ScreenPlus: A comprehensive, multi-disorder newborn screening program.

The increasing availability of novel therapies highlights the importance of screening newborns for rare genetic disorders so that they may benefit from early therapy, when it is most likely to be effective. Pilot newborn screening (NBS) studies are a way to gather objective evidence about the feasibility and utility of screening, the accuracy of screening assays, and the incidence of disease. They are also an optimal way to evaluate the complex ethical, legal and social implications (ELSI) that accompany NBS expansion for disorders. ScreenPlus is a consented pilot NBS program that aims to enroll over 100,000 infants across New York City. The initial ScreenPlus panel includes 14 disorders and uses an analyte-based, multi-tiered screening platform in an effort to enhance screening accuracy. Infants who receive an abnormal result are referred to a ScreenPlus provider for confirmatory testing, management, and therapy as needed, along with longitudinal capture of outcome data. Participation in ScreenPlus requires parental consent, which is obtained in active and passive manners. Patient-facing documents are translated into the ten most common languages spoken at our nine pilot hospitals, all of which serve diverse communities. At the time of consent, parents are invited to receive a series of online surveys to capture their opinions about specific ELSI-related topics, such as NBS policy, residual dried blood spot retention, and the types of disorders that should be on NBS panels. ScreenPlus has developed a stakeholder-based, collective funding model that includes federal support in addition to funding from 14 advocacy and industry sponsors, all of which have a particular interest in NBS for at least one of the ScreenPlus disorders. Taken together, ScreenPlus is a model, multi-sponsored pilot NBS program that will provide critical data about NBS for a broad panel of disorders, while gathering key stakeholder opinions to help guide ethically sensitive decision-making about NBS expansion.

Short-term outcomes of infants born to mothers with SARS-CoV-2 infection.

OBJECTIVE: The rate of transmission of SARS-CoV-2 from mothers to infants in the peri- and post-natal period remains an area of ongoing investigation. This study aims to determine rates of development of clinically significant COVID-19 disease within 1 month among infants born to symptomatic and asymptomatic SARS-CoV-2 positive mothers. MATERIALS AND METHODS: This was a single-center, retrospective cohort study of all infants born to SARS-CoV-2 positive mothers who were admitted to the Well Baby Nursery (WBN) at New York University Langone Hospital-Brooklyn from 23 March-23 September 2020. Infants born to asymptomatic mothers were allowed to room-in, while infants born to mothers with symptoms of SARS-CoV-2 were isolated and discharged home to an alternate primary caregiver. A phone follow-up program contacted mothers at 2 weeks and 1 month post discharge to inquire about newborn symptoms, maternal symptoms, personal protective equipment (PPE) usage, and any presentations to care. Medical records were also reviewed for clinic and hospital visits to determine if exposed infants developed any symptoms following discharge. RESULTS: Of 1903 deliveries during the study period, 131 mothers (21 symptomatic, 110 asymptomatic) tested positive for SARS-CoV-2 and had infants admitted to the WBN. 57 infants (21 born to symptomatic mothers, 36 born to asymptomatic mothers) were tested prior to discharge, and none were positive. 121 of 133 infants had at least 1 follow up call in the study period. Of these, 31 had symptoms potentially concerning for SARS-CoV-2 infection or Multisystem Inflammatory Syndrome in Children, and 19 presented to medical care for these symptoms. 4 infants had SARS- CoV-2 testing after discharge, and none were positive. 2 infants were admitted to the hospital for fever but neither had a positive SARS-CoV-2 result. 65% of mothers reported always adhering to PPE recommendations. CONCLUSION: Our results suggest that infants born both to symptomatic and asymptomatic mothers are unlikely to develop clinically significant COVID-19 disease in the peri- and post-natal periods.

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..

Horizontal Transmission of COVID-19 in a 24-Week Premature Infant and Post-discharge Follow-Up.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has rapidly spread across the globe. The clinical spectrum of infection with SARS-CoV-2 among the most vulnerable extremely premature patient population in the neonatal intensive care units (NICUs), particularly those with chronic lung disease (CLD), remains unclear. Additionally, post-COVID conditions have been described in children with limited published data among infants. Symptoms in children appear similar to those described in the adults. We report a case of SARS-CoV-2 infection in a 24-week preterm infant with CLD acquired via horizontal transmission while still in the NICU. We also provide follow-up data on patient until one year post-discharge. Our patient developed fever prompting testing for SARS-CoV-2. Although extremely premature infants with CLD are known to be at high risk for morbidities if they acquire respiratory viral infections, infection with SARS-CoV-2 in this case report presented with relatively mild clinical symptoms. He remained clinically stable on respiratory support (nasal cannula) with eventual weaning to room air. Our patient was followed until one year post-discharge (chronological age: 20 months) and had follow-up by various subspecialties for chronic lung disease, hypothyroidism, chronic kidney disease, and poor growth. We did not observe any specific post-COVID symptoms. This case illustrates that horizontal transmission of SARS-CoV-2 infection among extremely premature infants with CLD is possible in the NICU but likely presents with mild clinical symptoms during acute infection and less chances of post-COVID conditions. Additionally, this case highlights the need for adherence to infection prevention guidelines to prevent nosocomial transmission amid the ongoing pandemic.

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..

Characteristics of Hospitalized Children With SARS-CoV-2 in the New York City Metropolitan Area.

OBJECTIVES: To describe the characteristics of hospitalized children with severe acute respiratory syndrome coronavirus 2 in New York City metropolitan area. PATIENTS AND METHODS: This was a multicenter, retrospective cohort study at 4 hospitals comprising 82 hospitalized children (0-21 years) who tested positive for severe acute respiratory syndrome coronavirus 2 after symptoms and risk screening between March 1 and May 10, 2020. We subdivided patients on the basis of their admission to acute or critical care units and by age groups. Further subanalyses were performed between patients requiring respiratory support or no respiratory support. RESULTS: Twenty-three (28%) patients required critical care. Twenty-nine (35%) patients requiring respiratory support, with 9% needing mechanical ventilation, and 1 required extracorporeal support. All patients survived to discharge. Children with any comorbidity were more likely to require critical care (70% vs 37%, P = .008), with obesity as the most common risk factor for critical care (63% vs 28%, P = .02). Children with asthma were more likely to receive respiratory support (28% vs 8%, P = .02), with no difference in need for critical care (P = .26). Children admitted to critical care had higher rates of renal dysfunction at presentation (43% vs 10%, P = .002). CONCLUSIONS: Children with comorbidities (obesity and asthma in particular) were at increased risk for critical care admission and/or need for respiratory support. Children with renal dysfunction at presentation were more likely to require critical care.

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.

Neonate Born to a Mother with a Diagnosis of Suspected Intra-Amniotic Infection versus COVID-19 or Both.

A diagnosis of intra-amniotic infection is typically made based on clinical criteria, including maternal intrapartum fever and one or more of the following: maternal leukocytosis, purulent cervical drainage, or fetal tachycardia. The diagnosis can also be made in patients with an isolated fever of 39°C, or greater, without any other clinical risk factors present. Coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, has been noted to have varying signs and symptoms over the course of the disease including fever, cough, fatigue, anorexia, shortness of breath, sputum production, and myalgia. In this report, we detail a case of a newborn born to a mother with a clinical diagnosis of intra-amniotic infection with maternal fever and fetal tachycardia, who was then found to be SARS-CoV-2 positive on testing. Due to the varying presentation of COVID-19, this case illustrates the low threshold needed to test mothers for SARS-CoV-2 in order to prevent horizontal transmission to neonates and to healthcare providers.

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.

Electrical Activity of the Diaphragm in a Small Cohort of Preterm Infants on Noninvasive Neurally Adjusted Ventilatory Assist and Continuous Positive Airway Pressure: A Prospective Comparative Pilot Study.

OBJECTIVE: To compare the electrical activity of the diaphragm (Edi) of premature infants placed on continuous positive airway pressure (CPAP) with the Edi of premature infants placed on noninvasive neurally adjusted ventilatory assist (NIV NAVA). The secondary aim was to evaluate the feasibility of the use of NIV NAVA mode in the busy tertiary neonatal unit. STUDY DESIGN: This was a prospective crossover pilot study of premature infants requiring noninvasive respiratory support. Infants were randomized to initially receive either CPAP/biphasic (group 1) or NIV NAVA (group 2) and were then crossed over to the alternate group. Continuous Edi signals were recorded for 24 h, with 12 h each on CPAP/biphasic, and NIV NAVA along with other clinical and respiratory parameters.  Results: Ten infants with a mean gestation age of 29 weeks (range 25-34 weeks) were enrolled, with a total cumulative Edi monitoring of 240 h. The average Edi peak on the biphasic/CPAP group (15.6 ± 7 mcV) was significantly higher (P < 0.005), compared to the Edi Peak on the NIV NAVA group (10.8 ± 3.3 mcV). The Edi min values were 3.23 ± 1.1 mcV, and 3.07 ± 0.5 mcV on CPAP/biphasic and NIV NAVA (P = 0.69) respectively. There were no significant differences in other clinical parameters between the two groups. No major adverse events were recorded during Edi catheter monitoring. CONCLUSION: The Edi peak values were significantly lower in NIV NAVA mode compared to CPAP/biphasic mode. The Edi catheter and NIV NAVA may also be used safely in premature infants.

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.