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Bedside biomarkers that allow early identification of infants with bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) are critically important given the higher risk of death in these infants.We hypothesized that infants with BPD-PH have patterns of intermittent hypoxemia that differ from infants with BPD without pulmonary hypertension.We conducted a matched case-control study of extremely preterm infants 22w 0d to 28w 6d born between 2018 and 2020 at the University of Alabama at Birmingham. BPD-PH status was determined using echocardiographic data performed after postnatal day 28. Physiologic data were compared between infants with BPD-PH (cases) and BPD alone (controls). Receiver operating characteristic (ROC) analysis estimated the predictive ability of cumulative hypoxemia, desaturation frequency, and duration of intermittent hypoxemic events in the week preceding echocardiography to discriminate between cases and controls.40 infants with BPD-PH were compared to 40 infants with BPD alone. Infants with and without PH had a similar frequency of IH events, but infants with PH had more prolonged hypoxemic events for desaturations below 80% (7s vs 6s; p=0.03) and 70% (105s vs 58s; p=0.008). Among infants with BPD-PH, infants who died had longer hypoxemic events below 70% (145s vs 72s; p=0.01). Using the duration of hypoxemic events below 70%, the areas under the ROC curves for diagnosis of BPD-PH and death in BPD-PH infants were 0.71 and 0.77, respectively.Longer duration of intermittent hypoxemic events was associated both with a diagnosis of BPD-PH and with death among infants with BPD-PH.

RATIONALE: Extremely preterm infants with evolving bronchopulmonary dysplasia (BPD) are at risk for development of BPD-associated pulmonary hypertension (BPD-PH). A patent ductus arteriosus (PDA) shunt may be a modifiable risk factor for BPD-PH development. OBJECTIVE: To determine whether the presence and duration of ductus arteriosus patency differs between extremely preterm infants with and without BPD-PH. METHODS: We conducted a retrospective case-control study among preterm infants of gestational age 22 weeks, 0 days, to 28 weeks, 6 days, who remained on respiratory support on postnatal day 28 at the University of Alabama at Birmingham from 2017 to 2020. Infants who were diagnosed with PH (cases) by echocardiography were compared with infants without PH (control subjects). Data from echocardiograms performed during the hospitalization after postnatal day 28 were included. Logistic regression adjusted for covariates that differed significantly between groups. A probit analysis related the duration of ductal patency to the development of BPD-PH. MEASUREMENTS AND MAIN RESULTS: A total of 138 infants developed BPD alone, and 82 infants developed BPD-PH. After adjustment for differing covariates between groups, both PDA (adjusted odds ratio, 4.29; 95% confidence interval, 1.89–9.77) and moderate to large PDA (adjusted odds ratio, 4.15; 95% confidence interval, 1.78–9.64) remained significantly related to BPD-PH at discharge. By probit analysis, each additional month of PDA and hemodynamically significant PDA exposure was associated with an increased probability for the composite outcome of BPD-PH at discharge or death with coefficients of 0.40 (P

ImportanceSocioeconomic status impacts pregnancy outcomes and child development after NICU discharge for infants born prematurely, but has not been well studied for outcomes during the NICU stay. The Area Deprivation Index (ADI) is a validated measure of neighborhood disadvantage that uses Census data on income, education, employment, and housing quality.ObjectiveIn NICUs in different US regions, determine if ADI predicts NICU mortality and morbidity in extremely premature infants.DesignWe conducted a retrospective cohort study.SettingFour level IV neonatal intensive care units (NICU) in different US geographic regions: Northeast, Mid-Atlantic, Midwest, and South.ParticipantsNon-Hispanic White and Black extremely premature infants (gestational age ExposuresADI, race, BW, sex, and outborn status (admitted after transfer from an outside birth hospital).Main Outcomes and MeasuresWe converted addresses to census blocks, identified by 12-digit Federal Information Processing Series (FIPS) codes, to link residences to the national ADI percentile of study participants. We analyzed the relationship between ADI and NICU mortality using Bayesian logistic regression adjusted for race, BW, outborn status, and sex. Predictors were considered significant if the 95% Credible Intervals excluded zero. We also analyzed the effect of ADI on NICU morbidities of late-onset sepsis, necrotizing enterocolitis, and severe intraventricular hemorrhage.ResultsWe studied 2,765 infants. In univariate analysis, infants with higher ADI were more likely to be Black, suffer from short-term morbidities, and die before NICU discharge. ADI did not correlate with BW (r = −0.05) or sex. Black infants also had higher mortality and lower BW. In a multivariable model, lower BW, higher ADI, and male sex were statistically significant risk factors, while Black race and outborn status were not. Using these methods, ADI was also identified as a risk factor for NICU morbidities.Conclusions and RelevanceAmong extremely preterm infants admitted to four NICUs in different US geographic regions, ADI was a risk factor for mortality and morbidity after adjusting for multiple covariates. These findings have implications for public health measures to improve prenatal and NICU care for patients from disadvantaged areas.Key PointsQuestionIs socioeconomic deprivation at the neighborhood level, measured by an Area Deprivation Index (ADI), an independent risk factor for NICU mortality and morbidity among extremely premature infants?FindingsIn a cohort of 2,765 extremely premature infants (gestational age MeaningThese findings have implications for public health measures to improve prenatal and NICU care for patients from disadvantaged areas.

