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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

Jano, Eni; Vaz, Michelle J; Mally, Pradeep V; Wachtel, Elena
Objective To evaluate the utility of brain natriuretic peptide (BNP), troponin, galectin-3 and 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 ECHO. Serial measurements of biomarkers were performed from 6-96 hours post-TH initiation in 40 patients. Results Of 40 infants in study, 10 (25%) developed PPHN and 30 (75%) did not. Baseline demographics and hemodynamics were similar between the groups. Patients with PPHN had significantly higher need for vasopressors compared to patients without PPHN (70% vs. 27%, p=0.007). Mean serum BNP and troponin levels were significantly higher in PPHN group peaking at 12-24 hours and decreasing following PPHN treatment initiation. MiRNA-126a-5p expression was increased in patients with PPHN compared to 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 to healthy infants from prior studies. Conclusion BNP and troponin are readily available, low-cost biomarkers that showed significant serial elevations in PPHN group of study, thus may have value in screening for PPHN in the setting of HIE. Galectin-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.
PMID: 35436801
ISSN: 1098-8785
CID: 5218182

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

Patil, Uday P; Gupta, Arpit; Heringman, Kevin; Hickman, Cherbrale; Paudel, Umesh; Wachtel, Elena V
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.
PMID: 38779231
ISSN: 2168-8184
CID: 5654852

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

Mally, Pradeep; Katz, Julia; Verma, Sourabh; Purrier, Sheryl; Wachtel, Elena V; Trillo, Rebecca; Bhutada, Kiran; Bailey, Sean M
OBJECTIVES/OBJECTIVE: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.
PMID: 36318716
ISSN: 1619-3997
CID: 5358552

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

Spilios, Maria; Bashqoy, Ferras; Saad, Anasemon; Wachtel, Elena V; Tracy, Joanna
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.
PMID: 38130492
ISSN: 1551-6776
CID: 5612172

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

Howell, Heather B; Lin, Matthew; Zaccario, Michele; Kazmi, Sadaf; Sklamberg, Felice; Santaniello, Nicholas; Wachtel, Elena
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/METHODS: 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: = 0.03, odds ratio [OR] = 0.8, 95% confidence interval [CI]: 0.6-0.97) when adjusted for birth weight and gestational age. CONCLUSION/CONCLUSIONS: 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/CONCLUSIONS:· 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..
PMID: 32971560
ISSN: 1098-8785
CID: 4636572

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

Kazmi, Sadaf H; Berman, Sarah; Caprio, Martha; Wachtel, Elena V
BACKGROUND:Preterm infants are at high risk for metabolic bone disease (MBD). Analysis of donor breast milk (DBM) shows lower levels of macronutrients compared to 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 (ND) outcomes in infants fed predominantly MOM vs. DBM. METHODS:Retrospective observational study of infants born < 1500g and < 32 weeks at NYU 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 CA. MBD was assessed using alkaline phosphatase (AlkPO4) levels and x-ray findings. Data was also collected on growth, feeding tolerance, and long-term ND outcomes. RESULTS:210 infants were included: 156 in MOM and 54 in DBM group. The DBM group had higher AlkPO4 levels compared to the MOM group for the first 3 weeks of life (p < 0.01). Growth was similar between the groups and both groups demonstrated catch-up growth after discharge. No difference was seen in feeding intolerance, incidence of NEC, or sepsis. The DBM group had lower cognitive (OR 0.93 [0.88-0.98], p < 0.01) and language (OR 0.95 [0.90-0.99], p < 0.01) scores at 18-month CA. CONCLUSIONS:Infants fed predominantly DBM had elevated AlkPO4 levels suggestive of MBD, but did not develop significant osteopenia. Despite appropriate growth and comparable short-term outcomes, infants fed DBM had lower cognitive and language scores at 18-month CA. This article is protected by copyright. All rights reserved.
PMID: 33909915
ISSN: 1941-2444
CID: 4853352


Arevalo-Marcano, S.; Mally, P. N.; Wachtel, E. V.
ISSN: 1081-5589
CID: 5243712

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

Cosnahan, Anna S; Angert, Robert M; Jano, Eni; Wachtel, Elena V
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/METHODS: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/CONCLUSIONS:Dexmedetomidine is effective and safe for sedation and analgesia during therapeutic hypothermia. It reduced total opioid usage, with no increased incidence of adverse events.
PMID: 33649447
ISSN: 1476-5543
CID: 4801292

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

Kunjumon, Bgee; Wachtel, Elena V; Lumba, Rishi; Quan, Michelle; Remon, Juan; Louie, Moi; Verma, Sourabh; Moffat, Michael A; Kouba, Insaf; Bennett, Terri-Ann; Mejia, Claudia Manzano De; Mally, Pradeep V; Lin, Xinhua; Hanna, Nazeeh
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/METHODS: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/CONCLUSIONS: 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/CONCLUSIONS:· 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..
PMID: 34182576
ISSN: 1098-8785
CID: 4965602

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

Verma, Sourabh; Bradshaw, Chanda; Auyeung, N S Freda; Lumba, Rishi; Farkas, Jonathan S; Sweeney, Nicole B; Wachtel, Elena V; Bailey, Sean M; Noor, Asif; Kunjumon, Bgee; Cicalese, Erin; Hate, Rahul; Lighter, Jennifer L; Alessi, Samantha; Schweizer, William E; Hanna, Nazeeh; Roman, Ashley S; Dreyer, Benard; Mally, Pradeep V
PMID: 32737153
ISSN: 1098-4275
CID: 4553402