Change in Prevalence of Chronic Conditions Between Childhood and Adolescence Among Extremely Low-Birth-Weight Children FREE

Therapeutic changes in perinatal care in the 1990s resulted in improved survival among extremely low-birth-weight (ELBW) infants (weight <1 kg). The school-aged outcomes for these children indicate very high rates of chronic health conditions and developmental problems compared with normal-birth-weight (NBW) controls.^{1 - 2} There have been few reports of the outcomes of ELBW children during adolescence, which is a time of enormous social, health, and developmental change.^{3 - 4}

We previously reported significantly higher rates of chronic conditions, functional limitations, and special health care needs among 8-year-old ELBW children born from 1992 through 1995 compared with NBW controls.¹ As part of a longitudinal cohort study, we sought to examine the critical changes in the rates of chronic conditions between the age of 8 years and the age of 14 years (adolescence) according to a noncategorical measure, the revised Questionnaire for Identifying Children With Chronic Conditions (QUICCC-R),⁵ and 2 specific conditions, asthma and obesity, which are major health problems that are prevalent among children today.

Based on reports of increased rates of chronic conditions during adolescence in normal populations⁶ and of adolescent catch-up growth among ELBW children,^{7 - 8} we hypothesized that the high rates of chronic conditions identified at the age of 8 years would increase by the age of 14 years and that catch-up growth would predispose them to obesity.

The population included survivors of the cohort of 344 ELBW children admitted to Rainbow Babies and Children's Hospital, Cleveland, Ohio, from 1992 through 1995.¹ Thirteen children (10 with major malformations, 2 with AIDS, and 1 with tuberous sclerosis) were excluded. Of the remaining 331 children, 238 survived and 181 (76%) were followed up at the ages of 8 and 14 years. They did not differ significantly from the 57 children who were not followed up regarding sociodemographic or birth data; however, fewer were male (39% vs 54%, respectively) and fewer had bronchopulmonary dysplasia during the neonatal period (41% vs 57%).

For the analyses concerning obesity, we excluded 35 children (31 with neurosensory impairment who may have had abnormal growth and 4 who had missing growth measures). The 146 children with growth measures compared with the 35 who were excluded had a significantly higher gestational age (26.5 vs 25.9 weeks, respectively) and fewer were male (35% vs 54%).

An NBW group of 176 children born at term gestation was recruited at the age of 8 years from the same schools as the ELBW children and of the same sex, race, and age within 3 months; of whom 115 children (65%) were reassessed at the age of 14 years.¹ They did not differ in sociodemographic factors, sex, rates of chronic conditions, or subnormal IQ from the 61 children who were not followed up. Two children had missing growth measures. Thus, 113 NBW children were considered for the obesity outcome.

Parent Report Questionnaires. During 2004 and 2009 at the ages of 8 and 14 years, respectively, questionnaires were administered to the parent and included the QUICCC-R⁵ and medical diagnoses of whether the child had ever been diagnosed with asthma and, if so, whether medications for asthma had been prescribed during the past 12 months. Race was self-identified by the parent from the list of racial and ethnic categories used for federal reporting.

The QUICCC questionnaire is based on a unified conceptual definition of chronic conditions and incorporates the consequences of these conditions lasting or expected to last 12 months or longer. It does not assess specific diagnoses but rather classifies children noncategorically. The original version, which we used when children were aged 8 years, has 39 questions.⁹ A shortened version, the QUICCC-R, which has 16 questions, was administered when children were aged 14 years and was compared with the same 16 questions administered in the longer version used at age 8 years.⁵ Similar to the QUICCC, the QUICCC-R is divided into 3 domains of health-related consequences of chronic conditions: (1) functional limitations, (2) dependence on compensatory aids, and (3) need or use of services above those routinely required by children.

To qualify as having a chronic condition, a child must have at least 1 of the consequences of a chronic condition, and each consequence must be attributable to a condition lasting or expected to last 12 months or longer. The QUICCC has good test-retest reliability⁹ and has an 89% agreement (κ = 0.78) with physician classification of chronic disease.¹⁰ Compared with the QUICCC, the QUICCC-R has a sensitivity of 87% and a specificity of 89% (κ = 0.75).⁵

Child Assessment. The children were measured by research assistants who were unaware of their birth-weight status. Participants were weighed unclothed at age 8 years but lightly clothed at age 14 years. To correct for this weight of clothing, we subtracted 0.5 kg from the measured weight of females and 1.0 kg from that of males. Height was measured with a Harpenden stadiometer.

