Growth patterns of uninfected children born to women living with perinatally versus nonperinatally acquired HIV

Wendy Yu, Denise L Jacobson, Paige L Williams, Kunjal Patel, Mitchell E Geffner, Russell B Van Dyke, Deborah Kacanek, Linda A DiMeglio, Jennifer Jao, Pediatric HIV/AIDS Cohort Study (PHACS), Wendy Yu, Denise L Jacobson, Paige L Williams, Kunjal Patel, Mitchell E Geffner, Russell B Van Dyke, Deborah Kacanek, Linda A DiMeglio, Jennifer Jao, Pediatric HIV/AIDS Cohort Study (PHACS)

Abstract

Objective: The aim of this study was to compare long-term growth between HIV-exposed uninfected children (CHEU) born to women with perinatally acquired HIV (CHEU-PHIV) and CHEU born to women with nonperinatally acquired HIV (CHEU-NPHIV).

Design: A longitudinal analysis of anthropometric measurements from a U.S.-based multisite prospective cohort study enrolling CHEU and their mothers since April 2007.

Methods: CHEU were evaluated for growth annually from birth through age 5 and again at age 7 years. Z-scores were calculated using U.S. growth references for weight (WTZ), height (HTZ), and weight-for-length or BMI-for-age (WLZ/BMIZ). Mid-upper arm circumference (MUACZ) and triceps skinfold thickness (TSFZ) Z-scores were obtained from ages 1 and 2, respectively, through age 7 years. Piecewise mixed-effects models, overall and stratified by race and sex, were fit to assess differential growth patterns across age by maternal PHIV status.

Results: One thousand four hundred fifty-four singleton infants (286 CHEU-PHIV and 1168 CHEU-NPHIV) were included. CHEU-PHIV had slower growth rates than CHEU-NPHIV for WTZ and WLZ/BMIZ at earlier ages and continued to have lower mean WTZ [-0.27, 95% confidence interval (95% CI): -0.50, -0.04] and WLZ/BMIZ (-0.39, 95% CI: -0.67, -0.11) through age 7. Among non-Black boys, CHEU-PHIV had slightly lower WTZ and WLZ/BMIZ at birth than CHEU-NPHIV and these growth deficits persisted through age 7 years.

Conclusion: Compared with CHEU-NPHIV, CHEU-PHIV had diminished growth in early childhood with differences most pronounced among non-Black male children. Further longitudinal follow-up of CHEU-PHIV into young adulthood is needed to understand whether these early effects of maternal PHIV status on growth persist and have other health consequences.

Conflict of interest statement

Conflicts of Interest:

MEG has a research contract with Novo Nordisk; is a member of advisory boards for Adrenas, Daiichi Sankyo, Eton Pharmaceuticals, Neurocrine Biosciences, Novo Nordisk, Pfizer, and QED; serves on a data safety monitoring board for Ascendis; and receives royalties from McGraw-Hill and UpToDate. For the remaining authors, no other funding sources or conflicts of interest were declared.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Figures

