Objective. To measure the health status (HS) and health-related quality of life (HRQL) of preschoolers who were admitted to a neonatal intensive care unit (NICU) at birth and their family caregivers and to investigate differences in HS and HRQL in relation to gestational age and major morbidity experienced during the NICU stay.
Methods. Retrospective cross-sectional survey was conducted in the province of British Columbia, Canada. A total of 1140 of 2221 children who were admitted at birth to the 3 tertiary care NICUs in the province and 393 of 718 healthy full-term children recruited from 2 of these hospitals were studied. The main outcome measures were Infant and Toddler Quality of Life Questionnaire (ITQOL), Health Status Classification System Preschool Version (HSCS-PS), and Child Behavior Checklist/1.5–5 (CBCL)
Results. The overall response rate was 55%; the response rate for families that we located was 67.1%. NICU children differed from healthy children on the ITQOL in physical abilities, growth and development, temperament/moods, behavior, and general health perceptions, and caregivers differed on both parent-impact scales. On the HSCS-PS, proportionally more NICU children had a health problem in the following areas: sight, speech, getting around, using hands and fingers, taking care of self, learning and remembering, thinking and solving problems, pain and discomfort, general health, and behavior. The NICU sample reported more behavioral problems on the CBCL/1.5–5. Poorer HS and HRQL were reported for infants who were born at <27 weeks’ gestation and for children who experienced ≥1 major morbidities during their NICU stay.
Conclusions. Preschool-aged children with conditions that require NICU care and their family caregivers had poorer HS and HRQL in a range of domains compared with healthy children. There were also differences within the sample by gestational age and major morbidity. The differences in health were small using the ITQOL and CBCL/1.5–5 but larger using the HSCS-PS.
Neonatal follow-up studies have helped to identify a range of negative health outcomes associated with neonatal intensive care. Commonly reported adverse outcomes include cerebral palsy, mental retardation, deafness, blindness, and more widespread problems such as learning disabilities and behavioral problems.1–13 Most research to date has focused on preterm infants, particularly the extremely low birth weight. Although many studies report on >1 outcome, a comprehensive assessment of the overall burden of morbidity is often lacking. However, an increasing number of generic multidimensional questionnaires can be used to measure child health more comprehensively.14–18 These measures are usually referred to as health-related quality of life (HRQL) instruments, although the term “health status” (HS) is sometimes used interchangeably. Such measures adopt the World Health Organization’s definition of health, which is “a state of complete physical, mental, and social well-being and not merely the absence of disease.”19
A systematic review14 and other reviews (15–18,20) describe the range of instruments available for use with children and adolescents. Only a few measures are appropriate for preschool-aged children.21–23 A number of neonatal intensive care unit (NICU) follow-up studies have included HS and HRQL instruments to measure health outcomes.24–29 Our study differs from these studies in that it is population based, focuses on preschool-aged children, and examines the full spectrum of NICU graduates.
In our study, we used 3 instruments to assess health at preschool age for children who were admitted at birth to level 3 NICUs (ie, regional neonatal-perinatal centers that provide care for high-risk pregnancies and intensive care for severely ill infants) in the province of British Columbia (Canada) and a comparison group of healthy full-term infants. Our hypotheses were that NICU children and their parents would have poorer reported HS and HRQL compared with a sample of healthy full-term children and that the HS and HRQL of NICU children would be worse for those of lower gestational age and those who experienced ≥1 major morbidities during their NICU stay.
Ethical approval was gained from the University of British Columbia and participating hospitals. Our NICU sample included 2221 surviving infants who were admitted for >24 hours to 1 of 3 level 3 NICUs in British Columbia, Canada, during a 16-month period (March 1996 to June 1997). These 3 hospitals (Children’s and Women’s Health Centre of British Columbia, Royal Columbian Hospital, and Victoria General Hospital) provided 100% of the tertiary care NICU beds in the province. Mothers’ name and contact details were obtained from the health records department at 2 hospitals and manually extracted from ledgers of the third hospital. Our list of infants was matched with provincial mortality records to exclude any infants who had died after discharge from the NICU.
