Harriet Friedman

Improved Survival Rates With Increased Neurodevelopmental Disability for Extremely Low Birth Weight Infants in the 1990s

Background. Advances in perinatal care have resulted in increased survival rates for extremely low birth weight children. We sought to examine the relative changes in rates of survival and neurodevelopmental impairment at 20 months of corrected age among 500- to 999-g birth weight infants born at our perinatal center during 2 periods, before and after the introduction of surfactant therapy in 1990. Methods. Four hundred ninety-six infants with birth weights of 500 to 999 g were born at our perinatal center during period I (1982–1989) (mean body weight: 762 g; mean gestational age: 25.8 weeks) and 682 during period II (1990–1998) (mean body weight: 756 g; mean gestational age: 25.5 weeks). Rates of death and survival with and without neurodevelopmental impairment at 20 months of corrected age for the 2 periods were compared with logistic regression analyses, with adjustment for gestational age. Results. Survival rates increased from 49% during period I to 67% during period II. Neonatal morbidity rates also increased during period II, including rates of sepsis (from 37% to 51%), periventricular leukomalacia (from 2% to 7%), and chronic lung disease, defined as oxygen dependence at 36 weeks of corrected age (from 32% to 43%). Rates of severe cranial ultrasound abnormalities were similar (22% vs 22%). Among children monitored, the rate of neurologic abnormalities, including cerebral palsy, increased from 16% during period I to 25% during period II and the rate of deafness increased from 3% to 7%. The overall rate of neurodevelopmental impairment (major neurosensory abnormality and/or Bayley Mental Developmental Index score of <70) increased from 26% to 36%. Compared with period I, in period II there were decreased rates of death (odds ratio [OR]: 0.3; 95% confidence interval [CI]: 0.2–0.4) and increased rates of survival with impairment (OR: 2.3; 95% CI: 1.7–3.3) but also increased rates of survival without impairment (OR: 1.7; 95% CI: 1.3–2.2). Compared with period I, for every 100 infants with birth weights of 500 to 999 g born in period II, 18 additional infants survived, of whom 7 were unimpaired and 11 were impaired. Conclusions. The improved survival rates in the 1990s occurred with an increased risk of significant neurodevelopmental impairment. Prospective parents of extremely low birth weight infants should be advised of this substantial risk, to facilitate decision-making in the delivery room.

Poor predictive validity of the Bayley Scales of Infant Development for cognitive function of extremely low birth weight children at school age.

Objective. The Bayley Scales of Infant Development, Second Edition (BSID II) are commonly used to assess outcomes of extremely low birth weight (ELBW) infants. We sought to assess the predictive validity of the BSID II Mental Developmental Index (MDI) for cognitive function at school age. Design/Methods. Of 330 ELBW infants admitted in 1992–1995, 238 (72%) survived to the age of 8 years, of whom 200 (84%) were tested at both 20 months’ corrected age (CA) and 8 years. Mean birth weight was 811 g, mean gestational age was 26.4 weeks, 41% were boys, and 60% were black. Measures included the BSID II at 20 months’ CA and the Kaufman Assessment Battery for Children (KABC) Mental Processing Composite (MPC) at 8 years’ postnatal age. BSID II MDI and MPC scores were compared and the predictive validity calculated for all 200 ELBW children and for the 154 ELBW neurosensory-intact subgroup. Predictors of stability or change in cognitive scores were examined via logistic regression adjusting for gender and sociodemographic status. Results. For all ELBW children, the mean MDI was 75.6 ± 16 versus a mean KABC of 87.8 ± 19. For the neurosensory-intact subgroup, the mean MDI was 79.3 ± 16 and the mean KABC was 92.3 ± 15. Rates of cognitive impairment, defined as an MDI or KABC of <70, dropped from 39% at 20 months’ CA to 16% at 8 years for the total ELBW population and from 29% to 7% for the neurosensory-intact subgroup. The positive predictive value of having an MPC of <70 given an MDI of <70 was 0.37 (95% confidence interval [CI]: 0.27, 0.49) for all ELBW infants, 0.20 (95% CI: 0.10, 0.35) for the neurosensory-intact subgroup, and 0.61 (95% CI: 0.42, 0.77) for the neurosensory-impaired subgroup. The negative predictive values were 0.98, 0.99, and 0.85 for the 3 groups, respectively. Neurosensory impairment at 20 months’ CA predicted lack of improvement of cognitive function (odds ratio: 6.9; 95% CI: 2.4, 20.2). Children whose cognitive scores improved between 20 months and 8 years had significantly better school performance than those whose scores stayed at <70, but they did less well than those whose scores were persistently >70. Conclusions. The predictive validity of a subnormal MDI for cognitive function at school age is poor but better for ELBW children who have neurosensory impairments. We are concerned that decisions to provide intensive care for ELBW infants in the delivery room might be biased by reported high rates of cognitive impairments based on the use and presumptive validity of the BSID II MDI.

