by
Ira Adams-Chapman;
Nellie I. Hansen;
Seetha Shankaran;
Edward F. Bell;
Nansi S. Boghossian;
Jeffrey C. Murray;
Abbot R. Laptook;
Michele C. Walsh;
Waldemar A. Carlo;
Pablo J. Sanchez;
Krisa P. Van Meurs;
Abhik Das;
Ellen C. Hale;
Nancy S. Newman;
M. Bethany Ball;
Rosemary D. Higgins;
Barbara J Stoll
OBJECTIVE:
Birth defects (BDs) are an important cause of infant mortality and disproportionately occur among low birth weight infants. We determined the prevalence of BDs in a cohort of very low birth weight (VLBW) infants cared for at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers over a 10-year period and examined the relationship between anomalies, neonatal outcomes, and surgical care.
METHODS:
Infant and maternal data were collected prospectively for infants weighing 401 to 1500 g at NRN sites between January 1, 1998, and December 31, 2007. Poisson regression models were used to compare risk of outcomes for infants with versus without BDs while adjusting for gestational age and other characteristics.
RESULTS:
A BD was present in 1776 (4.8%) of the 37 262 infants in our VLBW cohort. Yearly prevalence of BDs increased from 4.0% of infants born in 1998 to 5.6% in 2007, P < .001. Mean gestational age overall was 28 weeks, and mean birth weight was 1007 g. Infants with BDs were more mature but more likely to be small for gestational age compared with infants without BDs. Chromosomal and cardiovascular anomalies were most frequent with each occurring in 20% of affected infants. Mortality was higher among infants with BDs (49% vs 18%; adjusted relative risk: 3.66 [95% confidence interval: 3.41–3.92]; P < .001) and varied by diagnosis. Among those surviving >3 days, more infants with BDs underwent major surgery (48% vs 13%, P < .001).
CONCLUSIONS:
Prevalence of BDs increased during the 10 years studied. BDs remain an important cause of neonatal morbidity and mortality among VLBW infants.
Background:The health implications of in utero alcohol exposure have been difficult to study in very-low-birth-weight newborns (VLBW) because of an inability to identify maternal alcohol exposure. Fatty acid ethyl esters (FAEEs) are elevated in meconium of alcohol-exposed term newborns. We hypothesized that meconium FAEEs would be similarly elevated in alcohol-exposed VLBW premature newborns.
Methods:In a retrospective cohort study of 64 VLBW neonates, newborns were classified into Non-Exposed, Any Exposure, or Weekly Exposure groups based on an in-depth structured maternal interview. Meconium FAEE concentrations were quantified via gas chromatography mass spectrometry.
Results:Alcohol exposure during Trimester 1 (Any Exposure) occurred in ∼30% of the pregnancies, while 11% of the subjects reported drinking ≥ 1 drink/week (Weekly Exposure). Meconium ethyl linolenate was higher in Any Exposure (P = 0.01) and Weekly Exposure groups (P = 0.005) compared to the Non-Exposed VLBW group. There was a significant positive correlation between Trimester 1 drinking amounts and the concentration of meconium ethyl linolenate (P = 0.005). Adjusted receiver operating characteristic (ROC) curves evaluating ethyl linolenate to identify alcohol-exposed VLBW newborns generated areas under the curve of 88% with sensitivities of 86-89% and specificities of 83-88%.
Conclusion:Despite prematurity, meconium FAEEs hold promise to identify the alcohol-exposed VLBW newborn.
