Association between intermittent hypoxemia and neurodevelopmental outcomes in extremely premature infants: A single-center experience.

OBJECTIVE: To describe the association between intermittent hypoxemic events (IHEs) and severe neurodevelopmental impairment (SNDI) or death in extremely premature infants. STUDY DESIGN: Retrospective study of extremely premature infants 230/7-276/7 weeks gestational age (GA) and birthweight (BW) ≤1250 grams (g) admitted to a level IV neonatal intensive care unit (NICU) from 2013 to 2017. IHEs, defined as events with SpO2 ≤ 80 % lasting 10 s to 5 min, were algorithmically identified using data extracted from bedside monitors at 2 s intervals (0.5 Hz). The primary outcome was SNDI at 18-24 months corrected age (CA), defined as a Bayley-III motor, language or cognitive composite score ≤69, or death before discharge while the secondary outcome was SNDI alone. We used mixed-effects regression models to evaluate the relationship between mean daily IHE rate per postnatal week of life for the first 12 weeks and the outcomes, and logistic regression models to assess the association between outcomes and summary measures of hypoxic burden for the entire NICU hospitalization. RESULTS: The mortality rate was 7 % (18/249) during NICU hospitalization. Of 249 infants born during this time period, IHE and neurodevelopmental outcome data were fully available for 65 infants (mean GA 26 ± 1.4 weeks, mean birth weight (BW) 738 ± 199 g. The outcome of SNDI alone occurred in 34 % (22/65) with a majority demonstrating motor or language delay on the Bayley-III. Although mean daily IHE rate/week was not associated with SNDI or death, total IHE duration was associated with increased odds of SNDI (OR (95 % CI) 1.03 (1.01, 1.05), p = 0.008) in models adjusted for GA. CONCLUSIONS: In a cohort of extremely premature infants 23-27 weeks GA, each hour of total IHE duration (SpO2 ≤ 80 %) was associated with a 2.7 % (0.7 %, 4.8 %) increase in the odds of SNDI at 18-24 months CA.

Assessment of Neurodevelopment in Infants With and Without Exposure to Asymptomatic or Mild Maternal SARS-CoV-2 Infection During Pregnancy.

Importance: Associations between prenatal SARS-CoV-2 exposure and neurodevelopmental outcomes have substantial public health relevance. A previous study found no association between prenatal SARS-CoV-2 infection and parent-reported infant neurodevelopmental outcomes, but standardized observational assessments are needed to confirm this finding. Objective: To assess whether mild or asymptomatic maternal SARS-CoV-2 infection vs no infection during pregnancy is associated with infant neurodevelopmental differences at ages 5 to 11 months. Design, Setting, and Participants: This cohort study included infants of mothers from a single-site prospective cross-sectional study (COVID-19 Mother Baby Outcomes [COMBO] Initiative) of mother-infant dyads and a multisite prospective cohort study (Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy [ESPI]) of pregnant individuals. A subset of ESPI participants was subsequently enrolled in the ESPI COMBO substudy. Participants in the ongoing COMBO study were enrolled beginning on May 26, 2020; participants in the ESPI study were enrolled from May 7 to November 3, 2021; and participants in the ESPI COMBO substudy were enrolled from August 2020 to March 2021. For the current analysis, infant neurodevelopment was assessed between March 2021 and June 2022. A total of 407 infants born to 403 mothers were enrolled (204 from Columbia University Irving Medical Center in New York, New York; 167 from the University of Utah in Salt Lake City; and 36 from the University of Alabama in Birmingham). Mothers of unexposed infants were approached for participation based on similar infant gestational age at birth, date of birth, sex, and mode of delivery to exposed infants. Exposures: Maternal symptomatic or asymptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Infant neurodevelopment was assessed using the Developmental Assessment of Young Children, second edition (DAYC-2), adapted for telehealth assessment. The primary outcome was age-adjusted standard scores on 5 DAYC-2 subdomains: cognitive, gross motor, fine motor, expressive language, and receptive language. Results: Among 403 mothers, the mean (SD) maternal age at delivery was 32.1 (5.4) years; most mothers were of White race (240 [59.6%]) and non-Hispanic ethnicity (253 [62.8%]). Among 407 infants, 367 (90.2%) were born full term and 212 (52.1%) were male. Overall, 258 infants (63.4%) had no documented prenatal exposure to SARS-CoV-2 infection, 112 (27.5%) had confirmed prenatal exposure, and 37 (9.1%) had exposure before pregnancy or at an indeterminate time. In adjusted models, maternal SARS-CoV-2 infection during pregnancy was not associated with differences in cognitive (ß = 0.31; 95% CI, -2.97 to 3.58), gross motor (ß = 0.82; 95% CI, -1.34 to 2.99), fine motor (ß = 0.36; 95% CI, -0.74 to 1.47), expressive language (ß = -1.00; 95% CI, -4.02 to 2.02), or receptive language (ß = 0.45; 95% CI, -2.15 to 3.04) DAYC-2 subdomain scores. Trimester of exposure and maternal symptom status were not associated with DAYC-2 subdomain scores. Conclusions and Relevance: In this study, results of a novel telehealth-adapted observational neurodevelopmental assessment extended a previous finding of no association between prenatal exposure to maternal SARS-CoV-2 infection and infant neurodevelopment. Given the widespread and continued high prevalence of COVID-19, these data offer information that may be helpful for pregnant individuals who experience asymptomatic or mild SARS-CoV-2 infections.

Respiratory Outcomes for Ventilator-Dependent Children With Bronchopulmonary Dysplasia.

OBJECTIVES: To describe outpatient respiratory outcomes and center-level variability among children with severe bronchopulmonary dysplasia (BPD) who require tracheostomy and long-term mechanical ventilation. METHODS: Retrospective cohort of subjects with severe BPD, born between 2016 and 2021, who received tracheostomy and were discharged on home ventilator support from 12 tertiary care centers participating in the BPD Collaborative Outpatient Registry. Timing of key respiratory events including time to tracheostomy placement, initial hospital discharge, first outpatient clinic visit, liberation from the ventilator, and decannulation were assessed using Kaplan-Meier analysis. Differences between centers for the timing of events were assessed via log-rank tests. RESULTS: There were 155 patients who met inclusion criteria. Median age at the time of the study was 32 months. The median age of tracheostomy placement was 5 months (48 weeks' postmenstrual age). The median ages of hospital discharge and first respiratory clinic visit were 10 months and 11 months of age, respectively. During the study period, 64% of the subjects were liberated from the ventilator at a median age of 27 months and 32% were decannulated at a median age of 49 months. The median ages for all key events differed significantly by center (P ≤ .001 for all events). CONCLUSIONS: There is wide variability in the outpatient respiratory outcomes of ventilator-dependent infants and children with severe BPD. Further studies are needed to identify the factors that contribute to variability in practice among the different BPD outpatient centers, which may include inpatient practices.

Intracranial ultrasound abnormalities and mortality in preterm infants with and without fetal growth restriction stratified by fetal Doppler study results.

OBJECTIVE: To evaluate whether fetal growth restriction (FGR) with or without abnormal Dopplers is associated with intracranial abnormalities and death in premature infants. STUDY DESIGN: Premature infants with and without FGR born between 2016 and 2019 were included. Primary outcome was death, severe intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL). Groups were compared using standard bivariate testing and multivariable regression. RESULTS: Among 168 FGR and 560 non-FGR infants, FGR infants with abnormal Dopplers had an increased incidence of death, severe IVH or PVL compared to non-FGR infants (13% (16/123) vs. 7% (41/560); p = 0.03) while FGR infants with normal Dopplers had a nonsignificant decrease. In a logistic regression model, FGR with abnormal Dopplers was associated with more than three times higher odds of death, severe IVH or PVL (OR 3.2, 95% CI 1.54,6.49; p < 0.001). CONCLUSIONS: Growth-restricted infants with abnormal Dopplers had an increased risk of death, intracranial abnormalities, and prematurity-related morbidities.

Improving Neonatal Follow-up: A Quality Improvement Study Analyzing In-hospital Interventions and Long-term Show Rates.

Neonatal follow-up (NFU) clinics play an essential role in the multidisciplinary care of preterm patients. Despite the inherent value of NFU clinics, many clinical programs report poor compliance with follow-up visits. Preterm infants followed with difficulty in the long-term have higher rates of disability and lower IQ scores, even after adjustment of significant perinatal and sociodemographic variables. This quality improvement study aimed to improve the show rate for preterm infants from 60% to 80% at the initial 6-month adjusted age visit by implementing a multilevel education bundle. METHODS: Participants included neonatal intensive care unit (NICU) physicians, physician extenders, registered nurses, and parents of preterm patients admitted to the NICU who qualified for NFU. Our 75-bed NICU is the regional perinatal center within an urban free-standing children's hospital. Our bundle included NICU provider education, discharge planning, and parent education. A tracking system was developed to identify qualifying patients to streamline workflow. RESULTS: The monthly first visit show rate improved from 60% to 76% during the intervention period. Seventy-five percent of families who received parent education presented for their initial visit, compared to 51% of families who did not receive parent education. In anonymous surveys of families who presented for their initial visits, 95% indicated that bedside education played the most important role in appointment attendance. Interdisciplinary rounds are crucial for reaching all families before discharge. CONCLUSION: Implementing a multidimensional in-hospital education bundle and tracking system is feasible and can improve NFU clinic show rates, but may require dedicated personnel for sustainability.

A Randomized Clinical Trial of Umbilical Cord Milking vs Delayed Cord Clamping in Preterm Infants: Neurodevelopmental Outcomes at 22-26 Months of Corrected Age.

OBJECTIVE: To compare the effect of umbilical cord milking vs delayed cord clamping (DCC) on neurodevelopmental and health outcomes in very preterm infants at 22-26 months of corrected age. STUDY DESIGN: Neurodevelopmental outcomes at 2 years of age were assessed using the Bayley Scales of Infant Development, third edition, and a standardized neurologic examination. Data regarding pulmonary morbidities, neurosensory impairments, and hospitalizations were obtained by parental interview. Intention-to-treat was used for primary analyses. RESULTS: Of the 197 infants enrolled in the original study there were 15 deaths, 5 in the umbilical cord milking group and 10 in DCC group. Of the remaining infants, 135 (74%) were assessed at 22-26 months of corrected age. Demographics in umbilical cord milking (n = 70) and DCC (n = 65) groups were similar. Infants randomized to umbilical cord milking at birth had significantly higher cognitive and language composite scores, and were less likely to have a cognitive composite score of <85 (4% vs 15%; P = .04). Motor function was similar in both groups. There were no differences in the incidences of mild or moderate to severe neurodevelopmental impairment, hearing or visual impairments, pulmonary morbidities, or rehospitalizations between the 2 groups. CONCLUSIONS: Infants randomized to umbilical cord milking had higher language and cognitive scores compared with those randomized to DCC. There was no difference in rates of mild or moderate to severe neurodevelopmental impairment. TRIAL REGISTRATION: clinicaltrials.gov: NCT01434732.

Pedi-cap color change precedes a significant increase in heart rate during neonatal resuscitation.

INTRODUCTION: Heart rate is the most important indicator of infant well-being during neonatal resuscitation. The Nellcor Pedi-Cap turns gold when exposed to exhaled gas with CO2>15 mmHg. The aim of this study was to determine if Pedi-Cap gold color change during neonatal resuscitation precedes an increase in heart rate in babies with bradycardia receiving mask ventilation. METHODS: This was a single-center retrospective review of video recordings and physiologic data of newborns with bradycardia receiving mask positive pressure ventilation during neonatal resuscitation. Subjects were included if the baby's HR<100 BPM within the first 90 s of resuscitation. The primary outcome was the change in HR prior to Pedi-Cap gold color change compared to the HR after Pedi-Cap gold color change. RESULTS: Forty-one newborns during the study period had HR<100 BPM and received mask positive pressure ventilation with a Pedi-Cap. The median heart rate 10s prior to Pedi-Cap gold color change was 75 BPM (IQR 62-85) and increased to 136 BPM (IQR 113-158) 30 s after gold color change (p<0.001). SpO2 increased from 45 ± 17% prior to Pedi-Cap gold color change to 52 ± 17% 30s after gold color change (p=0.001). CONCLUSIONS: Colorimetric CO2 detection during mask positive pressure ventilation in neonatal resuscitation precedes a significant increase in heart rate and SpO2. The Pedi-Cap can be easily applied during resuscitation, requires no electricity, provides immediate feedback and may be a useful, simple tool early in resuscitation and may be especially useful in resource limited settings.

The effects of umbilical cord milking on hemodynamics and neonatal outcomes in premature neonates.

OBJECTIVE: To determine whether umbilical cord milking (UCM) improves systemic blood flow and reduces neonatal morbidities compared with immediate cord clamping (ICC). STUDY DESIGN: Women admitted to a tertiary care center and delivering before 32 weeks' gestation were randomized to receive UCM or ICC. Three blinded serial echocardiograms were performed in the first 2 days of the infant's life. The primary outcome was measured systemic blood flow (superior vena cava flow) at each time point. RESULTS: Of the 60 neonates who were enrolled and randomized, 30 were assigned to cord milking and 30 to ICC. Neonates randomized to cord milking had greater measures of superior vena cava flow and right ventricular output in the first 6 hours and 30 hours of life. Neonates receiving UCM also had greater serum hemoglobin, received fewer blood transfusions, fewer days on oxygen therapy, and less frequent use of oxygen at 36 weeks' corrected postmenstrual age. CONCLUSIONS: We demonstrate greater systemic blood flow with UCM in preterm neonates compared with ICC. Future large prospective trials are needed to determine whether UCM reduces intraventricular hemorrhage and other long-term morbidities.

Tidal volume threshold for colorimetric carbon dioxide detectors available for use in neonates.

OBJECTIVE: Colorimetric carbon dioxide detectors are used for confirmation of endotracheal intubation. The colorimetric carbon dioxide detectors that are used for neonates are labeled for use with infants and small children >1 and <15 kg. The objective of this study was to determine the minimal tidal volume that causes a breath-to-breath color change on 2 colorimetric carbon dioxide detectors. METHODS: Using an artificial-lung model, we determined the tidal volume threshold of 2 colorimetric carbon dioxide detectors (Pedi-Cap [Nellcor, Pleasanton, CA] or Mini StatCO(2) [Mercury Medical, Clearwater, FL]) during ventilation with a T-piece resuscitator or neonatal ventilator. Digital video recordings of the colorimetric carbon dioxide detectors were made during 20 seconds of ventilation at each tidal volume. Seven clinicians who were blinded to the tidal volume reviewed the videos in random order and graded the color change to determine adequacy for clinical application. RESULTS: The Mini StatCO(2) tidal volume threshold was 0.83 mL, and the Pedi-Cap tidal volume threshold was 1.08 mL. CONCLUSIONS: The lung model revealed that the tidal volume threshold for the tested colorimetric carbon dioxide detectors is less than the expected tidal volume of a 400-g infant and suggests that these devices are appropriate for use with any neonate to confirm intubation.