Risk Assessment of Cognitive Impairment at 2 Years of Age in Infants Born Extremely Preterm Using the INTERGROWTH-21st Growth Standards.

OBJECTIVE: To assess the risk of cognitive impairment among infants born extremely preterm using the INTERGROWTH-21st standards. STUDY DESIGN: We analyzed anthropometric data at birth and 36 weeks postmenstrual age (PMA) from infants born extremely preterm (24-26 weeks of gestation) admitted to US neonatal units between 2008 and 2018. To determine INTERGROWTH-21st z-score values that indicate an increased risk of cognitive impairment at 2 years of age (Bayley cognitive score <85), we employed classification and regression trees and redefined growth failure (weight, length, and head circumference z-scores at 36 weeks PMA) and growth faltering (weight, length, and head circumference z-score declines from birth to 36 weeks PMA). RESULTS: Among 5393 infants with a mean gestational age of 25 weeks, growth failure defined as a weight z-score of -1.8 or below at 36 weeks PMA and growth faltering defined as a weight z-score decline of 1.1 or greater from birth to 36 weeks PMA indicated a higher likelihood of cognitive impairment. A length z-score less than -1 at 36 weeks PMA had the highest sensitivity to detect cognitive impairment at 2 years (80%). A head circumference z-score decline of 2.43 or greater from birth to 36 weeks PMA had the highest specificity (86%). Standard definitions had fair to low sensitivity and specificity for risk detection of cognitive impairment. CONCLUSIONS: Length and head circumference z-scores had the highest sensitivity and specificity for risk detection of cognitive impairment. Monitoring these growth parameters could guide earlier individualized interventions with potential to reduce cognitive impairment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID Generic Database: NCT00063063.

Secular Trends in Patent Ductus Arteriosus Management in Infants Born Preterm in the National Institute of Child Health and Human Development Neonatal Research Network.

We evaluated changes in patent ductus arteriosus (PDA) diagnosis and treatment from 2012 through 2021 in a network of US academic hospitals. PDA treatment decreased among infants born at 26-28 weeks but not among infants born at 22-25 weeks. Rates of indomethacin use and PDA ligation decreased while acetaminophen use and transcatheter PDA closure increased.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Relationships between retinopathy of prematurity without ophthalmologic intervention and neurodevelopment and vision at 2 years.

BACKGROUND: Severe retinopathy of prematurity (ROP) is associated with adverse outcomes. Relationships between milder ROP and outcomes have not been defined. We hypothesized that children with ROP stage ≤3 who did not receive ophthalmologic intervention would have worse motor, cognitive, and language skills and more vision abnormalities than children without ROP. METHODS: This was a secondary analysis of a randomized trial evaluating the effects of myo-inositol on ROP in the NICHD Neonatal Research Network. Primary outcomes were Bayley Scales of Infant Development composite scores; secondary outcomes included behavioral difficulties and ophthalmologic measures. Outcomes were compared using adjusted linear or modified Poisson models. RESULTS: Of 506 children, 173 (34%) had no ROP, 262 (52%) had ROP stage ≤3 without intervention, and 71 (14%) had ROP with intervention. There was no difference in motor, cognitive, or language scores between children with ROP stage ≤3 without intervention and children without ROP. Children with ROP stage ≤3 without intervention had a higher rate of strabismus compared to children without ROP (p = 0.040). CONCLUSION: Children with ROP stage ≤3 without intervention did not have adverse neurodevelopmental outcomes at 2 years' corrected age compared to children without ROP but did have an increased incidence of strabismus. IMPACT: This study addresses a gap in the literature regarding the relationship between milder forms of retinopathy of prematurity (ROP) that regress without intervention and neurodevelopment and vision outcomes. Children with a history of ROP stage ≤3 without intervention have similar neurodevelopmental outcomes at 2 years' corrected age as children born extremely preterm without a history of ROP and better outcomes than children with a history of ROP with ophthalmologic intervention. Counseling about likely neurodevelopment and vision outcomes for children born extremely preterm with a history of ROP may be tailored based on the severity of ROP. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: Inositol to Reduce Retinopathy of Prematurity Trial: NCT01954082.

Hypothyroxinemia Detected at 4 Weeks of Life in Preterm Infants Born at Less than 30 Weeks of Gestation.

