Clinical effectiveness of ferric carboxymaltose (iv) versus iron sucrose (iv) in treatment of iron deficiency anaemia in pregnancy: A systematic review and meta-analysis.

BACKGROUND OBJECTIVES: Iron deficiency anaemia (IDA) during pregnancy is treated with oral and parenteral iron. The objective of this review was to compare the clinical effectiveness, safety, pregnancy and neonatal outcomes of intravenous (iv) ferric carboxymaltose (FCM) and iv iron sucrose (IS) in treating IDA in pregnancy. METHODS: The Department of Health Research funded this study. PubMed, Cochrane Library, EMBASE and Scopus were searched to include studies published till November 2022. The protocol was registered in PROSPERO (CRD42022306092). Pregnant women (15-49 yr) in second and third trimesters, diagnosed with moderate-to-severe iron deficiency anaemia, treated with either of the drugs were included. The included studies were critically assessed using appropriate tools. We conducted a qualitative synthesis of the studies and meta-analysis for improvement in haematological parameters and incidence of adverse events. RESULTS: A total of 18 studies were included. The risk of bias was low to moderate. A rise in haemoglobin up to four weeks was higher with FCM than IS by 0.57 (0.24, 0.9) g/dl. Intravenous FCM is associated with fewer adverse events than IS [pooled odds ratio: 0.5 (0.32, 0.79)]. The included studies had limited evidence on pregnancy and neonatal outcomes after iv iron treatment. INTERPRETATION CONCLUSIONS: Intravenous FCM is effective and safer than intravenous IS in terms of haematological parameters, in treating IDA in pregnancy. Further research is required on the effects of iv FCM and iv IS on the pregnancy and neonatal outcomes when used for treating IDA in pregnancy.

Public Health System's Preparedness to Address Polycystic Ovarian Syndrome: A Rapid Assessment Survey of Health-care Providers in India.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders largely affecting women of reproductive age group. OBJECTIVES: This study aimed to understand the Indian public health-care systems' preparedness in addressing PCOS. MATERIALS AND METHODS: A multicentric rapid assessment cross-sectional study was undertaken among 173 health-care providers serving across various public health-care facilities in India. This study was a component of a larger task force study that aimed to estimate the community-based prevalence of PCOS in India. Information on PCOS cases reported that knowledge about PCOS diagnosis, management practices, availability of diagnostic facilities, and drugs was explored. RESULTS: Irregular menstrual cycle was the most commonly reported PCOS symptom. Most of the health-care providers (HCPs) lacked correct knowledge about diagnostic criteria and investigation needed for the diagnosis of PCOS. Diagnostic facilities and drugs were inadequate. However, some facilities had access to investigations through public-private partnerships. Awareness programs on PCOS in the community were negligible, and PCOS cases were not documented. Training HCPs on PCOS along with the availability of specialists and strengthening diagnostic facilities were some major demands from the HCPs. CONCLUSION: Results suggest the need for training HCPs, strengthening infrastructure with good referral linkages, and adequate supply of drugs to help improve PCOS management at public health-care facilities in India. There is a need to develop national technical and operational guidelines to address PCOS using a multidisciplinary approach across all levels of care. Creating demand for services and advocating healthy lifestyles through community awareness can help early diagnosis and prevention of complications.

Cost-effectiveness and budget impact of adding tranexamic acid for management of post-partum hemorrhage in the Indian public health system.

BACKGROUND: Postpartum hemorrhage (PPH) is the global leading cause of maternal mortality, affecting nearly 3 to 6 percent of all women giving birth in India. The World Health Organization (WHO) has updated its guidelines to recommend the early use of intravenous (IV) tranexamic acid (TXA) in addition to standard care for all diagnosed PPH cases. This study aimed to assess the cost-effectiveness of introducing TXA for PPH management in the Indian public health system. METHODS: A decision analytic model was built using a decision tree to determine the cost-effectiveness of administering IV TXA to women experiencing PPH within 3 h of birth to existing management with uterotonics and supportive care. Using a disaggregated societal perspective, the costs and consequences for a hypothetical cohort of women experiencing PPH in public health facilities was estimated. The model was populated using probabilities, clinical parameters, and utilities from published literature, while cost parameters were largely derived from a primary economic costing study. The primary outcome of interest was the incremental cost-utility ratio (ICUR). Associated clinical events and net benefits were estimated. One-way and probabilistic sensitivity analysis (PSA) was undertaken. The budget impact was estimated for a national-level introduction. RESULTS: For an estimated annual cohort of 510,915 PPH cases in India, the addition of IV TXA would result in a per-patient disaggregated societal cost of INR 6607 (USD 95.15) with a discounted gain of 20.25 QALYs, as compared to a cost of INR 6486 (USD 93.41) with a discounted gain of 20.17 QALYs with standard care PPH management. At an ICUR value of INR 1470 per QALY gained (USD 21), the addition of IV TXA is cost-effective in Indian public health settings. The intervention is likely to prevent 389 maternal deaths, 177 surgeries, and 128 ICU admissions per 100,000 PPH cases. The findings are robust under uncertainty, with 94.5% of PSA simulations remaining cost-effective. A cumulative increase of 2.3% financial allocation for PPH management over five years will be incurred for TXA introduction. CONCLUSIONS: Addition of tranexamic acid for primary PPH management, as recommended by WHO, is cost-effective in Indian public health settings. Policy guidelines, training manuals, and facility checklists should be updated to reflect this recommendation.

Health facility-based interventions and the uptake of contraception among people living with HIV: A systematic review & meta-analysis.

BACKGROUND OBJECTIVES: The prong 2 of 4 prong strategy introduced by the World Health Organization aims at averting unintended pregnancies among people living with HIV (PLHIV). This systematic review aimed to generate evidence on the effectuality of facility-based interventions in improving uptake of modern and dual contraception, for reducing unmet family planning (FP) needs and unintended pregnancies among PLHIV. METHODS: Articles evaluating facility-based interventions to integrate human immunodeficiency virus (HIV) and FP published in English language were included. Eligible studies were identified from electronic and lateral search from three databases (PubMed, Cochrane Library and Web of Science) and grey literature. HIV care with no/minimal focus on FP was considered a comparator. Quality was assessed using design-appropriate tools. Descriptive analysis was presented in tables. Uptake of dual methods, unmet FP needs and unintended pregnancies were included in the meta-analysis to estimate pooled odds ratio (OR) with random effect model, P and I2 values. RESULTS: The search yielded 2112 results. After excluding duplicates and unfit articles, 17 were found eligible for review and nine for meta-analysis. The pooled OR for uptake of dual contraception was 1.69 (1.14, 2.5) ( P =0.008; I2 =90%), for unmet FP needs was 0.58 (0487, 0.69) ( P <0.00001; I2 =0%) and for unintended pregnancies was 0.6 (0.32, 1.1) ( P =0.1, I2 =38%). INTERPRETATION CONCLUSIONS: The results of this meta-analysis suggest that health facility-based interventions to integrate HIV and FP services do result in improved uptake of dual methods and reduce unmet need for contraception along with a protective trend on incidence of unintended pregnancies. Such facility-based integration would ensure universal access to effective contraception and facilitate in achieving Sustainable Development Goals that aim at ending epidemics like HIV.

Health system cost for providing antiretroviral therapy, family planning, and pregnancy-related services to women living with HIV in public health settings, Mumbai, India.

Background: Integration of HIV care into family planning (FP) services would help in reducing unintended pregnancies among women living with HIV. Objectives: This study focuses on determining the health system cost for providing the linked HIV-FP services per beneficiary for the year 2019-2020. Materials and Methods: Using mixed micro-costing approach costs were collected from two tertiary hospitals in Maharashtra, India. The economic costs collected from gynaecology department and anti-retroviral treatment center were combined and added with package, program, and intervention costs to obtain health-system costs. We conducted probabilistic sensitivity analysis. Results: The unit cost and annual per-capita cost for providing HIV care (without considering cost of drugs and investigations) per beneficiary were INR 1033.8 (USD 13.6) and INR 9304.2 (USD 122.7), respectively. The unit cost was least for the outpatient services INR 197.5 (USD 2.6), followed by inpatient services INR 2735.92 (USD 36.21) and operation theater INR 4410 (USD 58.2). Cost was highest for dual-permanent (INR 13866.8 [USD 182.9]) followed by dual-reversible user (INR 2104.8 [USD 24.8]). It was the least for a person who only used condoms at INR 1674.1 (USD 22.1). In pregnancy-related services, cost for ante-natal services was least (INR 2043.6 [USD 27.96]), followed by vaginal delivery (INR 7120.5 [USD 93.93]), abortion (INR 11530.5 [USD 152.097]), and C-section (INR 18703.8 [USD 246.7]). Conclusion: We found no staggeringly additional costs for providing FP and pregnancy-related services to HIV-affected population, in comparison to general population. The findings could improve programs and insurance with a focus on this vulnerable population.

Cost of providing family planning services & management of pregnancy outcomes at public health facilities in India.

Background & objectives: Lack of costing data is a critical gap that exists in the field of family planning (FP) in India. The aim of this study was to estimate health system costs of FP in India for existing modern methods, and potential newer methods (etonorgestrel implant and levonorgestrel intrauterine device) and pregnancy-related services in India. Methods: A bottom-up micro-costing study was conducted in five public health facilities of an Indian State. Data of last one year were collected from existing hospital records and hospital staff was interviewed. Collected data were analyzed using standard costing methods. Results: Package costs of delivering FP services ranged from ₹ 807 (95% CI 685, 931) for condoms and ₹ 10,539 (8796, 12269) for tubal ligation. Estimates of etonorgestrel implant and levonorgestrel intrauterine system were ₹ 3,200 (2800, 3625) and 3,426 (3232, 3623). Cost of antenatal care along with vaginal delivery, caesarean and abortion were ₹ 10,916 (8744, 13078), 22,136 (17570, 26910) and 8,574 (6791, 10379), respectively. One way sensitivity analysis showed that the three most influential factors on the costs of FP services were prices of drugs and consumables, number of beneficiaries and health personnel cost. Interpretation & conclusions: The present study has generated package costs for FP and pregnancy-related services in India which could be used by publicly-funded insurance schemes, for budgeting, economic evaluations and improve resource allocation of services. The cost estimates from this study add to the limited literature in India on costs of FP.

Assessing the potential of self-help group women for improving reproductive health of women in a tribal block of Maharashtra, India.

Background & objectives: In the current health system, cash incentives are given to accredited social health activists for referring women to public health facilities for specific maternal and child health services, however many reproductive health problems are not included in these services. The objective of this study was to assess the impact of involvement of self-help groups (SHGs) in improving reproductive health seeking behaviour and service utilization by tribal women. Methods: An experimental study was conducted in two tribal blocks of Nasik district (Kalvan and Surgana) in Maharashtra, India, over a period of 18 months. Interventions included training of SHG women and providing incentives to them for conducting health education sessions for reproductive age group women in the community and referring those with the requisite problems, to the health facilities. Pre- and post-intervention focus group discussions and in-depth interviews among SHG women were conducted. Training of service providers on diagnosis and treatment of reproductive morbidities was done, and health service utilization was assessed. Results: Sixty five per cent of the referred women with reproductive morbidities availed services at the public health facilities. A review of records of women seeking services for reproductive health problems showed that there was a significant improvement in the intent for seeking services in the study block as compared to the control block (χ[2]-9.06, P<0.002). Interpretation & conclusions: This study demonstrates the feasibility of utilizing the potential of SHGs for improving reproductive health seeking behaviour of the tribal women. The results suggest that this model could be scaled up to address the neglected reproductive health needs of women without burdening the existing human resources.

An integrated multidisciplinary model of care for addressing comorbidities beyond reproductive health among women with polycystic ovary syndrome in India.

Background & objectives: Polycystic Ovary Syndrome (PCOS) is becoming an area of global and national health concern. It requires a life cycle approach from adolescence to menopause. To comprehensively address the wide spectrum of this disorder, a multidisciplinary model of care was established for women with PCOS in a government setting in India with an objective to screen and manage multifaceted manifestations of PCOS and to diagnose and treat associated comorbidities such as metabolic syndrome, dermatologic manifestations and psychological issues. Methods: A model of integrated multidisciplinary PCOS clinic was implemented for services and research at ICMR-National Institute for Research in Reproductive and Child Health (NIRRCH), Mumbai Maharashtra, India. This is a one-stop holistic centre for managing menstrual, cosmetic, infertility, obesity, metabolic and psychological concerns of women affected with PCOS. Two hundred and twenty six women diagnosed with PCOS using the Rotterdam criteria were screened for metabolic comorbidities with anthropometry, ultrasonography, hormonal and biochemical tests and for psychological problems. Analysis was performed using SPSS version 19.0. Results: Mean body mass index (BMI) was 26.1 kg/m2, higher for Asians. Hirsutism was observed in 53.6 per cent of women. Metabolic syndrome was seen among 35.3 per cent and non-alcoholic fatty liver in 18.3 per cent. Psychological issues such as anxiety and depression were identified in majority of the women 31.4 per cent of women could achieve pregnancy at the end of one year of multidisciplinary management. Interpretation & conclusions: The results of the present study suggest that an integrated multidisciplinary approach led to the early identification and treatment of comorbidities of PCOS, especially metabolic syndrome. There is hence an urgent need to implement multidisciplinary PCOS clinics in government health facilities.

Enablers & challenges of tribal women & health system for implementation of screening of non-communicable diseases & common cancers: A mixed-methods study in Palghar district of Maharashtra, India.

Background & objectives: Non-communicable diseases (NCDs) and cancers of breast, oral cavity and cervix contribute to around 5.87 million (60%) deaths in India. Despite this, there is limited evidence on preparedness of the tribal health system in mitigating these conditions. This mixed-methods study aimed at identifying enablers and challenges using a multistakeholder approach for the screening of NCDs and common cancers in a tribal block of Maharashtra, India. Methods: This study was conducted in a tribal community of Dahanu taluka in Palghar district of Maharashtra. A total of nine focus group discussions (FGDs) among tribal women and accredited social health activists (ASHAs), 13 key informant interviews (KIIs) among auxiliary nurse midwives (ANMs) and community health officers (CHO) and facility surveys of five public health facilities were conducted. The FGDs and KIIs were conducted using guides, recorded digitally, transcribed, analyzed and triangulated to identify emerging themes. Results: The tribal women had limited knowledge about NCDs and common cancers. Paucity of health facilities, out-of-pocket expenditure, misconceptions, belief on traditional healers and inability to prioritize health were identified as major challenges. The ASHAs were recognized as a key connecting link between health system and community while provision of culturally appropriate IEC materials and adequate training were recognized as critical enablers by healthcare providers in implementing screening for NCDs and common cancers. Interpretation & conclusions: The study recommends incorporating socioculturally relevant strategies in the tribal population and strengthening health facilities in terms of infrastructure and training with involvement of ASHAs for successful implementation of the National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) through health and wellness centres.

A systematic review on clinical effectiveness, side-effect profile and meta-analysis on continuation rate of etonogestrel contraceptive implant.

