Multisystem inflammatory syndrome in neonates (MIS-N): a systematic review.

Recently, a new pattern of multisystem inflammatory syndrome following an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged globally. The initial cases were described in the adult population followed by sporadic cases in the pediatric population also. By the end of 2020, similar reports were recognised in the neonatal age group. The purpose of this study was to systematically review clinical characteristics, laboratory parameters, treatment, and outcomes of neonates with multisystem inflammatory syndrome in neonates (MIS-N). A systematic review was conducted after registering with PROSPERO and electronic databases including MEDLINE, EMBASE, PubMed, SCOPUS, Google Scholar, and Web of Science were searched from January 1st 2020 till September 30th 2022. A total of 27 studies describing 104 neonates were analysed. The mean gestation age and birth weight was 35.9 ± 3.3 weeks and 2255.7 ± 783.7 g respectively. A large proportion (91.3%) of the reported cases belonged to the South-East Asian region. The median age of presentation was 2 days (range: 1-28 days) with cardiovascular system being the predominant system involved in 83.65% followed by respiratory (64.42%). Fever was noted in only 20.2%. Commonly elevated inflammatory markers were IL-6 in 86.7% and D-dimer in 81.1%. Echocardiographic evaluation suggested ventricular dysfunction in 35.8% and dilated coronary arteries in 28.3%. Evidence of SARS-CoV-2 antibodies (IgG or IgM) was seen in 95.9% neonates and evidence of maternal SARS-CoV-2 infection, either as history of COVID infection or positive antigen or antibody test, was noted in 100% of the cases. Early MIS-N was reported in 58 (55.8%) cases, late MIS-N in 28 (26.9%), and 18 cases (17.3%) did not report the timing of presentation. There was a statistically increased proportion of preterm infants (67.2%, p < 0.001), and a trend towards increased low birth weight infants, in the early MIS-N group when compared to the infants with late MIS-N. Fever (39.3%), central nervous system (50%), and gastrointestinal manifestations (57.1%) were significantly higher in the late MIS-N group (p = 0.03, 0.02, 0.01 respectively). The anti-inflammatory agents used for the treatment of MIS-N included steroids 80.8% which were given for a median of 10 (range 3-35) days and IVIg in 79.2% with a median of 2 (range 1-5) doses. The outcomes were available for 98 cases, of whom 8 (8.2%) died during treatment in hospital and 90 (91.8%) were successfully discharged home.   Conclusion: MIS-N has a predilection for late preterm males with predominant cardiovascular involvement. The diagnosis is challenging in neonatal period due to overlap with neonatal morbidities and a high risk of suspicion is warranted, especially in presence of supportive maternal and neonatal clinical history. The major limitation of the review was inclusion of case reports and case series, and highlights need of global registries for MIS-N. What is Known: • A new pattern of multisystem inflammatory syndrome following SARS-CoV-2 infection has emerged in adult population with sporadic cases now being reported in neonates. What is New: • MIS-N is an emerging condition with a heterogeneous spectrum and has a predilection for late preterm male infants. Cardiovascular system is the predominant system involved  followed by respiratory, however fever remains an uncommon presentation unlike other age-groups. There are two subtypes based on timing of presentation, with early MIS-N being reported more in preterm and low-birth weight infants.

Favourable outcome of a severe bradyarrhythmia in a neonate: a case report.

We report the case of a term neonate with severe fetal bradycardia with an unusually benign clinical course with follow-up till infancy.

Th1 cytokine gene polymorphism and the corresponding plasma cytokine levels: A comparative study in HIV-1 positive and exposed uninfected infants.

The pro-inflammatory (Th1) cytokines namely interleukin (IL)-2, IL-6, IL-12, interferon (IFN)-γ, tumor necrosis factor-α (TNF-α) are vital in the clearance of HIV infection. This prospective cohort study aimed to evaluate the polymorphisms of Th1 cytokine genes and their corresponding plasma cytokine levels in HIV-1 positive and exposed uninfected (EU) infants born to HIV-1 positive mothers. CD4 count, viral load of HIV-1 positive mothers was done using commercially available reagents. Cytokine genotyping analysis and levels were done in 20 HIV-1 positive and 54 EU infants. The polymorphisms of Th1 cytokines were done using the PCR-SSP method. Plasma cytokine levels were estimated using Bio-Plex-Pro cytokine assay (BIO-RAD; USA). Results revealed treatment status of the mothers and viral load were the two confounding factors having a significant effect on HIV status of the infant. TNF-α GG genotype is significantly higher in EU infants as compared with HIV-1 positive infants. GG genotype was associated with high TNF- α levels in HIV-1 positive infants but the difference was not statistically significant. HIV-1 positive infants with -IFN-γ (+874) TT genotype was significantly associated with high IFN-γ levels. To the best of our knowledge, this is the first study reporting the role of Th1 cytokine gene polymorphisms and their corresponding plasma cytokine levels in HIV-1 positive and EU infants from India.

Post-INSURE Administration of Heated Humidified High-Flow Therapy Versus Nasal Continuous Positive Airway Pressure in Preterm Infants More Than 28 Weeks Gestation with Respiratory Distress Syndrome: A Randomized Non-Inferiority Trial.

In preterm infants with respiratory distress syndrome (RDS), non-invasive ventilation (NIV) is usually provided using nasal continuous positive airway pressure (NCPAP) or non-invasive mechanical ventilation after surfactant administration by INtubation-SURfactant-Extubation (INSURE) method. Heated humidified high-flow nasal cannula (HHHFNC) is a mode of NIV with advantages of ease of application, less grades of nasal injury and easy handling. This study was done to compare the effectiveness of HHHFNC therapy administration as post-INSURE respiratory support in preterm infants as compared to NCPAP. The primary outcome was to compare the rate of treatment failure within 7 days of randomization to HHHFNC or NCPAP as a post-INSURE ventilatory modality. It was a pilot trial wherein all preterm infants more than 1 kg and more than 28 weeks gestational age with RDS who required surfactant were randomized to receive NCPAP or HHHFNC. Infants with an urgent need for intubation and mechanical ventilation were considered to have treatment failure. Thirty babies were enrolled-15 in each group. Baseline demographic characteristics were comparable. There was no significant difference in the primary outcome of early failure rate, i.e. mechanical ventilation rate within 7 days of starting treatment. There were no significant differences in other outcomes except nasal injury which was significantly lesser in the HHHFNC group. In conclusion, HHHFNC appears to be non-inferior to NCPAP when used in preterm infants more than 28 weeks gestation with RDS as a post-INSURE ventilatory modality.

A single-center observational study on clinical features and outcomes of 21 SARS-CoV-2-infected neonates from India.

Coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an ongoing pandemic with significant morbidity and mortality. Neonates represent a vulnerable population, in which we have limited knowledge of its natural history, optimal management, and outcomes. In this retrospective observational study from a low-middle-income setting, clinical characteristics and outcomes of neonatal SARS-CoV-2 infection were evaluated. We report an incidence of 10.6% of SARS-CoV-2 infection (21 neonates), among a group of 198 neonates with suspected infection. Most of the SARS-CoV-2-infected neonates were term (80.9%) and none required any resuscitation. The infection was detected by a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2. Neonatal COVID-19 manifestations developed in one-third (33.3%) of the infected neonates. Most of them demonstrated the involvement of respiratory (33.3%) and gastrointestinal systems (4.8%). Laboratory parameters suggested multi-systemic involvement, with elevated creatine kinase (CK) (76.2%), creatine kinase-myocardial band (CK-MB) (76.2%), and lactate dehydrogenase (LDH) (71.4%) levels. Supportive treatment was given to infected neonates with intensive care required in six neonates (28.6%). This included four preterm and two term neonates, of which two received non-invasive and one received invasive ventilation with intra-tracheal surfactant instillation. IgM antibodies against COVID-19 were detected in one neonate. All neonates with COVID-19 improved and were successfully discharged.Conclusion: SARS-CoV-2 in neonates has a wide clinical spectrum. Further studies are needed which are adequately powered to completely understand the course of this infection in neonates, its implications not only in the neonatal period but also on long-term follow-up. What is Known: • SARS-CoV-2 infection has a predilection for all age groups but with limited literature on clinical profile, outcomes, and long-term follow-up in neonates. What is New: • SARS-CoV-2 infection in neonates has a wide clinical spectrum and displays a significant overlap with common neonatal conditions. • Most neonates with COVID-19 improved with supportive care, though a subset required intensive care, emphasizing the need for cautious monitoring and management.

Correlation of haematological parameters and C-reactive protein between cord blood and first post-natal blood sample in preterm neonates: A prospective observational study.

AIM: There is some recent evidence on the utility of the cord blood as a reliable source for admission complete blood count in preterm neonates. However, there is a need to validate other laboratory parameters from the cord blood such as C-reactive protein (CRP) to rule out neonatal sepsis. The present study was carried out to evaluate the correlation between haematological parameters and CRP obtained from the cord blood to the first post-natal blood sample, for it to be considered as a reliable alternative. METHODS: A total of 89 paired cord blood and first post-natal blood samples were prospectively analysed to assess the haematological parameters (complete blood count) and CRP. Pearson's coefficient was calculated to assess the correlation between the cord blood and the first post-natal blood sample. RESULTS: When Pearson's correlation coefficient was calculated for various haematological parameters, it showed good correlation coefficient of 0.84 for total leukocyte count, 0.84 for absolute neutrophil count count, 0.87 for immature to total neutrophil ratio and 0.95 for CRP. The correlation coefficient was 0.64 for haemoglobin and 0.36 for platelet count. CONCLUSION: There is a strong correlation between the majority of haematological parameters and CRP obtained from the cord blood with the first post-natal blood sample in preterm neonates, except the platelet count. Hence, umbilical cord blood is a feasible and reliable alternative source for assessment of haematological parameters and CRP for the first post-natal blood sample, thereby avoiding a painful prick in these fragile preterm neonates.

Anti-retroviral therapy failure in HIV-1 infected pregnant women and its associated risk of HIV transmission.

BACKGROUND: The HIV perinatal transmission in India even after interventions is still high. The anti-retroviral therapy failure rate and the risk of HIV vertical transmission to infants from women with failed treatment during pregnancy also largely remains unevaluated. METHODS: This is a prospective, observational and follow-up study of 18 months to determine the association of ART failure in pregnant women and the subsequent risk of HIV transmission to their infants. A total of 81 mothers were evaluated for ART success/failure by analysing their viral loads. RESULTS: Analyses revealed that a high percentage (19.75%) of women on ART had high viral loads, while the overall HIV transmission rate to the infants was 8.64%. The rate of transmission from women with high viral load was significantly high compared to women with low viral load (37.5% vs. 1.54%; p = 0.0015). CD4 level was not associated with HIV transmission. However, CD4 levels in women, who had successful or failed ART, were significantly different (p = 0.0031). Factors such as mother's age, baby's sex and weight as well as delivery mode were not associated with HIV transmission, however, breastfeeding and viral loads were found to be independently associated with HIV transmission to the neonates. CONCLUSIONS: This study highlights that a significant proportion of women on ART had impaired viral load control. The rate of HIV transmission to infants was also significantly high among these women. This warrants viral load monitoring of HIV infected women to reduce the overall transmission to the infants.

Is Routine Monitoring for Hypoglycemia Required in Intramural Asymptomatic Infant of Diabetic Mother? An Audit in a Tertiary Care Hospital.

AIMS: This retrospective audit aimed to analyze whether routine frequent monitoring for hypoglycemia is required in asymptomatic infant of diabetic mother born in tertiary care hospital. METHODS: The study analyzed the blood sugar level of 196 infants of diabetic mothers. RESULTS: The overall incidence of hypoglycemia from 196 study participants was 9.18% (N = 18). The incidence of hypoglycemia at 2 h of life was maximum (83.33%) and it was significant when compared to 3, 6, 9 and 12 h (p < 0.0001). Blood glucose levels were significantly more at 6 (p = 0.0002)), 9 (p = 0.0001) and 12 h (p = 0.0001) when compared to glucose level at 2 h except at 3 h of life (p = 0.062). Similarly blood glucose at 9 (p = 0.0001) and 12 h of life (p = 0.0002) were significantly more than at 3 h of life. Blood glucose at 9 h was significantly more than at 6 h of life (0.032) and at 12 hours of life (p = 0.0237) was significantly higher than at 6 h of life. CONCLUSION: The frequent blood glucose monitoring for hypoglycemia in infant of diabetic mother as per American Academy of Pediatrics may be reduced as per the findings in our study. However, this needs to be confirmed by a properly designed observational study/adequately powered randomized controlled trial.

Red Cell Distribution Width (RDW): Normative Data in Indian Neonates.

Red cell distribution width (RDW) is altered because of prematurity and fetal growth restriction (FGR). We conducted a prospective observational study to determine normal RDW values in Indian neonates (N=964) with significant FGR. Mean RDW values in preterm neonates were higher than term neonates (P<0.0004). The RDW values in Indian neonates (with significant FGR) were higher than their western counterparts (P<0.0001). The mean RDW values for different gestational ages in Indian neonates are higher than those observed in other studies. This could be attributable to the FGR component among Indian neonates.

Effect of different methods of pasteurization on bactericidal action of human milk: A prospective observational study.

Background & objectives: Pasteurization involves not only inactivation of pathogens, but also loss of immunological functions and bactericidal action of human milk. Hence, this study was aimed to explore the stability of such bactericidal action after subjecting human milk samples to thermal pasteurization under different condition of time and temperature. Methods: In this observational study 48 human milk samples were analyzed over a period of three months. The effect of holder and flash methods of pasteurization on bactericidal action against Escherichia coli was evaluated compared to the control sample before and after 72 h of storage at -18°C. Results: Both holder and flash methods of pasteurization showed significant reduction in the E. coli growth to 46.4 and 25.5 per cent, respectively, after 24 h of incubation (P <0.001). The bactericidal activity was significantly more in samples subjected to holder method compared to flash method before and after 72 h of storage (46.41±15.38 vs. 25.50±30.74, P <0.001 and 42.27±20.38 vs. 18.33±28.55, P <0.001). Interpretation & conclusions: Our results showed that the bactericidal activity of human milk was better preserved by the holder method of pasteurization. Further well-powered and well-designed randomized trials are needed to confirm the findings.

Placental Findings in Singleton Stillbirths: A Case-control Study.

Aims: This prospective observational study compared placental lesions of stillbirth cases and live birth controls, and aimed to determine the cause of stillbirth. Methods: The study enrolled 85 stillbirths and 85 live births at the time of delivery. Results: There was significantly increased incidence of placental abruption (p = 0.005) and gestational diabetes (p = 0.032) in mothers with stillbirths. Histopathological examination of placenta was significantly abnormal in stillbirths compared with live births (p = 0.004). Delayed villous maturation was significantly more in stillbirths (38.82 vs. 16.47%; p = 0.002). Acute (30.59 vs. 16.47%; p = 0.04) and chronic diffuse villitis (16.47 vs. 4.7%; p = 0.02), chorionic plate acute vasculitis (28.235 vs. 14.11%; p = 0.04) were significantly more in stillbirths. Foetal vascular thrombi in the chorionic plate (30.58 vs. 14.12%; p = 0.02) and avascular villi (24.7 vs. 8.23%; p = 0.006) were significantly more in stillbirths. Conclusion: These abnormal placental patterns could provide information about the etiopathogenisis in stillbirths of unknown aetiology.

Polymorphisms in TH1-TH2 cytokine and receptor genes associated with risk of vertical HIV transmission, in Mumbai, India.

BACKGROUND: Vertical HIV transmission does not occur in all exposed infants. Many infants remain HIV uninfected even after exposure. This is partly attributed to the host genes involving cytokine production, which is rarely documented in vertical transmission. METHODS: Here, an observational cohort study evaluated whether polymorphisms in cytokine, receptor and antagonist genes are associated with perinatal HIV transmission. Single nucleotide polymorphism (SNP) genotyping was performed via the polymerase chain reaction with sequence-specific primers method. Haplotype block structure was determined and statistical analysis was performed using appropriate software in each case. RESULTS: Twenty-two SNPs were analysed in 30 seropositive and 61 seronegative children. Confounding factors such as mother's viral load, treatment regimen, breast feeding options, etc., were documented. Analysis revealed the association of two SNPs: IL1R1 (rs2234650) and TNFA (rs1800629) with vertical HIV transmission. CT genotype at IL1R1 was observed at a higher frequency in positive children (76.66% versus 42.62%, p = 0.002), whereas the CC genotype was significantly increased in exposed uninfected children (47.54% versus 16.66%, p = 0.004). Similarly, the GG genotype of TNFA was significantly higher in uninfected children compared to infected ones (76.66% versus 46.66%, p = 0.005), whereas the GA genotype frequency was higher among infected children (53.33% versus 21.66%, p = 0.003). The frequency of the 'G' allele of TNFA and 'C' allele of IL1R1 was significant (p = 0.018) in negative children. Haplotypes of SNPs belonging to IL1, TNFA and IL4 were also found to associate with transmission. CONCLUSIONS: The present study confirms the association of SNPs IL1R1 (rs2234650) and TNFA (rs1800629) with the risk of vertical transmission. These SNPs can be exploited as possible predictive markers of HIV transmission.

Effect of Expressed Breast Milk versus Swaddling versus Oral Sucrose Administration on Pain Associated with Suctioning in Preterm Neonates on Assisted Ventilation: A Randomized Controlled Trial.

OBJECTIVE: The objective of our study was to assess the pain associated with suctioning in preterm neonates on assisted ventilation and comparing the use of expressed breast milk (EBM), sucrose, and swaddling to alleviate pain. METHODS: Study design: A randomized controlled clinical trial. INCLUSION CRITERIA: Preterm neonates on assisted ventilation. EXCLUSION CRITERIA: Major congenital anomalies and severe encephalopathy. STUDY DURATION AND SITE: 6 months in level III neonatal Intensive Care Unit. In the first phase, we used premature infant pain profile (PIPP) score to assess pain associated with suctioning in preterm neonates on assisted ventilation. In the second phase, the effect of EBM, swaddling, and sucrose on pain relief during suctioning in neonates on assisted ventilation was assessed. RESULTS: There was a significant increase in pain associated with suctioning in preterm neonates on assisted ventilation (preprocedure PIPP score 7.90 ± 2.50; procedural PIPP score 13.63 ± 2.57; P < 0.05). The postintervention mean procedural PIPP score was not significantly different between the EBM, swaddling, and sucrose groups (P = 0.24). CONCLUSIONS: Suctioning is painful for preterm neonates on assisted ventilation. There was no difference between EBM, swaddling, and sucrose in relieving pain associated with suctioning.

Comparison of Neonatal Pain, Agitation, and Sedation Scale with Premature Infant Pain Profile for the Assessment of Acute Prolonged Pain in Neonates on Assisted Ventilation: A Prospective Observational Study.

AIM: This study aimed to compare Neonatal Pain, Agitation, and Sedation Scale (N-PASS) with Premature Infant Pain Profile (PIPP) for the assessment of acute prolonged pain in ventilated neonates. METHODS: This study was conducted in two phases. In phase 1 of the study, we assessed whether neonates on assisted ventilation experienced acute prolonged pain. In phase 2, the aim was to compare N-PASS with PIPP for the assessment of acute prolonged pain in neonates on assisted ventilation.. DESIGN: This is a prospective observational study. STUDY SETTING AND DURATION: This study was conducted at a tertiary care neonatal intensive care unit for 6 months. INCLUSION CRITERIA: Neonates on assisted ventilation for >48 h were selected for this study. EXCLUSION CRITERIA: Neonates with lethal congenital anomalies and severe encephalopathy were excluded from the study. N-PASS and PIPP tools were used to assess acute prolonged pain in ventilated neonates. Taking PIPP as gold standard and N-PASS as a new test, the correlation coefficient was calculated. The sensitivity, specificity, positive predictive value, and negative predictive value were also computed. The time taken to administer the tools was also computed. RESULTS: The average PIPP score for ventilated neonates was 8.33. The correlation coefficient of N-PASS when compared to PIPP was 0.62. The average time taken to apply the N-PASS scale was 4.42 min as compared to 8.20 min for PIPP scale. In term neonates, the sensitivity, specificity, positive predictive value, and negative predictive value of N-PASS were 75%, 100%, 100%, and 60%, respectively. The corresponding values in preterm neonates were lesser. CONCLUSIONS: The study proves that neonates on assisted ventilation experience acute prolonged pain. N-PASS is clinically reliable and valid to assess acute prolonged pain in ventilated term neonates. The N-PASS is quicker than PIPP in assessing acute prolonged pain in ventilated neonates. FUTURE DIRECTIONS: The modified N-PASS tool (including the gestational age) should be developed.

Diversity in KIR gene repertoire in HIV-1 exposed infected and uninfected infants: A study from India.

Natural killer (NK) cells have antiviral activity mediated through killer immunoglobulin receptors (KIRs). Studies have shown the importance of KIR receptors in HIV infection. However reports on association of KIR genes in HIV infection from Indian population are limited, not a single study is reported in HIV exposed uninfected (EU) and infected infants. This study compared the KIR gene repertoire of HIV-1 positive (n = 29) with EU (n = 76) infants to elucidate its association with transmission. KIR genotyping was analysed using the PCR-SSP method. Viral load of mothers, CD4 count of both mothers and infected infants were done using commercial kits. The data was analysed using SPSS software. Results revealed presence of significantly high frequencies of activating gene KIR 2DS5 (P = 0.040) and inhibitory gene KIR 2DL3 (P = 0.013) in EU infants as compared to HIV-1 positive infants, confirmed with multivariable linear regression modelling. Fifty-nine KIR genotypes were identified in these 105 infants. Nine genotypes were unique, reported for the first time. Twenty six genotypes were shared with the World populations. Twenty four genotypes were reported for the first time from India. Specific KIR genotype combinations (GIDs) were exclusively present either in HIV-1 positive (n = 19) or in EU infants (n = 30). The Linkage disequilibrium (LD) analysis shows a strong linkage between four pairs of genes in HIV-1 positive and three pairs of genes in EU infants. In conclusion, this study revealed that, besides maternal confounding factors such as ART and viral load, specific KIR genes are associated independently with perinatal HIV infection.

An audit of colistin use in neonatal sepsis from a tertiary care centre of a resource-limited country.

BACKGROUND & OBJECTIVES: Sepsis due to multidrug-resistant Gram-negative pathogens is a challenge for clinicians and microbiologists and has led to use of parenteral colistin. There is a paucity of data regarding safety and efficacy of intravenous colistin use in neonates. The objective of this retrospective analysis was to study the efficacy and safety of intravenous colistin in the treatment of neonatal sepsis. METHODS: An audit of the data from neonates, admitted to a neonatal intensive care unit of a tertiary care hospital during January 2012 to December 2012, and who received intravenous colistin was carried out. RESULTS: Sixty two neonates received intravenous colistin (52 preterm and 10 term) for the treatment of pneumonia, bloodstream infections and meningitis. The isolated pathogens in decreasing order of frequency were Acinetobacter baumannii, Klebsiella pneumonia and Pseudomonas aeruginosa. Of the total 62 neonates, 41 (66.12%) survived and 21 (33.87%) died. Significantly higher mortality was observed in neonates with lower body weights (P < 0.05). A significant association of mortality was found in those with sepsis due to Klebsiella species. Only one of seven with this infection survived as against 15 of the 23 who grew other organisms [P = 0.03; crude odds ratio = 11.25 (1.2, 110.5)]. None of the neonates developed neurotoxicity or nephrotoxicity. INTERPRETATION & CONCLUSIONS: This retrospective study in neonates with sepsis showed that intravenous colistin was safe and effective in the treatment of neonatal sepsis. Further, well-controlled, prospective clinical trials need to be done to corroborate these findings.

Genetic variation in the promoter region of pro-inflammatory cytokine TNF-α in perinatal HIV transmission from Mumbai, India.

Various host factors such as cytokines and HLA, regulate the immune system and influence HIV transmission to infants exposed to HIV-1 through their mothers. Tumor Necrosis Factor Alpha (TNF-α) is a strong pro-inflammatory mediator and thought to influence vulnerability to HIV infection (and/or) transmission. Polymorphisms in regulatory regions are known to govern the production of this cytokine. However, the association of these variations in perinatal HIV transmission is yet to be established. Present study aimed to evaluate if polymorphisms in promoter region of TNF-α gene is associated with perinatal HIV transmission. With informed consent from parents, infants' blood was collected for HIV screening and SNPs analysis at 2 loci: TNF (rs1800629) and TNF (rs361525) using PCR-SSP method. HIV positive (n = 27) and negative (n = 54) children at the end of 18th month follow up were considered for this study. GG genotype, responsible for low expression of TNF (rs1800629) was significantly (p = 0.005) higher in uninfected children, while higher GA genotype frequency was observed in infected children. The 'G' allele frequency was significantly higher in negative children (p = 0.016). We conclude that genotypic variants of TNF (rs1800629) are a likely contributor to perinatal HIV transmission. This provides new insights in markers of differential susceptibility to perinatal HIV transmission.

Long-Term Growth and Neurodevelopmental Outcomes of Neonates Infected with SARS-CoV-2 during the COVID-19 Pandemic at 18-24 Months Corrected Age: A Prospective Observational Study.

INTRODUCTION: During the early coronavirus disease (COVID-19) pandemic in 2020, researchers cautioned about the potential neuroinvasive capability of the virus and long-term neurological consequences. Although a few preliminary studies have found delayed communication, fine motor, and problem-solving skills in infants after COVID-19 infection, there continues to be a paucity of data on long-term development of neonates diagnosed with COVID-19. METHODS: We conducted a prospective study of 20 neonates who acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first wave of the pandemic (April-July 2020). At 18-24 months corrected age, we assessed neurodevelopment by Bayley Scales of Infant and Toddler Development, the third edition (BSID-III), along with growth, hearing, and vision evaluation. RESULTS: The mean corrected age at assessment was 21 months 11 days ± 1 month 28 days. We found developmental delay in nearly half of the children with scores below one standard deviation in either of the BSID-III domains. Mild delay in either motor, cognitive, or language domains was found in 9 (45%) children and moderate delay in 2 (10%). Expressive language, fine motor, and receptive language were predominantly affected. None of the children had hearing impairment, blindness, or significant growth faltering including clinically severe microcephaly. The mean composite cognitive, language, and motor scores were significantly lower in those with neurodevelopmental delay (p value - 0.02, 0.000, and 0.03, respectively) without any differences in their disease characteristics. CONCLUSION: Neonates infected with SARS-CoV-2 have an increased risk of developmental delays in expressive language, fine motor, and receptive language skills at 18-24 months of age. The severity of delays is predominantly mild.

Risk Calculator for Bronchopulmonary Dysplasia in Preterm Neonates: A Prospective Observational Study.

OBJECTIVES: To determine the incidence, risk factors, and accuracy of a previously published risk estimator in predicting Bronchopulmonary dysplasia (BPD) in a very preterm cohort from India. METHODS: A single-center prospective observational study was conducted in preterm neonates born at 23-30 wk of gestation with a birth weight of 501-1249 g. The incidence and risk factors of BPD were evaluated, and the accuracy of BPD prediction at six pre-specified time points using the National Institute of Child Health and Human Development (NICHD) BPD risk estimator was assessed by comparing the estimated risk with the observed rates. RESULTS: A total of 310 neonates with mean gestation age of 28.7±1.5 wk and birth weight of 1023.6±171.4 g were enrolled in the study. The study cohort had 49.7% males and 32.3% neonates requiring resuscitation. Any BPD was observed in 54 (17.4%) neonates with severity being mild, moderate, and severe in 29 (53.7%), 17 (31.5%), and 8 (14.8%) neonates respectively. Hundred (32.3%) neonates died before discharge from the hospital. Sepsis, patent ductus arteriosus, retinopathy of prematurity, intraventricular hemorrhage, and blood transfusion were significant risk factors for the development of BPD. The calculator was accurate for the prediction of death or moderate-severe BPD on days 1 and 3 with the area under the curve of 0.82 and 0.77 respectively. CONCLUSIONS: The NICHD BPD estimator helped to accurately predict moderate-severe BPD early in Indian preterm infants.

A Quality Improvement Initiative to Increase the Milk Donation to the Human Milk Bank Post-Coronavirus Disease-19 Pandemic.

Background and Objective: Donor human milk (DHM) from the human milk bank (HMB) is the next best alterative in circumstances when mother's own milk is not available. There was a steep decline in the volume of DHM collected during the coronavirus disease-19 (COVID-19) pandemic due to various factors, while DHM demand increased. Hence, a quality improvement (QI) study was conducted to increase the volume of milk donation to HMB from postpandemic baseline of 300-400 to 1,000 mL/day over 8 weeks. Materials and Methods: Fish bone analysis was used to identify the potential barriers, and four Plan-Do-Study-Act (PDSA) cycles were conducted from January 2021 to March 2021 to address the key barriers. In the first PDSA cycle, training of health care providers was done. Sessions for educating mothers in the second PDSA cycle and individualized one-to-one counseling of mothers by a mother support group were done in the third PDSA cycle. The availability of breast pump was increased in the fourth PDSA cycle. Sustainability of the interventions was studied for 6 months and data were analyzed. Results: The average DHM collected per day at the end of each PDSA cycle was 900, 1,500, 1,000, and 1,100 mL. Although the sustenance phase was affected by the second COVID-19 wave, prompt identification of the issues and timely interventions prevented the donated volume from dropping to preintervention levels. Conclusion: QI initiatives customized for local settings can result in significant improvement in voluntary milk donation in HMB, which can result in more availability of DHM to premature babies.