OBJECTIVE: Data on free thyroxine (FT4) concentrations beyond first 2 weeks of preterm infants are limited. This study was aimed to describe the association between perinatal characteristics and FT4 concentrations and the incidence of hypothyroxinemia at 4 weeks. STUDY DESIGN: Retrospective analysis of serum thyroid function tests at 4 weeks in preterm infants <30 weeks of gestation. Association between FT4 at 4 weeks of life and perinatal characteristics were determined by bivariate analysis and multivariable regression. Incidence of hypothyroxinemia was determined using a gestational age adjusted definition based on in utero levels at the equivalent postmenstrual age. RESULTS: The study cohort consisted of 280 infants. FT4 concentrations at 4 weeks of life were significantly associated with gestational age, birth weight, gender, and maternal history of thyroid disease. Hypothyroxinemia was found in 32.8% of the study cohort. CONCLUSION: Perinatal characteristics are associated with FT4 concentrations at 4 weeks of life. Nearly one-third of infants born <30 weeks had hypothyroxinemia at 4 weeks of life when compared with in utero levels at the equivalent postmenstrual age.

Outcomes at 18 to 22 Months of Corrected Age for Infants Born at 22 to 25 Weeks of Gestation in a Center Practicing Active Management.

OBJECTIVE: To assess the outcomes in actively managed extremely preterm infants after admission to a neonatal intensive care unit. STUDY DESIGN: Retrospective cohort of 255 infants born at 22-25 weeks of gestation between 2006 and 2015 at a single study institution. Infants were excluded for congenital anomaly, death in delivery room, or parental request for palliation (n = 7). Neurodevelopmental outcomes were analyzed for 169 of 214 survivors (78.9%) at 18-22 months of corrected age. Outcomes were evaluated using the Mann-Whitney U, χ2, or Fisher exact test, where appropriate. In addition, cognitive scores of the Bayley Scales of Infant-Toddler Development (3rd edition) were assessed using generalized estimating equations. RESULTS: Seventy infants born at 22-23 weeks of gestation (22 weeks, n = 20; 23 weeks, n = 50) and 178 infants born at 24-25 weeks of gestation (24 weeks, n = 79; 25 weeks, n = 99 infants) were included. Survival to hospital discharge of those surviving to NICU admission was 78% (55/70; 95% CI, 69%-88%) at 22-23 weeks and 89% (159/178; 95% CI, 84%-93% at 24-25 weeks; P = .02). No or mild neurodevelopmental impairment in surviving infants was 64% (29/45; 95% CI, 50%-77%) at 22-23 weeks and 76% (94/124; 95% CI, 68%-83%; P = .16) at 24-25 weeks. CONCLUSIONS: Although survival was lower in infants born at 22-23 weeks than at 24-25 weeks of gestation, the majority of survivors in both groups had positive outcomes with no or mild neurodevelopmental impairments. Further evaluation of school performance is warranted.

Behavior Profiles at 2 Years for Children Born Extremely Preterm with Bronchopulmonary Dysplasia.

OBJECTIVE: To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD). STUDY DESIGN: We studied children born at 22-26 weeks of gestation and assessed at 22-26 months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36 weeks of postmenstrual age. CBCL syndrome scales were the primary outcomes. The relationship between BPD grade and behavior was evaluated, adjusting for perinatal confounders. Mediation analysis was performed to evaluate whether cognitive, language, or motor skills mediated the effect of BPD grade on behavior. RESULTS: Of 2310 children, 1208 (52%) had no BPD, 806 (35%) had grade 1 BPD, 177 (8%) had grade 2 BPD, and 119 (5%) had grade 3 BPD. Withdrawn behavior (P < .001) and pervasive developmental problems (P < .001) increased with worsening BPD grade. Sleep problems (P = .008) and aggressive behavior (P = .023) decreased with worsening BPD grade. Children with grade 3 BPD scored 2 points worse for withdrawn behavior and pervasive developmental problems and 2 points better for externalizing problems, sleep problems, and aggressive behavior than children without BPD. Cognitive, language, and motor skills mediated the effect of BPD grade on the attention problems, emotionally reactive, somatic complaints, and withdrawn CBCL syndrome scales (P values < .05). CONCLUSIONS: BPD grade was associated with increased risk of withdrawn behavior and pervasive developmental problems but with decreased risk of sleep problems and aggressive behavior. The relationship between BPD and behavior is complex. Cognitive, language, and motor skills mediate the effects of BPD grade on some problem behaviors.

Hormone levels in preterm and donor human milk before and after Holder pasteurization.

