Rate Of Composite Neonatal Morbidity Research Articles

Clinical significance of intermittent absent end-diastolic flow of the umbilical artery in fetal growth restriction

Fetal growth restriction can result from a variety of maternal, fetal, and placental conditions. Umbilical artery Doppler assesses the impedance to blood flow along the fetal component of the placental unit. An abnormal umbilical artery waveform reflects the presence of placental insufficiency and can help differentiate a growth-restricted fetus from the constitutionally small, thus guiding further management. The presence of persistently absent end-diastolic flow and reversed end-diastolic flow is an indication for inpatient antenatal surveillance and preterm delivery. There is no consensus on the optimal management of intermittent absent end-diastolic flow owing to a lack of data to support the ideal delivery timing for growth-restricted fetuses with this finding. This study aimed to estimate the risks of adverse perinatal outcomes among growth-restricted pregnancies with persistently elevated, intermittently absent, and persistently absent end-diastolic flow. Fetal growth restriction is a common condition that is associated with an increased risk of fetal morbidity and mortality. Intermittently absent umbilical artery end-diastolic flow may be identified among pregnancies with fetal growth restriction. The fetal risks associated with persistently absent end-diastolic flow have been described. However, the risks associated with intermittent absent end-diastolic flow are not as well-known. We performed a retrospective cohort study including nonanomalous, singleton, growth-restricted pregnancies that received umbilical artery Doppler assessment at our institution from 2009 to 2020. Fetuses were classified into the following 3 categories: elevated umbilical artery Doppler, intermittent absent end-diastolic flow, and persistently absent end-diastolic flow. The Doppler categories were classified by the most severe in the pregnancy. The primary outcome was a composite of neonatal morbidity. Total 233 fetuses met the criteria. Of which 78 (33.0%) had elevated umbilical artery Doppler waveforms, 37 (16.0%) had intermittent absent end-diastolic flow, and 119 (51.0%) had absent end-diastolic flow. The composite outcome was statistically different between the groups, occurring in 16.9% with elevated umbilical artery Doppler waveforms (13/77), 35.1% (12/39) with intermittent absent end-diastolic flow, and 56.3% (65/127) with absent end-diastolic flow (P<.001).The odds ratio for the composite outcome was significantly increased in absent end-diastolic flow (odds ratio, 6.15; 95% confidence interval, 3.14-12.80) and was not significantly increased for intermittently absent end-diastolic flow (odds ratio, 2.46; 95% confidence interval, 0.98-6.19) when compared with elevated umbilical artery Doppler waveforms. When adjusted for gestational age at delivery and antenatal steroids, no difference was seen in the primary outcome for intermittent absent end-diastolic flow (adjusted odds ratio, 0.73; 95% confidence interval, 0.20-2.68) and absent end-diastolic flow (adjusted odds ratio, 1.44; 95% confidence interval, 0.51-4.07). Among growth-restricted pregnancies, intermittent absent end-diastolic flow is associated with a similar rate of composite neonatal morbidity as persistently elevated Doppler waveforms. In addition, there is no difference in composite neonatal morbidity between the 3 groups when corrected for gestational age at delivery and antenatal steroid administration. These similar outcomes should be considered when creating an antenatal surveillance plan and discussing the potential for outpatient management.

Informing the Spectrum of Approaches: Institutional Review of Placenta Accreta Spectrum Disorders Management.

Placenta accreta spectrum (PAS) is a condition defined by abnormal adherence of the placenta. Cesarean hysterectomy is the preferred management, but practice patterns vary based on local resources and expertise. We retrospectively reviewed the clinical course of patients diagnosed antenatally with PAS who underwent surgical management in our centre. We conducted a retrospective records review involving patients with an antenatal diagnosis of PAS between 2014 and 2019. The primary outcome was a composite score of maternal morbidity, and secondary outcomes were total estimated blood loss and composite neonatal morbidity. Patients were stratifiedbased on the presence or absence of PAS on final pathology. Antenatal diagnosis by ultrasound and magnetic resonance imaging (MRI) was compared with final histologic diagnosis. A total of 34 patients were diagnosed with PAS antenatally and managed at our institution. Final histology confirmed PAS in 29 patients. The overall composite morbidity rate was 44%, with no significant difference between patients with and without PAS on pathology (P= 0.355). Intraoperative blood loss was similar between the 2 groups (2374 ± 2212 mL vs. 1080 ± 852 mL; P=0.232). The rate of composite neonatal morbidity was 47%. Ultrasound achieved a high positive predictive value in the diagnosis of PAS (96%) and more accurately predicted pathology than MRI. PAS is associated with high rates of morbidity. Dissemination of our local experience serves to inform best practices in the management of this complex condition.

