IMPORTANCE: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) extremely preterm birth outcome model is widely used for ...prognostication by practitioners caring for families expecting extremely preterm birth. The model provides information on mean outcomes from 1998 to 2003 and does not account for substantial variation in outcomes among US hospitals. OBJECTIVE: To update and validate the NRN extremely preterm birth outcome model for most extremely preterm infants in the United States. DESIGN, SETTING, AND PARTICIPANTS: This prognostic study included 3 observational cohorts from January 1, 2006, to December 31, 2016, at 19 US centers in the NRN (derivation cohort) and 637 US centers in Vermont Oxford Network (VON) (validation cohorts). Actively treated infants born at 22 weeks’ 0 days’ to 25 weeks’ 6 days’ gestation and weighing 401 to 1000 g, including 4176 in the NRN for 2006 to 2012, 45 179 in VON for 2006 to 2012, and 25 969 in VON for 2013 to 2016, were studied. VON cohorts comprised more than 85% of eligible US births. Data analysis was performed from May 1, 2017, to March 31, 2019. EXPOSURES: Predictive variables used in the original model, including infant sex, birth weight, plurality, gestational age at birth, and exposure to antenatal corticosteroids. MAIN OUTCOMES AND MEASURES: The main outcome was death before discharge. Secondary outcomes included neurodevelopmental impairment at 18 to 26 months’ corrected age and measures of hospital resource use (days of hospitalization and ventilator use). RESULTS: Among 4176 actively treated infants in the NRN cohort (48% female; mean SD gestational age, 24.2 0.8 weeks), survival was 63% vs 62% among 3702 infants in the era of the original model (47% female; mean SD gestational age, 24.2 0.8 weeks). In the concurrent (2006-2012) VON cohort, survival was 66% among 45 179 actively treated infants (47% female; mean SD gestational age, 24.1 0.8 weeks) and 70% among 25 969 infants from 2013 to 2016 (48% female; mean SD gestational age, 24.1 0.8 weeks). Model C statistics were 0.74 in the 2006-2012 validation cohort and 0.73 in the 2013-2016 validation cohort. With the use of decision curve analysis to compare the model with a gestational age–only approach to prognostication, the updated model showed a predictive advantage. The birth hospital contributed equally as much to prediction of survival as gestational age (20%) but less than the other factors combined (60%). CONCLUSIONS AND RELEVANCE: An updated model using well-known factors to predict survival for extremely preterm infants performed moderately well when applied to large US cohorts. Because survival rates change over time, the model requires periodic updating. The hospital of birth contributed substantially to outcome prediction.
To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates.
In a retrospective cohort study, ...we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 240/7 to 316/7 weeks of gestational age and birth weight <1500 g. Composite outcomes were in-hospital mortality or any of severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia (BPD); and same composite outcome excluding BPD. Secondary outcomes were mortality and individual morbidities. For each country, annual outcome trends and adjusted relative risks comparing epoch 2 (2012-2015) to epoch 1 (2007-2011) were analyzed.
For composite outcome including BPD, the trend decreased in Canada and Israel but increased in Australia and New Zealand, Japan, Spain, Sweden, and the United Kingdom. For composite outcome excluding BPD, the trend decreased in all countries except Spain, Sweden, Tuscany, and the United Kingdom. The risk of composite outcome was lower in epoch 2 than epoch 1 in Canada (adjusted relative risks 0.78; 95% CI 0.74-0.82) only. The risk of composite outcome excluding BPD was significantly lower in epoch 2 compared with epoch 1 in Australia and New Zealand, Canada, Finland, Japan, and Switzerland. Mortality rates reduced in most countries in epoch 2. BPD rates increased significantly in all countries except Canada, Israel, Finland, and Tuscany.
In most countries, mortality decreased whereas BPD increased for neonates born very preterm.
Mother's own milk (MOM) is the optimal feed for premature infants but may not always be sufficiently available. Alternative feeding includes donor human milk (DONOR), with or without fortification ...and preterm formula. This study evaluated the association between early feeding with exclusively and predominantly MOM (MAINLY-MOM) versus MOM supplemented with fortified DONOR (MOM + DONOR) or preterm formula (MOM + FORMULA) and in-hospital growth and neonatal morbidities.
