Uma Verma

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.

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.

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.

CEREBRAL FUNCTION MONITOR IN THE NEONATE, I: NORMAL PATTERNS

The cerebral function monitor (CFM) is a monitoring device which records integrated encephalograms (EEGs) on slow‐running paper, allowing continuous observations of cerebral activity for prolonged periods. The CFM was assessed in 49 normal neonates of different gestational ages and was found to reflect EEG activity accurately. Gestatibnal age and sleep‐wake states could be differentiated and normal patterns were defined. The establishment of normal patterns will allow further assessment of the CFM as a screening tool for the neonate at risk for cerebral hypoxic ischemic injury.

Cerebral function monitor in the neonate. II: Birth asphyxia.

The cerebral function monitor (CFM) records an integrated electroencephalogram on slow‐running paper, and therefore is suited to long‐term, continuous monitoring. This study describes CFM patterns of 31 neonates with birth asphyxia. Three distinct types emerged: (1) a normal pattern compatible with gestational age was uniformly associated with favorable clinical outcome; (2) a completely disorganized pattern was associated with severe injury and fatal outcome; and (3) a more subtle pattern showed reversal to a more immature gestational age. The three infants with the third pattern all survived, but with varying degrees of neurological deficit. It is concluded that the CFM can be of advantage in predicting outcome for asphyxiated neonates.

Perinatal outcome of triplet gestation: Does prophylactic cerclage make a difference?

OBJECTIVE To compare the perinatal outcome of triplet gestations with and without prophylactic cerclage. METHODS A retrospective chart review of all triplet gestations delivered between January 1988 and June 1997 was performed. Only women initiating prenatal care before 15 weeks gestation were included. The cerclage group was compared to the no-cerclage group for maternal and perinatal outcome variables. Student t-test, Chi-square, and Fishers exact test were used for analysis. RESULTS Twenty of the 59 (33.8%) sets of triplet gestations had prophylactic cerclage. There were no differences between groups when compared for maternal age, parity, preterm labor rate, gestational diabetes, anemia, antenatal steroid use, histologic chorioamnionitis, and postoperative endometritis. In addition, there were no differences in mean birth weight, Apgar scores, respiratory distress syndrome (RDS), intraventricular hemorrhage/periventricular leucomalacia (IVH/PVL), and neonatal mortality. Although the mean gestational age at delivery for the cerclage group (32.8+/-2.4 weeks) was not different from the no-cerclage group (31.5+/-3.6 weeks), the proportion of pregnancies delivered at 31 weeks or more, and at 32 weeks or more, was significantly higher in the cerclage group (90 vs. 62%, P = .02; 80 vs. 54%, P = .05), respectively. In addition, the incidence of extremely low birth weight (LBW) was significantly decreased in the cerclage compared with the no-cerclage group (1.7 vs. 15.4%, P = .005). CONCLUSIONS Prophylactic cerclage decreased significantly the incidence of extremely LBW neonates in triplet pregnancies. The proportion of neonates delivered at 31 weeks or more, and at 32 weeks or more was higher in the cerclage group.

Correlation of neonatal nucleated red blood cell counts in preterm infants with histologic chorioamnionitis

OBJECTIVE The aim of this study was to compare the neonatal nucleated red blood cell counts in preterm infants in the presence and absence of clinical and histologic chorioamnionitis while controlling for gestational age and birth weight percentile. STUDY DESIGN Nucleated red blood cell counts were obtained from preterm infants delivered after preterm labor or preterm premature rupture of membranes. Patients were divided on the basis of clinical and histologic chorioamnionitis. Nucleated red blood cell counts between groups were compared, and regression analysis controlling for gestational age and birth weight percentile was performed. RESULTS Of 359 patients, both measures of infection status were significantly associated with increased nucleated red blood cell counts. In the regression analysis histologic chorioamnionitis retained significance, whereas clinical chorioamnionitis did not. CONCLUSIONS Histologic chorioamnionitis produces an erythropoietic response in the fetus. Whether fetal erythropoiesis is a direct response to mediators of inflammation or whether it is the result of a rise in erythropoietin is unknown.