Maternal and Neonatal Morbidity Associated With Early Term Delivery of Large-for-Gestational-Age But Nonmacrosomic Neonates

To evaluate whether, at 37-39 weeks of gestation, delivery of a neonate with a birth weight that is 90% or greater for gestational age but less than 4,000 g is associated with increased composite maternal and neonatal morbidity. This retrospective cohort study used U.S. Vital Statistics datasets for the years 2011-2013. Inclusion criteria were singleton pregnancies delivered at 37-39 weeks of gestation after labor in which the neonates were nonanomalous, and either appropriate for gestational age or large for gestational age (LGA) neonates with birth weights of less than 4,000 g (our threshold for macrosomia). The coprimary outcomes were composite maternal morbidity (any of the following: maternal transfusion, ruptured uterus, unplanned hysterectomy, admission to intensive care unit, or unplanned procedure) and composite neonatal morbidity (any of the following: Apgar score less than 5 at 5 minutes, assisted ventilation for more than 6 hours, seizure or serious neurologic dysfunction, significant birth injury or neonatal mortality). Multivariable Poisson regression models were used to calculate adjusted relative risk (aRR) and 95% CI. Among the 3.9 million women who met inclusion criteria, 1.3% delivered neonates who were LGA but nonmacrosomic. The rate of composite maternal morbidity was 53% higher women who delivered nonmacrosomic LGA neonate (6.27 vs 4.09/1,000 live births; aRR 1.40, 95% CI 1.25-1.56). This increased risk of composite maternal morbidity persisted in analyses stratified by diabetes. The rate of composite neonatal morbidity was 83% higher for nonmacrosomic LGA neonates (11.09 vs 6.07/1,000 live births; aRR 1.47, 95% CI 1.35-1.60) and persisted in analyses stratified by diabetes. At 37-39 weeks of gestation, delivery of a neonate with a birth weight that is 90% or greater for gestational age but less than 4,000 g is associated with increased composite maternal and neonatal morbidity.

402: Basal insulin analogs versus neutral protamine hagedorn for type 2 diabetics

Based on data from non-pregnant women, American Diabetes Association (ADA) recommends long- acting basal analogs (glargine or detemir) be used instead of intermediate-acting insulin (neutral protamine hagedorn [NPH]) to reduce adverse outcomes in type 2 diabetic (T2DM) (Diabetes Care, 2018). However, in pregnant women with T2DM there is a paucity of reports focused exclusively on T2DM. The aim of this study was to compare whether basal insulin analogs reduces rate of composite neonatal morbidity (CNM) and maternal adverse outcomes compared to NPH in women with T2DM. A retrospective cohort study of all women with T2DM and singleton pregnancy (March 2012 to May 2018) managed at a single tertiary center. Exclusion criteria were known major anomalies, diabetic nephropathy or proliferative retinopathy. The primary outcome was a CNM of any of the following: large for gestational age, shoulder dystocia, NICU admission, hypoglycemia (BS< 40 mg/dL in the first 24 hours of life or <50 mg/dL after 24 hours or requiring medical therapy) or RDS. Secondary outcomes were rates of maternal hypoglycemia events, hypertensive disorders, admission for glucose control, preterm birth (< 37 wks) and primary cesarean delivery. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated. Of 233 women with T2DM, 114 (49%) were treated with basal insulin analogs and 119 (51%) with NPH. Table 1 compares demographic and clinical characteristics. Significant differences on univariate analysis are bolded. The rate of CNM was similar between groups (73% vs 60%, aRR 1.16, 95% CI 0.90-1.49). Basal insulin treatment was associated with a lower risk for a primary cesarean delivery compared to NPH (21% vs 36%, aRR 0.43; 95% CI 0.24- 0.76). There were no differences in the rates of maternal hypoglycemic events, admission for glucose control, preeclampsia or preterm birth between the groups (Table2). The rate of CNM, neonatal or maternal hypoglycemia—were similar for T2DM managed with either basal or NPH insulin regimen. Since this is a retrospective study, a randomized trial enrolling patients with T2DM prior to 20 weeks of gestation and comparing short and long-term maternal and neonatal outcomes between the two treatment regimens is warranted.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The Relationship of Assisted Reproductive Technology on Perinatal Outcomes in Triplet Gestations.