Weight and height z scores were computed from the revised Centers for Disease Control and Prevention growth data, which are age- and sex-specific.¹¹ Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared and the z scores were computed using the Centers for Disease Control and Prevention's norms.¹¹ Obesity was defined as a BMI in the 95th percentile or higher.¹¹

The study protocol was approved by the institutional review board of University Hospitals Case Medical Center. Written informed consent was obtained from parents when the children were aged 8 and 14 years and written assent from children at 14 years.

Univariate comparisons between groups were made using t tests for continuous variables. χ² Tests or logistic regression was used to examine differences in dichotomous outcomes. We considered 3 measures of chronic conditions. First, chronic conditions lasting or expected to last 12 months or longer were analyzed as binary variables (ie, the proportion having ≥1 consequences) and also as the mean number of consequences. Second, asthma was considered as ever diagnosed and as requiring medication during the most recent 12 months. Third, obesity was defined using age- and sex-specific BMI z scores and rates of obesity.¹¹ Sample sizes of 181 ELBW children and 115 NBW controls provide 80% power to detect odds ratios (ORs) of 3.40, 2.60, 2.06, and 1.97 when comparing proportions with a binary outcome at each age, assuming rates of 0.05, 0.10, 0.25, and 0.50, respectively in the NBW group, an increased rate in ELBW group, and 2-sided tests with a significance level of .05.

McNemar tests were used to test the significance of within-group changes in the prevalence of chronic conditions in children between the ages of 8 and 14 years; paired t tests were used to compare the BMI z scores. Generalized estimating equations logistic regression (using SAS Proc GENMOD, SAS Institute Inc, Cary, North Carolina) was used to compare changes in chronic conditions between the ELBW children and the NBW controls at the ages of 8 and 14 years, controlling for the variables of socioeconomic status, race, sex, and neurosensory impairment. Interactions between birth-weight status and age at time of study were examined. Analogous analyses were performed on the BMI z scores using linear mixed models with SAS Proc MIXED (SAS Institute Inc) and generalized estimating equations models with the identity-link function were used to analyze the total numbers of chronic conditions because these outcomes had a skewed nonnormal distribution.

Socioeconomic status was defined as the mean of the sample z scores for maternal education and median family income according to the 2000 Census tract of the family's neighborhood. We did not adjust for multiple comparisons. Statistical analyses were conducted using SPSS version 19 (SPSS Inc, Chicago, Illinois) and SAS version 9.2 (SAS Institute Inc). Two-sided tests were used and a P value of less than .05 was considered statistically significant.

The ELBW children and NBW controls did not differ significantly in maternal sociodemographic descriptors. Among the ELBW children, neonatal complications included bronchopulmonary dysplasia defined as oxygen dependence at 36 weeks corrected age in 74 children (41%) and a severely abnormal cerebral ultrasound in 44 children (24%). Thirty-one ELBW children (17%) had neurosensory impairments.

Compared with NBW controls, ELBW children had significantly higher rates of subnormal IQ and enrollment in individual education programs (Table 1). The ELBW children were significantly younger than the NBW children at the time of the 8-year follow-up (mean [SD] age: 8.7 [0.6] years vs 9.2 [0.8] years, respectively) but their ages were similar at the time of the 14-year follow-up (mean [SD] age: 14.7 [0.7] years vs 14.8 [0.7] years).

Within the ELBW cohort, the overall rates of chronic conditions did not change between the ages of 8 and 14 years (75% and 74%, respectively; Table 2) but there was a significant decrease in the mean number of chronic conditions per child (Table 3). Within the domains of the QUICCC-R, the rates of functional limitations decreased significantly from 56% to 46% (P = .02); the rates did not decrease for compensatory dependencies or needs for services. Specific decreases in functional limitations included the parent report of mental or emotional delay. Service needs that decreased included occupational or physical therapy and rehospitalizations (Table 4).

Within the NBW cohort, neither the overall rates and numbers of chronic conditions nor the functional limitations or special health care needs changed. However, the rates of compensatory dependencies increased significantly from 22% to 34% (P = .02) due to an increase in prescribed medication.

Group comparisons revealed that the significantly higher rates and numbers of chronic conditions among the ELBW children at age 8 years persisted at age 14 years (74% for ELBW children vs 47% for NBW controls; adjusted OR [AOR], 2.8 [95% confidence interval {CI}, 1.7-4.6]; Table 2 and Table 4). At age 14 years, 46% of ELBW children had functional limitations compared with 16% of NBW controls (AOR, 4.2; 95% CI, 2.2-7.9), including mental or emotional delay, trouble understanding simple instructions, and speaking and communicating.

