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1.
Am J Clin Nutr ; 115(3): 770-780, 2022 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-34849536

RESUMEN

BACKGROUND: Maternal vitamin D status during pregnancy and lactation is a modifiable factor that may influence offspring musculoskeletal outcomes. However, few randomized trials have tested the effects of prenatal or postpartum vitamin D supplementation on offspring bone and muscle development. OBJECTIVES: The aim was to examine hypothesized effects of improvements in early-life vitamin D status on childhood musculoskeletal health in Dhaka, Bangladesh. METHODS: In a previously completed, double-blind, dose-ranging trial, healthy pregnant women (n = 1300) were recruited at 17-24 weeks' gestation and randomly assigned to a prenatal/postpartum regimen of 0/0, 4200/0, 16,800/0, 28,000/0, or 28,000/28,000 IU cholecalciferol (vitamin D3)/wk until 26 wk postpartum. In this new report, we describe additional follow-up at 4 y of age (n = 642) for longer-term outcomes. Bone mineral content (BMC) and areal bone mineral density (aBMD) were measured by DXA. Grip strength was tested using a hand-held dynamometer. The primary comparison was children of women assigned to 28,000 IU/wk prenatally compared with placebo. Differences are expressed as means and 95% CIs. RESULTS: Total-body-less-head (TBLH) BMC, TBLH aBMD, and grip strength were similar in the combined high-dose prenatal (28,000/0 and 28,000/28,000 IU/wk) compared with placebo groups (mean difference [95% CI] = 0.61 g [-10.90, 12.13], 0.0004 g/cm2 [-0.0089, 0.0097], and 0.02 kg [-0.26, 0.31], respectively). In dose-ranging analyses, TBLH BMC and aBMD, whole-body BMC and aBMD, and grip strength in each of the prenatal vitamin D groups were not significantly different from placebo (P > 0.05 for all comparisons). Only head aBMD was greater in children of women assigned to the 28,000/28,000-IU regimen compared with placebo (mean difference [95% CI] = 0.024 g/cm2 [0.0009, 0.047], P = 0.042); the effect was attenuated upon adjustment for child height, weight, and sex (P = 0.11). CONCLUSIONS: Maternal prenatal, with or without postpartum, vitamin D supplementation does not improve child BMC, aBMD, or grip strength at 4 y of age. The MDIG trial and present follow-up study were registered prospectively at www.clinicaltrials.gov as NCT01924013 and NCT03537443, respectively.


Asunto(s)
Densidad Ósea , Vitamina D , Bangladesh , Niño , Preescolar , Colecalciferol/farmacología , Suplementos Dietéticos , Femenino , Estudios de Seguimiento , Humanos , Fuerza Muscular , Periodo Posparto , Embarazo , Vitaminas
2.
J Pediatric Infect Dis Soc ; 10(9): 901-909, 2021 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-34213544

RESUMEN

BACKGROUND: We examined the effect of maternal vitamin D supplementation during pregnancy and lactation on risk of acute respiratory infection (ARI) in infants up to 6 months of age in Bangladesh. METHODS: This study was nested in a randomized, double-blind, placebo-controlled, 5-arm dose-ranging trial of prenatal and postpartum vitamin D supplementation. One group of women received 0 IU vitamin D per week during pregnancy and for 26 weeks post delivery ("placebo" group), one group received high-dose prenatal vitamin D supplementation of 28 000 IU per week and 26 weeks post delivery, and there were 3 additional dose-ranging groups receiving vitamin D supplementation during pregnancy only (4200, 16 800, and 28 000 IU per week, respectively). Episodes of ARI were identified by active and passive surveillance. The primary outcome was microbiologically confirmed ARI, and the primary analysis compared the high-dose prenatal plus postpartum vitamin D vs placebo groups. RESULTS: In total, 1174 mother-infant pairs were included. Among infants born to mothers in the placebo group, 98% had a venous umbilical cord 25(OH)D level below 30 nmol/L compared with none in the high-dose prenatal plus postdelivery vitamin D group. Incidence of microbiologically confirmed ARI in the high-dose prenatal plus postpartum vitamin D (1.21 episodes per 6 person-months; N = 235) and placebo groups (1.07 episodes per 6 person-months; N = 234) was not significantly different (hazard ratio of 1.12 [95% confidence intervals: 0.90-1.40]). There were no differences in the incidence of microbiologically confirmed or clinical ARI, upper, lower, or hospitalized lower respiratory tract infection between high-dose prenatal plus postpartum vitamin D and placebo groups. CONCLUSIONS: Despite a high prevalence of maternal baseline vitamin D deficiency and significant effects of maternal vitamin D supplementation on infant vitamin D status, the intervention did not reduce the risk of microbiologically confirmed ARI in infants up to 6 months of age.


Asunto(s)
Infecciones del Sistema Respiratorio , Vitamina D , Bangladesh/epidemiología , Suplementos Dietéticos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Lactante , Lactancia , Embarazo , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/prevención & control
3.
N Engl J Med ; 379(6): 535-546, 2018 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-30089075

RESUMEN

BACKGROUND: It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants' length-for-age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group). RESULTS: Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length-for-age z scores. Scores were as follows: placebo, -0.93±1.05; prenatal 4200, -1.11±1.12; prenatal 16,800, -0.97±0.97; prenatal 28,000, -1.06±1.07; and prenatal and postpartum 28,000, -0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25-hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose. CONCLUSIONS: In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013 .).


Asunto(s)
Suplementos Dietéticos , Crecimiento/efectos de los fármacos , Complicaciones del Embarazo/tratamiento farmacológico , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/uso terapéutico , Vitaminas/uso terapéutico , Adulto , Bangladesh , Estatura/efectos de los fármacos , Países en Desarrollo , Suplementos Dietéticos/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Retardo del Crecimiento Fetal/tratamiento farmacológico , Humanos , Lactante , Recién Nacido/crecimiento & desarrollo , Lactancia , Periodo Posparto , Embarazo , Atención Prenatal , Vitamina D/administración & dosificación , Vitamina D/efectos adversos , Vitamina D/análogos & derivados , Vitamina D/sangre , Vitaminas/administración & dosificación , Vitaminas/efectos adversos
4.
BMC Pregnancy Childbirth ; 16(1): 309, 2016 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-27737646

RESUMEN

BACKGROUND: Early infancy is a high-risk period for severe acute respiratory infection (ARI), particularly in low-income countries with resource-limited health systems. Lower respiratory tract infection (LRTI) is commonly preceded by upper respiratory infection (URTI), and often caused by respiratory syncytial virus (RSV), influenza and other common community-acquired viral pathogens. Vitamin D status is a candidate modifiable early-life determinant of the host antiviral immune response and thus may influence the risk of ARI-associated morbidity in high-risk populations. METHODS/DESIGN: In the Maternal Vitamin D for Infant Growth (MDIG) study in Dhaka, Bangladesh (NCT01924013), 1300 pregnant women are randomized to one of five groups: placebo, 4200 IU/week, 16,800 IU/week, or 28,000 IU/week from 2nd trimester to delivery plus placebo from 0-6 months postpartum; or, 28,000 IU/week prenatal and until 6-months postpartum. In the Maternal Vitamin D for ARI in Infancy (MDARI) sub-study nested within the MDIG trial, trained personnel conduct weekly postnatal home visits to inquire about ARI symptoms and conduct a standardized clinical assessment. Supplementary home visits between surveillance visits are conducted when caregivers make phone notifications of new infant symptoms. Mid-turbinate nasal swab samples are obtained from infants who meet standardized clinical ARI criteria. Specimens are tested by polymerase chain reaction (PCR) for 8 viruses (influenza A/B, parainfluenza 1/2/3, RSV, adenovirus, and human metapneumovirus), and nasal carriage density of Streptococcus pneumoniae. The primary outcome is the incidence rate of microbiologically-positive viral ARI, using incidence rate ratios to estimate between-group differences. We hypothesize that among infants 0-6 months of age, the incidence of microbiologically-confirmed viral ARI will be significantly lower in infants whose mothers received high-dose prenatal/postpartum vitamin D supplements versus placebo. Secondary outcomes include incidence of ARI associated with specific pathogens (influenza A or B, RSV), clinical ARI, and density of pneumococcal carriage. DISCUSSION: If shown to reduce the risk of viral ARI in infancy, integration of maternal prenatal/postpartum vitamin D supplementation into antenatal care programs in South Asia may be a feasible primary preventive strategy to reduce the burden of ARI-associated morbidity and mortality in young infants. TRIAL REGISTRATION: NCT02388516 , registered March 9, 2015.


Asunto(s)
Suplementos Dietéticos , Enfermedades del Recién Nacido/prevención & control , Lactancia , Atención Prenatal/métodos , Infecciones del Sistema Respiratorio/prevención & control , Vitamina D/administración & dosificación , Vitaminas/administración & dosificación , Enfermedad Aguda , Adulto , Bangladesh , Lactancia Materna , Protocolos Clínicos , Femenino , Humanos , Lactante , Recién Nacido , Enfermedades del Recién Nacido/virología , Masculino , Fenómenos Fisiologicos Nutricionales Maternos , Embarazo , Estudios Prospectivos , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/virología , Infecciones del Sistema Respiratorio/virología , Resultado del Tratamiento
5.
Trials ; 16: 300, 2015 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-26169781

RESUMEN

BACKGROUND: Vitamin D regulates bone mineral metabolism and skeletal development. Some observational studies have suggested that prenatal vitamin D deficiency increases the risk of adverse pregnancy and/or birth outcomes; however, there is scant evidence from controlled trials, leading the World Health Organization to advise against routine vitamin D supplementation in pregnancy. Importantly, little is known about the effect of maternal vitamin D status on infant linear growth in communities in South Asia where stunting is highly prevalent and maternal-infant vitamin D status is commonly suboptimal. METHODS/DESIGN: The Maternal Vitamin D for Infant Growth study is a randomized, placebo-controlled, dose-ranging trial of maternal vitamin D supplementation during pregnancy and lactation in Dhaka, Bangladesh. The primary aims are to estimate (1) the effect of maternal prenatal oral vitamin D3 supplementation (4200 IU/wk, 16,800 IU/wk, or 28,000 IU/wk, administered as weekly doses) versus placebo on infant length at 1 year of age and (2) the effect of maternal postpartum oral vitamin D3 supplementation (28,000 IU/wk) versus placebo on length at 1 year of age among infants born to women who received vitamin D 28,000 IU/wk during pregnancy. Generally healthy pregnant women (n = 1300) in the second trimester (17-24 weeks of gestation) are randomized to one of five parallel arms: placebo 4200 IU/wk, 16,800 IU/wk, or 28,000 IU/wk in the prenatal period and placebo in the postpartum period or 28,000 IU/wk in the prenatal period and 28,000 IU/wk in the postpartum period. Household- and clinic-based follow-up of mother-infant pairs is conducted weekly by trained personnel until 26 weeks postpartum and every 3 months thereafter. The primary trial outcome measure is length for age z-score at 1 year of age. Anthropometric measurements, clinical information, and biological specimens collected at scheduled intervals will enable the assessment of a range of maternal, perinatal, and infant outcomes. DISCUSSION: The role of vitamin D in maternal and infant health remains unresolved. This trial is expected to contribute unique insights into the effects of improving maternal-infant vitamin D status in a low-income setting where stunting and adverse perinatal outcomes represent significant public health burdens. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01924013. Registered on 13 August 2013.


Asunto(s)
Desarrollo Infantil , Colecalciferol/administración & dosificación , Suplementos Dietéticos , Trastornos del Crecimiento/prevención & control , Lactancia , Fenómenos Fisiologicos Nutricionales Maternos , Estado Nutricional , Administración Oral , Factores de Edad , Bangladesh/epidemiología , Estatura , Preescolar , Protocolos Clínicos , Países en Desarrollo , Método Doble Ciego , Esquema de Medicación , Femenino , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/fisiopatología , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Masculino , Embarazo , Prevalencia , Proyectos de Investigación , Factores de Tiempo , Resultado del Tratamiento
6.
Tex Rep Biol Med ; 35: 221-9, 1977.
Artículo en Inglés | MEDLINE | ID: mdl-358450

RESUMEN

Extracts from interferon-treated, not virus infected EAT cells differ in several biochemical characteristics from extracts of untreated cells. Some of these differences are manifested only if the extracts are supplemented with ds RNA and ATP. Thus, in the extracts from interferon-treated cells these supplements activate a protein kinase and an endonuclease activity as well as an inhibitor of the translation of messenger RNA. The effect of the same supplements in extracts of untreated cells is much less pronounced. Other differences between the two types of extracts do not seem to depend on the addition of ds RNA and ATP. These include an impairment of mRNA cap methylation and an inhibition of peptide chain elongation that can be overcome by the addition of tRNA. The treatment of human (HeLa S3) cells with human interferon is manifested in the cell extract similarly to the treatment of EAT cells with mouse interferon. Studies are underway to isolate and characterize the ds RNA activated enzymes and the inhibitors and to establish how the presence of these in extracts from interferon-treated cells can account for the impairment of virus replication by interferon.


Asunto(s)
Interferones/farmacología , Biosíntesis de Proteínas/efectos de los fármacos , ARN Mensajero/metabolismo , ARN Viral/metabolismo , Adenosina Trifosfato/farmacología , Animales , Endonucleasas/metabolismo , Humanos , Metilación , Ratones , Proteínas Quinasas/metabolismo , ARN/farmacología , ARN de Transferencia/farmacología , Reoviridae/metabolismo , Proteínas Virales/biosíntesis , Replicación Viral/efectos de los fármacos
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