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BACKGROUND: Incubator oxygen may improve respiratory stability in preterm infants compared with nasal cannula oxygen. METHODS: Single center randomized trial of infants <29 weeks' gestation on supplemental oxygen at ≥32 weeks' postmenstrual age. Infants were crossed-over every 24 hours for 96 hours between incubator oxygen and nasal cannula ≤1.0 L/kg/min. We measured episodes of intermittent hypoxemia (oxygen saturations (SpO2) < 85% ≥10 seconds), bradycardia, cerebral and abdominal hypoxemia, and end-tidal carbon dioxide. RESULTS: We enrolled 25 infants with a gestational age of 26 weeks 4 days±15 days (mean ± SD) and birth weight 805 ± 202 grams. There were no differences in episodes of intermittent hypoxemia, bradycardia, or cerebral hypoxemia between groups. There were fewer episodes of abdominal hypoxemia <40% ≥10 seconds with incubator oxygen compared with nasal cannula (132 ± 130 versus 158 ± 125; p < 0.01). Time with SpO2 < 85% and abdominal hypoxemia was lower among infants on incubator oxygen. Carbon dioxide values were higher while on incubator oxygen (41 ± 11 versus 36 ± 10 mmHg; p < 0.02). CONCLUSION: There was no difference in intermittent hypoxemia between incubator and nasal cannula oxygen among preterm infants on supplemental oxygen. Infants had higher levels of carbon dioxide while on incubator oxygen, which may have improved some measures of respiratory stability. CLINCALTRIALS. GOV IDENTIFIERS: NCT03333174 and NCT03174301. IMPACT STATEMENT: In this randomized cross-over trial of preterm infants on supplemental oxygen, incubator oxygen did not decrease episodes of intermittent hypoxemia compared with nasal cannula oxygen. Incubator oxygen reduced time with oxygen saturations less than 85%, reduced abdominal hypoxemia, and increased carbon dioxide levels. Differences in measures of respiratory stability on incubator oxygen may be partly due to higher carbon dioxide levels compared with nasal cannula oxygen. The mode of supplemental oxygen administration may impact control of breathing in preterm infants through its effect on hypopharyngeal oxygen stability and carbon dioxide levels.
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Background: The Neonatal Oxygenation Prospective Meta-analysis found that in infants <28â weeks gestational age, targeting an oxygen saturation (S pO2 ) range of 85-89% versus 91-95% resulted in lower rates of retinopathy of prematurity but increased mortality. We aimed to evaluate the accuracy of the heart rate characteristics index (HRCi) in assessing the dynamic risk of mortality among infants managed with low and high target S pO2 ranges. Methods: We linked the SUPPORT and HRCi datasets from one centre in which the randomised controlled trials overlapped. We examined the maximum daily HRCi (MaxHRCi24) to predict mortality among patients randomised to the lower and higher target S pO2 groups by generating predictiveness curves and calculating model performance metrics, including area under the receiver operating characteristics curve (AUROC) at prediction windows from 1-60â days. Cox proportional hazards models tested whether MaxHRCi24 was an independent predictor of mortality. We also conducted a moderation analysis. Results: There were 84 infants in the merged dataset. MaxHRCi24 predicted mortality in infants randomised to the lower target S pO2 (AUROC of 0.79-0.89 depending upon the prediction window) and higher target S pO2 (AUROC 0.82-0.91). MaxHRCi24 was an important additional predictor of mortality in multivariable modelling. In moderation analysis, in a model that also included demographic predictor variables, the individual terms and the interaction term between MaxHRCi24 and target S pO2 range all predicted mortality. Conclusions: Associations between HRCi and mortality, at low and high S pO2 target ranges, suggest that future research may find HRCi metrics helpful to individually optimise target oxygen saturation ranges for hospitalised preterm infants.
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Importance: Neonatal mortality is a major public health concern that was potentially impacted by the COVID-19 pandemic. To prepare for future health crises, it is important to investigate whether COVID-19 pandemic-related interventions were associated with changes in neonatal mortality. Objective: To investigate whether social distancing during the pandemic was associated with a higher neonatal mortality rate. Design, Setting, and Participants: This cohort study examined maternal-linked birth and infant death records from the National Center for Health Statistics, a population-level US database, from 2016 through 2020. The mortality rates were correlated using machine learning-based autoregressive integrated moving average (ARIMA) models with the social distancing index (SDI). The reference period was January 2016 through February 2020, and the pandemic period was March through December 2020. Statistical analysis was performed from March 2023 to May 2024. Exposures: SDI, computed from 6 mobility metrics. Main Outcomes and Measures: The primary outcome was neonatal mortality rate, defined as death at age less than 28 days. Results: The study included 18â¯011â¯173 births, of which 15â¯136â¯596 were from the reference period (7â¯753â¯555 [51.22%] male; 11â¯643â¯094 [76.92%] with maternal age of 20 to 34 years) and 2â¯874â¯577 were from the pandemic period (1â¯472â¯539 [51.23%] male; 2â¯190â¯158 [76.19%] with maternal age of 20 to 34 years). Through ARIMA-adjusted analyses, accounting for the declining mortality trend in the reference period, the mortality rates during the pandemic period did not significantly differ from the expected rates. SDI did not exhibit significant correlations with neonatal mortality (unadjusted: correlation coefficient [CC], 0.14 [95% CI, -0.53 to 0.70]; ARIMA adjusted: CC, 0.29 [95% CI, -0.41 to 0.77]), early neonatal mortality (unadjusted: CC, 0.33 [95% CI, -0.37 to 0.79]; ARIMA adjusted: CC, 0.45 [95% CI, -0.24 to 0.84]), and infant mortality (unadjusted: CC, -0.09 [95% CI, -0.68 to 0.57]; ARIMA adjusted: CC, 0.35 [95% CI, -0.35 to 0.80]). However, lag analyses found that SDI was associated with higher neonatal and early neonatal mortality rates with a 2-month lag period, but not with infant mortality rate. SDI was also associated with increases in 22-to-27 weeks' and 28-to-32 weeks' preterm delivery with a 1-month lag period. Conclusions and Relevance: In this population-level study of National Center for Health Statistics databases, neonatal, early neonatal, and infant mortality rates did not increase during the initial COVID-19 pandemic period. However, associations were observed between the pandemic period social distancing measures and higher rates of neonatal and early neonatal mortality, as well as preterm birth rate with a lag period, suggesting the importance of monitoring infant health outcomes following pandemic-related population behavior changes.
Subject(s)
COVID-19 , Infant Mortality , Physical Distancing , SARS-CoV-2 , Humans , COVID-19/mortality , COVID-19/epidemiology , Infant Mortality/trends , Infant, Newborn , United States/epidemiology , Female , Infant , Pandemics , Adult , Male , Cohort Studies , PregnancyABSTRACT
OBJECTIVE: Characterisation of oxygen saturation (SpO2)-related predictors that correspond with both bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) development and survival status in infants with BPD-PH may improve patient outcomes. This investigation assessed whether (1) infants with BPD-PH compared with infants with BPD alone, and (2) BPD-PH non-survivors compared with BPD-PH survivors would (a) achieve lower SpO2 distributions, (b) have a higher fraction of inspired oxygen (FiO2) exposure and (c) have a higher oxygen saturation index (OSI). DESIGN: Case-control study between infants with BPD-PH (cases) and BPD alone (controls) and by survival status within cases. SETTING: Single-centre study in the USA. PATIENTS: Infants born at <29 weeks' gestation and on respiratory support at 36 weeks' postmenstrual age. EXPOSURES: FiO2 exposure, SpO2 distributions and OSI were analysed over the week preceding BPD-PH diagnosis. MAIN OUTCOMES AND MEASURES: BPD-PH, BPD alone and survival status in infants with BPD-PH. RESULTS: 40 infants with BPD-PH were compared with 40 infants with BPD alone. Infants who developed BPD-PH achieved lower SpO2 compared with infants with BPD (p<0.001), were exposed to a higher FiO2 (0.50 vs 0.34; p=0.02) and had a higher OSI (4.3 vs 2.6; p=0.03). Compared with survivors, infants with BPD-PH who died achieved a lower SpO2 (p<0.001) and were exposed to a higher FiO2 (0.70 vs 0.42; p=0.049). CONCLUSIONS: SpO2-related predictors differed between infants with BPD-PH and BPD alone and among infants with BPD-PH by survival status. The OSI may provide a non-invasive predictor for BPD-PH in preterm infants.
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Importance: Providing assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants. Objective: To determine whether assisted ventilation in extremely preterm infants (23 0/7 to 28 6/7 weeks' gestational age [GA]) followed by cord clamping reduces intraventricular hemorrhage (IVH) or early death. Design, Setting, and Participants: This phase 3, 1:1, parallel-stratified randomized clinical trial conducted at 12 perinatal centers across the US and Canada from September 2, 2016, through February 21, 2023, assessed IVH and early death outcomes of extremely preterm infants randomized to receive 120 seconds of assisted ventilation followed by cord clamping vs delayed cord clamping for 30 to 60 seconds with ventilatory assistance afterward. Two analysis cohorts, not breathing well and breathing well, were specified a priori based on assessment of breathing 30 seconds after birth. Intervention: After birth, all infants received stimulation and suctioning if needed. From 30 to 120 seconds, infants randomized to the intervention received continuous positive airway pressure if breathing well or positive-pressure ventilation if not, with cord clamping at 120 seconds. Control infants received 30 to 60 seconds of delayed cord clamping followed by standard resuscitation. Main Outcomes and Measures: The primary outcome was any grade IVH on head ultrasonography or death before day 7. Interpretation by site radiologists was confirmed by independent radiologists, all masked to study group. To estimate the association between study group and outcome, data were analyzed using the stratified Cochran-Mantel-Haenszel test for relative risk (RR), with associations summarized by point estimates and 95% CIs. Results: Of 1110 women who consented to participate, 548 were randomized and delivered infants at GA less than 29 weeks. A total of 570 eligible infants were enrolled (median [IQR] GA, 26.6 [24.9-27.7] weeks; 297 male [52.1%]). Intraventricular hemorrhage or death occurred in 34.9% (97 of 278) of infants in the intervention group and 32.5% (95 of 292) in the control group (adjusted RR, 1.02; 95% CI, 0.81-1.27). In the prespecified not-breathing-well cohort (47.5% [271 of 570]; median [IQR] GA, 26.0 [24.7-27.4] weeks; 152 male [56.1%]), IVH or death occurred in 38.7% (58 of 150) of infants in the intervention group and 43.0% (52 of 121) in the control group (RR, 0.91; 95% CI, 0.68-1.21). There was no evidence of differences in death, severe brain injury, or major morbidities between the intervention and control groups in either breathing cohort. Conclusions and Relevance: This study did not show that providing assisted ventilation before cord clamping in extremely preterm infants reduces IVH or early death. Additional study around the feasibility, safety, and efficacy of assisted ventilation before cord clamping may provide additional insight. Trial Registration: ClinicalTrials.gov Identifier: NCT02742454.
Subject(s)
Infant, Extremely Premature , Umbilical Cord Clamping , Humans , Infant, Newborn , Female , Male , Umbilical Cord Clamping/methods , Canada , Respiration, Artificial/methods , Cerebral Intraventricular Hemorrhage/prevention & control , Umbilical Cord , Continuous Positive Airway Pressure/methods , Gestational Age , Time Factors , United StatesABSTRACT
OBJECTIVE: The objective of this study was to examine the association of cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, with late-onset sepsis for extremely preterm infants (<29 weeks of gestational age) on vs off invasive mechanical ventilation. STUDY DESIGN: This is a retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in 5 level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean gestational age: 26.4 weeks, SD 1.71). Monitoring data were available and analyzed for 719 infants (47 512 patient-days); of whom, 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72 hours after birth and ≥5-day antibiotics). RESULTS: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer events with oxygen saturation <80% (IH80) and more bradycardia events before sepsis. IH events were associated with higher sepsis risk but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model including postmenstrual age, cardiorespiratory variables (apnea, periodic breathing, IH80, and bradycardia), and ventilator status predicted sepsis with an area under the receiver operator characteristic curve of 0.783. CONCLUSION: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.
Subject(s)
Apnea , Bradycardia , Hypoxia , Infant, Extremely Premature , Sepsis , Humans , Bradycardia/epidemiology , Bradycardia/etiology , Apnea/epidemiology , Retrospective Studies , Infant, Newborn , Hypoxia/complications , Female , Male , Sepsis/complications , Sepsis/epidemiology , Infant, Premature, Diseases/epidemiology , Infant, Premature, Diseases/diagnosis , Respiration, Artificial , Intensive Care Units, Neonatal , Gestational AgeABSTRACT
Importance: Redirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding. Objective: To examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm. Design, Setting, and Participants: This is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks' gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic). Main Outcomes and Measures: The primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks' gestation, death and neurodevelopmental impairment at 22 to 26 months' corrected age. Results: Of the 15â¯629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13â¯643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%]; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%]; non-Hispanic, 2020/13â¯408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type. Conclusions and Relevance: For infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.
Subject(s)
Infant, Extremely Premature , Social Determinants of Health , Humans , Female , Infant, Newborn , Male , Retrospective Studies , United States , Adult , Infant , Prospective StudiesABSTRACT
OBJECTIVE: Optimal timing of continuous positive airway pressure (CPAP) cessation in preterm infants remains undetermined. We hypothesised that CPAP extension compared with weaning to low-flow nasal cannula (NC) reduces intermittent hypoxaemia (IH) and respiratory instability in preterm infants meeting criteria to discontinue CPAP. DESIGN: Single-centre randomised clinical trial. SETTING: Level 4 neonatal intensive care unit. PATIENTS: 36 infants <34 weeks' gestation receiving CPAP≤5 cmH2O and fraction of inspired oxygen (FiO2) ≤0.30 and meeting respiratory stability criteria. INTERVENTIONS: Extended CPAP was compared with weaning to low-flow NC (0.5 L/kg/min with a limit of 1.0 L/min) for 24 hours. OUTCOMES: The primary outcome was IH (number of episodes with SpO2<85% lasting ≥10 s). Secondary outcomes included: coefficient of variability of SpO2, proportion of time in various SpO2 ranges, episodes (≥10 s) with SpO2<80%, median cerebral and renal oxygenation, median effective FiO2, median transcutaneous carbon dioxide and bradycardia (<100/min for≥10 s). RESULTS: The median (IQR) episodes of IH per 24-hour period was 20 (6-48) in the CPAP group and 76 (18-101) in the NC group (p=0.03). Infants continued on CPAP had less bradycardia, time with SpO2 <91% and <85%, and lower FiO2 (all p<0.05). There were no statistically significant differences in IH<80%, median transcutaneous carbon dioxide or median cerebral or renal oxygenation. CONCLUSION: In preterm infants meeting respiratory stability criteria for CPAP cessation, extended CPAP decreased IH, bradycardia and other hypoxaemia measures compared with weaning to low-flow NC during the 24-hour intervention. TRIAL REGISTRATION NUMBER: NCT04792099.
Subject(s)
Cannula , Continuous Positive Airway Pressure , Hypoxia , Infant, Premature , Humans , Continuous Positive Airway Pressure/methods , Infant, Newborn , Hypoxia/therapy , Hypoxia/etiology , Female , Male , Intensive Care Units, Neonatal , Oxygen Inhalation Therapy/methods , Oxygen Inhalation Therapy/instrumentation , Respiratory Distress Syndrome, Newborn/therapy , Oxygen Saturation , Bradycardia/therapy , Ventilator Weaning/methodsABSTRACT
Objectives: Detection of changes in cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, may facilitate earlier detection of sepsis. Our objective was to examine the association of cardiorespiratory events with late-onset sepsis for extremely preterm infants (<29 weeks' gestational age (GA)) on versus off invasive mechanical ventilation. Study Design: Retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in five level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean GA 26.4w, SD 1.71). Monitoring data were available and analyzed for 719 infants (47,512 patient-days), of whom 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72h after birth and ≥5d antibiotics). Results: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer IH80 events and more bradycardia events before sepsis. IH events were associated with higher sepsis risk, but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model predicted sepsis with an AUC of 0.783. Conclusion: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.
Subject(s)
Black or African American , Infant Mortality , Humans , Infant , Black People , Gestational Age , United States/epidemiologyABSTRACT
Importance: Health insurance status is associated with differences in access to health care and health outcomes. Therefore, maternal health insurance type may be associated with differences in infant outcomes in the US. Objective: To determine whether, among infants born in the US, maternal private insurance compared with public Medicaid insurance is associated with a lower infant mortality rate (IMR). Design, Setting, and Participants: This cohort study used data from the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research expanded linked birth and infant death records database from 2017 to 2020. Hospital-born infants from 20 to 42 weeks of gestational age were included if the mother had either private or Medicaid insurance. Infants with congenital anomalies, those without a recorded method of payment, and those without either private insurance or Medicaid were excluded. Data analysis was performed from June 2022 to August 2023. Exposures: Private vs Medicaid insurance. Main Outcomes and Measures: The primary outcome was the IMR. Negative-binomial regression adjusted for race, sex, multiple birth, any maternal pregnancy risk factors (as defined by the CDC), education level, and tobacco use was used to determine the difference in IMR between private and Medicaid insurance. The χ2 or Fisher exact test was used to compare differences in categorical variables between groups. Results: Of the 13â¯562â¯625 infants included (6â¯631â¯735 girls [48.9%]), 7â¯327â¯339 mothers (54.0%) had private insurance and 6â¯235â¯286 (46.0%) were insured by Medicaid. Infants born to mothers with private insurance had a lower IMR compared with infants born to those with Medicaid (2.75 vs 5.30 deaths per 1000 live births; adjusted relative risk [aRR], 0.81; 95% CI, 0.69-0.95; P = .009). Those with private insurance had a significantly lower risk of postneonatal mortality (0.81 vs 2.41 deaths per 1000 births; aRR, 0.57; 95% CI, 0.47-0.68; P < .001), low birth weight (aRR, 0.90; 95% CI, 0.85-0.94; P < .001), vaginal breech delivery (aRR, 0.80; 95% CI, 0.67-0.96; P = .02), and preterm birth (aRR, 0.92; 95% CI, 0.88-0.97; P = .002) and a higher probability of first trimester prenatal care (aRR, 1.24; 95% CI, 1.21-1.27; P < .001) compared with those with Medicaid. Conclusions and Relevance: In this cohort study, maternal Medicaid insurance was associated with increased risk of infant mortality at the population level in the US. Novel strategies are needed to improve access to care, quality of care, and outcomes among women and infants enrolled in Medicaid.
Subject(s)
Premature Birth , Infant , Pregnancy , United States/epidemiology , Infant, Newborn , Humans , Female , Cohort Studies , Premature Birth/epidemiology , Insurance, Health , Medicaid , Infant MortalityABSTRACT
Establishing full enteral nutrition in critically ill preterm infants with immature gastrointestinal function is challenging. In this article, we will summarize emerging clinical evidence from randomized clinical trials suggesting the feasibility and efficacy of feeding interventions targeting the early establishment of full enteral nutrition. We will also examine trial outcomes of higher volume feedings after the establishment of full enteral nutrition. Only data from randomized clinical trials will be discussed extensively. Future opportunities for clinical research will also be presented.
Subject(s)
Enteral Nutrition , Infant, Premature , Humans , Infant, Newborn , Enteral Nutrition/methods , Clinical Trials as TopicABSTRACT
Importance: Socioeconomic 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. Objective: To determine whether ADI is associated with neonatal intensive care unit (NICU) mortality and morbidity in extremely premature infants. Design, Setting, and Participants: This 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. Exposures: ADI, race, birth weight, sex, and outborn status. Main Outcomes and Measures: In 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. Results: A 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 Relevance: The 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.
Subject(s)
Infant, Extremely Premature , Intensive Care Units, Neonatal , Infant , Pregnancy , Female , Infant, Newborn , Humans , Male , Birth Weight , Cohort Studies , Retrospective Studies , Bayes Theorem , Morbidity , Cerebral HemorrhageABSTRACT
OBJECTIVE: To characterize the relationships between social determinants of health (SDOH) and outcomes for children born extremely preterm. STUDY DESIGN: This is a cohort study of infants born at 22-26 weeks of gestation in National Institute of Child Health and Human Development Neonatal Research Network centers (2006-2017) who survived to discharge. Infants were classified by 3 maternal SDOH: education, insurance, and race. Outcomes included postmenstrual age (PMA) at discharge, readmission, neurodevelopmental impairment (NDI), and death postdischarge. Regression analyses adjusted for center, perinatal characteristics, neonatal morbidity, ethnicity, and 2 SDOH (eg, group comparisons by education adjusted for insurance and race). RESULTS: Of 7438 children, 5442 (73%) had at least 1 risk-associated SDOH. PMA at discharge was older (adjusted mean difference 0.37 weeks, 95% CL 0.06, 0.68) and readmission more likely (aOR 1.27, 95% CL 1.12, 1.43) for infants whose mothers had public/no insurance vs private. Neither PMA at discharge nor readmission varied by education or race. NDI was twice as likely (aOR 2.36, 95% CL 1.86, 3.00) and death 5 times as likely (aOR 5.22, 95% CL 2.54, 10.73) for infants with 3 risk-associated SDOH compared with those with none. CONCLUSIONS: Children born to mothers with public/no insurance were older at discharge and more likely to be readmitted than those born to privately insured mothers. NDI and death postdischarge were more common among children exposed to multiple risk-associated SDOH at birth compared with those not exposed. Addressing disparities due to maternal education, insurance coverage, and systemic racism are potential intervention targets to improve outcomes for children born preterm.
Subject(s)
Aftercare , Infant, Extremely Premature , Infant, Newborn , Infant , Pregnancy , Female , Humans , Child , Cohort Studies , Social Determinants of Health , Patient Discharge , Gestational AgeABSTRACT
OBJECTIVE: Determine if targeting higher transcutaneous carbon dioxide improves respiratory stability among very preterm infants on ventilatory support. DESIGN: Single-centre pilot randomised clinical trial. SETTING: The University of Alabama at Birmingham. PATIENTS: Very preterm infants on ventilatory support after postnatal day 7. INTERVENTIONS: Infants 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 MEASURES: We collected cardiorespiratory data evaluating episodes of intermittent hypoxaemia (oxygen saturations (SpO2)<85% for ≥10 s), bradycardia (<100 bpm for ≥10 s), and cerebral and abdominal hypoxaemia on near-infrared spectroscopy. RESULTS: We 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 SpO2<85%, SpO2<80%, cerebral hypoxaemia or abdominal hypoxaemia did not differ (all p>0.05). There was moderate negative correlation between mean transcutaneous carbon dioxide and bradycardia episodes (r=-0.56; p<0.001). CONCLUSION: Targeting 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 NUMBER: NCT03333161.
Subject(s)
Hypercapnia , Infant, Premature, Diseases , Infant , Humans , Infant, Newborn , Infant, Premature , Carbon Dioxide , Bradycardia , Pilot Projects , HypoxiaABSTRACT
Background: Oxygen supplementation is commonly used to maintain oxygen saturation (SpO2) levels in preterm infants within target ranges to reduce intermittent hypoxemic (IH) events, which are associated with short- and long-term morbidities. There is not much information available about differences in oxygenation patterns in infants undergoing such supplementations nor their relation to observed IH events. This study aimed to describe oxygenation characteristics during two types of supplementation by studying SpO2 signal features and assess their performance in hypoxemia risk screening during NICU monitoring. Subjects and methods: SpO2 data from 25 infants with gestational age <32 weeks and birthweight <2,000â g who underwent a cross over trial of low-flow nasal cannula (NC) and digitally-set servo-controlled oxygen environment (OE) supplementations was considered in this secondary analysis. Features pertaining to signal distribution, variability and complexity were estimated and analyzed for differences between the supplementations. Univariate and regularized multivariate logistic regression was applied to identify relevant features and develop screening models for infants likely to experience a critically high number of IH per day of observation. Their performance was assessed using area under receiver operating curves (AUROC), accuracy, sensitivity, specificity and F1 scores. Results: While most SpO2 measures remained comparable during both supplementations, signal irregularity and complexity were elevated while on OE, pointing to more volatility in oxygen saturation during this supplementation mode. In addition, SpO2 variability measures exhibited early prognostic value in discriminating infants at higher risk of critically many IH events. Poincare plot variability at lag 1 had AUROC of 0.82, 0.86, 0.89 compared to 0.63, 0.75, 0.81 for the IH number, a clinical parameter at observation times of 30â min, 1 and 2â h, respectively. Multivariate models with two features exhibited validation AUROC > 0.80, F1 score > 0.60 and specificity >0.85 at observation times ≥ 1â h. Finally, we proposed a framework for risk stratification of infants using a cumulative risk score for continuous monitoring. Conclusion: Analysis of oxygen saturation signal routinely collected in the NICU, may have extensive applications in inferring subtle changes to cardiorespiratory dynamics under various conditions as well as in informing clinical decisions about infant care.
ABSTRACT
Importance: Active 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. Objective: To determine if regions with higher rates of active postnatal care will have higher gestational age-specific survival rates among periviable infants. Design, Setting, and Participants: This 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 Measures: Regional 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. Results: We included 41â¯707 periviable infants, of whom 32â¯674 (78%) were singletons and 19â¯467 (46.7%) were female. Among those studied 34â¯983 (83.9%) had evidence of active care, and 26â¯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 < .05). Regional rates of antenatal corticosteroids exposure were also positively correlated with regional rates of survival at 22 weeks' gestation (rτ[8] = 0.60; r2 = 0.36; P = .02). Conclusions and Relevance: In this cohort study of 41â¯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.
Subject(s)
Intensive Care, Neonatal , Postnatal Care , Infant, Newborn , Infant , Humans , Female , Pregnancy , Male , Cohort Studies , Gestational Age , Infant Mortality , Adrenal Cortex HormonesABSTRACT
Rationale: 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. Objectives: We hypothesized that infants with BPD-PH have patterns of intermittent hypoxemia (IH) that differ from infants with BPD without PH. Methods: We conducted a matched case-control study of extremely preterm infants from 22 weeks 0 days to 28 weeks 6 days 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 (control subjects). 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 control subjects. Measurements and Main Results: Forty infants with BPD-PH were compared with 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% (7 s vs. 6 s; P = 0.03) and 70% (105 s vs. 58 s; P = 0.008). Among infants with BPD-PH, infants who died had longer hypoxemic events below 70% (145 s vs. 72 s; 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. Conclusions: Longer duration of intermittent hypoxemic events was associated both with a diagnosis of BPD-PH and with death among infants with BPD-PH.
Subject(s)
Bronchopulmonary Dysplasia , Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Infant , Infant, Newborn , Humans , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/diagnostic imaging , Case-Control Studies , Gestational Age , Infant, Extremely Premature , Hypoxia/complications , Pulmonary Arterial Hypertension/complicationsABSTRACT
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.
Subject(s)
Acute Kidney Injury , Heart Failure , Water-Electrolyte Imbalance , Infant , Infant, Newborn , Child , Adult , Humans , Acute Kidney Injury/etiology , Risk Factors , Water-Electrolyte Imbalance/etiology , Water-Electrolyte Imbalance/therapy , Water-Electrolyte Balance , KidneyABSTRACT
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 < 0.001) and 0.45 (P < 0.001), respectively. Conclusions: In extremely preterm infants on respiratory support on postnatal day 28, both the presence of and a longer duration of ductus arteriosus patency were associated with the development of BPD-PH.