Children Exposed to But Uninfected With HIV Are Smaller at Birth

Although children exposed to but uninfected with HIV (HEU) were smaller and shorter at birth compared with children unexposed to HIV, the difference was not adversely associated with growth in early childhood, according to Danish study results published in Clinical Infectious Diseases.

Using data from the Danish HIV birth cohort study, researchers included all singleton-gestation HEU children born between 2000 and 2016 and followed-up to age 5 years. To compare anthropometric outcomes, HEU children were matched by sex, parity, and maternal country of birth to a control group of children unexposed to HIV in a 1:5 ratio. The primary outcome was z-scores for age-stratified results for weight, length, body mass index (BMI), as well as weight with respect to length.

The final analysis included 485 HEU children and 2495 children unexposed to HIV. Compared with the control group, HEU children were smaller at birth, with an adjusted difference in mean z-scores for weight and length with respect to age of −0.29 (95% CI, −0.46 to −0.12; P ≤.001) and −0.51 (95% CI, −0.71 to −0.31; P ≤.001), respectively. After adjusting for social and maternal factors, there was a trend towards increasing z-scores for weight and length with respect to age in HEU children. There was no significant difference in z-scores of age-stratified weight data after 14 days of age (−0.13; 95% CI, −0.27 to 0.01; P =.07) and no difference in z-scores for length with respect to age after 6 months of age (−0.15; 95% CI, −0.32 to 0.02; P =.08).

In the adjusted analysis, HEU children born at gestation ≥37 weeks had a higher mean z-scores for weight with respect to length data until 6 months of age compared with children unexposed to HIV (0.27; 95% CI, 0.13-0.40; P ≤.001). While HEU children had smaller z-scores for the ratio of length-stratified weight and age-stratified BMI data compared with children unexposed to HIV after the age 6 months, this difference was not statistically significant.

In a sub-group analysis adjusted for breastfeeding, during the first year of life, HEU children had lower z-scores for length with respect to age and higher z-scores for ratio of length-stratified weight and age-stratified BMI data, but there was no significant difference in z-scores for weight with respect to age in any group. Because none of the HEU children were breastfed, researchers postulated that “the difference in z-scores [for age-stratified weight data] seen between groups may be related to infant feeding mode.”

In addition, researchers noted that key factors associated with lower z-scores for age-stratified weight and length data were maternal treatment with protease inhibitor-based regimens and being born in 2009 or later. However, the study sample was too small to stratify by drug class.

A key study limitation was the exclusion of premature children in the analysis of the ratio of length-stratified weight and age-stratified BMI data, since more HEU children were born prematurely compared with children who were unexposed to HIV.

Given that low birth-weight and rapid catch-up growth in early childhood may have a negative impact on health in adulthood such as “increased risk of obesity, insulin resistance, and increased risk for cardiovascular disease,” the researchers noted that “any possible difference in the timing of catch-up growth between HEU and [children unexposed to HIV] should be investigated in future studies.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Moseholm E, Helleberg M, Sandholdt H, et al. Children exposed or unexposed to HIV: weight, height and BMI during the first five years of life. A Danish nationwide cohort study [published online July 4, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz605