Joni Evans

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.

Factors predictive of outcome in severe lupus nephritis

In 1992, we published the results of a prospective, controlled trial of aggressive therapy (high-dose prednisone plus oral cyclophosphamide alone or with plasmapheresis) in 86 patients with severe lupus nephritis. During this study, remission (serum creatinine < or =1.4 mg/dL [< or =123 micromol/L] and proteinuria < or =330 mg/d of protein) in renal disease occurred in 37 patients (43%). To assess the long-term effect of remission on patient and renal survival, we now report the results of our extended follow-up of these patients. After an average of 10 years of follow-up in the 86 patients, patient survival rates at both 5 and 10 years were 95% in the group that had a remission and 69% at 5 years and 60% at 10 years in the no-remission group (P < 0.001). Renal survival rates were 94% at both 5 and 10 years in the remission group compared with 46% at 5 years and 31% at 10 years in the no-remission group (P < 0. 0001). Features predictive of remission included stable renal function after 4 weeks on therapy, category IV lesion, lower chronicity index, white race, lower urine protein excretion level at baseline, and lower baseline serum creatinine level. The features predictive of end-stage renal disease were higher baseline serum creatinine level, presence of anti-Ro antibodies, and failure to attain a remission. Thus, in patients with the most severe forms of lupus nephritis, a remission of clinical renal abnormalities is associated with dramatic improvement in long-term patient and renal survival.

Severe Lupus Nephritis: Racial Differences in Presentation and Outcome

This study assessed whether certain clinicopathologic variables could explain the impact of race on outcome in 86 patients who had severe lupus nephritis and were available for long-term follow-up after participating in a prospective, controlled, clinical trial. Fifty-four (63%) patients were white, 21 (24%) were black, and 11 (13%) were categorized as other. The proportion of patients with anti-Ro, anti-nRNP, and anti-Sm was significantly greater among black patients. Biopsies with segmental active proliferative and necrotizing lesions that involved >or=50% of glomeruli +/- membranous glomerulonephritis (class III >or=50%+/-V) were significantly more common (white 44%, black 76%, other 36%; P < 0.05) and diffuse proliferative glomerulonephritis +/- membranous glomerulonephritis (class IV+/-V) was less common (white 54%, black 24%, other 64%) among black patients. Attainment of a remission was greatest among white patients (white 52%, black 29%, other 27%; P = 0.09). Features that were predictive of a remission were white race, baseline serum creatinine, and class IV+/-V lesions. Patient survival at 10 yr (white 81%, black 59%, other 73%; P = 0.029) and renal survival at 10 yr (white 68%, black 38%, other 61%; P = 0.015) were significantly poorer in black patients. Predictors of ESRD were serum creatinine, the presence of anti-Ro antibodies, class III >or=50%+/-V lesions, and failure to achieve a remission. In conclusion, racial differences were observed in the serologic and histologic features at presentation, response to treatment, and outcome of patients with severe lupus nephritis. In a population of patients with severe lupus nephritis, black patients were significantly more likely to have a serologic profile and renal lesions that were associated with more aggressive renal disease and resulted in worse outcomes than white patients.

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.

Determinants of preterm delivery in low-risk pregnancies

From 14,948 low-risk singleton pregnancies, we calculated incidence, risk ratios, and attributable risks for characteristics associated with spontaneous and medically induced preterm delivery. There were 754 women who gave birth prior to 37 weeks of gestation (50.4/1000 deliveries). The greatest fraction of the incidence of prematurity among low-risk pregnancies was due to unknown factors associated with carrying a first live birth, regardless of preterm delivery mechanism (i.e., spontaneous labor, PROM, medical intervention), with population-attributable risk percents (PAR%) ranging from 16.0 to 30.5%. Other than nulliparity, male sex of the fetus accounted for the greatest fraction of spontaneous labor-induced prematurity incidence (PAR% = 13.6%), and maternal age greater than 30 years or a positive urine culture accounted for the greatest fraction of PROM-induced prematurity incidence (PAR% = 7.9 and 6.7, respectively). All other risk factors for either preterm labor or PROM accounted for less than 5% of the incidence. Three characteristics explained a large fraction of medically induced prematurity: women over 150 pounds at the onset of pregnancy (PAR% = 23.8), a > or = 2+ prenatal urine protein (PAR% = 18.7%), and cigarette smoking during the first trimester (PAR% = 8.6). Our results suggest known risk factors may explain only a small fraction of spontaneous preterm delivery incidence in low-risk pregnancies.

Epidemiologic predictors of cesarean section in nulliparous patients at low risk

OBJECTIVES We sought to determine whether certain maternal and fetal characteristics influenced the risk of maternal- and fetal-indicated cesarean sections in pregnant women at low risk for adverse perinatal outcomes. STUDY DESIGN From a cohort of 6393 low-risk nulliparous patients maternal and fetal indicated cesarean section rates with 95% confidence intervals were calculated and stratified by demographic, anthropometric, and clinical tests and measurements. The strongest risk factors were modeled by means of multiple logistic regression. RESULTS Few risk factors distinguished maternal from fetal characteristics preceding cesarean delivery. Maternal age was associated with increased cesarean section risk in the tallest group of women only, and cesarean section rates decreased with increasing height, increased with higher prepregnancy weights, and was highest in women carrying male fetuses. Higher first prenatal visit diastolic blood pressure, increasing numbers of nonstress tests, > or = 2+ prenatal urine protein, late sonograms, geographic region, and practice type were statistically significant risk factors as well. Interestingly, results of prenatal visit tests and measurements contributed less to the prevalence of cesarean section than did age, fetal sex, and anthropometric parameters. However, the generalizability of these results is limited to low-risk (predominantly white) populations. CONCLUSIONS Of the risk factors we were able to assess, a large proportion of the incidence of cesarean section in this population of nulliparous patients at low risk was attributable to age, sex of fetus, and anthropometric patient profiles.