Nergesh Tejani

Obstetric antecedents of intraventricular hemorrhage and periventricular leukomalacia in the low-birth-weight neonate☆☆☆★

OBJECTIVE Neonatal intraventricular hemorrhage and periventricular leukomalacia have a strong correlation with eventual neurologic deficit. Our objective was to correlate obstetric factors with the development of these lesions. STUDY DESIGN Seven hundred forty-five consecutive inborn neonates with birth weights from 500 to 1750 gm were divided into three clinical groups: premature rupture of membranes, refractory preterm labor with intact membranes, and delivery initiated by the physician for maternal or fetal indications. Neonatal neurosonography was performed on days 3 and 7 of life and results were described as normal or abnormal. Abnormal scans included intraventricular hemorrhage seen within 3 days and echodense or echolucent periventricular leukomalacia seen within 7 days of life. Major abnormalities included intraventricular hemorrhage grades 3 and 4, intraventricular hemorrhage with periventricular leukomalacia, and echolucent periventricular leukomalacia. Abnormal scans were correlated with groups of origin and clinical and histologic chorioamnionitis. RESULTS Abnormal scans occurred in 33% of cases of premature rupture of membranes and in 38.9% of cases of preterm labor compared with 17.7% of physician-initiated cases (p < 0.000001). Major lesions occurred in 17.6% of cases of premature rupture of membranes, 21.4% of cases of preterm labor, and 1.1% of physician-initiated cases (p < 0.0000001). Clinical chorioamnionitis occurred in 19.7% of cases of premature rupture of membranes, 11.9% of cases of preterm labor, and 1.1% of physician-initiated cases (p < 0.001) and was associated with a significant increase in the incidence (p < or = 0.005) and severity (p < or = 0.007) of these lesions. Histologic chorioamnionitis occurred in 59.9% of cases of premature rupture of membranes, 43.2% of cases of preterm labor, and 8% of physician-initiated cases and did not correlate significantly with the incidence or severity of abnormal scans. These findings were independent of gestational age. CONCLUSIONS The incidence and severity of intraventricular hemorrhage and periventricular leukomalacia were significantly increased in premature rupture of membranes and preterm labor compared with the physician-initiated cases. Clinical chorioamnionitis increased the incidence and severity of these lesions.

Histologic chorioamnionitis, antenatal steroids, and perinatal outcomes.

Objective To determine the perinatal effects of histologic chorioamnionitis on preterm neonates and the effectiveness of antenatal steroids in the presence of histologic chorioamnionitis. Methods We studied neonates at our institution who weighed 1750 g or less at birth from January 1990 through December 1997. The population was stratified primarily by presence of histologic chorioamnionitis and secondarily by exposure to antenatal steroids. Subgroups were compared by various perinatal outcomes and confounding variables. Student t test, χ2, Fisher exact test, and logistic regression were used for analysis. Results Among 1260 neonates entered, the placentas of 527 had evidence of histologic chorioamnionitis and 733 did not. Those with histologic chorioamnionitis had a lower mean gestational age, lower birth weight, and higher rate of major neonatal morbidities than those without it. After adjusting for confounding variables, histologic chorioamnionitis independently associated with lower gestational age, lower birth weight, and neonatal death. Among neonates exposed to antenatal steroids who had histologic chorioamnionitis, there was a significantly lower incidence of low Apgar scores (18% compared with 33.5%, P < .001), respiratory distress syndrome (RDS) (39.6% compared with 55.9%, P < .001), intraventricular hemorrhage and periventricular leukomalacia (21.9% compared with 36.9%, P < .001), major brain lesions (7.7% compared with 18.4%, P < .001), patent ductus arteriosus (14.8% compared with 23.7%, P = .018), and neonatal death (8.3% compared with 16.2%, P = .02), with no increase in rate of proven neonatal sepsis (18.3% compared with 14%, P = .24). Conclusion Histologic chorioamnionitis increases major perinatal morbidity through its association with preterm birth and is independently associated with neonatal death. In the presence of histologic chorioamnionitis, antenatal steroids significantly decreased the incidence of RDS, intraventricular hemorrhage and periventricular leukomalacia, major brain lesions, and neonatal mortality, without increasing neonatal sepsis.

Placenta Accreta and Methotrexate Therapy: Three Case Reports

Placenta accreta is a complication that is rising in incidence. The reported experience of methotrexate treatment in the conservative management of placenta accreta is scant. Three cases of placenta accreta managed with methotrexate are presented.Case 1: A woman had an antenatal diagnosis of placenta percreta. A successful manual placental removal occurred on post-cesarean day 16. Case 2: A woman had retention of a placenta accreta after a term vaginal delivery. Successful dilation and curettage were performed on postpartum day 37. Case 3: A woman had an antenatal diagnosis of placenta previa-percreta with bladder invasion. A simple hysterectomy was performed on post-cesarean day 46.Conservative management and methotrexate treatment resulted in uterine preservation in two of our three patients; however, this treatment did not prevent significant delayed hemorrhage. In view of the rapid resolution of vascular invasion of the bladder, methotrexate may have an important role in the management of placenta percreta with bladder invasion. The utility of methotrexate treatment with the conservative management of placenta accreta requires further evaluation.

