Correlates of disability among primary care patients with common mental disorders and chronic medical conditions- a cross-sectional study from rural South India.

PURPOSE: We examined the correlates of disability among people with non-communicable diseases (NCDs) and comorbid common mental disorders (CMDs) from rural India. METHODS: The sample comprised 2,486 participants enrolled in a cluster randomized trial (cRCT), Healthier OPtions through Empowerment (HOPE). Participants were 30 years or older, with a diagnosis of major depressive disorder, dysthymia, generalized anxiety disorder, and/or panic disorder on the MINI-International Neuropsychiatric Interview, with hypertension, diabetes, dsylipidemia and/ or ischemic heart disease. Disability was measured with the 12-item version of WHODAS 2.0. The severity of depression and anxiety was measured using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Scale (GAD-7), respectively. Multiple linear regression analyses were used to examine associations. RESULTS: The mean age was 59 ± 10.0 years, three quarters (1864) of the participants were female, and 64.0% were married. More than half of the participants had no formal education (57.9%). Most of the participants had two or more chronic medical conditions (73.0%). The mean disability score was 24.3. The mean depression score was 8.5, and the mean anxiety score was 6.7. Higher levels of disability were reported by participants ≥ 60 years of age, those with moderate and severe depression, and moderate anxiety. Among female participants, being unmarried was associated with greater disability. Male participants without formal education reported greater levels of disability. CONCLUSION: Higher severity of CMDs is significantly associated with higher levels of disability. For women, being unmarried and for men having no formal education was associated with higher levels of disability. TRIAL REGISTRATION: ClinicalTrials.gov NCT02310932 [URL: https://clinicaltrials.gov/ct2/show/record/NCT02310932 ] registered on December 8, 2014, and Clinical Trials Registry India CTRI/2018/04/013001, registered on April 4, 2018. Retrospectively registered.

The Influence of Transmission-Based and Moral-Based HIV Stigma Beliefs on Intentions to Discriminate Among Ward Staff in South Indian Health Care Settings.

HIV stigma is comprised of several beliefs, including transmission fears and moral judgments against affected communities. We examined the relationships among HIV-related stigma beliefs, endorsement of coercive measures for people living with HIV (PLWH), and intentions to discriminate. We sought to understand to what degree the different stigma beliefs shape support for restrictive policies and discriminatory intentions. Data were drawn from the baseline assessment of DriSti, a cluster randomized controlled trial of an HIV stigma reduction intervention in Indian healthcare settings (NCT02101697). Participants completed measures assessing transmission fears and moral judgments of HIV, endorsement of coercive measures against PLWH (public disclosure of HIV status, refusal of healthcare services, marriage and family restrictions, required testing, and sharing of HIV information in a clinic), and intentions to discriminate against PLWH in professional and personal settings. We utilized multivariate regression modeling with backward elimination to identify the coercive measures and behavioral intentions most strongly associated with moral judgments. 1540 ward staff members completed the assessment. Participants had relatively high perceptions of transmission fears (M = 1.92, SD = 0.79) and moral judgments (M = 1.69, SD = 0.83); endorsed more intentions to discriminate in professional (M = 6.54, SD = 2.28) than personal settings (M = 2.07, SD = 1.49), and endorsed approximately half of all coercive measures (M = 9.47, SD = 2.68). After controlling for transmission fears, perceptions of stronger moral judgments against PLWH were significantly associated with higher endorsement of coercive measures related to refusing services (ß = 0.10, t = 4.14, p < 0.001) and sharing patients' HIV status in clinics (ß = 0.07, t = 3.04, p = 0.002), as well as with stronger behavioral intentions to discriminate in professional settings (ß = 0.05, t = 2.20, p = 0.022). HIV stigma interventions for hospital-based ward staff in India need to focus on both transmission fears and moral judgments that underlie prejudicial beliefs. While the moral judgments are not technically related to risk in a hospital setting, our findings suggest that personnel will continue to discriminate in their professional work so long as these beliefs bear on their decisions and actions.

Collaborative care compared to enhanced standard treatment of depression with co-morbid medical conditions among patients from rural South India: a cluster randomized controlled trial (HOPE Study).

BACKGROUND: Depression is common among primary care patients in LMIC but treatments are largely ineffective. In this cluster-randomized controlled trial, we tested whether depression outcomes are different among recipients of a collaborative care model compared to enhanced standard treatment in patients with co-morbid chronic medical conditions. METHODS: We conducted a cluster randomized controlled trial among participants 30 years or older seeking care at 49 primary health centers (PHCs) in rural Karnataka, diagnosed with major depressive disorder, dysthymia, generalized anxiety disorder, or panic disorder on the MINI-International Neuropsychiatric Interview plus either hypertension, diabetes, or ischemic heart disease. From a list of all PHCs in the district, 24 PHCs were randomized a priori to deliver collaborative care and 25 PHCs enhanced standard treatment. The collaborative care model consisted of a clinic-based and a community-based component. Study assessment staff was blinded to treatment arm allocation. The primary outcome was the individual-level PHQ-9 score over time. RESULTS: Between May 2015 and Nov 2018, 2486 participants were enrolled, 1264 in the control arm, and 1222 in the intervention arm. They were assessed at baseline, 3, 6 and 12 months. The mean PHQ-9 depression score was around 8.5 at baseline. At each follow-up PHQ-9 scores were significantly lower in the intervention (5.24, 4.81 and 4.22 at respective follow-ups) than in the control group (6.69, 6.13, 5.23, respectively). A significant time-by-treatment interaction (p < 0.001) in a multi-level model over all waves, nested within individuals who were nested within PHCs, confirmed that the decrease in depression score from baseline was larger for collaborative care than enhanced standard care throughout follow-up. CONCLUSIONS: The collaborative care intervention resulted in significantly lower depression scores compared to enhanced standard care among participants with co-morbid physical conditions. The findings have potential implications for integrating mental health and chronic disease treatment in resource constrained settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02310932 , registered on December 8, 2014, and Clinical Trials Registry India CTRI/2018/04/013001 , registered on April 4, 2018. Retrospectively registered.

HIV Transmission Worry Predicts Discrimination Intentions Among Nursing Students and Ward Staff in India.

Health facility stigma impedes HIV care and treatment. Worry of contracting HIV while caring for people living with HIV is a key driver of health facility stigma, however evidence for this relationship is largely cross-sectional. This study evaluates this relationship longitudinally amongst nursing students and ward staff in India. Worry of contracting HIV and other known predictors of intent to discriminate were collected at baseline and 6 months in 916 nursing students and 747 ward staff. Using fixed effects regression models, we assessed the effect of key predictors on intent to discriminate over a 6-month period. Worry of contracting HIV predicted intent to discriminate for nursing students and ward staff in care situations with low and high-risk for bodily fluid exposure, confirming prior cross-sectional study results and underscoring the importance of addressing worry of contracting HIV as part of health facility HIV stigma-reduction interventions.

Correlates of social support in individuals with a diagnosis of common mental disorders and non communicable medical diseases in rural South India.

PURPOSE: The purpose of the study was to examine the association between socio-demographic and clinical characteristics and perceived social support among patients with a diagnosis of depression and/or anxiety and co-morbid medical conditions from rural south India. METHODS: The study was conducted in 49 PHCs in Ramanagara district, Karnataka, and included 2481 participants, who were 30 years or older with co-morbid CMD (Common Mental Disorder) and hypertension, diabetes or ischemic heart disease. Socio-demographic characteristics of the participants were collected, and instrumental, emotional and total social support, quality of life, severity of disability, depression and anxiety were measured via face-to-face interviews using structured questionnaires. RESULTS: The sample predominantly consisted of Hindu (98.5%) females (75%) in their middle to late adulthood. In multivariate models, age showed a significant curvilinear relation with all forms of social support (B = 0.001 and p < 0.05), and emotional social support (B = - 0.056, p = 0.004) was lower in employed than non-working participants. Household size was positively related to all forms of social support (B = 0.029 for instrumental, B = 0.022 for emotional, B = 0.025 for total social support, all p < 0.001). Quality of life was positively associated with all forms of social support (B = 0.019 for instrumental, B = 0.016 for emotional, B = 0.018 for total social support, all p < 0.001). CONCLUSIONS: For this sample of outpatients diagnosed with both CMD and at least one comorbid medical condition in rural south India, greater household size was associated with better social support. The role of family in providing support can be utilized while designing interventions. TRIAL REGISTRATION NUMBER: http://Clinicaltrials.gov : NCT02310932 registered December 8, 2014 URL: https://clinicaltrials.gov/ct2/show/record/NCT02310932 ; Clinical Trials Registry India: CTRI/2018/04/013001 retrospectively registered on April 4, 2018.