BACKGROUND: Unintended pregnancies (UIP) have a significant impact on health of women and the health budget of countries. Contraception is an effective way to prevent UIPs. The study objective was to collate evidence on clinical effectiveness of etonogestrel subdermal implant (ESI), continuation rate and side effect profile among eligible women of reproductive age group, as compared to levonorgestrel intrauterine system (LNG-IUS), copper intrauterine device (Cu-IUD) and depot medroxy progesterone acetate injections; other types of contraceptive implants were excluded as comparators. METHODS: The protocol of the systematic review was registered in Prospero (registration number: CRD42018116580). MEDLINE via PubMed, Cochrane library and web of science were the electronic databases searched. A search strategy was formulated and studies from 1998 to 2019 were included. Clinical trial registries and grey literature search was done. Critical assessment of included studies was done using appropriate tools. A qualitative synthesis of included studies was done and a meta-analysis was conducted in RevMan software for continuation rates of ESI as compared to other long acting reversible contraceptives (LARC) e.g. LNG IUS and Cu-IUD. RESULTS: The search yielded 23,545 studies. After excluding 467 duplicates, 23,078 titles were screened and 51 studies were included for the review. Eight of the 15 studies reporting clinical effectiveness reported 100% effectiveness and overall pearl index ranged from 0 to 1.4. One-year continuation rates ranged from 57-97%; 44-95% at the end of second year and 25-78% by 3 years of use. Abnormal menstruation was the most commonly reported side effect. There was no significant difference in bone mineral density at 1 year follow-up. The meta-analyses showed that odds ratio (OR) of 1-year continuation rate was 1.55 (1.36, 1.76) for LNG-IUS vs. ESI and 1.34 (1.13, 1.58) for copper-IUD vs. ESI; showing that continuation rates at the end of one-year were higher in LNG-IUS and copper-IUD as compared to ESI. CONCLUSION: ESI is clinically effective and safe contraceptive method to use, yet 1-year continuation rates are lower as compared to LNG-IUS and copper-IUD, mostly attributed to the disturbances in the menstruation.

Significance of Vitamin D Binding Protein in Assessing Vitamin D Status Among Under-Five Children.

Despite ample sunshine, 50-90% Indian children have Vitamin D deficiency (VDD). This enigma of widespread VDD needs exploration especially among under-fives as physiological variations in Vitamin D Binding Protein (VDBP) levels could be potential confounders in the interpretation of total 25-hydroxyvitamin D [25(OH)D]. However, there is scarce information about relevance of VDBP levels in under-five age group. We therefore, explored association of VDBP levels among 1-5 year old children with VDD. Serum levels of 25(OH)D, VDBP, calcium, parathyroid hormone (PTH) and alkaline phosphatase were estimated in 210 apparently healthy children in the age group of 1-5 years. VDD was defined as serum 25(OH)D levels < 20 ng/ml as per the IOM classification. VDBP levels were classified as low if levels were < 168 µg/ml as per the kit. The prevalence of VDD was 79.5% (n = 167) and VDBP levels were low in 48.6% (n = 102) of children. 25(OH)D levels correlated positively with VDBP (r = 0.298, p = 0.0001). A significant number of children (52.7%) with VDD had low VDBP (p = 0.015). and despite adequate sun exposure, 43% of children showed VDD and 56.6% had low VDPB levels. The low VDBP levels largely explain low 25OHD levels without necessarily implying VDD. It may add a new dimension for better understanding of widespread VDD among under-five children. It thus, points towards the need for redefining cut offs and complete evaluation of vitamin D status among under-fives including VDBP.

Linking HIV & family planning services to improve dual methods of contraception among women infected with HIV in Mumbai, Maharashtra, India.

BACKGROUND & OBJECTIVES: Preventing unintended pregnancies among people living with HIV (PLHIV) is one of the strategies of WHO for preventing parent-to-child transmission (PPTCT). Given the limitation of only condom use, the objective of this study was to improve use of dual contraceptive methods among HIV infected women. METHODS: An experimental study among HIV positive women was conducted at two tertiary care level hospitals in Mumbai. Linking HIV with family planning services was the focus of intervention at one site and standard level of care was maintained at the control site. At each site, 150 HIV+ve women attending counselling and testing centres, who did not intend to get pregnant in the next one year and were eligible to use dual methods, were enrolled and followed up to one year. RESULTS: At the end of one year, 60 per cent women in the intervention group reached Family Planning centres compared to eight per cent in the control group. There was three times more acceptance and continuation of use of dual methods along with increase in consistent use of condoms and less number of unplanned pregnancies in the intervention group than the control group. INTERPRETATION & CONCLUSIONS: The study findings demonstrate that linking HIV and family planning services may facilitate the uptake of dual methods of contraception without reducing consistent condom use among HIV infected women. The PPTCT programmes need to focus on the component of Prong 2 of PPTCT which aims to prevent unintended pregnancies among HIV positive women.

Changes in sexual behavior and contraceptive use after HIV acquisition and factors associated with risky sexual practices among people living with HIV in selected Indian cities.

BACKGROUND: Sexual behavior and contraceptive use among HIV-infected persons are a neglected issue in public health programs. OBJECTIVES: To understand sexual practices and contraceptive use of people living with HIV (PLHIV) before and after being diagnosed with the infection and assess the providers' perspectives on provision of contraceptives to PLHIV, the quality of services provided and linkages between reproductive health and HIV services. METHODS: A mix method design study using a purposive sampling was undertaken enrolling PLHIV from ART centers and PLHIV networks across three cities in India. Doctors and counselors providing HIV services at public hospitals were also interviewed. RESULTS: Use of condoms increased from 35% to 81% after being diagnosed with HIV. Consistent condom use was 69% compared to only 8.7% before being diagnosed with HIV. Nearly 41% (297) of participants indulged in one or more forms of risky sexual behaviors. Significant correlates of risky sexual practices were: participants who were middle-aged (25-33 years), formerly married, currently not on antiretroviral therapy, and received negligible information on contraception from service providers leading to poor knowledge on safe sex and dual protection. Information from service providers reveals a lack of specific program guidelines to comprehensively address family planning (FP) issues through HIV programs. CONCLUSION: The study throws light on missed opportunities to address contraceptive needs of PLHIV and recommends training service providers and operationalizing a strategy to link HIV and FP services.

Level of suboptimal adherence to first line antiretroviral treatment & its determinants among HIV positive people in India.

BACKGROUND & OBJECTIVES: National Anti-retroviral treatment (ART) programme in India was launched in 2004. Since then, there has been no published country representative estimate of suboptimal adherence among people living with HIV (PLHIV) on first line ART in public settings. Hence a multicentric study was undertaken in 15 States of India to assess the level of suboptimal adherence and its determinants among PLHIV. METHODS: Using a prospective observational study design, 3285 PLHIV were enrolled and followed up to six months across 30 ART centres in India. Adherence was assessed using pill count and self-reported recall method and determinants of suboptimal adherence were explored based on the responses to various issues as perceived by them. RESULTS: Suboptimal adherence was found in 24.5 per cent PLHIV. Determinants of suboptimal adherence were illiteracy (OR--1.341, CI--1.080-1.665), on ART for less than 6 months (OR--1.540, CI--1.280-1.853), male gender (OR for females--0.807, CI--0.662-0.982), tribals (OR--2.246, CI--1.134-4.447), on efavirenz (EFA) regimen (OR--1.479, CI--1.190-1.837), presence of anxiety (OR--1.375, CI--1.117-1.692), non-disclosure of HIV status to family (OR--1.549, CI--1.176-2.039), not motivated for treatment (OR--1.389, CI--1.093-1.756), neglect from friends (OR--1.368, CI--1.069-1.751), frequent change of residence (OR--3.373, CI--2.659-4.278), travel expenses (OR--1.364, CI--1.138-1.649), not meeting the PLHIV volunteer/community care coordinator at the ART center (OR--1.639, CI--1.330-2.019). INTERPRETATION & CONCLUSIONS: To enhance identification of PLHIV vulnerable to suboptimal adherence, the existing checklist to identify the barriers to adherence in the National ART Guidelines needs to be updated based on the study findings. Quality of comprehensive adherence support services needs to be improved coupled with vigilant monitoring of adherence measurement.

Relevance of augmented kisspeptin signaling through H364 KISS1R in central precocious puberty.

Understanding the pathophysiology of idiopathic central precocious puberty (ICPP) is essential, in view of its consequences on reproductive health and metabolic disorders in later life. Towards this, estimation of circulating levels of the neuropeptides, viz; Kisspeptin (Kp-10), Neurokinin B (NKB) and Neuropeptide Y (NPY), acting upstream to Gonadotropin-Releasing Hormone (GnRH), has shown promise. Insights can also be gained from functional studies on genetic variations implicated in ICPP. This study investigated the pathophysiology of ICPP in a girl by exploring the therapeutic relevance of the circulating levels of Kp-10, NKB, NPY and characterizing the nonsynonymous KISS1R variant, L364H, that she harbours, in a homozygous condition. Plasma levels of Kp-10, NKB and NPY before and after GnRH analog (GnRHa) treatment, were determined by ELISA. It was observed that GnRHa treatment resulted in suppression of circulating levels of Kp-10, NKB and NPY. Further, the H364 variant in KISS1R was generated by site directed mutagenesis. Post transient transfection of either L364 or H364 KISS1R variant in CHO cells, receptor expression was ascertained by western blotting, indirect immunofluorescence and flow cytometry. Kp-10 stimulated signalling response was also determined by phospho-ERK and inositol phosphate production. Structure-function studies revealed that, although the receptor expression in H364 KISS1R was comparable to L364 KISS1R, there was an enhanced signalling response through this variant at high doses of Kp-10. Thus, elevated levels of Kp-10, acting through H364 KISS1R, contributed to the manifestation of ICPP, providing further evidence that dysregulation of Kp-10/KISS1R axis impacts the onset of puberty.

Common Hematological Reference Indices Among Healthy Reproductive Age Indian Women-Data Subset from Nationwide Study.

Despite the negative implications on women's health, pregnancy, and fetal outcomes, population-based studies on hematological indices among reproductive age women in India have received inadequate attention. This study aimed to generate normative ranges for various hematological parameters among these women. After ethics approval, apparently healthy (n = 5884) women (aged 18-40 years) were recruited from six eco-geographic zones of India. After various exclusions (n = 5412), including women having anemia, data of clinically, and biochemically healthy women (n = 472) was analysed to generate centiles (2.5 and 97.5th) and correlations. The mean age and mean BMI of women was 29.3 ± 6.5 years and 23.25 ± 3.26 kg/m2 with BP of 112.26 ± 8.9/74.04 ± 6.7 mmHg. The reference intervals for hemoglobin (12-15.1 gm/dl), RBC (3.68-5.55 millions/µl), WBC (4.1-11.26*109/L), platelet count (1.32-4.42*105/µl), and erythrocyte sedimentation rate (4.35-41.65 mm/hr) were different from currently used reference values (p < 0.05). However, these haematological indices did not vary among various age categories, geographical zones, ethnicities and rural or urban origins. Pearson's correlation revealed a statistically significant association between ESR, WBC, monocytes, and platelets with homeostasis model assessment of insulin resistance (HOMA-IR). Women with HOMA-IR > 2 displayed a statistically significant differences in parameters like MCV, ESR, eosinophil and platelet counts as compared to the women with HOMA-IR < 2. This study provides a pioneering reference data of hematological indices among women of reproductive age in India. Despite the small sample size results can be extrapolated to the national population given the representative sampling of various geographical zones. This may pave way for future comprehensive large-scale studies on the subject. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01714-6.

Molecular characterization of variants in mitochondrial DNA encoded genes using next generation sequencing analysis and mitochondrial dysfunction in women with PCOS.

Emerging studies indicates mitochondrial dysfunction and involvement of mitochondrial DNA (mtDNA) variants in the pathogenesis of polycystic ovary syndrome (PCOS). Cumulative effect of mtDNA rare variants are now gaining considerable interest apart from common variants in the pathogenesis of complex diseases. Rare variants may modify the effect of polymorphism or in combination with the common variants may affect the risk of disease. With the evolution of high throughput sequencing techniques, which can be utilized to identify common as well as rare variants along with heteroplasmy levels, comprehensive characterization of the mtDNA variants is possible. Till date, few studies reported common mtDNA variants using traditional sequencing techniques but rare variants in mtDNA encoding genes remain unexplored in women with PCOS. These mtDNA variants may be responsible for mitochondrial dysfunction and may contribute in PCOS pathogenesis. In this study we determined mtDNA copy number, a biomarker of mitochondrial dysfunction and first time analysed variants in mtDNA encoded genes in women with PCOS using mitochondrial Next Generation sequencing (NGS) approach and compared allele frequency from mitochondrial 1000 genome dataset. Variant annotation and prioritization was done using highly automated pipeline, MToolBox that excludes reads mapped from nuclear mitochondrial DNA sequences (NumtS) to identify unique mtDNA reads. The present study identified significant reduction in mtDNA copy number in women with PCOS compared to non-PCOS women. A total of unique 214 prioritized common to rare variants were identified in mtDNA encoded genes, 183 variants in OXPHOS complexes, 14 variants in MT-tRNA and 17 variants in MT-rRNA genes that may be involved in mitochondrial dysfunction in PCOS. Numerous variants were heteroplasmic, pathogenic in nature and occurred in evolutionary conserved region. Heteroplasmic variants were more frequently occurred in MT-CO3 gene. Non-synonymous variants were more than synonymous variants and mainly occurred in OXPHOS complex I and IV. Few variants were found to be associated with diseases in MITOMAP database. The study provides a better understanding towards pathogenesis of PCOS from novel aspects focusing on mitochondrial genetic defects as underlying cause for contributing mitochondrial dysfunction in women with PCOS.

Assessment of Health-Related Quality of Life Using EQ-5D-5L Tool With Indian Tariffs Among Reproductive Age Group Women Living With HIV in India.

OBJECTIVE: India is witnessing declining HIV prevalence because of dedicated efforts by the government. The highly active antiretroviral therapy has improved life span of people living with HIV but bearing many side effects. Women living with HIV (WLHIV) in reproductive age group have additional burden of pregnancy-related issues. This study aimed to estimate the health utility score among WLHIV in India, particularly in context of their contraceptive use, during pregnancy and postpartum period. METHODS: A primary cross-sectional study was conducted among 195 WLHIV availing antiretroviral treatment services at public health facilities of Mumbai. The EQ-5D-5L interview-based questionnaire in local language and Indian value set was used to estimate health-related quality of life (QOL) reported as mean (± SD) utility and visual analog scale (VAS) scores. The relationship between utility values and VAS scores was assessed. RESULTS: The WLHIV with mean age of 31.6 (6.4) years were on antiretroviral medication for nearly 7 years, and 63% had CD4+ cell count > 500 cells/mm3. Response of "11111," that is, in full health state, was reported by 66.7%. The mean utility and VAS scores were 0.976 (± 0.0519) and 82.21 (± 15.77). Reduced health-related QOL scores were associated with pain and discomfort dimension. Utility scores among contraceptive users (0.986 [± 0.029]) was higher than nonusers (0.976 [± 0.028]). Currently pregnant WLHIV had least utility score (0.959 [± 0.088]). CONCLUSIONS: WLHIV had better QOL while using contraceptives more so when they were sterilized. Pregnancy reduces the QOL. This emphasizes the need to promote effective contraceptive methods among WLHIV and prevent unintended pregnancies.

Addressing Challenges During Community based Screening of Women for Polycystic Ovary Syndrome (PCOS): A Research Experience from Maharashtra, India before and During COVID Pandemic.

Introduction: A multicentric community-based screening to determine prevalence of Polycystic Ovary Syndrome was undertaken in India. This article aims to describe the challenges faced at one site and strategies adopted to mitigate them. Material and Methods: Eligible women were enrolled at household-level and investigated for Polycystic Ovary Syndrome diagnosis as per Rotterdam criteria. Challenges faced were documented and alternate strategies were adopted. Results: Challenges ranged from identifying women as per the polling booth list, enrolling them, and getting them investigated. COVID-19 pandemic added to the challenges. Involving health system workforce, gaining community support, flexible timings, and alternate strategies for investigation including COVID-19 appropriate safety measures helped mitigate some of the challenges. Conclusion: Unforeseen challenges may crop up in community-based studies, like the ones faced during the COVID-19 pandemic. Planning, strategizing, using technology to keep communications on, and finding out of the box and amicable solutions for bottlenecks may help mitigate challenges.