BACKGROUND: After birth, breastfeeding is the exclusive source of hormonal signaling between mother and infant. Hospitalized infants often receive donor milk when their own mother's milk is unavailable. METHODS: The presence of insulin, leptin, cortisol, progesterone, and testosterone was examined in samples from milk bank donors and mothers of preterm infants. We further investigated the effect of Holder pasteurization (HoP) on hormone levels. RESULTS: Comparing nonpasteurized samples, leptin levels were nearly threefold higher in milk from mothers of preterm infants versus donated milk, and regardless of milk source, leptin levels were significantly decreased by HoP. Insulin concentrations were also decreased by HoP, and among mothers of preterm infants, obesity was associated with significantly higher content of leptin and insulin. While combined use of donor milk and HoP was associated with cortisol levels nearly threefold higher than those in nonpasteurized own mother's milk, progesterone and testosterone content did not differ by source or pasteurization. CONCLUSIONS: The hormonal composition of breast milk is impacted by HoP and maternal obesity. Compared to nonpasteurized maternal milk, use of pasteurized donor milk dramatically decreases the intake of leptin while increasing the intake of cortisol. Further research is necessary to define optimal breast milk processing practices.

Discordance in Antenatal Corticosteroid Use and Resuscitation Following Extremely Preterm Birth.

OBJECTIVE: To describe discordance in antenatal corticosteroid use and resuscitation following extremely preterm birth and its relationship with infant survival and neurodevelopment. STUDY DESIGN: A multicenter cohort study of 4858 infants 22-26 weeks of gestation born 2006-2011 at 24 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, with follow-up through 2013. Survival and neurodevelopmental outcomes were available at 18-22 months of corrected age for 4576 (94.2%) infants. We described antenatal interventions, resuscitation, and infant outcomes. We modeled the effect on infant outcomes of each hospital increasing antenatal corticosteroid exposure for resuscitated infants born at 22-24 weeks of gestation to rates observed at 25-26 weeks of gestation. RESULTS: Discordant antenatal corticosteroid use and resuscitation, where one and not the other occurred, were more frequent for births at 22 and 23 but not 24 weeks (rate ratio [95% CI] at 22 weeks: 1.7 [1.3-2.2]; 23 weeks: 2.6 [2.2-3.2]; 24 weeks: 1.0 [0.8-1.2]) when compared with 25-26 weeks. Among infants resuscitated at 23 weeks, adjusting each hospital's rate of antenatal corticosteroid use to the average at 25-26 weeks (89.2%) was projected to increase infant survival by 7.1% (95% CI 5.4-8.8%) and survival without severe impairment by 6.4% (95% CI 4.7-8.1%). No significant change in outcomes was projected for infants resuscitated at 22 weeks, where few (n = 22) resuscitated infants received antenatal corticosteroids. CONCLUSIONS: Infants born at 23 weeks were more frequently resuscitated without antenatal corticosteroids than other extremely preterm infants. When resuscitation is intended, consistent provision of antenatal corticosteroids may increase infant survival and survival without impairment. TRIAL REGISTRATION: ClinicalTrials.govNCT00063063 (Generic Database) and NCT00009633 (Follow-Up Study).

Weaning of Moderately Preterm Infants from the Incubator to the Crib: A Randomized Clinical Trial.

OBJECTIVE: To assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight. STUDY DESIGN: This trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33 weeks, birthweight <1600 g, and in an incubator were randomly assigned to a weaning weight of 1600 or 1800 g. Within 60 to 100 g of weaning weight, the incubator temperature was decreased by 1.0°C to 1.5°C every 24 hours until 28.0°C. The infants were weaned to the crib following stable temperature at 36.5°C to 37.4°C for 8 to 12 hours. Clothing and bedcoverings were standardized. The primary outcome was length of hospital stay from birth to discharge; secondary outcomes included length of stay and growth velocity from weaning to discharge. Adverse events were monitored. RESULTS: Of 1565 infants screened, 885 were eligible, and 366 enrolled-187 to the 1600-g and 179 to the 1800-g group. Maternal and neonatal characteristics did not differ among weight groups. Length of hospital stay was a median of 43 days in the lower and 41 days in the higher weight group (P = .12). Growth velocity from completion of weaning to discharge was higher in the lower weight group, 13.7 g/kg/day vs 12.8 g/kg/day (P = .005). Groups did not differ in adverse events. CONCLUSIONS: Among moderately preterm neonates, weaning from incubator to crib at a lower weight did not decrease length of stay, but was safe and was accompanied by higher weight gain after weaning. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02160002.