Forty-eight percent of ELBW children had compensatory dependencies compared with 34% of NBW controls (AOR, 1.7; 95% CI, 1.0-2.8), including prescribed medication and more needs for services such as special arrangements in school. The ELBW children had higher rates of postneonatal hospitalization compared with NBW controls at 8 years but not at 14 years.

The rate of ELBW children with asthma requiring medication did not change between the ages of 8 and 14 years (23% at both ages). For the NBW controls, the rate of asthma increased significantly between the ages of 8 and 14 years from 8% to 17%, respectively (P = .002). The significantly higher rates of asthma among the ELBW children compared with NBW controls at age 8 years persisted at age 14 years when defined as ever-diagnosed asthma (39% vs 21%, respectively; AOR, 2.7 [95% CI, 1.5-4.7]) but were no longer significant when defined as receiving medication during the previous 12 months (ie, current asthma) (23% vs 17%, respectively; AOR, 1.5 [95% CI, 0.8-2.8]). Fifty-two percent of ELBW children ever diagnosed with asthma at the 8-year follow-up had a history of bronchopulmonary dysplasia compared with 34% who had no history of asthma (P = .01).

The ELBW children had significantly lower BMI z scores than the NBW controls at age 8 years (0.06 vs 0.43, respectively; β, −0.4 [95% CI, −0.7 to −0.1]). The mean BMI z scores increased in ELBW children from 0.06 at age 8 years to 0.38 at age 14 years (P < .001) and the rates of obesity increased from 12% at age 8 years to 19% at age 14 years (P = .02). These scores and rates did not change among the NBW controls; at age 14 years, the mean BMI scores and rates of obesity did not differ significantly between the ELBW children and NBW controls (Table 2).

In the multivariable analyses, in addition to ELBW status, neurosensory impairments, lower socioeconomic status, and male sex were significantly associated with overall chronic conditions, functional limitations, and greater need for services; male sex was associated with higher rates of ever-diagnosed asthma (Table 2 and Table 4). Obesity was not associated with any of the examined variables.

We previously reported on the high rates of chronic health conditions among ELBW children compared with NBW controls at the age of 8 years and sought to examine possible changes during the critical period of adolescence. Our results reveal that the overall rates of chronic conditions among both ELBW children and NBW controls were relatively stable. During adolescence, ELBW children continue to have significantly higher rates of functional limitations, compensatory dependencies, and increased use of or need for services than NBW controls. Rates of asthma among ELBW children also remained stable whereas they increased among NBW controls such that when defined as current asthma, the differences between ELBW children and NBW controls were no longer significant at the age of 14 years.

Of major concern is the significant increase between the ages of 8 and 14 years in mean BMI z scores and rates of obesity among ELBW children compared with the relatively stable rates among NBW controls. Our results indicate both positive and negative changes in the health trajectories of ELBW children during adolescence.

Reports of adolescent health outcomes of ELBW children born in the 1990s pertain to the early adolescence of children born prior to 26 weeks gestation in Sweden and the United Kingdom.^{3 - 4} Similar to our finding, Farooqi et al³ reported significantly higher rates of chronic conditions as measured with the QUICCC at the ages of 11 to 12 years. Fawke et al⁴ reported significantly higher rates of impaired respiratory morbidity in the British Epicure study population at the age of 11 years and a current rate of asthma of 25%, which is similar to our rate of 23%. Longitudinal changes in these outcomes have not been reported.

The studies of children born prior to 1990 similarly reported significantly higher rates of chronic illnesses among ELBW children during adolescence. These pertained mainly to neurocognitive disorders^{13 - 14} and asthma,¹⁵ with functional problems and rehospitalizations resulting from a combination of these respiratory and neurological conditions.^{16 - 17} Similar to our findings, Saigal et al¹⁶ reported stability in the rates of chronic conditions among ELBW children born from 1977 through 1982 but reported an increase in medication use between the ages of 8 and 14 years.

