Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants.

BACKGROUND: The prophylactic administration of indomethacin reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants (those with birth weights below 1500 g). Whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in renal, intestinal, and cerebral blood flow is not known. METHODS: Soon after they were born, we randomly assigned 1202 infants with birth weights of 500 to 999 g (extremely low birth weight) to receive either indomethacin (0.1 mg per kilogram of body weight) or placebo intravenously once daily for three days. The primary outcome was a composite of death, cerebral palsy, cognitive delay, deafness, and blindness at a corrected age of 18 months. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly within the same time frame. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrhage, chronic lung disease, ultrasonographic evidence of intracranial abnormalities, necrotizing enterocolitis, and retinopathy. RESULTS: Of the 574 infants with data on the primary outcome who were assigned to prophylaxis with indomethacin, 271 (47 percent) died or survived with impairments, as compared with 261 of the 569 infants (46 percent) assigned to placebo (odds ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4; P=0.61). Indomethacin reduced the incidence of patent ductus arteriosus (24 percent vs. 50 percent in the placebo group; odds ratio, 0.3; P<0.001) and of severe periventricular and intraventricular hemorrhage (9 percent vs. 13 percent in the placebo group; odds ratio, 0.6; P=0.02). No other outcomes were altered by the prophylactic administration of indomethacin. CONCLUSIONS: In extremely-low-birth-weight infants, prophylaxis with indomethacin does not improve the rate of survival without neurosensory impairment at 18 months, despite the fact that it reduces the frequency of patent ductus arteriosus and severe periventricular and intraventricular hemorrhage.

Romanian adoption. The Manitoba experience.

OBJECTIVE: To study the developmental, behavioral, and medical features in a cohort of Romanian children adopted by Manitoba families. DESIGN: A prospective longitudinal study. SETTING: The Child Development Clinic, Children's Hospital, Winnipeg, Manitoba, from September 1990 to June 1992. PATIENTS: Developmental, behavioral, and medical features were assessed in 22 Romanian children adopted by 18 Manitoba families. RESULTS: Mean (+/- SD) age at adoption was 15.5 +/- 13 months. Mean (+/- SD) age at initial assessment was 19 +/- 12 months and at follow-up, 35 +/- 13 months. Medical complications included 6 children (27%) who were positive for the hepatitis B surface antigen, 5 with intestinal parasites (23%), 1 positive for the human immunodeficiency virus, 1 with rickets (5%), and 1 with monoplegia and cleft palate (5%). Initial growth parameters were less than the fifth percentile for age for head circumference in 10 children (45%), for weight in 8 (36%), and for height in 7 (32%). At follow-up, statistically significant improvement was seen in height and weight. Initial mean (+/- SD) developmental quotients were 82 +/- 20 for gross motor, 83 +/- 23 for fine motor, 83 +/- 19 for cognitive, and 79 +/- 18 for language domains. Follow-up mean developmental quotients improved in all domains (P < .05). Twelve children (55%) displayed abnormal behavior at the initial assessment; behavioral findings persisted in 8 (36%). Initial appropriate activity level and play behavior predicted normal cognitive outcome (P < .05). CONCLUSIONS: This longitudinal study of Romanian adoptees delineates improvements in growth and development once the children are placed in a nurturing environment. The persistence of abnormal behavior in some children underscores the importance of further follow-up.

The natural history and predictive value of early language delays in very low birth weight infants.

A cohort of 28 VLBW (less than or equal to 1500 g) infants was assessed at 1 and 3 years of age for hearing, language development and neurological status. Language delays were detected in 11 (39%) infants at 1 year, and in four (15%) at follow up at 3 years of age (P less than 0.05). Language quotients were significantly associated with perinatal variables at 1 but not at 3 years of age. Infants with neurological abnormalities had significantly lower language quotients at the 3-year follow up. No child with a normal language profile at 1 year exhibited a delay at 3 years of age.

Language development of very low birth weight infants and fullterm controls at 12 months of age.

Twenty-eight very low birth weight (VLBW) and 32 full term infants were prospectively assessed at one year of age for hearing, language development and neurological status. The prevalence of conductive hearing deficits was the same in both groups. Language scores in VLBW infants were significantly lower than in fullterm controls and 39% had significant language delays. VLBW infants exhibited a shorter attention span and were less likely to understand simple questions, to recognize objects or body parts when named, to initiate speech-gesture games, to follow simple commands and to imitate or use words consistently. Language quotients were directly associated with gestational age and five minute Apgar scores and inversely associated with severity of intraventricular hemorrhage, bronchopulmonary dysplasia and length of hospital stay. VLBW small for gestational age infants exhibited more advanced language skills than VLBW appropriate for gestational age infants. Language delays were more prevalent among, but not limited to, infants with mild to moderate neurological abnormalities. The influence of prematurity and VLBW on language development is complex and multifactorial and research is continuing to determine the predictive validity and long term significance of the early language delays described in this study.