Journal of Pediatric Psychology, Vol. 25, No. 8, 2000, pp. 583-587
© 2000 Society of Pediatric Psychology
Brief Report |
Effects of Pediatric HIV Infection on Mental and Psychomotor Development
1 Boston University Medical Center, 2 HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute, Columbia University, 3 St. Luke's/Roosevelt Hospital Center, 4 Bronx-Lebanon Hospital
All correspondence should be sent to Claude Ann Mellins, HIV Center for Clinical and Behavioral Studies, Box 15, 1051 Riverside Drive, New York, New York 10032. E-mail: cam14{at}columbia.edu .
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Abstract |
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Objective: To examine the effect of HIV status on infants' mental and psychomotor functioning, controlling for confounding factors such as prenatal drug exposure and birth conditions.
Methods: Twenty HIV-infected and 25 seroreverted infants (ages 3-30 months old) were administered the Bayley Scales of Infant Development (BSID) and a neurological examination at two time points, 4 to 12 months apart. The majority were from ethnic minority, socioeconomically disadvantaged families; 67% of the infants were prenatally drug-exposed.
Results: HIV-infected infants had significantly lower scores on the BSID at baseline (mental development) and follow-up (motor development) compared to seroreverters. When HIV and neurological deficits were considered together, HIV+ children with neurological deficits scored significantly lower than HIV+ children without neurological deficits and seroreverters, with and without neurological diagnoses. Prenatal drug exposure was not associated with performance on the BSID.
Conclusions: These data suggest that CNS involvement is a critical pathway by which HIV affects infants' neurodevelopment.
Key words: pediatric HIV/AIDS; cognitive development; psychomotor development; prenatal drug exposure; pediatric neurological dysfunction.
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Introduction |
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Studies examining the effects of HIV infection on children's cognitive performance have found significant impairment in the majority of symptomatic HIV-infected children, including language deficits, attentional problems, and delays in the acquisition of language and motor milestones (e.g., Levenson & Mellins, 1992
;
Mellins, Levenson, Zawadzki, Kairam, &
Weston, 1994; Nozyce et al.,
1994). The epidemiology of pediatric HIV infection has made it
difficult to establish a causal relationship between HIV and cognitive
impairment, given its association with a multitude of other risk factors
related to poor developmental outcomes in children (e.g., poverty, prenatal
drug exposure, birth complications, stress, and chronic illness)
(Bendersky & Lewis, 1994;
Chasnoff, Griffith, Freier, & Murray,
1992; Levenson & Mellins,
1992). Most studies on pediatric HIV and cognitive impairment have
not adequately controlled for these possible confounding factors.
Mellins et al. (1994)
evaluated the effects of HIV status, prenatal drug exposure, and neurological
dysfunction on children's mental and motor development, using the Bayley
Scales of Infant Development (BSID; Bayley,
1969). HIV-infected infants were compared to seroreverters
(infants born to HIV+ mothers who do not acquire the virus) and to prenatally
drug-exposed infants born to mothers who were not HIV-infected on the BSID.
All three groups were from socioeconomically disadvantaged, ethnic minority
communities. Infants who were both HIV-infected and prenatally drug exposed
performed significantly lower on mental and motor developmental indexes than
infants without both risk factors. Considerable overlap was noted between
serostatus and neurological dysfunction, suggesting that the association
between neurological dysfunction and BSID performance most likely reflected
the effects of HIV disease on the central nervous system (CNS). Unfortunately,
the study design did not allow for examination of these effects over time.
In the present study, the unique and combined contributions of HIV infection, neurological dysfunction, and prenatal drug exposure to infants' developmental functioning were examined over two time points. In a sample of 45 HIV-exposed infants, all from low socioeconomic status (SES) communities, the primary hypotheses were (1) HIV-infected infants' performance on the BSID will be significantly lower than that of uninfected infants over time, and (2) these differences will be associated with neurological impairment and will be present even after controlling for prenatal drug exposure.
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Method |
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Participants
Data were obtained from the medical records of 20 HIV-infected and 25 seroreverted infants, ages 3-30 months, receiving care at a family-based HIV primary care clinic in a large metropolitan hospital in New York. Infants were referred to the clinic by pediatricians and social workers at other primary care facilities and foster care agencies. The sample included all infants between 3 and 30 months who had (1) two developmental assessments with the BSID, conducted between 4 and 12 months apart (a smaller range was not possible given the sample size), and (2) two neurological assessments performed within 6 weeks of each developmental assessment. Forty-five children were eligible.