Figure 1:. Overall linear piecewise models of…
Figure 1:. Overall linear piecewise models of growth Z-scores over time in CHEU-PHIV vs CHEU-NPHIV
Abbreviations: WTZ=Weight Z-score; HTZ=Height Z-score; WLZ=Weight-for-length Z-score; BMIZ=Body mass index Z-score; MUACZ=Mid-upper arm circumference Z-score; CHEU-PHIV=Children HIV-exposed uninfected born to women with perinatally-acquired HIV; CHEU-NPHIV=Children HIV-exposed uninfected born to women with non-perinatally-acquired HIV. Based on models adjusted for child sex and race and maternal age at delivery, figures show the estimated slopes of CHEU-PHIV and CHEU-NPHIV before and after the change-point, as well as mean slope differences and differences (arrows) at certain ages with 95% confidence intervals (95% CI). When effect modification terms were excluded, we reported overall mean differences (95% CI) between groups. These models were adjusted for child sex and race as well as maternal age at delivery.
Figure 2:. Weight Z-scores over time in…
Figure 2:. Weight Z-scores over time in CHEU-PHIV vs CHEU-NPHIV stratified by race and sex
Abbreviations: WTZ=Weight Z-score; CHEU-PHIV=Children HIV-exposed uninfected born to women with perinatally-acquired HIV; CHEU-NPHIV=Children HIV-exposed uninfected born to women with non-perinatally-acquired HIV. Based on models adjusted for maternal age at delivery, figures show the estimated slopes of CHEU-PHIV and CHEU-NPHIV before and after the change-point, as well as mean slope differences and differences (arrows) at certain ages with 95% confidence intervals (95% CI). When effect modification terms were excluded, we reported overall mean differences (95% CI) between groups. These models were adjusted for maternal age at delivery.
Figure 3:. Height Z-scores over time in…
Figure 3:. Height Z-scores over time in CHEU-PHIV vs CHEU-NPHIV stratified by race and sex
Abbreviations: HTZ=Height Z-score; CHEU-PHIV=Children HIV-exposed uninfected born to women with perinatally-acquired HIV; CHEU-NPHIV=Children HIV-exposed uninfected born to women with non-perinatally-acquired HIV. Based on models adjusted for maternal age at delivery, figures show the estimated slopes of CHEU-PHIV and CHEU-NPHIV before and after the change-point, as well as mean slope differences and differences (arrows) at certain ages with 95% confidence intervals (95% CI). When effect modification terms were excluded, we reported overall mean differences (95% CI) between groups. These models were adjusted for maternal age at delivery.
Figure 4:. Weight-for-length or body mass index…
Figure 4:. Weight-for-length or body mass index Z-scores over time in CHEU-PHIV vs CHEU-NPHIV stratified by race and sex
Abbreviations: WLZ=Weight-for-length Z-score; BMIZ=Body mass index Z-score; CHEU-PHIV=Children HIV-exposed uninfected born to women with perinatally-acquired HIV; CHEU-NPHIV=Children HIV-exposed uninfected born to women with non-perinatally-acquired HIV. Based on models adjusted for maternal age at delivery, figures show the estimated slopes of CHEU-PHIV and CHEU-NPHIV before and after the change-point, as well as mean slope differences and differences (arrows) at certain ages with 95% confidence intervals (95% CI). When effect modification terms were excluded, we reported overall mean differences (95% CI) between groups. These models were adjusted for maternal age at delivery.

