Maternal-Fetal Medicine Units Research Articles

Ambulatory management of multiple gestation.

Ambulatory management of multiple gestation requires careful and continuing care by the obstetrician. The initial evaluation should include a comprehensive history, including use of fertility enhancing drugs and ART, family history, social history; a general physical examination, including a pelvic examination; laboratory evaluation, including complete blood cell count, dipstick urinalysis for protein and glucose, urine culture, blood type, Rh factor and irregular blood antibody determination, serology for rubella, syphilis, hepatitis B surface antigen and varicella (if there is no history). A Papanicolaou smear should be done at the time of the pelvic examination, as should evaluation for bacterial vaginosis. Ultrasound assessment of placentation should be done at 14 weeks' gestation, but vaginal or perineal ultrasound of cervical length should be done at the initial visit. Other testing procedures should include repeat ultrasound evaluation for fetal growth every 4 weeks in a dichorionic placentation and every 3 weeks if monochorionic placentation is present. Triple screen MSAFP at 16-18 weeks' gestation and blood sugar screening at 22-26 weeks should be performed. After the first trimester, the patient should schedule physician visits every 2 weeks or less. Routine medications should include one prenatal vitamin per day, additional folic acid supplementation of 1.0 mg per fetus, supplemental iron preparation, and additional calcium to equal 1500 mg/day. The use of low-dose aspirin to prevent preeclampsia in twin gestations has not been adequately studied. Continuing vigilance by the knowledgeable obstetrician should occur. Multiple gestations should not be cared for by non-physician providers or by family physicians. Referral to a maternal-fetal medicine unit is recommended.

Antibiotic Therapy for Reduction of Infant Morbidity After Preterm Premature Rupture of the Membranes

Mercer, Brian M.; Miodovnik, Menachem; Thurnau, Gary R.; Goldenberg, Robert L.; Das, Anita F.; Ramsey, Risa D.; Rabello, Yolanda A.; Meis, Paul J.; Moawad, Atef H.; Iams, Jay D.; Van Dorsten, J. Peter; Paul, Richard H. Bottoms Sidney F.; Merenstein, Gerald; Thom, Elizabeth A.; Roberts, James M.; McNellis, DonaldAuthor Information

The effect of maternal magnesium sulfate treatment on neonatal morbidity in < or = 1000-gram infants.

We evaluated the effect of maternal magnesium sulfate treatment on selected neonatal outcomes in < or =1000-g infants. In a 1-year (1992-1993) observational study, the National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units collected outcome data for 799 infants whose birth weights were < or =1000 g. Only singleton infants, with a gestational age >20 weeks who were not the product of an induced abortion were included. Our analysis was further limited to those infants without major congenital anomalies, who were deemed potentially viable by the obstetrician, whose mother would have undergone a cesarean delivery for fetal indications, and who survived greater than 2 days. Outcomes were compared in infants whose mothers did and did not receive magnesium sulfate for labor tocolysis. Among the 124 women who did and the 184 who did not receive magnesium sulfate tocolytic therapy, the frequencies of grade III or IV intraventricular hemorrhage (16 vs. 20%, p = 0.34), seizure activity (7 vs. 10%, p = 0.35), grade III or IV retinopathy of prematurity (21 vs. 18% p = 0.59), abnormal neurological exam (28 vs. 28%, p = 0.91), intact survival to 120 days or to discharge (48 vs. 44%, p = 0.54), and infant mortality (23 vs. 31%, p = 0.10) were similar. Multiple logistic regression analysis was used to control for the effect of potential confounders (specifically, gestational age) and confirmed the lack of a significant association between maternal magnesium sulfate treatment for tocolysis and selected neonatal outcomes in this population of < or =1000-gram infants.

Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network

Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network

Antibiotic Therapy for Reduction of Infant Morbidity After Preterm Premature Rupture of the Membranes

Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent. To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity. Randomized, double-blind, placebo-controlled trial. University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization. Intravenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization. The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed. In the total study population, the primary outcome (44.1 % vs 52.9%; P=.04), respiratory distress (40.5% vs 48.7%; P=.04), and necrotizing enterocolitis (2.3% vs 5.8%; P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%; P=.03), respiratory distress (40.8% vs 50.6%; P=.03), overall sepsis (8.4% vs 15.6%; P=.01), pneumonia (2.9% vs 7.0%; P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P<.001). We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity.

