Third Trimester Vitamin D Status Is Associated With Birth Outcomes and Linear Growth of HIV-Exposed Uninfected Infants in the United States

Abstract Background The prevalence of congenital cytomegalovirus infection (cCMV) at birth is 0.5%–1% in the United States. Most cCMV newborns are asymptomatic at birth with 10%–15% subsequently developing sequelae, such as hearing loss. Higher cCMV prevalence (2.5%–11.4%) is reported in infants born to HIV-infected women, associated with maternal immune suppression and lack of antiretroviral therapy (ART), with few studies addressing neurodevelopmental (ND) outcomes in their offspring. We report birth prevalence of cCMV in a cohort of HIV-exposed, uninfected infants (HEU) born to women on combination ART with well-controlled HIV and describe ND outcomes through age 5 years. Methods The Surveillance Monitoring for ART Toxicities (SMARTT) study is an ongoing NICHD-funded observational multi-centered cohort study (United States and Puerto Rico) of growth and development of HEU children that commenced in 2007. As of August 1, 2017, participants with stored blood pellets collected ≤3 weeks after birth and at least 1 ND assessment ≥1 year of age had pellets tested by DNA PCR to establish cCMV. Comparisons of ND outcomes (defined in figure) at ages 1, 2, and 5 by cCMV status were made using Wilcoxon and Fisher’s Exact tests. Results Of 895 children meeting study criteria (55% black; 32% white; 40% Latino), 8 had cCMV, yielding a birth prevalence of 0.89% (95% CI 0.39–1.75%). All were asymptomatic and similar to CMV-uninfected infants in gestational age and anthropometric measurements at birth. The last HIV viral load prior to delivery was undetectable in 88% of women. The last available CD4% was <20% in 3/8 mothers of cCMV newborns compared with 112/873 in those without (38% vs. 13%, P < 0.07). The mean duration of follow-up (± standard deviation) of children with cCMV was 7.2 years (1.6) and those without 5.9 (2.3) years (P < 0.11). ND assessments for language development (CDI at 1, A&S at 2, TOLD-P:3 at 5), cognition (Bayleys-III at 1), intelligence (WPPSI-III at 5), and hearing (PTA at 5) did not differ by cCMV status (figure). Conclusion Birth prevalence of cCMV in HEU children born within the last decade approaches national US prevalence. Preschool HEU children with asymptomatic cCMV at birth did not show poorer language, hearing, and developmental outcomes compared with CMV-uninfected HEU children. Disclosures All authors: No reported disclosures.

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The Vitamin D Hypothesis Revisited: Race-Based Disparities in Birth Outcomes in the United States and Ultraviolet Light Availability

American Journal of Epidemiology ◽

10.1093/aje/kwu023 ◽

2014 ◽

Vol 179 (8) ◽

pp. 947-955 ◽

Cited By ~ 8

Author(s):

Z. M. Thayer

Keyword(s):

United States ◽

Vitamin D ◽

Ultraviolet Light ◽

Birth Outcomes ◽

Light Availability ◽

The United States

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Vitamin D status in the United States, 2011–2014

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz037 ◽

2019 ◽

Vol 110 (1) ◽

pp. 150-157 ◽

Cited By ~ 44

Author(s):

Kirsten A Herrick ◽

Renee J Storandt ◽

Joseph Afful ◽

Christine M Pfeiffer ◽

Rosemary L Schleicher ◽

...

Keyword(s):

United States ◽

At Risk ◽

Vitamin D ◽

Dietary Intake ◽

Vitamin D Deficiency ◽

The United States ◽

Vitamin D Status ◽

Hydroxyvitamin D ◽

Hispanic Origin ◽

Medicare Part B

ABSTRACT Background Vitamin D is important for bone health; in 2014 it was the fifth most commonly ordered laboratory test among Medicare Part B payments. Objectives The aim of this study was to describe vitamin D status in the US population in 2011–2014 and trends from 2003 to 2014. Methods We used serum 25-hydroxyvitamin D data from NHANES 2011–2014 (n = 16,180), and estimated the prevalence at risk of deficiency (<30 nmol/L) or prevalence at risk of inadequacy (30–49 nmol/L) by age, sex, race and Hispanic origin, and dietary intake of vitamin D. We also present trends between 2003 and 2014. Results In 2011–2014, the percentage aged ≥1 y at risk of vitamin D deficiency or inadequacy was 5.0% (95% CI: 4.1%, 6.2%) and 18.3% (95% CI: 16.2%, 20.6%). The prevalence of at risk of deficiency was lowest among children aged 1–5 y (0.5%; 95% CI: 0.3%, 1.1%), peaked among adults aged 20–39 y (7.6%; 95% CI: 6.0%, 9.6%), and fell to 2.9% (95% CI: 2.0%, 4.0%) among adults aged ≥60 y; the prevalence of at risk of inadequacy was similar. The prevalence of at risk of deficiency was higher among non-Hispanic black (17.5%; 95% CI: 15.2%, 20.0%) than among non-Hispanic Asian (7.6%; 95% CI: 5.9%, 9.9%), non-Hispanic white (2.1%; 95% CI: 1.5%, 2.7%), and Hispanic (5.9%; 95% CI: 4.4%, 7.8%) persons; the prevalence of at risk of inadequacy was similar. Persons with higher vitamin D dietary intake or who used supplements had lower prevalences of at risk of deficiency or inadequacy. From 2003 to 2014 there was no change in the risk of vitamin D deficiency; the risk of inadequacy declined from 21.0% (95% CI: 17.9%, 24.5%) to 17.7% (95% CI: 16.0%, 19.7%). Conclusion The prevalence of at risk of vitamin D deficiency in the United States remained stable from 2003 to 2014; at risk of inadequacy declined. Differences in vitamin D status by race and Hispanic origin warrant additional investigation.

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Rates of Hospitalization and Infection-Related Hospitalization Among Human Immunodeficiency Virus (HIV)–Exposed Uninfected Children Compared to HIV-Unexposed Uninfected Children in the United States, 2007–2016

Clinical Infectious Diseases ◽

10.1093/cid/ciz820 ◽

2019 ◽

Vol 71 (2) ◽

pp. 332-339

Author(s):

Sarah M Labuda ◽

Yanling Huo ◽

Deborah Kacanek ◽

Kunjal Patel ◽

Krista Huybrechts ◽

...

Keyword(s):

United States ◽

Human Immunodeficiency Virus ◽

Poisson Regression ◽

The United States ◽

Hiv Disease ◽

Significant Difference ◽

Immunodeficiency Virus ◽

Maternal Hiv ◽

Hiv Exposed ◽

Exposed Uninfected

Abstract Background Studies from multiple countries have suggested impaired immunity in perinatally human immunodeficiency virus (HIV)–exposed uninfected children (HEU), with elevated rates of all-cause hospitalization and infections. We estimated and compared the incidence of all-cause hospitalization and infection-related hospitalization in the first 2 years of life among HEU and HIV-unexposed uninfected children (HUU) in the United States. Among HEU, we evaluated associations of maternal HIV disease–related factors during pregnancy with risk of child hospitalization. Methods HEU data from subjects enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities Study (SMARTT) cohort who were born during 2006–2017 were analyzed. HUU comparison data were obtained from the Medicaid Analytic Extract database, restricted to states participating in SMARTT. We compared rates of first hospitalization, total hospitalizations, first infection-related hospitalization, total infection-related hospitalizations, and mortality between HEU and HUU using Poisson regression. Among HEU, multivariable Poisson regression models were fitted to evaluate associations of maternal HIV factors with risk of hospitalization. Results A total of 2404 HEU and 3 605 864 HUU were included in the analysis. HEU children had approximately 2 times greater rates of first hospitalization, total hospitalizations, first infection-related hospitalization, and total infection-related hospitalizations compared with HUUs. There was no significant difference in mortality. Maternal HIV disease factors were not associated with the risk of child infection or hospitalization. Conclusions Compared with HUU, HEU children in the United States have higher rates of hospitalization and infection-related hospitalization in the first 2 years of life, consistent with studies in other countries. Closer monitoring of HEU infants for infection and further elucidation of immune mechanisms is needed.

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Immunologic and Virologic Factors Associated with Hospitalization in HIV-Exposed, Uninfected Infants in the United States

Clinical Infectious Diseases ◽

10.1093/cid/ciab272 ◽

2021 ◽

Author(s):

Christiana Smith ◽

Yanling Huo ◽

Kunjal Patel ◽

Kirk Fetters ◽

Shannon Hegemann ◽

...

Keyword(s):

United States ◽

Regression Models ◽

The United States ◽

Pediatric Hiv ◽

First Year ◽

Virus Family ◽

Vaccine Antigens ◽

Hiv Exposed ◽

First Year Of Life ◽

Exposed Uninfected

Abstract Background HIV-exposed, uninfected (HEU) infants experience higher rates of morbidity and mortality than HIV-unexposed uninfected (HUU) infants. Few studies have examined whether particular infections and/or immune responses are associated with hospitalization among HEU infants born in the United States. Methods We evaluated a subset of HEU infants enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1025 and/or Pediatric HIV/AIDS Cohort Study Surveillance Monitoring for ART Toxicities studies. We determined seroconversion to 6 respiratory viruses and measured antibody concentrations to 9 vaccine antigens using quantitative ELISA or electrochemiluminesence. Multivariable modified Poisson regression models were fit to evaluate the associations of seroconversion to each respiratory virus/family and antibody concentrations to vaccine antigens with the risk of hospitalization in the first year of life. Antibody concentrations to vaccine antigens were compared between HEU infants and HUU infants from a single site using multivariable linear regression models. Results Among 556 HEU infants, seroconversion to respiratory syncytial virus (RSV) and parainfluenza were associated with hospitalization [adjusted risk ratio: 1.95 (95% CI 1.21-3.15); 2.30 (1.42-3.73), respectively]. Antibody concentrations to tetanus toxoid, pertussis, and pneumococcal vaccine antigens were higher among 525 HEU compared with 100 HUU infants. No associations were observed between antibody concentrations to any vaccine and hospitalization among HEU infants. Conclusions RSV and parainfluenza contribute to hospitalization among HEU infants in the first year of life. HEU infants demonstrate robust antibody responses to vaccine antigens; therefore, humoral immune defects likely do not explain the increased susceptibility to infection observed in this population.

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