To assess whether assisted reproductive technology (ART) is associated with increased risk of adverse perinatal outcomes in triplet gestations compared with spontaneous conception. Secondary analysis of a multicenter randomized trial for the prevention of preterm birth in multiple gestations. Triplets delivered at ≥ 24 weeks were studied. The primary outcome was the rate of composite neonatal morbidity (CNM) that included one or more of the following: bronchopulmonary dysplasia, respiratory distress syndrome, necrotizing enterocolitis, culture proven sepsis, pneumonia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, or perinatal death. There were 381 triplets (127 women) of which 89 patients conceived via ART and 38 patients spontaneously. Women with ART were more likely to be older, Caucasian, married, nulliparous, have higher level of education, and develop pre-eclampsia. Spontaneously conceived triplets were more likely to delivery at an earlier gestation (31.2 ± 3.5 vs 32.8 ± 2.7 weeks) (p = 0.009) with a lower birth weight (p < 0.001). After adjusting for confounders, no differences were noted in culture proven sepsis, perinatal death, CNM, respiratory distress syndrome, or Apgar score < 7 at 5 minutes. All remaining perinatal outcomes were similar. Triplets conceived by ART had similar perinatal outcomes compared with spontaneously conceived triplets.

983: Rate of Hyperglycemia and Adverse Outcomes among Gestational Diabetics

The diagnosis of gestational diabetes (GDM) typically entails blood glucose (BG) monitoring 4 times daily: fasting (F) and three postprandial (PP) values. The ideal threshold at when therapy should be initiated or modified is uncertain, with some suggesting when > 33% of values are above pre-specified thresholds and others, when > 50% are abnormal. The aim of this study was to determine if there exists a threshold in the percentage of abnormal BG values at any of the 4 scheduled testing timeframes that is associated with adverse perinatal outcomes. This was a secondary analysis of a randomized controlled trial at 5 tertiary centers evaluating the frequency of BG testing among GDM patients. BG values were defined as abnormal if: F were ≥ 95 mg/dl or if 2-hr PP values were ≥ 120 mg/dl. Composite neonatal morbidity (CNM) included any one of the following: Shoulder dystocia, large-for-gestational age (birthweight >90th% for GA), NICU admission, neonatal hypoglycemia or hyperbilirubinemia. Composite maternal morbidity (CMM) was the presence of either pre-eclampsia or indicated delivery for uncontrolled BG values. Patients with missing data for any of these outcomes were excluded. A receiver operating characteristics (ROC) analysis was used for each time point to determine if the percentage of abnormal BG was associated with CNM or CMM. Of the 293 women randomized, 282 (96%) were eligible for analysis. The rate of CNM was 35%, and of CMM, 18%. On average, women had 32 BG values for evaluation for fasting and 2hr PP. Baseline maternal characteristics were similar among women with and without CNM. Almost three-quarter of the patients did not require medical treatment. The proportion of chorioamnionitis (0.5% vs. 5%, p=0.02) and preterm labor (3.3% vs. 18%, p<0.01) were higher among women with CNM. The mean percentage of abnormal values at all each of the 4 testing timeframes was similar between both groups (Table). There was no difference in proportion of patients with ≥50% abnormal values throughout pregnancy. Area under the ROC curves demonstrated that the percentages of abnormal BG value was poor at identifying CNM or CMM (Figure). Among women with GDM, the percentage rate of abnormal BG values was poor predictor of composite maternal or neonatal morbidity; concurrently identifying an optimal threshold was not feasible.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Large for Gestational Age Infants and Adverse Outcomes among Uncomplicated Pregnancies at Term.

