Intracranial Hemorrhage and 2-Year Neurodevelopmental Outcomes in Infants Born Extremely Preterm.

OBJECTIVES: To determine the incidence, timing, progression, and risk factors for intracranial hemorrhage (ICH) in infants 240/7 to 276/7 weeks of gestational age and to characterize the association between ICH and death or neurodevelopmental impairment (NDI) at 2 years of corrected age. STUDY DESIGN: Infants enrolled in the Preterm Erythropoietin Neuroprotection Trial had serial cranial ultrasound scans performed on day 1, day 7-9, and 36 weeks of postmenstrual age to evaluate ICH. Potential risk factors for development of ICH were examined. Outcomes included death or severe NDI as well as Bayley Scales of Infant and Toddler Development, 3rd Edition, at 2 years of corrected age. RESULTS: ICH was identified in 38% (n = 339) of 883 enrolled infants. Multiple gestation and cesarean delivery reduced the risk of any ICH on day 1. Risk factors for development of bilateral Grade 2, Grade 3, or Grade 4 ICH at day 7-9 included any ICH at day 1; 2 or more doses of prenatal steroids decreased risk. Bilateral Grade 2, Grade 3, or Grade 4 ICH at 36 weeks were associated with previous ICH at day 7-9. Bilateral Grade 2, any Grade 3, and any Grade 4 ICH at 7-9 days or 36 weeks of postmenstrual age were associated with increased risk of death or severe NDI and lower Bayley Scales of Infant and Toddler Development, 3rd Edition, scores. CONCLUSIONS: Risk factors for ICH varied by timing of bleed. Bilateral and increasing grade of ICH were associated with death or NDI in infants born extremely preterm.

Parental Enrollment Decision-Making for a Neonatal Clinical Trial.

OBJECTIVE: To describe the parental experience of recruitment and assess differences between parents who participated and those who declined to enroll in a neonatal clinical trial. STUDY DESIGN: This was a survey conducted at 12 US neonatal intensive care units of parents of infants who enrolled in the High-dose Erythropoietin for Asphyxia and encephaLopathy (HEAL) trial or who were eligible but declined enrollment. Questions assessed 6 factors of the parental experience of recruitment: (1) interactions with research staff; (2) the consent experience; (3) perceptions of the study; (4) decisional conflict; (5) reasons for/against participation; and (6) timing of making the enrollment decision. RESULTS: In total, 269 of 387 eligible parents, including 183 of 242 (75.6%) of those who enrolled their children in HEAL and 86 of 145 (59.3%) parents who declined to enroll their children in HEAL, were included in analysis. Parents who declined to enroll more preferred to be approached by clinical team members rather than by research team members (72.9% vs 49.2%, P = .005). Enrolled parents more frequently reported positive initial impressions (54.9% vs 10.5%, P < .001). Many parents in both groups made their decision early in the recruitment process. Considerations of reasons for/against participation differed by enrollment status. CONCLUSIONS: Understanding how parents experience recruitment, and how this differs by enrollment status, may help researchers improve recruitment processes for families and increase enrollment. The parental experience of recruitment varied by enrollment status. These findings can guide future work aiming to inform optimal recruitment strategies for neonatal clinical trials.

Factors Associated with Outpatient Therapy Utilization in Extremely Preterm Infants.

OBJECTIVE: Factors influencing utilization of outpatient interventional therapies for extremely low gestational age newborns (ELGANs) after discharge remain poorly characterized, despite a significant risk of neurodevelopmental impairment. We sought to assess the effects of maternal, infant, and environmental characteristics on outpatient therapy utilization in the first 2 years after discharge using data from the Preterm Erythropoietin Neuroprotection (PENUT) Trial. STUDY DESIGN: This is a secondary analysis of 818, 24 to 27 weeks gestation infants enrolled in the PENUT trial who survived through discharge and completed at least one follow-up call or in-person visit between 4 and 24 months of age. Utilization of a state early intervention (EI) program, physical therapy (PT), occupational therapy (OT), and speech therapy (ST) was recorded. Odds ratios and cumulative frequency curves for resource utilization were calculated for patient characteristics adjusting for gestational age, treatment group, and birth weight. RESULTS: EI was not accessed by 37% of infants, and 18% did not use any service (PT/OT/ST/EI). Infants diagnosed with severe morbidities (intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis), discharged with home oxygen, or with gastrostomy placement experienced increased utilization of PT, OT, and ST compared with peers. However, substantial variation in service utilization occurred by the state of enrollment and selected maternal characteristics. CONCLUSIONS: ELGANs with severe medical comorbidities are more likely to utilize services after discharge. Therapy utilization may be impacted by maternal characteristics and state of enrollment. Outpatient therapy services remain significantly underutilized in this high-risk cohort. Further research is required to characterize and optimize the utilization of therapy services following NICU discharge of ELGANs. KEY POINTS: · Outpatient therapy is underutilized in ELGANs.. · Medical comorbidities may impact therapy use.. · Maternal characteristics may impact therapy use.. · State of enrollment may impact therapy use..

