Effect of Vitamin D supplementation on recurrent wheezing in black infants who were born preterm the D-Wheeze randomized clinical trial

Anna Maria Hibbs, Kristie Ross, Leigh Ann Kerns, Carol Wagner, Mamta Fuloria, Sharon Groh-Wargo, Teresa Zimmerman, Nori Minich, Curtis Tatsuoka

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE Black infants born preterm face high rates of recurrent wheezing throughout infancy. Vitamin D supplementation has the potential to positively or negatively affect wheezing through modulation of the pulmonary and immune systems. OBJECTIVE To assess the effectiveness of 2 Vitamin D dosing strategies in preventing recurrent wheezing. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial enrolled 300 black infants born at 28 to 36 weeks’ gestation between January 2013 and January 2016 at 4 sites in the United States, and followed them up through March 2017. Randomization was stratified by site and maternal milk exposure. INTERVENTIONS Patients were enrolled prior to discharge from the neonatal intensive care unit or newborn nursery and received open-label multivitamin until they were consuming 200 IU/d of cholecalciferol from formula or fortifier added to human milk, after which they received either 400 IU/d of cholecalciferol until 6 months of age adjusted for prematurity (sustained supplementation) or placebo (diet-limited supplementation). One-hundred fifty three infants were randomized to the sustained group, and 147 were randomized to the diet-limited group. MAIN OUTCOMES AND MEASURES Recurrent wheezing by 12 months’ adjusted age was the primary outcome. RESULTS Among 300 patients who were randomized (mean gestational age, 33 weeks; median birth weight, 1.9 kg), 277 (92.3%) completed the trial. Recurrent wheezing was experienced by 31.1% of infants in the sustained supplementation group and 41.8% of infants in the diet-limited supplementation group (difference, −10.7% [95% CI, −27.4% to −2.9%]; relative risk, 0.66 [95% CI, 0.47 to 0.94]). Upper and lower respiratory tract infections were among the most commonly reported adverse events. Upper respiratory infections were experienced by 84 of 153 infants (54.9%) in the sustained group and 83 of 147 infants (56.5%) in the diet-limited group (difference, −1.6% [95% CI, −17.1% to 7.0%]). Lower respiratory infections were experienced by 33 of 153 infants (21.6%) in the sustained group and 37 of 147 infants (25.2%) in the diet-limited group (difference, −3.6% [95% CI, −16.4% to 4.4%]). CONCLUSIONS AND RELEVANCE Among black infants born preterm, sustained supplementation with Vitamin D, compared with diet-limited supplementation, resulted in a reduced risk of recurrent wheezing by 12 months’ adjusted age. Future research is needed to better understand the mechanisms and longer-term effects of Vitamin D supplementation on wheezing in children born preterm.

Original languageEnglish (US)
Pages (from-to)2086-2094
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume319
Issue number20
DOIs
StatePublished - May 22 2018

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Respiratory Sounds
Vitamin D
Randomized Controlled Trials
Diet
Respiratory Tract Infections
Cholecalciferol
Premature Infants
Ergocalciferols
Maternal Exposure
Nurseries
Neonatal Intensive Care Units
Human Milk
Random Allocation
Birth Weight
Gestational Age
Immune System
Milk
Placebos
Newborn Infant
Pregnancy

ASJC Scopus subject areas

  • Medicine(all)

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Effect of Vitamin D supplementation on recurrent wheezing in black infants who were born preterm the D-Wheeze randomized clinical trial. / Hibbs, Anna Maria; Ross, Kristie; Kerns, Leigh Ann; Wagner, Carol; Fuloria, Mamta; Groh-Wargo, Sharon; Zimmerman, Teresa; Minich, Nori; Tatsuoka, Curtis.

In: JAMA - Journal of the American Medical Association, Vol. 319, No. 20, 22.05.2018, p. 2086-2094.