Background While traumatic delivery with large for gestational age (LGA; birth weight above 90%) is acknowledged, there is paucity of data regarding other morbidity and mortality associated with LGA. Our hypothesis was that compared with appropriate for gestational age (AGA), LGA have a significantly higher rate of composite neonatal morbidity (CNM). Objective Our objective was to compare the CNM among uncomplicated LGA versus AGA at term (37 weeks or more) among all available Maternal-Fetal Medicine Units (MFMU) databases. We excluded women who delivered before 37 weeks, those with hypertension or diabetes, multiple gestations, and known anomalies, and those with birth weight less than 10% for GA. Using multivariable analysis, we compared the CNM between LGA and AGA. Random-effect logistic regressions were used to account for study heterogeneity, with adjustment for potential confounders. We calculated adjusted odds ratio (aOR) and 95% confidence intervals (CI). Results Approximately 60% (n = 50,734) of all participants met inclusion criteria. Among uncomplicated pregnancies, the rate of LGA was 12.1%. The rate of CNM was 15% in LGA and 10% in AGA (aOR: 1.58; 95% CI: 1.46-1.70). The likelihood of stillbirth and neonatal mortality was similar among both groups. Subgroup analysis revealed that CNM was increased among both birth weight > 95% and birth weight 90 to 95% and at different GA at delivery. Conclusion Among uncomplicated pregnancies at term, LGA newborns, compared with AGA, have a significantly higher likelihood of CNM but similar stillbirth and neonatal death risk. Trials are warranted to determine appropriate management of LGA to decrease these risks.

Amniotic fluid discordance in monochorionic diamniotic twin pregnancies is associated with increased risk for twin anemia-polycythemia sequence.

To estimate the risk for twin anemia-polycythemia sequence (TAPS) and adverse perinatal outcome in monochorionic diamniotic (MCDA) twin pregnancies with amniotic fluid discordance (AFD). Retrospective cohort study of 34 MCDA pregnancies with AFD (intertwin difference of ≥3 cm in maximal vertical pocket measurement) without meeting the criteria for twin to twin transfusion syndrome or selective intrauterine growth restriction. Perinatal outcome measures and the risk for TAPS were compared with a control group consisted of 101 MCDA twin pregnancies without AFD, twin to twin transfusion syndrome, or selective intrauterine growth restriction. Composite neonatal morbidity was defined as the presence of respiratory distress syndrome, intraventricular hemorrhage grades 3 and 4, necrotizing enterocolitis or sepsis. Overall, in the AFD group, seven twin pairs (20.6%) were complicated by TAPS compared with none in the controls (p < 0.001). In the AFD group, women who developed TAPS had significantly higher AFD compared with women who did not develop TAPS (7.3 cm vs 4.2 cm, p < 0.01). Patients in the AFD group delivered earlier (34.6 vs 35.8 weeks, p < 0.001) and had significantly higher rate of composite neonatal morbidity compared with the control group (13.2 vs 2.5%, p = 0.002). Despite the overall favorable outcome, MCDA twins with AFD are at increased risk for developing TAPS. © 2016 John Wiley & Sons, Ltd.

Small-for-gestational-age infants among uncomplicated pregnancies at term: a secondary analysis of 9 Maternal-Fetal Medicine Units Network studies

Most small (birthweight <10%) for-gestational-age cases occur at term, in uncomplicated pregnancies, and are not identified during prenatal visits as having fetal growth restriction. Hence, they do not benefit from antepartum surveillance and timed delivery. There is dismissive and disquieting opinion that small for gestational age among uncomplicated pregnancies is not associated with increased morbidities and, therefore, does not warrant improved detection. Our hypothesis was that among uncomplicated pregnancies at term, small for gestational agehave significantly higher morbidity and mortality than appropriate (birthweight 10-89%) for gestational age. We sought to compare composite neonatal morbidity among uncomplicated term singleton pregnancies with small vs appropriate for gestational age. We culled collected data from 9 completed Maternal-Fetal Medicine Units studies conducted from 1989 through 2004. All data were collected prospectively by trained staff. We excluded women who delivered <37 weeks and those with hypertension or diabetes, multiple gestation, known anomalies, and birthweight of ≥90% for gestational age. Using multivariable analysis, we compared composite neonatal morbidity, which included stillbirth and neonatal mortality between small and appropriate for gestational age. Random effect logistic regressions were used to account for study heterogeneity, with adjustment for potential confounders. We calculated adjusted odds ratios and 95% confidence intervals. Of the >91,000 women enrolled in the studies, 60% (n=50,011) met the inclusion criteria. Among the uncomplicated pregnancies, 10.8% (n= 5416) were small for gestational age. The rate of composite neonatal morbidity of 16% in small for gestational age and 10% in appropriate for gestational age persisted (adjusted odds ratio, 1.75; 95% confidence interval, 1.71-1.78). After adjustment for confounders, the following neonatal morbidities were significantly more common among term small than appropriate for gestational age: Apgar <4 at 5 minutes, respiratory distress syndrome, mechanical ventilation, necrotizing enterocolitis grade 2 or 3, and neonatal sepsis. Lastly, rate of stillbirths (3.5 vs 0.9/1000 births; adjusted odds ratio, 3.49; 95% confidence interval, 1.83-6.67) and neonatal mortality (1.1 vs 0.4/1000 births; adjusted odds ratio, 2.56; 95% confidence interval, 1.83-3.57) were significantly more common with small than appropriate for gestational age. In secondary analyses the composite neonatal morbidity among newborns at <5% and at 5-9% was significantly higher than appropriate for gestational age. Lastly, in subgroup analyses of women who delivered at 37.0-38.6 weeks or at ≥39.0 weeks, the increased rate of composite neonatal morbidity, stillbirth, and neonatal mortality among small for gestational age persisted. Among uncomplicated pregnancies at term, small- compared to appropriate-for-gestational-age newborns have a significantly higher likelihood of composite neonatal morbidity, stillbirth, and neonatal mortality. A large multicenter trial is warranted to determine if improved detection of small for gestational age among uncomplicated pregnancies can mitigate morbidities and mortality, without disproportionate interventions and iatrogenic complications.

