Growth-promoting hormonal alterations in pregnant women living with HIV receiving dolutegravir-based antiretroviral treatment are associated with lower infant 1-year weight z-scores

Kathleen M Powis^1,2,3*Jennifer Jao^4,5Justine Legbedze⁶Caroline Dunk^7,8Keolebogile N Mmasa⁹Samuel W Kgole¹⁰Gosego Masasa¹⁰Terence Mohammed¹⁰Joseph Makhema¹⁰Sikhulile Moyo¹⁰Mitchell Eugene Geffner¹¹Elaine J Abrams^12,13Lena Serghides^14,7,8

• ¹Pediatrics, Harvard Medical School, Boston, Massachusetts, United States
• ²Departments of Internal Medicine and Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, United States
• ³Harvard T.H. Chan School of Public Health, Boston, MA, United States
• ⁴Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
• ⁵Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States
• ⁶Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States
• ⁷Toronto General Research Institute (TGRI), Toronto, Ontario, Canada
• ⁸University Health Network (UHN), Toronto, Ontario, Canada
• ⁹County Durham and Darlington NHS Foundation Trust, Seaham, United Kingdom
• ¹⁰Botswana Harvard Health Partnership, Gaborone, Botswana
• ¹¹The Saban Research Institute of Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California, United States
• ¹²ICAP at Columbia University, New York, United States
• ¹³Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York City, New York, United States
• ¹⁴Department of Immunology and Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada

Background: Several maternal hormones regulate fetal growth, but concentrations of these hormones in pregnancy among women living with HIV and associations between hormone levels and infant anthropometrics is limited.Methods: Pregnant women with HIV receiving dolutegravir/tenofovir/emtricitabine and HIVseronegative women and their infants prospectively enrolled in the Botswana-based Tshilo Dikotla study were included in this analysis. Estradiol, sex-hormone binding globulin (SHBG), progesterone, cortisol, pituitary growth hormone-1 (GH1), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-1 (IGFBP-1) concentrations were measured in maternal plasma collected between 24-29 weeks' gestation. Bioavailable estradiol was derived using estradiol and SHBG concentrations. Generalized linear models were fit to evaluate associations between HIV status and each maternal hormone. Similar models were fit to assess effect modification by HIV status on the relationship between each maternal hormone and infant anthropometrics at birth and 1-year of age.Results: Maternal plasma specimens were available from 114 women (46 with HIV). Women with HIV had lower mean log bioavailable estradiol (β: -0.22, p=0.031), cortisol (β: -0.22, p=0.001), and IGF-1 (β: -0.81, p=0.007), but higher GH1 (β: 0.91, p=0.007) than women without HIV. Infant HIV-exposure status modified associations of log GH1 (β: -0.21, p=0.05) and log IGF-1 (β: 0.40, p=0.004) with infant 1-year weight-for-age z-score (WAZ), adjusting for maternal age, BMI, exclusive breastfeeding duration, and birth WAZ. Among infants who were HIV exposed uninfected, lower GH1 and higher IGF1 levels were associated with higher WAZ at 1 year of age. This associations were not observed in HIV-unexposed infants.Associations between maternal growth-promoting hormones and infant weight at 1 year of life differ significantly by maternal HIV status, reflecting potential perturbations in the maternal-fetal-infant growth axis among pregnant women with HIV. Additional research is needed to identify mechanisms and possible interventions.