Faculty Bibliography

OBJECTIVE:To assess the impact of separation of SARS-CoV-2 PCR-positive mother-newborn dyads on breastfeeding outcomes. STUDY DESIGN/METHODS:This is an observational longitudinal cohort study of SARS-CoV-2 PCR-positive mothers and their infants at three NYU Langone Health hospitals from March 25, 2020 through May 30, 2020. Mothers were surveyed by telephone regarding pre-delivery feeding plans, in-hospital feeding, and home feeding of their neonates. Any change prompted an additional question to determine whether this change was due to COVID-19. RESULTS:Of the 160 mother-newborn dyads, 103 mothers were reached by telephone, and 85 consented to participate. No significant difference was observed in pre-delivery feeding plan between the separated and unseparated dyads (P = .268). Higher rates of breastfeeding were observed in the unseparated dyads compared with the separated dyads in the hospital (p<0.001), and at home (p=0.012). Only two mothers in each group reported expressed breast milk as the hospital feeding source (5.6% of unseparated vs 4.1% of separated). COVID-19 was more commonly cited as the reason for change among the separated compared with the unseparated group (49.0% vs 16.7%, p<0.001). When dyads were further stratified by symptom status into four groups (asymptomatic separated, asymptomatic unseparated, symptomatic separated, and symptomatic unseparated), results remained unchanged. CONCLUSION/CONCLUSIONS:In the setting of COVID-19, separation of mother-newborn dyads impacts breastfeeding outcomes, with lower rates of breastfeeding both during hospitalization and at home following discharge compared with unseparated mothers and infants. No evidence of vertical transmission was observed; one case of postnatal transmission occurred from an unmasked symptomatic mother who held her infant at birth.

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.

BACKGROUND: Pediatric HIV has evolved from a pre-antiretroviral era (pre-1989 or Pre-ART) to an antiretroviral (ART) era (1989-1996) & to a highly active antiretroviral therapy (HAART) era (post-1996). As we have passed the 3rd decade following these individuals, we thought it useful to review clinical, laboratory, & social outcomes. METHODS: A retrospective, cross-sectional study of 399 children infected perinatally. They were divided into Pre-ART, ART & HAART groups. A Kaplan-Meier plot was constructed. 179 have been lost to follow-up at an average of 7.6 (0.3-27.6) years. RESULTS: Approximately 40, 80 and 90% of individuals in the Pre-ART, ART and HAART groups have long-term survival. 121 died at an average of 5.1 (0-26.1) years. Pre-ART, ART, & HAART groups had mean most recent CD4% values (+/-SEM) of 16.74(1.09), 22.97(0.96) & 33.07 (2.09), respectively (p<0.001). Pre-ART RNA is limited in that era and present if they survived to another era. In this group the median RNA values in those who died (311,300, n=16) was greater than in survivors (19,402, n=45). 43 % of the individuals in the ART group 77% of individuals in the HAART group had most recent HIV RNA<400 copies/ml.18 individuals >18 years of age have only a grade school or no education. 55 have graduated high school or received an equivalency diploma. 23 more have completed college. Nadir & recent CD4% of those who did & did not complete high school was equivalent to college graduates. 16 survivors (1/2 male) have had 18 uninfected children. CONCLUSIONS: This first long term follow-up study demonstrates remarkable survival and social skills of our patients.

Children younger than 18 years account for a substantial proportion of patients with tuberculosis worldwide. Available treatments for paediatric drug-susceptible and drug-resistant tuberculosis, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxic effects, and an overall scarcity of suitable child-friendly formulations. Several new drugs and regimens with promising activity against both drug-susceptible and drug-resistant strains have entered clinical development and are either in various phases of clinical investigation or have received marketing authorisation for adults; however, none have data on their use in children. This consensus statement, generated from an international panel of opinion leaders on childhood tuberculosis and incorporating reviews of published literature from January, 2004, to May, 2014, addressed four key questions: what drugs or regimens should be prioritised for clinical trials in children? Which populations of children are high priorities for study? When can phase 1 or 2 studies be initiated in children? What are the relevant elements of clinical trial design? The consensus panel found that children can be included in studies at the early phases of drug development and should be an integral part of the clinical development plan, rather than studied after regulatory approval in adults is obtained.

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.

SETTING: Recent reports indicate a role of chemokine inducible protein 10 (IP-10) in Mycobacterium tuberculosis infection substantiated by the detection of elevated levels in plasma and at infection foci in individuals infected with M. tuberculosis. OBJECTIVE: To evaluate IP-10 as a potential marker for the diagnosis of M. tuberculosis infection in children living in a region of low tuberculosis (TB) prevalence. DESIGN: IP-10 levels were obtained after whole blood stimulation with M. tuberculosis-specific antigens in 127 children. IP-10 results were evaluated upon gradations of exposure risk to M. tuberculosis and correlation with tuberculin skin test and an interferon-gamma release assay (IGRA). RESULTS: IP-10 reactivity correlated well to risk of exposure to M. tuberculosis in children. There was a strong correlation between IP-10 and IGRA results. IP-10 responses, unlike interferon-gamma (IFN-gamma), were not age-dependent and detected more positive results in children aged <5 years. In the children with active disease, the IGRA was more sensitive than IP-10 at detecting M. tuberculosis infection. CONCLUSION: Our findings suggest that IP-10 in combination with IFN-gamma may enhance the diagnostic performance of IGRAs in detecting M. tuberculosis infection, especially in young children

BACKGROUND: The QuantiFERON-TB Gold test was the first blood test to be approved for the diagnosis of latent tuberculosis infection. Although it has been shown to be sensitive and specific in adults, limited data on its performance in children are available. METHODS: This was a prospective study of children receiving health care in New York, New York. Each child was assessed for risk factors for Mycobacterium tuberculosis infection, underwent tuberculin skin testing, and had a QuantiFERON-TB Gold In-Tube test performed. The concordance between tuberculin skin test and QuantiFERON-TB Gold In-Tube test results was calculated, and the results were analyzed according to the likelihood of exposure to M tuberculosis. RESULTS: Data for 207 children with valid tuberculin skin test and QuantiFERON-TB Gold In-Tube test results were analyzed. There was excellent correlation between negative tuberculin skin test results and negative QuantiFERON-TB Gold In-Tube test results; however, only 23% of children with positive tuberculin skin test results had positive QuantiFERON-TB Gold In-Tube test results. Positive QuantiFERON-TB Gold In-Tube test results were associated with increased likelihood of M tuberculosis exposure, and interferon gamma levels were higher in children with known recent exposure to M tuberculosis, compared with children with older exposure histories. Younger children produced lower interferon gamma levels in response to the mitogen (phytohemagglutinin) control used in the QuantiFERON-TB Gold In-Tube test, but indeterminant results were low for children of all ages. Performance characteristics were similar across all age groups. CONCLUSION: The QuantiFERON-TB Gold In-Tube test is a specific test for M tuberculosis exposure in children, with performance characteristics similar to those for adults residing in regions with low levels of endemic disease. Concerns about test sensitivity, especially for children <2 years of age, will require additional prospective long-term evaluation