A comparison group of 718 healthy full-term infants were recruited from the 2 hospitals with a hospital-based primary care unit (Children’s and Women’s Health Centre of British Columbia and the Royal Columbian Hospital). This sample included all infants who were delivered over 11 months (March 1996 and January 1997) by primary care physicians at these 2 clinics. Multiple births, infants with a sibling in the NICU sample, and infants who were subsequently admitted to a NICU for >24 hours were excluded. Contact details for the mother were obtained from the health records department at 1 hospital and directly from the primary care unit at the other.
From both groups, we excluded the following families: those who were unable to complete the questionnaire because of language barriers, those for whom we discovered that the child or the mother had died, and those who completed the questionnaire on the wrong child.
Recruitment and Data Collection
A questionnaire booklet was sent to each mother as her child turned 3.5 years of age. A consent letter was included to obtain permission to link the questionnaire data with hospital birth records. We asked that the caregiver who spends the most amount of time with the child complete our questionnaire. All nonrespondents were followed up with a reminder letter and up to 2 more copies of the questionnaire. Remaining nonrespondents received a telephone call, and when the telephone number was not in service or was reassigned or a questionnaire was returned to us from the post office, we searched the Internet telephone directories and contacted the mothers’ primary care physician for a new address. For all families that provided consent, hospital birth record data were obtained from the Canadian Neonatal Network Database30 and linked with the questionnaire data.
The questionnaire booklet included the following 3 instruments:
Infant and Toddler Quality of Life Questionnaire (ITQOL).23,31,32 This 103-item generic measure of HRQL for children aged 2 months to 5 years was developed by Jeanne Langraf and validated in Canada by Klassen et al.23,32 The ITQOL measures 8 child concepts—physical abilities (10 items), growth and development (10), pain and discomfort (3), temperament and moods (18), general behavior (13), getting along with others (15), general health perception (12), and change in health (1)—and 5 parental concepts—anxiety and worry as a result of their child’s health (7 items), limitations in time to meet their own needs as a result of their child’s health (7), mental health (5), general health perception (1), and family cohesion (1). For each scale, item responses are scored, summed, and transformed to a scale from 0 (worst health) to 100 (best health).
Health Status Classification System Preschool Version (HSCS-PS).33 This 14-item HS instrument assesses the following 12 health attributes: seeing, hearing, speaking, getting around, using hands and fingers, taking care of self, feelings, learning and remembering, thinking and solving problems, pain and discomfort, general health, and behavior, each with 3 to 5 levels of severity. Scores for the 12 health attributes of the HSCS-PS were dichotomized into either “no health problem” or “any health problem,” which could be mild, moderate, or severe.
Child Behavior Checklist 1.5–5 (CBCL).34 This 100-item domain-specific measure of child behavioral, emotional, and social function can produce an internalizing and externalizing syndromes score and a total problem score. For each syndrome scale, the contributing items can be summed to give a severity score, with higher scores reflecting more symptoms.
We also included a number of questions to collect sociodemographic information.
Aggregate hospital birth record data (stripped of identifiers) were obtained for nonrespondents to investigate nonresponse bias. Bivariate analysis was used to explore whether response to the survey (yes or no) was associated with sample characteristics (gestational age; small for gestational age; Apgar score <7 at 5 minutes; congenital anomalies; gender; multiple birth; cesarean section; antenatal steroid use; and outborn status, ie, born at a hospital other than the hospital in which the NICU was located) and the following outcomes: 1) major morbidity (defined as at least 1 of the following: chronic lung disease [at 36 weeks], severe intraventricular hemorrhage [≥grade 3], nosocomial infection, necrotizing enterocolitis, and retinopathy of prematurity [≥stage 3]); 2) Neonatal Therapeutic Intensity Scoring System (a continuous variable calculated from a checklist of 63 NICU therapies used in a 24-hour period, weighted according to invasiveness and cost35); and 3) Score for Neonatal Acute Physiology-Version II (a continuous measure of neonatal illness severity, calculated from 6 empirically weighted physiologic measurements made during the first 12 hours of admission to the NICU36).