Effectiveness of antenatal steroids in obstetric subgroups

OBJECTIVE To determine the effectiveness of antenatal steroids in the reduction of neonatal morbidity and mortality in obstetric subgroups of preterm labor with intact membranes, preterm premature rupture of membranes (PROM), and pregnancy-associated hypertension. The secondary objective was to determine the effect of antenatal steroids in appropriate for gestational age (AGA) and growth-restricted neonates. METHODS We studied the neonatal outcomes for all women who delivered infants weighing 1750 g or less at birth between January 1990 and July 1997 at our institution. The study population was divided primarily into three clinical groups: preterm labor with intact membranes, PROM, and pregnancy-associated hypertension. Secondarily, the total population was divided based on birth weight and gestational age into AGA and growth-restricted neonates. Within each obstetric subgroup, neonates exposed to antenatal steroids were compared with unexposed neonates for respiratory distress syndrome (RDS), intraventricular hemorrhage and periventricular leukomalacia, the incidence of major brain lesions, necrotizing enterocolitis, proved neonatal sepsis, patent ductus arteriosus, and neonatal death. The subgroups were also compared for gestational age at delivery, birth weight, birth weight percentile, Apgar scores, postnatal surfactant exposure, and clinical and histologic chorioamnionitis. Descriptive statistics, Student t test, chi2, Fisher exact test, and logistic regression were used for analysis. RESULTS A total of 1148 neonates weighing 1750 g or less were delivered during the study period. There were 447 and 410 neonates delivered after preterm labor with intact membranes and PROM, respectively, and 245 neonates born to mothers with pregnancy-associated hypertension. Nine hundred twenty-eight neonates were AGA and the remaining 220 neonates were growth restricted. Antenatal steroids significantly decreased the incidence of RDS, the incidence and severity of intraventricular hemorrhage and periventricular leukomalacia, necrotizing enterocolitis, and neonatal mortality in preterm labor with intact membranes. In the presence of PROM, it significantly decreased the incidence and severity of intraventricular hemorrhage and periventricular leukomalacia and decreased neonatal mortality, with no apparent effect on the incidence of RDS. Antenatal steroids did not show any beneficial effect in pregnancy-associated hypertension and fetal growth restriction (FGR). Additionally, a significant increase was observed in the incidence of proved neonatal sepsis when antenatal steroids were used in pregnancy-associated hypertension. CONCLUSION The effectiveness of antenatal steroids varies with the obstetric population studied. Antenatal steroids significantly decreased the incidence of major neonatal morbidity and mortality in the AGA preterm neonate delivered after preterm labor with intact membranes. Antenatal steroids did not show any benefit in cases of pregnancy associated with maternal hypertension or FGR. Its effect in the presence of PROM is limited to a significant reduction in the incidence and severity of intraventricular hemorrhage and periventricular leukomalacia and in neonatal death.

Amniocentesis for selection before rescue cerclage

Objective To determine whether diagnostic amniocentesis should be part of evaluations of women under consideration for rescue cerclage. Methods We reviewed the obstetric records of 25 candidates for rescue cerclage seen between June 30, 1995, and July 1, 1997. Rescue cerclage was defined as a procedure on a cervix with an internal os dilated at least 2 cm and 50% effaced, with membranes visible at the external os. Transabdominal amniocentesis was offered as part of the preoperative evaluation, and amniotic fluid (AF) was sent for glucose and lactate dehydrogenase level determinations, Gram staining, and culture for aerobic and anaerobic bacteria. Placentas were examined for histopathologic evidence of inflammation. The women were divided into three groups. Eleven women had rescue cerclage after amniocentesis, seven had rescue cerclage after declining amniocentesis, and seven had amniocentesis but were treated conservatively because of AF markers of infection. Analysis of variance and χ2 statistics were used. Results The group that had rescue cerclage after amniocentesis had a significantly longer mean admission-to-delivery interval, higher mean gestational age at delivery, higher mean birth weight, and higher neonatal survival rate than did the group that had rescue cerclage without amniocentesis and the group that had no cerclage after amniocentesis (P < .001). Conclusion Amniocentesis before rescue cerclage placement identified women with subclinical chorioamnionitis who would not benefit from cerclage.

