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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

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.

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 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.

ObjectiveTo test the hypothesis that kangaroo mother care (KMC) initiated either at birth or at 1 hour after birth reduces moderate or severe hypothermia in term neonates at (A) 1 hour after birth and (B) at discharge when compared with standard thermoregulation care.MethodsTerm neonates born at a tertiary delivery centre in Zambia were randomised in two phases (phase 1: birth to 1 hour, phase 2: 1 hour to discharge) to either as much KMC as possible in combination with standard thermoregulation care (KMC group) or to standard thermoregulation care (control group). The primary outcomes were moderate or severe hypothermia (axillary temperature ResultsThe proportion of neonates with moderate or severe hypothermia did not differ between the KMC and control groups at 1 hour after birth (25% vs 27%, relative risk (RR)=0.93, 95% CI 0.59 to 1.4, P=0.78) or at discharge (7% vs 2%, RR=2.8, 95% CI 0.6 to 13.9, P=0.16). Hypothermia was not found among the infants who had KMC for at least 9 hours or 80% of the hospital stay.ConclusionsKMC practised as much as possible in combination with standard thermoregulation care initiated either at birth or at 1 hour after birth did not reduce moderate or severe hypothermia in term infants compared with standard thermoregulation care. The current study also shows that duration of KMC either for at least 80% of the time or at least 9 hours during the day of birth was effective in preventing hypothermia in term infants.Clinical trial registrationNCT02189759.

Despite major improvements in reducing childhood mortality worldwide, over 5 million pregnancies per year end in stillbirths or neonatal deaths. The vast majority of these deaths occur in low- and middle-income countries. Many of these deaths are preventable with readily available evidence-based care practices. This review focuses on educational programs developed to reduce preventable deaths in newborn infants in low- and middle-income countries, including Essential Newborn Care and Helping Babies Breathe, a simplified version of the Neonatal Resuscitation Program. Innovative pragmatic large-scale trials conducted in the Global Network for Women's and Children's Health Research of the National Institutes of Health in the USA have evaluated these programs in low-resource settings. The results of these studies and the implications for future programs designed to decrease childhood mortality are reviewed.

Objective To determine if postnatal transfer or birth in a non-tertiary hospital is associated with adverse outcomes. Design Observational cohort study with propensity score matching. Setting National health service neonatal care in England; population data held in the National Neonatal Research Database. Participants Extremely preterm infants born at less than 28 gestational weeks between 2008 and 2015 (n=17 577) grouped based on birth hospital and transfer within 48 hours of birth: upward transfer (non-tertiary to tertiary hospital, n=2158), non-tertiary care (born in non-tertiary hospital; not transferred, n=2668), and controls (born in tertiary hospital; not transferred, n=10 866). Infants were matched on propensity scores and predefined background variables to form subgroups with near identical distributions of confounders. Infants transferred between tertiary hospitals (horizontal transfer) were separately matched to controls in a 1:5 ratio. Main outcome measures Death, severe brain injury, and survival without severe brain injury. Results 2181 infants, 727 from each group (upward transfer, non-tertiary care, and control) were well matched. Compared with controls, infants in the upward transfer group had no significant difference in the odds of death before discharge (odds ratio 1.22, 95% confidence interval 0.92 to 1.61) but significantly higher odds of severe brain injury (2.32, 1.78 to 3.06; number needed to treat (NNT) 8) and significantly lower odds of survival without severe brain injury (0.60, 0.47 to 0.76; NNT 9). Compared with controls, infants in the non-tertiary care group had significantly higher odds of death (1.34, 1.02 to 1.77; NNT 20) but no significant difference in the odds of severe brain injury (0.95, 0.70 to 1.30) or survival without severe brain injury (0.82, 0.64 to 1.05). Compared with infants in the upward transfer group, infants in the non-tertiary care group had no significant difference in death before discharge (1.10, 0.84 to 1.44) but significantly lower odds of severe brain injury (0.41, 0.31 to 0.53; NNT 8) and significantly higher odds of survival without severe brain injury (1.37, 1.09 to 1.73; NNT 14). No significant differences were found in outcomes between the horizontal transfer group (n=305) and controls (n=1525). Conclusions In extremely preterm infants, birth in a non-tertiary hospital and transfer within 48 hours are associated with poor outcomes when compared with birth in a tertiary setting. We recommend perinatal services promote pathways that facilitate delivery of extremely preterm infants in tertiary hospitals in preference to postnatal transfer.