Sildenafil Exposure in the Neonatal Intensive Care Unit.

OBJECTIVE: Pulmonary hypertension causes substantial morbidity and mortality in infants. Although Food and Drug Administration approved to treat pulmonary arterial hypertension in adults, sildenafil is not approved for infants. We sought to describe sildenafil exposure and associated diagnoses and outcomes in infants. STUDY DESIGN: Retrospective cohort of neonates discharged from more than 300 neonatal intensive care units from 2001 to 2016. RESULTS: Sildenafil was administered to 1,336/1,161,808 infants (0.11%; 1.1 per 1,000 infants); 0/35,977 received sildenafil in 2001 versus 151/90,544 (0.17%; 1.7 per 1,000 infants) in 2016. Among infants <32 weeks' gestational age (GA) with enough data to determine respiratory outcome, 666/704 (95%) had bronchopulmonary dysplasia (BPD). Among infants ≥32 weeks GA, 248/455 (55%) had BPD and 76/552 (14%) were diagnosed with meconium aspiration. Overall, 209/921 (23%) died prior to discharge. CONCLUSION: The use of sildenafil has increased since 2001. Exposed infants were commonly diagnosed with BPD. Further studies evaluating dosing, safety, and efficacy of sildenafil are needed.

Essential Care for Every Baby: improving compliance with newborn care practices in rural Nicaragua.

BACKGROUND: Neonatal mortality comprises an increasing proportion of childhood deaths in the developing world. Essential newborn care practices as recommended by the WHO may improve neonatal outcomes in resource limited settings. Our objective was to pilot a Helping Babies Breathe and Essential Care for Every Baby (HBB and ECEB) implementation package using HBB-ECEB training combined with supportive supervision in rural Nicaragua. METHODS: We employed an HBB-ECEB implementation package in El Ayote and Santo Domingo, two rural municipalities in Nicaragua and used a pre- and post- data collection design for comparison. Following a period of pre-intervention data collection (June-August 2015), care providers were trained in HBB and ECEB using a train-the- trainer model. An external supportive supervisor monitored processes of care and collected data. Data on newborn care processes and short-term outcomes such as hypothermia were collected from facility medical records and analyzed using standard run charts. Home visits were used to determine breastfeeding rates at 7, 30 and 60 days. RESULTS: There were 480 institutional births during the study period (June 2015-June 2016). Following the HBB-ECEB implementation package, cord care improved (pre-intervention median 66%; post-intervention shift to ≥85%) and early skin-to-skin care improved (pre-intervention median 0%; post-intervention shift to ≥56%, with a high of 92% in June 2016). Rates of administration of ophthalmic ointment and vitamin K were high pre-intervention (median 97%) and remained high. Early initiation of breastfeeding increased with a pre-intervention median of 25% and post-intervention shift to ≥28%, with a peak of 81% in June 2016. Exclusive breastfeeding rates increased short-term but were not significantly different by 60-days of life (9% pre-intervention versus 21% post-intervention). CONCLUSIONS: The implementation of the HBB-ECEB programs combined with supportive supervision improved the quality of care for newborns in terms of cord care, early skin-to-skin care and early initiation of breastfeeding. The rates of administration of ophthalmic ointment and vitamin K were high pre- intervention and remained high afterwards. These findings show that HBB-ECEB programs implemented with supportive supervision can improve quality of care for newborns.

What is new for patent ductus arteriosus management in premature infants in 2015?

PURPOSE OF REVIEW: A patent ductus arteriosus (PDA) in premature infants is common and is associated with a number of adverse outcomes. The purpose of this review is to discuss recent literature in PDA diagnosis and management. RECENT FINDINGS: The diagnosis of a 'hemodynamically significant' PDA is challenging and a robust definition is lacking. The risks and benefits of therapies, either medical or surgical, designed to close the PDA, are controversial. Oral acetaminophen has gained increasing attention as an alternative pharmaceutical agent for PDA closure in premature infants, although safety concerns remain. Compared to surgical ligation, transcatheter PDA closure may be associated with less risk and fewer adverse events. Both aggressive and conservative management of PDA has similar clinically important outcomes, although the strength of evidence is derived mostly from cohort studies. SUMMARY: Clinicians should weigh the potential adverse effects of pharmaceutical or surgical PDA closure against the likelihood of spontaneous closure. The infant population most likely to benefit from PDA closure remains ill-defined and clinical context is recommended.

Nutrition and the gut-brain axis in neonatal brain injury and development.

Early nutritional exposures, including during embryogenesis and the immediate postnatal period, affect offspring outcomes in both the short- and long-term. Alterations of these modifiable exposures shape the developing gut microbiome, intestinal development, and even neurodevelopmental outcomes. A gut-brain axis exists, and it is intricately connected to early life feeding and nutritional exposures. Here, we seek to discuss the (1) origins of the gut-brain access and relationship with neurodevelopment, (2) components of human milk (HM) beyond nutrition and their role in the developing newborn, and (3) clinical application of nutritional practices, including fluid management and feeding on the development of the gut-brain axis, and long-term neurodevelopmental outcomes. We conclude with a discussion on future directions and unanswered questions that are critical to provide further understanding and insight into how clinicians and healthcare providers can optimize early nutritional practices to ensure children not only survive, but thrive, free of neurodevelopmental impairment.

Time to regain birthweight and association with neurodevelopmental outcomes among extremely preterm newborns.

OBJECTIVE: Determine association between time to regain birthweight and 2-year neurodevelopment among extremely preterm (EP) newborns. STUDY DESIGN: Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial evaluating time to regain birthweight, time from birth to weight nadir, time from nadir to regain birthweight, and cumulative weight loss with 2-year corrected Bayley Scales of Infant and Toddler Development 3rd edition. RESULTS: Among n = 654 EP neonates, those with shorter nadir-to-regain had lower cognitive scores (≤1 day versus ≥8 days: -5.0 points, [CI -9.5, -0.6]) and lower motor scores (≤1 day versus ≥8 days: -4.6 points [CI -9.2, -0.03]) in adjusted stepwise forward regression modeling. Increasingly cumulative weight loss was associated with lower cognitive scores (≤-50 percent-days: -5.6, [CI -9.4, -1.8]), motor scores (≤-50 percent-days: -4.2, [CI -8.2, -0.2]); and language scores (≤-50 percent-days: -6.0, [CI -10.1, -1.9]). CONCLUSION: Faster nadir-to-regain and excessive cumulative weight loss are associated with adverse 2-year neurodevelopmental outcomes. TRIAL REGISTRATION: PENUT Trial Registration: NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273 . CLINICAL TRIAL REGISTRATION: This study is a post-hoc secondary analysis of pre-existing data from the PENUT Trial (NCT #01378273).

Expanding Medicaid Payment for Pasteurized Donor Human Milk in High-Risk Neonates.

Pasteurized donor human milk (PDHM) is associated with a reduced incidence of necrotizing enterocolitis in very low birth weight (VLBW) infants. Absence of Medicaid and private insurance payment for PDHM use in neonatal intensive care units contributes to disparities based on state of birth and socioeconomic level. Before 2017, 5 states had policies for PDHM coverage, incorporating less than 30% of VLBW infants born nationally. In this case study, we outline the partnership of local American Academy of Pediatrics (AAP) chapters with the national AAP Section on Neonatal-Perinatal Medicine to create a PDHM Advocacy Toolkit to facilitate Medicaid PDHM coverage. Over 5 years, neonatologist-led advocacy, incentivized via AAP funds, contributed to 5 additional states providing Medicaid payment for PDHM, resulting in over 55% of VLBW infants born nationally in states with funded coverage. Partnerships with state AAP chapters, pilot grant funding with deliverables, emphasis on advocacy coaching, and modification of the generalized toolkit to suit local needs were essential in engineering Medicaid PDHM payment. Together these actions provide a template for other pediatric subspecialists to help advance niche-focused advocacy issues at the state level.

Early Fluid and Nutritional Management of Extremely Preterm Newborns During the Fetal-To-Neonatal Transition.

During the fetal-to-neonatal transitional period, extremely preterm newborns undergo significant intrabody fluid shifts and resulting weight loss due to increased insensible fluid losses due to immature skin, kidneys, among other factors. These ongoing physiologic changes make fluid and nutritional management complex in the neonatal-to-fetal transitional time period for extremely premature newborns. However, limited literature exists to guide optimal practices for providers caring for this population. Here, we review the evidence on optimal fluid and nutritional management during the fetal-to-neonatal transition of extremely preterm newborns.

Nonsurgical periodontal treatment during pregnancy and rates of preterm birth.

BACKGROUND: Periodontitis during pregnancy is associated with an increased risk of preterm birth (<37 weeks of gestation) or low birthweight (<2500 g) offspring. Beyond periodontal disease, the risk of preterm birth varies both by previous history of preterm birth and in association with social determinants prevalent among vulnerable and marginalized populations. This study hypothesized that the timing of periodontal treatment during pregnancy and/or social vulnerability measures modified the response to dental scaling and root planing for the treatment of periodontitis and prevention of preterm birth. OBJECTIVE: This study aimed to determine the association of timing of dental scaling and root planing for gravidae with a diagnosed periodontal disease on the rates of preterm birth or low birthweight offspring among subgroups or strata of gravidae as part of the Maternal Oral Therapy to Reduce Obstetric Risk randomized controlled trial. All participants in the study had clinically diagnosed periodontal disease and differed by the timing of the periodontal treatment (dental scaling and root planing at <24 weeks [per protocol] or after delivery) or by baseline characteristics. Although all participants met the well-accepted clinical criteria for periodontitis, not all participants acknowledged a priori that they had periodontal disease. STUDY DESIGN: This was a per-protocol analysis of data from 1455 participants of the Maternal Oral Therapy to Reduce Obstetric Risk trial evaluating dental scaling and root planing on the risk of preterm birth or low birthweight offspring. Adjusted multiple logistic regression to control for confounders was used to estimate associations comparing the timing of periodontal treatment in pregnancy to receiving treatment after pregnancy (referent control) on rates of preterm birth or low birthweight among subgroups of gravidae with known periodontal disease. Study analyses were stratified, and the associations with the following characteristics-body mass index, self-described race and ethnicity, household income, maternal education, recency of immigration, and self-acknowledgment of poor oral health, were explored. RESULTS: Dental scaling and root planing during the second or third trimester of pregnancy were associated with an increased adjusted odds ratio of preterm birth among those at the lower body mass index strata (18.5 to <25.0 kg/m2) (adjusted odds ratio, 2.21; 95% confidence interval, 1.07-4.98), but not among individuals who were overweight (body mass index of 25.0 to <30.0 kg/m2; adjusted odds ratio, 0.68; 95% confidence interval, 0.29-1.59) or obese (body mass index of ≥30 kg/m2; adjusted odds ratio, 1.26; 95% confidence interval, 0.65-2.49). There was no significant difference in pregnancy outcomes related to the other evaluated variables: self-described race and ethnicity, household income, maternal education, immigration status, or self-acknowledgment of poor oral health. CONCLUSION: In this per-protocol analysis of the Maternal Oral Therapy to Reduce Obstetric Risk trial, dental scaling and root planing had no preventive benefit against adverse obstetrical outcomes and were associated with increased odds of preterm birth among individuals at lower body mass index strata. There was no significant difference in the occurrence of preterm birth or low birthweight after dental scaling and root planing periodontitis treatment concerning other analyzed social determinants of preterm birth.

Increasing Sodium Variability in the First 96 Hours after Birth is Associated with Adverse In-Hospital Outcomes of Preterm Newborns.

Background: Neonatal intraventricular hemorrhage prevention bundles for preterm infants commonly defer daily weighing for the first 72 h, with reweighing occurring on day 4. Clinicians rely on maintaining stable sodium values as a proxy of fluid status to inform fluid management decisions over the first 96 h after birth. Yet, there exists a paucity of research evaluating whether serum sodium or osmolality are appropriate proxies for weight loss and whether increasing variability in sodium or osmolality during this early transitional period is associated with adverse in-hospital outcomes. Objectives: To evaluate whether serum sodium or osmolality change in the first 96 h after birth was associated with percent weight change from birth weight, and to assess potential associations between serum sodium and osmolality variability with in-hospital outcomes. Methods: This retrospective, cross-sectional study included neonates born at ≤30 gestational weeks or ≤1250 g. We evaluated associations between serum sodium coefficient of variation (CoV), osmolality CoV, and maximal weight loss percentage in the first 96 h after birth with in-hospital neonatal outcomes. Results: Among 205 infants, serum sodium and osmolality were poorly correlated with percent weight change in individual 24-h increments (R2 = 0.01-0.14). For every 1% increase in sodium CoV, there was an associated 2-fold increased odds of surgical necrotizing enterocolitis and 2-fold increased odds of in-hospital mortality (odds ratio, 2.07; 95% CI: 1.02, 4.54; odds ratio, 1.95; 95% CI: 1.10, 3.64, respectively). Sodium CoV was more strongly associated with outcomes than absolute sodium maximal change. Conclusions: In the first 96 h, serum sodium and osmolality are poor proxies for assessing percent weight change. Increasing variability of serum sodium is associated with later development of surgical necrotizing enterocolitis and all-cause in-hospital mortality. Prospective research is needed to evaluate whether reducing sodium variability in the first 96 h after birth, as assessed by CoV, improves newborn health outcomes.

Patterns of Infections among Extremely Preterm Infants.

Infections remain a leading cause of neonatal death, especially among the extremely preterm infants. To evaluate the incidence, pathogenesis, and in-hospital outcomes associated with sepsis among hospitalized extremely preterm infants born at 24-0/7 to 27-6/7 weeks of gestation, we designed a post hoc analysis of data collected prospectively during the Preterm Epo Neuroprotection (PENUT) Trial, NCT #01378273. We analyzed culture positive infection data, as well as type and duration of antibiotic course and described their association with in-hospital morbidities and mortality. Of 936 included infants, 229 (24%) had at least one positive blood culture during their hospitalization. Early onset sepsis (EOS, ≤3 days after birth) occurred in 6% of the infants, with Coagulase negative Staphylococci (CoNS) and Escherichia Coli the most frequent pathogens. Late onset sepsis (LOS, >day 3) occurred in 20% of the infants. Nearly all infants were treated with antibiotics for presumed sepsis at least once during their hospitalization. The risk of confirmed or presumed EOS was lower with increasing birthweight. Confirmed EOS had no significant association with in-hospital outcomes or death while LOS was associated with increased risk of necrotizing enterocolitis and death. Extremely premature infants with presumed sepsis as compared to culture positive sepsis had lower rates of morbidities. In conclusion, the use of antibiotics for presumed sepsis remains much higher than confirmed infection rates. Ongoing work exploring antibiotic stewardship and presumed, culture-negative sepsis in extremely preterm infants is needed.

Time to Regain Birthweight and Association with Neurodevelopmental Outcomes among Extremely Preterm Newborns.

Objective: Determine association between time to regain birthweight and 2-year neurodevelopment among extremely preterm (EP) newborns. Study Design: Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial evaluating time to regain birthweight, time from birth to weight nadir, time from nadir to regain birthweight, and cumulative weight loss with 2-year corrected Bayley Scales of Infant and Toddler Development 3rd edition. Results: Among n = 654 EP neonates, those with shorter nadir-to-regain had lower cognitive scores (2-4 days versus ≥ 8 days: -3.5, [CI -7.0, 0.0]; ≤1 day versus ≥ 8 days: -5.0, [CI -10.2, 0.0]) in fully adjusted stepwise forward regression modeling. Increasingly cumulative weight loss was associated with lower cognitive scores (-50 to <-23 percent-days: -4.0, [95% CI -7.6, -0.4]) and language scores (≤-50 percent-days: -5.7, [CI -9.8, -1.6]; -50 to <-23 percent-days: -6.1, [CI -10.2, -2.0]). Conclusion: Faster nadir-to-regain and prolonged, severe weight loss are associated with adverse 2-year neurodevelopmental outcomes. Trial registration: PENUT Trial Registration: NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273.

Effectiveness of a care bundle for primary prevention of intraventricular hemorrhage in high-risk neonates: a Bayesian analysis.

OBJECTIVE: To determine whether an intraventricular hemorrhage (IVH) prevention bundle featuring midline-elevated positioning reduced IVH among high-risk infants. STUDY DESIGN: In a retrospective study design, we compared outcomes of infants <1250 grams birth weight or <30 weeks gestation before (N = 205) and after (N = 360) implementation of an IVH prevention bundle, using Bayesian and frequentist logistic regression to determine whether the intervention decreased any grade IVH. RESULTS: In both the Bayesian and frequentist analyses, there was no difference in odds of any grade IVH before and after the implementation of the prevention bundle (OR 0.993; 95% Credible Interval 0.751-1.323 and OR 1.23; 95% Confidence Interval 0.818-1.864 respectively). Bias analyses suggested that these results were robust to bias from potential deaths attributable to IVH. CONCLUSION: In this retrospective analysis, we found no evidence for a protective effect of an IVH prevention bundle on IVH incidence among high-risk neonates at a level IV NICU.

Considering Risks to Researchers and Staff in Low-Resource Settings during Public Health Crises: A Proposed Conceptual Model.

Human subjects research protections have historically focused on mitigating risk of harm and promoting benefits for research participants. In many low-resource settings (LRS), complex and often severe challenges in daily living, poverty, geopolitical uprisings, sociopolitical, economic, and climate crises increase the burdens of even minimal risk research. While there has been important work to explore the scope of ethical responsibilities of researchers and research teams to respond to these wider challenges and hidden burdens in global health research, less attention has been given to the ethical dilemmas and risk experienced by frontline researcher staff as they perform research-related activities in LRS. Risks such as job insecurity, moral distress, infection, or physical harm can be exacerbated during public health crises, as recently highlighted by the COVID-19 pandemic. We highlight the layers of risk research staff face in LRS and present a conceptual model to characterize drivers of this risk, with particular attention to public health crises. A framework by which funders, institutions, principal investigators, and/or research team leaders can systematically consider these additional layers of risk to researchers and frontline staff is an important and needed addition to routine research proposals and protocol review.

Deaths in a Modern Cohort of Extremely Preterm Infants From the Preterm Erythropoietin Neuroprotection Trial.

Importance: Understanding why and how extremely preterm infants die is important for practitioners caring for these infants. Objective: To examine risk factors, causes, timing, and circumstances of death in a modern cohort of extremely preterm infants. Design, Setting, and Participants: A retrospective cohort review of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial between December 13, 2013, and September 26, 2016, was conducted. A total of 941 infants born between 24 0/7 and 27 6/7 weeks of gestation enrolled at 19 US sites comprising 30 neonatal intensive care units were included. Data analysis was performed from October 16, 2020, to December 1, 2021. Main Outcomes and Measures: Risk factors, proximal causes, timing, and circumstances of in-hospital death. Results: Of the 941 enrolled infants, 108 died (11%) before hospital discharge: 38% (n = 41) at 24 weeks' gestation, 30% (n = 32) at 25 weeks' gestation, 19% (n = 20) at 26 weeks' gestation, and 14% (n = 15) at 27 weeks' gestation. An additional 9 infants (1%) died following hospital discharge. In descending order, the primary causes of death included respiratory distress or failure, pulmonary hemorrhage, necrotizing enterocolitis, catastrophic intracranial hemorrhage, sepsis, and sudden unexplained death. Fifty percent of deaths occurred within the first 10 days after birth. The risk of death decreased with day of life and postmenstrual age such that an infant born at 24 weeks' gestation who survived 14 days had the same risk of death as an infant born at 27 weeks' gestation: conditional proportional risk of death, 0.08 (95% CI, 0.03-0.13) vs 0.06 (95% CI, 0.01-0.11). Preterm labor was associated with a decreased hazard of death (hazard ratio [HR], 0.45; 95% CI, 0.31-0.66). Infant clinical factors associated with death included birth weight below the tenth percentile for gestational age (HR, 2.11; 95% CI, 1.38-3.22), Apgar score less than 5 at 5 minutes (HR, 2.19; 95% CI, 1.48-3.24), sick appearance at birth (HR, 2.49; 95% CI, 1.69-3.67), grade 2b-3 necrotizing enterocolitis (HR, 7.41; 95% CI, 5.14-10.7), pulmonary hemorrhage (HR, 10.0; 95% CI, 6.76-18.8), severe intracranial hemorrhage (HR, 4.60; 95% CI, 3.24-5.63), and severe sepsis (HR, 4.93; 95% CI, 3.67-7.21). Fifty-one percent of the infants received comfort care before death. Conclusions and Relevance: In this cohort study, an association between mortality and gestational age at birth was noted; however, for each week that an infant survived, their risk of subsequent death approximated the risk observed in infants born 1 to 2 weeks later, suggesting the importance of an infant's postmenstrual age. This information may be useful to include in counseling of families regarding prognosis of survival.