Obesity as an independent risk factor for COVID-19 severity and mortality.

BACKGROUND: Since December 2019, the world has struggled with the COVID-19 pandemic. Even after the introduction of various vaccines, this disease still takes a considerable toll. In order to improve the optimal allocation of resources and communication of prognosis, healthcare providers and patients need an accurate understanding of factors (such as obesity) that are associated with a higher risk of adverse outcomes from the COVID-19 infection. OBJECTIVES: To evaluate obesity as an independent prognostic factor for COVID-19 severity and mortality among adult patients in whom infection with the COVID-19 virus is confirmed. SEARCH METHODS: MEDLINE, Embase, two COVID-19 reference collections, and four Chinese biomedical databases were searched up to April 2021. SELECTION CRITERIA: We included case-control, case-series, prospective and retrospective cohort studies, and secondary analyses of randomised controlled trials if they evaluated associations between obesity and COVID-19 adverse outcomes including mortality, mechanical ventilation, intensive care unit (ICU) admission, hospitalisation, severe COVID, and COVID pneumonia. Given our interest in ascertaining the independent association between obesity and these outcomes, we selected studies that adjusted for at least one factor other than obesity. Studies were evaluated for inclusion by two independent reviewers working in duplicate.  DATA COLLECTION AND ANALYSIS: Using standardised data extraction forms, we extracted relevant information from the included studies. When appropriate, we pooled the estimates of association across studies with the use of random-effects meta-analyses. The Quality in Prognostic Studies (QUIPS) tool provided the platform for assessing the risk of bias across each included study. In our main comparison, we conducted meta-analyses for each obesity class separately. We also meta-analysed unclassified obesity and obesity as a continuous variable (5 kg/m2 increase in BMI (body mass index)). We used the GRADE framework to rate our certainty in the importance of the association observed between obesity and each outcome. As obesity is closely associated with other comorbidities, we decided to prespecify the minimum adjustment set of variables including age, sex, diabetes, hypertension, and cardiovascular disease for subgroup analysis.  MAIN RESULTS: We identified 171 studies, 149 of which were included in meta-analyses.  As compared to 'normal' BMI (18.5 to 24.9 kg/m2) or patients without obesity, those with obesity classes I (BMI 30 to 35 kg/m2), and II (BMI 35 to 40 kg/m2) were not at increased odds for mortality (Class I: odds ratio [OR] 1.04, 95% confidence interval [CI] 0.94 to 1.16, high certainty (15 studies, 335,209 participants); Class II: OR 1.16, 95% CI 0.99 to 1.36, high certainty (11 studies, 317,925 participants)). However, those with class III obesity (BMI 40 kg/m2 and above) may be at increased odds for mortality (Class III: OR 1.67, 95% CI 1.39 to 2.00, low certainty, (19 studies, 354,967 participants)) compared to normal BMI or patients without obesity. For mechanical ventilation, we observed increasing odds with higher classes of obesity in comparison to normal BMI or patients without obesity (class I: OR 1.38, 95% CI 1.20 to 1.59, 10 studies, 187,895 participants, moderate certainty; class II: OR 1.67, 95% CI 1.42 to 1.96, 6 studies, 171,149 participants, high certainty; class III: OR 2.17, 95% CI 1.59 to 2.97, 12 studies, 174,520 participants, high certainty). However, we did not observe a dose-response relationship across increasing obesity classifications for ICU admission and hospitalisation. AUTHORS' CONCLUSIONS: Our findings suggest that obesity is an important independent prognostic factor in the setting of COVID-19. Consideration of obesity may inform the optimal management and allocation of limited resources in the care of COVID-19 patients.

Replacing salt with low-sodium salt substitutes (LSSS) for cardiovascular health in adults, children and pregnant women.

BACKGROUND: Elevated blood pressure, or hypertension, is the leading cause of preventable deaths globally. Diets high in sodium (predominantly sodium chloride) and low in potassium contribute to elevated blood pressure. The WHO recommends decreasing mean population sodium intake through effective and safe strategies to reduce hypertension and its associated disease burden. Incorporating low-sodium salt substitutes (LSSS) into population strategies has increasingly been recognised as a possible sodium reduction strategy, particularly in populations where a substantial proportion of overall sodium intake comes from discretionary salt. The LSSS contain lower concentrations of sodium through its displacement with potassium predominantly, or other minerals. Potassium-containing LSSS can potentially simultaneously decrease sodium intake and increase potassium intake.  Benefits of LSSS include their potential blood pressure-lowering effect and relatively low cost. However, there are concerns about potential adverse effects of LSSS, such as hyperkalaemia, particularly in people at risk, for example, those with chronic kidney disease (CKD) or taking medications that impair potassium excretion. OBJECTIVES: To assess the effects and safety of replacing salt with LSSS to reduce sodium intake on cardiovascular health in adults, pregnant women and children. SEARCH METHODS: We searched MEDLINE (PubMed), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection (Clarivate Analytics), Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCOhost), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) up to 18 August 2021, and screened reference lists of included trials and relevant systematic reviews. No language or publication restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and prospective analytical cohort studies in participants of any age in the general population, from any setting in any country. This included participants with non-communicable diseases and those taking medications that impair potassium excretion. Studies had to compare any type and method of implementation of LSSS with the use of regular salt, or no active intervention, at an individual, household or community level, for any duration. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full-text articles to determine eligibility; and extracted data, assessed risk of bias (RoB) using the Cochrane RoB tool, and assessed the certainty of the evidence using GRADE. We stratified analyses by adults, children (≤ 18 years) and pregnant women. Primary effectiveness outcomes were change in diastolic and systolic blood pressure (DBP and SBP), hypertension and blood pressure control; cardiovascular events and cardiovascular mortality were additionally assessed as primary effectiveness outcomes in adults. Primary safety outcomes were change in blood potassium, hyperkalaemia and hypokalaemia. MAIN RESULTS: We included 26 RCTs, 16 randomising individual participants and 10 randomising clusters (families, households or villages). A total of 34,961 adult participants and 92 children were randomised to either LSSS or regular salt, with the smallest trial including 10 and the largest including 20,995 participants. No studies in pregnant women were identified. Studies included only participants with hypertension (11/26), normal blood pressure (1/26), pre-hypertension (1/26), or participants with and without hypertension (11/26). This was unknown in the remaining studies. The largest study included only participants with an elevated risk of stroke at baseline. Seven studies included adult participants possibly at risk of hyperkalaemia. All 26 trials specifically excluded participants in whom an increased potassium intake is known to be potentially harmful. The majority of trials were conducted in rural or suburban settings, with more than half (14/26) conducted in low- and middle-income countries. The proportion of sodium chloride replacement in the LSSS interventions varied from approximately 3% to 77%. The majority of trials (23/26) investigated LSSS where potassium-containing salts were used to substitute sodium. In most trials, LSSS implementation was discretionary (22/26). Trial duration ranged from two months to nearly five years.  We assessed the overall risk of bias as high in six trials and unclear in 12 trials. LSSS compared to regular salt in adults: LSSS compared to regular salt probably reduce DBP on average (mean difference (MD) -2.43 mmHg, 95% confidence interval (CI) -3.50 to -1.36; 20,830 participants, 19 RCTs, moderate-certainty evidence) and SBP (MD -4.76 mmHg, 95% CI -6.01 to -3.50; 21,414 participants, 20 RCTs, moderate-certainty evidence) slightly.  On average, LSSS probably reduce non-fatal stroke (absolute effect (AE) 20 fewer/100,000 person-years, 95% CI -40 to 2; 21,250 participants, 3 RCTs, moderate-certainty evidence), non-fatal acute coronary syndrome (AE 150 fewer/100,000 person-years, 95% CI -250 to -30; 20,995 participants, 1 RCT, moderate-certainty evidence) and cardiovascular mortality (AE 180 fewer/100,000 person-years, 95% CI -310 to 0; 23,200 participants, 3 RCTs, moderate-certainty evidence) slightly, and probably increase blood potassium slightly (MD 0.12 mmol/L, 95% CI 0.07 to 0.18; 784 participants, 6 RCTs, moderate-certainty evidence), compared to regular salt.  LSSS may result in little to no difference, on average, in hypertension (AE 17 fewer/1000, 95% CI -58 to 17; 2566 participants, 1 RCT, low-certainty evidence) and hyperkalaemia (AE 4 more/100,000, 95% CI -47 to 121; 22,849 participants, 5 RCTs, moderate-certainty evidence) compared to regular salt. The evidence is very uncertain about the effects of LSSS on blood pressure control, various cardiovascular events, stroke mortality, hypokalaemia, and other adverse events (very-low certainty evidence). LSSS compared to regular salt in children: The evidence is very uncertain about the effects of LSSS on DBP and SBP in children. We found no evidence about the effects of LSSS on hypertension, blood pressure control, blood potassium, hyperkalaemia and hypokalaemia in children. AUTHORS' CONCLUSIONS: When compared to regular salt, LSSS probably reduce blood pressure, non-fatal cardiovascular events and cardiovascular mortality slightly in adults. However, LSSS also probably increase blood potassium slightly in adults. These small effects may be important when LSSS interventions are implemented at the population level. Evidence is limited for adults without elevated blood pressure, and there is a lack of evidence in pregnant women and people in whom an increased potassium intake is known to be potentially harmful, limiting conclusions on the safety of LSSS in the general population. We also cannot draw firm conclusions about effects of non-discretionary LSSS implementations. The evidence is very uncertain about the effects of LSSS on blood pressure in children.

Prevalence and Determinants of Vitamin D Deficiency in 1825 Cape Town Primary Schoolchildren: A Cross-Sectional Study.

Vitamin D deficiency (25-hydroxyvitamin D[25(OH)D] <50 nmol/L) is common among adults in Cape Town, South Africa, but studies investigating vitamin D status of children in this setting are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 1825 Cape Town schoolchildren aged 6−11 years. Prevalence of vitamin D deficiency was 7.6% (95% Confidence Interval [CI] 6.5% to 8.9%). Determinants of vitamin D deficiency included month of sampling (adjusted odds ratio [aOR] for July−September vs. January−March 10.69, 95% CI 5.02 to 22.77; aOR for October−December vs. January−March 6.73, 95% CI 2.82 to 16.08), older age (aOR 1.25 per increasing year, 95% CI: 1.01−1.53) and higher body mass index (BMI; aOR 1.24 per unit increase in BMI-for-age Z-score, 95% CI: 1.03−1.49). In a subset of 370 participants in whom parathyroid hormone (PTH) concentrations were measured; these were inversely related to serum 25(OH)D concentrations (p < 0.001). However, no association between participants with hyperparathyroidism (PTH >6.9 pmol/L) and vitamin D deficiency was seen (p = 0.42). In conclusion, we report that season is the major determinant of vitamin D status among Cape Town primary schoolchildren, with prevalence of vitamin D deficiency ranging from 1.4% in January−March to 22.8% in July−September.

Low-carbohydrate versus balanced-carbohydrate diets for reducing weight and cardiovascular risk.

BACKGROUND: Debates on effective and safe diets for managing obesity in adults are ongoing. Low-carbohydrate weight-reducing diets (also known as 'low-carb diets') continue to be widely promoted, marketed and commercialised as being more effective for weight loss, and healthier, than 'balanced'-carbohydrate weight-reducing diets. OBJECTIVES: To compare the effects of low-carbohydrate weight-reducing diets to weight-reducing diets with balanced ranges of carbohydrates, in relation to changes in weight and cardiovascular risk, in overweight and obese adults without and with type 2 diabetes mellitus (T2DM). SEARCH METHODS: We searched MEDLINE (PubMed), Embase (Ovid), the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection (Clarivate Analytics), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) up to 25 June 2021, and screened reference lists of included trials and relevant systematic reviews. Language or publication restrictions were not applied. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults (18 years+) who were overweight or living with obesity, without or with T2DM, and without or with cardiovascular conditions or risk factors. Trials had to compare low-carbohydrate weight-reducing diets to balanced-carbohydrate (45% to 65% of total energy (TE)) weight-reducing diets, have a weight-reducing phase of 2 weeks or longer and be explicitly implemented for the primary purpose of reducing weight, with or without advice to restrict energy intake.  DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and full-text articles to determine eligibility; and independently extracted data, assessed risk of bias using RoB 2 and assessed the certainty of the evidence using GRADE. We stratified analyses by participants without and with T2DM, and by diets with weight-reducing phases only and those with weight-reducing phases followed by weight-maintenance phases. Primary outcomes were change in body weight (kg) and the number of participants per group with weight loss of at least 5%, assessed at short- (three months to < 12 months) and long-term (≥ 12 months) follow-up. MAIN RESULTS: We included 61 parallel-arm RCTs that randomised 6925 participants to either low-carbohydrate or balanced-carbohydrate weight-reducing diets. All trials were conducted in high-income countries except for one in China. Most participants (n = 5118 randomised) did not have T2DM. Mean baseline weight across trials was 95 kg (range 66 to 132 kg). Participants with T2DM were older (mean 57 years, range 50 to 65) than those without T2DM (mean 45 years, range 22 to 62). Most trials included men and women (42/61; 3/19 men only; 16/19 women only), and people without baseline cardiovascular conditions, risk factors or events (36/61). Mean baseline diastolic blood pressure (DBP) and low-density lipoprotein (LDL) cholesterol across trials were within normal ranges. The longest weight-reducing phase of diets was two years in participants without and with T2DM. Evidence from studies with weight-reducing phases followed by weight-maintenance phases was limited. Most trials investigated low-carbohydrate diets (> 50 g to 150 g per day or < 45% of TE; n = 42), followed by very low (≤ 50 g per day or < 10% of TE; n = 14), and then incremental increases from very low to low (n = 5). The most common diets compared were low-carbohydrate, balanced-fat (20 to 35% of TE) and high-protein (> 20% of TE) treatment diets versus control diets balanced for the three macronutrients (24/61). In most trials (45/61) the energy prescription or approach used to restrict energy intake was similar in both groups. We assessed the overall risk of bias of outcomes across trials as predominantly high, mostly from bias due to missing outcome data. Using GRADE, we assessed the certainty of evidence as moderate to very low across outcomes.  Participants without and with T2DM lost weight when following weight-reducing phases of both diets at the short (range: 12.2 to 0.33 kg) and long term (range: 13.1 to 1.7 kg).  In overweight and obese participants without T2DM: low-carbohydrate weight-reducing diets compared to balanced-carbohydrate weight-reducing diets (weight-reducing phases only) probably result in little to no difference in change in body weight over three to 8.5 months (mean difference (MD) -1.07 kg, (95% confidence interval (CI) -1.55 to -0.59, I2 = 51%, 3286 participants, 37 RCTs, moderate-certainty evidence) and over one to two years (MD -0.93 kg, 95% CI -1.81 to -0.04, I2 = 40%, 1805 participants, 14 RCTs, moderate-certainty evidence); as well as change in DBP and LDL cholesterol over one to two years. The evidence is very uncertain about whether there is a difference in the number of participants per group with weight loss of at least 5% at one year (risk ratio (RR) 1.11, 95% CI 0.94 to 1.31, I2 = 17%, 137 participants, 2 RCTs, very low-certainty evidence).  In overweight and obese participants with T2DM: low-carbohydrate weight-reducing diets compared to balanced-carbohydrate weight-reducing diets (weight-reducing phases only) probably result in little to no difference in change in body weight over three to six months (MD -1.26 kg, 95% CI -2.44 to -0.09, I2 = 47%, 1114 participants, 14 RCTs, moderate-certainty evidence) and over one to two years (MD -0.33 kg, 95% CI -2.13 to 1.46, I2 = 10%, 813 participants, 7 RCTs, moderate-certainty evidence); as well in change in DBP, HbA1c and LDL cholesterol over 1 to 2 years. The evidence is very uncertain about whether there is a difference in the number of participants per group with weight loss of at least 5% at one to two years (RR 0.90, 95% CI 0.68 to 1.20, I2 = 0%, 106 participants, 2 RCTs, very low-certainty evidence).  Evidence on participant-reported adverse effects was limited, and we could not draw any conclusions about these.  AUTHORS' CONCLUSIONS: There is probably little to no difference in weight reduction and changes in cardiovascular risk factors up to two years' follow-up, when overweight and obese participants without and with T2DM are randomised to either low-carbohydrate or balanced-carbohydrate weight-reducing diets.

Agricultural and nutritional education interventions for reducing aflatoxin exposure to improve infant and child growth in low- and middle-income countries.

BACKGROUND: Aflatoxins are carcinogenic mycotoxins that contaminate many food crops. Maize and groundnuts are prone to aflatoxin contamination, and are the major sources of human exposure to aflatoxins, due to their high intake as staple foods, particularly in low- and middle-income countries (LMICs). Observational studies suggest an association between dietary exposure to aflatoxins during pregnancy and early childhood and linear growth in infants and young children. OBJECTIVES: To assess the effects on pre- and postnatal growth outcomes when agricultural and nutritional education interventions during the post-harvest period that aim to reduce aflatoxin exposure are compared to usual support or no intervention. We assessed this in infants, children, and pregnant and lactating women at the household or community level in LMICs. SEARCH METHODS: In July and August 2019, we searched: CENTRAL, MEDLINE, Embase, CINAHL, Web of Science Core Collection, Africa-Wide, LILACS, CAB Abstracts, Agricola, and two trials registers. We also checked the bibliographies of the included studies and contacted relevant mycotoxin organisations and researchers for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs of agricultural education and nutritional education interventions of any duration, at the household or community level, aimed at reducing aflatoxin intake by infants, children, and pregnant and lactating women, in LMICs during the post-harvest period, compared to no intervention or usual support. We excluded studies that followed participants for less than four weeks. We assessed prespecified prenatal (at birth) and postnatal growth outcomes (during infancy, childhood, and adolescence), with linear growth (as the primary outcome), infectious disease morbidity, and unintended consequences. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility using prespecified criteria, extracted data, and assessed risk of bias of included RCTs. We evaluated the certainty of the evidence using GRADE, and presented the main results in a 'Summary of findings' table. MAIN RESULTS: We included three recent cluster-RCTs reporting the effects of agricultural education plus post-harvest technologies, compared to usual agricultural support or no intervention. The participants were pregnant women and their children, lactating women and their infants (< 6 months), women of childbearing age, and young children (< 59 months), from rural, subsistence maize-farming communities in Kenya, Zimbabwe, and Tanzania. Two trials randomised villages to the intervention and control groups, including a total of at least 979 mother-child pairs from 60 villages. The third trial randomised 420 households, including 189 mother-child pairs and 231 women of childbearing age. Duration of the intervention and follow-up ranged between five and nine months. Due to risk of attrition bias, the overall risk of bias was unclear in one trial, and high in the other two trials. None of the included studies addressed the effects of nutritional education on pre- and postnatal growth. One trial reported outcomes not prespecified in our review, and we were unable to obtain unpublished growth data from the second trial, even after contacting the authors. The third trial, in lactating women and their infants in Tanzania, reported on the infants' weight-for-age z-score (WAZ) after six months. This trial found that providing agricultural education aimed at changing farmers' post-harvest practices to reduce aflatoxin exposure, by using demonstrations (e.g. handsorting, de-hulling of maize, drying sheets, and insecticides), may improve WAZ in infants from these farmers' households, on average, by 0.57 (95% confidence interval (CI) 0.16 to 0.98; 1 study; 249 participants; very low-certainty evidence), compared to infants from households where the farmers received routine agricultural extension services. Another way of reporting the effect on WAZ is to compare the proportion of underweight infants (WAZ > 2 SD below the reference median value) per group. This trial found that the intervention may reduce the proportion of underweight infants in the intervention households by 6.7% (95% CI -12.6 to -1.4; 249 participants; very low-certainty evidence) compared to control households. No studies reported on unintended effects of agricultural and nutritional education. AUTHORS' CONCLUSIONS: Evidence on the effects on child growth in LMICs of agricultural or nutritional education interventions that reduce aflatoxin exposure was very limited; no included study reported on linear growth. Very low-certainty evidence suggested that agricultural education aimed at changing farmers' post-harvest practices to reduce aflatoxin exposure by using demonstrations, may result in an increase in WAZ, when compared to usual or no education.

Effects of total fat intake on bodyweight in children.

BACKGROUND: As part of efforts to prevent childhood overweight and obesity, we need to understand the relationship between total fat intake and body fatness in generally healthy children. OBJECTIVES: To assess the effects and associations of total fat intake on measures of weight and body fatness in children and young people not aiming to lose weight. SEARCH METHODS: For this update we revised the previous search strategy and ran it over all years in the Cochrane Library, MEDLINE (Ovid), MEDLINE (PubMed), and Embase (Ovid) (current to 23 May 2017). No language and publication status limits were applied. We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing and unpublished studies (5 June 2017). SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children aged 24 months to 18 years, with or without risk factors for cardiovascular disease, randomised to a lower fat (30% or less of total energy (TE)) versus usual or moderate-fat diet (greater than 30%TE), without the intention to reduce weight, and assessed a measure of weight or body fatness after at least six months. We included prospective cohort studies if they related baseline total fat intake to weight or body fatness at least 12 months later. DATA COLLECTION AND ANALYSIS: We extracted data on participants, interventions or exposures, controls and outcomes, and trial or cohort quality characteristics, as well as data on potential effect modifiers, and assessed risk of bias for all included studies. We extracted body weight and blood lipid levels outcomes at six months, six to 12 months, one to two years, two to five years and more than five years for RCTs; and for cohort studies, at baseline to one year, one to two years, two to five years, five to 10 years and more than 10 years. We planned to perform random-effects meta-analyses with relevant subgrouping, and sensitivity and funnel plot analyses where data allowed. MAIN RESULTS: We included 24 studies comprising three parallel-group RCTs (n = 1054 randomised) and 21 prospective analytical cohort studies (about 25,059 children completed). Twenty-three studies were conducted in high-income countries. No meta-analyses were possible, since only one RCT reported the same outcome at each time point range for all outcomes, and cohort studies were too heterogeneous to combine.Effects of dietary counselling to reduce total fat intake from RCTsTwo studies recruited children aged between 4 and 11 years and a third recruited children aged 12 to 13 years. Interventions were combinations of individual and group counselling, and education sessions in clinics, schools and homes, delivered by dieticians, nutritionists, behaviourists or trained, supervised teachers. Concerns about imprecision and poor reporting limited our confidence in our findings. In addition, the inclusion of hypercholesteraemic children in two trials raised concerns about applicability.One study of dietary counselling to lower total fat intake found that the intervention may make little or no difference to weight compared with usual diet at 12 months (mean difference (MD) -0.50 kg, 95% confidence interval (CI) -1.78 to 0.78; n = 620; low-quality evidence) and at three years (MD -0.60 kg, 95% CI -2.39 to 1.19; n = 612; low-quality evidence). Education delivered as a classroom curriculum probably decreased BMI in children at 17 months (MD -1.5 kg/m2, 95% CI -2.45 to -0.55; 1 RCT; n = 191; moderate-quality evidence). The effects were smaller at longer term follow-up (five years: MD 0 kg/m2, 95% CI -0.63 to 0.63; n = 541; seven years; MD -0.10 kg/m2, 95% CI -0.75 to 0.55; n = 576; low-quality evidence).Dietary counselling probably slightly reduced total cholesterol at 12 months compared to controls (MD -0.15 mmol/L, 95% CI -0.24 to -0.06; 1 RCT; n = 618; moderate-quality evidence), but may make little or no difference over longer time periods. Dietary counselling probably slightly decreased low-density lipoprotein (LDL) cholesterol at 12 months (MD -0.12 mmol/L, 95% CI -0.20 to -0.04; 1 RCT; n = 618, moderate-quality evidence) and at five years (MD -0.09, 95% CI -0.17 to -0.01; 1 RCT; n = 623; moderate-quality evidence), compared to controls. Dietary counselling probably made little or no difference to HDL-C at 12 months (MD -0.03 mmol/L, 95% CI -0.08 to 0.02; 1 RCT; n = 618; moderate-quality evidence), and at five years (MD -0.01 mmol/L, 95% CI -0.06 to 0.04; 1 RCT; n = 522; moderate-quality evidence). Likewise, counselling probably made little or no difference to triglycerides in children at 12 months (MD -0.01 mmol/L, 95% CI -0.08 to 0.06; 1 RCT; n = 618; moderate-quality evidence). Lower versus usual or modified fat intake may make little or no difference to height at seven years (MD -0.60 cm, 95% CI -2.06 to 0.86; 1 RCT; n = 577; low-quality evidence).Associations between total fat intake, weight and body fatness from cohort studiesOver half the cohort analyses that reported on primary outcomes suggested that as total fat intake increases, body fatness measures may move in the same direction. However, heterogeneous methods and reporting across cohort studies, and predominantly very low-quality evidence, made it difficult to draw firm conclusions and true relationships may be substantially different. AUTHORS' CONCLUSIONS: We were unable to reach firm conclusions. Limited evidence from three trials that randomised children to dietary counselling or education to lower total fat intake (30% or less TE) versus usual or modified fat intake, but with no intention to reduce weight, showed small reductions in body mass index, total- and LDL-cholesterol at some time points with lower fat intake compared to controls. There were no consistent effects on weight, high-density lipoprotein (HDL) cholesterol or height. Associations in cohort studies that related total fat intake to later measures of body fatness in children were inconsistent and the quality of this evidence was mostly very low. Most studies were conducted in high-income countries, and may not be applicable in low- and middle-income settings. High-quality, longer-term studies are needed, that include low- and middle-income settings to look at both possible benefits and harms.

Effects of Iodized Salt and Iodine Supplements on Prenatal and Postnatal Growth: A Systematic Review.

