Molly Jacob

Anaemia remains a significant public health issue in India, despite five of control programs. Anaemia affects 52-67% of target populations in India despite five decades of control programmes. We conducted a review of reviews and meta-analyses (SRMAs) of regional studies to evaluate daily versus intermittent oral iron and iron-folic acid (IFA) supplementation across age groups. We identified 21 SRMAs (17 high-quality, 4 moderate-quality) and 44 regional studies from India and South Asia. IFA prophylaxis consistently improved haemoglobin levels (4.1-8.8 g/L increase) and ferritin concentrations, reducing anaemia risk by 23-70% across all age groups. IFA prophylaxis consistently improved haemoglobin levels (4.1-8.8 g/L increase) and ferritin concentrations, reducing anaemia risk by 23-70% across all age groups. Daily and intermittent regimens showed similar haematological outcomes in children, adolescents, and women of reproductive age. Among pregnant women, daily supplementation was superior for haemoglobin and ferritin levels, though intermittent dosing had fewer gastrointestinal side effects. These findings support weekly IFA supplementation for non-pregnant beneficiaries as an evidence-based strategy, even in settings where anaemia prevalence exceeds 40%. Further research on long-term safety in non-iron-deficient populations is needed.

Purpose: This cohort would aim to estimate the prevalence of anemia among children under 18 years, non-pregnant and non-lactating (NPNL) women, and pregnant women (by trimester), with further stratification by age group, year, and region of India. Cohort would also help address extended deliberation concerning etiological fraction of iron and other key erythropoietic micronutrient deficiencies contributing to anemia in India. Additionally, this will help assess the effectiveness of existing anaemia prevention and treatment interventions and examine factors associated with non-response, thereby supporting the “test–treat–track” approach. Participants: Children under 18 years, pregnant women, and non-pregnant-non-lactating women (NPNL) in India. Findings to date: This cohort profile comprises 88 datasets spanning between 1994 to 2023, encompassing a total of 319,721 participants for prevalence analysis [children(19,762), NPNL(17,883), and pregnant women(282,076)]. Additionally, 59,292 participants were included in intervention studies [children(13,435), NPNL(11,594), and pregnant women(34,263)]. RCTs comprised 55.7% (49/88) of the datasets whereas observational studies comprise 35.2% (31/88) of the datasets. Majority of the studies were from the norther region - 38 studies (43.2%), followed by the western part - 20 studies (22.7%). The southern part contributed 16 studies (18.2%). Major [59/88 (67%)] datasets in cohort were from community-based studies. The sample included NPNL and pregnant women with a median age of 26 years (IQR 23-32), and 23 years (IQR 21-25) respectively. Information from 6 months up to 18 years was pooled within the children’s cohort. Within the pregnancy cohort the mean gestational age at enrollment was 10.24 weeks(SD-17.65). Of total 10.8% (34,442/ 319,721), 9% (28,672), 4.5% (14,240) of the sample had information on complete blood count, ferritin and vitamin B12 respectively. A total of 33 datasets (sample - 59,292) were from intervention studies. Among pregnant women, a broader range of interventions was implemented, including intravenous iron sucrose, ferric carboxymaltose, iron isomaltoside, IV iron combined with vitamin B12, folic acid, and niacinamide, integrated interventions, as well as low-dose calcium supplementation. A similar set of interventions were delivered to NPNL group with being distinct which compared Ferrous sulfate tablets of 60 mg elemental iron daily with a control of 120 mg on alternate days. Ferrous sulfate was the major interventions amongst children along with food supplements and some were Ayush trials. Future plans: The PRAYAS will provide robust, high-quality evidence to inform public health policy in India. The findings will feed into the Anemia Mukt Bharat program recommendations for pregnant women, NPNL women and children to guide targeted strategies for reduction of anemia and its associated health burdens across vulnerable populations. Strengths and limitations of this study: The harmonized PRAYAS pooled Indian dataset is one of the largest, reliable and most comprehensive datasets on pregnant/ non-pregnant and non-lactating women and children. One of its kind of dataset with information on hemoglobin levels, relevant biochemical and key micronutrients parameters and varied interventions from across India. Heterogeneity of interventions, dosage, duration and data collection approaches. Studies lack critical parameters needed to assess changes in haemoglobin concentration like non-availability of key erythropoietic micronutrients in most of the studies, limiting the scope of certain analyses.

Ulcerative colitis (UC) is often associated with anemia. Hepcidin, the central regulator of iron homeostasis, is known to be induced by inflammation and suppressed by anemia. It is not clear how hepcidin is affected in those with UC, when both inflammation and anemia may co-exist.Such knowledge may hold implications for treatment. Hematological and iron-related parameters, C-reactive protein (CRP), growth differentiation factor 15 (GDF-15) and erythroferrone (ERFE) (erythroid regulators of hepcidin) levels were estimated in blood from those with UC and in control subjects. Values for hematological and iron-related parameters showed evidence of iron-deficiency and resultant anemia, in patients with UC. The presence of UC was significantly associated with inflammation. Serum levels of ERFE, but not of GDF-15, were significantly higher in patients with UC than in control patients, while hepcidin levels were significantly lower. Serum hepcidin concentrations in patients with UC correlated positively with serum iron, ferritin and GDF-15, and negatively with serum ERFE. The iron status and serum hepcidin levels in UC patients with co-existent anemia were significantly lower and serum ERFE values significantly higher than in those with UC without anemia. The effect of anemia on hepcidin predominated over that of inflammation in patients with UC, resulting in suppressed hepcidin levels. This effect is possibly mediated through erythroferrone. We suggest that a serum hepcidin-guided approach may be useful to guide use of oral iron supplements to treat co-existent iron-deficiency anemia in patients with UC and other chronic inflammatory diseases.

Increased body iron stores and inflammation in adipose tissue have been implicated in the pathogenesis of insulin resistance (IR) and type 2 diabetes mellitus. However, the underlying basis of these associations are unclear. In order to assess this, we studied how IR and associated inflammation in adipose tissue developed in the presence of increased body iron stores. Male hepcidin knock-out ( Hamp1 ^-/- ) mice, which have increased body iron stores, and wild-type (WT) mice were fed a high-fat diet (HFD) for 12 and 24 weeks. Development of IR and metabolic parameters linked to this, insulin signaling in tissue, and inflammation and iron-related parameters in visceral adipose tissue were studied in these animals. HFD-feeding resulted in impaired glucose tolerance in both genotypes of mice. In response to the HFD for 24 weeks, Hamp1-/- mice gained less body weight and developed less IR than corresponding WT mice. This was associated with less lipid accumulation in the liver and decreased inflammation and lipolysis in the adipose tissue in the knock-out mice, than in the WT animals. Fewer macrophages infiltrated the adipose tissue in the knockout mice than in wild-type mice, with these macrophages exhibiting a predominantly anti-inflammatory (M2-like) phenotype. These observations suggest a novel role of hepcidin (central regulator of systemic iron homeostasis) in the development of inflammation in adipose tissue and insulin resistance, in response to a high-fat diet. CLINICAL PERSPECTIVES: Elevated body iron stores and inflammation in adipose tissue have been implicated in the pathogenesis of insulin resistance (IR) and type 2 diabetes mellitus. However, the underlying molecular mechanisms linking them are unclear. In response to high-fat diet (HFD)-feeding (to induce IR), mice that lacked hepcidin ( Hamp1 ^-/- ) (and hence had elevated body iron stores) gained less body weight and developed less insulin resistance than wild-type (WT) mice. Inflammation and infiltration of macrophages into adipose tissue of HFD-fed Hamp1 ^-/- mice were less than in WT mice, with the macrophages exhibiting an anti-inflammatory M2-like phenotype. These findings suggest a novel role of iron and hepcidin in HFD-induced inflammation in adipose tissue and development of insulin resistance. They raise the possibility that modulation of body iron may represent a potential way to inhibit these processes.