Infants with gestational age between 22 0/7 and 23 6/7 weeks (referred to as nano-preterm infants) are at very high risk of adverse outcomes. Noninvasive respiratory support at birth improves outcomes in infants born at 24 0/7 to 27 6/7 weeks' gestational age. Evidence is limited on whether similar benefits of non-invasive respiratory support at birth extend to nano-preterm infants.To evaluate the hypothesis that intubation at 10 minutes or earlier after birth is associated with a higher incidence of bronchopulmonary dysplasia (BPD) or death by 36 weeks' postmenstrual age (PMA) in nano-preterm infants.This observational cohort study included all nano-preterm infants at a level IV neonatal intensive care unit who were delivered from January 1, 2014, to June 30, 2021. Infants receiving palliative or comfort care at birth were excluded.Infants were grouped based on first intubation attempt timing after birth (10 minutes after birth and ≤10 minutes as noninvasive and invasive respiratory support at birth groups, respectively).The primary outcome was the composite outcome of BPD (physiological definition) or death by 36 weeks' PMA.All 230 consecutively born, eligible nano-preterm infants were included, of whom 88 (median [IQR] gestational age, 23.6 [23.4-23.7] weeks; 45 [51.1%] female; 54 [62.1%] Black) were in the noninvasive respiratory support at birth group and 142 (median [IQR] gestational age, 23.0 [22.4-23.3] weeks; 71 [50.0%] female; 94 [66.2%] Black) were in the invasive respiratory support at birth group. The incidence of BPD or death by 36 weeks' PMA did not differ between the noninvasive and invasive respiratory support groups (83 of 88 [94.3%] in the noninvasive group vs 129 of 142 [90.9%] in the invasive group; adjusted odds ratio, 2.09; 95% CI, 0.60-7.25; P = .24). Severe intraventricular hemorrhage or death by 36 weeks' PMA was lower in the invasive respiratory support at birth group (adjusted odds ratio, 2.20; 95% CI, 1.07-4.51; P = .03).This cohort study's findings suggest that noninvasive respiratory support in the first 10 minutes after birth is feasible but is not associated with a decrease in the risk of BPD or death compared with intubation and early surfactant delivery in nano-preterm infants.

ImportanceSocioeconomic status affects pregnancy and neurodevelopment, but its association with hospital outcomes among premature infants is unknown. The Area Deprivation Index (ADI) is a validated measure of neighborhood disadvantage that uses US Census Bureau data on income, educational level, employment, and housing quality.ObjectiveTo determine whether ADI is associated with neonatal intensive care unit (NICU) mortality and morbidity in extremely premature infants.Design, Setting, and ParticipantsThis retrospective cohort study was performed at 4 level IV NICUs in the US Northeast, Mid-Atlantic, Midwest, and South regions. Non-Hispanic White and Black infants with gestational age of less than 29 weeks and born between January 1, 2012, and December 31, 2020, were included in the analysis. Addresses were converted to census blocks, identified by Federal Information Processing Series codes, to link residences to national ADI percentiles.ExposuresADI, race, birth weight, sex, and outborn status.Main Outcomes and MeasuresIn the primary outcome, the association between ADI and NICU mortality was analyzed using bayesian logistic regression adjusted for race, birth weight, outborn status, and sex. Risk factors were considered significant if the 95% credible intervals excluded zero. In the secondary outcome, the association between ADI and NICU morbidities, including late-onset sepsis, necrotizing enterocolitis (NEC), and severe intraventricular hemorrhage (IVH), were also analyzed.ResultsA total of 2765 infants with a mean (SD) gestational age of 25.6 (1.7) weeks and mean (SD) birth weight of 805 (241) g were included in the analysis. Of these, 1391 (50.3%) were boys, 1325 (47.9%) reported Black maternal race, 498 (18.0%) died before NICU discharge, 692 (25.0%) developed sepsis or NEC, and 353 (12.8%) had severe IVH. In univariate analysis, higher median ADI was found among Black compared with White infants (77 [IQR, 45-93] vs 57 [IQR, 32-77]; P < .001), those who died before NICU discharge vs survived (71 [IQR, 45-89] vs 64 [IQR, 36-86]), those with late-onset sepsis or NEC vs those without (68 [IQR, 41-88] vs 64 [IQR, 35-86]), and those with severe IVH vs those without (69 [IQR, 44-90] vs 64 [IQR, 36-86]). In a multivariable bayesian logistic regression model, lower birth weight, higher ADI, and male sex were risk factors for mortality (95% credible intervals excluded zero), while Black race and outborn status were not. The ADI was also identified as a risk factor for sepsis or NEC and severe IVH.Conclusions and RelevanceThe findings of this cohort study of extremely preterm infants admitted to 4 NICUs in different US geographic regions suggest that ADI was a risk factor for mortality and morbidity after adjusting for multiple covariates.

To assess the correlation between infant mortality and extreme prematurity by state. This ecological study included data on 28,526,534 infants from 2007 to 2013 in all 50 US states and DC using CDC WONDER linked birth and infant death records. Regression analyses determined the correlation between infant and neonatal mortality rates and the proportion of extremely preterm, extremely low birth weight, and black births by state. State infant and neonatal mortality rates were directly and highly correlated with the proportion of extremely preterm births (infant, r2 = 0.71, P

Test the hypothesis potential missed opportunities for antenatal corticosteroids increase as gestational age decreases and are associated with adverse outcomes.Observational cohort study.24 US centers in the Neonatal Research Network.Actively treated infants 22-25 weeks' gestation and birth weight 401-1000 grams, without major birth defects, born 2006-2018.Potential missed opportunity was defined as no antenatal corticosteroids but did have prenatal antibiotics, and/or magnesium sulfate, and/or prolonged rupture of membranes. Poisson regression models adjusted for baseline characteristics.Antenatal corticosteroid exposure, mortality, and severe intracranial hemorrhage or periventricular leukomalacia.6966 (87.5%) were exposed to antenatal corticosteroids, 454 (5.7%) had no exposure but potential missed opportunities for antenatal corticosteroid exposure, and 537 (6.7%) had no exposure and no evidence of potential missed opportunities. Compared with infants born at 25 weeks, potential missed opportunities for antenatal corticosteroid exposure were more likely at 22 weeks (adjusted relative risk (aRR) [95% CI] 11.06 [7.52-16.27]) and 23 weeks (3.24 [2.44-4.29]) but did not differ at 24 weeks (1.08 [0.82-1.42]). Potential missed opportunities for antenatal corticosteroids decreased over time at 22-23 weeks' gestation. Antenatal corticosteroid exposed infants had lower risk of death (31.0% vs 54.8%; 0.77 [0.70-0.84]) and survivors had lower risk of severe brain injury (25.0% v 44.5%; 0.64 [0.55-0.73]) compared with infants with potential missed opportunities.Potential missed opportunities for antenatal corticosteroid exposure increased with decreasing gestational age and were associated with higher rates of death and severe brain injury among actively treated periviable births.

ObjectiveDetermine if targeting higher transcutaneous carbon dioxide improves respiratory stability among very preterm infants on ventilatory support.DesignSingle-centre pilot randomised clinical trial.SettingThe University of Alabama at Birmingham.PatientsVery preterm infants on ventilatory support after postnatal day 7.InterventionsInfants were randomised to two different transcutaneous carbon dioxide levels targeting 5 mm Hg (0.67 kPa) changes with four sessions each lasting 24 hours for 96 hours: baseline-increase-baseline-increase or baseline-decrease-baseline-decrease.Main outcome measuresWe collected cardiorespiratory data evaluating episodes of intermittent hypoxaemia (oxygen saturations (SpO2)ResultsWe enrolled 25 infants with a gestational age of 24 w 6 d±11 d (mean±SD) and birth weight 645±142 g on postnatal day 14±3. Continuous transcutaneous carbon dioxide values (56.8±6.9 in the higher group vs 54.5±7.8 in the lower group; p=0.36) did not differ significantly between groups during the intervention days. There were no differences in intermittent hypoxaemia (126±64 vs 105±61 per 24 hours; p=0.30) or bradycardia (11±16 vs 15±23 per hour; p=0.89) episodes between groups. The proportion of time with SpO220.05). There was moderate negative correlation between mean transcutaneous carbon dioxide and bradycardia episodes (r=−0.56; pConclusionTargeting 5 mm Hg (0.67 kPa) changes in transcutaneous carbon dioxide did not improve respiratory stability among very preterm infants on ventilatory support but the intended carbon dioxide separation was difficult to achieve and maintain.Trial registration numberNCT03333161.