Inhibition of premature labor: A multicenter comparison of ritodrine and ethanol

A randomized controlled study was carried out at three medical centers to compare the efficacy and side effects of ethanol and ritodrine in the treatment of threatened premature labor. One hundred and thirty-five patients judged to be between the twentieth and thirty-sixth week of gestation and presenting with clinical symptoms of premature labor were included. Sixty-seven patients were treated with intravenous infusion of 10 per cent ethanol. Sixty-eight patients were treated with intravenous infusion of ritodrine for 12 hours followed by oral ritodrine. If labor recurred prematurely, up to two additional courses of ethanol or ritodrine were given. Delivery was postponed for more than 72 hours in 49 of 67 patients (73 per cent) with ethanol and in 61 of 68 patients (90 per cent) with ritodrine; this difference was significant. Patients in the ethanol group gained a mean of 27.6 days while patients in the ritodrine group gained a mean of 44.0 days. Fifty-four per cent of the ethanol group and 72 per cent of the ritodrine group carried their infants to 36 weeks of gestation. Five infants in the ethanol group and one infant in the ritodrine group died from respiratory distress syndrome. The most frequent side effect of ethanol were nausea and vomiting. The most frequent side effects of ritodrine were tachycardia and blood pressure changes which were easily controlled by lowering the infusion rate. Ethanol and ritodrine were both found to be effective inhibitors of premature labor with ritodrine giving the most favorable results.

Evaluation of amniotic fluid cytokines in preterm labor and intact membranes

Objective. To compare the amniotic fluid (AF) concentration of pro-inflammatory cytokines between women with preterm labor and intact membranes that delivered within 7 days, with those that delivered after 7 days of the amniocentesis according to the result of the AF culture. Methods. Fifty-two women with preterm labor and intact membranes between 21 and 35 weeks of gestation were included in the study. Transabdominal amniocentesis was performed to rule out intra-amniotic infection, and AF concentrations of interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF) were determined with sensitive and specific enzyme-linked immunosorbent assays. Amniotic fluid was cultured for aerobic and anaerobic bacteria, Ureaplasma urealyticum, and Mycoplasma hominis. Exclusion criteria included preterm premature rupture of membranes, vaginal bleeding, multiple gestations, uterine anomalies, fetal congenital anomalies, ominous fetal heart rate tracings and fetal deaths. Proportions were compared using χ2 or Fishers exact test. Receiver operator characteristic (ROC) curve analysis was performed for each cytokine for the prediction of delivery within 7 days. Results. Sixty-two percent (32/52) of women delivered within 7 days and 38% (20/52) delivered after 7 days of amniocentesis. All women that delivered after 7 days of the procedure had negative AF cultures. In contrast, 28% (9/32) of women that delivered within 7 days had positive AF cultures and 72% (23/32) had negative AF cultures. Women that delivered within 7 days regardless of AF cultures had a lower birth weight and a shorter amniocentesis-to-delivery interval than those that delivered after 7 days of amniocentesis. Among women that delivered within 7 days, those with positive AF cultures had a lower gestational age at delivery and a higher frequency of histologic chorioamnionitis than those with negative AF cultures. The AF concentrations of all cytokines were significantly higher in women that delivered within 7 days with positive AF cultures than in those with negative AF cultures. Similarly, the AF concentrations of IL-1α, IL-6, and IL-8 were significantly higher in women that delivered within 7 days than those that delivered after 7 days of the amniocentesis, regardless of the AF culture results. Diagnostic indexes were calculated for all cytokines using critical values derived from ROC curve analysis for the prediction of delivery within 7 days. Conclusions. Women with preterm labor and intact membranes that delivered within 7 days had higher AF concentrations of pro-inflammatory cytokines than those who delivered after 7 days of the amniocentesis regardless of the AF culture results.

Antenatal steroids and neonatal periventricular leukomalacia

Objective To evaluate the effect of antenatal steroid treatment on the development of neonatal periventricular leukomalacia. Methods This retrospective cohort study included 1161 neonates with gestational ages of 24–34 weeks and birth weights of 500–1750 g, divided into two groups on the basis of antenatal steroid treatment. Neonatal neurosonograms were done on days 3 and 7 of life and labeled normal or abnormal. The abnormal outcomes evaluated were periventricular leukomalacia or intraventricular hemorrhage, periventricular leukomalacia with intraventricular hemorrhage, and isolated periventricular leukomalacia. The group treated with antenatal steroids was compared with the untreated group for these outcomes. Results Antenatal steroids were associated with significantly less periventricular leukomalacia or intraventricular hemorrhage (23% versus 31%, P = .005), periventricular leukomalacia with intraventricular hemorrhage (5% versus 11%, P = .001), and isolated periventricular leukomalacia (3% versus 7%, P = .009). Logistic regression analysis of antenatal steroid treatment, controlling for confounding maternal and neonatal characteristics, indicated that neonates treated with antenatal steroids had a 56% lower likelihood of periventricular leukomalacia with intraventricular hemorrhage (adjusted odds ratio [OR] 0.44, 95% confidence interval [CI] 0.25, 0.77) and a 58% lower likelihood of isolated periventricular leukomalacia (adjusted OR 0.42, 95% CI 0.20, 0.88). Conclusion Antenatal steroid treatment was associated with over 50% reduction in the incidence of periventricular leukomalacia in preterm neonates. Increased use of antenatal steroid therapy might improve long-term neonatal neurologic outcomes.

