Post-discharge Care Practices, Challenges, and Outcomes in Newborn Infants of Mothers With SARS-CoV-2 Infection: Insights From Public Hospitals.

Background The data regarding the care at home and outcomes in infants of mothers infected with SARS-CoV-2 continue to evolve. There is a paucity of studies beyond the immediate newborn period. Our research aims to improve the understanding in these areas by studying the newborn population discharged from public hospitals in several boroughs of New York City (NYC) through the first year of the COVID-19 pandemic. Objective The objective of this study is to assess parental perspective and describe post-discharge care practices, patterns of healthcare utilization, challenges in obtaining care, and outcomes in infants between six and 12 months of age born to mothers infected with SARS-CoV-2 at the time of delivery. Methods We conducted an institutional review board (IRB)-approved multi-center retrospective cohort study of infants born to SARS-CoV-2-positive mothers at five NYC public hospitals between March and December of 2020. Clinical and demographic data were collected from electronic medical records. A phone interview of the caregivers using a standard questionnaire was conducted to collect data about care at home, healthcare utilization patterns, and challenges with access to healthcare. Results Our study cohort included 216 infants born to SARS-CoV-2-positive mothers with 16 (7.4%) mothers being symptomatic at discharge. Ten infants tested positive, and two showed symptoms before discharge. Two hundred seven (95.8%) infants were discharged home to their parents, and eight (3.7%) were transferred to other facilities. One hundred thirty-eight (66%) infants had at least one visit to the emergency room (ER) for various complaints where two were found to have COVID-19 with one needing hospitalization. One hundred seventy-two (79.6%) families responded to the phone interview. Most mothers (78%) cohabitated with their infants at home, and 70.3% elected to breastfeed. However, only 56.3% of mothers reported using all the recommended infection prevention practices at home. More than half (57%) of the families reported financial hardship related to the pandemic. Although 46.2% of patients missed their in-person health maintenance visits, telemedicine was highly utilized for follow-up with most being phone visits (70.3%). The majority of the infants (95.5%) remained up-to-date with their routine immunizations. Conclusions Our results suggest that infants born to SARS-CoV-2-infected mothers showed increased utilization of medical care and telemedicine between six and 12 months of age. Mothers reported low adherence to infection prevention practices at home; however, infants rarely showed clinically significant SARS-CoV-2 infection while maintaining high breastfeeding rates after discharge.

Incidence of Intracranial Hemorrhage in Patients Younger Than 2 Months Receiving Sodium Bicarbonate 4.2% vs 8.4.

OBJECTIVE: To assess the incidence of intracranial hemorrhage (ICH), including intraventricular hemorrhage, in infants receiving 4.2% or 8.4% sodium bicarbonate. METHODS: This is a single-center retrospective chart review of neonates and infants with a gestational age (GA) >32 weeks and a postnatal age <2 months who received sodium bicarbonate in an intensive care unit at an academic tertiary children's hospital. The primary outcome was the incidence of ICH in patients with baseline and follow-up head imaging. The secondary outcome was the incidence of ICH on follow-up head imaging, with or without baseline head imaging. RESULTS: There were 351 patients screened, with 135 meeting inclusion criteria. Of these, 84% were born ≥37 weeks GA. Forty-two met the criteria for the primary outcome. Study participants were further subdivided into 3 groups based on the concentration of sodium bicarbonate received: only 4.2%, only 8.4%, or a mixed group that received at least 1 dose each of 4.2% and 8.4%. Intracranial hemorrhage was noted in 1 patient in each group: 8.3%, 5.6%, and 8.3%, respectively (p = 1.00). For the secondary outcome, 11 ICHs were seen on head imaging: 11.3%, 3.8%, and 10%, respectively. There was no statistically significant difference in the incidence of ICH (p = 0.325). CONCLUSIONS: The incidence of ICH in term neonates and infants was not significantly different in those receiving 4.2% vs 8.4% sodium bicarbonate. Although additional studies are needed, this study suggests it may be possible to safely expand the use of 8.4% in neonates/infants ≥37 weeks GA. These results should not be applied to preterm neonates (<37 weeks GA and/or <1500 g) or neonates with additional ICH risk factors.

Impact on neonatal morbidities after a change in policy to administer antenatal corticosteroids to mothers at risk for late preterm delivery.

OBJECTIVES: Antenatal corticosteroids (ACS) administered to mothers at risk for preterm delivery before 34 weeks has been standard care to improve neonatal outcomes. After introducing a new obstetric policy based on updated recommendations advising the administration of ACS to pregnant women at risk for late preterm (LPT) delivery (34-36 6/7 weeks), we set out to determine the short-term clinical impact on those LPT neonates. METHODS: Retrospective chart review of LPT neonates delivered at NYU Langone Medical Center both one year before and after the policy went into place. We excluded subjects born to mothers with pre-gestational diabetes, multiple gestations, and those with congenital/genetic abnormalities. We also excluded subjects whose mothers already received ACS previously in pregnancy. Subjects were divided into pre-policy and post-policy groups. Neonatal and maternal data were compared for both groups. RESULTS: 388 subjects; 180 in the pre-policy and 208 in the post-policy group. This policy change resulted in a significant increase in ACS administration to mothers who delivered LPT neonates (67.3 vs. 20.6%, p<0.001). In turn, there was a significant reduction in LPT neonatal intensive care unit (NICU) admissions (44.2 vs. 54.4%, p=0.04) and need for respiratory support (27.9 vs. 42.8%, p<0.01). However, we also found an increased incidence of hypoglycemia (49.5 vs. 28.3%, p<0.001). CONCLUSIONS: This LPT ACS policy appears effective in reducing the need for LPT NICU level care overall. However, clinicians must be attentive to monitor for adverse effects like hypoglycemia, and there remains a need for better understanding of potential long-term impacts.

Pilot Study Investigating Brain Natriuretic Peptide, Troponin, Galectin-3, and miRNA-126a-5p as Biomarkers of Persistent Pulmonary Hypertension in Neonates with Hypoxic-Ischemic Injury Receiving Therapeutic Hypothermia.

OBJECTIVE: The objective was to evaluate the utility of brain natriuretic peptide (BNP), troponin, galectin-3 (Gal-3), and microRNA (miRNA)-126a-5p as screening biomarkers for persistent pulmonary hypertension of the newborn (PPHN) by comparing expression in serum of infants with hypoxic-ischemic injury that develop PPHN to those that do not. STUDY DESIGN: This was a prospective, observational pilot study including neonates with hypoxic-ischemic injury undergoing therapeutic hypothermia (TH) at two regional perinatal medical centers. PPHN in this population was diagnosed clinically and confirmed by echocardiogram. Serial measurements of biomarkers were performed from 6 to 96 hours post-TH initiation in 40 patients. RESULTS: Of 40 infants in the study, 10 (25%) developed PPHN and 30 (75%) did not. Baseline demographics and hemodynamics were similar between the groups. Patients with PPHN had a significantly higher need for vasopressors compared with patients without PPHN (70 vs. 27%, p = 0.007). Mean serum BNP and troponin levels were significantly higher in the PPHN group peaking at 12 to 24 hours and decreasing following PPHN treatment initiation. miRNA-126a-5p expression was increased in patients with PPHN compared with patients without, with statistical significance detected at 12 hours (p = 0.005) and 96 hours (p = 0.01). Mean circulating Gal-3 levels were not statistically different between the two groups; however, Gal-3 was elevated in all patients with hypoxic-ischemic injury on TH compared with healthy infants from prior studies. CONCLUSION: BNP and troponin are readily available, low-cost biomarkers that showed significant serial elevations in the PPHN group of the study and, thus, may have value in screening for PPHN in the setting of hypoxic-ischemic encephalopathy (HIE). Gal-3 was elevated in all patients with HIE and may be a useful biomarker of hypoxic injury in infants being evaluated for TH. Elevations in miRNA-126a-5p were not consistently seen in this study. Larger studies are required to establish an association between PPHN and these biomarkers in patients with and without HIE. KEY POINTS: · Serum biomarkers of persistent pulmonary hypertension of the newborn. · Serum biomarkers of hypoxic-ischemic injury.

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.

Breast Milk and Breastfeeding of Infants Born to SARS-CoV-2 Positive Mothers: A Prospective Observational Cohort Study.

OBJECTIVE: There are limited published data on the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from mothers to newborns through breastfeeding or from breast milk. The World Health Organization released guidelines encouraging mothers with suspected or confirmed COVID-19 to breastfeed as the benefits of breastfeeding outweighs the possible risk of transmission. The objective of this study was to determine if SARS-CoV-2 was present in the breast milk of lactating mothers who had a positive SARS-CoV-2 nasopharyngeal swab test prior to delivery, and the clinical outcomes for their newborns. STUDY DESIGN: This was a single-center, observational, prospective cohort study. Maternal-newborn dyads that delivered at New York University Langone Hospital Brooklyn with confirmed maternal SARS-CoV-2 positive screen test at the time of admission were recruited for the study. Breast milk samples were collected during postpartum hospitalization and tested for the presence of SARS-CoV-2 genes N1 and N2 by two-step reverse transcription polymerase chain reaction. Additionally, the clinical characteristics of the maternal newborn dyad, results of nasopharyngeal SARS-CoV-2 testing, and neonatal follow-up data were collected. RESULTS: A total of 19 mothers were included in the study and their infants who were all fed breast milk. Breast milk samples from 18 mothers tested negative for SARS-CoV-2, and 1 was positive for SARS-CoV-2 RNA. The infant who ingested the breast milk that tested positive had a negative nasopharyngeal test for SARS-CoV-2, and had a benign clinical course. There was no evidence of significant clinical infection during the hospital stay or from outpatient neonatal follow-up data for all the infants included in this study. CONCLUSION: In a small cohort of SARS-CoV-2 positive lactating mothers giving birth at our institution, most of their breast milk samples (95%) contained no detectable virus, and there was no evidence of COVID-19 infection in their breast milk-fed neonates. KEY POINTS: · Breast milk may rarely contain detectable SARS-CoV-2 RNA and was not detected in asymptomatic mothers.. · Breast milk with detectable SARS-CoV-2 RNA from a symptomatic mother had no clinical significance for her infant.. · Breast feeding with appropriate infection control instructions appears to be safe in mother with COVID infection..

Dexmedetomidine versus intermittent morphine for sedation of neonates with encephalopathy undergoing therapeutic hypothermia.

OBJECTIVE: In March 2019, the sedative in the therapeutic hypothermia protocol at Bellevue Hospital Center and NYU Langone Health changed from morphine to dexmedetomidine. This study evaluated the impact of this change on efficacy and safety parameters. STUDY DESIGN: This was a retrospective, observational cohort study including neonates with HIE undergoing therapeutic hypothermia (N = 70) at two regional perinatal medical centers. RESULTS: Baseline demographics, pain scores, hemodynamics, and time to enteral feeds were similar between dexmedetomidine (N = 34) and morphine (N = 36) patients. Dexmedetomidine patients received more breakthrough morphine (0.13 ± 0.13 vs 0.04 ± 0.09 mg/kg, p = 0.001), but less cumulative morphine (0.13 ± 0.13 vs 1.79 ± 0.23 mg/kg, p < 0.0001). Morphine patients on invasive ventilation required increased support (0 vs 31.58%, p = 0.02). CONCLUSION: Dexmedetomidine is effective and safe for sedation and analgesia during therapeutic hypothermia. It reduced total opioid usage, with no increased incidence of adverse events.

Outcomes of Maternal-Newborn Dyads After Maternal SARS-CoV-2.

BACKGROUND AND OBJECTIVES: Infection with a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. There are limited data describing the impact of SARS-CoV-2 infection on pregnant mothers and their newborns. The objective of this study is to describe characteristics and outcomes of maternal-newborn dyads with confirmed maternal SARS-CoV-2. METHODS: This was a multicenter, observational, descriptive cohort study with data collection from charts of maternal-newborn dyads who delivered at 4 major New York City metropolitan area hospitals between March 1 and May 10, 2020, with maternal SARS-CoV-2 infection. RESULTS: There were a total of 149 mothers with SARS-CoV-2 infection and 149 newborns analyzed (3 sets of twins; 3 stillbirths). Forty percent of these mothers were asymptomatic. Approximately 15% of symptomatic mothers required some form of respiratory support, and 8% required intubation. Eighteen newborns (12%) were admitted to the ICU. Fifteen (10%) were born preterm, and 5 (3%) required mechanical ventilation. Symptomatic mothers had more premature deliveries (16% vs 3%, P = .02), and their newborns were more likely to require intensive care (19% vs 2%, P = .001) than asymptomatic mothers. One newborn tested positive for SARS-CoV-2, which was considered a case of horizontal postnatal transmission. CONCLUSIONS: Although there was no distinct evidence of vertical transmission from mothers with SARS-CoV-2 to their newborns, we did observe perinatal morbidities among both mothers and newborns. Symptomatic mothers were more likely to experience premature delivery and their newborns to require intensive care.

Neonatal intensive care unit preparedness for the Novel Coronavirus Disease-2019 pandemic: A New York City hospital perspective.

In January 2020, China reported a cluster of cases of pneumonia associated with a novel pathogenic coronavirus provisionally named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2). Since then, Coronavirus Disease 2019 (COVID-19) has been reported in more than 180 countries with approximately 6.5 million known infections and more than 380,000 deaths attributed to this disease as of June 3rd , 2020 (Johns Hopkins University COVID map; https://coronavirus.jhu.edu/map.html) The majority of confirmed COVID-19 cases have been reported in adults, especially older individuals with co-morbidities. Children have had a relatively lower rate and a less serious course of infection as reported in the literature to date. One of the most vulnerable pediatric patient populations is cared for in the neonatal intensive care unit. There is limited data on the effect of COVID-19 in fetal life, and among neonates after birth. Therefore there is an urgent need for proactive preparation, and planning to combat COVID-19, as well as to safeguard patients, their families, and healthcare personnel. This review article is based on the Centers for Disease Control and Prevention's (CDC) current recommendations for COVID-19 and its adaptation to our local resources. The aim of this article is to provide basic consolidated guidance and checklists to clinicians in the neonatal intensive care units in key aspects of preparation needed to counter exposure or infection with COVID-19. We anticipate that CDC will continue to update their guidelines regarding COVID-19 as the situation evolves, and we recommend monitoring CDC's updates for the most current information.

Update on the current management of newborns with neonatal encephalopathy.

Hypoxic-ischemic encephalopathy is a subtype of neonatal encephalopathy and a major contributor to global neonatal morbidity and mortality. Despite advances in obstetric and neonatal care there are still challenges in accurate determination of etiology of neonatal encephalopathy. Thus, identification of intrapartum risk factors and comprehensive evaluation of the neonate is important to determine the etiology and severity of neonatal encephalopathy. In developed countries, therapeutic hypothermia as a standard of care therapy for neonates with hypoxic-ischemic encephalopathy has proven to decrease incidence of death and neurodevelopmental disabilities, including cerebral palsy in surviving children. Advances in neuroimaging, brain monitoring modalities, and biomarkers of brain injury have improved the ability to diagnose, monitor, and treat newborns with encephalopathy. However, challenges remain in early identification of neonates at risk for hypoxic-ischemic brain injury, and determination of the timing and extent of brain injury. Using imaging studies such as Neonatal MRI and MR spectroscopy have proven to be most useful in predicting outcomes in infants with encephalopathy within the first week of life, although comprehensive neurodevelopmental assessments still remains the gold standard for determining long term outcomes. Future studies are needed to identify other newborns with encephalopathy that might benefit from therapeutic hypothermia and to determine the efficacy of other adjunctive neuroprotective strategies. This review focuses on newer evidence and advances in diagnoses and management of infants with neonatal encephalopathy, including novel therapies, as well as prognostication of outcomes to childhood.

Therapeutic hypothermia during neonatal transport at Regional Perinatal Centers: active vs. passive cooling.

Background Earlier initiation of therapeutic hypothermia in term infants with hypoxic-ischemic encephalopathy has been shown to improve neurological outcomes. The objective of the study was to compare safety and effectiveness of servo-controlled active vs. passive cooling used during neonatal transport in achieving target core temperature. Methods We undertook a prospective cohort quality improvement study with historic controls of therapeutic hypothermia during transport. Primary outcome measures were analyzed: time to cool after initiation of transport, time to achieve target temperature from birth and temperature on arrival to cooling centers. Safety was assessed by group comparison of vital signs, diagnosis of persistent pulmonary hypertension (PPHN) and coagulation profiles on arrival. Results A total of 65 infants were included in the study. Time to cool after initiation of transport and time to achieve target temperature from birth were statistically significantly shorter in the actively cooled group with time reduction of 24% with P<0.01 and 15.6% with P<0.01, respectively. On arrival to our cooling center, we noted a significance difference in the mean core temperature (active 33.8°C vs. passive 35.4°C, P<0.01). Seven percent (2/30) of infants in the passively cooled group were overcooled (temperature <33°C). Patients in the actively cooled group had significantly lower mean heart rate compared to the passively cooled group. There was no statistically significant difference in diagnosis of PPHN or coagulation profiles on admission. Conclusion Our study indicates that active cooling with a servo-controlled device on neonatal transport is safe and more effective in achieving target temperature compared to passive cooling.

Subcutaneous Fat Necrosis and Hypercalcemia After Therapeutic Hypothermia in Patients With Hypoxic-ischemic Encephalopathy: A Case Series.

Therapeutic hypothermia (TH) is provided to newborns with moderate to severe hypoxic-ischemic encephalopathy (HIE) to improve survival and long-term neurodevelopmental outcomes. Although the benefits certainly outweigh the risks associated with therapeutic hypothermia, it is important to be mindful of potential rare side effects in the background of asphyxia-related injury to various body organs. One of those side effects includes subcutaneous fat necrosis (SCFN) that can occur in term newborns after perinatal hypoxia-ischemia or other stressing factors such as systemic hypothermia. It is usually a self-limited condition, however, in some cases, it can lead to severe hypercalcemia. We report three such cases of SCFN in newborns with HIE treated with TH. Due to potential long-term complications, such as metastatic calcifications, caregivers should be informed about this potential complication prior to discharge from hospital so that they can help diagnose or continue to monitor cases of severe hypercalcemia.

Serum biomarkers of neuronal injury in newborns evaluated for selective head cooling: a comparative pilot study.

Background Evaluation of newborns for hypoxic ischemic encephalopathy (HIE) includes laboratory and clinical parameters, as well as amplitude integrated electroencephalogram (aEEG). Based on qualifying criteria, selective head cooling (SHC) is initiated for infants with evidence of moderate to severe HIE. However, some newborns may not qualify for hypothermia therapy based on normal aEEG. Objective To compare levels of serum glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-1 (UCHL-1) protein and phosphorylated axonal neurofilament heavy chain (pNF-H), in newborns who met initial screening criteria for HIE but did not qualify for head cooling, to the levels in healthy newborns. Study design Newborns ≥36 weeks of gestational age at risk for HIE, who were evaluated but did not qualify for SHC from July 2013 through June 2014 at NYU Langone Medical Center and Bellevue Hospital center were enrolled. A control group included healthy newborns from the newborn nursery (NBN). Serum samples were collected between 24 and 48 h of life from both groups. Results There was no significant difference in the serum levels of GFAP, UCHL-1 protein and pNF-H between the two groups of infants. Conclusion Newborns at risk for HIE who met the initial criteria for head cooling but who were excluded based on normal aEEG did not show significant elevation of biomarkers of brain injury compared to healthy newborns. These findings may help to validate using aEEG as an additional evaluation criteria in cooling.

Implicit Physician Biases in Periviability Counseling.

OBJECTIVE: To assess whether neonatologists show implicit racial and/or socioeconomic biases and whether these are predictive of recommendations at extreme periviability. STUDY DESIGN: A nationwide survey using a clinical vignette of a woman in labor at 232/7 weeks of gestation asked physicians how likely they were to recommend intensive vs comfort care. Participants were randomized to 1 of 4 versions of the vignette in which racial and socioeconomic stimuli were varied, followed by 2 implicit association tests (IATs). RESULTS: IATs revealed implicit preferences favoring white (mean IAT score = 0.48, P < .001) and greater socioeconomic status (mean IAT score = 0.73, P < .001). Multivariable linear regression analysis showed that physicians with implicit bias toward greater socioeconomic status were more likely than those without bias to recommend comfort care when presented with a patient of high socioeconomic status (P = .037). No significant effect was seen for implicit racial bias. CONCLUSIONS: Building on previous demonstrations of unconscious racial and socioeconomic biases among physicians and their predictive validity, our results suggest that unconscious socioeconomic bias influences recommendations when counseling at the limits of viability. Physicians who display a negative socioeconomic bias are less likely to recommend resuscitation when counseling women of high socioeconomic status. The influence of implicit socioeconomic bias on recommendations at periviability may influence neonatal healthcare disparities and should be explored in future studies.

Utility of routine urine CMV PCR and total serum IgM testing of small for gestational age infants: a single center review.

BACKGROUND: Due to the extremely low incidence of TORCH (toxoplasmosis, rubella, CMV, herpes simplex virus) infections, diagnostic testing of all small for gestational age (SGA) infants aimed at TORCH etiologies may incur unnecessary tests and cost. OBJECTIVE: To determine the frequency of urine CMV PCR and total IgM testing among infants with birth weight <10% and the rate of test positivity. To evaluate the frequency of alternative etiologies of SGA in tested infants. METHODS: Retrospective chart review of SGA infants admitted to the neonatal intensive care unit (NICU) at NYU Langone Medical Center between 2007 and 2012. Subjects were classified as being SGA with or without intrauterine growth restriction (IUGR). The IUGR subjects were then further categorized as having either symmetric or asymmetric IUGR utilizing the Fenton growth chart at birth. Initial testing for TORCH infections, which included serum total IgM, CMV PCR and head ultrasound, were reviewed and analyzed. RESULTS: Three hundred and eighty-six (13%) infants from a total of 2953 NICU admissions had a birth weight ≤10th percentile. Of these, 44% were IUGR; 34% being symmetric IUGR and 10% asymmetric. A total of 32% of SGA infants had urine CMV PCR and total IgM tested with no positive results. As expected, significantly higher percentage of symmetric IUGR infants were tested compared to asymmetric IUGR and non-IUGR SGA infants, (64% vs. 47% vs. 19%) P≤0.01. However, 63% of infants with a known cause for IUGR had same testing done aimed at TORCH infections. We calculated additional charges of $64,065 that were incurred by such testing. CONCLUSIONS: The majority of infants in our study who received testing for urine CMV PCR and total IgM aimed at TORCH infections had one or more other known non-infectious etiologies for IUGR. Because the overall yield of such testing is extremely low, we suggest tests for possible TORCH infections may be limited to symmetric IUGR infants without other known etiologies. Improved guidelines testing for TORCH infections can result in reducing hospital charges and unnecessary studies.

Efficacy of and potential morbidities associated with the use of antacid medications in preterm neonates.

OBJECTIVES: Antacid medications are frequently administered to preterm infants. These medications can change gastric pH levels and can affect regular gastrointestinal function and gut micro-bacterial flora. We hypothesized that preterm infants exposed to antacid medications are at a greater risk of necrotizing enterocolitis (NEC) and sepsis, and set out to determine any association, as well as to assess the clinical efficacy of these medications. MATERIALS AND METHODS: Retrospective chart review of preterm infants ≤30 weeks' gestational age or birth weight ≤1250 g over a 2-year period at New York University Langone Medical Center. Subjects were divided into two groups: those who had been treated with antacid medications and those who had not. We then examined for any difference in NEC (≥Bell stage 2) or culture proven sepsis. RESULTS: The study comprised 65 eligible neonates, 28 in antacid treatment group and 37 in control. The incidence of NEC (21.4% vs. 2.7%, P=0.04) was significantly higher in the antacid group, but these infants tended to be born more prematurely than control subjects. There was a trend toward more culture proven sepsis cases in the antacid group. We found no difference in signs generally associated with neonatal reflux (apnea, bradycardia, and desaturation events) in subjects treated with antacid medications after treatment began. CONCLUSIONS: Treatment of preterm infants with antacid medications is potentially associated with a higher risk of NEC, and possibly sepsis, while appearing to provide little benefit.

Clinical characteristics and factors associated with term and late preterm infants that do not respond to inhaled nitric oxide (iNO).