The t test and Mann Whitney U test were used to test equality of mean scores and ranks for the ITQOL domains and CBCL/1.5–5 (depending on the distribution of the data). We used the benchmarks for standard deviation (SD) units suggested by Cohen37 to estimate the importance of the differences in HRQL between groups (ie, .20 is small, .0 is moderate, and .80 is large). The χ2 test was used to test for differences in the proportion to report an HS problem on the HSCS-PS.
Multiple and logistic regression was used to examine differences in HRQL and HS scores between the NICU and healthy infant groups, after adjusting for the following sample characteristics: annual household income (<$30 000, $30 000–$50 000, $50 000–$80 000, >$80 000), caregiver education (university, trade/technical/community school or college, high school graduate, no high school diploma), marital status (married or common-law vs other), smoking status (yes or no), other smoker in the house (yes or no), biological parent (yes or no), caregiver’s gender, caregiver’s age (continuous variable), gender of the child, and whether child was part of a multiple birth (yes or no). Only those sample characteristics that were significantly related to the outcome variable in bivariate analysis were entered into the regression analyses.
Analysis of variance or Kruskal-Wallis test for continuous data was used to examine differences in scores between gestational age groups (<27, 28–32, 33–37, >37) and the number of major morbidities experienced during the NICU stay (0, 1, ≥2). A Pearson χ2 test was used to examine differences in proportion, and for a linear trend, for categorical data by gestational age group and major morbidity group.
Questionnaires and consent forms were mailed to 2221 NICU families and 718 healthy infant families. Fifty percent of the sample moved at least once since the birth of their infant, and we located 82.8% (n = 2434). A total of 150 infants (123 NICU; 27 healthy children) did not meet our inclusion criteria for the following reasons: language (n = 95), infant died (n = 34), mother died (n = 6), questionnaire completed for wrong child (n = 7), comparison group infant admitted to NICU (n = 7), and not applicable (n = 1). The overall response rate (after exclusions) was 55% (54.3% NICU, 56.9% healthy infant group). The response rate for located families was 67.4% (n = 1140) for the NICU group and 66.4% (n = 393) for the comparison group. Five NICU respondents returned a signed consent form without a completed questionnaire and were dropped from the analysis.
Nonrespondents Versus Respondents
The children of nonrespondents (located) were of older gestational age (35.3 vs 34.7 mean weeks; P = .006 on t test), were less likely to be outborn (11.4% vs 15.2%; P = .044 on χ2 test), were less likely to have experienced a major morbidity in the NICU (3.3% vs 7.4%; P = .001 on χ2 test), had less intensive therapy in the NICU (Neonatal Therapeutic Intensity Scoring System score: 9.1 vs 11.1 [mean]; P < .001 on Mann-Whitney test), and had lower Score for Neonatal Acute Physiology-Version II scores (4.9 vs 7.2 [mean]; P < .001 on Mann-Whitney U test).
The NICU sample included 181 children who were part of a multiple-birth group: 171 twins and 10 triplets. The average age of children in both samples was 47 months (range: 39–65). The NICU sample was composed of 1.8% fewer biological parents, 2.6% more male respondents, and 11.9% more families who earned <$50 000 per year (Table 1).
Table 2 shows the difference in mean scores and β coefficients for the adjusted scores for the NICU and healthy infant groups for each domain of the ITQOL. The NICU children had poorer HRQL in 5 domains. These differences were small in size (SD: ≤0.32), with the largest difference for general health perceptions domain (SD: 0.43).
NICU caregivers reported more anxiety and worry as a result of their child’s health and had less time to meet their own personal needs. These differences were also small (SD: ≤0.24). On the multivariate analysis, we did not find a difference between groups in the scores for general health perception.
On the HSCS-PS, 55.2% of healthy children had no health problems in any area, compared with 39.8% of NICU children (P < .001 on χ2). In 10 of the 12 areas, a significantly larger proportion of NICU children had a health problem than did the healthy infant group (Table 3). The largest difference between groups was for taking care of self, where 12.5% more NICU parents reported that their child required more than the usual help to eat, bathe, dress, or use the toilet. The same pattern of results was found after adjusting for sample characteristics within logistic regression models.
Caregivers of NICU children reported more symptoms on the CBCL/1.5–5 than caregivers of healthy children (Table 4). NICU boys were reported as having more internalizing symptoms and total problems scores than healthy boys, whereas NICU girls had more symptoms on all 3 scales compared with healthy girls. All differences were small in size (SD: ≤0.22). In logistic regression used to adjust for sample characteristics, no differences were found between samples on any scale score scored dichotomously (ie, normal vs borderline or clinical).
Data for gestational age (and major morbidity below) was available for 75% of the NICU sample (ie, caregivers who consented to data linkage). Table 5 shows sample characteristics by gestational age group. On the ITQOL, for physical abilities, children in the 33- to 37-week gestational age group had the highest mean score, and the <27-week gestational age group had the lowest (P = .001 on Kruskal-Wallis test). For general health perception, children in the 33- to 37-week gestational age group had a significantly higher mean score compared with children in the <27-week gestational age group (P = .014 on 1-way analysis of variance). The general health perception scores of caregivers differed significantly (P = .004 on 1-way analysis of variance): parents of children in the 33- to 37-week gestational age group reported lower scores than those in the 28- to 32- and >37-week gestational age groups. These differences were small in size (SD: ≤0.44).
On the HSCS-PS, significant differences by gestational age group were apparent for the following attributes: sight, getting around, using hands and fingers, taking care of self, and learning and remembering. For these 5 attributes, a larger proportion of children in the <27-week gestational age group had a problem compared with the other groups (Table 6), and proportionally fewer children of 33- to 37-week gestational age group had problems in these areas. Although the χ2 test for a linear trend was significant for sight (P = .025) and taking care of self (P = .023), only part of the observed variation between groups for these attributes could be attributed to a linear trend. Compared with the healthy infant group (Table 3), in all areas assessed, children in all 4 gestational age groups reported more health problems. There was no difference between gestational age groups in the CBCL/1.5–5 symptom severity scores.
NICU children experienced the following types of morbidity: nosocomial infection (n = 53), chronic lung disease at 36 weeks (n = 52), intraventricular hemorrhage ≥grade 3 (n = 12), necrotizing enterocolitis (n = 9), and retinopathy of prematurity ≥stage 3 (n = 8). A total of 56 (4.9%) children experienced 1 major morbidity, 20 (1.8%) experienced 2, 10 (0.9%) experienced 3, and 2 (0.2%) experienced 4.
The sample was grouped according to number of morbidities experienced (0, 1, ≥2). On the ITQOL, significant differences were found for physical abilities (P < .001 on Kruskal-Wallis test), growth and development (P < .001 on Kruskal-Wallis test), and general health perception (P < .001 on 1-way analysis of variance); the group with no major morbidity reported the highest mean score, whereas the group with ≥2 morbidities reported the lowest mean score. The differences were small for the first 2 domains (SD: ≤−0.42), but large (SD: 0.98) for general health perception. No differences were found on the parental domains.
On the HSCS-PS, the proportion of children to have a reported problem by morbidity group differed for 9 attributes (Table 7). The group with ≥2 had the largest proportion of children with a problem. The χ2 test for a linear trend was significant for all 9 attributes. However, in only 4 attributes (speech, taking care of self, learning and remembering, and general health) could almost all of the variation between groups be attributed to a linear trend.
Compared with the healthy infant group (Table 3), all groups (including those with no morbidity) had more children with a health attribute problem in the 12 areas. For example, the proportion with a problem in getting around was >4 times greater in those with no morbidity than in the sample of healthy children. Similarly, the proportion with a problem in learning and remembering was 3 times greater in NICU children with no morbidity compared with the healthy infant group. In addition, when only preterm children (<37 weeks) without a major morbidity were compared with the healthy infant group, a significantly larger proportion of preterm children had a reported problem for 10 of 12 health attributes (exceptions: hearing and feelings). There were no differences noted between morbidity groups in CBCL/1.5–5 symptom severity scores.
