Turning the Gaze from Survive to Thrive for Children in India: Learnings from Two Case Studies.

Despite significant efforts and progress made in newborn care programs in India, implementation gaps persist across the continuum of care. The present case studies of two districts in Himachal Pradesh revealed that pathways of care were often fragmented with inconsistent linkages between facility and community due to poor documentation, lack of tiered referral, health system weaknesses, low utilization of primary level institutions, and inadequate post-natal home visits by Accredited Social Health Activists (ASHAs). Involvement of healthcare providers (HCPs) and frontline health workers (FHWs) was low and uneven in generating awareness across the districts with limited participation in supporting care in the community. Ensuring functionality of health centers and first-level care facilities; strengthening referral systems; adequate/trained human resources; strengthening routine health management systems, discharge processes and community-based care with adequate integration with facilities are necessary in closing access gaps.

The Hearing Status of Preterm Infant's ≤ 34 Weeks as Revealed by Otoacoustic Emissions (OAE) Screening and Diagnostic Brainstem Evoked Response Audiometry (BERA): A Tertiary Center Experience.

To know the prevalence of hearing loss in preterm infants & to evaluate the sensitivity & specificity of otoacoustic emission (OAE) in detecting hearing loss in preterm infants ≤ 34 weeks. A total of 70 preterm babies from 28 to 34 weeks of gestational age were enrolled in the study. Detailed prenatal, perinatal, postnatal & family history and physical examination of the babies were carried out. First OAE was done at discharge or two weeks after birth, whichever was earlier and the second OAE assessment was done at 36-40 weeks of corrected age. Diagnostic brainstem evoked response audiometry (BERA) was done in all infants at 36-40 weeks of corrected age, at the time of second OAE. Neonates with hearing impairment were advised for early hearing aid amplification and were referred to the rehabilitation center for further management. The sensorineural hearing loss (SNHL) in either one of the ears was identified in 13 (18.57%) preterm babies. Bilateral profound SNHL was found in 5 (7.14%) babies. Auditory neuropathy profile was found in 7 (53.8%) out of 13 babies who had hearing loss. The sensitivity, specificity, positive and negative predictive values of second TEOAE compared with diagnostic BERA was 46.15%, 85.96%, 42.85%, and 87.5% respectively. Neonatal jaundice (p = 0.009) and history of exchange transfusion (p = 0.019) were found to be significant risk factors of hearing loss in our study. Other risk factors like mode of delivery, birth asphyxia, low APGAR score, meningitis, ototoxic drugs, and seizures were not associated with hearing loss. The prevalence of hearing loss in preterm infants < 34 weeks is very high. OAE alone is not an ideal screening test for high-risk neonates ≤ 34 weeks because of its low sensitivity. OAE combined with diagnostic BERA should be done in all high-risk infants preterm neonates ≤ 34 weeks to identify cases of auditory neuropathy spectrum disorders.

Growth Faltering Among Discharged Babies from Inpatient Newborn Care Facilities: Learnings from Two Districts of Himachal Pradesh.

OBJECTIVE: To determine the burden of early growth faltering and understand the care practices for small and sick babies discharged from newborn units in the district. STUDY DESIGN: Observational and follow-up study. PARTICIPANTS: 512 babies discharged from two Special Newborn Care Units (SNCUs) and four Newborn Stabilization Units (NBSUs) in two districts of Himachal Pradesh. METHODS: Anthropometric assessments, interview of mothers and Accredited Social Health Activists (ASHAs) conducted between August, 2018 and March, 2019. Change in weight-for-age z-score (DWAZ) of <-0.67SD between birth and assessment was used to define growth faltering. OUTCOMES: Proportion of growth faltering (or catch-down growth) in small and sick babies discharged from SNCUs and NBSUs, and infant care practices. RESULTS: Growth faltering was observed in a significant proportion of both term (30%) and preterm (52.6%) babies between 1 to 4 months of age. Among babies with growth faltering (n=180), 73.9% received a home visit by ASHA, and only 36.7% received a follow-up visit at a facility. There were 71.3% mothers counselled at discharge (mostly informed about breast feeding). Most (96.7%) mothers did not perceive inadequate weight gain in their babies post-discharge. During home visits, ASHAs weighed 61.6% of the infants with growth faltering. Amongst infants who had growth faltering, only 49.6% of mothers had been provided information about their infant's growth and 57.1% mothers had received breastfeeding counselling. CONCLUSION: Small and sick newborn infants (both term and preterm babies) discharged from special care newborn units are at increased risk of early growth faltering. Follow-up care provided to these infants is inadequate. There is a need to strengthen both facility-based and home-based follow up of small and sick newborn infants discharged from newborn care facilities.

Study Design: Observational Studies.

Observational study designs are those where the investigator/researcher just observes and does not carry out any intervention(s)/actions to alter the outcome. The three most common types of observational studies are cross-sectional, case control and cohort (or longitudinal). In cross-sectional studies, both the exposure/risk factor(s) and the outcome(s) are determined at a single time point. They can provide information on prevalence of a condition and snapshot of probable associations that can be used to generate hypothesis. Case-control studies are where subjects are selected based on presence/absence of outcome and the risk factors are determined during the study after enrolment of study subjects. The association between exposure and outcome is reported as odds ratio. These studies; however, have high risk of bias, which must be taken care of during study design. Cohort studies are prospective in nature, where subjects are selected based on presence/absence of exposure, and the outcome(s) is determined at the end of study. These studies can provide incidence of disease/outcome and the association between exposure and outcome is reported as relative risk. They are useful to ascertain causality. High dropouts of study participants and confounding can be problems encountered in these studies.

Flow Cytometry: An Important Diagnostic Tool in Critically Ill Preterm Neonates with Suspected Sepsis.

OBJECTIVE: Sepsis is a major cause of neonatal mortality. The gold standard for diagnosis is blood culture which suffers from low sensitivity and huge turn-around time. Flow cytometry has been extensively applied to malignant disorders and is an upcoming tool for diagnosis of nonmalignant disorders due to its rapidity and accuracy in detecting cells, cell products, and their functional states. The aim of this study was to investigate the utility of flow cytometric expression of neutrophil CD64, monocyte human leukocyte antigen (HLA-DR) and CD16 in diagnosis in suspected preterm neonates. STUDY DESIGN: In total, 100 preterm neonates with clinical signs of sepsis were enrolled in the study. Blood culture, C-reactive protein (CRP) and flow cytometry for nCD64, mHLA-DR, and mCD16 were performed. The neonates were divided into two groups: culture positive and culture negative and CRP and flow cytometric findings compared. ROC analysis was performed to determine the best cut-off for nCD64, mHLA-DR, and mCD16 values along with estimation of sensitivity, specificity, and predictive values. Probability of <0.05 was taken as significant. RESULTS: Out of the 100 enrolled neonates, 34 (34%) were culture positive. CRP was not found to be significantly different in the two groups. Expression of nCD64 (p = 0.03) was significantly upregulated in the blood culture positive cases with a cut-off mean fluorescence intensity (MFI) value = 4.72 and sensitivity of 92% and specificity of 52%. Expression of mCD16 (p = 0.02) was also upregulated in the blood culture positive cases with a cut-off MFI value = 4.9, with sensitivity of 41%, specificity of 83%. CONCLUSION: The study concluded that nCD64 and mCD16 can be potential biomarkers for early diagnosis of neonatal sepsis with a high sensitivity and specificity. KEY POINTS: · Neutrophil CD64 significantly upregulated in septic neonates.. · Monocyte CD16 significantly upregulated in septic neonates.. · C-reactive protein values were not significantly different in septic versus nonseptic neonates..

Gestational weight gain trajectories in GARBH-Ini pregnancy cohort in North India and a comparative analysis with global references.

BACKGROUND: To describe the pattern of gestational weight gain (GWG), derive reference centiles for GWG specific to North Indian population, and to compare the weight gain across different periods of gestation with the INTERGROWTH-21st reference. METHODS: A prospective pregnancy (GARBH-Ini) cohort was initiated and followed between May 2015 and June 2019 in a district hospital, Gurguram, North India. GWG centile curves were modelled by Generalized Additive Models for Location, Scale and Shape method (n = 2844) and compared with INTERGROWTH-21st reference. The independent association of GWG with biological and social predictors was assessed using multivariable regression analysis. RESULTS: Percentiles (3rd, 10th, 50th, 90th and 97th) for each completed week from 18-40 weeks of gestation were derived from smoothed centile curves. The median GWG across pregnancy during specific antenatal visits was 1.29 at 18, 4.44 at 26, 5.8 at 30 and 9.06 kg at 40 weeks of gestation. Nearly 26% of participants had GWG < 10th centile at 18-20 weeks as per INTERGROWTH-21st reference and this increased to 45% at delivery. Significant predictors of GWG included maternal age, height, first trimester body mass index, parity, type of family, and use of clean fuel for cooking. CONCLUSION: These GWG percentiles will serve as a useful reference, particularly during the WHO recommended antenatal visit schedule for optimum pregnancy outcomes, for clinicians and researchers. Multiple independent biological and social predictors of GWG suggest that single interventions are unlikely to bridge the gap between general Indian population and international references.

Complete genomic analysis of uncommon G12P[11] rotavirus causing a nosocomial outbreak of acute diarrhea in the newborns in New Delhi, India.

Rotaviruses (RVs) are the major causative agents of acute gastroenteritis in children, but in neonates, RV infections are generally nosocomial in origin and mostly asymptomatic. However, there have been infrequent reports of nosocomial outbreaks of clinical disease in this population. In this study, we describe uncommon RV genotype; G12P[11] associated with an outbreak of acute gastroenteritis in the neonatal ward and neonatal intensive care unit (NICU) in New Delhi, North India. Full-genome analyses of the pathogenic G12P[11] strain was carried out to map the genotype constellation and further to explore the variations in the antigenic epitopes on the immunodominant VP7 and VP4 proteins, the amino acid sequences were compared with neonatal strains; ROTAVAC® (G9P[11]) and asymptomatic G12P[11] and also other G/P-type matched strains. The study revealed G12-P[11]-I1-R1-C1-M1-A1-N1-T1-E1-H1 human Wa-like genotype constellation and highlights evidence of gene reassortment. No significant differences were observed in the sequences of structural (except VP3) and nonstructural encoding genes of G12P[11] strains recovered from symptomatic and asymptomatic neonates. Presence of additional N-linked glycosylation site was noted in the G12 strains, as a consequence of a change from Asp→Asn at amino acid position 238. Interestingly, only two and four amino acids substitution within the 7-1a and 8-1 antigenic epitope were observed, respectively, compared with asymptomatic G12P[11] strain. The study emphasizes the importance of close monitoring of RV outbreaks in neonates for early alarming of novel strain.

Indian Academy of Pediatrics Position Paper on Nurturing Care for Early Childhood Development.

Early childhood development (ECD) refers to the physical, motor, socio-emotional, cognitive, and linguistic development of a young child. The 'Countdown to 2030' global distribution of 'children at risk of poor development' indicates the need for urgent action and investment in ECD. Nurturing care enhances ECD, even in the presence of adversities. Strategic actions should exist at multiple levels: the family, community, health care providers and government. Previously, child health related policies and programs of the Government of India functioned in isolation, but have recently started demonstrating multi-sectoral collaboration. Nonetheless, the status of ECD in India is far from optimal. There is strong evidence that parenting programs improve outcomes related to ECD. This is dependent on key programmatic areas (timing, duration, frequency, intensity, modality, content, etc.), in addition to political will, funding, partnership, and plans for scaling up. Each country must implement its unique ECD program that is need-based and customized to their stakeholder community. Barriers like inadequate sensitization of the community and low competency of health care providers need to be overcome. IAP firmly believes that responsive parenting interventions revolving around nurturing care should be incorporated in office practice. This paper outlines IAP's position on ECD, and its recommendations for pediatricians and policy makers. It also presents the roadmap in partnership with other stakeholders in maternal, neonatal, and child health; Federation of Obstetric and Gynaecological Societies of India (FOGSI), National Neonatology Forum (NNF), World Health Organization (WHO), and United Nation Children Fund (UNICEF).

Parental and professional perceptions of informed consent and participation in a time-critical neonatal trial: a mixed-methods study in India, Sri Lanka and Bangladesh.

INTRODUCTION: Time-critical neonatal trials in low-and-middle-income countries (LMICs) raise several ethical issues. Using a qualitative-dominant mixed-methods design, we explored informed consent process in Hypothermia for encephalopathy in low and middle-income countries (HELIX) trial conducted in India, Sri Lanka and Bangladesh. METHODS: Term infants with neonatal encephalopathy, aged less than 6 hours, were randomly allocated to cooling therapy or usual care, following informed parental consent. The consenting process was audio-video (A-V) recorded in all cases. We analysed A-V records of the consent process using a 5-point Likert scale on three parameters-empathy, information and autonomy. In addition, we used exploratory observation method to capture relevant aspects of consent process and discussions between parents and professionals. Finally, we conducted in-depth interviews with a subgroup of 20 parents and 15 healthcare professionals. A thematic analysis was performed on the observations of A-V records and on the interview transcripts. RESULTS: A total of 294 A-V records of the HELIX trial were analysed. Median (IQR) score for empathy, information and autonomy was 5 (0), 5 (1) and 5 (1), respectively. However, thematic analysis suggested that the consenting was a ceremonial process; and parental decision to participate was based on unreserved trust in the treating doctors, therapeutic misconception and access to an expensive treatment free of cost. Most parents did not understand the concept of a clinical trial nor the nature of the intervention. Professionals showed a strong bias towards cooling therapy and reported time constraints and explaining to multiple family members as key challenges. CONCLUSION: Despite rigorous research governance and consent process, parental decisions were heavily influenced by situational incapacity and a trust in doctors to make the right decision on their behalf. Further research is required to identify culturally and context-appropriate strategies for informed trial participation.

Effect of home-based newborn care on neonatal and infant mortality: a cluster randomised trial in India.

BACKGROUND: Home-based newborn care has been found to reduce neonatal mortality in rural areas. Study evaluated effectiveness of home-based care delivered by specially recruited newborn care workers- Shishu Rakshak (SR) and existing workers- anganwadi workers (AWW) in reducing neonatal and infant mortality rates. METHODS: This three-arm, community-based, cluster randomised trial was conducted in five districts in India. Intervention package consisted of pregnancy surveillance, health education, care at birth, care of normal/low birthweight neonates, identification and treatment of sick neonates and young infants using oral and injectable antibiotics and community mobilisation. The package was similar in both intervention arms-SR and AWW; difference being healthcare provider. The control arm received routine health services from the existing health system. Primary outcomes were neonatal and young infant mortality rates at 'endline' period (2008-2009) assessed by an independent team from January to April 2010 in the study clusters. FINDINGS: A total of 6623, 6852 and 5898 births occurred in the SR, AWW and control arms, respectively, during the endline period; the proportion of facility births were 69.0%, 64.4% and 70.6% in the three arms. Baseline mortality rates were comparable in three arms. During the endline period, the risk of neonatal mortality was 25% lower in the SR arm (adjusted OR 0.75, 95% CI 0.57 to 0.99); the risks of early neonatal mortality, young infant mortality and infant mortality were also lower by 32%, 27%, and 33%, respectively. The risks of neonatal, early neonatal, young infant, infant mortality in the AWW arm were not different from that of the control arm. INTERPRETATION: Home-based care is effective in reducing neonatal and infant mortality rates, when delivered by a dedicated worker, even in settings with high rates of facility births. TRIAL REGISTRATION NUMBER: The study was registered with Clinical Trial Registry of India (CTRI/2011/12/002181).

Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy.

A rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth, predicts adverse neurodevelopmental outcome eighteen months after neonatal encephalopathy. We performed next generation sequencing on whole blood ribonucleic acid obtained within six hours of birth from the first 47 encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX) trial. Two infants with blood culture positive sepsis were excluded, and the data from remaining 45 were analysed. A total of 855 genes were significantly differentially expressed between the good and adverse outcome groups, of which RGS1 and SMC4 were the most significant. Biological pathway analysis adjusted for gender, trial randomisation allocation (cooling therapy versus usual care) and estimated blood leukocyte proportions revealed over-representation of genes from pathways related to melatonin and polo-like kinase in babies with adverse outcome. These preliminary data suggest that transcriptomic profiling may be a promising tool for rapid risk stratification in neonatal encephalopathy. It may provide insights into biological mechanisms and identify novel therapeutic targets for neuroprotection.

Early prediction of feed intolerance in very low birth weight preterm infants using superior mesenteric artery blood flow velocity.

Objective: To evaluate the utility of superior mesenteric artery (SMA) flow velocity post feeding for predicting time to achieve full enteral feeds in very low birth weight (VLBW) neonates.Subjects: In this prospective cohort study preterm VLBW infants were followed until they achieved full enteral feeding.Results: There was no significant difference between prefeed and post feed SMA flow measurements in study subjects. At baseline, it was observed that Small for gestational age (SGA) babies had a significantly lower peak systolic velocity. Time-averaged mean velocity (TAMV) was significantly lower in SGA babies at baseline, 15, 30, 45, and 60 min post feed, but there were no within-group differences noted over time.Conclusion: SMA blood flow velocity measured pre-feed and post-feed times do not correlate with the time to achieve full enteral feeding in very low birth weight neonates. The clinical significance of lower Peak systolic velocity (PSV) and TAMV in SGA infants is unclear.

Prediction of nutritive sucking in preterm babies (<34 weeks) and preterm sucking readiness scale.

OBJECTIVE: To determine predictors of nutritive-sucking in babies < 34 weeks and estimate the appropriate preterm sucking readiness (PTSR) score as an indicator of readiness of nutritive-sucking. METHODS: Prospective longitudinal observational study conducted in Neonatal unit of a referral hospital attached to Medical College. Forty-nine inborn babies of 28-34 weeks' gestation and on full gavage feeds were enrolled. RESULTS: (a) Nutritive-sucking was achieved at a median age of 14 days (Range 7-50). (b) Low birth weight (LBW) (< 1531.1 ± 142.8) and lesser gestational age (GA) (< 32.8 ± 1) were poor predictors (p < 0.05) and have a significant independent negative association (Correlation birth weight (BW) - 0.0222, GA - 2.2177) with age at which established nutritive-sucking was achieved. (c) PTSR score of ≥9 had the best prediction for achievement of nutritive-sucking at 14-days of life, with a sensitivity of 92.3% and specificity of 100%. CONCLUSION: PTSR score is a sensitive and specific tool to predict the readiness for nutritive-sucking in preterm babies < 34 weeks.