This was a multicentre (n = 13 units) cohort study of infants born at <32 weeks' gestation. Data captured at the point of care were extracted from the UK National Neonatal Research Database. The study groups were defined based on feeding patterns within the first 2 weeks of life using predefined cut-offs. The primary outcome was the in-hospital growth rate.
Data from 1,272 infants were analysed. Infants fell into two groups: extremely preterm (EPT) infants and very preterm (VPT) infants, born after <28 weeks and 28 to <32 weeks of gestation, respectively. Only 11 of 365 EPT infants received formula supplements, precluding a useful comparison of MOM + DONOR and MOM + FORMULA. There was no difference in median (25th-75th centile) growth velocity over the first 30 days of life between the MAINLY-MOM (n = 248) and MOM + DONOR (n = 106) groups: 10 (8-13) versus 10 (7-13) g/kg/day. Similarly, for VPT infants, there was no difference in growth velocities between MAINLY-MOM (n = 407), MOM + DONOR (N = 196), and MOM + FORMULA (N = 304): 11 (8-14) versus 11 (8-14) versus 11 (8-14) g/kg/day. Head growth did not differ (p value = 0.670). Cox regression analysis showed no difference in time to discharge between feeding types or any difference in major neonatal morbidities. In both EPT and VPT infants, growth velocity from the time of regaining birth weight to discharge was significantly lower in the MAINLY-MOM group compared to the MOM-DONOR group (EPT: 12.5 11-14.2 vs. 14 12.3-15.9 p = 0.45, VPT 13.5 11-15.7 vs. 14.5 12.6-16.8 p = 0.015).
Early feeding with fortified DONOR, in comparison to formula, to supplement MOM was not associated with any differences in short-term growth, length of stay, and neonatal morbidities. However, early feeding with mainly maternal milk, compared to maternal milk supplemented with DONOR, was associated with significantly lower overall weight gain.
IMPORTANCE: Infections and necrotizing enterocolitis, major causes of mortality and morbidity in preterm infants, are reduced in infants fed their own mother’s milk when compared with formula. When ...own mother’s milk is not available, human donor milk is considered a good alternative, albeit an expensive one. However, most infants at modern neonatal intensive care units are predominantly fed with own mother's milk. The benefits of add-on donor milk over formula are not clear. OBJECTIVE: To determine whether providing donor milk instead of formula as supplemental feeding whenever own mother’s milk is insufficiently available during the first 10 days of life reduces the incidence of serious infection, necrotizing enterocolitis, and mortality. DESIGN, SETTINGS, AND PARTICIPANTS: The Early Nutrition Study was a multicenter, double-blind randomized clinical trial in very low-birth-weight infants (birth weight <1500 g) admitted to 1 of 6 neonatal intensive care units in the Netherlands from March 30, 2012, through August 17, 2014. Intent-to-treat analysis was performed. INTERVENTIONS: Infants received pasteurized donor milk or preterm formula during the first 10 days of life if own mother’s milk was not (sufficiently) available. MAIN OUTCOMES AND MEASURES: The primary end point was cumulative occurrence of serious infection (sepsis or meningitis), necrotizing enterocolitis, or mortality during the first 60 days of life. RESULTS: A total of 930 infants were screened for inclusion; 557 were excluded, resulting in 373 infants (183 receiving donor milk and 190 receiving formula) who were evaluated by intent-to-treat analysis (median birth weight, 1066 g; mean gestational age, 28.4 weeks). Own mother’s milk comprised 89.1% and 84.5% of total mean intake during the intervention period for the donor milk and formula groups, respectively. The incidence of the combined outcome was not different (85 44.7% formula vs 77 42.1% donor milk; mean difference, 2.6%; 95% CI, −12.7% to 7.4%). The adjusted hazard ratio was 0.87 (95% CI, 0.63-1.19; P = .37). CONCLUSIONS AND RELEVANCE: In the current study, pasteurized donor milk and preterm formula as supplemental feeding during the first 10 days of life yielded similar short-term outcomes in very low-birth-weight infants regarding safety and efficacy when own mother’s milk availability was insufficient. Future studies investigating longer duration of use of human donor milk on short-term and long-term outcomes are necessary. TRIAL REGISTRATION: trialregister.nl Identifier: NTR3225
Abstract Infants born at extreme preterm gestation are at risk for both death and disability. Although rates of survival have improved for this population, and some evidence suggests a trend toward ...decreased neuromotor impairment over the past decades, a significant improvement in overall early neurodevelopmental outcome has not yet been realized. This review will examine the rates and types of neurodevelopmental impairment seen after extremely preterm birth, including neurosensory, motor, cognitive, and behavioral outcomes. We focus on early outcomes in the first 18–36 months of life, as the majority of large neonatal studies examining neurodevelopmental outcomes stop at this age. However, this early age is clearly just a first glimpse into lifetime outcomes; the neurodevelopmental effects of extreme prematurity may last through school age, adolescence, and beyond. Importantly, prematurity appears to be an independent risk factor for adverse development, but this population demonstrates considerable variability in the types and severity of impairments. Understanding both the nature and prevalence of neurodevelopmental impairment among extremely preterm infants is important because it can lead to targeted interventions that in turn may lead to improved outcomes.