References

    1. Van Dyke RB, Patel K, Siberry GK, Burchett SK, Spector SA, Chernoff MC, et al. Antiretroviral treatment of US children with perinatally acquired HIV infection: temporal changes in therapy between 1991 and 2009 and predictors of immunologic and virologic outcomes. J Acquir Immune Defic Syndr 2011; 57(2):165–173.
    1. Patel K, Karalius B, Powis K, Kacanek D, Berman C, Moscicki AB, et al. Trends in post-partum viral load among women living with perinatal HIV infection in the USA: a prospective cohort study. Lancet HIV 2020; 7(3):e184–e192.
    1. Slogrove AL, Powis KM, Johnson LF, Stover J, Mahy M. Estimates of the global population of children who are HIV-exposed and uninfected, 2000–18: a modelling study. Lancet Glob Health 2020; 8(1):e67–e75.
    1. Little KM, Taylor AW, Borkowf CB, Mendoza MC, Lampe MA, Weidle PJ, et al. Perinatal Antiretroviral Exposure and Prevented Mother-to-child HIV Infections in the Era of Antiretroviral Prophylaxis in the United States, 1994–2010. Pediatr Infect Dis J 2017; 36(1):66–71.
    1. Fowler MG, Garcia P, Hanson C, Sansom S. Progress in Preventing Perinatal HIV Transmission in the United States. Emerg Infect Dis 2004; 10(11):e1. doi: 10.3201/eid1011.040622_040601.
    1. Afran L, Garcia Knight M, Nduati E, Urban BC, Heyderman RS, Rowland-Jones SL. HIV-exposed uninfected children: a growing population with a vulnerable immune system? Clin Exp Immunol 2014; 176(1):11–22.
    1. Evans C, Jones CE, Prendergast AJ. HIV-exposed, uninfected infants: new global challenges in the era of paediatric HIV elimination. The Lancet Infectious Diseases 2016; 16(6):e92–e107.
    1. Barker DJ. The origins of the developmental origins theory. J Intern Med 2007; 261(5):412–417.
    1. Ross AC, Leong T, Avery A, Castillo-Duran M, Bonilla H, Lebrecht D, et al. Effects of in utero antiretroviral exposure on mitochondrial DNA levels, mitochondrial function and oxidative stress. HIV Med 2012; 13(2):98–106.
    1. Wedderburn CJ, Evans C, Yeung S, Gibb DM, Donald KA, Prendergast AJ. Growth and Neurodevelopment of HIV-Exposed Uninfected Children: a Conceptual Framework. Curr HIV/AIDS Rep 2019; 16(6):501–513.
    1. Ernst GD, de Jonge LL, Hofman A, Lindemans J, Russcher H, Steegers EA, et al. C-reactive protein levels in early pregnancy, fetal growth patterns, and the risk for neonatal complications: the Generation R Study. Am J Obstet Gynecol 2011; 205(2):132 e131–112.
    1. Dirajlal-Fargo S, Sattar A, Kulkarni M, Bowman E, Funderburg N, McComsey GA. HIV-positive youth who are perinatally infected have impaired endothelial function. AIDS 2017; 31(14):1917–1924.
    1. Judd A, Lodwick R, Noguera-Julian A, Gibb DM, Butler K, Costagliola D, et al. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe. HIV Med 2017; 18(3):171–180.
    1. Singhal A Long-Term Adverse Effects of Early Growth Acceleration or Catch-Up Growth. Ann Nutr Metab 2017; 70(3):236–240.
    1. Singhal A, Cole TJ, Fewtrell M, Deanfield J, Lucas A. Is slower early growth beneficial for long-term cardiovascular health? Circulation 2004; 109(9):1108–1113.
    1. Leunissen RW, Kerkhof GF, Stijnen T, Hokken-Koelega A. Timing and tempo of first-year rapid growth in relation to cardiovascular and metabolic risk profile in early adulthood. JAMA 2009; 301(21):2234–2242.
    1. Baird J, Fisher D, Lucas P, Kleijnen J, Roberts H, Law C. Being big or growing fast: systematic review of size and growth in infancy and later obesity. BMJ 2005; 331(7522):929.
    1. Ong KK, Loos RJ. Rapid infancy weight gain and subsequent obesity: systematic reviews and hopeful suggestions. Acta Paediatr 2006; 95(8):904–908.
    1. Pongcharoen T, Ramakrishnan U, DiGirolamo AM, Winichagoon P, Flores R, Singkhornard J, et al. Influence of prenatal and postnatal growth on intellectual functioning in school-aged children. Arch Pediatr Adolesc Med 2012; 166(5):411–416.
    1. Ong KK, Ahmed ML, Emmett PM, Preece MA, Dunger DB. Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. BMJ 2000; 320(7240):967–971.
    1. Newell ML, Borja MC, Peckham C, European Collaborative S. Height, weight, and growth in children born to mothers with HIV-1 infection in Europe. Pediatrics 2003; 111(1):e52–60.
    1. Jao J, Agwu A, Mhango G, Kim A, Park K, Posada R, et al. Growth patterns in the first year of life differ in infants born to perinatally vs. nonperinatally HIV-infected women. AIDS 2015; 29(1):111–116.
    1. Andrea SB, Hooker ER, Messer LC, Tandy T, Boone-Heinonen J. Does the association between early life growth and later obesity differ by race/ethnicity or socioeconomic status? A systematic review. Ann Epidemiol 2017; 27(9):583–592 e585.