by
Jennifer James;
David Munson;
Sara B. DeMauro;
John C. Langer;
April Dworetz;
Girija Natarajan;
Margarita Bidegain;
Christine A. Fortney;
Ruth Seabrook;
Betty R. Vohr;
Jon E. Tyson;
Edward F. Bell;
Brenda B. Poindexter;
Seetha Shankaran;
Rosemary D. Higgins;
Abhik Das;
Barbara Stoll;
Haresh Kirpalani
Objectives To describe the frequency of postnatal discussions about withdrawal or withholding of life-sustaining therapy (WWLST), ensuing WWLST, and outcomes of infants surviving such discussions. We hypothesized that such survivors have poor outcomes. Study design This retrospective review included registry data from 18 centers of the National Institute of Child Health and Human Development Neonatal Research Network. Infants born at 22-28 weeks of gestation who survived >12 hours during 2011-2013 were included. Regression analysis identified maternal and infant factors associated with WWLST discussions and factors predicting ensuing WWLST. In-hospital and 18- to 26-month outcomes were evaluated. Results WWLST discussions occurred in 529 (15.4%) of 3434 infants. These were more frequent at 22-24 weeks (27.0%) compared with 27-28 weeks of gestation (5.6%). Factors associated with WWLST discussion were male sex, gestational age (GA) of ≤24 weeks, birth weight small for GA, congenital malformations or syndromes, early onset sepsis, severe brain injury, and necrotizing enterocolitis. Rates of WWLST discussion varied by center (6.4%-29.9%) as did WWLST (5.2%-20.7%). Ensuing WWLST occurred in 406 patients; of these, 5 survived to discharge. Of the 123 infants for whom intensive care was continued, 58 (47%) survived to discharge. Survival after WWLST discussion was associated with higher rates of neonatal morbidities and neurodevelopmental impairment compared with babies for whom WWLST discussions did not occur. Significant predictors of ensuing WWLST were maternal age >25 years, necrotizing enterocolitis, and days on a ventilator. Conclusions Wide center variations in WWLST discussions occur, especially at ≤24 weeks GA. Outcomes of infants surviving after WWLST discussions are poor. Trial registration ClinicalTrials.gov: NCT00063063.
Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensive knowledge of the mechanisms underlying alcohol's effects on the developing immune system only will become clear once researchers establish improved methods for identifying newborns exposed to alcohol in utero.
by
Ravi Patel;
Sarah Kandefer;
Michele C. Walsh;
Edward F. Bell;
Waldemar A. Carlo;
Abbot R. Laptook;
Pablo J. Sánchez;
Seetha Shankaran;
Krisa P. Van Meurs;
M. Bethany Ball;
Ellen C. Hale;
Nancy S. Newman;
Abhik Das;
Rosemary D. Higgins;
Barbara Stoll
BACKGROUND: Understanding the causes and timing of death in extremely premature infants may guide research efforts and inform the counseling of families. METHODS: We analyzed prospectively collected data on 6075 deaths among 22,248 live births, with gestational ages of 22 0/7 to 28 6/7 weeks, among infants born in study hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. We compared overall and cause-specific in-hospital mortality across three periods from 2000 through 2011, with adjustment for baseline differences. RESULTS: The number of deaths per 1000 live births was 275 (95% confidence interval [CI], 264 to 285) from 2000 through 2003 and 285 (95% CI, 275 to 295) from 2004 through 2007; the number decreased to 258 (95% CI, 248 to 268) in the 2008-2011 period (P=0.003 for the comparison across three periods). There were fewer pulmonary-related deaths attributed to the respiratory distress syndrome and bronchopulmonary dysplasia in 2008-2011 than in 2000-2003 and 2004-2007 (68 [95% CI, 63 to 74] vs. 83 [95% CI, 77 to 90] and 84 [95% CI, 78 to 90] per 1000 live births, respectively; P=0.002). Similarly, in 2008-2011, as compared with 2000-2003, there were decreases in deaths attributed to immaturity (P=0.05) and deaths complicated by infection (P=0.04) or central nervous system injury (P<0.001); however, there were increases in deaths attributed to necrotizing enterocolitis (30 [95% CI, 27 to 34] vs. 23 [95% CI, 20 to 27], P=0.03). Overall, 40.4% of deaths occurred within 12 hours after birth, and 17.3% occurred after 28 days. CONCLUSIONS: We found that from 2000 through 2011, overall mortality declined among extremely premature infants. Deaths related to pulmonary causes, immaturity, infection, and central nervous system injury decreased, while necrotizing enterocolitis-related deaths increased. (Funded by the National Institutes of Health.).