We reconsider the effect of very low birth weight classification on infant mortality. We demonstrate that the estimates are highly sensitive to the exclusion of observations in the immediate vicinity ...of the 1,500-g threshold, weakening the confidence in the results originally reported in Almond, Doyle, Kowalski, and Williams (2010).
Hypothermia during delivery room stabilization of very low birth weight (VLBW) newborns is independently associated with mortality, yet it occurred frequently both in collaborative networks and at ...our institution. We aimed to attain admission temperatures in the target range of 36 °C to 38 °C in ≥ 90% of inborn VLBW neonates through implementation of a thermoregulation bundle.
This quality improvement project extended over 60 consecutive months, using sequential plan-do-check-act cycles. During the 14 baseline months, we standardized temperature measurements and developed the Operation Toasty Tot thermoregulation bundle (including consistent head and torso wrapping with plastic, warmed blankets, and a closed stabilization room). We introduced this bundle in month 15 and added servo-controlled, battery-powered radiant warmers for stabilization and transfer in month 21. We provided results and feedback to staff throughout, using simple graphics and control charts.
There were 164 inborn VLBW babies before and 477 after bundle implementation. Introduction and optimization of the bundle decreased the incidence of hypothermia, with rates remaining in the target range for the last 13 study months. The incidence of temperatures >38 °C was ~ 2% both before and after bundle implementation.
This thermoregulation bundle resulted in sustained improvement in normothermia rates during delivery room stabilization of VLBW newborns. Our benchmark goal of ≥ 90% admission temperatures above 36 °C was met without increasing hyperthermia rates. Because these results compare favorably with those of recently published research or improvement collaboratives, we aim to maintain our performance through routine surveillance of admission temperatures.
Immediately after the 1994 Back-to-Sleep campaign, sudden unexpected infant death (SUID) rates decreased dramatically, but they have remained relatively stable (93.4 per 100 000 live births) since ...2000. In this study, we examined trends in SUID rates and disparities by race/ethnicity since the Back-to-Sleep campaign.
We used 1995-2013 US period-linked birth-infant death data to evaluate SUID rates per 100 000 live births by non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, American Indian/Alaska Native, and Asian/Pacific Islander racial/ethnic groupings. To examine racial/ethnic disparities, we calculated rate ratios with NHWs as the referent group. Unadjusted linear regression was used to evaluate trends (
< .05) in rates and rate ratios. The distribution and rates of SUID by demographic and birth characteristics were compared for 1995-1997 and 2011-2013, and χ
tests were used to evaluate significance.
From 1995 to 2013, SUID rates were consistently highest for American Indian/Alaska Natives, followed by NHBs. The rate for NHBs decreased significantly, whereas the rate for NHWs also declined, but not significantly. As a result, the disparity between NHWs and NHBs narrowed slightly. The SUID rates for Hispanics and Asian/Pacific Islanders were lower than the rates for NHWs and showed a significant decrease, resulting in an increase in their advantage over NHWs.
Each racial/ethnic group showed a unique trend in SUID rates since the Back-to-Sleep campaign. When implementing risk-reduction strategies, it is important to consider these trends in targeting populations for prevention and developing culturally appropriate approaches for racial/ethnic communities.