Origins of neonatal leptin deficiency in preterm infants.

BACKGROUND: Cord blood leptin increases with advancing gestation. Preterm delivery leads to premature separation from the maternal and placental leptin source predisposing infants to postnatal leptin deficiency, but this has not been fully described. METHOD: Blood leptin levels were measured for infants born before 33 weeks gestation daily for the first 2 days, then weekly until 36 weeks postmenstrual age (PMA). Cord blood was obtained to provide gestational age (GA)-specific standards. RESULTS: Cord blood leptin levels were positively associated with GA at birth, maternal body mass index (BMI) and pregnancy weight gain (all P < 0.05). Following birth, infant leptin levels decreased rapidly (74% decrease within 48 h). The extent of this decline correlated with GA (P < 0.05). Postnatal leptin began to increase by 33-36 weeks PMA, but remained below cord blood leptin levels (P < 0.01). At 36 weeks PMA, leptin levels were influenced by infant's weight and sex (P < 0.01), with females having higher leptin levels (1213 pg/ml vs. 984, P < 0.05). CONCLUSION: Cord blood leptin is influenced by maternal weight gain and BMI, suggesting an important role for trans-placental leptin delivery. Preterm delivery leads to sustained leptin deficiency through 36 weeks PMA, with the most premature male infants facing the longest and harshest deficiency.

Between-hospital variation in treatment and outcomes in extremely preterm infants.

BACKGROUND: Between-hospital variation in outcomes among extremely preterm infants is largely unexplained and may reflect differences in hospital practices regarding the initiation of active lifesaving treatment as compared with comfort care after birth. METHODS: We studied infants born between April 2006 and March 2011 at 24 hospitals included in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Data were collected for 4987 infants born before 27 weeks of gestation without congenital anomalies. Active treatment was defined as any potentially lifesaving intervention administered after birth. Survival and neurodevelopmental impairment at 18 to 22 months of corrected age were assessed in 4704 children (94.3%). RESULTS: Overall rates of active treatment ranged from 22.1% (interquartile range [IQR], 7.7 to 100) among infants born at 22 weeks of gestation to 99.8% (IQR, 100 to 100) among those born at 26 weeks of gestation. Overall rates of survival and survival without severe impairment ranged from 5.1% (IQR, 0 to 10.6) and 3.4% (IQR, 0 to 6.9), respectively, among children born at 22 weeks of gestation to 81.4% (IQR, 78.2 to 84.0) and 75.6% (IQR, 69.5 to 80.0), respectively, among those born at 26 weeks of gestation. Hospital rates of active treatment accounted for 78% and 75% of the between-hospital variation in survival and survival without severe impairment, respectively, among children born at 22 or 23 weeks of gestation, and accounted for 22% and 16%, respectively, among those born at 24 weeks of gestation, but the rates did not account for any of the variation in outcomes among those born at 25 or 26 weeks of gestation. CONCLUSIONS: Differences in hospital practices regarding the initiation of active treatment in infants born at 22, 23, or 24 weeks of gestation explain some of the between-hospital variation in survival and survival without impairment among such patients. (Funded by the National Institutes of Health.).

Causes and circumstances of death in a neonatal unit over 20 years.

BackgroundWe examined changes in the causes and circumstances of death in our neonatal intensive care unit (NICU) over 20 years.MethodsFor 551 infants who died between 1993 and 2013, the principal cause of death was recorded. Circumstances of death were assigned to one of the following four categories: death following cardiopulmonary resuscitation (CPR), death while being mechanically ventilated without CPR, death after withholding life-support interventions, and death after withdrawal of life support. Data were compared across four 5-year epochs.ResultsThe mortality rate decreased from 5.9% in the first epoch to 3.0% in the last epoch (P<0.0001). The leading cause of death in all epochs was congenital anomalies. The percentage of deaths due to all other categories decreased or remained stable. Withdrawal of life support was the most common circumstance of death in all four epochs. Only 16% of deaths followed CPR. The percentage of neonates with documented do-not-resuscitate orders was highest in the final cohort (52%).ConclusionsThe mortality rate per admission decreased between 1993 and 2013. Each cause of death was stable or decreased as a percentage of all deaths except for deaths due to congenital anomalies. Withdrawal of life-support interventions is the most common circumstance of death in neonates.

The changing relationship between bronchopulmonary dysplasia and cognition in very preterm infants.

