence of clinically significant neonatal abstinence syndrome (NAS) based on maternal antenatal methadone dosing in women with a history of narcotic dependence. STUDY DESIGN: A retrospective review of 174 pregnant women on methadone maintenance was performed. Data were stratified based on maternal methadone dose at delivery: low (0-50 mg/day, n = 59), medium (51-100 mg/day, n = 63), and high (>100 mg/day, n = 52). NAS was defined by Finnegan as score greater than 7 on two occasions. Outcome measures were rate and severity of NAS, birth weight, preterm birth rate, and neonatal morbidities and mortality. RESULTS: The rates of NAS (40.7% vs. 52.4% vs. 40.8%, p > .05), birth weight, and neonatal morbidities were similar regardless of the maternal methadone dose. Although there was a trend toward earlier delivery, the rate of preterm birth among the three groups (low dose, 17%; medium dose, 19%; high dose, 27%; p > .05) was not statistically significant. CONCLUSION: Higher maintenance dosing of methadone is not associated with increased rate or severity of NAS or other adverse perinatal outcomes. Concerns about NAS should not restrict the methadone dosing during pregnancy. Methadone dosing should not be restricted to lower dosing during pregnancy.

High-risk fetal congenital pulmonary airway malformations have a variable response to steroids.

BACKGROUND/PURPOSE: Anecdotal reports suggest that maternal steroids may arrest the growth of congenital pulmonary airway malformations (CPAMs), preventing or reversing hydrops. We reviewed our experience with CPAMs to determine the fetal response to steroid therapy. METHODS: This study is a retrospective review of all fetal CPAMs from 2004 to 2008. Fetuses with high-risk CPAMs that received at least one course of steroids were identified. Fetal magnetic resonance imaging and ultrasound data were used to classify the CPAMs, identify hydrops fetalis and follow the fetuses poststeroid dosing. RESULTS: Forty-four fetuses with CPAM were identified. Fifteen patients were found to have received at least one course of steroids. Thirteen were hydropic and 2 were nonhydropic. Seven of the 13 hydropic fetuses (54%) showed an initial response to steroid administration, whereas the 2 nonhydropic high-risk fetuses progressed to birth without developing hydrops. Seven of the 15 patients, however, resulted in fetal demise or early postnatal death, giving a survival rate of 53%. CONCLUSIONS: High-risk CPAMs have a variable response to steroids. This variable response demonstrates the need for a placebo-controlled randomized study to more accurately determine the effect of steroids on hydrops and CPAM growth rates. Repeated steroid courses may not be helpful, and progression in CPAM volume to head circumference ratio (CVR) or hydrops should prompt open fetal surgery to prevent irreversible fetal insult.

Prenatal MRI findings of fetuses with congenital high airway obstruction sequence.

OBJECTIVE: To define the MRI findings of congenital high airway obstruction sequence (CHAOS) in a series of fetuses. MATERIALS AND METHODS: Prenatal fetal MR images were reviewed in seven fetuses with CHAOS at 21 to 27 weeks of gestation. The MRI findings were reviewed. The MRI parameters evaluated included the appearance of the lungs and diaphragm, presence or absence of hydrops, amount of amniotic fluid, airway appearance, predicted level of airway obstruction, and any additional findings or suspected genetic syndromes. RESULTS: All the fetuses viewed (7 of 7) demonstrated the following MRI findings: dilated airway below the level of obstruction, increased lung signal, markedly increased lung volumes with flattened or inverted hemidiaphragms, massive ascites, centrally positioned and compressed heart, as well as placentomegaly. Other frequent findings were anasarca (6 of 7) and polyhydramnios (3 of 7). MRI identified the level of obstruction as laryngeal in five cases and tracheal in two cases. In four of the patients, surgery or autopsy confirmed the MRI predicted level of obstruction. Associated abnormalities were found in 4 of 7 (genetic syndromes in 2). Postnatal radiography (n = 3) showed markedly hyperinflated lungs with inverted or flattened hemidiaphragms, strandy perihilar opacities, pneumothoraces and tracheotomy. Two fetuses were terminated and one fetus demised in utero. Four fetuses were delivered via ex utero intrapartum treatment procedure. CONCLUSION: MRI shows a consistent pattern of abnormalities in fetuses with CHAOS, accurately identifies the level of airway obstruction, and helps differentiate from other lung abnormalities such as bilateral congenital pulmonary airway malformation by demonstrating an abnormally dilated airway distal to the obstruction.

Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial.

OBJECTIVE: We sought to determine the effect of supplemental antioxidant vitamins C and E on the rate of preeclampsia in high-risk pregnant women. STUDY DESIGN: Women at risk for preeclampsia (previous preeclampsia, chronic hypertension, pregestational diabetes, or multifetal gestation) were recruited at 14 to 20 weeks' gestation and randomly assigned to receive either 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily in addition to their regular prenatal vitamins. The primary outcome was the occurrence of preeclampsia. An estimated sample size of 220 women in each arm was determined to be necessary to demonstrate a 50% reduction in the rate of preeclampsia. RESULTS: Funding was terminated after 109 women had been recruited; 9 were lost to follow-up or withdrew. We analyzed data from the remaining 100 women to look for differences in outcome and to estimate the required sample size for future studies. The rate of preeclampsia was not different: 17.3% in women who received supplemental vitamins C and E, versus 18.8% in the placebo group. Assuming a baseline rate of preeclampsia in the placebo group between 15% and 20%, we can estimate that 500 to 950 women in each arm will be required to show a clinically important reduction in the rate of preeclampsia. CONCLUSION: The potential benefit of vitamin C and E supplementation to prevent preeclampsia in women with clinical risk factors is smaller than we estimated. Future studies of antioxidant vitamin supplementation in this population will require more than 500 women in each arm.