Evaluation of IL-4 and IL-13 Single Nucleotide Polymorphisms and Their Association With Childhood Asthma and Its Severity: A Hospital-Based Case-Control Study.

BACKGROUND AND OBJECTIVES: Asthma is a common, chronic, atopic respiratory disease that is on the rise among children and adults worldwide. Various environmental, genetic, and biological interactions contribute to the surge in susceptibility to this disease. Interleukin (IL) genes, particularly IL-4 and IL-13, have been linked to asthma pathogenesis. The present study aims to investigate the genetic aberrations, specifically single nucleotide polymorphisms (SNPs) of IL-4 and IL-13, and their association with childhood asthma and its severity. METHODS: An unmatched hospital-based case-control study was conducted in a tertiary care hospital in Assam, India. The sample size was calculated to be 120 (60 cases and 60 controls) using the Epi Info software version 7.2 (Centers for Disease Control and Prevention, Atlanta, GA, USA), assuming a confidence interval of 95%, a power of the study at 80%, a ratio of control to cases as 1, a proportion of controls with exposure at 22%, and a proportion of cases with exposure at 46%. A total of 53 clinically diagnosed cases of childhood asthma in the age range of three to 12 years and 39 healthy controls free from respiratory diseases and having no history of asthma and/or allergy of the same age group attending a tertiary care hospital were included in the study. Children who never had asthma or allergies and who did not suffer from any upper or lower respiratory infections for the previous four weeks were considered controls. Prior informed consent and ethical clearance were obtained. Very seriously ill cases and controls were excluded from the study. The genetic investigation used polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP), to discover SNPs in the IL-4 and IL-13 genes. Sequencing analysis was done for the cases with +2044 G>A of the IL-13 gene in relation to the severity of the disease. The difference in the proportions of specific SNPs between cases and controls was analyzed using the χ2 test (a p-value of <0.05 was considered significant). RESULTS: Both the rs2070874 and rs2243250 polymorphisms of IL-4 showed no statistically significant associations. The mutation of the IL-13 gene in 1111C>T was higher among cases than controls. Both genotypic and allelic distributions of the +2044G>A polymorphism of the IL-13 gene revealed a significant association (p<0.05) with the severity of the disease. CONCLUSION: Genetic aberrations in SNPs of IL-4 and IL-13 are prevalent among the pediatric patients of the study region. The SNP +2044G>A of IL-13 is instrumental in disease manifestation and severity among the pediatric population of the study region.

Risk factors for labour induction and augmentation: a multicentre prospective cohort study in India.

Background: Guidelines for labour induction/augmentation involve evaluating maternal and fetal complications, and allowing informed decisions from pregnant women. This study aimed to comprehensively explore clinical and non-clinical factors influencing labour induction and augmentation in an Indian population. Methods: A prospective cohort study included 9305 pregnant women from 13 hospitals across India. Self-reported maternal socio-demographic and lifestyle factors, and maternal medical and obstetric histories from medical records were obtained at recruitment (≥28 weeks of gestation), and women were followed up within 48 h after childbirth. Maternal and fetal clinical information were classified based on guidelines into four groups of clinical factors: (i) ≥2 indications, (ii) one indication, (iii) no indication and (iv) contraindication. Associations of clinical and non-clinical factors (socio-demographic, healthcare utilisation and lifestyle related) with labour induction and augmentation were investigated using multivariable logistic regression analyses. Findings: Over two-fifths (n = 3936, 42.3%, 95% confidence interval [CI] 41.3-43.3%) of the study population experienced labour induction and more than a quarter (n = 2537, 27.3%, 95% CI 26.4-28.2%) experienced augmentation. Compared with women with ≥2 indications, those with one (adjusted odds ratio [aOR] 0.50, 95% CI 0.42-0.58) or no indication (aOR 0.24, 95% CI 0.20-0.28) or with contraindications (aOR 0.12, 95% CI 0.07-0.20) were less likely to be induced, adjusting for non-clinical characteristics. These associations were similar for labour augmentation. Notably, 34% of women who were induced or augmented did not have any clinical indication. Several maternal demographic (age at labour, parity and body mass index in early pregnancy), healthcare utilization (number of antenatal check-ups, duration of iron-folic acid supplementation and individuals managing childbirth) and socio-economic factors (religion, living below poverty line, maternal education and partner's occupation) were independently associated with labour induction and augmentation. Interpretation: Although decisions about induction and augmentation of labour in our study population in India were largely guided by clinical recommendations, we cannot ignore that more than a third of the women did not have an indication. Decisions could also be influenced by non-clinical factors which need further research. Funding: The MaatHRI platform is funded by a Medical Research Council Career Development Award (Grant Ref: MR/P022030/1) and a Transition Support Award (Grant Ref: MR/W029294/1).

Maternal and fetal factors associated with stillbirth in singleton pregnancies in 13 hospitals across six states in India: A prospective cohort study.

OBJECTIVE: This study aimed to investigate the incidence of and risk factors for stillbirth in an Indian population. METHODS: We conducted a secondary data analysis of a hospital-based cohort from the Maternal and Perinatal Health Research collaboration, India (MaatHRI), including pregnant women who gave birth between October 2018-September 2023. Data from 9823 singleton pregnancies recruited from 13 hospitals across six Indian states were included. Univariable and multivariable Poisson regression analysis were performed to examine the relationship between stillbirth and potential risk factors. Model prediction was assessed using the area under the receiver-operating characteristic (AUROC) curve. RESULTS: There were 216 stillbirths (48 antepartum and 168 intrapartum) in the study population, representing an overall stillbirth rate of 22.0 per 1000 total births (95% confidence interval [CI]: 19.2-25.1). Modifiable risk factors for stillbirth were: receiving less than four antenatal check-ups (adjusted relative risk [aRR]: 1.75, 95% CI: 1.25-2.47), not taking any iron and folic acid supplementation during pregnancy (aRR: 7.23, 95% CI: 2.12-45.33) and having severe anemia in the third trimester (aRR: 3.37, 95% CI: 1.97-6.11). Having pregnancy/fetal complications such as hypertensive disorders of pregnancy (aRR: 1.59, 95% CI: 1.03-2.36), preterm birth (aRR: 4.41, 95% CI: 3.21-6.08) and birth weight below the 10th percentile for gestational age (aRR: 1.35, 95% CI: 1.02-1.79) were also associated with an increased risk of stillbirth. Identified risk factors explained 78.2% (95% CI: 75.0%-81.4%) of the risk of stillbirth in the population. CONCLUSION: Addressing potentially modifiable antenatal factors could reduce the risk of stillbirths in India.

The complex relationship between iron status and anemia in pregnant and postpartum women in India: Analysis of two Indian study cohorts of uncomplicated pregnancies.

Low hemoglobin is widely used as an indicator of iron deficiency anemia in India and other low-and-middle income counties, but anemia need not accurately reflect iron deficiency. We examined the relationship between hemoglobin and biomarkers of iron status in antenatal and postnatal period. Secondary analysis of uncomplicated singleton pregnancies in two Indian study cohorts: 1132 antenatal women in third trimester and 837 postnatal women 12-72 h after childbirth. Associations of hemoglobin with ferritin in both data sets, and with sTfR, TSAT, and hepcidin in the postnatal cohort were examined using multivariable linear regression. Multinomial logistic regression was used to examine the association between severity of anemia and iron status. Regression models were adjusted for potential confounders. Over 55% of the women were anemic; 34% of antenatal and 40% of postnatal women had low ferritin, but 4% antenatal and 6% postnatal women had high ferritin. No evidence of association between hemoglobin and ferritin was observed (antenatal: adjusted coefficient [aCoef] -0.0004, 95% confidence interval [CI] -0.001, 0.001; postnatal: aCoef -0.0001, 95% CI -0.001, 0.001). We found a significant linear association of hemoglobin with sTfR (aCoef -0.04, 95% CI -0.07, -0.01), TSAT (aCoef -0.005, 95% CI -0.008, -0.002), and hepcidin (aCoef 0.02, 95% CI 0.02, 0.03) in postnatal women. Likelihood of low ferritin was more common in anemic than non-anemic women, but high ferritin was also more common in women with severe anemia in both cohorts. Causes of anemia in pregnant and postpartum women in India are multifactorial; low hemoglobin alone is not be a useful marker of iron deficiency.

Focused Cardiac Ultrasound to Guide the Diagnosis of Heart Failure in Pregnant Women in India.

BACKGROUND: Cardiac complications are a leading cause of maternal death. Cardiac imaging with echocardiography is important for prompt diagnosis, but it is not available in many low-resource settings. The aim of this study was to determine whether focused cardiac ultrasound performed by trained obstetricians and interpreted remotely by experts can identify cardiac abnormalities in pregnant women in low-resource settings. METHODS: A cross-sectional study was conducted among 301 pregnant and postpartum women recruited from 10 hospitals across three states in India. Twenty-two obstetricians were trained in image acquisition using a portable cardiac ultrasound device following a simplified protocol adapted from focus-assessed transthoracic echocardiography protocol. It included parasternal long-axis, parasternal short-axis, and apical four-chamber views on two-dimensional and color Doppler. Independent image interpretation was performed remotely by two experts, in the United Kingdom and India, using a standard semiquantitative assessment protocol. Interrater agreement between the experts was examined using Cohen's κ. Diagnostic accuracy of the method was examined in a subsample for whom both focused and conventional scans were available. RESULTS: Cardiac abnormalities identified using the focused method included valvular abnormalities (27%), rheumatic heart disease (6.6%), derangements in left ventricular size (4.7%) and function (22%), atrial dilatation (19.5%), and pericardial effusion (30%). There was substantial agreement on the cardiac parameters between the two experts, ranging from 93.6% (κ = 0.84) for left ventricular ejection fraction to 100% (κ = 1) for valvular disease. Image quality was graded as good in 79% of parasternal long-axis, 77% of parasternal short-axis and 64% of apical four-chamber views. The chance-corrected κ coefficients indicated fair to moderate agreement (κ = 0.28-0.51) for the image quality parameters. There was good agreement on diagnosis between the focused method and standard echocardiography (78% agreement), compared in 36 participants. CONCLUSIONS: The focused method accurately identified cardiac abnormalities in pregnant women and could be used for screening cardiac problems in obstetric settings.

Relationship between anaemia, coagulation parameters during pregnancy and postpartum haemorrhage at childbirth: a prospective cohort study.

OBJECTIVES: To investigate the association between coagulation parameters and severity of anaemia (moderate anaemia: haemoglobin (Hb) 7-9.9 g/dL and severe anaemia: Hb <7 g/dL) during pregnancy and relate these to postpartum haemorrhage (PPH) at childbirth. DESIGN: A prospective cohort study of pregnant women recruited in the third trimester and followed-up after childbirth. SETTING: Ten hospitals across four states in India. PARTICIPANTS: 1342 pregnant women. INTERVENTION: Not applicable. METHODS: Hb and coagulation parameters: fibrinogen, D-dimer, D-dimer/fibrinogen ratio, platelets and international normalised ratio (INR) were measured at baseline. Participants were followed-up to measure blood loss within 2 hours after childbirth and PPH was defined based on blood loss and clinical assessment. Associations between coagulation parameters, Hb, anaemia and PPH were examined using multivariable logistic regression models. OUTCOMES MEASURES: Adjusted OR with 95% CI. RESULTS: In women with severe anaemia during the third trimester, the D-dimer was 27% higher, mean fibrinogen 117 mg/dL lower, D-dimer/fibrinogen ratio 69% higher and INR 12% higher compared with women with no/mild anaemia. Mean platelets in severe anaemia was 37.8×109/L lower compared with women with moderate anaemia. Similar relationships with smaller effect sizes were identified for women with moderate anaemia compared with women with no/mild anaemia. Low Hb and high INR at third trimester of pregnancy independently increased the odds of PPH at childbirth, but the other coagulation parameters were not found to be significantly associated with PPH. CONCLUSION: Altered blood coagulation profile in pregnant women with severe anaemia could be a risk factor for PPH and requires further evaluation.

Maternal and perinatal Health Research Collaboration, India (MaatHRI): methodology for establishing a hospital-based research platform in a low and middle income country setting.

Background: Maternal and perinatal Health Research collaboration, India (MaatHRI) is a research platform that aims to improve evidence-based pregnancy care and outcomes for mothers and babies in India, a country with the second highest burden of maternal and perinatal deaths. The objective of this paper is to describe the methods used to establish and standardise the platform and the results of the process. Methods: MaatHRI is a hospital-based collaborative research platform. It is adapted from the UK Obstetric Surveillance System (UKOSS) and built on a pilot model (IndOSS-Assam), which has been extensively standardised using the following methods: (i) establishing a network of hospitals; (ii) setting up a secure system for data collection, storage and transfer; (iii) developing a standardised laboratory infrastructure; and (iv) developing and implementing regulatory systems. Results: MaatHRI was established in September 2018. Fourteen hospitals participate across four states in India - Assam, Meghalaya, Uttar Pradesh and Maharashtra. The research team includes 20 nurses, a project manager, 16 obstetricians, two pathologists, a public health specialist, a general physician and a paediatrician. MaatHRI has advanced standardisation of data and laboratory parameters, real-time monitoring of data and participant safety, and secure transfer of data. Four observational epidemiological studies are presently being undertaken through the platform. MaatHRI has enabled bi-directional capacity building. It is overseen by a steering committee and a data safety and monitoring board, a process that is not normally used, but was found to be highly effective in ensuring data safety and equitable partnerships in the context of low and middle income countries (LMICs). Conclusion: MaatHRI is the first prototype of UKOSS and other similar platforms in a LMIC setting. The model is built on existing methods but applies new standardisation processes to develop a collaborative research platform that can be replicated in other LMICs.