AIM: To characterise the relationship between bronchopulmonary dysplasia (BPD) severity and cognition in the post-surfactant era. METHODS: This was a single-centre retrospective analysis of a cohort of infants born 2009-2012. Inclusion criteria were as follows: admission within 48 hours of birth, gestational age 22-0/7-31-6/7 weeks, birthweight 400-1500 g and Bayley Scales of Infant and Toddler Development-III testing at 18-26 months corrected age. Infants (n = 151) were classified by BPD severity with the NIH Workshop definition. Generalised linear modelling and multivariate logistic regression were performed. RESULTS: Bayley cognitive score was not associated with BPD severity in univariate (p = 0.053) or multivariate (p = 0.503) analysis. About 27% of infants with no/mild BPD, 33% of infants with moderate BPD and 40% of infants with severe BPD had a cognitive score <85. There was no difference in the odds of cognitive score <85 based on BPD severity in univariate (p = 0.485) or multivariate analysis (p = 0.225). All infants with cognitive score <70 had severe BPD, although the association between cognitive score <70 and BPD severity was not significant. CONCLUSION: We found no independent effect of BPD severity level on cognition. The likelihood of a cognitive score <85 was not associated with BPD severity.

Role of Early Pulmonary Hypertension as a Risk Factor for Late Pulmonary Hypertension in Extremely Preterm Infants.

OBJECTIVE: The evidence on the role of early pulmonary vascular disease (PVD) in the development of late pulmonary hypertension (PH) in the extremely preterm infants is limited. Objectives were to determine the incidence of early and late PH in extreme preterm infants and to evaluate the role of early PH as a risk factor for development of clinically detected late PH. METHODS: It was a retrospective analysis of early echocardiograms (day of life 5-14) in preterm infants, 22 to 27 weeks' gestation, admitted to the University of Iowa NICU between July 01, 2012 to June 30, 2015. Late echocardiograms performed for clinical suspicion of PH were also analyzed. RESULTS: A total of 154 infants were included in the study. Early PH was diagnosed in 31 (20%) infants. Twenty-four (16%) infants were evaluated for clinically suspected PH. Eight (5%) infants were diagnosed with late PH. Infants with early PH had echocardiograms performed earlier than infants without the evidence of early PH. Early PH was not associated with the development of late PH (p = 0.99). CONCLUSION: Early PH is common among extremely preterm infants (20%). Five percent of infants had clinically detected late PH. Infants with early PH had echocardiograms performed earlier than infants without the evidence of early PH. Early PH was not associated with the development of clinically detected late PH.

Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial.

Importance: Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. Objective: To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age. Design, Setting, and Participants: Randomized clinical trial included 638 infants younger than 28 weeks' gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group. Interventions: A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks. Main Outcomes and Measures: Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP. Results: Among 638 infants (mean, 26 weeks' gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks' postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%). Conclusions and Relevance: Among premature infants younger than 28 weeks' gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.

Neutrophil Phenotype Correlates With Postoperative Inflammatory Outcomes in Infants Undergoing Cardiopulmonary Bypass.

OBJECTIVES: Infants with congenital heart disease frequently require cardiopulmonary bypass, which causes systemic inflammation. The goal of this study was to determine if neutrophil phenotype and activation status predicts the development of inflammatory complications following cardiopulmonary bypass. DESIGN: Prospective cohort study. SETTING: Tertiary care PICU with postoperative cardiac care. PATIENTS: Thirty-seven patients 5 days to 10 months old with congenital heart disease requiring cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Laboratory and clinical data collected included length of mechanical ventilation, acute kidney injury, and fluid overload. Neutrophils were isolated from whole blood at three time points surrounding cardiopulmonary bypass. Functional analyses included measurement of cell surface protein expression and nicotinamide adenine dinucleotide phosphate oxidase activity. Of all patients studied, 40.5% displayed priming of nicotinamide adenine dinucleotide phosphate oxidase activity in response to N-formyl-Met-Leu-Phe stimulation 24 hours post cardiopulmonary bypass as compared to pre bypass. Neonates who received steroids prior to bypass demonstrated enhanced priming of nicotinamide adenine dinucleotide phosphate oxidase activity at 48 hours. Patients who displayed priming post cardiopulmonary bypass were 8.8 times more likely to develop severe acute kidney injury as compared to nonprimers. Up-regulation of neutrophil surface CD11b levels pre- to postbypass occurred in 51.4% of patients, but this measure of neutrophil priming was not associated with acute kidney injury. Subsequent analyses of the basal neutrophil phenotype revealed that those with higher basal CD11b expression were significantly less likely to develop acute kidney injury. CONCLUSIONS: Neutrophil priming occurs in a subset of infants undergoing cardiopulmonary bypass. Acute kidney injury was more frequent in those patients who displayed priming of nicotinamide adenine dinucleotide phosphate oxidase activity after cardiopulmonary bypass. This pilot study suggests that neutrophil phenotypic signature could be used to predict inflammatory organ dysfunction.