Research output: Contribution to journalArticle

Hibbs, Anna Maria ; Ross, Kristie ; Kerns, Leigh Ann ; Wagner, Carol ; Fuloria, Mamta ; Groh-Wargo, Sharon ; Zimmerman, Teresa ; Minich, Nori ; Tatsuoka, Curtis. / Effect of Vitamin D supplementation on recurrent wheezing in black infants who were born preterm the D-Wheeze randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2018 ; Vol. 319, No. 20. pp. 2086-2094.
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title = "Effect of Vitamin D supplementation on recurrent wheezing in black infants who were born preterm the D-Wheeze randomized clinical trial",
abstract = "IMPORTANCE Black infants born preterm face high rates of recurrent wheezing throughout infancy. Vitamin D supplementation has the potential to positively or negatively affect wheezing through modulation of the pulmonary and immune systems. OBJECTIVE To assess the effectiveness of 2 Vitamin D dosing strategies in preventing recurrent wheezing. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial enrolled 300 black infants born at 28 to 36 weeks’ gestation between January 2013 and January 2016 at 4 sites in the United States, and followed them up through March 2017. Randomization was stratified by site and maternal milk exposure. INTERVENTIONS Patients were enrolled prior to discharge from the neonatal intensive care unit or newborn nursery and received open-label multivitamin until they were consuming 200 IU/d of cholecalciferol from formula or fortifier added to human milk, after which they received either 400 IU/d of cholecalciferol until 6 months of age adjusted for prematurity (sustained supplementation) or placebo (diet-limited supplementation). One-hundred fifty three infants were randomized to the sustained group, and 147 were randomized to the diet-limited group. MAIN OUTCOMES AND MEASURES Recurrent wheezing by 12 months’ adjusted age was the primary outcome. RESULTS Among 300 patients who were randomized (mean gestational age, 33 weeks; median birth weight, 1.9 kg), 277 (92.3{\%}) completed the trial. Recurrent wheezing was experienced by 31.1{\%} of infants in the sustained supplementation group and 41.8{\%} of infants in the diet-limited supplementation group (difference, −10.7{\%} [95{\%} CI, −27.4{\%} to −2.9{\%}]; relative risk, 0.66 [95{\%} CI, 0.47 to 0.94]). Upper and lower respiratory tract infections were among the most commonly reported adverse events. Upper respiratory infections were experienced by 84 of 153 infants (54.9{\%}) in the sustained group and 83 of 147 infants (56.5{\%}) in the diet-limited group (difference, −1.6{\%} [95{\%} CI, −17.1{\%} to 7.0{\%}]). Lower respiratory infections were experienced by 33 of 153 infants (21.6{\%}) in the sustained group and 37 of 147 infants (25.2{\%}) in the diet-limited group (difference, −3.6{\%} [95{\%} CI, −16.4{\%} to 4.4{\%}]). CONCLUSIONS AND RELEVANCE Among black infants born preterm, sustained supplementation with Vitamin D, compared with diet-limited supplementation, resulted in a reduced risk of recurrent wheezing by 12 months’ adjusted age. Future research is needed to better understand the mechanisms and longer-term effects of Vitamin D supplementation on wheezing in children born preterm.",
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T1 - Effect of Vitamin D supplementation on recurrent wheezing in black infants who were born preterm the D-Wheeze randomized clinical trial