At time 1, children's ages ranged from 3 to 21 months (M = 11.4, SD = 5.4); at time 2, they ranged from 7.9-27.7 months (M = 18.6, SD = 5.5); 24 were male and 21 female. The majority were African American (n = 23) or Latino (n = 20), and prenatally drug exposed (n = 30), according to mothers' self-reported drug use during pregnancy and/or a positive infant toxicology test.
HIV infection was determined by persistence of HIV antibodies at 
18
months of age by ELISA method with confirmation by Western blot. Sixteen of
the 20 HIV-infected children were classifiable according to the Centers for
Disease Control (CDC) system, which is based on the clinical manifestations of
HIV infection and the degree of immune suppression
(CDC, 1994). Four HIV-infected
children at each time were not classifiable due to insufficient medical record
data; 11 of 16 HIV-infected children at time 1, and 12 of 16 children at time
2 were classified as symptomatic. Given that the majority of children were
symptomatic at both times, we could not examine differences between
symptomatic and asymptomatic children and, thus, compared them as one group
(HIV-infected) to seroreverters. Data on antiretroviral or other medical
treatment were not available to the authors. Study data were collected prior
to the use of the currently Highly Active Antiretroviral Treatments (HAART),
including protease inhibitors.
Fourteen (70%) HIV-infected children and 16 (64%) seroreverters were prenatally drug exposed. All children in both groups were Medicaid recipients. Data on prenatal conditions were not consistently available, particularly on the seroreverters, and were not included in this set of analyses.
As noted, each participant received two neurological and developmental evaluations as part of routine care. Neurological evaluations were conducted by pediatric neurologists who were not blind to the children's serostatus in order to monitor progression of HIV disease. Psychologists, blind to the children's HIV status, conducted the developmental evaluations. Written consent for use of the data in research was obtained from the participant's caregiver at the time of the evaluation.
Measures
The BSID is an individually administered psychometric assessment of
developmental functioning, consisting of two scales: Mental Development Index
(MDI) and Psychomotor Development Index (PDI). BSID standard scores range from
50 to 150 (M = 100, SD = 16). Raw scores cannot be converted
to standard scores lower than 50. Because this limited floor has been
problematic in previous research (e.g.,
Levenson & Zino, 1979;
Mellins et al., 1994),
Naglieri (1981) developed a
method for extrapolating the standard scores of children scoring out of range
on the BSID using estimates of children's performance based on statistically
derived expected scores. Extrapolated scores have previously been used with
low-functioning populations (Goldstein,
Smith, Waldrep, & Inderbitzen, 1987;
Levenson & Zino, 1979) and
were used in the present study. The data collection for this study began in
1991, when the first version of the Bayley was the most widely used and
psychometrically sound measure of infant development (see
Sattler, 1988).
Neurological functioning was assessed with the Neurological Evaluation for
Children (NEC; Chiriboga, Kairam, &
Kline, 1990), a standardized pediatric neurological evaluation
with adequate interrater reliability. The NEC yields systematic clinical
neurological diagnoses (e.g., microcephaly, hypertonia, motor weakness) based
on a clinical history and physical neurological examination. At each time
point, participants were classified on the NEC as either neurologically
impaired (presence of abnormal neurological diagnosis) or normal (no
neurological disorders were detected).
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Results |
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Association Between Demographic Variables and Serostatus
Using analyses of variance (ANOVAS) or chi-square tests of independence, we found no significant group differences between HIV-infected and seroreverted children for gender, ethnicity, age, or prenatal drug exposure (p = ns).
HIV-Infected Versus Seroreverters on the MDI and PDI
(Table I)
At both time points, HIV-infected children had lower scores on the MDI and
PDI than seroreverters. At time 1, these differences were statistically
significant on the MDI (t = 2.6, p 
.05) and not
significant, although borderline, on the PDI (t = 1.9, p
=.07). At time 2, these differences were statistically significant on the PDI
(t = 2.2, p .05), but not on the MDI (t = 1.7,
p = ns). Across groups, Pearson correlations were highly significant
between time 1 and time 2 MDI scores (r =.68, p <.01) and
between time 1 and time 2 PDI scores (r =.61, p
.01).
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Neurological Diagnoses
At both times, children with abnormal neurological diagnoses scored lower
on the MDI and PDI than those with normal neurological diagnoses (t
tests ranged from 2.0, p <.05, to 3.2, p .01).
HIV Status and Neurological Diagnoses
Chi-square analyses indicated an association between neurological diagnosis
and HIV status at time 1 (
2 = 7.61, p <.01), but
not at time 2 (p = ns). Approximately half of the HIV-infected
children had abnormal neurological diagnoses at times 1 and 2 compared to 14%
and 28% of the seroreverters at times 1 and 2, respectively. The majority of
seroreverters with abnormal neurological diagnoses (100% at time 1 and 71% at
time 2) and HIV-infected children with abnormal neurological diagnoses (64% at
time 1 and 70% at time 2) were prenatally drug exposed.