Vitamin B-12 Supplementation during Pregnancy and Early Lactation Does Not Affect Neurophysiologic Outcomes in Children Aged 6 Years.

BACKGROUND: Deficiency of vitamin B-12 is common in pregnant Indian women. Assessment of neurophysiological measures using event-related potentials (ERPs) may yield additional information on the effects of maternal B-12 supplementation on child brain function. OBJECTIVES: The objective of the study was to evaluate the effects of vitamin B-12 supplementation (50 µg daily orally) during pregnancy on the childhood ERP measures of positive waveform ∼300 ms after stimulus (P300) and mismatch negativity. METHODS: This study was a follow-up of children born to pregnant women who received oral vitamin B-12 supplements (n = 62) compared with children of pregnant women who received placebo (n = 70) from a randomized controlled trial. The mean ± SD child age was 72 ± 1 mo. We used the Enobio system to assess the ERP measures P300 and mismatch negativity. RESULTS: There were no significant differences in the primary outcomes, amplitudes, and latencies of the P300 results and the mismatch negativity between children in the supplementation and placebo groups. We combined the intervention and placebo groups for secondary analyses. On multiple variable regression analysis after adjusting for treatment group, intrauterine growth restriction, and home environment, P300 amplitude in children was significantly higher in the lowest tertile of third-trimester maternal methylmalonic acid (MMA) concentrations (ß = 3034.04; 95% CI: 923.24, 5144.83) compared with the highest MMA tertile (ß = 1612.12; 95% CI: -258.86, 3483.10, P = 0.005). CONCLUSIONS: While no significant effects of maternal vitamin B-12 supplementation on children's ERP measures were seen at 72 mo, elevated maternal MMA concentrations in the third trimester were negatively associated with P300 amplitude in children. It may be worthwhile to study the impact of maternal and infant vitamin B-12 supplementation on childhood brain structure and function in longer and larger trials. The parent trial was registered at clinicaltrials.gov as NCT00641862.

Reducing HIV stigma among healthcare providers in India using a partly tablet-administered intervention: the DriSti trial.

HIV stigma has long been recognized as a significant barrier in the worldwide fight against HIV. Across cultures, stigma has been shown to cause psychological distress and act as a barrier to engagement in care. Health professionals can serve as a crucial source of HIV stigma, with drivers that include fears and transmission misconceptions and pre-existing negative attitudes towards marginalized groups. To increase their impact, stigma reduction interventions need to be scalable and sustainable as well as adaptable to different cultural contexts. The DriSti intervention was designed to meet these needs through an easily adaptable, mostly tablet-administered, interactive intervention delivered to ward staff (n = 1,557) and nursing students (n = 1,625) in 62 Indian institutions, using a cRCT design, with wait-list controls. Six-month outcome analyses, showed significant reductions in misconceptions (p < .001) and worry about acquiring HIV at work (p < .001). Intervention participants also reported significantly greater reductions in endorsement of coercive policies (p < .001) and in the number of situations in which they intended to discriminate against PLWH (p < .001) than control participants. This brief, scaleable intervention could be adapted for similar populations in the region, using different mHealth platforms and thus has important implications for current global stigma reduction initiatives and training curricula.

Characterization of residue-specific glutathionylation of CSF proteins in multiple sclerosis - A MS-based approach.

Reduction of a disulfide linkage between cysteine residues in proteins, a standard step in the preanalytical preparation of samples in conventional proteomics approach, presents a challenge to characterize S-glutathionylation of proteins. S-glutathionylation of proteins has been reported in medical conditions associated with high oxidative stress. In the present study, we attempted to characterize glutathionylation of CSF proteins in patients with multiple sclerosis which is associated with high oxidative stress. Using the nano-LC/ESI-MS platform, we adopted a modified proteomics approach and a targeted database search to investigate glutathionylation at the residue level of CSF proteins. Compared to patients with Intracranial hypertension, the following CSF proteins: Extracellular Superoxide dismutase (ECSOD) at Cys195, α1-antitrypsin (A1AT) at Cys232, Phospholipid transfer protein (PLTP) at Cys318, Alpha-2-HS-glycoprotein at Cys340, Ectonucleotide pyrophosphate (ENPP-2) at Cys773, Gelsolin at Cys304, Interleukin-18 (IL-18) at Cys38 and Ig heavy chain V III region POM at Cys22 were found to be glutathionylated in patients with multiple sclerosis during a relapse. ECSOD, A1AT, and PLTP were observed to be glutathionylated at the functionally important cysteine residues. In conclusion, in the present study using a modified proteomics approach we have identified and characterized glutathionylation of CSF proteins in patients with multiple sclerosis.

Elevated levels of glutathionyl haemoglobin as an oxidative stress marker in patients with major depressive disorder.

Background & objectives: Oxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD), but biomarkers to assess oxidative stress in patients with MDD have yielded ambiguous results. Glutathionyl haemoglobin (GS-Hb) has been reported as a stable and potential biomarker for oxidative stress in various clinical conditions. The objective of the study was to evaluate GS-Hb as a potential biomarker of oxidative stress in patients with MDD through its quantification and to compare the levels of GS-Hb in age- and gender-matched healthy controls. Methods: The levels of GS-Hb were estimated using liquid chromatography coupled to electrospray ionization mass spectrometry in patients diagnosed with MDD and in a subset of patients after six weeks of treatment with selective serotonin reuptake inhibitors (SSRIs). Results: GS-Hb levels in drug-naïve patients with MDD (n=26) were significantly elevated compared to matched healthy controls (n=17). GS-Hb levels were not significantly different between MDD patients with and without co-morbid anxiety disorders. There were no significant differences in GS-Hb levels following six weeks of treatment with SSRIs compared to baseline. Interpretation & conclusions: Compared to controls, GS-Hb level in patients with MDD was significantly elevated, suggestive of increased oxidative stress associated with MDD. However, six weeks of antidepressant treatment was not sufficient to modify the alterations in antioxidant/oxidant system. Further studies need to be done with a large sample of MDD patients with a longer duration of antidepressant treatment.

Downregulation of apolipoprotein A-IV in plasma & impaired reverse cholesterol transport in individuals with recent acts of deliberate self-harm.

Background & objectives: The major limiting factor in the prevention of suicide is the limited knowledge on molecular insights in individuals at risk. Identification of peripheral protein markers which can classify individuals at high-risk of suicide might aid in early diagnosis and effective medical intervention. The aim of the present study was, therefore, to analyze the differential regulation of plasma proteins in individuals with deliberate self-harm compared to controls. Methods: Using two-dimensional gel electrophoresis coupled with matrix-assisted laser desorption-ionization mass spectrometry, differentially expressed plasma proteins were identified in study participants with deliberate self-harm compared to age- and gender-matched controls. The finding was validated using mass spectrometry-based isotope-labelled relative quantification and Western blot analysis in a new set of individuals with deliberate self-harm and controls. Results: The plasma proteomic analysis showed that apolipoprotein A-IV (Apo A-IV ) was downregulated by 2.63-fold (confidence interval: 1.52-4.54) in individuals with deliberate self-harm (n=10) compared to matched controls, which was consistent in mass spectrometry-based relative quantification and Western blot analysis performed in an independent set of individuals with deliberate self-harm (n=18). In addition, plasma levels of total cholesterol, esterified cholesterol and high-density lipoprotein (HDL) were observed to be significantly lower individuals with deliberate self-harm compared to controls. Interpretation & conclusions: Apo A-IV, which plays a crucial role in the esterification of free cholesterol, was found to be downregulated with concomitantly decreased levels of HDL, esterified cholesterol and total cholesterol in individuals with deliberate self-harm compared to matched controls. The present findings might provide a link between the differential regulation of plasma proteins and the previously reported results on altered cholesterol levels in individuals with deliberate self-harm.

Effect of Maternal Vitamin B12 Supplementation on Cognitive Outcomes in South Indian Children: A Randomized Controlled Clinical Trial.

Objectives To examine the effects of oral maternal vitamin B12 supplementation during pregnancy and early lactation on cognitive development in children. Method We studied 218 children born to mothers enrolled in a placebo-controlled, randomized trial of vitamin B12 supplementation during pregnancy through 6 weeks post-partum. Cognitive functions were assessed at 30 months using the Bayley Scales of Infant Development- 3rd edition (BSID III). The association of maternal sociodemographic characteristics, maternal biochemical status during pregnancy, birth weight and home environment with each sub-domain of BSID-III was examined using linear regression analysis. Separate multiple linear regression analyses for each of the BSID-III sub-domains with maternal trimester specific nutritional biomarker status was conducted. Results Children of mothers who received oral vitamin B12 supplementation had significantly higher scores on expressive language compared to children of mothers who received placebo (ß = 0.14, P = 0.03). Children of mothers with elevated serum total homocysteine (tHcy) in the second and third trimesters of pregnancy had significantly lower scores on expressive language (ß = - 0.18, P = 0.03 and ß = - 0.19, P = 0.02, respectively) and gross motor domains (ß = - 0.23, P = 0.008 and ß = - 0.30, P = 0.001, respectively) of BSID-III adjusted for treatment arm and multiple confounders, compared with children whose mothers did not have elevated tHcy. Conclusions for practice Maternal B12 supplementation during pregnancy was associated with higher expressive language scores in children at 30 months. Elevated maternal tHcy levels during pregnancy had negative associations with expressive language and gross motor domains of BSID-III. Larger trials of maternal B12 supplementation are needed to confirm these findings.

Socio-economic, environmental and nutritional characteristics of urban and rural South Indian women in early pregnancy: findings from the South Asian Birth Cohort (START).

OBJECTIVE: High frequency of low birth weight (LBW) is observed in rural compared with urban Indian women. Since maternal BMI is known to be associated with pregnancy outcomes, the present study aimed to investigate factors associated with BMI in early pregnancy of urban and rural South Indian women. DESIGN: Prospective observational cohort. SETTING: A hospital-based study conducted at an urban and a rural health centre in Karnataka State. SUBJECTS: Pregnant women (n 843) aged 18-40 years recruited in early pregnancy from whom detailed sociodemographic, environmental, anthropometric and dietary intake information was collected. RESULTS: A high proportion of low BMI (32 v. 26 %, P<0·000) and anaemia (48 v. 23 %, P<0·000) was observed in the rural v. the urban cohort. Rural women were younger, had lower body weight, tended to be shorter and less educated. They lived in poor housing conditions, had less access to piped water and good sanitation, used unrefined fuel for cooking and had lower standard of living score. The age (ß=0·21, 95 % CI 0·14, 0·29), education level of their spouse (ß=1·36, 95 % CI 0·71, 2·71) and fat intake (ß=1·24, 95 % CI 0·20, 2·28) were positively associated with BMI in urban women. CONCLUSIONS: Our findings indicate that risk factors associated with BMI in early pregnancy are different in rural and urban settings. It is important to study population-specific risk factors in relation to perinatal health.

Improving mental health through integration with primary care in rural Karnataka: study protocol of a cluster randomized control trial.

BACKGROUND: People who are diagnosed with both mental and chronic medical illness present unique challenges for the health care system. In resource-limited settings, such as rural India, people with depression and anxiety are often under-served, due to both stigma and lack of trained providers and resources. These challenges can lead to complications in the management of chronic disease as well as increased suffering for patients, families and communities. In this study, we evaluate the effects of integrating mental health and chronic disease treatment of patients in primary health care (PHC) settings using a collaborative care model to improve the screening, diagnosis and treatment of depression in rural India. METHODS: This study is a multi-level randomized controlled trial among patients with depression or anxiety and co-morbid diabetes, or cardiovascular disease. Aim 1 examines whether patients screened at community health-fairs are more likely to be diagnosed and treated for these co-morbid conditions than patients screened after presenting at PHCs. Aim 2 evaluates the impact of collaborative care compared to usual care in a cluster RCT, randomizing at the level of the PHCs. Intervention arm PHC staff are trained in mental health diagnoses, treatment, and the collaborative care model. The intervention also involves community-based "Healthy Living groups" co-led by Ashas, using cognitive-behavioral strategies to promote healthy behaviors. The primary outcome is severity of common mental disorders, with secondary outcomes being diabetes and cardiovascular risk, staff knowledge and patient perceptions. DISCUSSION: If effective, our results will contribute to the field in five ways: 1) expand on implementation research in low resource settings by examining how multiple chronic diseases can be treated using integrated low-cost, evidence-based strategies, 2) build the capacity of PHC staff to diagnose and treat mental illness within their existing clinic structure and strengthen referral linkages; 3) link community members to primary care through community-based health fairs and healthy living groups; 4) increase mental health awareness in the community and reduce mental health stigma; 5) demonstrate the potential for intervention scale-up and sustainability. TRIAL REGISTRATION: http://Clinicaltrials.gov : NCT02310932 registered December 8, 2014 URL: https://clinicaltrials.gov/ct2/show/record/NCT02310932 ; Clinical Trials Registry India: CTRI/2018/04/013001 retrospectively registered on April 4, 2018.

Effects of maternal vitamin B12 supplementation on early infant neurocognitive outcomes: a randomized controlled clinical trial.

Maternal nutritional status during pregnancy impacts fetal brain development. Vitamin B12 plays a vital role in neuronal development. However, findings from studies on the association between maternal B12 status and child cognitive functions have been inconsistent. We performed a randomized, placebo-controlled clinical trial of oral B12 supplementation (50 µg) beginning at <14 weeks of gestation through a 6-week post-partum. In the present study, we report the effects of maternal B12 supplementation on cognitive development in infants at 9 months of age on Bayley Scales of Infant Development-III (BSID-III). One hundred eighty-three pregnant women received vitamin B12, and 183 received placebo. Nine-month BSID-III development score was available in 178 infants. There were no significant differences in maternal sociodemographic characteristics and baseline biochemical measures between infants who underwent BSID-III evaluation and infants who were not evaluated. There were no significant differences in any of the subscales of BSID-III between infants born to mothers who received B12 supplementation (n = 78) vs. placebo (n = 100). On multiple regression analysis, elevated maternal total homocysteine (tHcy) levels adjusted for treatment group, birthweight, parity, income and home environment at second trimester of pregnancy were significantly negatively associated with expressive language (ß = 3.13 points, P < 0.001), and in third trimester of pregnancy with expressive language (ß = -2.29 points, P < 0.001) and fine motor (ß = -1.41 points, P = 0.005) domains of BSID-III. While no significant effects of maternal B12 supplementation were seen on cognitive development in infants at 9 months of age, elevated maternal tHcy levels were associated with poorer cognitive performance in some of the subdomains of BSID-III. In pregnant women with elevated tHcy levels and or B12 deficiencies, it may be worthwhile to study the impact of longer term maternal supplementation on infant cognitive outcomes.

Association between maternal nutritional status in pregnancy and offspring cognitive function during childhood and adolescence; a systematic review.

BACKGROUND: The mother is the only source of nutrition for fetal growth including brain development. Maternal nutritional status (anthropometry, macro- and micro-nutrients) before and/or during pregnancy is therefore a potential predictor of offspring cognitive function. The relationship of maternal nutrition to offspring cognitive function is unclear. This review aims to assess existing evidence linking maternal nutritional status with offspring cognitive function. METHODS: Exposures considered were maternal BMI, height and weight, micronutrient status (vitamins D, B12, folate and iron) and macronutrient intakes (carbohydrate, protein and fat). The outcome was any measure of cognitive function in children aged <18 years. We considered observational studies and trials with allocation groups that differed by single nutrients. We searched Medline/PubMed and the Cochrane Library databases and reference lists of retrieved literature. Two reviewers independently extracted data from relevant articles. We used methods recommended by the Centre for Reviews and Dissemination, University of York and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Of 16,143 articles identified, 38 met inclusion criteria. Most studies were observational, and from high-income settings. There were few randomized controlled trials. There was consistent evidence linking maternal obesity with lower cognitive function in children; low maternal BMI has been inadequately studied. Among three studies of maternal vitamin D status, two showed lower cognitive function in children of deficient mothers. One trial of folic acid supplementation showed no effects on the children's cognitive function and evidence from 13 observational studies was mixed. Among seven studies of maternal vitamin B12 status, most showed no association, though two studies in highly deficient populations suggested a possible effect. Four out of six observational studies and two trials (including one in an Iron deficient population) found no association of maternal iron status with offspring cognitive function. One trial of maternal carbohydrate/protein supplementation showed no effects on offspring cognitive function. CONCLUSIONS: Current evidence that maternal nutritional status during pregnancy as defined by BMI, single micronutrient studies, or macronutrient intakes influences offspring cognitive function is inconclusive. There is a need for more trials especially in populations with high rates of maternal undernutrition. SYSTEMATIC REVIEW REGISTRATION: Registered in PROSPERO CRD42013005702 .

"We have to ask and only then do": Unpacking agency and autonomy in women's reproductive health in urban India.

The limited autonomy and agency of women in developing countries is recognized as a key barrier to improving their reproductive health. Using an existing perinatal cohort in urban South India, we interviewed 36 women who had recently been through childbirth, and we carried out observations of family life and clinic encounters. Critical domains involved in women's agency and autonomy were women's participation in employment and group action and their mobility. Household decision making was considered a joint rather than individual responsibility. We call for a more nuanced understanding of these domains and their relationship to women's reproductive health, particularly for urban populations.

The iodized salt programme in Bangalore, India provides adequate iodine intakes in pregnant women and more-than-adequate iodine intakes in their children.

OBJECTIVE: To compare the iodine status of pregnant women and their children who were sharing all meals in Bangalore, India. DESIGN: A cross-sectional study evaluating demographic characteristics, household salt iodine concentration and salt usage patterns, urinary iodine concentrations (UIC) in women and children, and maternal thyroid volume (ultrasound). SETTING: Antenatal clinic of an urban tertiary-care hospital, which serves a low-income population. SUBJECTS: Healthy pregnant women in all trimesters, aged 18-35 years, who had healthy children aged 3-15 years. RESULTS: Median (range) iodine concentrations of household powdered and crystal salt were 55·9 (17·2-65·9) ppm and 18·9 (2·2-68·2) ppm, respectively. The contribution of iodine-containing supplements and multi-micronutrient powders to iodine intake in the families was negligible. Adequately iodized salt, together with small amounts of iodine in local foods, were providing adequate iodine during pregnancy: (i) the overall median (range) UIC in women was 172 (5-1024) µg/l; (ii) the median UIC was >150 µg/l in all trimesters; and (iii) thyroid size was not significantly different across trimesters. At the same time, the median (range) UIC in children was 220 (10-782) µg/l, indicating more-than-adequate iodine intake at this age. Median UIC was significantly higher in children than in their mothers (P=0·008). CONCLUSIONS: In this selected urban population of southern India, the iodized salt programme provides adequate iodine to women throughout pregnancy, at the expense of higher iodine intake in their children. Thus we suggest that the current cut-off for median UIC in children indicating more-than-adequate intake, recommended by the WHO/UNICEF/International Council for the Control of Iodine Deficiency Disorders may, need to be reconsidered.

Vitamin B-12 supplementation during pregnancy and early lactation increases maternal, breast milk, and infant measures of vitamin B-12 status.

Pregnant women in resource-poor areas are at risk of multiple micronutrient deficiencies, and indicators of low vitamin B-12 status have been associated with adverse pregnancy outcomes, including anemia, low birth weight, and intrauterine growth retardation. To evaluate whether daily oral vitamin B-12 supplementation during pregnancy increases maternal and infant measures of vitamin B-12 status, we performed a randomized, placebo-controlled clinical trial. Pregnant women <14 wk of gestation in Bangalore, India, were randomly assigned to receive daily oral supplementation with vitamin B-12 (50 µg) or placebo through 6 wk postpartum. All women were administered iron and folic acid supplements throughout pregnancy. One hundred eighty-three women were randomly assigned to receive vitamin B-12 and 183 to receive placebo. Compared with placebo recipients, vitamin B-12-supplemented women had significantly higher plasma vitamin B-12 concentrations at both the second (median vitamin B-12 concentration: 216 vs. 111 pmol/L, P < 0.001) and third (median: 184 vs. 105 pmol/L, P < 0.001) trimesters. At 6 wk postpartum, median breast milk vitamin B-12 concentration was 136 pmol/L in vitamin B-12-supplemented women vs. 87 pmol/L in the placebo group (P < 0.0005). Among vitamin B-12-supplemented women, the incidence of delivering an infant with intrauterine growth retardation was 33 of 131 (25%) vs. 43 of 125 (34%) in those administered placebo (P = 0.11). In a subset of infants tested at 6 wk of age, median plasma vitamin B-12 concentration was 199 pmol/L in those born to supplemented women vs. 139 pmol/L in the placebo group (P = 0.01). Infant plasma methylmalonic acid and homocysteine concentrations were significantly lower in the vitamin B-12 group as well. Oral supplementation of urban Indian women with vitamin B-12 throughout pregnancy and early lactation significantly increases vitamin B-12 status of mothers and infants. It is important to determine whether there are correlations between these findings and neurologic and metabolic functions. This trial was registered at clinicaltrials.gov as NCT00641862.

Enhanced care by community health workers in improving treatment adherence to antidepressant medication in rural women with major depression.

BACKGROUND & OBJECTIVES: Depression remains largely undiagnosed in women residing in rural India and consequently many do not seek help. Moreover, among those who are diagnosed, many do not complete treatment due to high rates of attrition. This study was aimed to compare the effectiveness of enhanced care with usual care in improving treatment seeking and adherence to antidepressant medication in women with depression living in rural India. METHODS: Six villages from rural Bangalore were randomized to either community health worker supported enhanced care or usual care. A total of 260 adult depressed women formed the final participants for the analysis. The outcome measures were number of women who sought and completed treatment, number of clinic visits, duration of treatment with antidepressant, changes in severity of depression (HDRS) and changes in quality of life [WHO-QOL (Brev) scale]. RESULTS: A significantly greater number of women from the treatment intervention (TI) group completed the treatment and were on treatment for a longer duration compared to the treatment as usual (TAU) group. However, there were no significant differences in the severity of depression or quality of life between the TI and the TAU groups or between treatment completers and treatment dropouts at six months. INTERPRETATION & CONCLUSIONS: Enhanced care provided by the trained community health workers to rural women with major depression living in the community resulted in greater number of women seeking help and adhering to treatment with antidepressants. However, despite enhanced care a significant number of rural women diagnosed with depression either did not seek help or discontinued treatment prematurely. These findings have significant public health implications, as untreated depression is associated with considerable disability.

Nutritional factors associated with antenatal depressive symptoms in the early stage of pregnancy among urban South Indian women.

Many women of reproductive age from developing countries have poor nutritional status, and the prevalence of depression during pregnancy is high. The objective of the present study was to assess the prevalence of antenatal depressive symptoms in early pregnancy, and to identify the demographic and nutritional factors associated with these symptoms in a sample of urban South Indian pregnant women. This cross-sectional study was the baseline assessment of a prospective randomized controlled trial of vitamin B12 supplementation in urban pregnant south Indian women between the ages of 18 and 40 years ( www.clinicaltrials.gov : NCT00641862). 365 women in their first trimester of pregnancy were screened for depressive symptoms at an urban clinic in Karnataka, South India, using the Kessler Psychological Distress Scale (K-10). Nutritional, clinical and biochemical factors were also assessed. Mean (SD) age of the cohort was 22.6 (3.7) years and mean (SD) BMI was 20.4 (3.3) kg/m(2). 121 (33 %) of the women in the 1st trimester had symptoms consistent with depression (K-10 score >6). In multivariate log binomial regression analysis, presence of antenatal depressive symptoms in the first trimester were positively associated with vomiting, prevalence ratio (PR) = 1.54 (95 % CI 1.10, 2.16) and negatively with anemia, PR = 0.67 (95 % CI 0.47, 0.96). Nutrient intakes, serum vitamin B12, methylmalonic acid, homocysteine and red cell folate levels were not associated with measures of depression. Antenatal depressive symptoms in early pregnancy are highly prevalent in urban Indian women and are more common in women with vomiting and without anemia. In this cross-sectional data, blood concentrations of vitamin B12 and folate were not associated with depressive symptoms. The relationship between nutritional status and depressive symptoms may require larger and longitudinal studies.