OBJECTIVES Our objective with this quality improvement initiative was to reduce rates of severe intracranial hemorrhage (ICH) or death in the first week after birth among extremely preterm infants. METHODS The quality improvement initiative was conducted from April 2014 to September 2020 at the University of Alabama at Birmingham’s NICU. All actively treated inborn extremely preterm infants without congenital anomalies from 22 + 0/7 to 27 + 6/7 weeks’ gestation with a birth weight ≥400 g were included. The primary outcome was severe ICH or death in the first 7 days after birth. Balancing measures included rates of acute kidney injury and spontaneous intestinal perforation. Outcome and process measure data were analyzed by using p-charts. RESULTS We studied 820 infants with a mean gestational age of 25 + 3/7 weeks and median birth weight of 744 g. The rate of severe ICH or death in the first week after birth decreased from the baseline rate of 27.4% to 15.0%. The rate of severe ICH decreased from a baseline rate of 16.4% to 10.0%. Special cause variation in the rate of severe ICH or death in the first week after birth was observed corresponding with improvement in carbon dioxide and pH targeting, compliance with delayed cord clamping, and expanded use of indomethacin prophylaxis. CONCLUSIONS Implementation of a bundle of evidence-based potentially better practices by using specific electronic order sets was associated with a lower rate of severe ICH or death in the first week among extremely preterm infants.

Excessive accumulation of fluid may result in interstitial edema and multiorgan dysfunction. Over the past few decades, the detrimental impact of fluid overload has been further defined in adult and pediatric populations. Growing evidence highlights the importance of monitoring, preventing, managing, and treating fluid overload appropriately. Translating this knowledge to neonates is difficult as they have different disease pathophysiologies, and because neonatal physiology changes rapidly postnatally in many of the organ systems (i.e., skin, kidneys, and cardiovascular, pulmonary, and gastrointestinal). Thus, evaluations of the optimal targets for fluid balance need to consider the disease state as well as the gestational and postmenstrual age of the infant. Integration of what is known about neonatal fluid overload with individual alterations in physiology is imperative in clinical management. This comprehensive review will address what is known about the epidemiology and pathophysiology of neonatal fluid overload and highlight the known knowledge gaps. Finally, we provide clinical recommendations for monitoring, prevention, and treatment of fluid overload.

ImportanceActive postnatal care has been associated with center differences in survival among periviable infants. Regional differences in outcomes among periviable infants in the US may be associated with differences in active postnatal care.ObjectiveTo determine if regions with higher rates of active postnatal care will have higher gestational age-specific survival rates among periviable infants.Design, Setting, and ParticipantsThis cohort study included live births from 22 to 25 weeks’ gestation weighing 400 to 999 g in the US Centers for Disease Control and Prevention (CDC) WONDER 2017 to 2020 (expanded) database. Infants with congenital anomalies were excluded. Active postnatal care was defined using the CDC definition of abnormal conditions of newborn as presence of any of the following: neonatal intensive care unit (NICU) admission, surfactant, assisted ventilation, antibiotics, and seizures. Data were analyzed from August to November 2022.Main Outcomes and MeasuresRegional gestational age-specific survival rates were compared with rates of active postnatal care in the 10 US Health and Human Services regions using Kendall τ test.ResultsWe included 41 707 periviable infants, of whom 32 674 (78%) were singletons and 19 467 (46.7%) were female. Among those studied 34 983 (83.9%) had evidence of active care, and 26 009 (62.6%) survived. Regional rates of active postnatal care were positively correlated with regional survival rates at 22 weeks’ gestation (rτ[8] = 0.56; r2 = 0.31; P = .03) but the correlation was not significant at 23 weeks’ gestation (rτ[8] = 0.47; r2 = 0.22; P = .07). There was no correlation between active care and survival at 24 or 25 weeks’ gestation. Regional rates of both NICU admission and assisted ventilation following delivery were positively correlated with regional rates of survival at 22 weeks’ gestation (both P rτ[8] = 0.60; r2 = 0.36; P = .02).Conclusions and RelevanceIn this cohort study of 41 707 periviable infants, regional differences in rates of active postnatal care, neonatal intensive care unit admission, provision of assisted ventilation and antenatal corticosteroid exposure were moderately correlated with survival at 22 weeks’ gestation. Further studies focused on individual-level factors associated with active periviable care are warranted.