Objective To determine whether exposure to any antenatal corticosteroids is associated with a lower rate of death at each gestational age at which administration is currently recommended. Design Prospective cohort study. Settings 300 participating neonatal intensive care units of the Pediatrix Medical Group in the United States. Participants 117 941 infants 23 0/7 to 34 6/7 weeks’ gestational age born between 1 January 2009 and 31 December 2013. Exposure Any antenatal corticosteroids. Main outcomes measures Death or major hospital morbidities analyzed by gestational age and exposure to antenatal corticosteroids with models adjusted for birth weight, sex, mode of delivery, and multiple births. Results Infants exposed to antenatal corticosteroids (n=81 832) had a significantly lower rate of death before discharge at each gestation 29 weeks or less, 31 weeks, and 33-34 weeks compared with infants without exposure (range of adjusted odds ratios 0.32 to 0.55). The number needed to treat with antenatal corticosteroids to prevent one death before discharge increased from six at 23 and 24 weeks’ gestation to 798 at 34 weeks’ gestation. The rate of survival without major hospital morbidity was higher among infants exposed to antenatal corticosteroids at the lowest gestations. Infants exposed to antenatal corticosteroids had lower rates of severe intracranial hemorrhage or death, necrotizing enterocolitis stage 2 or above or death, and severe retinopathy of prematurity or death compared with infants without exposure at all gestations less than 30 weeks and most gestations for infants born at 30 weeks’ gestation or later. Conclusion Among infants born from 23 to 34 weeks’ gestation, antenatal exposure to corticosteroids compared with no exposure was associated with lower mortality and morbidity at most gestations. The effect size of exposure to antenatal corticosteroids on mortality seems to be larger in infants born at the lowest gestations.

To explore the association between administration-to-birth interval of antenatal corticosteroids (ACS) and survival in extremely preterm infants.Population-based prospective cohort study.All obstetric and neonatal units in Sweden from 1 April 2004 to 31 March 2007.All live-born infants (n = 707) born at 22-26 completed weeks of gestation.The relationship between time from first administration of ACS to delivery and survival was investigated using Cox proportional hazards regression analysis.Neonatal (0-27 days) and infant (0-365 days) survival, and infant survival without major neonatal morbidity (intraventricular haemorrhage grade ≥ 3, retinopathy of prematurity stage ≥ 3, periventricular leukomalacia, necrotising enterocolitis, or severe bronchopulmonary dysplasia).Five-hundred and ninety-one (84%) infants were exposed to ACS. In the final adjusted model, infant survival was lower in infants unexposed to ACS [hazard ratio (HR) = 0.26; 95% confidence interval 0.15-0.43], in infants born24 h [HR = 0.53 (0.33-0.87)] and7 days after ACS [HR = 0.56 (0.32-0.97)], but not in infants born 24-47 h after ACS [HR = 1.60 (0.73-3.50)], as compared with infants born 48 h to 7 days after administration. The findings were similar for neonatal survival. Survival without major neonatal morbidity among live-born infants was 14% in unexposed infants and 30-39% in steroid-exposed groups, indicating that any ACS exposure was valuable.Administration of ACS 24 h to 7 days before extremely preterm birth was associated with significantly higher survival than in unexposed infants and in infants exposed to ACS at shorter or longer administration-to-birth intervals.Timing of antenatal corticosteroids is important for extremely preterm infants' survival.