First-time mothers' breast-feeding maintenance: role of experiences and changes in maternal perceptions.

OBJECTIVE: Breast-feeding initiation rates have increased in the USA; however, maintenance of breast-feeding for recommended durations is low. The objective of the present study was to identify factors that may facilitate breast-feeding for longer durations among first-time mothers, including physiological and social experiences and changes in maternal perceptions. DESIGN: Survival analysis and linear regression methods were used to explore the relationship between experiences and breast-feeding duration, and the possible mediating effect of changes in maternal perceptions. SETTING: Secondary data from the Infant Feeding Practices Study II, conducted in the USA between 2005 and 2007. SUBJECTS: Data from 762 first-time mothers who ever breast-fed were analysed. RESULTS: Experiencing trouble with baby's latch, problems with milk flow/supply and painful breast-feeding were significantly associated with breast-feeding duration (64, 26 and 36 % shorter duration, respectively). Meanwhile, positive changes in perception with respect to breast-feeding self-efficacy, opinion about infant feeding and belief about breast milk were associated with 16-27 % longer duration. Furthermore, changes in perception were observed to partially mediate the impact of physiological experiences on breast-feeding duration. CONCLUSIONS: Perceptions of breast-feeding self-efficacy, beliefs and opinions can change over time and are influenced by breast-feeding experiences. The combined effect of experience and perception plays a key role in influencing breast-feeding duration. Future research should explore interventions to maintain or improve these perceptions while accounting for physiological experiences to support breast-feeding for recommended durations among first-time mothers.

Influence of Experiences and Perceptions Related to Breastfeeding One's First Child on Breastfeeding Initiation of Second Child.

Introduction Multiparas tend to initiate breastfeeding less than primiparas. While mothers often repeat the feeding method used for their first child with their second child, the way in which experiences and maternal perceptions related to breastfeeding one's first child may influence breastfeeding initiation with a second child remain underexplored. The objective of this study was to investigate whether physiological or social experiences, and related psychological factors, reported at the end of breastfeeding one's first child influence breastfeeding initiation with a second child. Methods Data from 174 multiparas who participated in the Infant Feeding Practices Study II, breastfed their first child, and completed the Year 6 Follow Up were analyzed using exact logistic regression. Results Mothers who reported experiencing trouble with the first baby's suck or latch had lower odds of initiating breastfeeding (OR 0.15, 95% CI 0.04-0.56) than those who did not report this experience, whereas mothers who agreed that breastfed children are less likely to become obese had greater odds of initiating breastfeeding with a second child (OR 11.49, 95% CI 1.56-513.18) than those who did not agree. Discussion Efforts to facilitate breastfeeding initiation among multiparas may consider mothers' previous experiences and beliefs associated with breastfeeding. Strategies to facilitate initiation may focus on addressing barriers mothers experienced while breastfeeding their first child and increasing awareness about how breastfeeding may prevent childhood obesity. Future research should explore how such approaches may impact breastfeeding outcomes with subsequent children.

Noninvasive Neurally Adjusted Ventilatory Assist in Premature Infants Postextubation.

Background Neurally adjusted ventilatory assist (NAVA) has distinct advantages when used invasively compared with conventional ventilation techniques. Evidence supporting the use of noninvasive NAVA is less robust, especially in the very low birth weight (VLBW) population. Objective To determine whether synchronized noninvasive ventilation via neurally adjusted ventilatory assist (NIV NAVA) supports ventilation postextubation in premature infants. Methods A retrospective analysis of a cohort of twenty-four former VLBW (<1.5 kg) infants from July 2011 to October 2012. Decreased or unchanged capillary pCO2 after increasing NAVA support was used as a marker for adequately supported noninvasive ventilation. The Wilcoxon signed-rank test was used to compare pre- and post-NAVA intervention (α = 0.05). Results Ventilation improved after an increase in NIV NAVA level in 83% of the premature infants studied (20/24) with a decrease in median pCO2 by 5 mm Hg (p = 0.0001). Conclusion NIV NAVA can provide synchronized postextubation ventilatory support as measured by decreased pCO2 in premature infants.