EARLY NEURODEVELOPMENT OF INFANTS BORN TO
HIV-SEROPOSITIVE MOTHERS.
Short running title: Neurodevelopment in HIV infected infants
Orawan Louthrenoo, M.D., Thanyawee Puthanakit, M.D., Nongyow Wongnum, P.N., Virat
Sirisanthana, M.D.
From the Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Thailand.
Corresponding author: Orawan Louthrenoo, M.D., Department of Pediatrics, Faculty of Medicine,
Chiang Mai University, Chiang Mai, 50200, Thailand. E-mail: olouthre@mail.med.cmu.ac.th
Abstract
Objective: To examine neurodevelopment during the first 12 months of life in infants born to HIV
infected mothers.
Methods: Infants born to HIV infected mothers receiving prenatal zidovudine monotherapy, who
were followed at the Infectious Disease Clinic, Chiang Mai University Hospital, were enrolled in
this study. Neurodevelopmental assessment was administered at the age of 12 months by using
Bayley Scales of Infant Development (BSID). Confirmed HIV infection status was performed at
18 months of age.
Results: Thirty-nine infants, 10 infected and 29 uninfected cases, were studied. Demographic
and perinatal characteristics including birth weight, length, head circumference, prematurity,
maternal age, and maternal education were not different between 2 groups. At 12 months,
growth parameters of HIV infected and non-infected groups were not different, but Mental
Developmental Index (MDI) and Psychomotor Developmental Index (PDI) were lower
significantly in HIV-infected group than non-infected group (MDI=90 vs. 99, p=0.001; PDI=83 vs.
96, p <0.001, respectively). In the HIV infected group, infants with symptomatic HIV infection
had lower MDI and PDI scores than asymptomatic ones.
Conclusion: HIV infected infants showed early lower developmental scores. Neurodevelopment
may be one of the early markers of disease progression of infants with HIV infection within the
first 12 months.
Key words: neurodevelopment, infants, HIV infection
พัฒนาการระยะแรกของเด็กทารกที่เกิ ดจากแม่ติดเชื้อเอชไอวี
หัวเรื่องย่อสัน้ : พัฒนาการของเด็กทารกติดเชือ้ เอชไอวี
อรวรรณ เลาห์เรณู, พ.บ., ธันยวีร์ ภูธนกิจ, พ.บ., นงเยาว์ วงศ์นุ่ม, ประกาศนียบัตรผูช้ ่วยพยาบาล,
วิรตั ศิรสิ นั ธนะ, พ.บ.
ภาควิชากุมารเวชศาสตร์, คณะแพทยศาสตร์ มหาวิทยาลัยเชียงใหม่, เชียงใหม่ 50200
ผูร้ บั ผิดชอบบทความ: พ.ญ. อรวรรณ เลาห์เรณู ภาควิชากุมารเวชศาสตร์, คณะแพทยศาสตร์
มหาวิทยาลัยเชียงใหม่, เชียงใหม่ 50200
บทคัดย่อ
วัตถุประสงค์ เพื่อตรวจประเมินพัฒนาการในช่วง 12 เดือนแรก
ในเด็กทารกทีเ่ กิดจากมารดาติดเชือ้ เอชไอวี
วิธกี าร ได้ทาการตรวจประเมินพัฒนาการในเด็กทารกทีเ่ กิดจากมารดาติดเชือ้ เอชไอวีซง่ึ ได้รบั ยา
zidovudine ป้ องกันขณะตัง้ ครรภ์ ทีไ่ ด้ตดิ ตามการรักษาในหน่วยโรคติดเชือ้
ตึกผูป้ ่ วยนอกกุมารเวชกรรม โรงพยาบาลมหาราชนครเชียงใหม่ เมือ่ อายุ 12 เดือนโดยใช้ Bayley
Scales of Infant Development (BSID)
และทาการตรวจยืนยันสถานะการติดเชือ้ เอชไอวีของเด็กเมือ่ อายุ 18 เดือน
ผลการศึกษา เด็กจานวน 39 คน ติดเชือ้ 10 คนและไม่ตดิ เชือ้ 29
คนไม่พบความแตกต่างของลักษณะทางสังคมและภาวะระหว่างการตัง้ ครรภ์ ซึง่ รวมถึงน้าหนัก
ความยาว และเส้นรอบวงศีรษะแรกคลอด การคลอดก่อนกาหนด
อายุและการศึกษาของมารดาระหว่างเด็กทัง้ สองกลุ่ม ทีอ่ ายุ 12
เดือนการเจริญเติบโตไม่มคี วามแตกต่างแต่ค่าดัชนีของพัฒนาการทัง้ Mental Developmental Index
(MDI) และ Psychomotor Developmental Index (PDI) ต่ากว่าในเด็กทีต่ ดิ เชือ้ (MDI=90 และ 99,
p=0.001; PDI=83 และ 96, p <0.001 ตามลาดับ) ในกลุ่มเด็กทีต่ ดิ เชือ้
เด็กทีแ่ สดงอาการของโรคเอชไอวีมคี ่าดัชนีของพัฒนาการต่ากว่าเด็กทีไ่ ม่มอี าการ
สรุปผลการศึกษา เด็กทีต่ ดิ เชือ้ เอชไอวีแสดงพัฒนาการช้าได้ตงั ้ แต่ช่วงแรกของอายุ
พัฒนาการอาจเป็ นตัวบ่งชีอ้ นั หนึ่งทีบ่ อกถึงการดาเนินโรคในเด็กทีต่ ดิ เชือ้ เอชไอวีในช่วงอายุ 12
เดือนแรก
คาสาคัญ: พัฒนาการ, เด็กทารก, การติดเชือ้ เอชไอวี
HIV infection often causes impairment of growth and development in children. Numerous
observational data describe neurological involvement and developmental delay in pediatric HIV
infection.1-6 Neurological abnormalities are related to a primary HIV infection or may be from
HIV-related morbidity. The most common neurological findings in children with HIV infection
include progressive encephalopathy, nonprogressive developmental delay, and motor
dysfunction.1, 7 Failure to gain weight could also be a direct consequence of HIV infection,
secondary to HIV-related illness, or be associated with adverse social environment and may
occur later. Immunological markers were identified to be associated with disease progression.
Neurological involvement and impaired developmental milestones are often early markers of HIV
infected infants as well and may precede other signs of disease progression.8, 9 Therefore, the
purpose of this study is to examine neurodevelopment on the mental and motor functioning
during the first 12 months of life in infants born to HIV infected mothers.
Methods
Study population: From January 2001 to December 2002, infants born to HIV infected
mothers who were followed up in the Infectious Disease Clinic, Chiang Mai University Hospital
were enrolled. Oral informed consent was obtained from their parents. At the time of this study,
zidovudine monotherapy is included in standard perinatal care,10, 11 so all of the mothers
received prenatal zidovudine.
Measurement:
Demographic characteristics and perinatal history were obtained by interviewing mothers
and from medical records.
Growth and neurodevelopmental assessments were performed at 12 months of age using
the Bayley Scales of Infant Development (BSID).12 The BSID consists of mental and
psychomotor scales. It is widely used to evaluate sensory-perceptual acuity, discrimination and
response ability, problem solving ability, verbal communication, and motor coordination and
skills for infants from 0-42 months of age. The neurodevelopmental assessment was performed
by the developmental pediatrician (O.L.). Prematurity was adjusted as per instructions for
calculating developmental scores. Results are described as Mental Developmental Index (MDI)
and Psychomotor Developmental Index (PDI) which have an average of 100 and a standard
deviation of 15. A score of MDI or PDI less than 85 is considered below average.
The HIV infection status of infants was documented and confirmed at 18 months of age.
Because HIV status was not certain in infants at 12 months of age, there was a natural blinding
of the examiner during this time.
The study was approved by the Research Ethics Committee of Faculty of Medicine.
Statistical analysis: Data were analyzed by using the SPSS 10.0 program (SPSS Inc,
Chicago, IL). A Chi square for proportions and a Student t test for continuous variables were
used to compare the two groups. A p value of less than 0.05 is considered statistically
significant.
Results
Between January 2001 to December 2002, there were 40 pairs of infants and caregivers
enrolled in the study. Because 1 mother refused the blood test to confirmed HIV status at the
age of 18 months, 39 infants were studied including 10 infected cases. Perinatal characteristics
including birth weight were not different between HIV infected and non-infected infants (Table
1). More male infants were found in the infected group but not statistically different. Infected and
uninfected infants were from similar social backgrounds as the mother’s age and education
were not significantly different between the two groups. All of the mothers received zidovudine
monotherapy prenatally except for one in the non-infected group.
At 12 months of age there was no significant difference in growth parameters between HIV
infected and non-infected groups (Table 2). Mean MDI and PDI were significantly lower in HIVinfected infants. Abnormal MDI or PDI was found only in HIV infected group. Among 10 infected
cases, 5 had non-specific HIV symptoms and had lower MDI and PDI scores than asymptomatic
infected and non-infected infants (Table 3).
