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.

Post-natal gestational age assessment using targeted metabolites of neonatal heel prick and umbilical cord blood: A GARBH-Ini cohort study from North India.

Background: Accurate assessment of gestational age (GA) and identification of preterm birth (PTB) at delivery is essential to guide appropriate post-natal clinical care. Undoubtedly, dating ultrasound sonography (USG) is the gold standard to ascertain GA, but is not accessible to the majority of pregnant women in low- and middle-income countries (LMICs), particularly in rural areas and small secondary care hospitals. Conventional methods of post-natal GA assessment are not reliable at delivery and are further compounded by a lack of trained personnel to conduct them. We aimed to develop a population-specific GA model using integrated clinical and biochemical variables measured at delivery. Methods: We acquired metabolic profiles on paired neonatal heel prick (nHP) and umbilical cord blood (uCB) dried blood spot (DBS) samples (n = 1278). The master data set consists of 31 predictors from nHP and 24 from uCB after feature selection. These selected predictors including biochemical analytes, birth weight, and placental weight were considered for the development of population-specific GA estimation and birth outcome classification models using eXtreme Gradient Boosting (XGBoost) algorithm. Results: The nHP and uCB full model revealed root mean square error (RMSE) of 1.14 (95% confidence interval (CI) = 0.82-1.18) and of 1.26 (95% CI = 0.88-1.32) to estimate the GA as compared to actual GA, respectively. In addition, these models correctly estimated 87.9 to 92.5% of the infants within ±2 weeks of the actual GA. The classification models also performed as the best fit to discriminate the PTB from term birth (TB) infants with an area under curve (AUC) of 0.89 (95% CI = 0.84-0.94) for nHP and an AUC of 0.89 (95% CI = 0.85-0.95) for uCB. Conclusion: The biochemical analytes along with clinical variables in the nHP and uCB data sets provide higher accuracy in predicting GA. These models also performed as the best fit to identify PTB infants at delivery.

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.

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.

Longitudinal changes in serum immune markers during normal pregnancy in a North-Indian population.

PROBLEM: The objective of this study was to examine levels of cytokines across normal term pregnancy in an Indian population. Additionally we have also explored for possible associations between inflammatory markers and fetal growth parameters. METHOD OF STUDY: A multiplex panel of 24 analytes was used to examine levels of inflammatory markers in maternal serum at three time points during pregnancy and in cord blood from women with no reported comorbidities who delivered a singleton live baby at term (N = 23), enrolled in the GARBH-Ini pregnancy cohort. Linear mixed models were applied to construct longitudinal cytokine trajectories with gestational age. Pearson correlation was used to calculate intra-visit correlation between cytokines. Principal component analysis (PCA) was performed to examine cytokine combinations prevalent across pregnancy, and their association with fetal growth parameters was determined by multivariable regression. RESULTS: Significant increase in sFLT-1, Flt3L, PLGF, IL-4, and IL-18 and a decrease in VCAM-1 concentrations was seen across pregnancy. The cytokine concentrations in cord blood differed substantially as compared to maternal levels across gestation. Some cytokines were closely correlated with each other in distinct patterns across pregnancy. Gestational age specific combination of cytokines were seen to be associated with different fetal growth parameters. CONCLUSIONS: This study for the first time provides reference concentrations for the longitudinal expression of immune markers across pregnancy in an Indian population providing a much needed baseline to compare with pregnancies leading to adverse outcomes. Growth factors showed maximum longitudinal variation with gestational age and strong correlations were identified between various cytokines at all time points across pregnancy.

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.

Maxillary reservoir denture to overcome radiation-induced xerostomia - Light at the end of the tunnel.

Xerostomia is a subjective symptom of dry mouth. It can occur as a part of the systemic disease, drug-induced side effect, or following therapeutic radiation therapy to the head-and-neck region. The primary complication faced by these xerostomic patients is the difficulty in retention of removable dentures. It is important to recognize that the prosthodontic management of these patients requires special attention and care. In an attempt to overcome the presence of xerostomia, several techniques of introducing reservoirs into the dentures containing salivary substitutes have been proposed. This case report presents a simplified approach for the construction of a reservoir in the maxillary denture, specifically in patients where other treatment modalities have failed. This technique provided excellent lubrication to oral tissues, hygienic for the patient, and utilized routine denture base material.

Rehabilitation of ocular defect: A modified technique to produce corneal prominence.

Esthetics is a vital social concern. The loss of any part of the body can be an extremely discouraging occasion in a person's life. Loss of an eye because of tumors, congenital abnormalities, and trauma is one such troublesome situation. Eye prosthesis boosts the morale and makes the life socially acceptable. A correctly placed ocular prosthesis should reestablish the normal opening of the eye, support the eyelids, reestablish a degree of movement, and be satisfactorily held and esthetically satisfying. A customized acrylic eye fulfills all these requirements. In the current article, a new and economic technique was used to duplicate corneal prominence using a clear acrylic shell. The characterization was further done to give a life-like appearance to the eye prostheses.

Denture barcoding in forensic dentistry: A future option.

Neurodegenerative disorders are commonly seen in elderly individuals. Parkinson's disease (PD) is the most common example with memory loss, lack of logic, reasoning and analytical thinking. In this case report simple method of 2D Bar code technique of denture marking has been explained which will not only useful in patients with memory loss but it is very helpful in identifying the individuals in case of natural calamities like floods, earthquake, tornedo, state of unconsciousness and accidents. Such patients can be traced easily by denture barcoding. This technique is a major breakthrough in the field of forensic dentistry.