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

ABSTRACT: BACKGROUND:Vitamin D status in pregnancy may influence the risk of prematurity, birth size, and child postnatal growth, but few studies have examined the relationship among pregnant women living with HIV. METHODS:We conducted a prospective cohort study of 257 HIV-infected mothers and their HIV-exposed uninfected infants who were enrolled in the 2009-2011 nutrition substudy of the Surveillance Monitoring for ART Toxicities (SMARTT) study. HIV-infected pregnant women had serum 25-hydroxyvitamin D (25(OH)D) assessed in the third trimester of pregnancy, and their infants' growth and neurodevelopment were evaluated at birth and approximately 1 year of age. RESULTS:The mean third trimester serum 25(OH)D concentration was 35.4 ± 14.2 ng/mL with 15% of women classified as vitamin D deficient (<20 ng/mL) and 21% as insufficient (20-30 ng/mL). In multivariable models, third trimester vitamin D deficiency and insufficiency were associated with -273 g [95% confidence interval (CI): -450 to -97] and -203 g (95% CI: -370 to -35) lower birth weights compared with vitamin D sufficient women, respectively. Maternal vitamin D deficiency was also associated with shorter gestation (mean difference -0.65 weeks; 95% CI: -1.22 to -0.08) and lower infant length-for-age z-scores at 1 year of age (mean difference: -0.65; 95% CI: -1.18 to -0.13). We found no association of vitamin D status with infant neurodevelopment at 1 year of age. CONCLUSION:Third trimester maternal vitamin D deficiency was associated with lower birth weight, shorter length of gestation, and reduced infant linear growth. Studies and trials of vitamin D supplementation in pregnancy for women living with HIV are warranted.

SUBMITTER: Sudfeld CR

PROVIDER: S-EPMC6565449 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Sudfeld Christopher R CR Jacobson Denise L DL Rueda Noé M NM Neri Daniela D Mendez Armando J AJ Butler Laurie L Siminski Suzanne S Hendricks Kristy M KM Mellins Claude A CA Duggan Christopher P CP Miller Tracie L TL

Journal of acquired immune deficiency syndromes (1999) 20190701 3

<h4>Background</h4>Vitamin D status in pregnancy may influence the risk of prematurity, birth size, and child postnatal growth, but few studies have examined the relationship among pregnant women living with HIV.<h4>Methods</h4>We conducted a prospective cohort study of 257 HIV-infected mothers and their HIV-exposed uninfected infants who were enrolled in the 2009-2011 nutrition substudy of the Surveillance Monitoring for ART Toxicities (SMARTT) study. HIV-infected pregnant women had serum 25-hy ...[more]

PMID: 31021992

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Project description:HIV-exposed, uninfected (HEU) infants suffer high morbidity and mortality in the first year of life compared to HIV-unexposed, uninfected (HUU) infants, but accurate data on the contribution of malaria are limited.The incidence of febrile illnesses and malaria were evaluated in a birth cohort of HEU infants. Infants were prescribed daily trimethoprim-sulfamethoxazole (TS) prophylaxis from 6 weeks of age until exclusion of HIV-infection after cessation of breastfeeding. Infants were followed for all illnesses using passive surveillance and routine blood smears were done monthly. Malaria was diagnosed as a positive blood smear plus fever. Placental malaria was determined by histopathology, placental blood smear and PCR. Risk factors for time to first episode of malaria were assessed using a Cox proportional hazards model. Malaria incidence among HEU infants aged 6-12 months was compared to that in other cohorts of HEU and HUU infants from the same region.Among 361 HEU infants enrolled, 248 completed 12 months of follow-up resulting in 1562 episodes of febrile illness and 253 episodes of malaria after 305 person-years of follow-up. The incidence of febrile illness was 5.12 episodes per person-year (PPY), ranging from 4.13 episodes PPY in the first 4 months of life to 5.71 episodes PPY between 5 and 12 months of age. The overall malaria incidence was 0.83 episodes per person-year (PPY), increasing from 0.03 episodes PPY in the first 2 months of life to 2.00 episodes PPY between 11 and 12 months of age. There were no episodes of complicated malaria. The prevalence of asymptomatic parasitaemia was 1.2 % (19 of 1568 routine smears positive). Infants born to mothers with parasites detected from placental blood smears were at higher risk of malaria (hazard ratio = 4.51, P < 0.001). HEU infants in this study had a 2.4- to 3.5-fold lower incidence of malaria compared to HUU infants in other cohort studies from the same area.The burden of malaria in this birth cohort of HEU infants living in a high-transmission setting and taking daily TS prophylaxis was relatively low. Alternative etiologies of fever should be considered in HEU-infants taking daily TS prophylaxis who present with fever. Trial Registration NCT00993031, registered 8 October, 2009.

Project description:ObjectivesHIV-exposed uninfected (HEU) infants have higher rates of severe and fatal infections compared with HIV-unexposed (HUU) infants, likely due to immune perturbations. We hypothesized that alterations in natural killer (NK) cell activity might occur in HEU infants and predispose them to severe infections.DesignCase-control study using cryopreserved peripheral blood mononuclear cells (PBMCs) at birth and 6 months from HEU infants enrolled from 2002 to 2009 and HUU infants enrolled from 2011 to 2013.MethodsNK cell phenotype and function were assessed by flow cytometry after 20-h incubation with and without K562 cells.ResultsThe proportion of NK cells among PBMCs was lower at birth in 12 HEU vs. 22 HUU (1.68 vs. 10.30%, p < 0.0001) and at 6 months in 52 HEU vs. 72 HUU (3.09 vs. 4.65%, p = 0.0005). At birth, HEU NK cells demonstrated increased killing of K562 target cells (p < 0.0001) and increased expression of CD107a (21.65 vs. 12.70%, p = 0.047), but these differences resolved by 6 months. Stimulated HEU NK cells produced less interferon (IFN)γ at birth (0.77 vs. 2.64%, p = 0.008) and at 6 months (4.12 vs. 8.39%, p = 0.001), and showed reduced perforin staining at 6 months (66.95 vs. 77.30%, p = 0.0008). Analysis of cell culture supernatants indicated that lower NK cell activity in HEU was associated with reduced interleukin (IL)-12, IL-15, and IL-18. Addition of recombinant human IL-12 to stimulated HEU PBMCs restored IFNγ production to that seen in stimulated HUU cultures.ConclusionNK cell proportion, phenotype, and function are altered in HEU infants. NK cell cytotoxicity and degranulation are increased in HEU at birth, but HEU NK cells have reduced IFNγ and perforin production, suggesting an adequate initial response, but decreased functional reserve. NK cell function improved with addition of exogenous IL-12, implicating impaired production of IL-12 by accessory cells. Alterations in NK cell and accessory cell function may contribute to the increased susceptibility to infection in HEU infants.

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

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

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