The Preterm Prediction Study: Association of cesarean delivery with increases in maternal weight and body mass index

Objective: Our purpose was to evaluate whether maternal weight and body mass index measured either before or during pregnancy are associated with an increased risk of cesarean delivery. Study design: Maternal weight and height were prospectively collected on 2929 women in the National Institutes of Health Maternal-Fetal Medicine Units Network Preterm Prediction Study. Prepregnancy and 27- to 31-week maternal weight and height were used to calculate the body mass index, and its contribution to the risk of cesarean delivery was determined. Women with prenatally diagnosed congenital anomalies ( n = 89) and pregestational diabetes ( n = 31) were excluded from analysis. Results: Univariate analysis of risk factors for cesarean delivery in the 2809 eligible women revealed a decreased risk of cesarean delivery with maternal age <18 years and multiparity; increased risk of cesarean delivery was noted with maternal age >35 years and a male fetus. Increases in either prepregnancy or 27- to 31-week maternal weight (5-pound units) or body mass index (1.0 kg/m 2 units) were significantly associated with an increased odds of cesarean delivery ( p = 0.0001). Each unit increase in prepregnancy or 27- to 31-week body mass index resulted in a parallel increase in the odds of cesarean delivery of 7.0% and 7.8%, respectively. Multivariable stepwise logistic regression analysis confirmed the association of male fetus, age, nulliparity, and body mass index as significant variables contributing to cesarean delivery risk. Conclusions: The risk of cesarean delivery is associated with incremental changes in maternal weight and body mass index before and during pregnancy after adjustment for potential confounding factors. Prepregnancy counseling about optimizing maternal weight and monitoring weight gain during pregnancy to decrease the risk of cesarean delivery are supported by this study. (Am J Obstet Gynecol 1997;177:333-41.)

Obstetric determinants of neonatal survival: Influence of willingness to perform cesarean delivery on survival of extremely low-birth-weight infants

OBJECTIVE: Our purpose was to evaluate the relationship between the approach to obstetric management and survival of extremely low-birth-weight infants. STUDY DESIGN: In this prospective observational study we evaluated 713 singleton births of infants weighing ≤1000 gm during 1 year at the 11 tertiary perinatal care centers of the National Institutes of Child Health and Human Development network of maternal-fetal medicine units. Major anomalies, extramural delivery, antepartum stillbirth, induced abortion, and gestational age <21 weeks were excluded. The obstetrician's opinion of viability and willingness to perform cesarean delivery in the event of fetal distress were ascertained from the medical record or interview when documentation was unclear. Grade 3 and 4 intraventricular hemorrhage, grade 3 and 4 retinopathy of prematurity, necrotizing enterocolitis requiring surgery, oxygen dependence at discharge or 120 days, and seizures were considered serious morbidity. Survival without serious morbidity was considered intact survival. Logistic regression was used to evaluate the influence of the approach to obstetric management, adjusted for birth weight, growth, gender, presentation, and ethnicity. RESULTS: Willingness to perform cesarean delivery was associated with increased likelihood of both survival (adjusted odds ratio 3.7, 95% confidence interval 2.3 to 6.0) and intact survival (adjusted odds ratio 1.8, 95% confidence interval 1.0 to 3.3). Willingness to intervene for fetal indications appeared to virtually eliminate intrapartum stillbirth and to reduce neonatal mortality. Below 800 gm or 26 weeks, however, willingness to perform cesarean delivery was linked to an increased chance of survival with serious morbidity. Although obstetricians were willing to intervene for fetal indications in most cases by 24 weeks, willingness to perform cesarean delivery was associated with twice the risk for serious morbidity at that gestational age. CONCLUSIONS: The approach to obstetric management significantly influences the outcome of extremely low-birth-weight infants. Above 800 gm or 26 weeks the obstetrician should usually be willing to perform cesarean delivery for fetal indications. Between 22 and 25 weeks willingness to intervene results in greater likelihood of both intact survival and survival with serious morbidity. In these cases patients and physicians should be aware of the impact of the approach to obstetric management and consider the likelihood of serious morbidity and mortality when formulating plans for delivery. (Am J Obstet Gynecol 1997;176:960-6.)