Oxygen therapy is an essential part of neonatal care. Targeting oxygen saturations and preventing hypoxemia and hyperoxemia is difficult, particularly in preterm infants. The mode of oxygen delivery directly affects the stability of oxygen saturations, hypoxemia, and hyperoxemia. This stability has important clinical implications. New methods of noninvasive oxygen administration, including closed-loop automated control and servo-controlled oxygen environments, have been developed to improve oxygen saturation targeting and decrease episodes of hyperoxemia and hypoxemia.

Key Points Question Are racial/ethnic disparities in care practices and major outcomes increasing or decreasing among extremely preterm infants in the US? Findings In this cohort study of 20 092 extremely preterm infants, racial/ethnic disparities in rates of antenatal corticosteroids and cesarean delivery decreased over time. Changes in rates of mortality and most major morbidities did not differ among white, black, and Hispanic infants, and while mortality decreased over time from 2002 to 2016, rates of moderate-severe neurodevelopmental impairment increased over time in all groups. Meaning Racial/ethnic disparities in rates of potentially life-saving care practices decreased over time in the US, with reductions in mortality but increases in neurodevelopmental impairment in all racial/ethnic groups., Importance Racial/ethnic disparities in quality of care among extremely preterm infants are associated with adverse outcomes. Objective To assess whether racial/ethnic disparities in major outcomes and key care practices were changing over time among extremely preterm infants. Design, Setting, and Participants This observational cohort study used prospectively collected data from 25 US academic medical centers. Participants included 20 092 infants of 22 to 27 weeks’ gestation with a birth weight of 401 to 1500 g born at centers participating in the National Institute of Child Health and Human Development Neonatal Research Network from 2002 to 2016. Of these infants, 9316 born from 2006 to 2014 were eligible for follow-up at 18 to 26 months’ postmenstrual age (excluding 5871 infants born before 2006, 2594 infants born after 2014, and 2311 ineligible infants including 64 with birth weight >1000 g and 2247 infants with gestational age >26 6/7 weeks), of whom 745 (8.0%) did not have known follow-up outcomes at 18 to 26 months. Main Outcomes and Measures Rates of mortality, major morbidities, and care practice use over time were evaluated using models adjusted for baseline characteristics, center, and birth year. Data analyses were conducted from 2018 to 2019. Results In total, 20 092 infants with a mean (SD) gestational age of 25.1 (1.5) weeks met the inclusion criteria and were available for the primary outcome: 8331 (41.5%) black infants, 3701 (18.4%) Hispanic infants, and 8060 (40.1%) white infants. Hospital mortality decreased over time in all groups. The rate of improvement in hospital mortality over time did not differ among black and Hispanic infants compared with white infants (black infants went from 35% to 24%, Hispanic infants went from 32% to 27%, and white infants went from 30% to 22%; P = .59 for race × year interaction). The rates of late-onset sepsis among black infants (went from 37% to 24%) and Hispanic infants (went from 45% to 23%) were initially higher than for white infants (went from 36% to 25%) but decreased more rapidly and converged during the most recent years (P = .02 for race × year interaction). Changes in rates of other major morbidities did not differ by race/ethnicity. Death before follow-up decreased over time (from 2006 to 2014: black infants, 14%; Hispanic infants, 39%, white infants, 15%), but moderate-severe neurodevelopmental impairment increased over time in all racial/ethnic groups (increase from 2006 to 2014: black infants, 70%; Hispanic infants, 123%; white infants, 130%). Rates of antenatal corticosteroid exposure (black infants went from 72% to 90%, Hispanic infants went from 73% to 83%, and white infants went from 86% to 90%; P = .01 for race × year interaction) and of cesarean delivery (black infants went from 45% to 59%, Hispanic infants went from 49% to 59%, and white infants went from 62% to 63%; P = .03 for race × year interaction) were initially lower among black and Hispanic infants compared with white infants, but these differences decreased over time. Conclusions and Relevance Among extremely preterm infants, improvements in adjusted rates of mortality and most major morbidities did not differ by race/ethnicity, but rates of neurodevelopmental impairment increased in all groups. There were narrowing racial/ethnic disparities in important care practices, including the use of antenatal corticosteroids and cesarean delivery., This cohort study evaluates whether racial/ethnic disparities in key care practices and major outcomes changed among extremely preterm infants from 2002 to 2016 at centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.

