Thacher, Thomas D

Background: Perinatal factors including gestational age, birthweight, size for gestational age, delivery route, maternal parity, maternal age, maternal education, socioeconomic status, race, and sex, are associated with the future risk of obesity and co-morbid conditions. This study evaluated the relationship of birthweight for gestational age and perinatal factors with severe obesity and dyslipidemia in adulthood. Methods: We conducted a population-based, retrospective birth cohort study of infants born to residents of Olmsted County, MN between 1976 and 1982. Outcomes were assessed after age 18 years until October 2020, including severe obesity (BMI ≥ 40 kg/m 2 ) and dyslipidemia (total cholesterol ≥200 mg/dL, non-high density lipoprotein [non-HDL] cholesterol ≥145 mg/dL or HDL cholesterol <40 mg/dL). We obtained mother’s age, education level, and parity as well as newborn sex, race, type of delivery, single/multiple birth, gestational age, and birthweight from birth certificate data. Individual-level socioeconomic status (SES) of the household at birth was determined with the HOUSES index. Results: Of 10 938 birth cohort subjects, 7394 had clinic visits after age 18 years and were included, with 2630 having severe obesity (n = 798) or dyslipidemia (n = 2357) as adults. In multivariable models, female sex, singleton birth, less maternal education, and lower SES defined by HOUSES were independently associated with an increased risk of severe obesity in adulthood. Non-white race, singleton birth, and lower birthweight were independently associated with adult dyslipidemia. Birthweight for gestational age was not associated with severe obesity or dyslipidemia. Conclusion: Perinatal factors were associated with both severe obesity and dyslipidemia in adulthood. Lower SES at birth was predictive of severe obesity in adulthood, highlighting the opportunity to investigate modifiable perinatal social determinants to reduce the risk of severe obesity.

Laboratory evidence provides a biological rationale for the benefits of vitamin D in COVID-19, and vitamin D supplementation is associated with reduced risk of respiratory infections. Most of the clinical studies of vitamin D in COVID-19 have been observational, and the most serious problem with observational study design is that of confounding. Observational studies typically assess the relationship of 25(OH)D values with COVID-19 outcomes. Many conditions associated with low vitamin D status are also associated with worse COVID-19 outcomes. Randomized controlled trials (RCTs) overcome the problem of confounding, typically comparing outcomes between groups receiving vitamin D supplementation or placebo. However, any benefit of vitamin D in COVID-19 may be related to the dose, duration, daily vs. bolus administration, interaction with other treatments, and timing of administration prior to or during the illness. Serum 25(OH)D values >50 nmol/L have been associated with reduced infection rates, severity of COVID-19, and mortality in observational studies. Few RCTs of vitamin D supplementation have been completed, and they have shown no benefit of vitamin D in hospitalized patients. Vitamin D may benefit those with mild or asymptomatic COVID-19, and those with greater 25(OH)D values may have lower risk of acquiring infection. Because those at greatest risk of COVID-19 are also at greatest risk of vitamin D deficiency, it is reasonable to recommend vitamin D supplementation 15–20 mcg (600–800 IU) daily for the general population during the COVID-19 pandemic. Vitamin D doses greater than 100 mcg (4000 IU) daily should not be used without monitoring serum 25(OH)D and calcium.

Background: Vitamin D deficiency may increase the risk of severe COVID-19 disease. Objectives: To determine if 25-hydroxyvitamin D [25(OH)D] levels in patients hospitalized for COVID-19 were associated with the clinical outcomes of days on oxygen, duration of hospitalization, ICU admission, need for assisted ventilation, or mortality. Methods: We conducted a retrospective study of 92 patients admitted to the hospital with SARS-CoV-2 infection between April 16, 2020 and October 17, 2020. Multivariable regression was performed to assess the independent relationship of 25(OH)D values on outcomes, adjusting for significant covariates and the hospitalization day the level was tested. Results: About 15 patients (16.3%) had 25(OH)D levels <20 ng/mL. Only 1 patient (3.4%) who had documented vitamin D supplementation prior to admission had 25(OH)D <20 ng/mL. Serum 25(OH)D concentrations were not significantly associated with any of our primary outcomes of days on oxygen, duration of hospitalization, intensive care unit (ICU) admission, need for mechanical ventilation, or mortality in any of the adjusted multivariable models. Adjusting for the hospital day of 25(OH)D sampling did not alter the relationship of 25(OH)D with any outcomes. Conclusion: Vitamin D status was not related to any of the primary outcomes reflecting severity of COVID-19 in hospitalized patients. However, our sample size may have lacked sufficient power to demonstrate a small effect of vitamin D status on these outcomes.

Abstract Context Nutritional rickets results from the interaction of low vitamin D status and limited calcium intake. Serum alkaline phosphatase (AP) activity is a biomarker of impaired mineralization in rickets. Objective To assess the performance of serum AP activity in identifying nutritional rickets in calcium-deprived Nigerian children. Methods We reanalyzed data from a case-control study of children with active rickets and matched control subjects without rickets, using a multivariate logistic regression to assess the odds of rickets associated with AP activity, adjusting for age, sex, and weight-for-age z-score. Results A total of 122 children with rickets and 119 controls were included. Rachitic children had a mean (±SD) age of 54 ± 29 months, and 55 (45.1%) were male. Cases and controls had low dietary calcium intakes (216 ± 87 and 214 ± 96 mg/day, respectively). Serum AP activity levels in cases and controls were 812 ± 415 and 245 ± 78 U/L, respectively (P &lt; 0.001). AP was negatively associated with 25-hydroxyvitamin D values (r = −0.34; P &lt; 0.001). In the adjusted model, the odds ratio (95% CI) receiver operating characteristic curve was 0.978. AP &gt; 350 U/L identified nutritional rickets in Nigerian children with sensitivity 0.93, specificity 0.92, positive likelihood ratio 11.3, and negative likelihood ratio 0.07. Conclusion An AP &gt; 350 U/L effectively discriminated between Nigerian children with and without nutritional rickets. AP is a low-cost biochemical test that could be used to screen for nutritional rickets, but cutoff values require validation in other populations, and laboratory values need to be standardized for widespread population studies.

Background: Thiamin deficiency is a major public health concern in several low- and middle-income countries (LMICs)—current attention to the problem is lacking. Aim: This review discusses prevalence of thiamin insufficiency and thiamin-deficiency disorders (TDDs) in LMICs, outlines programmatic experience with thiamin interventions, and offers recommendations to improve public-health and research attention to thiamin in LMICs. Discussion: Thiamin insufficiency, i.e. low-blood-thiamin status, is endemic among several Southeast Asian countries: Cambodia (70–100% of infants and 27–100% of reproductive-age women); Laos (13% of hospitalized infants); Thailand (16–25% of children and 30% of elderly adults). Thiamin deficiency accounts for up to 45% of under-5 deaths in Cambodia, 34% of infant deaths in Laos, and 17% of infant deaths in Myanmar. Deficiency also exists in Africa, Asia, and the Americas, but these instances have typically been isolated. Exclusively breastfed infants of thiamin-deficient mothers are at highest risk for TDD and related death. Intervention strategies that have been employed to combat thiamin deficiency include food processing, fortification, supplementation, dietary diversification, and dietary behaviors, all of which have shown varying levels of effectiveness. Conclusions: We recommend universal thiamin-fortification of context-specific staple-foods in LMICs as a promising solution, as well as thiamin supplementation, particularly for pregnant and lactating women. Food processing regulations, dietary diversification, and modification of dietary behaviors to increase consumption of thiamin-rich foods may provide benefits in some circumstances, especially in countries without universal fortification programs or in populations dependent on food aid.

Abstract Vitamin D is an essential nutrient for bone health and may influence the risks of respiratory illness, adverse pregnancy outcomes, and chronic diseases of adulthood. Because many countries have a relatively low supply of foods rich in vitamin D and inadequate exposure to natural ultraviolet B (UVB) radiation from sunlight, an important proportion of the global population is at risk of vitamin D deficiency. There is general agreement that the minimum serum/plasma 25‐hydroxyvitamin D concentration (25(OH)D) that protects against vitamin D deficiency–related bone disease is approximately 30 nmol/L; therefore, this threshold is suitable to define vitamin D deficiency in population surveys. However, efforts to assess the vitamin D status of populations in low‐ and middle‐income countries have been hampered by limited availability of population‐representative 25(OH)D data, particularly among population subgroups most vulnerable to the skeletal and potential extraskeletal consequences of low vitamin D status, namely exclusively breastfed infants, children, adolescents, pregnant and lactating women, and the elderly. In the absence of 25(OH)D data, identification of communities that would benefit from public health interventions to improve vitamin D status may require proxy indicators of the population risk of vitamin D deficiency, such as the prevalence of rickets or metrics of usual UVB exposure. If a high prevalence of vitamin D deficiency is identified (>20% prevalence of 25(OH)D < 30 nmol/L) or the risk for vitamin D deficiency is determined to be high based on proxy indicators (e.g., prevalence of rickets >1%), food fortification and/or targeted vitamin D supplementation policies can be implemented to reduce the burden of vitamin D deficiency–related conditions in vulnerable populations.

Background: The American Academy of Pediatrics and the National Academy of Medicine recommend vitamin D supplementation for breastfeeding infants. However, compliance with this recommendation is poor. Maternal supplementation with vitamin D is a safe and effective alternative to achieving vitamin D sufficiency in breastfeeding infants, and mothers have indicated a preference for self-supplementation over infant supplementation. Research aim: We sought to explore Family Medicine clinicians’ knowledge, attitudes, and practices regarding vitamin D supplementation recommendations for breastfeeding dyads. Methods: Fifty-six Family Medicine clinicians (including faculty physicians, resident physicians, and nurse practitioners/physician assistants) completed an online, anonymous survey regarding their knowledge and practices concerning vitamin D supplementation for breastfeeding infants. Results: The vast majority of clinicians (92.9%) correctly identified the American Academy of Pediatrics’ 2008 recommended dose for vitamin D supplementation in breastfeeding infants and estimated recommending vitamin D supplementation of exclusively breastfeeding infants 70.1% of the time. If all options were equivalent, clinicians would prefer to offer maternal or infant supplementation (50%) or maternal supplementation (37.5%) over infant supplementation (12.5%). Most (69.6%) preferred daily over monthly supplementation regimens. Conclusion: Family Medicine clinicians are knowledgeable regarding current recommendations for vitamin D supplementation in breastfeeding infants. They are also open to recommending maternal supplementation or offering parents a choice of maternal or infant vitamin supplementation.