HISTOLOGIC FEATURES OF CHORIOAMNION MEMBRANE RUPTURE: Development of Methodology

This study developed a set of histologic features that will allow subclassification of placentas with preterm premature rupture of membranes. Placentas were obtained from patients participating in a multi-institutional NICHD Maternal-Fetal Medicine Unit Network study of antimicrobial therapy after preterm premature rupture of membranes. The rupture site was sampled by inking the open sac margin and rolling a membrane strip in four quadrants from the ink to the placental margin. Independently, four pathologists used a provisional feature list to score the slides from 15 placentas. A concordance analysis was performed on those results. With those results, the slides were reviewed concurrently to discover the source of disagreements and to revise the feature list. The sampling method frequently demonstrated a rupture site with histology distinct from that of the remainder of the membranes. After review of the preliminary scoring results, 29 features of membrane histology present in preterm premature rupture could be objectively described with agreement among four pathologists. The feature list allows both novel and commonly recognized histologic features of fetal membranes to be recorded with objectivity. This list, with the described sampling technique, is presented as a tool for clinical correlation in studies of membrane rupture, especially in preterm, premature rupture.

Histologic Features of Chorioamnion Membrane Rupture: Development of Methodology

This study developed a set of histologic features that will allow subclassification of placentas with preterm premature rupture of membranes. Placentas were obtained from patients participating in a multi-institutional NICHD Maternal-Fetal Medicine Unit Network study of antimicrobial therapy after preterm premature rupture of membranes. The rupture site was sampled by inking the open sac margin and rolling a membrane strip in four quadrants from the ink to the placental margin. Independently, four pathologists used a provisional feature list to score the slides from 15 placentas. A concordance analysis was performed on those results. With those results, the slides were reviewed concurrently to discover the source of disagreements and to revise the feature list. The sampling method frequently demonstrated a rupture site with histology distinct from that of the remainder of the membranes. After review of the preliminary scoring results, 29 features of membrane histology present in preterm premature rupture could be objectively described with agreement among four pathologists. The feature list allows both novel and commonly recognized histologic features of fetal membranes to be recorded with objectivity. This list, with the described sampling technique, is presented as a tool for clinical correlation in studies of membrane rupture, especially in preterm, premature rupture.

Route of delivery for the breech presentation: A conundrum

OBJECTIVE: Our purpose was to determine the feasibility of resolving the controversy regarding route of delivery for breech presentation in a randomized, prospective fashion.STUDY DESIGN: The National Institute of Child Health and Human Development-sponsored Maternal-Fetal Medicine Units Network, which is composed of 11 perinatal centers, was surveyed to determine the feasibility of a randomized clinical trial of cesarean section versus trial of labor for breech presentation. A review of the literature was performed to determine the experience of other investigators with designing and conducting an adequate prospective, randomized trial.RESULTS: Principal investigators and faculty from seven of 11 centers within the Maternal-Fetal Medicine Units Network agreed to participate and felt that they could adequately recruit patients for a trial in very-low-birth-weight infants. This would provide approximately 200 very-low-birth-weight fetuses in a breech presentation per year. Sample size calculations indicated that 1700 infants would be required. Investigators also had strong reservations about performing a trial of vaginal breech delivery for other gestational ages. A review of the literature indicates that other authors have encountered difficulty in attempting randomized clinical trials of this nature.CONCLUSIONS: The Maternal-Fetal Medicine Units Network with its pool of 60,000 deliveries per year agreed that a randomized, controlled delivery route of labor in the 24- to 28-week breech presentation was not feasible in a reasonable period of time. A randomized clinical trial of larger fetuses in a breech presentation was also considered extremely difficult. These findings are similar to those of other authors who have attempted or proposed randomized clinical trials to determine the safety of planned vaginal delivery of the breech presentation at various gestational ages.

Antibiotic treatment of preterm labor with intact membranes: A multicenter, randomized, double-blinded, placebo-controlled trial

Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes. A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos. Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization. The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes.