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Summary of Key Points. Although relatively rare, invasive meningococcal disease continues to be a health concern, especially in young children. This systematic review clearly delineates both the near- and long-term morbidities that can occur after, and persist beyond, the period of acute illness. Background. Although rare, invasive meningococcal disease (IMD) continues to be a health concern in highincome countries because of its severe morbidity and relatively high case fatality rate, especially in young children. However, studies measuring sequelae of IMD across the spectrum of invasive syndromes have not been systematically reviewed. We conducted a systematic review of sequelae attributable to IMD and quality of life (QoL) in IMD survivors in high-income countries. Methods. We searched Medline, Embase, and HealthSTAR for primary studies that assessed sequelae or QoL in individuals of any age with and without IMD. Two independent reviewers screened articles, abstracted data, and performed quality appraisal. The findings were summarized qualitatively. Results. Of 1884 citations screened, 17 studies were included. The most commonly assessed sequelae were hearing impairment, cognitive impairment, and psychological problems. In general, children with IMD had a greater incidence of hearing loss and psychological disorders, including attention-deficit/hyperactivity disorder. However, its effects on intelligence in children remain unclear. No statistical differences in overall cognitive function in adults were reported. The odds of death were significantly increased with IMD at hospital discharge and up to 30 years after disease. Lower overall QoL was observed in those who had IMD versus controls. Conclusions. The results of this systematic review delineate both the short- and long-term morbidities that can occur after, and persist beyond, the period of acute illness. A better understanding of the full spectrum of IMD sequelae is critical for assessing the burden of IMD and supporting healthcare planning and decision making in light of new vaccines. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the risk of recurrence of adverse events following immunization (AEFIs) upon revaccination and to determine among patients with suspected vaccine allergy whether allergy skin test positivity was associated with AEFI recurrence.Study Design: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 with AEFIs who required revaccination with the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Special Immunization Clinic physicians used guidelines to inform their recommendations. Participants were followed up after revaccination to capture AEFI recurrences. Data were transferred to a central database for descriptive analysis.Results: Overall, 588 participants were assessed for 627 AEFIs; 570 (91%) AEFIs occurred in children <18 years of age. AEFIs included immediate hypersensitivity (130/627; 21%), large local reactions (110/627; 18%), nonurticarial rash (51/627; 8%), seizures (26/627; 4%), and thrombocytopenia (11/627; 2%). Revaccination was recommended to 513 of 588 (87%) participants. Among participants recommended and due for revaccination during the study period, 63% (299/477) were revaccinated. AEFI recurrence was 10% (31/299) overall, 31% (15/49) for large local reactions, and 7% (5/66) for immediate hypersensitivity. No recurrence was serious. Among 92 participants with suspected vaccine allergy who underwent skin testing and were revaccinated, the negative predictive value of skin testing for AEFI recurrence was 96% (95% CI 92.5%-99.5%).Conclusions: Most individuals with AEFIs were safely revaccinated. Among those with suspected vaccine allergy, skin testing may help determine the safety of revaccination. [ABSTRACT FROM AUTHOR]

Invasive fungal infection (IFI) is an important cause of mortality in immunocompromised children, particularly after hematopoietic stem cell transplantation. We describe 5 cases of Fusarium IFI in immunocompromised children seen at our institution over a 15-year period. A summary of all published pediatric cases of invasive Fusarium infection is presented. A focus on antifungal management challenges in these patients will be discussed. [ABSTRACT FROM AUTHOR]

Background: Decreasing trends in measles mortality have been reported in recent years. However, such estimates of measles mortality have depended heavily on assumed regional measles case fatality risks (CFRs) and made little use of mortality data from low- and middle-income countries in general and India, the country with the highest measles burden globally, in particular. Methods: We constructed a dynamic model of measles transmission in India with parameters that were empirically inferred using spectral analysis from a time series of measles mortality extracted from the Million Death Study, an ongoing longitudinal study recording deaths across 2.4 million Indian households and attributing causes of death using verbal autopsy. The model was then used to estimate the measles CFR, the number of measles deaths, and the impact of vaccination in 2000–2015 among under-five children in India and in the states of Bihar and Uttar Pradesh (UP), two states with large populations and the highest numbers of measles deaths in India. Results: We obtained the following estimated CFRs among under-five children for the year 2005: 0.63% (95% confidence interval (CI): 0.40–1.00%) for India as a whole, 0.62% (0.38–1.00%) for Bihar, and 1.19% (0.80–1.75%) for UP. During 2000–2015, we estimated that 607,000 (95% CI: 383,000–958,000) under-five deaths attributed to measles occurred in India as a whole. If no routine vaccination or supplemental immunization activities had occurred from 2000 to 2015, an additional 1.6 (1.0–2.6) million deaths for under-five children would have occurred across India. Conclusions: We developed a data- and model-driven estimation of the historical measles dynamics, CFR, and vaccination impact in India, extracting the periodicity of epidemics using spectral and coherence analysis, which allowed us to infer key parameters driving measles transmission dynamics and mortality. Electronic supplementary material The online version of this article (doi:10.1186/s12916-017-0908-3) contains supplementary material, which is available to authorized users.

Travellers' perception of their risk for acquiring travel-related conditions is an important contributor to decisions and behaviors during travel. In this study, we aimed to assess the differences between traveller-perceived and expert-assessed risk of travel-related conditions in children and adults travelling internationally and describe factors that influence travellers' perception of risk. Children and adults were recruited at the Hospital for Sick Children's Family Travel Clinic between October 2014 and July 2015. A questionnaire was administered to participants to assess their perceived risk of acquiring 32 travel-related conditions using a 7-point Likert scale. Conditions were categorized as vector-borne diseases, vaccine-preventable diseases, food and water borne diseases, sexually transmitted infections and other conditions. Two certified travel medicine experts reviewed each patient's chart and assigned a risk score based on the same 7-point Likert scale. Traveller and expert risk scores were compared using paired t-tests. In total, 207 participants were enrolled to participate in this study, 97 children (self-reported, n = 8; parent-reported, n = 89), and 110 adults. Travel-related risk for adults and parents answering for their children were significantly underestimated when compared to expert-assessed risk for 26 of the 32 assessed conditions. The underestimated conditions were the same for both adults and parents answering for children. Travel-related risk was not over-estimated for any condition. Adults underestimated their children's and their own risk for most travel-related conditions. Strategies to improve the accuracy of risk perception of travel-related conditions by travellers are needed to optimize healthy travel for children and their families. • Understanding travellers' perception of risk is key for pre-departure counselling. • Adults underestimate their child and their own risk of travel-acquired conditions. • A large proportion of travel-acquired conditions are unknown to travellers. [ABSTRACT FROM AUTHOR]

Objective: To quantify the impact on mortality of offering a hypothetical set of technically feasible, high-impact interventions for maternal and child survival during India’s 2010–2013 measles supplementary immunization activity. Methods: We developed Lives Saved Tool models for 12 Indian states participating in the supplementary immunization, based on state- and sex-specific data on mortality from India’s Million Deaths Study and on health services coverage from Indian household surveys. Potential add-on interventions were identified through a literature review and expert consultations. We quantified the number of lives saved for a campaign offering measles vaccine alone versus a campaign offering measles vaccine with six add-on interventions (nutritional screening and complementary feeding for children, vitamin A and zinc supplementation for children, multiple micronutrient and calcium supplementation in pregnancy, and free distribution of insecticide-treated bednets). Findings: The measles vaccination campaign saved an estimated 19 016 lives of children younger than 5 years. A hypothetical campaign including measles vaccine with add-on interventions was projected to save around 73 900 lives (range: 70 200–79 300), preventing 73 700 child deaths (range: 70 000–79 000) and 300 maternal deaths (range: 200–400). The most effective interventions in the whole package were insecticide-treated bednets, measles vaccine and preventive zinc supplementation. Girls accounted for 66% of expected lives saved (12 712/19 346) for the measles vaccine campaign, and 62% of lives saved (45 721/74 367) for the hypothetical campaign including add-on interventions. Conclusion: In India, a measles vaccination campaign including feasible, high-impact interventions could substantially increase the number of lives saved and mitigate gender-related inequities in child mortality.

Highlights: [•] We use a nationally representative sample of deaths to estimate national and sub-national measles mortality in India. [•] Measles killed about 92,000 children under 5 years of age and 107,000 children under 15 years of age in India in 2005. [•] Over 70% of under 5 measles deaths occurred in just 6 States. [•] The overall risk of dying from measles was nearly 70% higher in girls than in boys under 5 years of age. [ABSTRACT FROM AUTHOR]

Background: It is estimated that India has more deaths from rabies than any other country. However, existing estimates are indirect and rely on non-representative studies. Methods and Principal Findings: We examined rabies deaths in the ongoing Million Death Study (MDS), a representative survey of over 122,000 deaths in India that uses enhanced types of verbal autopsy. We estimated the age-specific mortality rates of symptomatically identifiable furious rabies and its geographic and demographic distributions. A total of 140 deaths in our sample were caused by rabies, suggesting that in 2005 there were 12,700 (99% CI 10,000 to 15,500) symptomatically identifiable furious rabies deaths in India. Most rabies deaths were in males (62%), in rural areas (91%), and in children below the age of 15 years (50%). The overall rabies mortality rate was 1.1 deaths per 100,000 population (99%CI 0.9 to 1.4). One third of the national rabies deaths were found in Uttar Pradesh (4,300) and nearly three quarters (8,900) were in 7 central and south-eastern states: Chhattisgarh, Uttar Pradesh, Odisha, Andhra Pradesh, Bihar, Assam, and Madhya Pradesh. Conclusions and Significance: Rabies remains an avoidable cause of death in India. As verbal autopsy is not likely to identify atypical or paralytic forms of rabies, our figure of 12,700 deaths due to classic and clinically identifiable furious rabies underestimates the total number of deaths due to this virus. The concentrated geographic distribution of rabies in India suggests that a significant reduction in the number of deaths or potentially even elimination of rabies deaths is possible. Author Summary: Rabies, a disease of antiquity, has been partially controlled in many countries and eliminated in a few. However, according to the World Health Organization, rabies continues to kill thousands of people in India each year, more than in any other country. We used an enhanced type of verbal autopsy (a structured interview of the relatives or close associates of the dead by non-medical staff with central medical coding by at least two doctors) to identify the causes of over 122,000 deaths in a large scale, representative sample in India in 2001–03. Using these data, we estimate that in 2005 approximately 12,700 people died from symptomatically identifiable furious rabies. Because verbal autopsy is not able to identify atypical presentations of rabies, our figure underestimates the actual number of rabies deaths in India. The majority of rabies deaths occurred in males, in rural areas, in children below the age of 15 years, and in a few states. The concentrated geographic distribution of rabies in India suggests that targeting with preventive campaigns including vaccination of animals and post exposure vaccination of humans might achieve a significant reduction in the number of deaths or potentially even elimination of deaths from this disease. [ABSTRACT FROM AUTHOR]

Background: It is estimated that India has more deaths from rabies than any other country. However, existing estimates are indirect and rely on non-representative studies. Methods and Principal Findings: We examined rabies deaths in the ongoing Million Death Study (MDS), a representative survey of over 122,000 deaths in India that uses enhanced types of verbal autopsy. We estimated the age-specific mortality rates of symptomatically identifiable furious rabies and its geographic and demographic distributions. A total of 140 deaths in our sample were caused by rabies, suggesting that in 2005 there were 12,700 (99% CI 10,000 to 15,500) symptomatically identifiable furious rabies deaths in India. Most rabies deaths were in males (62%), in rural areas (91%), and in children below the age of 15 years (50%). The overall rabies mortality rate was 1.1 deaths per 100,000 population (99%CI 0.9 to 1.4). One third of the national rabies deaths were found in Uttar Pradesh (4,300) and nearly three quarters (8,900) were in 7 central and south-eastern states: Chhattisgarh, Uttar Pradesh, Odisha, Andhra Pradesh, Bihar, Assam, and Madhya Pradesh. Conclusions and Significance: Rabies remains an avoidable cause of death in India. As verbal autopsy is not likely to identify atypical or paralytic forms of rabies, our figure of 12,700 deaths due to classic and clinically identifiable furious rabies underestimates the total number of deaths due to this virus. The concentrated geographic distribution of rabies in India suggests that a significant reduction in the number of deaths or potentially even elimination of rabies deaths is possible. [ABSTRACT FROM AUTHOR]

Background: Little is known about the causes of death in children in India after age five years. The objective of this study is to provide the first ever direct national and sub-national estimates of infectious disease mortality in Indian children aged 5 to 14 years. Methods: A verbal autopsy based assessment of 3 855 deaths is children aged 5 to 14 years from a nationally representative survey of deaths occurring in 2001-03 in 1?1 million homes in India. Results: Infectious diseases accounted for 58% of all deaths among children aged 5 to 14 years. About 18% of deaths were due to diarrheal diseases, 10% due to pneumonia, 8% due to central nervous system infections, 4% due to measles, and 12% due to other infectious diseases. Nationally, in 2005 about 59 000 and 34 000 children aged 5 to 14 years died from diarrheal diseases and pneumonia, corresponding to mortality of 24?1 and 13?9 per 100 000 respectively. Mortality was nearly 50% higher in girls than in boys for both diarrheal diseases and pneumonia. Conclusions: Approximately 60% of all deaths in this age group are due to infectious diseases and nearly half of these deaths are due to diarrheal diseases and pneumonia. Mortality in this age group from infectious diseases, and diarrhea in particular, is much higher than previously estimated. [ABSTRACT FROM AUTHOR]

Background As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transitions to endemicity and respiratory syncytial virus (RSV) and influenza reestablish their seasonal circulation patterns, understanding their comparative burden on infants and children can guide health system responses and funding priorities. Methods This was a population-based cohort study of children aged <5 years in Ontario, Canada, from September 2018 to August 2023 using linked health administrative databases. Results Seasonal cohorts comprised 731 838 to 763 660 children. RSV- and influenza-related hospital admission rates immediately decreased in March 2020. In 2021–2022, RSV-related admissions rebounded but remained 8%–11% lower than prepandemic seasons, whereas 2022–2023 RSV-related admissions increased 105%–113% versus prepandemic seasons and peak admissions occurred in November versus December. Influenza did not rebound until 2022–2023, when admissions were 28%–37% higher than prepandemic seasons. Coronavirus disease 2019 (COVID-19)–related admissions remained low until 2021–2022 and were lower than RSV-related admissions across all age groups during prepandemic and pandemic seasons. By contrast, 2021–2022 COVID-19-related admissions exceeded prepandemic influenza-related admissions by 30%–40% but decreased by 45% in 2022–2023 and were lower than prepandemic influenza-related admissions, except among infants aged <12 months who remained at highest risk. There was no distinct seasonal pattern for COVID-19–related admissions during the study. Conclusions RSV remains a major cause of childhood hospitalization. Although COVID-19 appears to be receding, its disease burden as it transitions to endemicity remains to be established. The unprecedented peaks in RSV-related hospital admissions during 2022–2023, together with the return of influenza and ongoing SARS-CoV-2 transmission, underscore the need to strengthen systems for real-time surveillance and to proactively prepare for critical healthcare scenarios. [ABSTRACT FROM AUTHOR]

Background: Vaccination is the most cost-effective medical intervention known to prevent morbidity and mortality. However, data are limited on the effectiveness of residency programs in delivering immunization knowledge and skills to trainees. The authors sought to describe the immunization competency needs of medical residents at the University of Toronto (UT), and to develop and evaluate a pilot immunization curriculum. Methods: Residents at the University of Toronto across nine specialties were recruited to attend a pilot immunization workshop in November 2018. Participants completed a questionnaire before and after the workshop to assess immunization knowledge and compare baseline change. Feedback was also surveyed on the workshop content and process. Descriptive statistics were performed on the knowledge questionnaire and feedback survey. A paired sample T-test compared questionnaire answers before and after the workshop. Descriptive coding was used to identify themes from the feedback survey. Results: Twenty residents from at least six residencies completed the pre-workshop knowledge questionnaire, seventeen attended the workshop, and thirteen completed the post-workshop questionnaire. Ninety-five percent (19/20) strongly agreed that vaccine knowledge was important to their career, and they preferred case-based teaching. The proportion of the thirty-four knowledge questions answered correctly increased from 49% before the workshop to 67% afterwards, with a mean of 2.24 (CI: 1.43, 3.04) more correct answers (P < 0.001). Sixteen residents completed the post-workshop feedback survey. Three themes emerged: first, they found the content specific and practical; second, they wanted more case-based learning and for the workshop to be longer; and third, they felt the content and presenters were of high quality. Conclusions: Findings from this study suggest current immunization training of UT residents does not meet their training competency requirements. The study's workshop improved participants' immunization knowledge. The information from this study could be used to develop residency immunization curriculum at UT and beyond. [ABSTRACT FROM AUTHOR]

BACKGROUND. The 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. METHODS. Using 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. RESULTS. The 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. CONCLUSION. This comprehensive assessment of human milk antibody profiles may be used to guide the development of passive protection strategies against infant morbidity and mortality. FUNDING. Bill 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). [ABSTRACT FROM AUTHOR]

Although COVID-19 vaccine safety in 5–11-year-old children has been documented, half of Ontarian children this age remain unvaccinated. This study aimed to assess caregivers' vaccine acceptance for 5–11-year-old children and identify factors associated with vaccine non-acceptance. A multi-language self-administered survey was sent to caregivers of 5–11-year-old children through schools and community health centers within the Greater Toronto Area from April–July 2022. Sociodemographic characteristics and immunization behaviours were collected for caregivers, their 5–11-year-old children, and any older siblings. The primary outcome, COVID-19 vaccine acceptance, was previous uptake of COVID-19 vaccine or caregiver intent to vaccinate for their 5–11-year-old child. Data were analyzed using descriptive statistics and multivariable logistic regression. In total, 807 caregivers were included in analysis. Although 93 % of caregivers had received two doses of COVID-19 vaccine, 77 % had a 5–11-year-old child who received at least one dose of vaccine. Caregivers age was associated with vaccine acceptance (vs. < 40 years; adjusted odds ratio [aOR] 2.1, 95 % confidence interval [CI] 1.4–3.1 for ages 40–49; aOR 2.8, 95 % CI 1.1–7.1 for ages ≥50 years). Immunization factors associated with vaccine acceptance included caregiver COVID-19 vaccination (aOR 38.1 vs. unvaccinated caregivers; 95 % CI 15.8–92.3), older siblings COVID-19 vaccination (aOR 49.2 vs. unvaccinated siblings; 95 % CI 18.3–132.3), and recent influenza vaccination for the child (aOR 6.9 vs. no influenza vaccine; 95 % CI 4.6–10.5). Among 189 caregivers with unvaccinated 5–11-year-old children, the most common reasons for non-acceptance were concerns about long-term side effects (59 %), lack of experience vaccinating children (41 %), and concerns that vaccines were developed too quickly (39 %). Acceptance of COVID-19 vaccination for 5–11-year-old children were associated with caregiver vaccine behaviors and sociodemographic factors. These findings highlight groups of caregivers that can be targeted for educational interventions and concerns that may be addressed to increase vaccine confidence. [ABSTRACT FROM AUTHOR]

Background: Southeast Asia is undergoing an epidemiological transition with non-communicable illnesses becoming increasingly important, yet infectious diseases (tuberculosis, HIV, hepatitis B, malaria) remain widely prevalent in some populations, while emerging and zoonotic diseases threaten. There are also limited population-level estimates of many important heath conditions. This restricts evidence-based decision-making for disease control and prevention priorities. Cross-sectional surveys can be efficient epidemiological tools to measure the prevalence of a wide range of diseases, but no systematic assessment of their coverage of different health conditions has been produced for the region. Methods: We conducted a systematic search in Medline, Embase, Global Health, CINAHL, Scopus, Web of Science Core Collection, and Global Index Medicus, and additionally Google Scholar. Our inclusion criteria were cross-sectional surveys conducted with community-based recruitment, in Bangladesh, Cambodia, Laos, Myanmar, and Thailand, published between January 1, 2010 and January 27, 2021, and reporting the prevalence of any health condition. Results: 542 publications from 337 surveys were included. Non-communicable conditions (n = 205) were reported by more surveys than infectious conditions (n = 124). Disability (n = 49), self-report history of any disease or symptoms (n = 35), and self-perceived health status (n = 34), which reflect a holistic picture of health, were studied by many fewer surveys. In addition, 45 surveys studied symptomatic conditions which overlap between non-communicable and infectious conditions. The most surveyed conditions were undernutrition, obesity, hypertension, diabetes, intestinal parasites, malaria, anemia, diarrhea, fever, and acute respiratory infections. These conditions overlap with the most important causes of death and disability in the Global Burden of Disease study. However, other high-burden conditions (e.g. hearing loss, headache disorder, low back pain, chronic liver and kidney diseases, and cancers) were rarely studied. Conclusion: There were relatively few recent surveys from which to estimate representative prevalences and trends of health conditions beyond those known to be high burden. Expanding the spectrum of health conditions in cross-sectional surveys could improve understanding of evolving disease patterns in the region. [ABSTRACT FROM AUTHOR]

Background: Endotracheal tube (ETT) placement is a critical procedure for newborns that are unable to breathe. Inadvertent esophageal intubation can lead to oxygen deprivation and consequent permanent neurological impairment. Current standard-of-care methods to confirm ETT placement in neonates (auscultation, colorimetric capnography, and chest x-ray) are time consuming or unreliable, especially in the stressful resuscitation environment. Point-of-care ultrasound (POCUS) of the neck has recently emerged as a powerful tool for detecting esophageal ETTs. It is accurate and fast, and is also easy to learn and perform, especially on children.Methods: This will be an observational diagnostic accuracy study consisting of two phases and conducted at the Aga Khan University Hospital in Karachi, Pakistan. In phase 1, neonatal health care providers that currently perform standard-of-care methods for ETT localization, regardless of experience in portable ultrasound, will undergo a two-hour training session. During this session, providers will learn to detect tracheal vs. esophageal ETTs using POCUS. The session will consist of a didactic component, hands-on training with a novel intubation ultrasound simulator, and practice with stable, ventilated newborns. At the end of the session, the providers will undergo an objective structured assessment of technical skills, as well as an evaluation of their ability to differentiate between tracheal and esophageal endotracheal tubes. In phase 2, newborns requiring intubation will be assessed for ETT location via POCUS, at the same time as standard-of-care methods. The initial 2 months of phase 2 will include a quality assurance component to ensure the POCUS accuracy of trained providers. The primary outcome of the study is to determine the accuracy of neck POCUS for ETT location when performed by neonatal providers with focused POCUS training, and the secondary outcome is to determine whether neck POCUS is faster than standard-of-care methods.Discussion: This study represents the first large investigation of the benefits of POCUS for ETT confirmation in the sickest newborns undergoing intubations for respiratory support.Trial Registration: ClinicalTrials.gov Identifier: NCT03533218. Registered May 2018. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]