Browsing by Subject "Infant, Low Birth Weight"

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    ItemOpen Access
    Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring.
    (International journal of obesity (2005), 2013-07) Vidal, AC; Murphy, SK; Murtha, AP; Schildkraut, JM; Soubry, A; Huang, Z; Neelon, SEB; Fuemmeler, B; Iversen, E; Wang, F; Kurtzberg, J; Jirtle, RL; Hoyo, C

    Objectives

    Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations.

    Methods

    Between 2009-2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions.

    Results

    After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (β-coefficient=-132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (β-coefficient=-135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight.

    Conclusion

    We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations.
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    Safety of sildenafil in premature infants with severe bronchopulmonary dysplasia (SILDI-SAFE): a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety study.
    (BMC pediatrics, 2020-12) Schneider, Simone; Bailey, Mary; Spears, Tracy; Esther, Charles R; Laughon, Matthew M; Hornik, Christoph P; Jackson, Wesley

    Background

    Pulmonary hypertension is a deadly complication of bronchopulmonary dysplasia, the most common pulmonary morbidity of prematurity. Despite these catastrophic consequences, no evidence-based therapies are available for the prevention of pulmonary hypertension in this population. Sildenafil is a potent pulmonary vasodilator approved by the US Food and Drug Administration for the treatment of pulmonary hypertension in adults. Preclinical models suggest a beneficial effect of sildenafil on premature lungs through improved alveolarization and preserved vascular development. Sildenafil may therefore prevent the development of pulmonary hypertension associated with lung disease of prematurity by reducing pulmonary vascular remodeling and lowering pulmonary vascular resistance; however, clinical trial evidence is needed. The present study, supported by the National Institutes of Health's National Heart Lung and Blood Institute, will generate safety, pharmacokinetics, and preliminary effectiveness data on sildenafil in a population of premature infants with severe bronchopulmonary dysplasia at risk for pulmonary hypertension.

    Methods

    We have designed a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety trial of sildenafil in premature infants with severe bronchopulmonary dysplasia. We will randomize 120 premature infants < 29 weeks gestational age with severe bronchopulmonary dysplasia at 32-40 weeks postmenstrual age in a dose-escalating approach 3:1 (sildenafil: placebo) sequentially into each of 3 cohorts at ~ 30 clinical sites. Participants will receive up to 34 days of study drug, followed by 28 days of safety monitoring. The primary outcome will be safety as determined by incidence of hypotension. Secondary outcomes will include pharmacokinetics and preliminary effectiveness of sildenafil based on presence or absence of pulmonary hypertension diagnosed by echocardiography at the end of treatment period.

    Discussion

    Sildenafil is a promising intervention to prevent the development of pulmonary hypertension in premature infants with bronchopulmonary dysplasia. Clinical trials of sildenafil specifically designed for premature infants are urgently needed. The current study will make substantial contributions to scientific knowledge of the safety of sildenafil in premature infants at risk for pulmonary hypertension. Results from the study will be used by investigators to inform the design of a pivotal efficacy trial.

    Trial registration

    ClinicalTrials.gov NCT04447989 . Registered 25 June 2020.
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    The effect of the WIC program on the health of newborns.
    (Health Serv Res, 2010-08) Foster, EM; Jiang, M; Gibson Davis, CM
    OBJECTIVE: To determine the effect of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) on birth outcomes. DATA SOURCE: The Child Development Supplement (CDS) of the Panel Study of Income Dynamics (PSID). The PSID provides extensive data on the income and well-being of a representative sample of U.S. families from 1968 to present. The CDS collects information on the children in PSID families ranging from cognitive, behavioral, and health status to their family and neighborhood environment. The first two waves of the CDS were conducted in 1997 and 2002, respectively. We use information on 3,181 children and their mothers. STUDY DESIGN: We use propensity score matching with multiple imputations to examine whether WIC program influences birth outcomes: birth weight, prematurity, maternal report of the infant's health, small for gestational age, and placement in the neonatal intensive care unit. Furthermore, we use a fixed-effects model to examine the above outcomes controlling for mother-specific unobservables. PRINCIPAL FINDINGS: After using propensity scores to adjust for confounding factors, WIC shows no statistically significant effects for any of six outcomes. Fixed-effects models, however, reveal some effects that are statistically significant and fairly substantial in size. These involve preterm birth and birth weight. CONCLUSIONS: Overall, the WIC program had moderate effects, but findings were sensitive to the estimation method used.