To our knowledge, this is the first population-based follow-up study to examine the full spectrum of admissions to NICUs at preschool age using multidimensional generic measures of HRQL and HS and including a sample of healthy infants for comparison. Our findings support our hypotheses. NICU children differed from healthy children across a range of domains of health. For the ITQOL and CBCL/1.5–5, the differences were small by Cohen’s benchmarks.37 The HSCS-PS seemed to be a more sensitive measure of the health problems of the NICU sample. On this measure, important differences were found between groups in most of the health attributes assessed. These findings are consistent with the literature on NICU outcomes, which show that NICU care is associated with increased risk for a range of health problems later in life.1–13
Caregiving has been related to increased burden and stress and reduced psychological well-being in parents of preterm children.38–44 We found a small but statistically significant difference in HRQL between parents of NICU children and parents of healthy children on the ITQOL emotional and time-impact scales. Parents of NICU children reported more stress and worry and less time to meet their own needs as a result of their child’s health. The interesting thing here is that whereas children 33 to 37 weeks had better HRQL than infants <33 weeks, the reverse was true for the caregivers. It is possible that caregivers of infants <33 weeks simply adapted themselves more because the problems were more severe and obvious.
Our finding of differences between NICU and healthy children in behavior were in agreement with a recent systematic review, which found that preterm children showed increases in externalizing and internalizing behaviors.1 Unlike a large-scale population-based survey of children aged 4 to 15 in the United Kingdom that found a birth weight gradient effect for behavior,45 we did not find differences in behavior within the NICU sample by gestational age. Additional research to improve understanding about the nature and the frequency of behavior problems and other “new morbidity” in NICU samples and how these are related to socioeconomic and predisposing risk factors is still needed.
A larger proportion of NICU children who were born before 33 weeks experienced health problems in a range of areas compared with those who were born later. In areas in which there were significant differences between groups, it was the <27-week gestational age group with the greater number of health problems and the 33- to 37-week gestational age group with the fewest. Infants >37 weeks tend to be admitted to the NICU for serious problems (eg, asphyxia) and are often not included in follow-up studies, which tend to focus on premature infants. However, our findings suggest that long-term outcome for infants who are admitted for reasons other than a preterm birth may also be compromised.
Children who experienced multiple major morbidities during their NICU stay had poorer reported health in a range of areas compared with children who experienced none or 1 major morbidity and with healthy children. In addition, we found that NICU children who did not experience a major morbidity (and within this group, even the ones born premature) reported poorer health in most areas compared with healthy children. These findings indicate that even in children without major NICU morbidity, subtle abnormalities that may lead to poorer health and function may occur in a range of areas later in life. Follow-up of NICU survivors should pay attention to this overlooked group.
Our study has certain limitations. First, although our response rate is within the range often obtained in a postal survey,46 nonresponse can introduce bias. Some nonrespondents indicated (verbally or in writing) that they were “too busy” to participate. It is also likely that some questionnaires that were returned to us blank were from non-English speakers. Second, where we had data and were able to explore response bias (NICU sample only), we found a few differences in birth-related sample characteristics and outcome that suggest that respondents had sicker infants. However, our study findings about health outcomes of NICU graduates are in agreement with the larger NICU literature, so it is unlikely that the differences that we found are entirely attributable to response bias. Third, our healthy infant sample was not randomly selected from all low-risk births in the province. They were instead composed of a consecutive sample of normal infants who were delivered at 2 of the study hospitals.
This population-based follow-up study of all NICU survivors in 1 Canadian province shows the extent of morbidity in a NICU cohort using 3 different questionnaires. NICU children and their caregivers experienced poorer HS and HRQL across a range of areas of health compared with healthy children and their parents. Infants who were born <27 weeks’ gestation and those who experienced ≥1 major morbidities during their NICU stay also experienced poorer health. These differences were small using the ITQOL and CBCL/1.5–5 but larger using the HSCS-PS.
The Hospital for Sick Children Foundation (Toronto) provided an operating grant for this study. Dr Klassen was the recipient of a Killam Postdoctoral Fellowship. From Canadian Institutes of Health Research, Dr Klassen holds a Senior Research Fellowship and Dr Raina holds a New Investigator Award.
We thank Jeanne Landgraf, Drs Mike Carkner, Michael Klein, Saroj Saigal, and the Canadian Neonatal Network.
- Received February 25, 2003.
- Accepted June 13, 2003.
- Reprint requests to (A.F.K.) Centre for Community Child Health Research, Department of Pediatrics, University of British Columbia, L408, 4480 Oak St, Vancouver, BC, V6H 3V4. E-mail:
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