Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18-24 months in very low birthweight infants?

BACKGROUND: Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85-95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3-0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence. METHODS: An international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks' gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months' and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity). DISCUSSION: The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18-24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. TRIAL REGISTRATION: The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.

Provincial Review of Adherence to Age-specific Guidelines for Umbilical Hernia Repair and Trends in Management.

BACKGROUND: Umbilical hernia (UH) is a common pediatric condition, for which delaying surgical repair for asymptomatic UH until after age 3 is recommended due to a high incidence of spontaneous closure. We aimed to determine the adherence to guidelines, rate of urgent surgical repair, outcomes, cost, and interinstitutional referral patterns of UH repair in the province of Quebec (Canada). METHODS: This was a population-based retrospective cohort study of children 28 days to 17 years old who underwent UH repair between 2010 and 2020 using health administrative databases. Children who had multiple procedures, or prolonged peri-operative stays were excluded. Early repair was defined as elective surgery at or under age 3. RESULTS: Of the 3215 children, 1744 (54.2%) were female, and 1872 (58.2%) were treated in a tertiary children's hospital. Guidelines were respected for 2853 out of 3215 children (89.7%). Patients living over 75 km from their treating hospitals (OR 2.36, 95% CI 1.33-4.16, P < 0.01), with pre-existing comorbidities (OR, 2.82; 95% CI, 1.96-4.05; P < 0.001), or being treated in a tertiary center (OR 2.10, 95% CI 1.45-3.03, P < 0.001) had a higher risk of early repair. Repair at or under age 3 and urgent surgery were associated with significant cost increases of 411$ (P < 0.001) and 558$ (P < 0.001), respectively. CONCLUSION: Quebec has a high rate of adherence to age-specific guidelines for UH repair. Future research should explore factors that explain transfers into tertiary centers, and the extent to which these reflect efficient use of resources. LEVEL OF EVIDENCE: level III. TYPE OF STUDY: Retrospective comparative study.

Association of Exclusive Breast Milk Intake and Outcomes in Infants With Uncomplicated Gastroschisis: A National Cohort Study.

BACKGROUND: Enteral feeding is an essential part of the management of infants with gastroschisis. We hypothesized that exclusive breast milk is associated with improved neonatal outcomes. METHODS: We conducted a retrospective review of infants with uncomplicated gastroschisis through the Canadian Pediatric Surgery Network (CAPSNet) and Canadian Neonatal Network (CNN). The primary outcome was time to full enteral feeds. RESULTS: We identified 411 infants with gastroschisis treated at CAPSNet centres from 2014 to 2022. 144 patients were excluded due to gestational age <32 weeks, birth weight <1500 g, other congenital anomalies, or complicated gastroschisis. Of the remaining 267 participants, 78% (n = 209) received exclusive breast milk diet in the first 28 days of life, whereas 22% (n = 58) received supplemental or exclusive formula. Infants who received exclusive breast milk experienced higher time to reach full enteral feeding (median 24 vs 22 days, p = 0.047) but were more likely to have undergone delayed abdominal closure (32% vs 17%, p = 0.03). After adjustment, there were no significant differences between groups in time to reach full enteral feeds, duration of parenteral nutrition, or length of stay. Infants who received supplemental or exclusive formula had a similar risk of necrotizing enterocolitis (4% vs 3%) but were less likely to transition to exclusive breast milk at discharge (73% vs 11%, p < 0.001). CONCLUSION: Early use of exclusive breast milk in infants with uncomplicated gastroschisis is associated with similar outcomes compared to supplemental or exclusive formula. Patients who received supplemental or exclusive formula were unlikely to transition to exclusive breastfeeding by discharge. LEVEL OF EVIDENCE: Level IIb (Individual Cohort Study).

Evaluation of the association between patent ductus arteriosus approach and neurodevelopment in extremely preterm infants.

OBJECTIVE: Assess if unit-level PDA management correlates with neurodevelopmental impairment (NDI) at 18-24 months corrected postnatal age (CPA) in extremely preterm infants. STUDY DESIGN: Retrospective analysis of infants born at <29 weeks (2014-2017) across two units having distinct PDA strategies. Site 1 utilized an echocardiography-based treatment strategy aiming for accelerated closure (control). Site 2 followed a conservative approach. PRIMARY ENDPOINT: NDI, characterized by cerebral palsy, any Bayley-III composite score <85, sensorineural/mixed hearing loss, or at least unilateral visual impairment. RESULTS: 377 infants were evaluated. PDA treatment rates remained unchanged in Site 1 but eventually reached 0% in Site 2. Comparable rates of any/significant NDI were seen across both sites (any NDI: 38% vs 36%; significant NDI: 13% vs 10% for Site 1 and 2, respectively). After adjustments, NDI rates remained similar. CONCLUSION: PDA management strategies in extremely preterm newborns showed no significant impact on neurodevelopment outcomes at 18-24 months CPA.

Early cardiac function and death, severe bronchopulmonary dysplasia and pulmonary hypertension in extremely preterm infants.

BACKGROUND: Association between early cardiac function and neonatal outcomes are scarcely reported. The aim of the current study was to describe this association with death, severe bronchopulmonary dysplasia (BPD) and BPD-related pulmonary hypertension (PH). METHODS: Retrospective cohort study of infants <29 weeks born between 2015 and 2019. Infants with clinically acquired echocardiography at ≤21 days after birth were included and data were extracted by an expert masked to outcomes. RESULTS: A total of 176 infants were included. Echocardiogram was performed at a median of 9 days (IQR 5-13.5). Of these, 31 (18%) had death/severe BPD and 59 (33.5%) had death/BPD-related PH. Infants with death/severe BPD were of lower birth weight (745 [227] vs 852 [211] grams, p = 0.01) and more exposed to invasive ventilation, late-onset sepsis, inotropes and/or postnatal steroids. Early echocardiograms demonstrated decreased right ventricular [Tricuspid Annular Plane Systolic Excursion: 5.2 (1.4) vs 6.2 (1.5) cm, p = 0.03] and left ventricular function [Ejection fraction 53 (14) vs 58 (10) %, p = 0.03]. Infants with death/BPD-related PH had an increased Eccentricity index (1.35 [0.20] vs 1.26 [0.19], p = 0.02), and flat/bowing septum (19/54 [35%] vs 20/109 [18%], p = 0.021). CONCLUSIONS: In extremely premature infants, altered ventricular function and increased pulmonary pressure indices within the first 21 days after birth, were associated with the combined outcome of death/severe BPD and death/BPD-related PH. IMPACT: Decreased cardiac function on echocardiography performed during first three weeks of life is associated with severe bronchopulmonary dysplasia in extremely premature infants. In extreme preterm infants, echocardiographic signs of pulmonary hypertension in early life are associated with later BPD-related pulmonary hypertension close to 36 weeks post-menstrual age. Early cardiac markers should be further studied as potential intervention targets in this population. Our study is adding comprehensive analysis of echocardiographic data in infants born below 29 weeks gestational age.

Enteral supplementation with high-dose docosahexaenoic acid on the risk of bronchopulmonary dysplasia in very preterm infants: a collaborative study protocol for an individual participant data meta-analysis.

INTRODUCTION: Severe bronchopulmonary dysplasia (BPD) is a well-known factor consistently associated with impaired cognitive outcomes. Regarding reported benefits on long-term neurodevelopmental outcomes, the potential adverse effects of high-dose docosahexaenoic acid (DHA) supplementation on this short-term neonatal morbidity need further investigations in infants born very preterm. This study will determine whether high-dose DHA enteral supplementation during the neonatal period is associated with the risk of severe BPD at 36 weeks' postmenstrual age (PMA) compared with control, in contemporary cohorts of preterm infants born at less than 29 weeks of gestation. METHODS AND ANALYSIS: As part of an Australian-Canadian collaboration, we will conduct an individual participant data (IPD) meta-analysis of randomised controlled trials targeting infants born at less than 29 weeks of gestation and evaluating the effect of high-dose DHA enteral supplementation in the neonatal period compared with a control. Primary outcome will be severe grades of BPD (yes/no) at 36 weeks' PMA harmonised according to a recent definition that predicts early childhood morbidities. Other outcomes will be survival without severe BPD, death, BPD severity grades, serious brain injury, severe retinopathy of prematurity, patent ductus arteriosus and necrotising enterocolitis requiring surgery, sepsis, combined neonatal morbidities and growth. Severe BPD will be compared between groups using a multivariate generalised estimating equations log-binomial regression model. Subgroup analyses are planned for gestational age, sex, small-for-gestational age, presence of maternal chorioamnionitis and mode of delivery. ETHICS AND DISSEMINATION: The conduct of each trial was approved by institutional research ethics boards and written informed consent was obtained from participating parents. A collaboration and data sharing agreement will be signed between participating authors and institutions. This IPD meta-analysis will document the role of DHA in nutritional management of BPD. Findings will be disseminated through conferences, media interviews and publications to peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023431063. TRIAL REGISTRATION NUMBER: NCT05915806.

Association of Gestational Age at Birth With Left Cardiac Dimensions at Near-Term Corrected Age Among Extremely Preterm Infants.

BACKGROUND: Remodeling and altered ventricular geometry have been described in adults born preterm. Although they seem to have an adverse cardiac phenotype, the impact of various degrees of prematurity on cardiac development has been scarcely reported. In this study, we evaluated the impact of gestational age (GA) at birth on cardiac dimensions and function at near-term age among extremely preterm infants. METHODS: This is a retrospective single-center cohort study of infants born at <29 weeks of GA between 2015 and 2019. Infants with available clinically acquired echocardiography between 34 and 43 weeks were included. Two groups were investigated: those born <26 weeks and those born ≥26 weeks. All measurements were done by an expert masked to clinical data using the raw images. The primary outcome was measurements of cardiac dimensions and function based on GA group. Secondary outcomes were the association between cardiac dimensions and postnatal steroid exposure and with increments of GA at birth. RESULTS: A total of 205 infants were included (<26 weeks, n = 102; ≥26 weeks, n = 103). At time of echocardiography, weight (2.4 ± 0.5 vs 2.5 ± 0.5 kg, P = .86) and age (37.2 ± 1.6 vs 37.1 ± 1.9 weeks, P = .74) were similar between groups. There was no difference in metrics of right-sided dimensions and function. However, left-sided dimensions were decreased in infants born <26 weeks, including systolic left ventricle (LV) diameter (1.06 ± 0.20 cm vs 1.12 ± 0.18 cm, P = .02), diastolic LV length (2.85 ± 0.37 vs 3.02 ± 0.57 cm, P = .02), and estimated LV end-diastolic volume (5.36 ± 1.69 vs 6.01 ± 1.79 mL, P = .02). CONCLUSIONS: In our cohort of very immature infants, birth at the extreme of prematurity was associated with smaller left cardiac dimensions around 36 weeks of corrected age. Future longitudinal prospective studies should evaluate further the impact of prematurity on LV development and performance and their long-term clinical impact.

Association of nurse staffing and unit occupancy with mortality and morbidity among very preterm infants: a multicentre study.

OBJECTIVE: In a healthcare system with finite resources, hospital organisational factors may contribute to patient outcomes. We aimed to assess the association of nurse staffing and neonatal intensive care unit (NICU) occupancy with outcomes of preterm infants born <33 weeks' gestation. DESIGN: Retrospective cohort study. SETTING: Four level III NICUs. PATIENTS: Infants born 23-32 weeks' gestation 2015-2018. MAIN OUTCOME MEASURES: Nursing provision ratios (nursing hours worked/recommended nursing hours based on patient acuity categories) and unit occupancy rates were averaged for the first shift, 24 hours and 7 days of admission of each infant. Primary outcome was mortality/morbidity (bronchopulmonary dysplasia, severe neurological injury, retinopathy of prematurity, necrotising enterocolitis and nosocomial infection). ORs for association of exposure with outcomes were estimated using generalised linear mixed models adjusted for confounders. RESULTS: Among 1870 included infants, 823 (44%) had mortality/morbidity. Median nursing provision ratio was 1.03 (IQR 0.89-1.22) and median unit occupancy was 89% (IQR 82-94). In the first 24 hours of admission, higher nursing provision ratio was associated with lower odds of mortality/morbidity (OR 0.93, 95% CI 0.89 to 0.98), and higher unit occupancy was associated with higher odds of mortality/morbidity (OR 1.19, 95% CI 1.04 to 1.36). In causal mediation analysis, nursing provision ratios mediated 47% of the association between occupancy and outcomes. CONCLUSIONS: NICU occupancy is associated with mortality/morbidity among very preterm infants and may reflect lack of adequate resources in periods of high activity. Interventions aimed at reducing occupancy and maintaining adequate resources need to be considered as strategies to improve patient outcomes.

The association between BMI trajectories and bronchopulmonary dysplasia among very preterm infants.

OBJECTIVE: To investigate the association between change in body mass index (BMI) from birth to 36 weeks gestation (ΔBMI) and bronchopulmonary dysplasia (BPD) among infants born <30 weeks gestation. METHODS: This was a multicenter retrospective cohort study (2015-2018) of infants born <30 weeks gestation and alive at ≥34 weeks corrected. Main exposure was a change in BMI z score from birth to 36 weeks corrected age grouped into quartiles of change. Association between ΔBMI z scores and BPD was assessed using generalized linear mixed models. RESULTS: Among 772 included infants, 51% developed BPD. From birth to 36 weeks CGA, the weight z score of infants with BPD decreased less than for BPD-free infants, despite a greater decrease in length z score and similar caloric intake resulting in increases in BMI z score (median [IQR], 0.16 [-0.64; 1.03] vs -0.29 [-1.03; 0.49]; P < 0.01). In the adjusted analysis, higher ΔBMI z score quartiles were associated with higher odds of BPD (Q3 vs Q2, AOR [95% CI], 2.02 [1.23; 3.31] and Q4 vs Q2, AOR [95% CI], 2.00 [1.20; 3.34]). CONCLUSION: Among preterm infants, an increase in BMI z score from birth to 36 weeks corrected is associated with higher odds of BPD. IMPACT: Preterm infants with evolving lung disease often experience disproportionate growth in the neonatal period. In this multicenter cohort study, increases in BMI z score from birth to 36 weeks CGA were associated with higher odds of BPD. Despite similar caloric intake, infants with BPD had a higher weight- but lower length-for-age, resulting in higher BMI z score compared to BPD-free infants. This suggests that infants with evolving BPD may require different growth and nutritional targets compared to BPD-free infants.

Thrombocytopenia and neonatal outcomes among extremely premature infants exposed to maternal hypertension.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with neonatal hematological disturbances, such as thrombocytopenia. The association of HDP to platelet counts in the context of extreme prematurity, to trends of platelet counts during neonatal hospitalization, and to frequency of platelet transfusions remain to be explored. PROCEDURE: Retrospective study of infants born at less than 29 weeks born between 2015 and 2019. Platelet counts were collected on initial complete blood count, at 2 weeks, 32 weeks post-menstrual age (PMA), 36 weeks PMA, and closest to discharge. We examined the association between HDP and platelet counts at each time point, frequency of platelet transfusions and intraventricular hemorrhage (IVH) grade 3 or more. RESULTS: Total 296 infants were included, 43 exposed to HDP. Infants exposed had lower platelet counts at each time point, as well as a higher prevalence of platelet less than 150 × 109 /L on one of the time points (32% vs. 65%, p < .001). Infants exposed to maternal hypertension were more frequently exposed to platelet transfusions (63% vs. 18%, p < .001). Mixed effect model demonstrated an association between HDP and a lower trend in platelet counts at each time point (ß = -94 × 103 /µl, p < .001). Although initial platelet count was associated with severe IVH, it was not associated to exposure to HDP. CONCLUSION: Premature infants exposed to HDP have a higher prevalence of thrombocytopenia, increased frequency of platelet transfusion, and an altered trend in platelet counts during neonatal hospitalization.

Age at First Extubation Attempt and Death or Respiratory Morbidities in Extremely Preterm Infants.

OBJECTIVE: To describe the timing of first extubation in extremely preterm infants and explore the relationship between age at first extubation, extubation outcome, and death or respiratory morbidities. STUDY DESIGN: In this subanalysis of a multicenter observational study, infants with birth weights of 1250 g or less and intubated within 24 hours of birth were included. After describing the timing of first extubation, age at extubation was divided into early (within 7 days from birth) vs late (days of life 8-35), and extubation outcome was divided into success vs failure (reintubation within 7 days after extubation), to create 4 extubation groups: early success, early failure, late success, and late failure. Logistic regression analyses were performed to evaluate associations between the 4 groups and death or bronchopulmonary dysplasia, bronchopulmonary dysplasia among survivors, and durations of respiratory support and oxygen therapy. RESULTS: Of the 250 infants included, 129 (52%) were extubated within 7 days, 93 (37%) between 8 and 35 days, and 28 (11%) beyond 35 days of life. There were 93, 36, 59, and 34 infants with early success, early failure, late success, and late failure, respectively. Although early success was associated with the lowest rates of respiratory morbidities, early failure was not associated with significantly different respiratory outcomes compared with late success or late failure in unadjusted and adjusted analyses. CONCLUSIONS: In a contemporary cohort of extremely preterm infants, early extubation occurred in 52% of infants, and only early and successful extubation was associated with decreased respiratory morbidities. Predictors capable of promptly identifying infants with a high likelihood of early extubation success or failure are needed.

Incidence and risk factors for autism spectrum disorder among infants born <29 weeks' gestation.

Objective: This study was aimed to assess the incidence of and risk factors for autism spectrum disorder (ASD) among preterm infants born <29 weeks' gestational age (GA). Methods: A retrospective cohort study of infants born <29 weeks' GA admitted to two tertiary neonatal intensive care units (2009 to 2017) and followed ≥18 months corrected age (CA) at a neonatal follow-up clinic. The primary outcome was ASD, diagnosed using standardized testing or provisional diagnosis at ≥18 months CA. Patient data and 18-month CA developmental outcomes were obtained from the local Canadian Neonatal Follow Up Network database and chart review. Stepwise logistic regression assessed factors associated with ASD. Results: Among 300 eligible infants, 26 (8.7%) were diagnosed with confirmed and 21 (7.0%) with provisional ASD for a combined incidence of 15.7% (95% confidence interval [CI] 11.7 to 20.3). The mean follow-up duration was 3.9 ± 1.4 years and the mean age of diagnosis was 3.7 ± 1.5 years. Male sex (adjusted odds ratio [aOR] 4.63, 95% CI 2.12 to 10.10), small for gestational age status (aOR 3.03, 95% CI 1.02 to 9.01), maternal age ≥35 years at delivery (aOR 2.22, 95% CI 1.08 to 4.57) and smoking during pregnancy (aOR 5.67, 95% CI 1.86 to 17.29) were significantly associated with ASD. Among ASD infants with a complete 18-month CA developmental assessment, 46% (19/41) had no neurodevelopmental impairment (Bayley-III<70, deafness, blindness, or cerebral palsy). Conclusions: ASD is common among infants born <29 weeks' GA and possibly associated with identified risk factors. Such findings emphasize the importance of ASD evaluation among infants <29 weeks' GA and for continued reporting of developmental outcomes beyond 18-months of corrected age.

Organizational Risk Factors and Clinical Impacts of Unplanned Extubation in the Neonatal Intensive Care Unit.

OBJECTIVES: To assess the association between organizational factors and unplanned extubation events in the neonatal intensive care unit (NICU) and to evaluate the association between unplanned extubation event and bronchopulmonary dysplasia (BPD) among infants born at <29 weeks of gestational age. STUDY DESIGN: This is a retrospective cohort study of infants admitted to a tertiary care NICU between 2016 and 2019. Nursing provision ratios, daily nursing overtime hours/total nursing hours ratio, and unit occupancy were compared between days with and days without unplanned extubation events. The association between unplanned extubation events (with and without reintubation) and the risk of BPD was evaluated in infants born at <29 weeks who required mechanical ventilation using a propensity score-matched cohort. Multivariable logistic regression analysis was used to assess the association between exposures and outcomes while adjusting for confounders. RESULTS: On 108 of 1370 days there was ≥1 unplanned extubation event for a total of 116 unplanned extubation event events. Higher median nursing overtime hours (20 hours vs 16 hours) and overtime ratios (3.3% vs 2.5%) were observed on days with an unplanned extubation event compared with days without an unplanned extubation event (P = .01). Overtime ratio was associated with higher adjusted odds of a unplanned extubation event (aOR, 1.09; 95% CI, 1.01-1.18). In the subgroup of infants born at <29 weeks, those with an unplanned extubation event who were reintubated had a longer postmatching duration of mechanical ventilation (aOR, 13.06; 95% CI, 4.88-37.69) and odds of BPD (aOR, 2.86; 95% CI, 1.01-8.58) compared with those without an unplanned extubation event. CONCLUSIONS: Nursing overtime ratio is associated with an increased number of unplanned extubation events in the NICU. In infants born at <29 weeks of gestational age, reintubation after an unplanned extubation event is associated with a longer duration of mechanical ventilation and increased risk of BPD.

Neonatal outcomes of twins <29 weeks gestation of mothers with hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with dysfunctional placentation and are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancies have a larger placental mass and are a risk factor for HDP. The effect of HDP on neonatal outcomes in twin pregnancies is unknown. METHODS: Retrospective cohort study using the Canadian Neonatal Network database from 2010-2018 of twin infants <29 weeks gestation born to mothers with HDP and normotensive pregnancies. Using multivariable models, we determined adjusted odds ratios (AORs) and 95% confidence intervals (CI) for mortality, bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity (ROP), necrotizing enterocolitis, and nosocomial infection in twin infants of mothers with HDP compared to twin infants of normotensive mothers. RESULTS: Of the 2414 eligible twin infants <29 weeks gestational age, 164 (6.8%) were born to mothers with HDP and had higher odds of severe ROP (AOR 2.48, 95% CI 1.34-4.59). Preterm twin infants born to mothers with HDP also had higher odds of mortality (AOR 2.02, 95% CI 1.23-3.32). There was no difference in other outcomes. CONCLUSION: Preterm twin infants <29 weeks gestation of HDP mothers have higher odds of severe ROP and mortality. IMPACT: Hypertensive disorders of pregnancy, associated with placental dysfunction, are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancy, associated with a larger placental mass, is a risk factor for hypertensive disorders of pregnancy. The effect of hypertensive disorders of pregnancy on outcomes of preterm twins is unknown. Preterm twins of mothers with hypertensive disorders of pregnancy are at higher risk of severe retinopathy of prematurity and mortality. Our data can be used to counsel parents and identify infants at higher risk of severe retinopathy of prematurity and mortality.

Association of 24-Hour In-house Neonatologist Coverage with Outcomes of Extremely Preterm Infants.

OBJECTIVE: This study aimed to assess if 24-hour in-house neonatologist (NN) coverage is associated with delivery room (DR) resuscitation/stabilization and outcomes among inborn infants <29 weeks' gestational age (GA). STUDY DESIGN: Survey-linked cohort study of 2,476 inborn infants of 23 to 28 weeks' gestation, admitted between 2014 and 2015 to Canadian Neonatal Network Level-3 neonatal intensive care units (NICUs) with a maternity unit. Exposures were classified using survey responses based on the most senior provider offering 24-hour in-house coverage: NN, fellow, and no NN/fellow. Primary outcome was death and/or major morbidity (bronchopulmonary dysplasia, severe neurological injury, late-onset sepsis, necrotizing enterocolitis, and retinopathy of prematurity). Multivariable logistic regression analysis was used to assess the association between exposures and outcomes and adjust for confounders. RESULTS: Among the 28 participating NICUs, most senior providers ensuring 24-hour in-house coverage were NN (32%, 9/28), fellows (39%, 11/28), and no NN/fellow (29%, 8/28). No NN/fellow coverage and 24-hour fellow coverage were associated with higher odds of infants receiving DR chest compressions/epinephrine compared with 24-hour NN coverage (adjusted odds ratio [aOR] = 4.72, 95% confidence interval [CI]: 2.12-10.6 and aOR = 3.33, 95% CI: 1.44-7.70, respectively). Rates of mortality/major morbidity did not differ significantly among the three groups: NN, 63% (249/395 infants); fellow, 64% (1092/1700 infants); no NN/fellow, 70% (266/381 infants). CONCLUSION: 24-hour in-house NN coverage was associated with lower rates of DR chest compressions/epinephrine. There was no difference in neonatal outcomes based on type of coverage; however, further studies are needed as ecological fallacy cannot be ruled out. KEY POINTS: · Lower rates of DR cardiopulmonary resuscitation with 24h in-house NN coverage. · The type of 24h in-house coverage was not associated with mortality and/or major morbidity.. · High-volume centers more often have 24h in-house neonatal fellow coverage.

Natural evolution of the patent ductus arteriosus in the extremely premature newborn and respiratory outcomes.

OBJECTIVE: Evaluate spontaneous closure of the patent ductus arteriosus (PDA) in extremely preterm infants and their respiratory outcomes, especially at <26 weeks gestational age (GA). STUDY DESIGN: Retrospective study in <29 weeks, admitted within 24 h after birth (Feb 2015 and Dec 2019). Infants without any intervention to promote ductal closure, ≥1 echocardiography, and alive at discharge were included. RESULTS: Two hundred and fourteen infants (average GA 26.3 ± 1.5 weeks) were included; 84 (39%) <26 weeks. PDA closed spontaneously in 194 (91%); 76/84 (90%) for infants <26 weeks. PDA closure was ascertained on an echocardiography performed at a median age of 36.4 [34.4-40.1] weeks. Rate of moderate-to-severe bronchopulmonary dysplasia decreased throughout the study period (OR for year of birth: 0.70 [95% CI: 0.57-0.87], p = 0.001). CONCLUSION: Majority of extremely preterm infants, including <26 weeks, had spontaneous closure of the ductus before term corrected age. There was a concomitant improvement of respiratory outcomes.

Outcomes of Extremely Premature Infants Comparing Patent Ductus Arteriosus Management Approaches.

OBJECTIVE: To evaluate the change in the proportion of deaths/bronchopulmonary dysplasia (BPD) among premature infants (born <26 and 26-29 weeks of gestational age) following a policy change to a strict nonintervention approach, compared with standard treatment. STUDY DESIGN: We examined 1249 infants (341 born <26 weeks of gestational age) at 2 comparable sites. Site 1 (control) continued medical treatment/ligation, and site 2 (exposed) changed to a nonintervention policy in late 2013. Using the difference-in-differences approach, which accounts for time-invariant differences between sites and secular trends, we assessed changes in death or BPD separately among infants born 26-29 weeks and <26 weeks of gestational age in 2 epochs (epoch 1: 2011-2013; epoch 2: 2014-2017). RESULTS: Baseline characteristics were similar across sites and epochs. Medical treatment/ligation use remained stable at site 1 but declined progressively to 0% at site 2, indicating adherence to policy. We saw no difference in death/BPD among infants born at 26-29 weeks of gestational age (12%, 95% CI -1% to 24%). However, incidence of death/BPD increased by 31% among infants born <26 weeks of gestational age (95% CI 10%-51%) in site 2, whereas there was no change in outcomes in site 1. The Score for Neonatal Acute Physiology-Version II, used as a control outcome, did not change in either site, suggesting that our findings were not due to changes in patients' severity. CONCLUSIONS: Adherence to a strict conservative policy did not impact death or BPD among 26 weeks but was associated with a significant rise in infants born <26 weeks.

Neurodevelopmental outcomes of preterm infants conceived by assisted reproductive technology.

BACKGROUND: There have been concerns about the development of children conceived through assisted reproductive technology. Despite multiple studies investigating the outcomes of assisted conception, data focusing specifically on the neurodevelopmental outcomes of infants conceived through assisted reproductive technology and born preterm are limited. OBJECTIVE: This study aimed to evaluate and compare the neurodevelopmental outcomes of preterm infants born at <29 weeks' gestation at 18 to 24 months' corrected age who were conceived through assisted reproductive technology and those who were conceived naturally. STUDY DESIGN: This retrospective cohort study included inborn, nonanomalous infants, born at <29 weeks' gestation between January 1, 2010, and December 31, 2016, who had a neurodevelopmental assessment at 18 to 24 months' corrected age at any of the 10 Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment at 18 to 24 months, defined as the presence of any of the following: cerebral palsy; Bayley-III cognitive, motor, or language composite score of <85; sensorineural or mixed hearing loss; and unilateral or bilateral visual impairment. Secondary outcomes included mortality, composite of mortality or neurodevelopmental impairment, significant neurodevelopmental impairment, and each component of the primary outcome. We compared outcomes between infants conceived through assisted reproductive technology and those conceived naturally, using bivariate and multivariable analyses after adjustment. RESULTS: Of the 4863 eligible neonates, 651 (13.4%) were conceived using assisted reproductive technology. Maternal age; education level; and rates of diabetes mellitus, receipt of antenatal corticosteroids, and cesarean delivery were higher in the assisted reproduction group than the natural conception group. Neonatal morbidity and death rates were similar except for intraventricular hemorrhage, which was lower in the assisted reproduction group (33% [181 of 546] vs 39% [1284 of 3318]; P=.01). Of the 4176 surviving infants, 3386 (81%) had a follow-up outcome at 18 to 24 months' corrected age. Multivariable logistic regression adjusting for gestational age, antenatal steroids, sex, small for gestational age, multiple gestations, mode of delivery, maternal age, maternal education, pregnancy-induced hypertension, maternal diabetes mellitus, and smoking showed that infants conceived through assisted reproduction was associated with lower odds of neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86) and the composite of death or neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.54-0.84). Conception through assisted reproductive technology was associated with decreased odds of a Bayley-III composite cognitive score of <85 (adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.99) and composite language score of <85 (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.88). CONCLUSION: Compared with natural conception, assisted conception was associated with lower odds of adverse neurodevelopmental outcomes, especially cognitive and language outcomes, at 18 to 24 months' corrected age among preterm infants born at <29 weeks' gestation. Long-term follow-up studies are required to assess the risks of learning disabilities and development of complex visual-spatial and processing skills in these children as they reach school age.

Fluid status in the first 10 days of life and death/bronchopulmonary dysplasia among preterm infants.

OBJECTIVE: To investigate the association between fluid and sodium status in the first 10 postnatal days and death/bronchopulmonary dysplasia (BPD) among infants born <29 weeks' gestation. STUDY DESIGN: Single center retrospective cohort study (2015-2018) of infants born 23-28 weeks'. Three exposure variables were evaluated over the first 10 postnatal days: cumulative fluid balance (CFB), median serum sodium concentration, and maximum percentage weight loss. Primary outcome was death and/or BPD. Multivariable logistic regression adjusting for patient covariates was used to assess the association between exposure variables and outcomes. RESULTS: Of 191 infants included, 98 (51%) had death/BPD. Only CFB differed significantly between BPD-free survivors and infants with death/BPD: 4.71 dL/kg (IQR 4.10-5.12) vs 5.11 dL/kg (IQR 4.47-6.07; p < 0.001). In adjusted analyses, we found an association between higher CFB and higher odds of death/BPD (AOR 1.56, 95% CI 1.11-2.25). This was mainly due to the association of CFB with BPD (AOR 1.60, 95% CI 1.12-2.35), rather than with death (AOR 1.08, 95% CI 0.54-2.30). CONCLUSION: Among preterm infants, a higher CFB in the first 10 days after delivery is associated with higher odds of death/BPD. IMPACT: Previous studies suggest that postnatal fluid status influences survival and respiratory function in neonates. Fluid balance, serum sodium concentration, and daily weight changes are commonly used as fluid status indicators in neonates. We found that higher cumulative fluid balance in the first 10 days of life was associated with higher odds of death/bronchopulmonary dysplasia in neonates born <29 weeks. Monitoring of postnatal fluid balance may be an appropriate non-invasive strategy to favor survival without bronchopulmonary dysplasia. We developed a cumulative fluid balance chart with corresponding thresholds on each day to help design future trials and guide clinicians in fluid management.

Risk factors for re-hospitalization following neonatal discharge of extremely preterm infants in Canada.

OBJECTIVE: Survivors of extremely preterm birth are at risk of re-hospitalization but risk factors in the Canadian population are unknown. Our objective is to identify neonatal, sociodemographic, and geographic characteristics that predict re-hospitalization in Canadian extremely preterm neonates. METHODS: This is a retrospective analysis of a prospective observational cohort study that included preterm infants born 22 to 28 weeks' gestational age from April 1, 2009 to September 30, 2011 and seen at 18 to 24 months corrected gestational age in a Canadian Neonatal Follow-Up Network clinic. Characteristics of infants re-hospitalized versus not re-hospitalized are compared. The potential neonatal, sociodemographic, and geographic factors with significant association in the univariate analysis are included in a multivariate model. RESULTS: From a total of 2,275 preterm infants born at 22 to 28 weeks gestation included, 838 (36.8%) were re-hospitalized at least once. There were significant disparities between Canadian provincial regions, ranging from 25.9% to 49.4%. In the multivariate logistic regression analysis, factors associated with an increased risk for re-hospitalization were region of residence, male sex, bronchopulmonary dysplasia, necrotizing enterocolitis, prolonged neonatal intensive care unit (NICU) stay, ethnicity, Indigenous ethnicity, and sibling(s) in the home. CONCLUSION: Various neonatal, sociodemographic, and geographic factors predict re-hospitalization of extremely preterm infants born in Canada. The risk factors of re-hospitalization provide insights to help health care leaders explore potential preventative approaches to improve child health and reduce health care system costs.