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Original Article

School-Age Outcomes in Children with Birth Weights under 750 g

List of authors.
  • Maureen Hack,
  • H. Gerry Taylor,
  • Nancy Klein,
  • Robert Eiben,
  • Christopher Schatschneider,
  • and Nori Mercuri-Minich

Abstract

Background

Since the mid-1980s, increasing numbers of children with birth weights under 750 g have survived to school age.

Methods

We matched a regional cohort of 68 surviving children born from 1982 through 1986 with birth weights under 750 g (mean, 670 g; gestational age, 25.7 weeks) with 65 children weighing 750 to 1499 g at birth and 61 children born at term. Growth, neurosensory status, and functioning at school age in the three groups were compared. Associations of biologic and social risk factors with major developmental outcomes were examined by means of logistic-regression analyses.

Results

Children with birth weights under 750 g were inferior to both comparison groups in cognitive ability, psychomotor skills, and academic achievement. They had poorer social skills and adaptive behavior and more behavioral and attention problems. The mean (±SD) Mental Processing Composite score for the cohort was 87 ±15, as compared with 93 ±14 for children with birth weights of 750 to 1499 g and 100 ±13 for children born at term (P<0.001). The rates of mental retardation (IQ <70) in the three groups were 21, 8, and 2 percent, respectively; the rates of cerebral palsy were 9, 6, and 0 percent; and the rates of severe visual disability were 25, 5, and 2 percent. Major cerebral ultrasonographic abnormalities were associated with mental retardation (odds ratio, 5.4; 95 percent confidence interval, 1.8 to 15.8) and cerebral palsy (odds ratio, 15.2; 95 percent confidence interval, 3.0 to 77.4). Oxygen dependence at 36 weeks of corrected age was associated with mental retardation (odds ratio, 4.5; 95 percent confidence interval, 1.2 to 10.7) and severe visual disability (odds ratio, 4.3; 95 percent confidence interval, 1.3 to 14.2). Social disadvantage, though associated with several neuropsychological outcomes, was not associated with major developmental impairment.

Conclusions

Children with birth weights under 750 g who survive represent a subgroup of very-low-birth-weight children who are at high risk for neurobehavioral dysfunction and poor school performance.

Introduction

During the past decade, advances in perinatal care have resulted in increases in the survival of extremely small and immature infants1,2. Whereas few infants with birth weights below 750 g were actively treated before the 1980s, treatment is now accepted practice for most infants born in North America with birth weights of at least 500 g, those born at 24 or more weeks' gestation, or both. The high rates of neonatal morbidity among extremely-low-birth-weight infants who survive have been well documented, as has a 20 to 50 percent rate of neurodevelopmental impairment during early childhood1,2. However, few reports have discussed outcomes at early school age, which are critical indicators of how these children will ultimately function in society3-6.

We studied the health and developmental outcomes at early school age of children with birth weights below 750 g who were born from 1982 through 1986, the period when increasing numbers of survivors were first reported1. We hypothesized that such children would function at lower levels at school age than either children with birth weights of 750 to 1499 g or classmates born at term.

Methods

Study Group

The study subjects included the survivors of the cohort of 243 children with birth weights below 750 g who were born from 1982 through 1986 in a six-county region of Ohio including the greater Cleveland area and who were admitted to the three tertiary-level neonatal intensive care units in the region. During this period, the region had 147,732 live births; 408 (0.3 percent) of these infants weighed 500 to 749 g. One hundred seventy-seven were born in the three perinatal centers and the remainder in community hospitals; 66 of these infants were deemed viable and were transferred to two of the centers. Seventy-three (30 percent) of the 243 children born weighing less than 750 g who were admitted to the three neonatal intensive care units survived to discharge. At school age, 68 of the 73 survivors (93 percent) were available for study. We were unable to recruit the remaining 5 children, but with respect to mean birth weight (684 g), gestational age (26 weeks), and the occurrence of early sequelae, they were similar to the 68 children who were followed. We had information that one was blind and that two functioned in the low-normal range.

Comparison Groups

Two comparison groups were recruited, a group of children born weighing 750 to 1499 g and a group born at full term. For each child weighing below 750 g, we selected the next survivor who was born weighing 750 to 1499 g, was treated at the same perinatal center, and was of the same race and sex. Of the 68 matches, 28 children born weighing 750 to 1499 g could not be scheduled for assessment, and 1 child had esophageal atresia with multiple sequelae related to the malformation rather than to prematurity. The next child born weighing 750 to 1499 g and appropriately matched was then selected to replace the originally matched child. Three children were not assessed because of multiple missed appointments. Thus, the comparison group of children with birth weights of 750 to 1499 g included 65 children of school age.

The comparison group of children born at term was formed by randomly selecting a full-term child from the same classroom as the child born weighing less than 750 g who was of the same sex, race, and birth date, within three months. Matches were not selected for seven children (five were in schools out of the city, one was not at school, and the parent of one refused permission to contact the school). For the 61 children born at term who were selected, 10 parents of the children originally matched declined to participate, and a second match with a full-term child was thus selected.

School-Age Assessments

Table 1. Table 1. Measures of Neuropsychological Achievement.

The children with birth weights below 750 g were examined at a mean (±SD) age of 6.7 ±0.9 years, those born weighing 750 to 1499 g at 6.9 ±0.9 years, and the children born at term at 7.0 ±0.9 years. A complete physical and neurologic examination was performed. Hearing was measured with pure-tone audiometric screening, and visual acuity was tested with Snellen's letters. The children were classified neurologically as normal or abnormal (i.e., having a major neurologic or sensory abnormality). The psychometric testing of the children included assessments of neuropsychological abilities and academic achievement as described in Table 1 7-19. All tests were scored on the basis of the child's postnatal age. IQ-equivalent scores were assigned to all children on the basis of the Kaufman Assessment Battery for Children Mental Processing Composite Short Form or, in three cases of children who could not be tested with these procedures, with alternative tests. An IQ equivalent of 55 was assigned to five children who could not be tested by any procedures because of severe neurosensory disability.

A parent, usually the mother, was interviewed to obtain background demographic, health, and developmental data, and both the parent and the teacher completed questionnaires on the child's behavior and performance at school (Table 1)20-24.

A composite score for social risk, which we have used previously,25 included maternal race (with scores of 0 for white and 1 for black), maternal education (0 for high school or above and 1 for less than a high-school education), and marital status (0 for married and 1 for unmarried). The composite scale ranged from 0, for lowest social risk, to 3, for highest social risk. In this study the composite scale had a higher correlation with the Kaufman Assessment Battery in the comparison group born at term (-0.58) than did any of the components analyzed separately.

Study Design and Statistical Analysis

We compared the three groups of children with regard to outcomes at early school age. The outcome measures were standardized for age before analysis26. Overall differences between groups on continuous measures of outcome were examined by an analysis of variance or a multivariate analysis of variance. The alpha level was set at 0.05 for each domain, and Bonferroni adjustments in the alpha level were used in making univariate comparisons within multiple-measure domains. Two-tailed tests were used to examine differences between each pairing of the three groups.

Logistic regression was used to assess associations of social and neonatal risk factors with major developmental outcomes among children in the two very-low-birth-weight (<1500-g) groups27. The outcomes considered in these analyses included mental retardation (IQ equivalent, <70), cerebral palsy, and visual disability (i.e., unilateral or bilateral blindness or vision ≤ 20/200 without glasses, in at least one eye). The index of social disadvantage was first entered into these analyses as a covariate. Five neonatal risk factors were then entered in a stepwise fashion to identify the factors that best predicted each outcome, independently of social status. These included septicemia, necrotizing enterocolitis, maximal serum bilirubin concentration greater than 10 mg per deciliter (171 μmol per liter), apnea of prematurity, and severe cerebral ultrasonographic abnormality (grade 3 or 4 periventricular bleeding,28 persistent ventricular dilatation, or both). Interaction terms (the effect of each neonatal complication according to birth-weight group) were entered into the logistic-regression equations after the group and all neonatal-complication factors had been entered. Chronic lung disease (defined as dependence on oxygen for at least 36 weeks of corrected age [i.e., postmenstrual plus postnatal age] vs. dependence on oxygen for less than 36 weeks of corrected age29) was then entered in the regression equations, with control for social disadvantage and those neonatal-complication factors that were found to be associated with outcome. We separated the early neonatal correlates of outcome from the later measures of chronic lung disease in order to identify early prognostic indicators that might be relevant to critical therapeutic decisions in the neonatal period. Interactions of oxygen dependence with group were entered in the final stage of the analyses.

The study protocol was reviewed and approved by the institutional review board at each center. Informed consent was obtained from the parents of the study children.

Results

Comparison of Demographic and Birth Data

Table 2. Table 2. Maternal Demographic Risk Factors and Perinatal Data.

The three groups of infants were similar with regard to their mothers' age, marital status, and racial background (Table 2). There were no differences between groups in the composite index of social disadvantage. Sixty-six percent of the sample was female because of the greater survival of girls in the group born weighing less than 750 g.

Perinatal and Neonatal Risk Factors in the Very-Low-Birth-Weight Groups

Table 3. Table 3. Perinatal and Neonatal Descriptors of the Very-Low-Birth-Weight Children.

There were no material differences between the two very-low-birth-weight groups with regard to the rate of maternal complications of pregnancy, the mode of delivery, or the rate of infant transfers from community hospitals (Table 3). All children were born before the use of surfactant. Infants weighing less than 750 g at birth had significantly higher rates of intrauterine growth failure, respiratory distress requiring assisted ventilation, patent ductus arteriosus, apnea of prematurity, and septicemia. Significantly fewer infants in this group had normal cerebral ultrasonograms than did infants weighing 750 to 1499 g at birth. Shunt-dependent hydrocephalus developed in two children in each group. The group weighing less than 750 g at birth had significantly longer dependence on oxygen and mechanical ventilation and longer hospital stays. Forty-three percent of these infants required oxygen at 36 weeks of corrected age, as compared with 11 percent of the infants with birth weights of 750 to 1499 g.

Neurosensory and Physical Outcomes

Table 4. Table 4. Neurosensory and Growth Outcomes. Figure 1. Figure 1. Percentage of Children in Each Study Group with Each of Four Major Impairments.

Cerebral palsy was defined to include hemiplegia, diplegia, or quadriplegia; visual impairment to include unilateral or bilateral blindness or visual acuity ≤ 20/200 without glasses in at least one eye; and subnormal head size and height as less than 2 SD below the mean for the child's age.31,32.

Ten children weighing less than 750 g at birth (15 percent) had major neurosensory impairment, including cerebral palsy, blindness, and deafness, as compared with five of those weighing 750 to 1499 g (8 percent) and none of those born at term. Two children in each of the very-low-birth-weight groups could not walk. Table 4 summarizes the abnormal neurosensory and growth outcomes. Selected results are shown in Figure 1.

Developmental Outcomes

The mean (±SD) Mental Processing Composite score for the children weighing less than 750 g at birth who were tested was 87 ±15, as compared with 93 ±14 for the children weighing 750 to 1499 g and 100 ±13 for the children born at term. As compared with the children born at term, the group born weighing less than 750 g had significantly poorer scores on all the measures listed in Table 1, except for one test of verbal memory. Those born weighing less than 750 g had significantly poorer outcomes than those weighing 750 to 1499 g with regard to cognitive ability, language-processing skills, gross motor and visual motor function, attention skills, academic achievement, ratings of school performance by a parent or a teacher, behavior and social skills, and adaptive behavior.

Table 5. Table 5. Incidence of Findings Suggestive of Disabling Conditions. Figure 2. Figure 2. Percentage of Children in Each Study Group with Subnormal Functioning.

Subnormal functioning was defined as a standard score of less than 70 for cognitive function,7 academic skills,19 visual motor function,14 and adaptive function24 and a score of less than 30 for gross motor function.13.

The fact that the groups also differed in the frequency of severe deficits in test performance or elevated ratings of behavioral problems (Table 5) suggests that the differences between groups are clinically meaningful. Representative results are shown in Figure 2. Differences in measures of cognition, psychomotor function, attention, and academic achievement remained significant when the comparisons were further restricted to children who were both neurologically intact and of normal intelligence (Mental Processing Composite score ≥ 85).

Relation of Social Risk and Gestational Age to Outcome

The index of social disadvantage was significantly correlated with many of the outcome measures, including the IQ equivalent (r = -0.34, P<0.001), the Vineland Adaptive Behavior Composite score (r = -0.21, P<0.01), the Woodcock-Johnson Skills Cluster (r = -0.17), and the Expressive One-Word Picture Vocabulary Test (r = -0.42, P<0.001). Correlations with measures of motor performance and behavioral-problem ratings were not significant. Gestational age was significantly related to the IQ equivalent in the two very-low-birth-weight groups combined (r = 0.19, P<0.03), but not when each group was considered separately.

Association between Social Risk and Medical Factors and Very-Low-Birth-Weight Outcomes

According to logistic-regression analysis, the index of social disadvantage was not associated with any of the three major developmental outcomes. Neonatal complications, however, were associated with all three outcomes. The stepwise entry into the analysis of the five neonatal complications under consideration revealed that higher risks of both mental retardation and cerebral palsy were associated with severe ultrasonographic abnormality. Even after we controlled for social disadvantage, the odds ratios for a child's having mental retardation or cerebral palsy, given a severely abnormal ultrasonogram, were 5.4 (95 percent confidence interval, 1.8 to 15.8) and 15.2 (95 percent confidence interval, 3.0 to 77.4), respectively. After the entry of social disadvantage and cerebral-ultrasonogram status into the equation, dependence on oxygen at 36 weeks' corrected age was also associated with mental retardation and visual disability. The adjusted odds ratios for mental retardation and visual disability, given dependence on oxygen at 36 weeks' corrected age, were 4.5 (95 percent confidence interval, 1.2 to 10.7) and 4.3 (95 percent confidence interval, 1.3 to 14.2), respectively. The associations of severe ultrasonographic abnormalities and oxygen dependence with adverse outcomes did not vary with birth-weight group. Furthermore, the entry of the very-low-birth-weight group (<750 g vs. 750 to 1499 g) into the equation after ultrasonographic status and oxygen dependence had already been added did not significantly improve the prediction of any of the three outcomes. This last finding suggests that the effects of birth weight were mediated by neonatal complications. Two measures available at discharge, the modified Hobel neonatal risk score, which we have used previously,25 and the length of the hospital stay, also predicted mental retardation, cerebral palsy, and severe visual disability.

Discussion

The results of this study of very-low-birth-weight children at early school age confirm our hypothesis that these children are at serious disadvantage in every skill required for adequate performance in school. Twenty-one percent of our sample had subnormal mental abilities, and 45 percent required some special education in school. A substantial percentage also had visual disability and subnormal growth. This study presents regional outcomes, avoiding the selection bias inherent in hospital-based studies.

Previous reports of the school-age outcomes of very-low-birth-weight children included very few children weighing less than 750 g at birth, because few survived before the 1980s. Our results are consistent with those of two small, hospital-based studies3,5. The only other regional outcome study reported a mean IQ of 89 among 48 children born from 1977 to 1984 weighing less than 800 g at birth4. We and other investigators have not corrected the children's ages for preterm birth, since performance relative to uncorrected age is the standard by which they are judged at school.

Because of concern over the reliability of using gestational ages, most reports, including our own, examine outcome according to birth weight. The estimation of gestational age based on obstetrical information is problematic when the mothers have not received prenatal care, whereas the postnatal assessment of gestational age results in overestimates2. However, Johnson et al. recently reported that 22 of 42 children born at less than 27 weeks' gestation had moderate-to-severe disability at four years of age6.

The results of our study also confirm the hypothesis that although outcomes at early school age are related to both social and biologic risks, major developmental outcomes were more closely associated with neonatal complications than with social disadvantage. Of the biologic risk factors we considered, major cerebral abnormality on ultrasonographic examination and dependence on oxygen at 36 weeks' corrected age were associated with mental retardation. Major ultrasonographic abnormality was also associated with cerebral palsy, and prolonged oxygen dependence predicted severe visual impairment.

Poor outcomes at early school age after severe periventricular hemorrhage and cerebral atrophy have been previously described33,34. This report documents poor outcomes associated with cerebral abnormalities detected ultrasonographically in children with birth weights of less than 750 g. We suspect that in some cases the smallest and least mature infants with severe brain hemorrhage are allowed to die. This would explain why the rates of severe ultrasonographic abnormality did not differ significantly between the two very-low-birth-weight groups, whereas the rates of the other neonatal complications and medical outcomes, including chronic lung disease, visual disability, and subnormal growth, were higher in the group weighing less than 750 g at birth. The significant relation of prolonged dependence on oxygen to outcomes is probably due to multiple factors, including hypoxic episodes and the effects of prolonged hospitalization and poor growth35. We have previously reported on the relation of subnormal head growth to poor later outcomes25. In the current study, 36 percent of the children with birth weights under 750 g had subnormal head sizes at school age, as compared with 14 percent of children with birth weights of 750 to 1499 g. The high rates of visual impairment in the children we studied are consistent with recent reports of poor visual outcomes in early childhood for children weighing less than 750 g at birth. We did not perform ophthalmologic fundal examinations, but reports from the children's ophthalmologists suggested that retinopathy of prematurity was primarily responsible for the visual impairment.