Effectiveness of multidose antenatal steroids

Objective To compare effectiveness between single and multiple courses of antenatal steroids in preterm births and determine adverse effects attributable to multiple courses. Methods We studied retrospectively the neonatal outcomes of infants who weighed 1750 g or less at birth between January 1990 and December 1997. Infants exposed to a single course were compared with those exposed to two or more courses of antenatal steroids, with respect to various perinatal outcome variables. Results Ninety-three neonates were exposed to two or more courses of antenatal steroids and 261 neonates had been given single courses. The mean (± standard deviation) gestational age (29.6 ± 2.8 weeks compared with 28.7 ± 2.7 weeks; P = .007) and birth weight (1252 ± 321 g compared with 1159 ± 339 g; P = .013) were significantly higher among neonates exposed to multiple courses. There were no significant differences between groups in perinatal outcomes; however, those exposed to multiple courses had a significantly lower rate of respiratory distress syndrome (RDS) (17 [18%] compared with 107 [41%]; P ≤ .001) and surfactant use (40 [43%] compared with 149 [57%]; P = .02). Adjusting for confounding variables, multiple courses of steroids were significantly associated with a 65% reduction in the incidence of RDS (odds ratio 0.35; 95% confidence interval = 0.18, 0.70; P = .003). Conclusion Compared with single courses, multiple courses of antenatal steroids reduced significantly the incidence of RDS with no apparent increase in neonatal sepsis or disturbances in fetal growth.

Maternal magnesium sulfate and the development of neonatal periventricular leucomalacia and intraventricular hemorrhage.

OBJECTIVE Neonatal periventricular leucomalacia and intraventricular hemorrhage are strong correlates of cerebral palsy. Our objective was to evaluate the effect of maternal magnesium sulfate exposure on the incidence and severity of periventricular leucomalacia and intraventricular hemorrhage in preterm neonates. METHODS Nine hundred eighteen consecutive inborn neonates with birth weights from 500 to 1750 g were divided primarily into two groups on the basis of maternal exposure to magnesium sulfate. The groups were divided secondarily into two clinical groups, a physician-initiated group, which consisted of neonates delivered for maternal or fetal indications, and a preterm delivery group, which included neonates delivered as a result of preterm labor or preterm premature rupture of membranes. These clinical groups were stratified further into magnesium sulfate-exposed and -unexposed subgroups. Neonatal neurosonograms were performed on days 3 and 7 of life and described as normal or abnormal. Abnormal sonograms included any periventricular leucomalacia or intraventricular hemorrhage. Severe lesions included periventricular leucomalacia, periventricular leucomalacia with intraventricular hemorrhage, or grades 3 or 4 intraventricular hemorrhage. The magnesium sulfate groups and the clinical groups with their magnesium sulfate strata were compared for the incidence and severity of abnormal sonograms. They also were compared for maternal and neonatal characteristics. RESULTS Maternal magnesium sulfate exposure was not associated with reduction in the incidence of abnormal sonograms when compared with the unexposed group (27% compared with 33%, P = .06). However, fewer severe lesions were observed in the exposed group (14% compared with 21%, P = .004). When clinical groups were examined, magnesium sulfate was not associated with a decrease in abnormal sonograms (adjusted odds ratio [OR] 1.09, 95% confidence interval [CI] 0.78, 1.52, P = .40) or severe lesions (adjusted OR 1.11, 95% CI 0.73, 1.68, P = .42). Logistic regression analyses of magnesium sulfate exposure within clinical groups controlling for the confounding effects of maternal and neonatal characteristics revealed no protective effect of magnesium sulfate exposure on the incidence of abnormal sonograms (adjusted OR 1.01, 95% CI 0.70, 1.44, P = .97) or severe lesions (adjusted OR 1.01, 95% CI 0.70, 1.74, P = .69). Within clinical groups, the preterm delivery group exhibited an increased risk for abnormal sonograms (adjusted OR 1.63, 95% CI 1.01, 2.67, P = .05) and severe lesions (adjusted OR 9.79, 95% CI 3.27, 29.29, P = .001) when compared with the physician-initiated delivery group, independent of maternal magnesium sulfate exposure. CONCLUSION Maternal magnesium sulfate exposure had no protective effect on the incidence or severity of periventricular leucomalacia and intraventricular hemorrhage in preterm neonates. The prevalence of these lesions was correlated better with the clinical group of origin and indication for its use.