Alcoholic patients have an increased risk of respiratory infections, which is partially due to an impaired immune response of alveolar macrophages. The mechanisms by which alcohol impairs alveolar macrophage function are poorly understood. In this study, we demonstrated in a guinea pig model that chronic ethanol ingestion significantly impaired alveolar macrophage differentiation and function. Isolated alveolar macrophages were separated into 4 different subpopulations with varying densities and levels of maturation. Compared to control values, chronic ethanol ingestion decreased the percentage of alveolar macrophages in the mature fractions by ~60%. Alveolar macrophage function in each subpopulation was determined by measuring phagocytosis of FITC-labeled S. aureus. Alveolar macrophages from ethanol-fed animals had ~80% decrease in the phagocytic index. Western blot and immunohistochemical analysis of the differential markers GM-CSF receptor α (GM-CSFR-α), PU.1, CD11c, and CD11b verified that alcoholic macrophages displayed impaired terminal differentiation. While oral supplementation with the glutathione precursor S-adenosyl-methionine (SAM) did not alter the maturational status of control animals, SAM s supplementation shifted the distribution of macrophages to more mature fractions, normalized the phagocytic index; as well as normalized expression of CD11c, CD11b, PU.1, and GM-CSFR-α. Chronic ethanol ingestion also impaired the differentiation status of interstitial macrophages which was normalized by SAM supplementation. This improvement in the maturational status suggested that ethanol-induced oxidant stress is a central feature in impaired terminal differentiation of macrophages in the interstitial and alveolar space. Therefore, strategies targeting pulmonary oxidant stress may restore macrophage differentiation and function even after chronic ethanol ingestion.
by
Cristina T. Navarrete;
Lisa A. Wrage;
Waldemar A. Carlo;
Michele C. Walsh;
Wade Rich;
Marie G. Gantz;
Abhik Das;
Kurt Schibler;
Nancy S. Newman;
Anthony Piazza;
Brenda B. Poindexter;
Seetha Shankaran;
Pablo J. Sanchez;
Brenda H. Morris;
Ivan D. Frantz III;
Krisa P. Van Meurs;
C. Michael Cotten;
Richard A. Ehrenkranz;
Edward F. Bell;
Kristi L. Watterberg;
Rosemary D. Higgins;
Shahnaz Duara
Objective: To test whether infants randomized to a lower oxygen saturation (peripheral capillary oxygen saturation [SpO 2 ]) target range while on supplemental oxygen from birth will have better growth velocity from birth to 36 weeks postmenstrual age (PMA) and less growth failure at 36 weeks PMA and 18-22 months corrected age.
Study design: We evaluated a subgroup of 810 preterm infants from the Surfactant, Positive Pressure, and Oxygenation Randomized Trial, randomized at birth to lower (85%-89%, n = 402, PMA 26 ± 1 weeks, birth weight 839 ± 186 g) or higher (91%-95%, n = 408, PMA 26 ± 1 weeks, birth weight 840 ± 191 g) SpO 2 target ranges. Anthropometric measures were obtained at birth, postnatal days 7, 14, 21, and 28; then at 32 and 36 weeks PMA; and 18-22 months corrected age. Growth velocities were estimated with the exponential method and analyzed with linear mixed models. Poor growth outcome, defined as weight < 10th percentile at 36 weeks PMA and 18-22 months corrected age, was compared across the 2 treatment groups by the use of robust Poisson regression.
Results: Growth outcomes including growth at 36 weeks PMA and 18-22 months corrected age, as well as growth velocity were similar in the lower and higher SpO 2 target groups.
Conclusion: Targeting different oxygen saturation ranges between 85% and 95% from birth did not impact growth velocity or reduce growth failure in preterm infants.