Discussion:
Of the 39 infants, 10 were found to be infected at the age of 18 months, confirmed by HIV
antibodies. There was no difference in characteristic background including gender, growth
parameters at birth, or prematurity. In previous studies,13, 14 birth weight was not associated with
HIV infection status of infants born to HIV-infected women, which was consistent with this study.
Maternal age and education were similar between infected and uninfected infants. All but one
mother in the uninfected group received prenatal zidovudine. All pregnancies were normal labor
without a complication of chorioamnionitis which has been reported to be a risk factor for
perinatal transmission of HIV.15
At the 12 months of age, when HIV status was not yet definite, growth parameters were not
different between infected and non-infected groups. The slower of growth of infected infants can
occur from HIV-related symptoms, so asymptomatic cases may not show growth failure.
However, neurodevelopment quotients in terms of MDI and PDI were found to be significant
lower in infected infants than infants who were HIV exposed but uninfected. The rate of
development was reported to be slower in infected infants at 3 months of age which was much
slower over time.3 Contrary, it was also reported that the difference of development was not
found until 12 months of age.16 The relationship of head circumference and neurodevelopment
was not found in this study. Growth impairment might occur later than neurological involvement.
A small difference in growth of infected and non-infected infants was found as early as 3-4
months of age before the time of prenatal zidovudine monotherapy.17-19 Below average MDI or
PDI score or developmental delay were found only in the infected group.
In symptomatic cases, MDI and PDI scores were significant lower than infected infants who
had no symptoms. More severe neurological involvement was described in infants with the
clinical manifestations of symptomatic HIV infection.20 The study sample was too small to
evaluate the effects of HIV status and other variables, such as prematurity and maternal
education of less than 9 completed years, that may be associated with low developmental
score.8
There were some limitations in this study. The small sample size may affect the statistical
result of the study. The study population was not randomized and only some of the
demographic data were obtained to compare between infected and non-infected infants.
In summary, our findings documented early abnormal neurodevelopmental outcome in
pediatric HIV infection which were similar to previous studies conducting prior to the time of
prenatal zidovudine.3-5, 16, 21, 22 Larger sample and long-term follow up would give more
information. Careful monitoring of developmental growth is a necessary component of
comprehensive medical care in infants with HIV infection.
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Table 1. Demographic and perinatal characteristics of HIV infected and non-infected infants.
HIV-infected
HIV-negative
p Value
(n=10)
(n=29)
Gender: male
5/10 (50%)
8/29 (28%)
0.25
Prematurity
2/10 (20%)
5/29 (17%)
0.59
Birthweight (gm)
2679  576
2648  420
0.86
Length (cm)
47.4  3.2
46.9  2.6
0.64
Head circumference (cm)
32.4  1.6
32.1  2.4
0.75
Maternal age (yr)
26.5  5.0
28.1  4.9
0.39
Maternal education (yr)
9.5  4.7
9.5  3.1
0.97
Table 2. Growth parameters at 12 months of age and developmental indices of HIV infected and
non-infected infants.
HIV-infected
HIV-negative
(n=10)
(n=29)
12.3  0.8
12.2  0.2
0.21
Weight (gm)
9194  1683
9305  1177
0.82
Length (cm)
72.4  4.3
73.3  2.8
0.44
Head circumference (cm)
45.4  1.6
44.8  1.4
0.32
Mean Mental Developmental Index
90.0  9.6
99.2  6.4
0.001
Mean Psychomotor Developmental Index
83.3  9.8
96.0  7.9
< 0.001
Abnormal MDI or PDI score
5/10 (50%)
0/29 (0%)
< 0.001
Age (mo)
p Value
Table 3. Mental and Psychomotor Developmental Indices of symptomatic and asymptomatic HIV
infected and non-infected infants.
HIV-infected
HIV-negative
p Value
Symptomatic (n=5)
Asymptomatic (n=5)
(n=29)
Mean MDI
88.0  13.3
92.0  4.3
99.2  6.4
0.005
Mean PDI
79.2  12.7
87.4  3.6
96.0  7.9
< 0.001
Figure 1 Mental and Psychomotor Developmental Indices in infants of mothers with HIV
infection.
Mental Developmental Index (MDI)
p value = 0.005
120
100
80
60
symptomatic HIV asymptomatic HIV HIV uninfected
Psychomotor Developmental Index (PDI)
p value = <0.001
120
100
80
60
symptomatic HIV asymptomatic HIV HIV uninfected