AIM: Inhaled nitric oxide (iNO) is used to treat neonates with hypoxic respiratory failure (HRF). The aim of this study was to determine clinical characteristics and factors associated with non-response to iNO therapy that may assist in clinical management and weaning strategies. METHODS: Retrospective chart review. The study cohort included gestational age ≥34 weeks' infants with acute HRF who received iNO within 7 days of birth. Subjects were stratified as responders or non-responders to iNO. Non-responders were defined as infants with failure to improve their PaO2 >20 mm Hg within 6 h of iNO initiation, need for extracorporeal membrane oxygenation (ECMO), or mortality. Clinical and laboratory characteristics were then compared between groups. RESULTS: Forty four subjects were included. There were 31 responders and 13 non-responders to iNO therapy. Regression analysis showed significant correlation between a non-response to iNO therapy and changes in PaO2 and pH levels. We found for every 10 mm Hg decrease in PaO2 immediate post-iNO therapy there is a 17.5% decrease in the likelihood of responding to iNO (odds ratio [OR] 0.98, P=0.012). Similarly, for every 0.15 point decrease in pH, there is a 16.3% increased chance of not responding to iNO therapy (OR 1.16, P=0.002). The need for pressor support prior to iNO initiation was also found to be associated with a non-response (OR 2. 94, P=0.034). CONCLUSIONS: Hypotension requiring treatment with pressors at the time of iNO therapy, as well as changes in pH and PaO2 after iNO initiation can be used as early clinical predictors to identify patients quickly who may be iNO non-responders.

Impact of Respiratory Morbidities on Neurodevelopmental Outcome of Late Preterm Infants.

OBJECTIVE: This study aims to evaluate impact of respiratory and other neonatal comorbidities on neurodevelopmental outcome in late preterm infants (LPT). METHOD: Retrospective study of LPT infants (34 (0/7)-36 (6/7) weeks' gestation) discharged from the New York University Langone Medical Center neonatal intensive care unit, during January 2006 to December 2010 and received follow-up care up to 2 years of age. Neonatal morbidities were correlated with neurodevelopmental outcomes and assessed by performance on the Mullen Scales of Early Learning during three developmental follow-up visits. RESULTS: A total of 99 LPT completed neurodevelopmental assessment up to 2 years of age. Infants with diagnosis of moderate-to-severe respiratory distress syndrome showed a significantly lower performance in the visual reception on the second (p<0.01) and third visit (p=0.02), as well as lower performance in the receptive language (visit 2, p=0.02; visit 3, p<0.01). A diagnosis of persistent pulmonary hypertension was found to be associated with significantly lower performance in the visual reception at all visits (p<0.01; p=0.02; p=0.02) and in the receptive language on the second and third visit (p=0.03; p=0.02). Combined respiratory morbidities were also associated with lower developmental scores in fine motor (visit 2, p<0.01; visit 3, p=0.04) as well as expressive language (visit 3, p=0.02). CONCLUSION: LPT with significant respiratory morbidities are at higher risk for long-term developmental delays, mainly affecting cognitive developmental domains.

Current management of the infant who presents with neonatal encephalopathy.

Neonatal encephalopathy after perinatal hypoxic-ischemic insult is a major contributor to global child mortality and morbidity. Brain injury in term infants in response to hypoxic-ischemic insult is a complex process evolving over hours to days, which provides a unique window of opportunity for neuroprotective treatment interventions. Advances in neuroimaging, brain monitoring techniques, and tissue biomarkers have improved the ability to diagnose, monitor, and care for newborn infants with neonatal encephalopathy as well as predict their outcome. However, challenges remain in early identification of infants at risk for neonatal encephalopathy, determination of timing and extent of hypoxic-ischemic brain injury, as well as optimal management and treatment duration. Therapeutic hypothermia is the most promising neuroprotective intervention to date for infants with moderate to severe neonatal encephalopathy after perinatal asphyxia and has currently been incorporated in many neonatal intensive care units in developed countries. However, only 1 in 6 babies with encephalopathy will benefit from hypothermia therapy; many infants still develop significant adverse outcomes. To enhance the outcome, specific diagnostic predictors are needed to identify patients likely to benefit from hypothermia treatment. Studies are needed to determine the efficacy of combined therapeutic strategies with hypothermia therapy to achieve maximal neuroprotective effect. This review focuses on important concepts in the pathophysiology, diagnosis, and management of infants with neonatal encephalopathy due to perinatal asphyxia, including an overview of recently introduced novel therapies.