Early Findings of a Preterm Twin Cohort Study Examining the Effect of General Anesthesia on Developmental Outcomes.

PURPOSE: The premature infant brain may be particularly vulnerable to anesthesia effects, but there is conflicting evidence on the association between anesthesia exposure and developmental outcomes. Twin studies can control for confounding factors. A twin cohort of premature twins provides internal control of difficulty to measure confounders and delivers added power to a study examining the effects of anesthesia on neurodevelopmental outcomes. METHODS: We conducted a retrospective cohort study of sets of premature twins and multiples born at an academic medical center, in which 1 member of the set was exposed to general anesthesia. The primary outcome was the composite scores using Bayley Scale of Infant and Toddler Development III performed at age 6 months to 18 months. Unpaired and paired analyses were performed with linear regression models, Wilcoxon signed rank test, and Mann-Whitney U test. RESULTS: We identified 81 children born at less than 32 weeks gestation within 39 sets of twins and 1 set of triplets for a total of 18 paired observations. All of the exposed infants had a single exposure to general anesthesia. There was no significant association between anesthesia exposure and a diagnosis of developmental delay (OR = 0.8; 95% confidence interval, 0.2-3.2; p = 0.99). Regression models demonstrated no association between anesthesia exposure and cognitive (96.67 vs 97.50; p = 0.74), language (98.33 vs 98.61; p = 0.94), or motor (96.25 vs. 96.44; p = 0.91) composite Bayley scores. There was no association between duration of anesthesia and the 3 composite Bayley scores (p = 0.33; p = 0.40; p = 0.74). CONCLUSION: Using a premature twin cohort with discordant exposure to anesthesia, our data did not demonstrate any association between anesthesia exposure and developmental delay in this vulnerable population of premature infants.

Changes in regional tissue oxygen saturation values during the first week of life in stable preterm infants.

OBJECTIVES: Near infrared spectroscopy (NIRS) is a non-invasive method for monitoring regional tissue oxygen saturation (rSO2). The purpose of this study is to investigate the changes that occur in cerebral, splanchnic, and renal rSO2 and fractional tissue oxygen extraction (FTOE) in stable preterm infants in the first week of life. METHODS: Prospective observational study of infants born 30-34 weeks gestation at NYU Langone Health between November 2017 and November 2018. Cerebral, renal, and splanchnic rSO2 were monitored from 12 to 72 h of life, and at seven days. Subjects were divided into gestational age (GA) cohorts. Average rSO2, splanchnic cerebral oxygen ratio (SCOR), FTOE, and regional intra-subject variability was calculated at each location at five different time intervals: 0-12 h, 12-24 h, 24-48 h, 48-72 h, and one week of life. RESULTS: Twenty subjects were enrolled. The average cerebral rSO2 ranged from 76.8 to 92.8 %, renal rSO2 from 65.1 to 91.1 %, and splanchnic rSO2 from 36.1 to 76.3 %. The SCOR ranged from 0.45 to 0.94. The strongest correlation between the GA cohorts was in the cerebral region (R2=0.94) and weakest correlation was in the splanchnic region (R2=0.81). The FTOE increased in all three locations over time. Intra-subject variability was lowest in the cerebral region (1.3 % (±1.9)). CONCLUSIONS: The cerebral region showed the strongest correlation between GA cohorts and lowest intra-subject variability, making it the most suitable for clinical use when monitoring for tissue hypoxia. Further studies are needed to further examine rSO2 in preterm infants.

Developmental screening of full-term infants at 16 to 18 months of age after in-utero exposure to maternal SARS-CoV-2 infection.

OBJECTIVE: To screen for neurodevelopmental delays in a cohort of full-term infants born to mothers with SARS-CoV-2. STUDY DESIGN: This was a prospective, descriptive cohort study of full-term infants born to mothers with SARS-CoV-2 during pregnancy. Subjects underwent neurodevelopmental screening using the Ages and Stages Questionnaires®-Third Edition (ASQ®-3) at 16 to 18 months age. RESULTS: Of 51 subjects, twelve (24%) were below cutoff, and twenty-seven (53%) were either below or close to the cutoff in at least one developmental domain. Communication (29%), fine motor (31%), and problem-solving (24%) were the most affected domains. There were no differences in outcomes between infants born to asymptomatic and mildly symptomatic mothers. CONCLUSION: We observed increased risk of neurodevelopmental delays during screening of infants born at full-term to mothers with SARS-CoV-2 at 16 to 18 months age. These results highlight the urgent need for follow-up studies of infants born to mothers with SARS-CoV-2.

Virtual Care Across the Neonatal Intensive Care Continuum.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for establishing effective parent and family engagement throughout all aspects of medicine. Though there has been some discussion in the literature regarding the transition from typical outpatient visits to telehealth visits, there has been less written about the inpatient approach to family inclusion. Here, we seek to describe our institution's experience with implementing virtual medicine across the full continuum of the neonatal intensive care unit (NICU) experience, including inpatient rounding, child life family visits, and outpatient high-risk developmental follow-up after discharge.

Near-infrared spectroscopy in the medical management of infants.

Near-infrared spectroscopy (NIRS) is a technology that is easy to use and can provide helpful information about organ oxygenation and perfusion by measuring regional tissue oxygen saturation (rSO2) with near-infrared light. The sensors can be placed in different anatomical locations to monitor rSO2 levels in several organs. While NIRS is not without limitations, this equipment is now becoming increasingly integrated into modern healthcare practice with the goal of achieving better outcomes for patients. It can be particularly applicable in the monitoring of pediatric patients because of their size, and especially so in infant patients. Infants are ideal for NIRS monitoring as nearly all of their vital organs lie near the skin surface which near-infrared light penetrates through. In addition, infants are a difficult population to evaluate with traditional invasive monitoring techniques that normally rely on the use of larger catheters and maintaining vascular access. Pediatric clinicians can observe rSO2 values in order to gain insight about tissue perfusion, oxygenation, and the metabolic status of their patients. In this way, NIRS can be used in a non-invasive manner to either continuously or periodically check rSO2. Because of these attributes and capabilities, NIRS can be used in various pediatric inpatient settings and on a variety of patients who require monitoring. The primary objective of this review is to provide pediatric clinicians with a general understanding of how NIRS works, to discuss how it currently is being studied and employed, and how NIRS could be increasingly used in the near future, all with a focus on infant management.

The Impact of Hypernatremia in Preterm Infants on Neurodevelopmental Outcome at 18 Months of Corrected Age.

OBJECTIVE: The study objective was to assess the correlation between hypernatremia during the first week of life and neurodevelopmental outcomes at 18 months of corrected age in premature infants. STUDY DESIGN: A retrospective observational study of preterm infants born at less than 32 weeks of gestation who had a neurodevelopmental assessment with the Bayley scales of infant and toddler development III at 18 ± 6 months of corrected age. Serum sodium levels from birth through 7 days of life were collected. The study cohort was divided into two groups: infants with a peak serum sodium of >145 mmol/L (hypernatremia group) and infants with a peak serum sodium level of <145 mmol/L (no hypernatremia group). Prenatal, intrapartum, and postnatal hospital course and neurodevelopmental data at 18 ± 6 months were collected. Logistic regression analysis was used to assess the correlation between neonatal hypernatremia and neurodevelopment with adjustment for selected population characteristics. RESULTS: Eighty-eight preterm infants with complete neurodevelopmental outcome data at 18 ± 6 months of corrected gestational age were included in the study. Thirty-five neonates were in the hypernatremia group and 53 were in the no hypernatremia group. Maternal and neonatal characteristics were similar between the two groups except that the hypernatremia group had a significantly lower average birth weight and gestational age. Comparison of the mean neurodevelopmental scores between the two groups showed that patients in the hypernatremia group as compared with those in the no hypernatremia group had significantly lower neurodevelopmental scaled scores in the fine motor domain (p = 0.01). This difference remained significant (p = 0.03, odds ratio [OR] = 0.8, 95% confidence interval [CI]: 0.6-0.97) when adjusted for birth weight and gestational age. CONCLUSION: Preterm infants born at less than 32 weeks of gestation with hypernatremia in the first week of life have lower fine motor scores at 18 months of corrected age. KEY POINTS: · Hypernatremia is a common electrolyte disturbance in preterm neonates.. · Hypernatremia may be associated with long-term neurodevelopmental outcomes in preterm infants.. · Hypernatremia is a potentially modifiable risk factor..

Effects of Inhaled Iloprost for the Management of Persistent Pulmonary Hypertension of the Newborn.

OBJECTIVE: The study aimed to evaluate the effects of inhaled iloprost on oxygenation indices in neonates with persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: We conducted a retrospective chart review of 30 patients with PPHN from January 2014 to November 2018, who did not respond to inhaled nitric oxide (iNO) alone and received inhaled iloprost. Twenty-two patients met the inclusion criteria and eight patients were excluded from the study (complex cardiac disease and extreme prematurity). Patients were categorized as responders or nonresponders (patients who required extracorporeal membrane oxygenation or died). Oxygenation index, mean airway pressure (MAP), and arterial partial pressure of oxygen (PaO2) were recorded. RESULTS: Among a total of 22 patients who were included in the study, 10 were classified as nonresponders as they required either extracorporeal membrane oxygenation or died. Gestational age and gender did not differ between responders and nonresponders. The median PaO2 was lower (37 vs. 42 mm Hg; p < 0.05) and median MAP was higher (20 vs. 17 cm H2O; p < 0.02) in nonresponders compared with responders just prior to initiating iloprost. Iloprost responders had a significant increase in median PaO2 and decrease in median oxygenation index in the 24 hours after initiating treatment (p < 0.05), with no significant change in required mean airway pressure over that same period. There was no change in vasopressor use or clinically significant worsening of platelets count, liver, and kidney functions after initiating iloprost. CONCLUSION: Inhaled iloprost is well tolerated and seems to have beneficial effects in improving oxygenation indices in neonates with PPHN who do not respond to iNO. There is a need of well-designed prospective trials to further ascertain the benefits of using inhaled iloprost as an adjunct treatment in neonates with PPHN who do not respond to iNO alone. KEY POINTS: · Inhaled iloprost seems to have beneficial effects in improving oxygenation indices in PPHN.. · Inhaled iloprost is generally well tolerated in newborns with PPHN.. · There is a need for prospective randomized controlled trials to further ascertain the benefits of using inhaled iloprost..

The impact of donor breast milk on metabolic bone disease, postnatal growth, and neurodevelopmental outcomes at 18 months' corrected age.

BACKGROUND: Preterm infants are at risk for metabolic bone disease (MBD). Analysis of donor breast milk (DBM) shows lower levels of macronutrients compared with mother's own milk (MOM). The purpose of this study was to investigate the prevalence of MBD, rate of postnatal growth, and long-term neurodevelopmental outcomes in infants fed predominantly MOM vs DBM. METHODS: Retrospective observational study of infants born <1500g and <32 weeks at New York University Langone Health or Bellevue Hospital from January 2014 to January 2018. Infants were divided into two groups: those who received >70% of feeds with either MOM or DBM by 34 weeks' corrected age (CA). MBD was assessed using alkaline phosphatase (AlkPO4) levels and radiographic findings. Data was also collected on growth, feeding tolerance, and long-term neurodevelopmental outcomes. RESULTS: A total of 210 infants were included (MOM =156 and DBM =54). The DBM group had higher AlkPO4 levels for the first 3 weeks of life (P < .01). Growth was similar between the groups, and both groups demonstrated catch-up growth after discharge. No difference was seen in feeding intolerance, incidence of necrotizing enterocolitis, or sepsis. The DBM group had lower cognitive (odds ratio [OR], 0.93 [0.88-0.98]; P < .01) and language (OR, 0.95 [0.90-0.99]; P < .01) scores at 18 months' CA. CONCLUSION: Infants fed predominantly DBM had elevated AlkPO4 levels suggestive of MBD but did not develop osteopenia. Despite appropriate growth and comparable short-term outcomes, infants fed DBM had lower cognitive and language scores at 18 months' CA.

Neurodevelopmental outcomes of children with congenital heart disease: A review.

Congenital heart defects are the most common birth anomaly affecting approximately 1% of births. With improved survival in this population, there is enhanced ability to assess long-term morbidities including neurodevelopment. There is a wide range of congenital heart defects, from those with minimal physiologic consequence that do not require medical or surgical intervention, to complex structural anomalies requiring highly specialized medical management and intricate surgical repair or palliation. The impact of congenital heart disease on neurodevelopment is multifactorial. Susceptibility for adverse neurodevelopment increases with advancing severity of the defect with initial risk factors originating during gestation. Complex structural heart anomalies may pre-dispose the fetus to abnormal circulatory patterns in utero that ultimately impact delivery of oxygen rich blood to the fetal brain. Thus, the brain of a neonate born with complex congenital heart disease may be particularly vulnerable from the outset. That vulnerability is compounded during the newborn period and through childhood, as this population endures a myriad of medical and surgical interventions. For each individual patient, these factors are likely cumulative and synergistic with progression from fetal life through childhood. This review discusses the spectrum of risk factors that may impact neurodevelopment in children with congenital heart disease, describes current recommendations and practices for neurodevelopmental follow-up of children with congenital heart disease and reviews important neurodevelopmental trends in this high risk population.

The Effect of Complete Blood Count Timing on Lumbar Puncture Rates in Asymptomatic Infants Born to Mothers with Chorioamnionitis.

Background Maternal chorioamnionitis is a risk factor for sepsis but, often, these infants are asymptomatic at birth. Different markers for infections, such as the immature to total (I/T) white blood cell (WBC) ratio, are used to help determine which infants require lumbar punctures (LPs), in addition to blood cultures and antibiotics. The timing of when the complete blood count (CBC) is obtained may have some effect on the length of antibiotic treatment. Aims The purpose of this proof-of-concept study was to assess if obtaining a CBC at greater than four hours of life as compared to less than four hours of life has an impact on the incidence of LPs performed in asymptomatic, full-term infants undergoing evaluation for sepsis secondary to maternal chorioamnionitis. Methods We performed a retrospective study of full-term, asymptomatic infants admitted for sepsis evaluation secondary to maternal chorioamnionitis. Subjects were grouped based upon the timing of their initial CBC (early = < four hours of life or late = > four hours of life). The incidence of LPs, duration of antibiotic treatment, and length of hospitalization were compared between the groups. Results A total of 230 subjects were included in the study (early group = 124, late group = 106). Subjects in the late group underwent significantly fewer LPs than subjects in the early group, 5.7% vs. 22.6% (p<0.001). There was no difference in length of treatment or hospitalization. Conclusions Asymptomatic full-term infants undergoing evaluation for sepsis secondary to maternal chorioamnionitis are less likely to undergo an LP if their initial CBC is obtained at greater than four hours of life.