Associations between maternal and infant selenium status and child growth in a birth cohort from Dhaka, Bangladesh.

Deficiency of essential trace element, Se, has been implicated in adverse birth outcomes and in child linear growth because of its important role in redox biology and associated antioxidant effects. We used data from a randomised controlled trial conducted among a cohort of pregnant and lactating women in Dhaka, Bangladesh to examine associations between Se biomarkers in whole blood (WBSe), serum and selenoprotein P (SEPP1) in maternal delivery and venous cord (VC) blood. Associations between Se biomarkers, birth weight and infant growth outcomes (age-adjusted length, weight, head circumference and weight-for-length z-scores) at birth, 1 and 2 years of age were examined using regression analyses. WB and serum Se were negatively associated with birth weight (adjusted ß, 95 % CI, WBSe delivery: −26·6 (­44·3, −8·9); WBSe VC: −19·6 (­33·0, −6·1)); however, delivery SEPP1 levels (adjusted ß: −37·5 (­73·0, −2·0)) and VC blood (adjusted ß: 82·3 (30·0, 134·7)) showed inconsistent and opposite associations with birth weight. Positive associations for SEPP1 VC suggest preferential transfer from mother to fetus. We found small associations between infant growth and WBSe VC (length-for-age z-score ß, 95 % CI, at birth: −0·05 (­0·1, −0·01)); 12 months (ß: −0·05 (­0·08, −0·007)). Weight-for-age z-score also showed weak negative associations with delivery WBSe (at birth: −0·07 (­0·1, −0·02); 12 -months: −0·05 (­0·1, −0·005)) and in WBSe VC (at birth: −0·05 (­0·08, −0·02); 12 months: −0·05 (­0·09, −0·004)). Given the fine balance between essential nutritional and toxic properties of Se, it is possible that WB and serum Se may negatively impact growth outcomes, both in utero and postpartum.

Implications for quantifying early life growth trajectories of term-born infants using INTERGROWTH-21st newborn size standards at birth in conjunction with World Health Organization child growth standards in the postnatal period.

BACKGROUND: The INTERGROWTH-21st sex and gestational age (GA) specific newborn size standards (IG-NS) are intended to complement the World Health Organization Child Growth Standards (WHO-GS), which are not GA-specific. We examined the implications of using IG-NS at birth and WHO-GS at postnatal ages in longitudinal epidemiologic studies. OBJECTIVES: The aim of this study was to quantify the extent to which standardised measures of newborn size and growth are affected when using WHO-GS versus IG-NS at birth among term-born infants. METHODS: Data from two prenatal trials in Bangladesh (n = 755) and The Gambia (n = 522) were used to estimate and compare size at birth and growth from birth to 3 months when using WHO-GS only ('WHO-GS') versus IG-NS at birth and WHO-GS postnatally ('IG-NS'). Mean length-for-age (LAZ), weight-for-age (WAZ) and head circumference-for-age (HCAZ), and the prevalence of undernutrition (stunting: LAZ < -2SD; underweight: WAZ < -2SD; and microcephaly: HCAZ < -2SD) were estimated overall and by GA strata [early-term (370/7 -386/7 ), full-term (390/7 -406/7 ) and late-term (410/7 -430/7 )]. We used Bland-Altman plots to compare continuous indices and Kappa statistic to compare categorical indicators. RESULTS: At birth, mean LAZ, WAZ and HCAZ, and the prevalence of undernutrition were most similar among newborns between 39 and 40 weeks of GA when using WHO-GS versus IG-NS. However, anthropometric indices were systematically lower among early-term infants and higher among late-term infants when using WHO-GS versus IG-NS. Early-term and late-term infants demonstrated relatively faster and slower growth, respectively, when using WHO-GS versus IG-NS, with the direction and magnitude of differences varying between anthropometric indices. Individual-level differences in attained size and growth, when using WHO-GS versus IG-NS, were greater than 0.2 SD in magnitude for >60% of infants across all anthropometric indices. CONCLUSIONS: Using IG-NS at birth with WHO-GS postnatally is acceptable for full-term infants but may give a misleading interpretation of growth trajectories among early- and late-term infants.

Digital Storytelling for Health-Related Outcomes in Older Adults: Systematic Review.

BACKGROUND: Older adults face a unique set of challenges and may experience a range of psychological comorbidities. Digital storytelling is an emerging tool for sharing and recording lived experiences and may have the potential to support well-being but is yet to be systematically reviewed for use among older adults. OBJECTIVE: The aim of this review is to examine the methods for creating digital stories, the health-related outcomes associated with creating digital stories, and the potential for implementing digital storytelling with older adults. METHODS: We systematically searched electronic databases to identify articles published in English that reported on at least one health-related outcome of digital storytelling for participants aged ≥60 years. Data were extracted and synthesized using qualitative content analysis and summarized in tables. The methodological quality of the studies was assessed using the Mixed Methods Appraisal Tool. RESULTS: A total of 8 studies were included in the review. Participants were primarily community-dwelling older adults living with dementia, involving family caregivers and professional care staff. Studies have taken various approaches to digital storytelling and reported diverse benefits associated with digital storytelling, including improvements in mood, memory, social engagement, and quality of relationships. Although the potential for implementation was not widely examined, some studies have presented evidence for acceptability and feasibility. Generally, studies were of high quality, despite the absence of comparator groups and confounder analyses. CONCLUSIONS: The evidence reviewed suggests that despite the various approaches taken, digital storytelling shows promise as an effective approach for supporting well-being in older adults. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42019145922; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019145922. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/15512.

Vitamin D Supplementation in Pregnancy and Lactation and Infant Growth.

BACKGROUND: It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants' length-for-age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group). RESULTS: Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length-for-age z scores. Scores were as follows: placebo, -0.93±1.05; prenatal 4200, -1.11±1.12; prenatal 16,800, -0.97±0.97; prenatal 28,000, -1.06±1.07; and prenatal and postpartum 28,000, -0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25-hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose. CONCLUSIONS: In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013 .).

User knowledge factors that hinder the design of new home healthcare devices: investigating thirty-eight devices and their manufacturers.

BACKGROUND: The demand for home healthcare devices arises; however, many home healthcare devices on the market are not designed to reflect the needs and features of the end-users. This study explored the user knowledge factors that hindered the design of new home healthcare devices and the interrelationships between the factors. METHODS: The abovementioned factors were identified from analysing the project documents of thirty-eight carefully selected home healthcare devices produced by five manufacturers; followed by interviewing the thirty stakeholders playing key roles in developing the devices. RESULTS: The design of the home healthcare devices was influenced by (1) the user insights utilised in formulating project strategies; (2) the sources of user information; (3) the execution of user research; and (4) the formulation of the manufacturers' principal innovation processes. CONCLUSIONS: The users' characteristics and needs were not sufficiently reflected in developing new home healthcare devices. One root cause was that the end-users were not perceived by the manufacturers as a key success factor in most cases, given that most of the devices were initiated following the public sector's requests. Actual or potential applications of this study include the facilitation of the appropriate application of human factors methods in developing new home healthcare devices and the improvement of the user performance of the end-devices.

Antimicrobial Prescribing during Infant Hospital Admissions in a Birth Cohort in Dhaka, Bangladesh.

Empirical antimicrobial use is common in hospitalized infants and may contribute to antimicrobial resistance in low- and middle-income countries. In this observational birth cohort study nested in a randomized controlled trial in Dhaka, Bangladesh, inpatient antimicrobial prescription data were extracted from serious adverse event forms completed for hospitalizations of infants (0-12 months of age). The primary outcome was the proportion of inpatient admissions where systemic antimicrobials were prescribed. Infant and hospitalization-related factors associated with antimicrobial prescriptions were determined. Among 1254 infants, there were 448 admissions to 32 facilities from 2014 to 2016. Antimicrobials were prescribed in 73% of admissions with a mean antimicrobial exposure rate of 0.25 antimicrobials per day of admission [95% confidence intervals (95% CIs): 0.24-0.27]. The most common antibiotics were aminoglycosides (29%), penicillins (26%) and third-generation cephalosporins (25%). In all, 58% of antibiotics were classified as 'access', 38% 'watch' and 1% 'reserve' using the World Health Organization (WHO) Essential Medicines List classification. WHO-recommended antimicrobial regimens were used in 68% of neonatal sepsis and 9% of lower respiratory tract infection (LRTI) admissions. 'Watch' antimicrobials were used in 26% of neonatal sepsis and 76% of LRTI admissions. Compared with private facilities, antimicrobial prescription rates were lower at government [rate ratio (RR) 0.71; 95% CI: 0.61-0.83] and charitable facilities (RR 0.39; 95% CI: 0.28-0.53), after adjustment for household wealth index and parental education. Younger infant age, older maternal age and longer admission were associated with higher prescription rates. These findings highlight the need for paediatric antimicrobial stewardship programs in Bangladesh.

Prenatal vitamin D supplementation and infant vitamin D status in Bangladesh.

OBJECTIVE: To determine the effect of prenatal maternal vitamin D supplementation on infant vitamin D status in a tropical region where vitamin D supplementation is not routine. DESIGN: A prospective observational follow-up of a randomized trial. SETTING: Maternal-child health facility in Dhaka, Bangladesh (23°N). SUBJECTS: Infants born to pregnant women (n 160) randomized to receive 875 µg (35 000 IU) cholecalciferol (vitamin D3) per week (VD) or placebo (PL) during the third trimester were followed from birth until 6 months of age (n 115). Infant serum 25-hydroxyvitamin D concentration (25(OH)D) was measured at <1, 2, 4 and 6 months of age. RESULTS: Mean infant 25(OH)D was higher in the VD v. PL group at <1 month of age (mean (sd): 80 (20) nmol/l v. 22 (18) nmol/l; P<0·001), but the difference was attenuated by 2 months (52 (19) nmol/l v. 40 (23) nmol/l; P=0·05). Groups were similar at 4 months (P=0·40) and 6 months (n 72; P=0·26). In the PL group, mean infant 25(OH)D increased to 78 (95 % CI 67, 88) nmol/l by 6 months of age (n 34). 25(OH)D was higher with infant formula-feeding and higher in summer v. winter. CONCLUSIONS: Prenatal third-trimester vitamin D supplementation (875 µg (35 000 IU)/week) significantly ameliorated infant vitamin D status during the neonatal period when the risk of vitamin D deficiency is greatest. Further research is warranted to determine factors that contribute to the rise in 25(OH)D during the first 6 months of life among breast-fed infants in this setting.

Prenatal high-dose vitamin D3 supplementation has balanced effects on cord blood Th1 and Th2 responses.

BACKGROUND: Antenatal vitamin D3 (vitD3) supplementation significantly increases maternal and neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentration, yet the effect of an improvement in maternal-fetal vitamin D status on the neonatal immune response is unclear. METHOD: To assess the effect of prenatal vitD3 supplementation on cord blood T cell function, healthy pregnant Bangladeshi women (n = 160) were randomized to receive either oral 35,000 IU/week vitD3 or placebo from 26 to 29 weeks of gestation to delivery. In a subset of participants (n = 80), cord blood mononuclear cells (CBMC) were cultured, non-adherent lymphocytes were isolated to assess T cell cytokine responses to phytohemagglutinin (PHA) and anti-CD3/anti-CD28 (iCD3/iCD28), measured by multiplex assay. In 12 participants, lymphocyte gene expression profiles were analyzed by PCR array. RESULT: In supplemented group, increased concentrations of IL-10 (P < 0.000) and TNF-α (P = 0.05) with iCD3/iCD28 stimulation and IFN-γ (p = 0.05) with PHA stimulation were obtained compared to placebo group. No differences in the gene expression profile were noted between the two groups. However, PHA stimulation significantly induced the expression of genes encoding Th1 and Th2 cytokines and down-regulated a number of genes involved in T-cell development, proliferation and differentiation of B cells, signal transduction pathway, transcriptional regulation and pattern recognition receptors (PRRs) in the vitamin D group (vitD group). CONCLUSION: Third-trimester high-dose vitD3 supplementation in healthy pregnant women had balanced effects on biomarkers of cord blood Th1 and Th2 responses. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01126528 ).

Tablets are preferred and more acceptable than powdered prenatal calcium supplements among pregnant women in Dhaka, Bangladesh.

Prenatal calcium supplementation is recommended by the WHO to decrease the risk of preeclampsia in women with low dietary calcium intake; yet, this recommendation has not been successfully implemented to date. One component of an effective population-based prenatal calcium intervention will be the selection of a widely accepted calcium vehicle to promote consistent, long-term consumption of the supplement. We aimed to evaluate preference and acceptability of 4 different options for delivering prenatal calcium (conventional tablets, chewable tablets, unflavored powder, and flavored powder) to pregnant women in urban Bangladesh. In a modified discrete-choice trial, pregnant women (n = 132) completed a 4-d "run-in period" in which each delivery vehicle was sampled once, followed by a 21-d "selection period" during which participants were instructed to freely select a single delivery vehicle of their choice each day. Preference was empirically defined as the probability that each delivery vehicle was selected on a given day, and measured from participants' daily delivery vehicle selections; acceptability was assessed by using mid- and post-trial questionnaires. Conventional tablets demonstrated the highest probability of selection (62%); the probability of selection of chewable tablets (19%), flavored powder (12%), and unflavored powder (5%) were all significantly lower than for conventional tablets (P < 0.001). The palatability and product characteristics of the conventional tablets were more acceptable than for the other 3 delivery vehicles. Our rigorous methodologic approach used both quantitative and self-reported measures that consistently identified the most preferred and accepted prenatal calcium delivery form. Through observation of pregnant women's actual supplement use, and perceptions of acceptability (i.e., ease of use, palatability), we demonstrated that conventional tablets are likely to be the most accepted and successful calcium delivery vehicle in future field studies and scale-up of the WHO recommendation in Bangladesh.

Vitamin D and fetal-neonatal calcium homeostasis: findings from a randomized controlled trial of high-dose antenatal vitamin D supplementation.

BACKGROUND: There is current interest in the maternal-fetal effects of antenatal vitamin D supplementation, yet little data regarding vitamin D's role in neonatal calcium homeostasis. We determined to assess the effect of high-dose antenatal vitamin D supplementation on fetal and neonatal calcium concentrations. METHODS: In a double-blinded, placebo-controlled trial in Bangladesh, 160 pregnant women were randomized to oral vitamin D3 (35,000 IU/wk) or placebo from 26 to 29 wk of gestation. RESULTS: Total serum calcium (Ca) was higher in cord blood of those supplemented vs. placebo (2.66 ± 0.1 vs. 2.61 ± 0.2 mmol/l; P = 0.04), but the difference in albumin-adjusted calcium was not statistically significant. Change in Ca concentration from birth to day 3 of life was attenuated by vitamin D (-0.10 ± 0.17) compared with placebo (-0.22 ± 0.18 mmol/l; P = 0.02). Maternal 25-hydroxyvitamin D (25(OH)D) (P = 0.04) and cord 25(OH)D (P < 0.01) were associated with day 3 infant Ca, suggesting that the effect of supplementation was mediated by change in maternal-infant vitamin D status. Six infants in each of the supplemented and placebo groups had transient hypercalcemia/hypercalcuria; in all the hypercalcemia/hypercalcuria was asymptomatic, spontaneously resolved, and unassociated with nephrocalcinosis at 1 mo of life. CONCLUSION: High-dose antenatal third-trimester vitamin D supplementation attenuated the early postnatal calcium nadir, without increasing the risk of postnatal hypercalcemia.

Prenatal vitamin D3 supplementation suppresses LL-37 peptide expression in ex vivo activated neonatal macrophages but not their killing capacity.

Vitamin D has regulatory effects on innate immunity. In the present study, we aimed to assess the effect of prenatal vitamin D3 (vitD3) supplementation on neonatal innate immunity in a randomised, placebo-controlled trial by evaluating cathelicidin (LL-37) expression and the killing capacity of macrophages. Healthy pregnant women (n 129) attending a clinic in Dhaka were randomised to receive either a weekly oral dose of 0·875 mg vitD3 or placebo starting from 26 weeks of gestation up to delivery. Serum, plasma and monocyte-derived macrophages (MDM) were obtained from the cord blood. 25-Hydroxyvitamin D (25(OH)D) concentration was measured in serum. MDM were stimulated with or without Toll-like-receptor 4 ligand (TLR4L). Innate immune function was assessed by measuring LL-37 peptide levels in the culture supernatant of MDM by ELISA, LL-37 transcript levels by quantitative PCR, and ex vivo bactericidal capacity of MDM. VitD3 supplementation did not increase LL-37 peptide levels in plasma or in the extracellular fluid of macrophages with or without TLR4L induction. However, stimulated intracellular LL-37 expression (ratio of stimulated:unstimulated MDM) was significantly reduced in the vitamin D group v. placebo (P=0·02). Multivariate-adjusted analyses showed that intracellular LL-37 peptide concentration from stimulated MDM was inversely associated with 25(OH)D concentration in serum (P=0·03). TLR4L stimulation increased the bactericidal capacity of MDM compared with the unstimulated ones (P=0·01); however, there was no difference in killing capacity between the two groups. A weekly dose of 0·875 mg vitD3 to healthy pregnant women suppressed the intracellular LL-37 peptide stores of activated macrophages, but did not significantly affect the ex vivo bactericidal capacity of cord blood MDM.

Digital Storytelling Intervention for Enhancing the Social Participation of People With Mild Cognitive Impairment: Co-Design and Usability Study.

BACKGROUND: Community-based social participation has shown promise in delaying cognitive decline in older adults with mild cognitive impairment (MCI) who are at risk of developing dementia. Although group storytelling interventions have proven effective, the need for a skilled workforce to support people with MCI can limit broader community implementation. Technology-based interventions may offer a solution to this limitation by replicating the abilities of therapists. OBJECTIVE: This study aims to co-design a digital storytelling intervention and evaluate its usability. METHODS: This co-design process involved 3 stages, engaging people with MCI (n=12), their caregivers (n=4), and therapists (n=5) in Beijing, China. In the first stage, we used card sorting and voting methods to identify potential incentives for social participation and target the specific abilities that people with MCI wanted to enhance. In the second stage, we conducted brainstorming sessions with people with MCI and their caregivers to identify the potential features of a digital storytelling application named Huiyou ("meeting new friends" in Chinese). Finally, we assessed Huiyou's usability with people with MCI and therapists, leading to iterative improvements based on the usability findings. RESULTS: We uncovered a crucial link between boosting the self-confidence of people with MCI and their ability to address social participation challenges. Notably, we identified memory improvement and enhanced language expression as key factors for effective communication with grandchildren. Subsequently, participants suggested features and interfaces to address these challenges, leading to the development of Huiyou, a group-based digital storytelling application featuring functions such as generating story materials, conducting memory retrieval activities, and sharing stories. It received an "excellent" rating in the User Experience Questionnaire benchmark, displaying high levels of attractiveness, dependability, stimulation, and novelty. People with MCI achieved an average task completion rate of 87% (n=19; SD 0.13) of the 22 tasks. However, feedback from people with MCI and therapists highlighted usability issues in navigation, activity management, user interface, and feature optimization, indicating a need for improved accessibility and efficiency. CONCLUSIONS: The co-design approach contributed to developing the Huiyou prototype, supporting community-based social participation. User feedback highlighted the potential of Huiyou to enhance well-being and facilitate meaningful social interactions while maintaining crucial existing relationships.

Examining behaviour change techniques (BCTs) in technology-based interventions for enhancing social participation in people with mild cognitive impairment (MCI) or dementia: a scoping review protocol.

INTRODUCTION: Technology-based interventions have improved the social participation of older adults with mild cognitive impairment (MCI) or dementia. Nevertheless, how these interventions modify social participation remains to be seen, and what efficient behaviour change techniques (BCTs) have been used. As such, this study aims to conduct a scoping review, identifying the features and BCTs behind technology-based interventions that improve social participation for individuals with MCI or dementia. METHODS AND ANALYSIS: The scoping review method will be used to search journal articles from electronic databases, such as PsycINFO, PubMed, MEDLINE, Web of Science, Scopus and reference lists. Following the population, concept and context structure, this study focuses on adults over 60 diagnosed with MCI or dementia. It delves into technology-based interventions, specifically focusing on BCTs, features and overall effectiveness for improving social participation. The research considers contextual factors, exploring the diverse settings where these interventions are used, including homes, healthcare facilities and community centres. This approach aims to provide nuanced insights into the impact of technology-based interventions on social participation in the targeted demographic. Two authors will independently screen titles, abstracts and full texts using Covidence software. Disagreements will be resolved through consensus or a third reviewer, and reasons for exclusion will be documented. We will conduct a detailed analysis of BCTs to pinpoint effective strategies applicable to future technology-based intervention designs. Through this scoping review, we aim to provide valuable insights that guide the direction of future research. Specifically, we seek to inform the development of effective technology-based interventions tailored to support social participation for people with MCI or dementia. ETHICS AND DISSEMINATION: Ethical approval is not necessary, as this review will use available articles from electronic databases. The outcome of the study will be published in a peer-reviewed journal. PROTOCOL REGISTRATION NUMBER: https://osf.io/tkzuf/.

Digital Interventions for Combating Internet Addiction in Young Children: Qualitative Study of Parent and Therapist Perspectives.

BACKGROUND: Internet addiction is an emerging mental health issue in this digital age. Nowadays, children start using the internet in early childhood, thus making them vulnerable to addictive use. Previous studies have reported that the risk of internet addiction tends to be higher in lower-income regions with lower quality of life, such as Indonesia. Indonesia has high risks and prevalence of internet addiction, including in children. Digital interventions have been developed as an option to combat internet addiction in children. However, little is known about what parents and therapists in Indonesia perceive about these types of interventions. OBJECTIVE: This study aims to investigate the experiences, perceptions, and considerations of parents and therapists regarding digital interventions for combating internet addiction in young Indonesian children. METHODS: This study used a qualitative exploratory approach through semistructured interviews. We involved 22 parents of children aged 7 to 11 years and 6 experienced internet addiction therapists for children. The interview data were transcribed and analyzed using thematic analysis. RESULTS: Participants in this study recognized 3 existing digital interventions to combat internet addiction: Google Family Link, YouTube Kids, and Apple parental control. They perceived that digital interventions could be beneficial in continuously promoting healthy digital behavior in children and supporting parents in supervision. However, the existing interventions were not highly used due to limitations such as the apps' functionality and usability, parental capability, parent-child relationships, cultural incompatibility, and data privacy. CONCLUSIONS: The findings suggest that digital interventions should focus not only on restricting and monitoring screen time but also on suggesting substitutive activities for children, developing children's competencies to combat addictive behavior, improving digital literacy in children and parents, and supporting parental decision-making to promote healthy digital behavior in their children. Suggestions for future digital interventions are provided, such as making the existing features more usable and relatable, investigating gamification features to enhance parental motivation and capability in managing their children's internet use, providing tailored or personalized content to suit users' characteristics, and considering the provision of training and information about the use of interventions and privacy agreements.

Prenatal but not continued postpartum vitamin D supplementation reduces maternal bone resorption as measured by C-terminal telopeptide of type 1 collagen without effects on other biomarkers of bone metabolism.

Vitamin D is a key regulator of bone mineral homeostasis and may modulate maternal bone health during pregnancy and postpartum. Using previously-collected data from the Maternal Vitamin D for Infant Growth (MDIG) trial in Dhaka, Bangladesh, we aimed to investigate the effects of prenatal and postpartum vitamin D3 supplementation on circulating biomarkers of bone formation and resorption at delivery and 6 months postpartum. MDIG trial participants were randomized to receive a prenatal;postpartum regimen of placebo or vitamin D3 (IU/week) as either 0;0 (Group A), 4200;0 (B), 16,800;0 (C), 28,000;0 (D) or 28,000;28,000 (E) from 17 to 24 weeks' gestation to 6 months postpartum. As this sub-study was not pre-planned, the study sample included MDIG participants who had data for at least 1 biomarker of interest at delivery or 6 months postpartum, with a corresponding baseline measurement (n = 690; 53 % of 1300 enrolled trial participants). Biomarkers related to bone turnover were measured in maternal venous blood samples collected at enrolment, delivery, and 6 months postpartum: osteoprotegerin (OPG), osteocalcin (OC), receptor activator nuclear factor kappa-B ligand (RANKL), fibroblast growth factor 23 (FGF23), procollagen type 1 N-terminal propeptide, (P1NP) and carboxy terminal telopeptide of type 1 collagen (CTx). Supplementation effects were expressed as percent differences between each vitamin D group and placebo with 95 % confidence intervals (95 % CI). Of 690 participants, 64 % had 25-hydroxyvitamin D concentrations (25OHD) <30 nmol/L and 94 % had 25OHD < 50 nmol/L at trial enrolment. At delivery, mean CTx concentrations were 27 % lower in group E versus placebo (95 % CI: -38, -13; P < 0.001), adjusting for enrolment concentrations. However, at 6 months postpartum, CTx concentrations were not statistically different in group E versus placebo (14 %; 95 % CI: -5.3, 37; P = 0.168), adjusting for delivery CTx concentrations. Effects on other biomarkers at delivery or postpartum were not statistically significant. In conclusion, prenatal high-dose vitamin D supplementation reduced bone resorption during pregnancy, albeit by only one biomarker, and without evidence of a sustained effect in the postpartum period. However, further evidence is needed to substantiate potential maternal bone health benefits of vitamin D in the postpartum period.

Detection and absolute quantification of Lactiplantibacillus plantarum ATCC 202195 by quantitative real-time PCR.

IMPORTANCE: When administered for seven consecutive days shortly after birth, the probiotic bacterium Lactiplantibacillus plantarum ATCC 202195 plus fructooligosaccharide (FOS) was reported to reduce sepsis and lower respiratory tract infection events during early infancy in a randomized trial in India. Since probiotic effects are often strain specific, strain-level detection and quantification by routine molecular methods enables the monitoring of safety outcomes, such as probiotic-associated bacteremia, and allows for the quality of probiotic interventions to be assessed and monitored (i.e., verify strain identity and enumerate). Despite the potential clinical applications of L. plantarum ATCC 202195, an assay to detect and quantify this strain has not previously been described. Herein, we report the design of primer and probe sequences to detect L. plantarum ATCC 202195 and the development and optimization of a real-time PCR assay to detect and quantify the strain with high specificity and high sensitivity.

Maternal Vitamin D Supplementation and Infantile Rickets: Secondary Analysis of a Randomized Trial.

BACKGROUND: The role of maternal vitamin D supplementation in the prevention of infantile rickets is unknown, particularly in low- and middle-income countries without routine infant vitamin D supplementation. Through secondary analysis of a randomized, placebo-controlled trial in Bangladesh, we examined the dose-ranging effects of maternal vitamin D supplementation on the risk of biochemical rickets at 6 to 12 months of age. METHODS: Pregnant women (n = 1300) were randomized into 5 groups: placebo, or vitamin D 4200 IU/week, 16 800 IU/week, or 28 000 IU/week from second trimester to delivery and placebo until 6 months postpartum; or 28 000 IU/week prenatally and until 6 months postpartum. Infants underwent biochemical rickets screening from 6 to 12 months of age (n = 790). Relative risks (RR) and 95% confidence intervals (95% CI) of biochemical rickets were estimated for each group versus placebo. RESULTS: Overall, 39/790 (4.9%) infants had biochemical rickets. Prevalence was highest in the placebo group (7.8%), and the risk was significantly lower among infants whose mothers received combined prenatal and postpartum vitamin D at 28 000 IU/week (1.3%; RR, 0.16; 95% CI, 0.03-0.72). Risks among infants whose mothers received only prenatal supplementation (4200 IU, 16 800 IU, 28 000 IU weekly) were not significantly different from placebo: 3.8% (RR, 0.48; 95% CI, 0.19-1.22), 5.8% (RR, 0.74; 95% CI, 0.33-1.69), and 5.7% (RR, 0.73; 95% CI, 0.32-1.65), respectively. CONCLUSIONS: Maternal vitamin D supplementation (28 000 IU/week) during the third trimester of pregnancy until 6 months postpartum reduced the risk of infantile biochemical rickets. Further research is needed to define optimal postpartum supplementation dosing during lactation.

Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG.

BACKGROUNDThe use of high-throughput technologies has enabled rapid advancement in the knowledge of host immune responses to pathogens. Our objective was to compare the repertoire, protection, and maternal factors associated with human milk antibodies to infectious pathogens in different economic and geographic locations.METHODSUsing multipathogen protein microarrays, 878 milk and 94 paired serum samples collected from 695 women in 5 high and low-to-middle income countries (Bangladesh, Finland, Peru, Pakistan, and the United States) were assessed for specific IgA and IgG antibodies to 1,607 proteins from 30 enteric, respiratory, and bloodborne pathogens.RESULTSThe antibody coverage across enteric and respiratory pathogens was highest in Bangladeshi and Pakistani cohorts and lowest in the U.S. and Finland. While some pathogens induced a dominant IgA response (Campylobacter, Klebsiella, Acinetobacter, Cryptosporidium, and pertussis), others elicited both IgA and IgG antibodies in milk and serum, possibly related to the invasiveness of the infection (Shigella, enteropathogenic E. coli "EPEC", Streptococcus pneumoniae, Staphylococcus aureus, and Group B Streptococcus). Besides the differences between economic regions and decreases in concentrations over time, human milk IgA and IgG antibody concentrations were lower in mothers with high BMI and higher parity, respectively. In Bangladeshi infants, a higher specific IgA concentration in human milk was associated with delayed time to rotavirus infection, implying protective properties of antirotavirus antibodies, whereas a higher IgA antibody concentration was associated with greater incidence of Campylobacter infection.CONCLUSIONThis comprehensive assessment of human milk antibody profiles may be used to guide the development of passive protection strategies against infant morbidity and mortality.FUNDINGBill and Melinda Gates Foundation grant OPP1172222 (to KMJ); Bill and Melinda Gates Foundation grant OPP1066764 funded the MDIG trial (to DER); University of Rochester CTSI and Environmental Health Sciences Center funded the Rochester Lifestyle study (to RJL); and R01 AI043596 funded PROVIDE (to WAP).