AU - Hibbs, Anna Maria

AU - Ross, Kristie

AU - Kerns, Leigh Ann

AU - Wagner, Carol

AU - Fuloria, Mamta

AU - Groh-Wargo, Sharon

AU - Zimmerman, Teresa

AU - Minich, Nori

AU - Tatsuoka, Curtis

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N2 - IMPORTANCE Black infants born preterm face high rates of recurrent wheezing throughout infancy. Vitamin D supplementation has the potential to positively or negatively affect wheezing through modulation of the pulmonary and immune systems. OBJECTIVE To assess the effectiveness of 2 Vitamin D dosing strategies in preventing recurrent wheezing. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial enrolled 300 black infants born at 28 to 36 weeks’ gestation between January 2013 and January 2016 at 4 sites in the United States, and followed them up through March 2017. Randomization was stratified by site and maternal milk exposure. INTERVENTIONS Patients were enrolled prior to discharge from the neonatal intensive care unit or newborn nursery and received open-label multivitamin until they were consuming 200 IU/d of cholecalciferol from formula or fortifier added to human milk, after which they received either 400 IU/d of cholecalciferol until 6 months of age adjusted for prematurity (sustained supplementation) or placebo (diet-limited supplementation). One-hundred fifty three infants were randomized to the sustained group, and 147 were randomized to the diet-limited group. MAIN OUTCOMES AND MEASURES Recurrent wheezing by 12 months’ adjusted age was the primary outcome. RESULTS Among 300 patients who were randomized (mean gestational age, 33 weeks; median birth weight, 1.9 kg), 277 (92.3%) completed the trial. Recurrent wheezing was experienced by 31.1% of infants in the sustained supplementation group and 41.8% of infants in the diet-limited supplementation group (difference, −10.7% [95% CI, −27.4% to −2.9%]; relative risk, 0.66 [95% CI, 0.47 to 0.94]). Upper and lower respiratory tract infections were among the most commonly reported adverse events. Upper respiratory infections were experienced by 84 of 153 infants (54.9%) in the sustained group and 83 of 147 infants (56.5%) in the diet-limited group (difference, −1.6% [95% CI, −17.1% to 7.0%]). Lower respiratory infections were experienced by 33 of 153 infants (21.6%) in the sustained group and 37 of 147 infants (25.2%) in the diet-limited group (difference, −3.6% [95% CI, −16.4% to 4.4%]). CONCLUSIONS AND RELEVANCE Among black infants born preterm, sustained supplementation with Vitamin D, compared with diet-limited supplementation, resulted in a reduced risk of recurrent wheezing by 12 months’ adjusted age. Future research is needed to better understand the mechanisms and longer-term effects of Vitamin D supplementation on wheezing in children born preterm.

AB - IMPORTANCE Black infants born preterm face high rates of recurrent wheezing throughout infancy. Vitamin D supplementation has the potential to positively or negatively affect wheezing through modulation of the pulmonary and immune systems. OBJECTIVE To assess the effectiveness of 2 Vitamin D dosing strategies in preventing recurrent wheezing. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial enrolled 300 black infants born at 28 to 36 weeks’ gestation between January 2013 and January 2016 at 4 sites in the United States, and followed them up through March 2017. Randomization was stratified by site and maternal milk exposure. INTERVENTIONS Patients were enrolled prior to discharge from the neonatal intensive care unit or newborn nursery and received open-label multivitamin until they were consuming 200 IU/d of cholecalciferol from formula or fortifier added to human milk, after which they received either 400 IU/d of cholecalciferol until 6 months of age adjusted for prematurity (sustained supplementation) or placebo (diet-limited supplementation). One-hundred fifty three infants were randomized to the sustained group, and 147 were randomized to the diet-limited group. MAIN OUTCOMES AND MEASURES Recurrent wheezing by 12 months’ adjusted age was the primary outcome. RESULTS Among 300 patients who were randomized (mean gestational age, 33 weeks; median birth weight, 1.9 kg), 277 (92.3%) completed the trial. Recurrent wheezing was experienced by 31.1% of infants in the sustained supplementation group and 41.8% of infants in the diet-limited supplementation group (difference, −10.7% [95% CI, −27.4% to −2.9%]; relative risk, 0.66 [95% CI, 0.47 to 0.94]). Upper and lower respiratory tract infections were among the most commonly reported adverse events. Upper respiratory infections were experienced by 84 of 153 infants (54.9%) in the sustained group and 83 of 147 infants (56.5%) in the diet-limited group (difference, −1.6% [95% CI, −17.1% to 7.0%]). Lower respiratory infections were experienced by 33 of 153 infants (21.6%) in the sustained group and 37 of 147 infants (25.2%) in the diet-limited group (difference, −3.6% [95% CI, −16.4% to 4.4%]). CONCLUSIONS AND RELEVANCE Among black infants born preterm, sustained supplementation with Vitamin D, compared with diet-limited supplementation, resulted in a reduced risk of recurrent wheezing by 12 months’ adjusted age. Future research is needed to better understand the mechanisms and longer-term effects of Vitamin D supplementation on wheezing in children born preterm.

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