Objective:To evaluate early feeding factors associated with exclusive human milk (EHM) feeding at discharge in a cohort of human milk-fed infants admitted to the neonatal intensive care unit (NICU).Study Design:Retrospective cohort of consecutively discharged infants from two NICUs over a 12-month period who received any human milk during the 24 h before hospital discharge. We used logistic regression to evaluate early feeding factors associated with EHM feeding at discharge. Result:We evaluated a total of 264 infants. EHM-fed infants were twice as likely to receive human milk at the first feeding compared with partial human milk-fed infants (65% vs 32%; P<0.01). In multivariable analysis, including adjustment for race and type of maternal insurance, infants receiving human milk as the initial feeding, compared with formula, had a greater odds of EHM feeding at hospital discharge (adjusted odds ratio (OR)=3.41; 95% confidence interval (CI)=1.82 to 6.39; P<0.001). Conclusion:Among infants admitted to the NICU whose mothers provide human milk, those receiving human milk as the first feeding were more likely to receive EHM feeding at discharge.Journal of Perinatology advance online publication, 17 April 2014; doi:10.1038/jp.2014.63.
Background: We hypothesized that maternal alcohol use occurs in pregnancies that end prematurely and that in utero alcohol exposure is associated with an increased risk of morbidities of premature newborns.
Methods: In an observational study of mothers who delivered very low birth weight newborns (VLBW) ≤1,500 g, maternal alcohol use was determined via a standardized administered questionnaire. We compared the effect of maternal drinking on the odds of developing late-onset sepsis (LOS), bronchopulmonary dysplasia (BPD), death, BPD or Death days on oxygen or any morbidity (either LOS, BPD or death). The effect of drinking amounts (light versus heavy) was also evaluated.
Results: A total of 129 subjects who delivered 143 VLBW newborns were enrolled. Approximately 1 in 3 (34%) subjects reported drinking alcohol during the first trimester ("exposed"). Within the exposed group, 15% reported drinking ≥7. drinks/week ("heavy") and 85% of the subjects reported drinking < 7. drinks/week ("light"). When controlling for maternal age, drug or tobacco use during pregnancy and neonatal gestational age, any drinking increased the odds of BPD or Death and any morbidity. Furthermore, light or heavy drinking increased the odds of BPD or Death and any morbidity, whereas heavy drinking increased the odds of LOS.
Conclusions: In utero alcohol exposure during the first trimester occurred in 34% of VLBW newborns. Maternal drinking in the first trimester was associated with significantly increased odds of neonatal morbidity. Further studies are warranted to determine the full effect of . in utero alcohol exposure on the adverse outcomes of VLBW premature newborns.
Infants with critical congenital heart defects (CCHD) are at high risk for feeding challenges and neurodevelopmental delays; however, few interventions promoting the neurodevelopmental progression of feeding have been studied with this population. Contingent mother’s voice has been successfully used as positive reinforcement for non-nutritive suck (NNS) in studies with preterm infants, leading to improved weight gain and more rapid cessation of tube feedings; however, this type of intervention has not been studied in infants with CCHD. This study aimed to determine whether an NNS-training protocol using the mother’s voice as positive reinforcement and validated in preterm infants could improve oral feeding outcomes in hospitalized infants with CCHD undergoing cardiac surgical procedures. Infants were randomized to receive the contingent mother’s voice intervention before or after cardiac surgery, with a control comparison group receiving passive exposure to the mother’s voice after surgery. There were no significant differences in discharge weight, PO intake, length of stay, time to full feeds, or feeding status at 1-month post-discharge between infants who received contingent mother’s voice compared to those who did not. There were significant differences in PO intake and time to full feeds following surgery based on infants’ pre-enrollment PO status and severity of illness. At 1-month post-discharge, parents of infants in the intervention group expressed a higher rate of positive feelings and fewer concerns regarding their infant’s feeding compared to parents of infants in the control group. While the current protocol of 5 sessions was not associated with improved feeding outcomes in infants with CCHD, it empowered parents to contribute to their infant’s care and demonstrated the feasibility of using the mother’s voice as positive reinforcement for infants with CCHD. Further study of timing, intensity, and duration of interventions leveraging the mother’s voice in this population is needed. ClinicalTrials.gov Identifier: NCT03035552.