Risk of late-preterm stillbirth and neonatal morbidity for monochorionic and dichorionic twins

The purpose of this study was to determine the prospective risk of intrauterine fetal death (IUFD) at ≥34 weeks' gestation for monochorionic and dichorionic twins receiving intensive antenatal fetal surveillance. The secondary objective was to calculate the incidence of prematurity-related neonatal morbidity/mortality rates that have been stratified by gestational week and chorionicity. A retrospective cohort study of all twins at ≥34 weeks' gestation who were delivered at the Medical University of South Carolina (1987-2010) was performed. Twins were cared for in a longstanding Twin Clinic with standardized treatment and surveillance protocols and supervised by a consistent Maternal-Fetal Medicine specialist. Gestational age-specific fetal/neonatal mortality rates and composite neonatal morbidity rates were compared by chorionicity. A generalized linear mixed model was used to identify variables that were associated with increased composite neonatal morbidity. Among 768 twin gestations (601 dichorionic and 167 monochorionic), only 1 dichorionic IUFD occurred. The prospective risk of IUFD at ≥34 weeks' gestation was 0.17% for dichorionic twins and 0% for monochorionic twins. Composite neonatal morbidity decreased with each gestational week (P < .0001). Morbidity was increased by white race, gestational diabetes mellitus, and elective indication for delivery. The nadir of composite neonatal morbidity occurred at 36/0-36/6 weeks' gestation for monochorionic twins and 37/0-37/6 weeks' gestation for dichorionic twins. Our data do not support concern for an increased risk of stillbirth in uncomplicated intensively monitored monochorionic twins at ≥34 weeks' gestation. However, our data do show significantly increased rates of neonatal morbidity in late preterm monochorionic twins that cannot be justified by a corresponding reduction in the risk of stillbirth. We believe that our data support delivery of uncomplicated monochorionic twins at 37 weeks' gestation.

Should patients with documented fetal lung immaturity after 34 weeks of gestation be treated with steroids?

The purpose of this study was to determine whether corticosteroid administration after 34 weeks of gestation is associated with improved neonatal outcome in the presence of fetal lung immaturity. We conducted a retrospective cohort study of women who underwent amniocentesis to determine fetal lung maturity from 34-37 weeks of gestation. Patients with negative results (167 women) received steroids based on physician preference and were categorized into 2 groups: study group treated with betamethasone (n = 83 women) and control group in which patients did not receive betamethasone therapy (n = 84 women). The 2 groups were compared with respect to neonatal outcomes. Composite neonatal morbidity was defined as the presence of respiratory distress syndrome, transient tachypnea of the newborn infant, or the need for respiratory support. The rate of composite neonatal morbidity was significantly lower among infants who were exposed to steroids compared with the control group (8.4% vs 21%; P = .02). Multiple regression analysis revealed that corticosteroid administration was associated independently with the composite morbidity outcome. Antenatal steroid administration after 34 weeks of gestation is associated with improved neonatal outcome and should be considered when fetal lung immaturity is documented.