Caffeine use in preterm infants has endured several paradigms: from standard of care to possible neurotoxin to one of the few medications for which there is evidence of bronchopulmonary dysplasia (BPD) risk reduction. The purpose of the review is to analyze this dynamic trajectory and discuss controversies that still remain after decades of caffeine use.Following concerns for caffeine safety in preterm infants, a large randomized controlled trial demonstrated a reduction in BPD and treatment for patent ductus arteriosus. The lower rate of death or neurodevelopmental impairment noted at 18-21 months was not statistically different at later timepoints; however, infants in the caffeine group had lower rates of motor impairment at 11-year follow-up. The time of caffeine therapy initiation is now substantially earlier, and doses used are sometimes higher that previously used, but there are limited data to support these practices.Caffeine therapy for apnea of prematurity (AOP) remains one of the pillars of neonatal care, although more evidence to support dosing and timing of initiation and discontinuation are needed.

OBJECTIVE: To compare changes in lung volumes, as measured by functional residual capacity (FRC), through to discharge in stable infants randomized to 2 weeks of extended continuous positive airway pressure CPAP (eCPAP) vs CPAP discontinuation (dCPAP). STUDY DESIGN: Infants born at ≤32 weeks of gestation requiring ≥24 hours of CPAP were randomized to 2 weeks of eCPAP vs dCPAP when meeting CPAP stability criteria. FRC was measured with the nitrogen washout technique. Infants were stratified by gestational age (

To assess the correlation between infant mortality and extreme prematurity by state.This ecological study included data on 28,526,534 infants from 2007 to 2013 in all 50 US states and DC using CDC WONDER linked birth and infant death records. Regression analyses determined the correlation between infant and neonatal mortality rates and the proportion of extremely preterm, extremely low birth weight, and black births by state.State infant and neonatal mortality rates were directly and highly correlated with the proportion of extremely preterm births (infant, rInterstate variation in infant and neonatal mortality rates are primarily driven by rates of extremely preterm and extremely low birth weight births which is closely related to the proportion of black births.

To determine whether early polyethylene bag use with skin-to-skin care compared with skin-to skin care alone reduce hypothermia among infants born at term in resource-limited settings.Infants born at term in the tertiary referral center in Lusaka, Zambia, were randomized using sequentially numbered sealed opaque envelopes in 2 phases: after birth (phase 1) and at 1 hour after birth (phase 2) to either skin-to-skin care with polyethylene bags or skin-to-skin care alone. Infant and maternal temperatures were recorded at birth, 1 hour, and every 4 hours until discharge or 24 hours.We enrolled 423 infants from May 2017 to August 2017. The rate of moderate-severe hypothermia (temperature36.0°C) at 1 hour was 72 of 208 (34.6%) in the skin-to-skin care with a polyethylene bag group compared with 101 of 213 (47.4%) in the skin-to-skin care alone group (relative risk, 0.71; 95% CI 0.56-0.90; P .01; number needed to treat = 8). phase 1 treatment assignment significantly modified the effect of phase 2 treatment (P = .02 for interaction effect). Among infants randomized to skin-to-skin care with a polyethylene bag in phase 1, the risk of moderate-severe hypothermia was decreased in infants randomized to continue this intervention until discharge compared with infants randomized to skin-to-skin care alone. The rates of severe hypothermia, hyperthermia, and other adverse events did not differ significantly between groups.Low-cost polyethylene bags started after birth in combination with skin-to-skin care reduced moderate or severe hypothermia at 1 hour and at discharge among infants born at term in a resource-limited setting compared with skin-to-skin care alone.ClinicalTrials.gov: NCT03141723.

We measured percent body fat by air-displacement plethysmography in 86 infants born at

Background: Trophic feeding compared to no enteral feeding prevents atrophy of the gastrointestinal tract. However, the practice of extending the duration of trophic feeding often delays initiation of full enteral feeding in extremely preterm infants. We hypothesized that a short duration of trophic feeding (3 days or less) is associated with early initiation of full enteral feeding. Methods: A total of 192 extremely preterm infants (23-28 weeks' gestation) born between 2013 and 2015 were included. Infants were divided into 2 groups according to the duration of trophic feeding (short vs. extended). The primary outcome was time to achieve full enteral feeding and the safety outcome was necrotizing enterocolitis (NEC) and/or death. Results: A short duration of trophic feeding was associated with a reduction in time to achieve full enteral feeding after adjustment for birth weight, gestational age, race, sex, type of enteral nutrition, and day of initiation of trophic feeding (mean difference favoring a short duration of trophic feeding: -4.1 days; 95% CI: -2.3 to -5.8; p < 0.001). A short duration of trophic feeding was not associated with a higher risk of NEC and/or death after achieving full enteral feeding (AOR: 0.91; 95% CI: 0.30-2.77; p = 0.87). Conclusions: A short duration of trophic feeding is associated with early initiation of full enteral feeding. A short duration of trophic feeding is not associated with a higher risk of NEC, but our study was underpowered for this safety outcome. Randomized trials are needed to test this study hypothesis.