Perinatal Correlates of Cerebral Palsy and Other Neurologic Impairment Among Very Low Birth Weight Children

Background and Objective. The etiology of neurologic impairments among very low birth weight (VLBW, <1.5 kg) children is poorly understood. We sought to investigate the perinatal predictors of major neurologic impairment, including cerebral palsy, among VLBW children. Methods. Antenatal, intrapartum, and neonatal events and therapies were compared between 72 singleton inborn VLBW children born between 1983 to 1991 who had neurologic impairment at 20 months corrected age (including 50 with cerebral palsy and 22 with other neurologic impairments) and 72 neurologically normal VLBW children matched by birth weight, gestational age, race, and sex via a retrospective case-control method. Multiple logistic regression was conducted, entering only those variables found to be significant at the bivariate level. Results. There were no significant differences in the rates of pregnancy-induced hypertension, maternal tocolytic use including magnesium, or antenatal steroid therapy. Higher rates of clinical chorioamnionitis were found among the mothers of the neurologically impaired children as compared with controls (31% vs 11%), but not among the subgroup of mothers of children with cerebral palsy (22% vs 12%). Significant differences in neonatal factors among the total neurologically-impaired group (n = 72) versus controls included oxygen dependence at 36 weeks (31% vs 15%), septicemia (53% vs 31%), severe cranial ultrasound abnormality (50% vs 17%), and hypothyroxinemia (43% vs 25%). In the subgroup with cerebral palsy (n = 50), significant differences included days on the ventilator (23 vs 14 days), septicemia (54% vs 33%), and severe cranial ultrasound abnormality (52% vs 12%). Multivariate analysis controlling for birth weight, gestational age, race, sex, and the birth period (before 1990 versus 1990 and after) revealed direct and independent effects of clinical chorioamnionitis [odds ratio (OR), 3.79; confidence interval (CI), 1.34–10.78], severe cranial ultrasound abnormality (OR, 9.97; CI, 3.84–25.87), and septicemia (OR, 2.46; CI, 1.10–5.52) on total neurologic impairment. Consideration of the 50 cases with cerebral palsy revealed direct and independent effects of severe cranial ultrasound abnormality only (OR, 15.01; CI, 4.34–51.93). Conclusions. Both antenatal and neonatal risk factors contribute to the development of severe neurologic impairment, including cerebral palsy among VLBW children. Because prevention of chorioamnionitis may not be feasible in the near future, attempts to decrease neonatal risk factors such as severe cranial ultrasound abnormalities and sepsis may be most feasible at this time.

Outcomes of extremely low birth weight (<1 kg) and extremely low gestational age (<28 weeks) infants with bronchopulmonary dysplasia: effects of practice changes in 2000 to 2003.

OBJECTIVE. The goal was to evaluate whether changes in neonatal intensive care have improved outcomes for children with bronchopulmonary dysplasia (oxygen dependence at corrected age of 36 weeks). METHODS. We compared outcomes of extremely low birth weight (<1 kg) and extremely low gestational age (<28 weeks) infants with bronchopulmonary dysplasia between 2 periods (period I, 1996–1999: extremely low birth weight, n = 122; extremely low gestational age, n = 118; period II, 2000–2003: extremely low birth weight, n = 109; extremely low gestational age, n = 107). RESULTS. For both groups, significant practice changes between period I and period II included increased prenatal and decreased postnatal steroid therapy and increased surfactant therapy, indomethacin therapy, and patent ductus arteriosus ligation. Significant morbidity changes included decreased rates of severe cranial ultrasound abnormalities and increased rates of ventilator dependence. Rates of bronchopulmonary dysplasia did not change (52% vs 53%). Follow-up evaluation revealed significantly lower rates of neurosensory abnormalities during period II (extremely low birth weight: 29% vs 16%; extremely low gestational age: 31% vs 16%). There were no changes in rates of Mental Developmental Index scores of <70 (extremely low birth weight: 42% vs 42%; extremely low gestational age: 37% vs 45%) or overall developmental impairment (extremely low birth weight: 51% vs 49%; extremely low gestational age: 50% vs 51%). For the extremely low gestational age group, predictors of neurosensory abnormalities were severe cranial ultrasound abnormality and postnatal steroid therapy. Predictors of overall impairment included severe cranial ultrasound abnormalities, ventilator dependence, postnatal steroid therapy, and patent ductus arteriosus ligation. For the extremely low birth weight group, the only predictor of neurosensory abnormalities was severe cranial ultrasound abnormality. Predictors of overall impairment included multiple birth, ventilator dependence, and severe cranial ultrasound abnormalities. CONCLUSIONS. Neurosensory outcomes of infants with bronchopulmonary dysplasia improved during 2000 to 2003 but overall neurodevelopmental outcomes did not change.

Viral hepatitis, type A. Identification by specific complement fixation and immune adherence tests.