17-Hydroxyprogesterone caproate to prolong pregnancy after preterm rupture of the membranes: early termination of a double-blind, randomized clinical trial

BackgroundProgestational agents may reduce the risk of preterm birth in women with various risk factors. We sought to test the hypothesis that a weekly dose of 17-hydroxyprogesterone caproate (17P) given to women with preterm rupture of the membranes (PROM) will prolong pregnancy and thereby reduce neonatal morbidity.MethodsDouble-blind, placebo-controlled randomized clinical trial. Women with PROM at 23.0 to 31.9 weeks of gestation were randomly assigned to receive a weekly intramuscular injection of 17P (250 mg in 1 mL castor oil) or placebo (1 mL castor oil). The primary outcome was the rate of continuing the pregnancy until 34.0 weeks of gestation or until documentation of fetal lung maturity at 32.0 to 33.9 weeks of gestation. Planned secondary outcomes were duration of latency period and rate of composite neonatal morbidity. Enrollment of 111 participants per group, 222 total, was planned to yield 80% power to detect an increase in the primary outcome from 30% with placebo to 50% with 17P.ResultsTwelve women were enrolled of whom 4 were randomly assigned to receive 17P and 8 to receive placebo. The trial was terminated prematurely because of two separate issues related to the supply of 17P. No adverse events attributable to 17P were identified.ConclusionBecause of premature termination, the trial does not have adequate statistical power to evaluate efficacy or safety of 17P in women with PROM. Nonetheless, ethical principles dictate that we report the results, which may contribute to possible future metaanalyses and systematic reviews.Trial RegistrationClinicalTrials.gov: NCT01119963Supported by a research grant from the Center for Research, Education, and Quality, Pediatrix Medical Group, Sunrise, FL

Omphalocele: Clinical outcomes in cases with normal karyotypes

Objective This study was undertaken to examine neonatal outcomes in karyotypically normal cases of omphalocele with respect to mode of delivery, presence of associated anomalies, presence of extracorporeal liver, and method of abdominal wall closure. Study design We reviewed 36 cases of omphalocele with delivery at University of North Carolina Hospitals between 1988 and 2001. Elective terminations and pregnancies resulting in miscarriage before 20 weeks' gestation were excluded. Results Perinatal mortality rate was 19%. Rate of composite neonatal morbidity was 25%. Associated major anomalies were present in 11 (31%) cases and were associated with increased neonatal mortality. Cesarean deliveries were performed in 21 (58%) cases and were not associated with increased primary closure rates or decreased neonatal morbidity and mortality. Extracorporeal liver was present in 27 (75%) cases and was associated with decreased rates of primary closure but did not affect neonatal outcome. Conclusion In cases of ongoing omphalocele, perinatal mortality rates are low in the absence of associated anomalies or genetic defects. Intracorporeal liver was not associated with increased rates of associated anomalies or was it associated with increased neonatal morbidity or mortality.

Single vs Weekly Courses of Antenatal Corticosteroids for Women at Risk of Preterm Delivery: A Randomized Controlled Trial

This randomized, double-blind, placebo-controlled trial compared single with weekly courses of antenatal corticosteroids in 502 women at 24 to 32 completed weeks' gestation, seen at 13 academic centers in the United States. They were viewed as being at high risk of preterm delivery because of preterm labor with intact membranes; premature membrane rupture; maternal medical illness such as preeclampsia, diabetes, or hypertension: or suspected fetal jeopardy (intrauterine growth restriction, oligohydramnios, abnormal fetal test findings, a progressive fetal anomaly consistent with life, or twin-twin transfusion syndrome). All women received a complete course of antenatal steroids (12 mg of betamethasone intramuscularly, repeated once in 24 hours, or 6 mg of dexamethasone intramuscularly, repeated at 12-hour intervals for four doses). Those who did not deliver within 1 week then were randomly assigned to receive either betamethasone in the same dose every week up to 34 weeks' gestation or delivery, whichever came first, or placebo on the same schedule. Apgar scores were comparable in all groups. Composite neonatal morbidity rates (which took account of severe respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, proved sepsis, and death before discharge from the nursery) were 22.5% in the weekly-course group and 28.0% in the single-course group. The unadjusted relative risk was 0.80 (95% confidence interval, 0.59-1.10). Neither group assignment nor the number of treatment courses could be related to reduced composite morbidity. The difference in morbidity rates was statistically significant only in neonates delivered before 28 weeks' gestation. A reduction in severe respiratory distress syndrome accounted for this difference. Severe intraventricular hemorrhage was more frequent with the weekly treatment course, although not significantly so. No patient exhibited clinical changes of Cushing syndrome. The investigators believe that these findings do not warrant routine weekly antenatal steroid treatment for women at risk of delivering before term.