Thoracoschisis is an extremely rare congenital anomaly associated with limb body wall defect and diaphragmatic hernia. We describe a case of a female infant who was noted at birth to have tissue coming through a left sided thoracic defect next to an accessory nipple. The stomach bubble was displaced superiorly on radiographs. At surgery the tissue was attached to the left lateral lobe of the liver and was protruding through the chest wall via an intercostal defect below an eventrated diaphragm. The tissue was resected and the defect closed. Pathological examination was consistent with a mesenchymal hamartoma. The diaphragm may have formed abnormally in this case due to the presence of the mesenchymal hamartoma in this location.

To determine whether higher-volume feedings improve postnatal growth among infants born very preterm.Randomized clinical trial with 1:1 parallel allocation conducted from January 2015 to June 2018 in a single academic medical center in the US. In total, 224 infants with a birth weight 1001-2500 g born at32 weeks of gestation were randomized to higher-volume (180-200 mL/kg/d) or usual-volume (140-160 mL/kg/d) feedings after establishing full enteral feedings (≥120 mL/kg/d). The primary outcome was growth velocity (g/kg/d) from randomization to study completion at 36 weeks of postmenstrual age or hospital discharge if earlier.Growth velocity increased among infants in the higher-volume group compared with the usual-volume group (mean [SD], 20.5 [4.5] vs 17.9 [4.5] g/kg/d; P .001). At study completion, all measurements were higher among infants in the higher-volume group compared with the usual-volume group: weight (2365 [324] g, z score -0.60 [0.73] vs 2200 [308] g, z score -0.94 [0.71]; P .001); head circumference (31.9 [1.3] cm, z score -0.30 [0.91] vs 31.4 [1.3] cm, z score -0.53 [0.84]; P = .01); length (44.9 [2.1] cm, z score -0.68 [0.88] vs 44.4 [2.0], z score -0.83 [0.84]; P = .04); and mid-arm circumference (8.8 [0.8] cm vs 8.4 [0.8] cm; P = .002). Bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, or other adverse outcomes did not differ between groups.In infants born very preterm weighing 1001-2500 g at birth, higher-volume feedings increased growth velocity, weight, head circumference, length, and mid-arm circumference compared with usual-volume feedings without adverse effects.ClinicalTrials.gov; NCT02377050.

Premature infants are at high risk for developing bronchopulmonary dysplasia (BPD), characterized by chronic inflammation and inhibition of lung development, which we have recently identified as being modulated by microRNAs (miRNAs) and alterations in the airway microbiome. Exosomes and exosomal miRNAs may regulate cell differentiation and tissue and organ development. We discovered that tracheal aspirates from infants with severe BPD had increased numbers of, but smaller, exosomes compared with term controls. Similarly, bronchoalveolar lavage fluid from hyperoxia-exposed mice (an animal model of BPD) and supernatants from hyperoxia-exposed human bronchial epithelial cells (in vitro model of BPD) had increased exosomes compared with air controls. Next, in a prospective cohort study of tracheal aspirates obtained at birth from extremely preterm infants, utilizing independent discovery and validation cohorts, we identified unbiased exosomal miRNA signatures predictive of severe BPD. The strongest signal of reduced miR-876-3p in BPD-susceptible compared with BPD-resistant infants was confirmed in the animal model and in vitro models of BPD. In addition, based on our recent discovery of increased Proteobacteria in the airway microbiome being associated with BPD, we developed potentially novel in vivo and in vitro models for BPD combining Proteobacterial LPS and hyperoxia exposure. Addition of LPS led to a larger reduction in exosomal miR 876-3p in both hyperoxia and normoxia compared with hyperoxia alone, thus indicating a potential mechanism by which alterations in microbiota can suppress miR 876-3p. Gain of function of miR 876-3p improved the alveolar architecture in the in vivo BPD model, demonstrating a causal link between miR 876-3p and BPD. In summary, we provide evidence for the strong predictive biomarker potential of miR 876-3p in severe BPD. We also provide insights on the pathogenesis of neonatal lung disease, as modulated by hyperoxia and microbial product–induced changes in exosomal miRNA 876-3p, which could be targeted for future therapeutic development.