IMPORTANCE: Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality. OBJECTIVE: To review 20-year trends in maternal/neonatal care, complications, and mortality ...among extremely preterm infants born at Neonatal Research Network centers. DESIGN, SETTING, PARTICIPANTS: Prospective registry of 34 636 infants, 22 to 28 weeks’ gestation, birth weight of 401 to 1500 g, and born at 26 network centers between 1993 and 2012. EXPOSURES: Extremely preterm birth. MAIN OUTCOMES AND MEASURES: Maternal/neonatal care, morbidities, and survival. Major morbidities, reported for infants who survived more than 12 hours, were severe necrotizing enterocolitis, infection, bronchopulmonary dysplasia, severe intracranial hemorrhage, cystic periventricular leukomalacia, and/or severe retinopathy of prematurity. Regression models assessed yearly changes and were adjusted for study center, race/ethnicity, gestational age, birth weight for gestational age, and sex. RESULTS: Use of antenatal corticosteroids increased from 1993 to 2012 (24% 348 of 1431 infants) to 87% (1674 of 1919 infants; P < .001), as did cesarean delivery (44% 625 of 1431 births to 64% 1227 of 1921; P < .001). Delivery room intubation decreased from 80% (1144 of 1433 infants) in 1993 to 65% (1253 of 1922) in 2012 (P < .001). After increasing in the 1990s, postnatal steroid use declined to 8% (141 of 1757 infants) in 2004 (P < .001), with no significant change thereafter. Although most infants were ventilated, continuous positive airway pressure without ventilation increased from 7% (120 of 1666 infants) in 2002 to 11% (190 of 1756 infants) in 2012 (P < .001). Despite no improvement from 1993 to 2004, rates of late-onset sepsis declined between 2005 and 2012 for infants of each gestational age (median, 26 weeks 37% {109 of 296} to 27% {85 of 320}; adjusted relative risk RR, 0.93 95% CI, 0.92-0.94). Rates of other morbidities declined, but bronchopulmonary dysplasia increased between 2009 and 2012 for infants at 26 to 27 weeks’ gestation (26 weeks, 50% 130 of 258 to 55% 164 of 297; P < .001). Survival increased between 2009 and 2012 for infants at 23 weeks’ gestation (27% 41 of 152 to 33% 50 of 150; adjusted RR, 1.09 95% CI, 1.05-1.14) and 24 weeks (63% 156 of 248 to 65% 174 of 269; adjusted RR, 1.05 95% CI, 1.03-1.07), with smaller relative increases for infants at 25 and 27 weeks’ gestation, and no change for infants at 22, 26, and 28 weeks’ gestation. Survival without major morbidity increased approximately 2% per year for infants at 25 to 28 weeks’ gestation, with no change for infants at 22 to 24 weeks’ gestation. CONCLUSIONS AND RELEVANCE: Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased. Survival increased most markedly for infants born at 23 and 24 weeks’ gestation and survival without major morbidity increased for infants aged 25 to 28 weeks. These findings may be valuable in counseling families and developing novel interventions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00063063.
Despite a major decrease in the incidence of sudden infant death syndrome (SIDS) since the American Academy of Pediatrics (AAP) released its recommendation in 1992 that infants be placed for sleep in ...a nonprone position, this decline has plateaued in recent years. Concurrently, other causes of sudden unexpected infant death that occur during sleep (sleep-related deaths), including suffocation, asphyxia, and entrapment, and ill-defined or unspecified causes of death have increased in incidence, particularly since the AAP published its last statement on SIDS in 2005. It has become increasingly important to address these other causes of sleep-related infant death. Many of the modifiable and nonmodifiable risk factors for SIDS and suffocation are strikingly similar. The AAP, therefore, is expanding its recommendations from focusing only on SIDS to focusing on a safe sleep environment that can reduce the risk of all sleep-related infant deaths, including SIDS. The recommendations described in this policy statement include supine positioning, use of a firm sleep surface, breastfeeding, room-sharing without bed-sharing, routine immunizations, consideration of using a pacifier, and avoidance of soft bedding, overheating, and exposure to tobacco smoke, alcohol, and illicit drugs. The rationale for these recommendations is discussed in detail in the accompanying "Technical Report--SIDS and Other Sleep-Related Infant Deaths: Expansion of Recommendations for a Safe Infant Sleeping Environment," which is included in this issue of Pediatrics (www.pediatrics.org/cgi/content/full/128/5/e1341).
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