Short-term Outcome and Predictors of Survival Among Neonates With Moderate or Severe Hypoxic Ischemic Encephalopathy: Data From the Indian Neonatal Collaborative

Background: Among term and late preterm infants, hypoxic ischemic encephalopathy (HIE) is an important cause of mortality, and neurologic morbidity among survivors. Objective: The primary objective was to study the incidence of survival to discharge among late preterm and term infants with moderate or severe HIE. Secondary objectives were to explore variation in the management of HIE across participating sites and to identify the predictors of survival. Setting: Indian Neonatal Collaborative (INNC), a network of 28 neonatal units in India. Study design: Retrospective cohort. Participants: Late preterm (34-36 weeks) and term (37-42 weeks) infants with moderate to severe HIE from 2018-2019. Outcome: The primary outcome was survival to discharge (including discharged home and transfer to other hospital). A multivariate logistic regression model was constructed to identify the predictors of survival. Results: Of 352 infants with moderate or severe HIE, 59% received therapeutic hypothermia. Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE (aOR 0.04; 95% CI 0.02-0.10), persistent pulmonary hypertension (PPHN) (aOR 0.22; 95% CI 0.08-0.61) and requirement of epinephrine during resuscitation (aOR 0.21; 95% CI 0.05-0.84) were independently associated with decreased odds of survival to discharge. Conclusion: Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE, requirement of epinephrine during resuscitation and PPHN decreased the odds

Update to Perinatal-Neonatal Management of COVID-19 Guidelines

The guidelines for diagnosing and managing perinatal SARS-CoV-2 infection for the Indian context were last updated in May 2020. Newer evidence, the evolution of the pandemic, and its significant impact on mother-infant dyads led us to review and revise the guideline. This article summarizes the salient changes inthe perinatal-neonatal management of COVID-19.

Oral nifedipine versus nitroglycerine patch for tocolysis in preterm labour

Background: Preterm delivery is a major cause of neonatal mortality and morbidity. Various modalities have been used to prediction of patient at risk of preterm labor. But due to multi-factorial etiology these predictors are not always useful. Tocolysis has a major role in arresting preterm labor. The purpose of this study was to compare the safety and efficacy of oral nifedipine with transdermal nitroglycerine in the inhibition of preterm labour.Methods: This single blinded randomized control trial was conducted in the labour room of department of Obstetrics and Gynecology from January 2011 to June 2012. One hundred women with singleton pregnancy between 28 weeks to 34 weeks preterm labour and no contraindication for tocolysis were enrolled in the study. After taking the informed consent subjects were randomized into two groups. Randomization was done by random number table. Fifty-one subjects in nifedipine group received oral nifedipine (Tab Depin 10mg). Forty-nine subjects receiving transdermal nitroglycerine patch (Nitroderm Patch 10) were included in NTG group. The variables analysed were delay in delivery for 48 hours, 7 days or more than 7 days, period of gestation at delivery and side effect profile of drugs.Results: The percentage of women delivering after 48hours of administration of nifedipine group (52.9%) and nitroglycerine group (53.1%). Failure of tocolysis, defined as delivery within 48 hours, with nitroglycerine group (32.7 %) was comparable to nifedipine (33.3 %). Headache was significantly higher in nitroglycerine group as compared to nifedipine group (p≤0.001). Maternal tachycardia was more common in nifedipine group compared to NTG group (p=0.001).Conclusions: Oral nifedipine and transdermal nitroglycerine have similar efficacy as tocolytic agent in patients with preterm labour.

Quality Improvement Collaborative for Preterm Infants in Healthcare Facilities

Across all healthcare settings, it is important not only to provide safe and effective healthcare, but also to ensure that it is timely, patient-centered, efficient and equitable. There is a wide variability in neonatal and perinatal outcomes in India and other developing countries,with certain units demonstrating clinical outcomes that match the developed world, while others showing higher than expectedmortality and morbidity. Collaborative quality improvement initiatives offer a pragmatic way to improve performance of healthcaredelivery within and between neonatal units. Variations in application of evidence-based healthcare process and dependent healthoutcomes can be identified and targeted for improvement in quality improvement cycles. We herein describe the concept ofCollaborative quality improvement, and the success stories of the best-known Collaborative quality improvement initiatives across theworld. We also highlight the process and progress of creating Collaborative quality improvement in our country.

Development of Quality Measures in Perinatal Care – Priority for Developing Countries

The ‘Every Newborn Action Plan’ envisions to end preventable newborn deaths and stillbirths by 2035. One important objective to realizethis vision is improvement in quality of maternal and neonatal healthcare. Monitoring the performance of the healthcare systems andconducting quality improvement activities need reliable systems for data collection, analysis and interpretation. Measures chosen tomonitor quality are about problems accounting for a significant health burden, for which effective interventions are available, there isevidence of variable or substandard care, and for which improvement can be undertaken by stakeholders. Data can be collected aboutsafety, effectiveness, efficiency, equity, patient-centeredness and timeliness of care. These data can be collected by direct observation,from existing records, and by interview of the involved stakeholders. Healthcare facilities and governments need to identify core sets ofquality of care indicators, regularly measure and track their performance and carry out informed quality assurance and qualityimprovement efforts

Neonatal Dengue With Enterococcus Sepsis

Dengue infection is possible in all the three trimesters of pregnancy and is associated with various maternal and neonatal complications. The occurrence of subclinical infections may lend further confusion to the situation. Here, we report a case of neonatal dengue diagnosed with dengue NS1 antigen positive and IgM positive followed by secondary sepsis with Enterococcus faecium. Case studies like these may contribute to increased awareness of the suspicion of the associated life-threatening infections that can occur with neonatal dengue, their manifestations, and the management, thus improving their outcome.

Neonatologist’s Viewpoint.

Summary In this trial, 200 mothers, who were positive for hepatitis-B e antigen (HBeAg) and who had hepatitis-B virus (HBV) DNA level >200,000 IU/mL, were randomly assigned to receive usual care without antiviral therapy or to receive tenofovir (TDF) at an oral dose of 300 mg/d from 30 to 32 weeks of gestation until postpartum week 4; the participants were followed until postpartum week 28. All the infants received immunoprophylaxis. The primary outcomes were the rates of mother-to-child transmission and birth defects. The secondary outcomes were the safety of TDF, the percentage of mothers with an HBV DNA level of <200,000 IU/mL at delivery, and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28. At delivery, 68% of the mothers in the TDF group (66 of 97 women), as compared with 2% in the control group (2 of 100), had an HBV DNA level <200,000 IU/mL. At postpartum week 28, the rate of mother-to-child transmission was significantly lower in the TDF group than in the control group, both in the intention-to-treat analysis (5% vs. 18%, P=0.007) and the per-protocol analysis (0 vs. 7%, P=0.01). The maternal and infant safety profiles were similar in the TDF group and the control group, including birth defect rates (2% vs. 1%, P=1.00), although more mothers in the TDF group had an increase in the creatine kinase level. After the discontinuation of TDF, alanine aminotransferase elevations above the normal range occurred more frequently in mothers in the TDF group than in those in the control group (45% vs. 30%, P=0.03). The authors concluded that in HBeAg-positive mothers with an HBV DNA level >200,000 IU/mL during the third trimester, the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy.

Bacteriological Profile of Neonatal Sepsis in a Tertiary-care Hospital of Northern India.

With an objective to study the bacteriological profile of neonatal sepsis a retrospective study was conducted in the neonatal unit of a referral teaching hospital in Northern India. Among neonates born over 5-year period (n=22363) incidence of culture-positive sepsis was 7.5/1000 live births (7.5%). Staphylococcus aureus (47.3%), Klebsiella pneumonia (14.9%) and Acinetobacter (14.9%) were most common organisms isolated. Sensitivity pattern of isolated organisms is presented.

Off-label Use of Drugs in Neonatal Intensive Care Units.

Objective: To estimate proportion of off-label medication use in neonates and to evaluate evidence of efficacy and safety of these medications. Methods: Chart audit in neonatal intensive care units of two institutions in Chandigarh, India. Results: Among 568 prescriptions in 156 neonates, 286 (50%) were off-label. Of these, 56% drugs were not approved for use in neonatal age group and 26% prescriptions were off-label for frequency, dose, indication, route or rate. Most common off-label drugs were anti-infective and antiepileptic. Despite lack of regulatory approval, one-third off-label drugs had level I-II evidence of safety and efficacy for use in neonates. Conclusion: Use of off-label drugs is common in sick neonates.

Phenobarbitone versus Phenytoin for Treatment of Neonatal Seizures: An Open-label Randomized Controlled Trial.

Objective: To compare the efficacy of phenobarbitone and phenytoin for treatment of neonatal seizures in term and nearterm neonates. Design: Open labeled randomized controlled trial. Setting: Neonatal intensive care unit of a level II unit from India, from November 2008 to September 2009. Participants: All term and late pre-term neonates admitted with clinically apparent seizures and not having any transient metabolic disorders (hypoglycemia or hypocalcemia) were randomly assigned. Intervention: Phenobarbitone (n=54) or phenytoin (n=55) intravenously 20 mg/kg/dose over 20-30 min. Neonates whose seizures were not controlled by the assigned drug were then crossed over to be treated with other drug in same dose. Primary outcome variable: Clinical control of seizures (seizure free period of 24 hours after giving anticonvulsant). Results: Baseline characteristics including mean birthweight, gestation age and sex were comparable in both groups. Seizures were controlled in 8 of the 55 (14.5%) neonates who received phenytoin, as compared to 39 of 54 (72.2%) neonates who received phenobarbitone (P <0.001). In babies not responding to assigned drugs, after cross-over to the other drug, seizure control was achieved in 44/55 (80%) of the neonates assigned to receive phenytoin first as compared to 49/54 (91%) of those assigned to receive phenobarbitone first (P=0.014). After maximum dose of phenobarbitone seizures were controlled in 49/55(89%) in phenytoin group and 52/54 (96%) in phenobarbitone group (P<0.05). Conclusion: Phenobarbitone is more efficacious than phenytoin in control of clinical seizures in term or near-term neonates, irrespective of etiology.

Comparison of Analgesic Effect of Direct Breastfeeding, Oral 25% Dextrose Solution and Placebo during 1st DPT Vaccination in Healthy Term Infants: A Randomized, Placebo Controlled Trial.

Objective: To compare analgesic effect of direct breast feeding, 25% dextrose solution and placebo as we give 1st intramuscular whole cell DPT injection to 6week - 3month old infants. Design: Randomized, placebo controlled trial. Setting: Immunization clinic of Department of Pediatrics, LLRM Medical College. Participants: Infants coming for their 1st DPT vaccination were randomized in to three groups of 40 each. Outcome measures: The primary outcome variable was the duration of cry after vaccination. Secondary outcome variables were Modified Facial Coding Score (MFCS) and latency of onset of cry. Results: 120 babies were equally enrolled in breast feed group, 25% dextrose fed group and distilled water fed group. Median (interquartile range) of duration of cry was significantly lower in breast fed (33.5 (17-54) seconds) and 25% dextrose fed babies (47.5 (31-67.5) seconds) as compared to babies given distilled water (80.5 (33.5-119.5) seconds) (P<0.001). MFCS at 1 min and 3 min was significantly lower in direct breast fed and dextrose fed babies. Conclusions: Direct breastfeeding and 25% dextrose act as analgesic in young infants undergoing DPT vaccination in young infants less than 3 month of age.

Bilirubin Nomogram for Prediction of Significant Hyperbilirubinemia in North Indian Neonates.

Objectives: (i) To construct hour-specific serum total bilirubin (STB) nomogram in neonates born at ≥35 weeks of gestation; (ii)To evaluate efficacy of pre-discharge bilirubin measurement in predicting hyperbilirubinemia needing treatment. Design: Diagnostic test performance in a prospective cohort study. Setting: Teaching hospital in Northern India. Subjects: Healthy neonates with gestation ≥35 weeks or birth weight ≥2000 g. Intervention: Serum total bilirubin was measured in all enrolled neonates at 24±6, 72-96 and 96-144 h of postnatal age and when indicated clinically. Neonates were followed up during hospital stay and after discharge till completion of 7th postnatal day. Outcome: Key outcome was significant hyperbilirubinemia (SHB) defined as need of phototherapy based on modified American Academy of Pediatrics (AAP) guidelines. In neonates born at 38 or more weeks of gestation middle line and in neonates born at 37 or less completed weeks of gestation, lower line of phototherapy thresholds were used to initiate phototherapy. For construction of nomogram, STB values were clubbed in six-hour epochs (age ± 3 hours) for postnatal age up to 48 h and twelvehour epochs (age ± 6 hours) for age beyond 48 h. Predictive ability of the nomogram was assessed by calculating sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio, by plotting receiver-operating characteristics (ROC) curve and calculating c-statistic. Results: 997 neonates (birth weight: 2627 ± 536 g, gestation: 37.8±1.5 weeks) were enrolled, of which 931 completed followup. Among enrolled neonates 344 (34.5%) were low birth weight. Rate of exclusive breastfeeding during hospital stay was more than 80%. Bilirubin nomogram was constructed using 40th, 75th and 95th percentile values of hour-specific bilirubin. Pre-discharge STB of ≥95th percentile was assigned to be in high-risk zone, between 75th and 94th centile in upper-intermediate risk zone, between 40th and 74th centile in lower-intermediate risk zone and below 40th percentile in low-risk zone. Among 49 neonates with pre-discharge STB in high risk zone. 34 developed SHB (positive predictive value: 69.4%, sensitivity: 17.1%, positive likelihood ratio: 8.26). Among 342 neonates with pre-discharge STB in low risk zone, 32 developed PHB (negative predictive value: 90.6% and specificity: 42.5%, positive likelihood ratio: 0.37). Area under curve for this risk assessment strategy was 0.73. Conclusion: Hour-specific bilirubin nomogram and STB measurement can be used for predicting subsequent need of phototherapy. Further studies are needed to validate performance of risk demarcation zones defined in this hour-specific bilirubin nomogram.

Risk factors for Perinatal Mortality Due to Asphyxia Among Emergency Obstetric Referrals in a Tertiary Hospital.

Objectives: To evaluate the clinical, behavioral and health-care associated risk factors of intrapartum perinatal mortality (IPPM). Design: Prospective cohort study. Setting: Labor room and postnatal wards of a teaching hospital in North India. Participants: Pregnant women were eligible for enrolment in the study if period of gestation at delivery was 35 weeks or more or baby weighed at least 2000 g at birth, index pregnancy was not booked in antenatal clinic of the study hospital and fetus was delivered within 24 h of admission in the hospital. Methods: Information about antenatal care and events surrounding labor and delivery were retrieved from antenatal care records, referral notes, hospital clinical records and interview of mothers. Multivariate analysis was conducted using forward stepwise logistic regression analysis. Main Outcome Measure: IPPM was defined as asphyxiaspecific stillbirth or asphyxia-specific early neonatal death. Results: Among 248 emergency obstetric referrals during the study period, rate of IPPM was 8% (20/248, 18 fresh stillbirths and 2 asphyxia-specific neonatal deaths). District hospitals and community health-centers/first referral units contributed threefourths of all referrals. On logistic regression analysis significant risk factors for IPPM were presence of obstructed labor (OR: 23, 95% CI: 1.9-275.8), father engaged in unskilled labor (OR: 10, 95% CI: 1.3-77.7) and absence of urine examination during antenatal period (OR: 5.5, 95% CI: 1.8-16.3). Conclusions: Low socioeconomic status, inadequate antenatal care and poor intrapartum care due to unskilled birth attendance are risk factors of IPPM.

Preliminary report on neonatal screening for congenital hypothyroidism, congenital adrenal hyperplasia and glucose-6-phosphate dehydrogenase deficiency: a chandigarh experience.

Objective To establish newborn screening in Indian scenario that could lay a framework for future such initiatives. Three disorders namely, congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH) and glucose-6- phosphate dehydrogenase deficiency (G-6-PDD) were selected for a preliminary study for newborn screening. Methods Heel-prick blood samples were collected from liveborn neonates at 24–48 h of birth as a part of a screening program after prior written consent from the parents. Blood levels of glucose-6-phosphate-dehydrogenase enzyme (G-6- PD), thyroid-stimulating hormone (TSH) and 17-α-OH progesterone (17-OHP) were measured using DELFIA time resolved fluoroimmunoassay. Results Six thousand eight hundred and thirteen (6,813) neonates (86.3%), out of a total of 7,893 live births in our institute during the period May’2007 through July’2009, were screened for CAH, CH and G6PD deficiency. Major reason for missing samples was early discharge of the neonates and admission to the neonatal intensive care unit. G-6-PD deficiency was confirmed in 61 cases, congenital hypothyroidism (CH) in 2 cases and congenital adrenal hyperplasia (CAH) in 1 neonate, accounting for an incidence of 1/112 for G-6-PDD, 1/ 3400 for CH and 1/6813 for CAH. Conclusions Preliminary data on prevalence of various genetic disorders viz. G-6-PDD, CH and CAH in the population of this region revealed that G-6-PDD is most prevalent disorder followed by CH and CAH. More efforts need to be undertaken to create awareness and emphasis on significance of preventive testing to make screening a successful program in India.

Bilirubin Rebound After Intensive Phototherapy for Neonatal Jaundice.

This study was conducted to determine the incidence and magnitude of postphototherapy bilirubin rebound in neonates. Subjects included inborn neonates needing phototherapy for hyperbilirubinemia. Standard guidelines were used to start and stop phototherapy. Rebound bilirubin was measured 24±6 h after stopping phototherapy. Significant bilirubin rebound (SBR) was defined as postphototherapy bilirubin level needing reinstitution of phototherapy. Among 245 neonates with hyperbilirubinemia, post-phototherapy bilirubin estimation was done in 232 neonates. A total of 17 (7.3%) neonates developed SBR. In neonates with SBR, bilirubin increased by 2.3 mg/dL (95% CI 1.6-3.0) after stopping phototherapy. Risk factors for SBR included birth at <35 weeks of gestation (RR 4.3, 95% CI 1.5-12.0), birthweight <2000 g (RR 3.2, 95% CI 1.0-10.3) and onset of jaundice at <60 h of age (RR 3.3, 95% CI 1.2-9.0). Post-phototherapy discharge and follow-up planning should take into account these risk factors.

Phenobarbitone for Prevention and Treatment of Unconjugated Hyperbilirubinemia in Preterm Neonates: A Systematic Review and Meta-analysis.

Objective: To evaluate the role of phenobarbitone in the management of unconjugated hyperbilirubinemia during first two weeks of life in preterm neonates. Design: Meta-analysis. Methods: A study was eligible for inclusion in the metaanalysis if it randomized preterm neonates into control and treatment groups. Standard search strategy of the Cochrane Neonatal Review Group was used. For categorical and continuous data the odds ratio (OR) and weighted mean difference (WMD) were calculated, respectively. 95% confidence intervals were used and a fixed effects model was assumed for the meta-analysis. Main outcome measures: Peak serum bilirubin, duration of phototherapy, need of phototherapy and exchange transfusion, neurodevelopmental outcome and adverse effects. Results: A total of 19 potentially relevant studies were identified. Of these, 3 studies (497 neonates) were included in the meta-analysis. Peak serum bilirubin was significantly lower in phenobarbitone group (mean difference: –1.78 mg/dL, 95% CI: –2.29 to –1.27). Duration of phototherapy was shorter (mean difference: –14.75 h, 95% CI: –26.67 to –2.83). Need of phototherapy (OR: 0.33, 95% CI: 0.13 to 0.81) and exchange transfusion (OR: 0.30, 95% CI: 0.14 to 0.64) were also reduced in phenobarbitone group. Conclusion: Phenobarbitone reduces peak serum bilirubin, duration and need of phototherapy and need of exchange transfusion in preterm very low birthweight neonates. Further studies are warranted to evaluate adverse effects and neurodevelopmental outcome.