Our results among the NBW controls are similar to those reported nationally. Rates of chronic conditions or special health care needs during childhood range from 12% to 37%, depending on the definition.^{18 - 20} Between the ages of 12 and 17 years, the rate of ever-diagnosed asthma is 16.6% and the rate of current asthma is 10.2%.²¹ Twenty percent of children are obese between the ages of 6 and 11 years and 18% are obese between the ages of 12 and 19 years.²² Chronic conditions and special health care needs are also reported to increase during adolescence.⁶ The high rate of chronic conditions in our NBW controls might be due to the lower socioeconomic status of our cohort (60% of whom are minorities) and to current parent perceptions of children's health.²⁰

Our findings of an increase in the rates of asthma in the NBW population during adolescence reflect epidemiological studies²³ and national trends.²⁴ The lack of an increase in our ELBW population during adolescence supports suggestions of a different asthma phenotype among preterm children.^{25 - 26} The major etiological determinant of asthma in normative populations is genetic susceptibility to atopic disease, which interacts with environmental factors, whereas the pathophysiology of asthma in preterm children is mainly associated with abnormal lung development, bronchopulmonary dysplasia, and obstructive airway disease.^{4 ,26 - 29} Improvement in pulmonary function^{28 - 29} and stabilization in the rates of asthma during adolescence have been reported among ELBW children^{16 ,29} ; however, the way in which the trajectory differs from that of NBW children has not been reported.

Our rates of adolescent obesity among ELBW children and NBW controls reflect the current obesity epidemic.²² The increase in BMI among ELBW children during adolescence compared with NBW children has been reported previously in addition to the long-term implications of catch-up growth for metabolic and cardiovascular disease.^{7 - 8 ,30 - 31} However, the considerable catch-up in obesity among ELBW children to the current very high prevalence among NBW children may further intensify the known threat to adult health.

Our findings of a significant association of neurosensory impairments and lower socioeconomic status with functional limitations and need for services indicates both biological and sociodemographic influences on children's health in both NBW and preterm children. The significant association of male sex with functional limitations, need for services, and childhood asthma has been reported.^{20 ,24 ,27 ,32}

Strengths of this study include our longitudinal design and use of both noncategorical and specific diagnostic categories of chronic illness, each of which has important epidemiological and clinical implications. Our use of a generic or noncategorical approach, independent of diagnoses, provides an assessment of the multiple chronic sequelae of preterm birth and also incorporates a functional classification as suggested by the World Health Organization.³³

Children's special health care needs are used for the identification and planning of federal aid and services and also provide an indirect measure of the enormous cost of providing health care and education for these children, of whom preterm survivors constitute an important subgroup.^{34 - 36} We chose to examine longitudinal changes in the rates of asthma and obesity because asthma is a common consequence of preterm birth and obesity may have long-term metabolic and cardiovascular implications.³⁰

We did not consider cerebral palsy or cognitive impairment, which are chronic conditions that are also prevalent among preterm children, because their rates are fairly stable after middle childhood³⁷ ; however, the QUICCC-R does include parent report of developmental problems and need for special education.

The possible limitations of our study include the fact that our population is based on birth weight rather than gestational age and that our sample of ELBW children represents an urban perinatal center and is not representative of the entire United States. The follow-up rate of the NBW controls is lower than that of the ELBW children, which is probably due to their lesser commitment to the study. However, there were no sociodemographic differences between the 2 groups.

We excluded children with neurosensory abnormalities from the examination of obesity because they tend to grow poorly, which might have influenced outcomes. Fewer of the ELBW children followed up had bronchopulmonary dysplasia compared with those children who were not followed up, which might have influenced their rates of asthma.

Our results are based mainly on parent report, which may be biased and inconsistent between periods. However, the QUICCC has been validated as a parent measure of child health.¹⁰ Some outcomes had small numbers of events, which was reflected in the wide 95% CIs. There is always the possibility of detection bias among ELBW children; however, the detection of an increased rate of asthma in NBW controls argues against this. Finally, because the QUICCC-R provides a noncategorical measure of chronic health conditions, specific diagnoses aside from asthma and obesity were not examined.

Because mortality of ELBW infants has reached a plateau with the majority of infants currently surviving, the residual rates of neonatal morbidity and resultant chronic illness have become critical.³⁸ Rates of neonatal morbidity have decreased since 2000 but there is, as yet, no evidence of improved health outcomes.

Our results may have relevance to current survivors. The ELBW status may be considered a marker for the risk of multiple chronic conditions that warrant closer than average health surveillance during adolescence. In addition to therapy for neurodevelopmental disorders, ELBW children with asthma or obesity should receive interventions such as smoking prevention and exercise encouragement to reduce the consequences of these conditions and to possibly enhance their long-term adult outcomes.^{39 - 40}