Children were stratified according to HIV and neurological status (Table I). On average, HIV-infected children with abnormal neurological diagnoses performed in the Borderline to "Deficient" range on the BSID at times 1 and 2, whereas all other groups performed in the Average range.
To examine the effects of neurological diagnosis and HIV status, adjusting
for the effects of each, we conducted four ANOVAs, one for each dependent
variable (MDI and PDI) at each time point. For time 1 MDI, ANOVAs revealed a
main effect of HIV status (F = 4.5, p .05), but not
neurological diagnosis or an interaction effect (p = ns). On the PDI,
a significant main effect of neurological diagnosis (F = 4.6,
p .05) was found, as well as an interaction effect of HIV and
neurological diagnosis (F = 4.6, p .05); there was no
main effect of HIV status (p = ns).
At time 2, there was no main effect on the MDI or PDI of HIV status
(p = ns). However, a significant main effect of neurological
diagnosis (F = 11.2, p .01) and an interaction effect of
HIV status and neurological diagnosis were found for the MDI (F =
4.5, p .05), but not the PDI (p = ns). As seen in
Table I, there were large
differences between HIV+ children with and without neurological diagnoses, and
minimal differences between HIV- children with and without neurological
diagnoses.
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Discussion |
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TopAbstractIntroductionMethodResultsDiscussionReferences |
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This study examined the effect of HIV status on children's mental and psychomotor functioning at two time points. HIV status and neurological impairment were associated with lower scores on the BSID at Baseline (MDI) and follow-up (PDI). When HIV and neurological status were considered together, HIV+ children with neurological deficits scored significantly lower than HIV+ children without neurological deficits and seroreverters, with and without neurological diagnoses.
The association of neurologic dysfunction with deficits in HIV-infected
children's mental and psychomotor development is consistent with the findings
of Mellins et al. (1994) in
which accounting for both HIV status and neurological diagnosis was important
in predicting MDI and PDI performance. This suggests that the CNS is the
primary pathway through which HIV affects mental and psychomotor development
rather than HIV infection leading to merely nonspecific debilitating effects.
These results also correspond with a recent study by Brouwers et al.
(1995) that demonstrated an
association between neurological abnormalities on CT scans and the degree of
cognitive decline in HIV-infected children.
Contrary to the findings of Mellins et al.
(1994), however, the present
investigation did not find children's BSID performance to be affected by
prenatal drug exposure. Unfortunately, our ability to adequately examine the
contribution of this variable was limited because the majority of children in
both groups were prenatally drug exposed.
There were several other limitations to the study. We did not have children who were unexposed to both drugs and HIV. Inclusion of children without multiple risk factors would be useful in uncovering the unique contributions of HIV. Given the epidemiology of pediatric HIV, it is hard to obtain a sample of these children in the United States. A small sample size limited our ability to consider multiple variables and potential interaction effects in more complex data analytic models. It also prevented us from interpreting nonsignificant findings and results of borderline significance, particularly differences between time 1 and time 2 findings on the MDI and PDI.
Finally, we did not have access to data on medication use and the data were
collected prior to use of HAART. Future studies will need to assess the impact
of the recent advances in HIV treatment, as well as the potential for
medication side effects. It may also prove useful to examine the impact of
environmental variables on HIV-infected children, given that factors that
co-occur with HIV, such as poverty, low SES, exposure to parental drug use,
and experiencing violence, can contribute to poor development (cf.
Osofsky & Jackson, 1994;
Pynoos & Nader, 1990).
The present follow-up study, accounting for several possible confounding variables, indicates that CNS involvement may be a critical pathway by which HIV affects infants' neurodevelopmental functioning. These results highlight the need to monitor the neurodevelopment of HIV-infected children and the need for specialized programs to address developmental delays and deficits early on.
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Acknowledgments |
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This research was supported by Center Grant P50-MH43520 from the National Institute of Mental Health to the HIV Center for Clinical and Behavioral Studies (PI, Anke Ehrhardt, PhD), a Behavioral Sciences Training Grant T32MH19139 from the National Institute of Mental Health (PI, Zena Stein, MD), and a grant from the Aaron Diamond Foundation (PI, Claude Ann Mellins, PhD). We thank Drs. Zena Stein, Michael Lewis, Margaret Bendersky, and Saul Rosenthal for their valuable consultations on this manuscript. We are saddened by the loss of our friend and mentor, Dr. Jacob Cohen, whose insightful comments were invaluable.
Received April 30, 1999; revision received August 19, 1999; accepted October 29, 1999
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