Development, validation and application of single molecule molecular inversion probe based novel integrated genetic screening method for 29 common lysosomal storage disorders in India.

BACKGROUND: Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India. RESULTS: 903 smMIPs were designed to target exon and exon-intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood. CONCLUSION: We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.

The COVID-19 Data Portal: accelerating SARS-CoV-2 and COVID-19 research through rapid open access data sharing.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic will be remembered as one of the defining events of the 21st century. The rapid global outbreak has had significant impacts on human society and is already responsible for millions of deaths. Understanding and tackling the impact of the virus has required a worldwide mobilisation and coordination of scientific research. The COVID-19 Data Portal (https://www.covid19dataportal.org/) was first released as part of the European COVID-19 Data Platform, on April 20th 2020 to facilitate rapid and open data sharing and analysis, to accelerate global SARS-CoV-2 and COVID-19 research. The COVID-19 Data Portal has fortnightly feature releases to continue to add new data types, search options, visualisations and improvements based on user feedback and research. The open datasets and intuitive suite of search, identification and download services, represent a truly FAIR (Findable, Accessible, Interoperable and Reusable) resource that enables researchers to easily identify and quickly obtain the key datasets needed for their COVID-19 research.

Protocol for Infant Massage in Home Settings: An e-Delphi Approach for Consensus Guidance Integrating Traditional Wisdom with Modern Medicine.

Infant massage is a highly prevalent traditional practice in India and other parts of Asia. Clear guidance on safe and effective uses of infant massage is lacking especially in the contemporary times when the traditional knowledge is on the verge of extinction and preparations may differ from in the past. This paper presents a consensus guidance in the form of a standardized protocol for routine massage of infants in home settings. Furthermore, a feasible method to develop an integrative protocol involving traditional and modern medicine experts is described. A modified e-Delphi method was used to develop the protocol. A group of seventeen experts, including academicians and practitioners from disciplines as modern paediatrics, Ayurveda paediatrics, Physiotherapy and Naturopathy participated in three rounds of a Delphi study to evolve the consensus guidance. The present protocol for massage of infants born beyond 34 weeks of gestation and weighing above 1.8 kg is recommended for use by care givers. This provides guidance on the preparation for infant massage such as when to begin massaging the infant, checking fitness of the infant for massage, the appropriate time, environment, person and substance for infant massage and a detailed description of the procedure for infant massage. Paediatricians, obstetricians and other child care practitioners can use this protocol to guide care givers on how to peform infant massage.

Predictors of length of hospital stay among preterm infants admitted to neonatal intensive care unit: Data from a multicentre collaborative network from India (INNC: Indian National Neonatal Collaborative).

AIM: Prediction of length of stay (LOS) among preterm neonates is important for counselling of parents and for assessing neonatal intensive care unit (NICU) census and economic burden. The aim of this study is to evaluate perinatal and postnatal factors that influence LOS in preterm infants (25-33 weeks of gestation) admitted to participating NICUs of Indian National Neonatal Collaborative (INNC). METHODS: From the INNC database, the data which were prospectively entered using uniformed pre-defined criteria were analysed. RESULTS: A total of 3095 infants were included from 12 centres. Every week decrease in gestation increased LOS by 9 days. The median LOS for infants with gestational age of 25, 26, 27, 28, 29, 30, 31, 32 and 33 weeks were 86, 70, 62, 52, 40, 30, 23, 16 and 10 days, respectively. On multivariate analysis, abnormal antenatal umbilical artery doppler, severe small for gestational age (SGA), requirement of resuscitation, respiratory distress syndrome (RDS), seizures, sepsis, necrotising enterocolitis (NEC), major malformations and bronchopulmonary dysplasia (BPD) increased LOS by 5.4 (3.5-7.4), 21.6 (19-23.9), 4.7 (3.3-6.1), 3 (1.7-4.3), 15.2 (8.5-22.1), 11.2 (9.1-13.2), 9.8 (5.2-14.4), 8.8 (4.4-13.3) and 5.6 (0.5-10.7) days, respectively. CONCLUSIONS: Apart from lower gestation and birth weight, abnormal antenatal umbilical artery doppler, severe SGA, resuscitation need, major malformations, RDS, seizures, sepsis, NEC and BPD influenced LOS in preterm infants. In comparison with other networks or data from developed countries, LOS in our network was comparatively less for similar gestational age infants.

Sentinel Surveillance for Congenital Rubella Syndrome - India, 2016-2017.

Rubella infection during pregnancy can result in miscarriage, fetal death, stillbirth, or a constellation of congenital malformations known as congenital rubella syndrome (CRS). The 11 countries in the World Health Organization (WHO) South-East Asia Region are committed to the elimination of measles and control of rubella and CRS by 2020. Until 2016, when the Government of India's Ministry of Health and Family Welfare and the Indian Council of Medical Research initiated surveillance for CRS in five sentinel sites, India did not conduct systematic surveillance for CRS. During the first 8 months of surveillance, 207 patients with suspected CRS were identified. Based on clinical details and serologic investigations, 72 (34.8%) cases were classified as laboratory-confirmed CRS, four (1.9%) as congenital rubella infection, 11 (5.3%) as clinically compatible cases, and 120 (58.0%) were excluded as noncases. The experience gained during the first phase of surveillance will be useful in expanding the surveillance network, and data from the surveillance network will be used to help monitor progress toward control of rubella and CRS in India.

Factors Associated with Time to Full Feeds in Preterm Very Low Birth Weight Infants.

BACKGROUND: Feeding intolerance prolongs time to full feeds (TFFs) in preterm infants. We studied factors associated with TFF in preterm infants on standardized feeding regimen (SFR) and routine probiotic supplementation (RPS). METHODS: This is a prospective cohort study of preterm infants ≤1500 g. Pearson's correlation, Mann-Whitney test and multivariate analysis were used. RESULTS: In total, 37 of 304 admitted infants died before reaching full feeds. Median (interquartile range) gestation, birth weight and TFF were 31.4 (30-33.05) weeks, 1210 (1066-1400) g and 11 (8-15) days, respectively. Gestation and birthweight were inversely correlated with TFF, whereas low Apgar's, sepsis, patent ductus arteriosus (PDA) and respiratory distress syndrome were directly correlated with TFF. Growth-restricted infants had significantly shorter TFF vs. appropriate for gestational age infants, probably because of higher gestation. On multivariate analysis gestation, sepsis and PDA were significant predictors of TFF. CONCLUSION: In preterm infants managed with SFR and RPS, gestation had inverse correlation with TFF, whereas sepsis and PDA had direct correlation with TFF.

Subcutaneous Emphysema of Scalp following Resuscitation in a Neonate.

BACKGROUND: Neonatal subcutaneous emphysema of scalp (SES) with air leaks is rare. Case characteristics: Neonate presented with SES in addition to pneumothorax and pneumomediastinum. OBSERVATION: SES resolved after the chest was drained to treat pneumothorax. OUTCOME: Neonate made full recovery. CONCLUSION: Neonatal SES may be associated with air leaks post-resuscitation, which has not been reported.

Burden of rare genetic disorders in India: twenty-two years' experience of a tertiary centre.

BACKGROUND: Rare disorders comprise of ~ 7500 different conditions affecting multiple systems. Diagnosis of rare diseases is complex due to dearth of specialized medical professionals, testing labs and limited therapeutic options. There is scarcity of data on the prevalence of rare diseases in different populations. India being home to a large population comprising of 4600 population groups, of which several thousand are endogamous, is likely to have a high burden of rare diseases. The present study provides a retrospective overview of a cohort of patients with rare genetic diseases identified at a tertiary genetic test centre in India. RESULTS: Overall, 3294 patients with 305 rare diseases were identified in the present study cohort. These were categorized into 14 disease groups based on the major organ/ organ system affected. Highest number of rare diseases (D = 149/305, 48.9%) were identified in the neuromuscular and neurodevelopmental (NMND) group followed by inborn errors of metabolism (IEM) (D = 47/305; 15.4%). Majority patients in the present cohort (N = 1992, 61%) were diagnosed under IEM group, of which Gaucher disease constituted maximum cases (N = 224, 11.2%). Under the NMND group, Duchenne muscular dystrophy (N = 291/885, 32.9%), trinucleotide repeat expansion disorders (N = 242/885; 27.3%) and spinal muscular atrophy (N = 141/885, 15.9%) were the most common. Majority cases of ß-thalassemia (N = 120/149, 80.5%) and cystic fibrosis (N = 74/75, 98.7%) under the haematological and pulmonary groups were observed, respectively. Founder variants were identified for Tay-Sachs disease and mucopolysaccharidosis IVA diseases. Recurrent variants for Gaucher disease (GBA:c.1448T > C), ß-thalassemia (HBB:c.92.+5G > C), non-syndromic hearing loss (GJB2:c.71G > A), albinism (TYR:c.832 C > T), congenital adrenal hyperplasia (CYP21A2:c.29-13 C > G) and progressive pseudo rheumatoid dysplasia (CCN6:c.298T > A) were observed in the present study. CONCLUSION: The present retrospective study of rare disease patients diagnosed at a tertiary genetic test centre provides first insight into the distribution of rare genetic diseases across the country. This information will likely aid in drafting future health policies, including newborn screening programs, development of target specific panel for affordable diagnosis of rare diseases and eventually build a platform for devising novel treatment strategies for rare diseases.

Bubble CPAP versus ventilator CPAP in preterm neonates with early onset respiratory distress--a randomized controlled trial.

UNLABELLED: Bubble continuous positive airway pressure (BCPAP) is a low cost nasal CPAP delivery system with potential benefits to developing nations. OBJECTIVE: To compare the efficacy and safety of BCPAP with ventilator-derived CPAP (VCPAP) in preterm neonates with respiratory distress. METHODS: In a randomized controlled trial, preterm neonates with Silverman-Anderson score ≥ 4 and oxygen requirement >30% within first 6 h of life were randomly allocated to BCPAP or VCPAP. Proportion of neonates with success or failure was compared. RESULTS: In all, 47 of 57 (82.5%) neonates from BCPAP group and 36 of 57 (63.2%) neonates from the VCPAP group completed CPAP successfully (p = 0.03). Neonates who failed CPAP had higher Silverman-Anderson score (p < 0.01), lower arterial to alveolar oxygenation ratio (p < 0.05) and needed surfactant more frequently (p < 0.01). CONCLUSION: BCPAP has higher success rate than VCPAP for managing preterm neonates with early onset respiratory distress, with comparable safety.

General Movement Assessment in Babies Born Preterm: Motor Optimality Score-Revised (MOS-R), Trajectory, and Neurodevelopmental Outcomes at 1 Year.

Objective: To assess the association between the General Movement Assessment (GMA) findings, including Motor Optimality Scores-Revised (MOS-R) at 16 weeks, and neuromotor outcome assessed by the Amiel-Tison Neurological Assessment at 9 months of corrected age and the Developmental Assessment Scales for Indian Infants (DASII) at 1 year of corrected age in preterm ≤32 weeks. Study design: Serial GMA videos of infants born preterm ≤32 weeks were recorded on day 7, 35 weeks of postmenstrual age, 40 weeks of postmenstrual age, and 16 weeks of corrected age. The association between GMA findings, including MOS-R scores and GM trajectory between 35 to 40 weeks and the Amiel-Tison Neurological Assessment and DASII scores, was assessed by Spearman correlation, Fisher exact tests, and ordinal regression. Results: Moderate correlations were observed between MOS-R and the DASII motor DQ (Spearman r = 0.70, P < .001) and between MOS-R and DASII Mental DQ (r = 0.65, P < .001). The GMA trajectory at 35-40 weeks was associated with DASII motor DQ (Fisher exact, P = .002), and also with the Amiel-Tison Neurological Assessment at 9 months of corrected age (P < .01 by the Fisher exact test). On analysis by performing ordinal regression of predictive values of the general movements (GM) at 7 days of age, GM at 35 weeks, GM at 40 weeks, GM at 16 weeks, and MOS-R at 16 weeks, MOS-R alone was a statistically significant predictor of motor DQ at 1 year of age (OR -0.59; 95% CI -0.97 to -0.22; Wald statistics, P < .02). Conclusions: Consistent with findings in high-income countries, GMA including MOS-R scores performed in Indian infants born preterm during the neonatal period and early infancy is associated with neurodevelopmental outcomes in the first year of life. GMA can help initiate focused early intervention in low- and middle-income settings, where resources may be limited.

Response to sirolimus in a case of diffuse congenital hyperinsulinaemic hypoglycaemia due to homozygous KCNJ11 mutation.

We present a case of a male neonate with refractory and persistent neonatal hypoglycaemia not responding to octreotide. On evaluation for hypoglycaemia, his cortisol was within the reference range while the serum insulin concentrations were high. Gallium-68 dotatate scan (GA-68 DOTA) showed diffuse pancreatic involvement. Genetic diagnosis of congenital hyperinsulinaemic hypoglycaemia due to KCNJ11 mutation was made. He was started on tablet sirolimus, after which the child was off all other medication and was euglycaemic. However, he developed bilateral pneumonia leading to acute respiratory distress syndrome with refractory shock. Our case highlights the response to sirolimus in a case of congenital hyperinsulinaemia (CHI) due to KCNJ11 mutation and severe adverse event thereafter.

Video-based screening for children with suspected autism spectrum disorder - experience during the COVID-19 pandemic in India.

Background: Assessments for children with autism spectrum disorder (ASD) must adapt to the current COVID-19 pandemic through innovation in screening and assessment strategies using technology. To our knowledge there are no such studies reported from India. We aimed to study the predictive ability of video-based screening tool with definitive diagnosis in children with ASD. Method: Thirty-nine children were screened independently by two examiners with a video-based screening tool to start intervention followed by an in-person evaluation by clinical DSM-5 diagnosis three months later. Result: Similar to studies from developed countries, videos assessments showed a 94.87% correlation with the final diagnosis. Interobserver video agreement had a kappa correlation of 0.803, which was classified as substantial agreement. Conclusion: Video-based evaluations may be used as an interim assessment to initiate early intervention in children with ASD in resource-limited setups in the current pandemic situation. Large, well-designed prospective studies are required to confirm our results.

Emerging Antibiotic Resistance Patterns in a Neonatal Intensive Care Unit in Pune, India: A 2-Year Retrospective Study.

Objective: Treating neonatal bloodstream infections and meningitis in South Asia remains difficult given high rates of antimicrobial resistance (AMR). To evaluate changing epidemiology of neonatal infections, we assessed pathogen-specific and clinical features of culture-proven infections in neonates admitted to a neonatal intensive care unit (NICU) in Pune, India. Materials and Methods: This retrospective cohort study was performed in the King Edward Memorial Hospital and Research Center NICU over 2 years between January 1, 2017 and December 31, 2018. We included all neonates admitted to the NICU with positive blood or cerebrospinal fluid cultures. Demographic, clinical, and microbiologic data were collected from the medical record. We reviewed antimicrobial susceptibility testing (AST) of all isolates. Results: There were 93 culture-positive infections in 83 neonates, including 11 cases of meningitis. Fifteen (18%) neonates died. Gram-negative pathogens predominated (85%) and AST showed 74% resistance to aminoglycosides, 95% resistance to third/fourth generation cephalosporins, and 56% resistance to carbapenems. Resistance to colistin was present in 30% of Klebsiella pneumoniae isolates. Birth weight <1,000 g [odds ratio (OR) 6.0, p < 0.002], invasive respiratory support (OR 7.7, p = 0.001), and antibiotics at the time of culture (OR 4.2, p = 0.019) were associated with increased risk of mortality. Rates of AMR to all major antibiotic classes were similar between early onset and late onset infections. There was no association between carbapenem resistance and mortality. Conclusion: In our NICU in India, there are high rates of AMR among Gram-negative pathogens that are predominantly responsible for infections. Given higher colistin resistance in this cohort than previously reported, hospitals should consider routinely testing for colistin resistance.

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 of survival.

Effect of early kangaroo mother care on time to full feeds in preterm infants - A prospective cohort study.

BACKGROUND: Kangaroo mother care (KMC) is known to reduce neonatal mortality and morbidity. In preterm neonates, KMC is usually initiated only after stabilization. AIMS: We aimed to assess if early initiation of KMC starting within the first week of life is safe, and reduces the time to full feeds (TFF) in preterm neonates. STUDY DESIGN: Prospective cohort study. SUBJECTS: Preterm neonates (Gestation ≤ 34 weeks, Birth weight ≤ 1250 g). This was studied in two epochs, (epoch 1) which was before early KMC vs. epoch 2 which was after implementation of early KMC even if they needed respiratory support, with umbilical/central lines in situ. OUTCOME: The primary outcome of the study was time to establish full feeds (TFF) of 150 ml/kg/day. RESULTS: The neonatal demographic characteristics were comparable between epoch 1 and epoch 2 except for lower gestational age, higher surfactant, and any respiratory support in epoch 2. On univariate analysis, early KMC significantly reduced TFF (12.5 vs. 9 days, P < 0.001). Feed intolerance, duration of parenteral nutrition were significantly reduced, and discharge weight Z score improved significantly in epoch 2. On multivariate regression analysis early KMC, exclusive mother's own milk feeding and blood culture-positive late-onset sepsis were important predictors of TFF. Early KMC was safe and well-tolerated. CONCLUSION: Early KMC was safe and associated with reduced TFF and other nutritional benefits in moderately ill preterm neonates.

Novel Mutations in the DGKE Gene in Two Indian Patients with Early-onset Atypical Haemolytic Uraemic Syndrome.

Atypical haemolytic uremic syndrome (aHUS) is a clinically and genetically heterogeneous condition caused by a complex interplay between genomic susceptibility factors and environmental influences. Pathogenic variants in the DGKE gene are recently identified in cases with infantile-onset autosomal recessive aHUS. The presence of low serum C3 levels, however, has rarely been described in cases of DGKE-associated aHUS. Molecular genetic testing was performed by a commercial next-generation sequencing (NGS) panel as well and by an in-house developed targeted NGS for DGKE gene. Copy number variations (CNVs) were computed from NGS data by calculating a normalised copy number ratio of aligned number of reads at targeted genomic regions against multiple reference regions of the same sample and multiple controls. We report here two such novel clinically relevant variants (c.727_730delTTGT and c.251_259delGCGCCTTC) in the DGKE gene, in two families of infantile aHUS with low serum C3 levels.

RAM cannula with Cannulaide versus Hudson prongs for delivery of nasal continuous positive airway pressure in preterm infants: an RCT.

Nasal continuous positive airway pressure (nCPAP) is the standard non-invasive respiratory support for newborns with respiratory distress. Nasal injury is a common problem with the interfaces used. To compare the incidence and severity of nasal injury in neonates with respiratory distress and supported on nCPAP with Hudson prong or RAM cannula with Cannulaide, a semipermeable membrane. This is an open-label, parallel-arm, gestational age-stratified, bi-centric, randomized control trial including neonates between 28 and 34 weeks gestational age and birth weight > 1000 g needing nCPAP. The size of the interface was chosen as per the manufacturer's recommendation. Of the 229 neonates enrolled, 112 were randomized to RAM cannula with Cannulaide and 117 to Hudson prong. The baseline characteristics were similar. Any nasal injury at CPAP removal was significantly lower in the RAM cannula with Cannulaide group [6 (5.4%) vs. 31 (26.4%); risk ratio-0.77 (95% CI 0.69-0.87); p = 0.0001]. The incidence of moderate to severe nasal injury, need for mechanical ventilation within 72 h of age, duration of oxygen, and requirement of nCPAP for > 3 days were similar. For preterm infants on nCPAP, RAM cannula with Cannulaide, compared to Hudson prongs, decreases nasal injury without increasing the need for mechanical ventilation.Trail registration: CTRI/2019/03/018333, http://www.ctri.nic.in .

A pilot study of comparison of BCPAP vs. VCPAP in preterm infants with early onset respiratory distress.

BACKGROUND: Bubble continuous positive airway pressure (BCPAP) is a low-cost nasal CPAP delivery system with potential benefits for developing nations. The objective of the study was to compare the efficacy and safety of BCPAP with ventilator CPAP (VCPAP) in preterm neonates with moderate respiratory distress. METHODS: In a pilot randomized controlled trial, 30 preterm neonates (gestation <37 weeks) with Silverman-Anderson score between 5 to 7 and oxygen requirement >30% within first 6 h of life were randomly allocated to BCPAP or VCPAP after informed parental consent. Proportion of neonates with success or failure, while using the allocated mode of CPAP delivery (primary outcome) was compared. RESULTS: The success rate was comparable [VCPAP: 80% (12/15) vs. BCPAP: 87% (13/15)] between the two groups. Dislodgement was commonest problem with equal frequency [10/15, (67%)] in each group. CONCLUSION: BCPAP appears to be a promising method of CPAP delivery in preterm neonates with moderate respiratory distress.

Retinopathy of prematurity: Maharashtra state model.

This report describes the goal, activities, and outcomes of the Queen Elizabeth Diamond Jubilee Trust funded retinopathy of prematurity (ROP) program in the state of Maharashtra in collaboration with the Public Health Foundation of India, Hyderabad. The project was initiated in July 2016 with the goal of establishing a sustainable ROP program in the special newborn care units (SNCUs) in public health facilities of five districts. Between 2016 and 2018, ophthalmology and neonatology teams from five district hospitals (DHs) were trained by nongovernment partner hospitals in the state. Infrastructure was developed by procuring equipment for ROP screening/treatment, and awareness generation activities were conducted with a range of stakeholders. Eight ophthalmologists were trained to perform ROP screening (from five DHs and one medical college), and five neonatology teams (pediatricians and nurses) from the project hospitals were trained in best neonatal practices to prevent ROP. The Pune district's hospital was developed as an ROP treatment center. Toward the end of the project period, six new facilities had an established ROP program. The state health department is in the process of scaling up the ROP program to a larger geographic region to ensure universal ROP screening coverage in the state of Maharashtra.