The known variations among institutions in neonatal mortality and morbidity2 and their effects on regional outcomes may limit the generalizability of our results to other regions. Furthermore, one of the problems inherent in neonatal follow-up studies is that many years pass before outcomes can be fully evaluated. The children in this study were born before many recent innovations in care, including surfactant therapy, treatment of chronic lung disease with steroids, and cryotherapy to ameliorate severe retinopathy of prematurity. There is no evidence that treatment with surfactant or postnatal steroids has decreased the rate of chronic lung disease among recent survivors38. Cryotherapy can decrease the rate of blindness, but its effects on less severe disorders of vision are still unclear39. The rate of severe ventricular hemorrhage may, however, have decreased40.

In summary, the results of this study indicate that surviving infants with birth weights less than 750 g represent a distinct subgroup of children whose extreme immaturity, low birth weight, or both predispose them to excessive pulmonary and central nervous system injury. These children are the survivors of only 0.3 percent of live births in the region and will not contribute substantially to the overall rate of school-age handicap; these facts, however, do not detract from the enormous expenditure in neonatal resources for each child or from the ongoing educational burden on the child, family, and school system. Although programs of early-childhood intervention may have some compensatory influences on development,41 they have little influence on structural deficits. The prevention of extreme prematurity is thus critical.

Funding and Disclosures

Supported by a grant (R01 HD26554) from the National Institutes of Health and by a Mental Retardation Training Grant (HD07176) from the National Institute of Child Health and Human Development.

We are indebted to Dr. John Moore (MetroHealth Medical Center, Cleveland), Dr. Lawrence Lilien (Fairview General Hospital, Cleveland), Dr. David Francis, Sharon Cohen, Mary Ann Ricci, Harriet Friedman, and Kathy Winter for their assistance in compiling and analyzing the data; to Dr. A.A. Fanaroff and Dr. Saeid B. Amini for their critical comments; and to Joyce Nolan for assistance in the preparation of the manuscript.

Author Affiliations

From the Department of Pediatrics, School of Medicine (M.H., H.G.T., R.E., N.M.-M.), and the Department of Psychology (C.S.), Case Western Reserve University; and the Department of Special Education (N.K.), Cleveland State University -- both in Cleveland.

Address reprint requests to Dr. Hack at Rainbow Babies and Children's Hospital, University Hospitals of Cleveland, 11100 Euclid Ave., Cleveland, OH 44106.

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Citing Articles (445)

    Letters

    Figures/Media

    1. Table 1. Measures of Neuropsychological Achievement.
      Table 1. Measures of Neuropsychological Achievement.
    2. Table 2. Maternal Demographic Risk Factors and Perinatal Data.
      Table 2. Maternal Demographic Risk Factors and Perinatal Data.
    3. Table 3. Perinatal and Neonatal Descriptors of the Very-Low-Birth-Weight Children.
      Table 3. Perinatal and Neonatal Descriptors of the Very-Low-Birth-Weight Children.
    4. Table 4. Neurosensory and Growth Outcomes.
      Table 4. Neurosensory and Growth Outcomes.
    5. Figure 1. Percentage of Children in Each Study Group with Each of Four Major Impairments.
      Figure 1. Percentage of Children in Each Study Group with Each of Four Major Impairments.

      Cerebral palsy was defined to include hemiplegia, diplegia, or quadriplegia; visual impairment to include unilateral or bilateral blindness or visual acuity ≤ 20/200 without glasses in at least one eye; and subnormal head size and height as less than 2 SD below the mean for the child's age.31,32.

    6. Table 5. Incidence of Findings Suggestive of Disabling Conditions.
      Table 5. Incidence of Findings Suggestive of Disabling Conditions.
    7. Figure 2. Percentage of Children in Each Study Group with Subnormal Functioning.
      Figure 2. Percentage of Children in Each Study Group with Subnormal Functioning.

      Subnormal functioning was defined as a standard score of less than 70 for cognitive function,7 academic skills,19 visual motor function,14 and adaptive function24 and a score of less than 30 for gross motor function.13.

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