    1. Bowers K, Laughon SK, Kiely M, Brite J, Chen Z, Zhang C. Gestational diabetes, pre-pregnancy obesity and pregnancy weight gain in relation to excess fetal growth: variations by race/ethnicity. Diabetologia 2013; 56(6):1263–1271.
    1. Beck AF, Edwards EM, Horbar JD, Howell EA, McCormick MC, Pursley DM. The color of health: how racism, segregation, and inequality affect the health and well-being of preterm infants and their families. Pediatr Res 2020; 87(2):227–234.
    1. Williams PL, Seage GR 3rd, Van Dyke RB, Siberry GK, Griner R, Tassiopoulos K, et al. A trigger-based design for evaluating the safety of in utero antiretroviral exposure in uninfected children of human immunodeficiency virus-infected mothers. Am J Epidemiol 2012; 175(9):950–961.
    1. Van Dyke RB, Chadwick EG, Hazra R, Williams PL, Seage GR 3rd. The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs. Front Immunol 2016; 7:199.
    1. Jacobson DL, Patel K, Williams PL, Geffner ME, Siberry GK, DiMeglio LA, et al. Growth at 2 Years of Age in HIV-exposed Uninfected Children in the United States by Trimester of Maternal Antiretroviral Initiation. Pediatr Infect Dis J 2017; 36(2):189–197.
    1. Siberry GK, Williams PL, Mendez H, Seage GR 3rd, Jacobson DL, Hazra R, et al. Safety of tenofovir use during pregnancy: early growth outcomes in HIV-exposed uninfected infants. AIDS 2012; 26(9):1151–1159.
    1. Addo OY, Himes JH. Reference curves for triceps and subscapular skinfold thicknesses in US children and adolescents. Am J Clin Nutr 2010; 91(3):635–642.
    1. Addo OY, Himes JH, Zemel BS. Reference ranges for midupper arm circumference, upper arm muscle area, and upper arm fat area in US children and adolescents aged 1–20 y. Am J Clin Nutr 2017; 105(1):111–120.
    1. Tassiopoulos K, Read JS, Brogly S, Rich K, Lester B, Spector SA, et al. Substance use in HIV-Infected women during pregnancy: self-report versus meconium analysis. AIDS Behav 2010; 14(6):1269–1278.
    1. Verbeke G, Molenberghs G. Linear Mixed Models for Longitudinal Data. Springer; New York; 2001.
    1. Min J, Wen X, Xue H, Wang Y. Ethnic disparities in childhood BMI trajectories and obesity and potential causes among 29,250 US children: Findings from the Early Childhood Longitudinal Study-Birth and Kindergarten Cohorts. Int J Obes (Lond) 2018; 42(9):1661–1670.
    1. Sharma D, Shastri S, Sharma P. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects. Clin Med Insights Pediatr 2016; 10:67–83.
    1. Byrne L, Sconza R, Foster C, Tookey PA, Cortina-Borja M, Thorne C. Pregnancy incidence and outcomes in women with perinatal HIV infection. AIDS 2017; 31(12):1745–1754.
    1. Jao J, Kacanek D, Williams PL, Geffner ME, Livingston EG, Sperling RS, et al. Birth Weight and Preterm Delivery Outcomes of Perinatally vs Nonperinatally Human Immunodeficiency Virus-Infected Pregnant Women in the United States: Results From the PHACS SMARTT Study and IMPAACT P1025 Protocol. Clin Infect Dis 2017; 65(6):982–989.
    1. Jao J, Sigel KM, Chen KT, Rodriguez-Caprio G, Posada R, Shust G, et al. Small for gestational age birth outcomes in pregnant women with perinatally acquired HIV. AIDS 2012; 26(7):855–859.
    1. Lazenby GB, Mmeje O, Fisher BM, Weinberg A, Aaron EK, Keating M, et al. Antiretroviral Resistance and Pregnancy Characteristics of Women with Perinatal and Nonperinatal HIV Infection. Infect Dis Obstet Gynecol 2016; 2016:4897501.
    1. Munjal I, Dobroszycki J, Fakioglu E, Rosenberg MG, Wiznia AA, Katz M, et al. Impact of HIV-1 infection and pregnancy on maternal health: comparison between perinatally and behaviorally infected young women. Adolescent health, medicine and therapeutics 2013; 4:51–58.
    1. Hu Z, Tylavsky FA, Kocak M, Fowke JH, Han JC, Davis RL, et al. Effects of Maternal Dietary Patterns during Pregnancy on Early Childhood Growth Trajectories and Obesity Risk: The CANDLE Study. Nutrients 2020; 12(2).
    1. Emmett PM, Jones LR. Diet and growth in infancy: relationship to socioeconomic background and to health and development in the Avon Longitudinal Study of Parents and Children. Nutr Rev 2014; 72(8):483–506.
    1. Tyrrell J, Richmond RC, Palmer TM, Feenstra B, Rangarajan J, Metrustry S, et al. Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight. JAMA 2016; 315(11):1129–1140.
    1. Giles LC, Whitrow MJ, Davies MJ, Davies CE, Rumbold AR, Moore VM. Growth trajectories in early childhood, their relationship with antenatal and postnatal factors, and development of obesity by age 9 years: results from an Australian birth cohort study. Int J Obes (Lond) 2015; 39(7):1049–1056.
    1. Blair PS, Drewett RF, Emmett PM, Ness A, Emond AM. Family, socioeconomic and prenatal factors associated with failure to thrive in the Avon Longitudinal Study of Parents and Children (ALSPAC). Int J Epidemiol 2004; 33(4):839–847.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir