Incidence of and risk factors for small vulnerable newborns in north India: a secondary analysis of a prospective pregnancy cohort.

BACKGROUND: Globally, recent estimates have shown there have been 3·6 million stillbirths and neonatal deaths in 2022, with nearly 60% occurring in low-income and middle-income countries. The Small Vulnerable Newborn Consortium has proposed a framework combining preterm birth (<37 weeks of gestation), small for gestational age (SGA) by INTERGROWTH-21st standard, and low birthweight (<2500 g) under the category small vulnerable newborns (SVN). Reliable data on SVN from sub-Saharan Africa, central Asia, and south Asia are sparse. We aimed to estimate the incidence of SVN and its types, and quantify risk factors, both overall and trimester-specific, from a pregnancy cohort in north India. METHODS: In the GARBH-Ini (Interdisciplinary Group for Advanced Research on Birth Outcomes-DBT India Initiative) pregnancy cohort, 8000 participants were enrolled with less than 20 weeks' gestation between May 11, 2015, and Aug 8, 2020, at a secondary-care hospital in north India. The cohort was followed up across the antenatal period for a detailed study on preterm birth. We conducted a secondary analysis of cohort data for the outcome of SVN, classified into its types: preterm-SGA, preterm-nonSGA, and term-SGA. We estimated the relative risk and population attributable fraction of candidate risk factors for SVN (modified Poisson regression) and its types (multinomial regression). FINDINGS: 7183 (89·9%) of 7990 participants completed the study. Among 6206 newborns included for analysis, the incidence of SVN was 48·4% (35·1% term-SGA newborns [n=2179], 9·7% preterm-nonSGA newborns [n=605], and 3·6% preterm-SGA newborns [n=222]). Compared with term-nonSGA newborns, proportions of stillbirths and neonatal deaths within 72 h of birth among SVN were three times and 2·5 times higher, respectively. Preterm-SGA newborns had the highest incidence of stillbirth (15 [6·8%] of 222) and neonatal deaths (six [4·2%] of 142). Low body-mass index (BMI <18·5 kg/m2) of participants at the start of pregnancy was associated with higher risk for preterm-SGA (adjusted relative risk [RR] 1·61 [95% CI 1·17-2·22]), preterm-nonSGA (1·35 [1·09-1·68]), and term-SGA (1·44 [1·27- 1·64]), with population attributable fraction ranging from 8·7% to 13·8%. Pre-eclampsia (adjusted RR 1·48 [95% CI 1·30-1·71]), short cervical length (1·15 [1·04-1·26]), and bacterial vaginosis (1·13 [0·88-1·45]) were other important antenatal risk factors. INTERPRETATION: In a comprehensive analysis of SVN and its types from north India, we identified risk factors to guide prioritisation of interventions. Complemented with risk-stratification tools, this focused approach will enhance antenatal care, and accelerate achievement of Sustainable Development Goals-namely, to end preventable deaths of newborns and children younger than 5 years by 2030 (target 3·2). FUNDING: Department of Biotechnology, Government of India and Grand Challenges India-Biotechnology Industry Research Assistance Council, Government of India. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Development and external validation of Indian population-specific Garbhini-GA2 model for estimating gestational age in second and third trimesters.

Background: A large proportion of pregnant women in lower and middle-income countries (LMIC) seek their first antenatal care after 14 weeks of gestation. While the last menstrual period (LMP) is still the most prevalent method of determining gestational age (GA), ultrasound-based foetal biometry is considered more accurate in the second and third trimesters. In LMIC settings, the Hadlock formula, originally developed using data from a small Caucasian population, is widely used for estimating GA and foetal weight worldwide as the pre-programmed formula in ultrasound machines. This approach can lead to inaccuracies when estimating GA in a diverse population. Therefore, this study aimed to develop a population-specific model for estimating GA in the late trimesters that was as accurate as the GA estimation in the first trimester, using data from GARBH-Ini, a pregnancy cohort in a North Indian district hospital, and subsequently validate the model in an independent cohort in South India. Methods: Data obtained by longitudinal ultrasonography across all trimesters of pregnancy was used to develop and validate GA models for the second and third trimesters. The gold standard for GA estimation in the first trimester was determined using ultrasonography. The Garbhini-GA2, a polynomial regression model, was developed using the genetic algorithm-based method, showcasing the best performance among the models considered. This model incorporated three of the five routinely measured ultrasonographic parameters during the second and third trimesters. To assess its performance, the Garbhini-GA2 model was compared against the Hadlock and INTERGROWTH-21st models using both the TEST set (N = 1493) from the GARBH-Ini cohort and an independent VALIDATION dataset (N = 948) from the Christian Medical College (CMC), Vellore cohort. Evaluation metrics, including root-mean-squared error, bias, and preterm birth (PTB) rates, were utilised to comprehensively assess the model's accuracy and reliability. Findings: With first trimester GA dating as the baseline, Garbhini-GA2 reduced the GA estimation median error by more than three times compared to the Hadlock formula. Further, the PTB rate estimated using Garbhini-GA2 was more accurate when compared to the INTERGROWTH-21st and Hadlock formulae, which overestimated the rate by 22.47% and 58.91%, respectively. Interpretation: The Garbhini-GA2 is the first late-trimester GA estimation model to be developed and validated using Indian population data. Its higher accuracy in GA estimation, comparable to GA estimation in the first trimester and PTB classification, underscores the significance of deploying population-specific GA formulae to enhance antenatal care. Funding: The GARBH-Ini cohort study was funded by the Department of Biotechnology, Government of India (BT/PR9983/MED/97/194/2013). The ultrasound repository was partly supported by the Grand Challenges India-All Children Thriving Program, Biotechnology Industry Research Assistance Council, Department of Biotechnology, Government of India (BIRAC/GCI/0115/03/14-ACT). The research reported in this publication was made possible by a grant (BT/kiData0394/06/18) from the Grand Challenges India at Biotechnology Industry Research Assistance Council (BIRAC), an operating division jointly supported by DBT-BMGF-BIRAC. The external validation study at CMC Vellore was partly supported by a grant (BT/kiData0394/06/18) from the Grand Challenges India at Biotechnology Industry Research Assistance Council (BIRAC), an operating division jointly supported by DBT-BMGF-BIRAC and by Exploratory Research Grant (SB/20-21/0602/BT/RBCX/008481) from Robert Bosch Centre for Data Science and Artificial Intelligence (RBCDSAI), IIT Madras. An alum endowment from Prakash Arunachalam (BIO/18-19/304/ALUM/KARH) partly funded this study at the Centre for Integrative Biology and Systems Medicine, IIT Madras.

Color Doppler evaluation of umbilical arteries in relation to bony landmarks in the fetal pelvis as a clue to the mid-trimester diagnosis of bladder exstrophy: A novel observation.

Color Doppler (CD) is an established diagnostic modality for bladder exstrophy. We present two mid-trimester difficult-to-diagnose cases with no obvious infraumbilical mass bulge, assessed by CD in sagittal and axial pelvic views. The first case was a classical bladder exstrophy at 19 weeks nestled under the umbilical-cord and the second case was an omphalocele-exstrophy-imperforate-anus-spinal complex at 18 weeks 4 days gestation with exstrophic bladder embedded under the omphalocele. The altered course of umbilical arteries in relation to pelvic bony landmarks seen in these fetuses could be an objective approach to complement mid-trimester diagnosis of bladder exstrophy regardless of mass bulge.

Developing Clinical Artificial Intelligence for Obstetric Ultrasound to Improve Access in Underserved Regions: Protocol for a Computer-Assisted Low-Cost Point-of-Care UltraSound (CALOPUS) Study.

BACKGROUND: The World Health Organization recommends a package of pregnancy care that includes obstetric ultrasound scans. There are significant barriers to universal access to antenatal ultrasound, particularly because of the cost and need for maintenance of ultrasound equipment and a lack of trained personnel. As low-cost, handheld ultrasound devices have become widely available, the current roadblock is the global shortage of health care providers trained in obstetric scanning. OBJECTIVE: The aim of this study is to improve pregnancy and risk assessment for women in underserved regions. Therefore, we are undertaking the Computer-Assisted Low-Cost Point-of-Care UltraSound (CALOPUS) project, bringing together experts in machine learning and clinical obstetric ultrasound. METHODS: In this prospective study conducted in two clinical centers (United Kingdom and India), participating pregnant women were scanned and full-length ultrasounds were performed. Each woman underwent 2 consecutive ultrasound scans. The first was a series of simple, standardized ultrasound sweeps (the CALOPUS protocol), immediately followed by a routine, full clinical ultrasound examination that served as the comparator. We describe the development of a simple-to-use clinical protocol designed for nonexpert users to assess fetal viability, detect the presence of multiple pregnancies, evaluate placental location, assess amniotic fluid volume, determine fetal presentation, and perform basic fetal biometry. The CALOPUS protocol was designed using the smallest number of steps to minimize redundant information, while maximizing diagnostic information. Here, we describe how ultrasound videos and annotations are captured for machine learning. RESULTS: Over 5571 scans have been acquired, from which 1,541,751 label annotations have been performed. An adapted protocol, including a low pelvic brim sweep and a well-filled maternal bladder, improved visualization of the cervix from 28% to 91% and classification of placental location from 82% to 94%. Excellent levels of intra- and interannotator agreement are achievable following training and standardization. CONCLUSIONS: The CALOPUS study is a unique study that uses obstetric ultrasound videos and annotations from pregnancies dated from 11 weeks and followed up until birth using novel ultrasound and annotation protocols. The data from this study are being used to develop and test several different machine learning algorithms to address key clinical diagnostic questions pertaining to obstetric risk management. We also highlight some of the challenges and potential solutions to interdisciplinary multinational imaging collaboration. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/37374.

COASY related pontocerebellar hypoplasia type 12: A common Indian mutation with expansion of the phenotypic spectrum.

Pontocerebellar hypoplasia (PCH) type 12 is a rare, perinatal lethal neurodegenerative genetic disorder caused by biallelic mutations in the COASY gene. Herein, we describe the clinical and neuroradiological profile of nine affected fetuses/neonates from five families identified with a common COASY: c.1486-3C>G biallelic variant. Four of the five families were identified after data reanalysis of unresolved, severe PCH like phenotype and the fifth family through collaboration. The common antenatal phenotype was cerebellar hypoplasia. Microcephaly, arthrogryposis, and intrauterine growth restriction were the shared postnatal findings. The neurological manifestations included seizures, poor sucking, and spasticity. Novel findings of corpus callosum agenesis, simplified gyral pattern, normal sized pons, optic neuropathy, and a small thorax are reported in this series. The allele frequency of the COASY: c.1486-3C>G variant was 0.62% in the available Asian Indian database. We describe this as a possible common Indian origin variant. To the best of our knowledge, this is the largest PCH12 series reported.

Evaluation of Role of Transabdominal and Transvaginal Ultrasound in Diagnosis of Female Genital Tuberculosis.

BACKGROUND: Female genital tuberculosis (FGTB) is a common problem in developing countries causing significant morbidity, especially infertility. Radiological imaging, especially ultrasound, can help in diagnosis of FGTB with tubo-ovarian masses. AIMS: The present study was performed to evaluate the role of ultrasound in diagnosis of FGTB and to see various findings of FGTB on ultrasound. STUDY SETTING AND DESIGN: It was a prospective cross-sectional study over 4-year period between August 2015 and August 2019 in a tertiary referral center. SUBJECTS AND METHODS: One hundred and seventy-five patients of infertility diagnosed to have FGTB on composite reference standard (CRS) of positive acid-fast bacilli on microscopy or culture of endometrial biopsy, positive polymerase chain reaction, positive GeneXpert, epithelioid granuloma on histology of endometrial biopsy, or definite or probable finding of FGTB on laparoscopy were subjected to transvaginal ultrasound by an experienced sonographer for various findings of FGTB. STATISTICAL ANALYSIS: Data analysis was carried out using STATA software 12.0. Comparison of categorical values was tested using Chi-square Fisher's exact test, with P < 0.05 being taken as significant. RESULTS: Mean age, body mass index, parity, and duration of infertility were 28.9 years, 22.9 kg/m2, 0.26, and 6.06 years, respectively. Menstrual dysfunction was common (44%). Diagnosis of FGTB was made by CRS. Ultrasound was normal in 112 (64%) cases and was abnormal in 63 (36%) cases. Various ultrasound findings were ovarian cyst (23.42%), tubo-ovarian masses (15.42%), unilateral or bilateral hydrosalpinx (13.71%), pyosalpinx (0.57%), adhesion (1.14%), adnexal fixity (6.28%), thin endometrium (24.57%), endometrial fluid (12.57%), endometrial calcification (1.7%), endometrial synechiae (4.57%), cornual synechiae (2.28%), impaired endometrial vascularity (21.71%), ascites (6.85%), and peritoneal or omental thickening (1.75%). CONCLUSION: Carefully performed ultrasound is a useful modality in diagnosis of FGTB, especially in adnexal masses.

Comparison of first trimester dating methods for gestational age estimation and their implication on preterm birth classification in a North Indian cohort.

BACKGROUND: Different formulae have been developed globally to estimate gestational age (GA) by ultrasonography in the first trimester of pregnancy. In this study, we develop an Indian population-specific dating formula and compare its performance with published formulae. Finally, we evaluate the implications of the choice of dating method on preterm birth (PTB) rate. This study's data was from GARBH-Ini, an ongoing pregnancy cohort of North Indian women to study PTB. METHODS: Comparisons between ultrasonography-Hadlock and last menstrual period (LMP) based dating methods were made by studying the distribution of their differences by Bland-Altman analysis. Using data-driven approaches, we removed data outliers more efficiently than by applying clinical parameters. We applied advanced machine learning algorithms to identify relevant features for GA estimation and developed an Indian population-specific formula (Garbhini-GA1) for the first trimester. PTB rates of Garbhini-GA1 and other formulae were compared by estimating sensitivity and accuracy. RESULTS: Performance of Garbhini-GA1 formula, a non-linear function of crown-rump length (CRL), was equivalent to published formulae for estimation of first trimester GA (LoA, - 0.46,0.96 weeks). We found that CRL was the most crucial parameter in estimating GA and no other clinical or socioeconomic covariates contributed to GA estimation. The estimated PTB rate across all the formulae including LMP ranged 11.27-16.50% with Garbhini-GA1 estimating the least rate with highest sensitivity and accuracy. While the LMP-based method overestimated GA by 3 days compared to USG-Hadlock formula; at an individual level, these methods had less than 50% agreement in the classification of PTB. CONCLUSIONS: An accurate estimation of GA is crucial for the management of PTB. Garbhini-GA1, the first such formula developed in an Indian setting, estimates PTB rates with higher accuracy, especially when compared to commonly used Hadlock formula. Our results reinforce the need to develop population-specific gestational age formulae.

Osteomyelitis of Fibula Rare Case with Various Differential Diagnosis.

INTRODUCTION: The osteomyelitis of fibula is a rare case to present. Osteomyelitis is clinical diagnosis with support of various investigation with proper surgical technique and various Differential Diagnosis it is treated with good satisfactory result. CASE REPORT: A 65-year-male operated 10 years back for tibial plateau fracture was asymptomatic but for last 3 months started pus discharging sinus from middle third of leg. We investigated and done implant removal with abnormal tissue abnormal bone was excised out, but very unusual presentation intraoperative necrotic massive debris was there like wood pieces mimic as neoplastic lesion, metastasis, fungal osteomyelitis, or granulomatous infection. However, after biopsy, it was diagnosed pyogenic osteomyelitis 2 weeks of injectable and 6 weeks of oral antibiotics were given. After that 4-6 weeks weight bearing was started, the patient returned to his obvious activities with normal range of motion. CONCLUSION: The osteomyelitis of fibula with various differential diagnosis clinically and intraoperatively with very rare necrotic tissues like wood pieces mimicked neoplasia fungal infection but after proper debridement curettage and biopsy report probable diagnosis is made with proper duration of antibiotic treatment chronic osteomyelitis is treated with satisfactory result with good outcome.

Results of endonasal dacryocystorhinostomy in pediatric patients.

We conducted a prospective interventional study to evaluate the role of endoscopic endonasal dacryocystorhinostomy in children. Our study population was made up of 20 patients-18 boys and 2 girls, aged 2 to 12 years (mean: 5.3)-who presented with signs and symptoms suggestive of nasolacrimal duct blockage that was refractory to conventional medical treatment. In all cases, blockage was confirmed by nasolacrimal duct syringing that demonstrated regurgitation from the opposite punctum. The primary outcome measures for success were resolution of symptoms and duct patency on lacrimal irrigation. At 6 months, 17 patients (85%) experienced complete symptomatic relief, 1 (5%) had partial relief, and 2 (10%) reported no relief. Moreover, the nasolacrimal duct was patent in 17 patients, partially patent in 2, and blocked in 1. We conclude that endoscopic endonasal dacryocystorhinostomy is a safe and effective procedure in children with nasolacrimal duct blockage when medical therapy and probing have been unsuccessful.

Antihyperglycemic, antihyperlipidemic, anti-inflammatory and adenosine deaminase- lowering effects of garlic in patients with type 2 diabetes mellitus with obesity.

INTRODUCTION: Type 2 diabetes mellitus is a chronic disorder characterized by chronic hyperglycemia, with long term macrovascular and microvascular complications. The treatment is lifestyle management, exercise, weight control, and antihyperglycemic drugs such as sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, and meglitinide. Recently, a direct association between high levels of C-reactive protein and serum adenosine deaminase levels in patients with uncontrolled diabetes with long-term complications has been seen. This study was conducted to assess the antihyperglycemic, lipid-lowering, anti-inflammatory, and improving glycemic control of garlic in type 2 diabetes patients with obesity. MATERIALS AND METHODS: This was an open-label, prospective, comparative study, conducted on 60 patients having type 2 diabetes mellitus and obesity. The patients were divided into two groups of 30 each, of either sex. Group 1 was given metformin tablets, 500 mg twice a day (BD)/three times a day (TDS), after meals, and group 2 was given metformin tablets, 500 mg BD/TDS, after meals, along with garlic (Allium sativum) capsules, 250 mg BD. Patients were routinely investigated for fasting and postprandial blood glucose, glycosylated hemoglobin (HbA(1c)), serum adenosine deaminase levels and lipid profile (serum cholesterol, high-density lipoprotein cholesterol, triglycerides and low-density lipoprotein cholesterol) at the start of the study. Patients were followed up for 12 weeks, with monitoring of fasting and postprandial blood glucose at 2 week intervals, and monitoring of the other parameters at the end of study. Data obtained at the end of the study was statistically analyzed using Student's t test. RESULTS: It was observed that both metformin alone and metformin with garlic reduced fasting blood glucose and postprandial blood glucose significantly, with a greater percentage reduction with metformin plus garlic; however, change in HbA(1c) levels was not significant. A fall in total cholesterol, triglyceride, and low-density lipoprotein and an increase in high-density lipoprotein were more pronounced in patients treated with metformin plus garlic. Similarly, a fall in C-reactive protein and adenosine deaminase levels was greater in patients taking metformin with garlic than in patients taking only metformin. CONCLUSION: Garlic has been shown to have antihyperglycemic and lipid-lowering properties. The additional lowering of C-reactive protein and serum adenosine deaminase levels with garlic suggests that garlic can be a valuable agent in providing good glycemic control and the prevention of long-term complications.

Drug-induced Angle-Closure Glaucoma.

Drug-induced angle-closure glaucoma is an important entity for the ophthalmologist as well as the general physician as it represents a preventable cause of potential blindness. This brief review highlights the fact that a high index of suspicion, in a susceptible individual followed by confirmation on appropriate imaging modality (UBM, ultrasound or anterior segment OCT) can alleviate the threat to sight and also help to institute appropriate therapy.