Growth at 2 Years of Age in HIV-exposed Uninfected Children in the United States by Trimester of Maternal Antiretroviral Initiation

Abstract

Background Abnormal childhood growth may affect future health. Maternal tenofovir (TFV) use was associated with lower body length and head circumference at one year of age in HIV-exposed uninfected (HEU) US children. Methods We studied 509 HEU children in the US-based Surveillance Monitoring of ART Toxicities cohort whose HIV-infected mothers were not using antiretrovirals at the last menstrual period and began combination antiretroviral therapy (cART) in pregnancy (cART-initiators). We examined adjusted associations between antiretrovirals and CDC 2000 growth z-scores at 2 years of age within trimester of cART initiation: weight (WTZ), length (LNZ), weight-for-length (WFLZ), triceps skinfold z-score (TSFZ), and head circumference (HCZ). Results Mothers mean age was 28.6 years; 57% were black non-Hispanic and 19% delivered at <37 weeks gestation. At 2 years, mean WTZ, LNZ, WFLZ, and HCZ, were above average (P<0.05), while TSFZ (P=0.57) did not differ from average. WFLZ was >1.64 SD (>95th percentile) in 13%. Among children of first trimester cART-initiators, TFV+emtricitabine -exposed children had slightly higher mean WFLZ (0.45 SD, 95%CI −0.10, 1.00) and lower TSFZ (−0.55 SD, 95%CI −1.07, −0.02) compared to zidovudine+lamivudine-exposed. TSFZ was lower in those exposed to boosted protease inhibitors. In contrast, growth in children of second trimester cART-initiators did not differ by antiretroviral exposures. Conclusion Growth was above average in HEU; 13% were obese. Maternal TFV use was not associated with lower length or head circumference at age two, as hypothesized, but may be related to greater weight among those exposed to cART early in pregnancy.

Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance

“…Additional data on infant safety (including bone growth) from studies of pregnant women receiving antiretroviral therapy found no increase in adverse events among TDF-exposed versus unexposed infants. (71)(72)(73) Although a previous study of HIV-infected pregnant mothers found TDFexposed infants to have 12% lower whole-body bone mineral content than unexposed infants, (74) the followup study showed no differences at 2 years of age. (71) Whether invasive procedures during pregnancy, such as amniocentesis, increase the risk of HBV infection in the infants is unclear.…”

“…(71)(72)(73) Although a previous study of HIV-infected pregnant mothers found TDFexposed infants to have 12% lower whole-body bone mineral content than unexposed infants, (74) the followup study showed no differences at 2 years of age. (71) Whether invasive procedures during pregnancy, such as amniocentesis, increase the risk of HBV infection in the infants is unclear. Two studies including 21 and 47 HBsAg mother-infant pairs respectively concluded that the risk of HBV transmission by amniocentesis is low.…”

“…Both studies found no difference in the rates of prematurity, congenital malformations, or Apgar scores. Additional data on infant safety (including bone growth) from studies of pregnant women receiving antiretroviral therapy found no increase in adverse events among TDF‐exposed versus unexposed infants . Although a previous study of HIV‐infected pregnant mothers found TDF‐exposed infants to have 12% lower whole‐body bone mineral content than unexposed infants, the follow‐up study showed no differences at 2 years of age …”

Management of hepatitis B virus infection, updated Swedish guidelines

“…Teratogenic effects of antiviral therapy during pregnancy have not been demonstrated. One study showed that exposure to TDF during pregnancy led to a 12% decrease in bone mineralization in exposed children after birth [78], but this difference had completely disappeared at the age of 2 [79]. No transmission was demonstrated in studies where highly viremic women received antiviral therapy during the last trimester, and where the children were vaccinated and received HBIG soon after childbirth [80,81].…”

Chronic Hepatitis B in Pregnancy

“…LactMed does not advise against breastfeeding with either LAM or tenofovir, given minimal drug exposure in nursing infants. Although concern for bone toxicity has been raised with infants exposed to TDF, there appear to be no differences in bone growth at 2 years of infant follow‐up . Data on TBV safety in breastfeeding remain limited, further supporting use of alternate antivirals in pregnant and postpartum women meeting HBV treatment indications.…”