Donald McNellis

Low-Dose Aspirin to Prevent Preeclampsia in Women at High Risk

Background Whether low-dose aspirin prevents preeclampsia is unclear. It is not recommended as prophylaxis in women at low risk for preeclampsia but may reduce the incidence of the disease in women at high risk. Methods We conducted a double-blind, randomized, placebo-controlled trial in four groups of pregnant women at high risk for preeclampsia, including 471 women with pregestational insulin-treated diabetes mellitus, 774 women with chronic hypertension, 688 women with multifetal gestations, and 606 women who had had preeclampsia during a previous pregnancy. The women were enrolled between gestational weeks 13 and 26 and received either 60 mg of aspirin or placebo daily. Results Outcome data were obtained on all but 36 of the 2539 women who entered the study. The incidence of preeclampsia was similar in the 1254 women in the aspirin group and the 1249 women in the placebo group (aspirin, 18 percent; placebo, 20 percent; P = 0.23). The incidences in the aspirin and placebo groups for each of the four hi...

Risk factors for preeclampsia, abruptio placentae, and adverse neonatal outcomes among women with chronic hypertension

Background Women with chronic hypertension who become pregnant have an increased risk of preeclampsia and adverse neonatal outcomes. However, within this group, the risk factors for these adverse events are not known. Methods We analyzed data on outcomes for 763 women with chronic hypertension enrolled in a multicenter trial of low-dose aspirin for the prevention of preeclampsia. Preeclampsia was defined as new-onset proteinuria (urinary protein excretion, ≥300 mg per 24 hours) in the 682 women without proteinuria at base line. It was defined according to strict clinical criteria in the 81 women who had proteinuria at base line. The end points were maternal and neonatal outcomes. Results Among the 763 women, 193 (25 percent) had preeclampsia. The frequency of preeclampsia was not affected by the presence of proteinuria at base line (27 percent among women with proteinuria, vs. 25 percent among those without it), but it was greater in women who had had hypertension for at least four years (31 percent vs. 2...

A randomized trial of prenatal ultrasonographic screening: Impact on the detection, management, and outcome of anomalous fetuses

OBJECTIVE The objective of this randomized clinical trial was to test the hypothesis that ultrasonographic screening would significantly alter perinatal outcome as a result of the antenatal detection of fetal congenital malformations. STUDY DESIGN Pregnant women without a specific indication for ultrasonography were randomly assigned to have either two screening sonograms (15 to 22 weeks and 31 to 35 weeks) or conventional obstetric care with ultrasonography used only as determined by the clinical judgment of the patients physician. The frequency of birth defect detection in the screened and control populations was compared, as was the impact of discovery on pregnancy outcome. RESULTS Major congenital malformations occurred in 2.3% of the 15,281 fetuses and infants in this study. Antenatal ultrasonography detected 35% of the anomalous fetuses in the screened group versus only 11% in the control population (relative detection rate 3.1; 95% confidence interval 2.0 to 5.1). Ultrasonography screening did not, however, significantly influence the management or outcome of pregnancies complicated by congenital malformations. Specifically, only 9 abortions were performed for anomalies among 7685 fetuses in the screened group whereas 4 pregnancies were terminated for fetal anomalies detected among 7596 control subjects. Ultrasonography screening also had no significant impact on survival rates among infants with potentially treatable, life-threatening anomalies despite the opportunity to take precautionary measures such as delivery in a tertiary center. CONCLUSIONS Ultrasonography screening in a low-risk pregnant population had no significant impact on the frequency of abortion for fetal anomalies. Survival rates for anomalous fetuses were also unaffected by screening.

The preterm prediction study: Fetal fibronectin testing and spontaneous preterm birth*

Objective To evaluate the presence of fetal fibronectin in the cervix and vagina as a screening test for spontaneous preterm birth. Methods Two thousand nine hundred twenty-nine women at ten centers were routinely screened every 2 weeks from 22–24 to 30 weeks for cervical and vaginal fetal fibronectin. A positive test was defined as a value equal to or greater than 50 ng/mL. The relation between a positive test at four gestational ages and spotaneous pretern birth at various intervals after the test was determined. Results In each testing period 3–4% of the fetal fibronectin tests were positive. The correlation between cervical and vaginal fetal firbonectin at the same visit was always approximately 0.7 (P < .001), and that between cervical or vaginal fetal fibronectin in consecutive visits was between 0.17 and 0.25 (P < .001). The sensitivity of fetal fibronectin at 22–24 weeks to predict spontaneous preterm birth at less than 28 weeks was 0.63, and the relative risk for a positive versus negative test was 59. The specificity was always 96–98%, whereas the positive predictive value rose from 13% to 36% as the upper limit of the definition of preterm birth was increased from less than 28 to less than 37 weeks. The relative risk for spontaneous preterm birth after a positive fetal fibronectin test compared with a negative fetal fibronectin test varied substantially by testing period and by the definition of spontaneous preterm birth, but always remained greater than 4 and statistically significant. Conclusion A positive cervical or vaginal fetal fibronectin test at 22–24 weeks predicted more than half of the spontaneous preterm births at less than 28 weeks (sensitivity 0.63). As the definition of spontaneous preterm birth was extended to include later gestational ages or when the fetal fibronectin test was performed later in pregnancy, the level of association between a positive fetal fibronectin test and spontaneous preterm birth, while remaining highly significant, tended to decrease. Although fetal fibronectin is an excellent test for predicting spontaneous preterm birth, we present no evidence that the use of this test will result in a reduction in spontaneous preterm birth.

Asthma during pregnancy

OBJECTIVE: To determine neonatal and maternal outcomes stratified by asthma severity during pregnancy by using the 1993 National Asthma Education Program Working Group on Asthma and Pregnancy definitions of asthma severity. The primary hypothesis was that moderate or severe asthmatics would have an increased incidence of delivery at <32 weeks of gestation compared with nonasthmatic controls. METHODS: This was a multicenter, prospective, observational cohort study conducted over 4 years at 16 university hospital centers. Asthma severity was defined according to the National Asthma Education Program Working Group on Asthma and Pregnancy classification and modified to include medication requirements. This study had 80% power to detect a 2- to 3-fold increase in delivery less than 32 weeks of gestation among the cohort with the moderate or severe asthma compared with controls. Secondary outcome measures included obstetrical and neonatal outcomes. RESULTS: The final analysis included 881 nonasthmatic controls, 873 with mild asthma, 814 with moderate, and 52 with severe asthma. There were no significant differences in the rates of preterm delivery less than 32 weeks (moderate or severe 3.0%, mild 3.4%, controls 3.3%; P = .873) or less than 37 weeks of gestation. There were no significant differences for neonatal outcomes except discharge diagnosis of neonatal sepsis among the mild group compared with controls, adjusted odds ratio 2.9, 95% confidence interval 1.2, 6.8. There were no significant differences for maternal complications except for an increase in overall cesarean delivery rate among the moderate-or-severe group compared with controls (adjusted odds ratio 1.4, 95% confidence interval 1.1, 1.8). CONCLUSION: Asthma was not associated with a significant increase in preterm delivery or other adverse perinatal outcomes other than a discharge diagnosis of neonatal sepsis. Cesarean delivery rate was increased among the cohort with moderate or severe asthma. LEVEL OF EVIDENCE: II-2

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

OBJECTIVE 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. STUDY DESIGN 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. RESULTS 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. CONCLUSION The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes.

Predictors of pre-eclampsia in women at high risk

OBJECTIVE We assessed several variables as predictors for pre-eclampsia risk in a group of women at high risk. STUDY DESIGN We studied 2503 women with either diabetes mellitus, chronic hypertension, multifetal gestation, or pre-eclampsia in a previous pregnancy who participated in a multicenter study comparing aspirin and placebo in preventing pre-eclampsia. We evaluated multiple variables for predicting pre-eclampsia risk with use of univariate and multivariable analysis. RESULTS Parity and mean arterial pressure at randomization were most predictive of pre-eclampsia risk. The risk was 8% with a mean arterial pressure at enrollment of <75 mm Hg versus 27% with a mean arterial pressure >85 mm Hg (relative risk and 95% confidence interval 3.3 [2.4 to 4.4]). The risk of pre-eclampsia was 26% in nulliparous patients versus 17% in parous subjects (relative risk and 95% confidence interval 1.5 [1.3-1.8]). CONCLUSIONS The finding that second-trimester mean arterial pressure affects pre-eclampsia risk suggests that the pathophysiologic process of preeclampsia is initiated before that time.

A randomized trial of prenatal ultrasonographic screening: Impact on maternal management and outcome

OBJECTIVES This randomized clinical trial of 15,530 women was designed to test the hypothesis that screening ultrasonography in low-risk pregnancies would improve perinatal outcome. A secondary hypothesis addressed in this article was that screening ultrasonography would have a favorable impact on maternal management or outcome. STUDY DESIGN Pregnant women without a specific indication for ultrasonographic examination in early pregnancy were randomly assigned to have either two screening sonograms or conventional obstetric care. Pregnancy interventions and maternal outcomes were compared in the two groups. RESULTS No significant differences were found in maternal outcomes. Use of ultrasonography was markedly higher in the screened group. The rates of induced abortion, amniocentesis, tests of fetal well-being, external version, induction, and cesarean section and the distribution of total hospital days were similar in the two groups. Use of tocolytics and the rate of postdate pregnancy were both slightly lower in the screened group. CONCLUSION Screening ultrasonography resulted in no clinically significant benefit.

Frequency of congenital varicella syndrome in a prospective cohort of 347 pregnant women

OBJECTIVE To estimate the rate of congenital varicella zoster virus syndrome in neonates born to women developing varicella zoster virus infections during pregnancy. METHODS Pregnant women with clinical varicella zoster virus infection were enrolled at ten perinatal centers. Maternal and fetal immunoglobulin (Ig) G and IgM by fluorescent antibody confirmed 74.3% of cases. Specialists examined neonates at 0–6 months, 7–18 months, and 19–30 months after delivery to detect abnormalities of their eyes, hearing, and physical and developmental features. A hierarchical set of criteria was used to define congenital varicella syndrome. A jury of four investigators assigned the classification of all findings. RESULTS In 362 women enrolled from 1993 to 1996, 15 had herpes zoster, and 347 had primary varicella zoster virus infection. Varicella zoster virus affected 140 women (38.7%) in the first trimester, 122 (33.7%) in the second trimester, and 100 (27.6%) in the third trimester. Five twin pairs were included. Only one case (0.4%) of definite congenital varicella syndrome was found, a 3360‐g female infant having a left retinal macular lesion with typical skin scars after maternal varicella at 24 weeks. The maternal blood sample at birth was negative for IgG antibodies to toxoplasmosis and cytomegalovirus. Two cases involved fetal death at 20 weeks and fetal hydrops at 17 weeks after maternal varicella at 11 and 5 weeks, respectively. We found no cases of limb hypoplasia, microcephalus, or cataract. CONCLUSION The frequency of congenital varicella syndrome is very low (0.4%) in a prospectively studied cohort. Eye examinations of exposed infants had a low yield.

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/m2 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.