: Hepatitis A antibody was detected by specific immune adherence and complement-fixation tests in a study involving 473 serum specimens from 20 patients who had viral hepatitis, Type A. In all 20 patients who had no detectable immune adherence antibody (less than 1:5) before onset of hepatitis high levels (greater than or equal to 1:1024) developed one to four weeks later, occasionally reaching peak levels exceeding greater than or equal to 1:81,920 several months thereafter. Five to 10 years later the immune adherence antibody levels ranged between 1:640 and 1:20,480. In general, the complement-fixation test was not as sensitive or as specific as the immune adherence test. These findings indicate that the immune adherence test should be a valuable tool for diagnosis, for epidemiologic surveys, for identification of susceptible and immune persons, for quantitative assays of gamma globulin and for identification of hepatitis A virus in attempts to propagate the virus in cell culture.

Severe respiratory failure in neonates: mortality and morbidity rates and neurodevelopmental outcomes.

OBJECTIVE To compare the survival, neurodevelopmental, and health outcomes of children with severe respiratory illness treated with and without extracorporeal membrane oxygenation (ECMO). DESIGN Prospective collection of clinical and demographic data of all neonates reaching illness severity criteria, with follow-up at 8 and 20 months of age. Patients were assigned to treatment by the attending physician. PATIENTS Consecutive sample of 74 neonates during a 24-month period with an alveolar-to-arterial gradient exceeding 620 for 8 or more hours. RESULTS Eighteen (69%) of 26 neonates treated with conventional therapy survived to 20 months, in comparison with 43 (90%) of 48 neonates treated with ECMO. The conventionally treated group had significantly more chronic lung disease, longer duration of oxygen therapy, more chronic reactive airway disease, and more rehospitalizations than those treated with ECMO. Hospital charges were similar in the two groups. Macrocephaly was noted in 24% of those treated with ECMO and in none of the conventional group. Of those completing evaluation, 4 (24%) of 17 conventionally treated survivors and 20 (26%) of 38 ECMO-treated survivors had neurodevelopmental impairment. CONCLUSION Survivors of severe neonatal respiratory illness have significant pulmonary and neurodevelopmental impairment, regardless of the treatment used. Neonates treated with ECMO had neurodevelopmental outcomes similar to those of patients treated conventionally, but better pulmonary outcomes.

The effect of neonatal maternal milk feeding on the neurodevelopmental outcome of very low birth weight infants.

ABSTRACT. The effect of maternal milk feeding during the first 4 weeks of life on neurodevelopmental outcomes at 20 months corrected age (CA) of singleton very low birth weight (VLBW) (<1.5 kg) infants was examined. Ninety-eight VLBW infants born from January 1997 to February 1999 were followed to 20 months CA (mean birth weight, 1012 g; gestational age, 27 weeks). Maternal milk intake was calculated as both mean milliliters per kilogram per day and graded doses. Outcomes included the Bayley Mental Development Index (MDI) and Psychomotor Development Index (PDI), and rates of cerebral palsy (CP) and of overall neurodevelopmental impairment. After adjusting for neonatal and social risk, results revealed no effect of maternal milk on outcomes. MDI was predicted by both social and neonatal risk, and PDI, CP, and neurodevelopmental impairment were predicted by neonatal risk. In this small, high-risk group of VLBW infants, the effects of social and neonatal risk appear to outweigh any possible benefits of maternal milk on neurodevelopmental outcome.

Hepatitis A and B: serologic survey of various population groups.

Seven population groups were tested by radioimmunoassay for the presence of hepatitis A antibody (anti-HAV), hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). Detection of anti-HAV was indicative of past hepatitis A infection and presence of HBsAg or anti-HBs indicated past hepatitis B infection. The results of tests of 680 serum specimens from the seven groups were as follows: (1) of 100 newly admitted children to Willowbrook where hepatitis A and B were hyperendemic, 32% had anti-HAV and 4% had anti-HAV and 4% had HBsAg (1%) plus anti-HBs (3%); (2) of 100 Willowbrook residents who lived in the institution about three or more years, 97% had anti-HAV and 90% had HBsAg (32%) plus anti-HBs (58%); (3) of 100 new Willowbrook employees, 50% had anti-HAV and 13% had anti-HBs; (4) of 100 Willowbrook employees who worked in the institution more than three years, 75% had anti-HAV and 30% had HBsAg (3%) plus anti-HBs (27%); (5) of 80 house staff physicians, 27.5% had anti-HAV and 10% had anti-HBs; (6) of 100 student 34% had anti-HAV and 6% had anti-HBs; and (7) of 100 suburban teenagers 4% had anti-HAV and 5% had anti-HBs. This study confirmed the variability of the prevalence of hepatitis A and B markers among different population groups and the effect of socioeconomic status and environmental factors on the incidence of past infection caused by hepatitis A and B viruses.

Pulmonary Hemorrhage in VLBW (<1.5 kg) Infants: Correlates of Death and Neonatal and Neurodevelopmental Outcomes of Survivors. † 1348

Pulmonary Hemorrhage in VLBW (<1.5 kg) Infants: Correlates of Death and Neonatal and Neurodevelopmental Outcomes of Survivors. † 1348

Major Congenital Malformations in VLBW (<1.5 kg) Infants. High Mortality and Neurodevelopmental Handicap ♦ 1265

Major Congenital Malformations in VLBW (<1.5 kg) Infants. High Mortality and Neurodevelopmental Handicap ♦ 1265