Background: When intubating newborns, clinicians aim to place the tip of the endotracheal tube (ETT) in the mid-trachea. Clinicians usually estimate the ETT insertion depth based on weight. ETT tips are often incorrectly positioned in newborns. Estimating the insertion depth based on gestation may be more accurate. Objective: To determine whether estimating the ETT insertion depth using gestation, compared to weight, results in more correctly placed ETTs. Methods: Newborn infants without congenital anomalies who were intubated orally were randomised to having their ETT insertion depth estimated using weight [insertion depth (cm) = weight (kg) + 6] or gestation [value determined from a table]. The primary outcome was correct ETT position, defined as an ETT tip between the upper border of the first thoracic vertebra (T1) and the lower border of the second thoracic vertebra (T2) on a chest X-ray. The primary outcome was determined by one paediatric radiologist who was masked to group assignment. Results: Ninety infants were enrolled and the groups were well matched. The proportion of correctly placed ETTs was not significantly different between the groups [weight, 25/49 (51%), vs. gestation, 16/41 (39%), p = 0.293]. We found no significant differences in the secondary outcomes measured. Conclusion: Estimating the ETT insertion depth in newborns using gestation compared to weight did not result in more correctly placed ETTs.

OBJECTIVE: To test the hypothesis that environmental compared with nasal cannula oxygen decreases episodes of intermittent hypoxemia (oxygen saturations

Preterm infants have a higher incidence of life-threatening events including apnea (cessation of breathing), bradycardia (slowing of heart rate) and hypoxemia (oxygen de-saturation). In Neonatal Intensive Care Units, clinicians face a demanding task of assessing the risk of these infants based on their physiological signals. In this study, we propose an algorithm of heart rate dynamics that could potentially be employed for risk stratification of preterm infants. We collected and analysed heart rate (HR) measures in beats per minute (bpm) in 18 preterm infants for 24 hours during oxygen therapy. We investigated whether the HR fluctuations in the first one hour could predict the number of bradycardia events N (i.e. HR below 100 bpm) in the subsequent 23 hours. Since RR intervals estimated from HR (i.e. RR = 60/HR) in seconds follow a lognormal distribution, we employed an algorithm based on a point process modelling framework to capture HR fluctuations. We found that the instantaneous variance σ2(t) calculated by the point process model for the first 1-hour correlates significantly with N. We also found that σ2(t) correlates with number of hypoxemia in the subsequent 23 hours. Thus, we conclude that the fluctuations in the HR data captured using a point process model can be used to predict life threatening events.

Antenatal corticosteroids are given primarily to induce fetal lung maturation but results from meta-analyses of randomized controlled trials have not shown mortality or pulmonary benefits for extremely preterm infants although these are the infants most at risk of mortality and pulmonary disease.We sought to determine if exposure to antenatal corticosteroids is associated with a lower rate of death and pulmonary morbidities by 36 weeks' postmenstrual age.Prospectively collected data on 11,022 infants 22 0/7 to 28 6/7 weeks' gestational age with a birthweight of ≥401 g born from Jan. 1, 2006, through Dec. 31, 2014, were analyzed. The rate of death and the rate of physiologic bronchopulmonary dysplasia by 36 weeks' postmenstrual age were analyzed by level of exposure to antenatal corticosteroids using models adjusted for maternal variables, infant variables, center, and epoch.Infants exposed to any antenatal corticosteroids had a lower rate of death (2193/9670 [22.7%]) compared to infants without exposure (540/1302 [41.5%]) (adjusted relative risk, 0.71; 95% confidence interval, 0.65-0.76; P.0001). Infants exposed to a partial course of antenatal corticosteroids also had a lower rate of death (654/2520 [26.0%]) compared to infants without exposure (540/1302 [41.5%]); (adjusted relative risk, 0.77; 95% confidence interval, 0.70-0.85; P.0001). In an analysis by each week of gestation, infants exposed to a complete course of antenatal corticosteroids had lower mortality before discharge compared to infants without exposure at each week from 23-27 weeks' gestation and infants exposed to a partial course of antenatal corticosteroids had lower mortality at 23, 24, and 26 weeks' gestation. Rates of bronchopulmonary dysplasia in survivors did not differ by antenatal corticosteroid exposure. The rate of death due to respiratory distress syndrome, the rate of surfactant use, and the rate of mechanical ventilation were lower in infants exposed to any antenatal corticosteroids compared to infants without exposure.Among infants 22-28 weeks' gestational age, any or partial antenatal exposure to corticosteroids compared to no exposure is associated with a lower rate of death while the rate of bronchopulmonary dysplasia in survivors did not differ.