Hypothyroidism due to iodine deficiency can impair physical development, most visibly in the marked stunting of myxedematous cretinism caused by severe in utero iodine deficiency. Whether iodine repletion improves growth in noncretinous children is uncertain. Therefore, the aim of our systematic review was to assess the effects of iodine fortification or supplementation on prenatal and postnatal growth outcomes in noncretinous children. Following Cochrane methods and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines, we searched 10 databases including 2 Chinese databases (latest search February 2017). We included randomized and nonrandomized controlled trials (RCTs; non-RCTs), controlled before-after (CBA) studies, and interrupted time-series studies in pregnant women and children (≤18 y), which compared the effects of iodine (any form, dose, regimen) to placebo, noniodized salt, or no intervention on prenatal and postnatal growth outcomes. We calculated mean differences with 95% CIs, performed random-effects meta-analyses, and assessed the quality of evidence with the use of GRADE (Grading of Recommendations Assessment, Development and Evaluation). We included 18 studies (13 RCTs, 4 non-RCTs, 1 CBA) (n = 5729). Iodine supplementation of severely iodine-deficient pregnant women increased mean birthweight [mean difference (MD): 200 g; 95% CI: 183, 217 g; n = 635; 2 non-RCTs] compared to controls, but the quality of this evidence was assessed as very low. Iodine repletion across the other groups showed no effects on primary growth outcomes (quality of evidence mostly low and very low). Meta-analyses showed a positive effect in moderate-to-mildly iodine-deficient schoolchildren on insulin-like growth factor-1 (MD: 38.48 ng/mL; 95% CI: 6.19, 70.76 ng/mL; n = 498; 2 RCTs, low-quality evidence) and insulin-like growth factor binding protein-3 (MD: 0.46 µg/mL; 95% CI: 0.25, 0.66 µg/mL; n = 498; 2 RCTs, low-quality evidence). In conclusion, we identified few well-designed trials examining the effects of iodine repletion on growth. We are uncertain whether prenatal iodine repletion increases infant growth. Postnatal iodine repletion may improve growth factors but has no clear effects on somatic growth. Our systematic review was registered with PROSPERO as CRD42014012940.

An analysis of methods used to synthesize evidence and grade recommendations in food-based dietary guidelines.

Evidence-informed guideline development methods underpinned by systematic reviews ensure that guidelines are transparently developed, free from overt bias, and based on the best available evidence. Only recently has the nutrition field begun using these methods to develop public health nutrition guidelines. Given the importance of following an evidence-informed approach and recent advances in related methods, this study sought to describe the methods used to synthesize evidence, rate evidence quality, grade recommendations, and manage conflicts of interest (COIs) in national food-based dietary guidelines (FBDGs). The Food and Agriculture Organization's FBDGs database was searched to identify the latest versions of FBDGs published from 2010 onward. Relevant data from 32 FBDGs were extracted, and the findings are presented narratively. This study shows that despite advances in evidence-informed methods for developing dietary guidelines, there are variations and deficiencies in methods used to review evidence, rate evidence quality, and grade recommendations. Dietary guidelines should follow systematic and transparent methods and be informed by the best available evidence, while considering important contextual factors and managing conflicts of interest.

Effects of total fat intake on bodyweight in children.

BACKGROUND: As part of efforts to prevent childhood overweight and obesity, we need to understand the relationship between total fat intake and body fatness in generally healthy children. OBJECTIVES: To assess the effects of total fat intake on measures of weight and body fatness in children and young people not aiming to lose weight. SEARCH METHODS: For this update we revised the previous search strategy and ran it over all years in the Cochrane Library, MEDLINE (Ovid), MEDLINE (PubMed), and Embase (Ovid) (current to 23 May 2017). No language and publication status limits were applied. We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing and unpublished studies (5 June 2017). SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children aged 24 months to 18 years, with or without risk factors for cardiovascular disease, randomised to a lower fat (30% or less of total energy (TE)) versus usual or moderate-fat diet (greater than 30%TE), without the intention to reduce weight, and assessed a measure of weight or body fatness after at least six months. We included prospective analytical cohort studies in these children if they related baseline total fat intake to weight or body fatness at least 12 months later. We duplicated inclusion decisions and resolved disagreement by discussion with other authors. DATA COLLECTION AND ANALYSIS: We extracted data on participants, interventions or exposures, controls and outcomes, and trial or cohort quality characteristics, as well as data on potential effect modifiers, and assessed risk of bias for all included studies. We extracted outcome data using the following time point ranges, when available: RCTs: baseline to six months, six to 12 months, one to two years, two to five years and more than five years; cohort studies: baseline to one year, one to two years, two to five years, five to 10 years and more than 10 years. We planned to perform random-effects meta-analyses with relevant subgrouping, and sensitivity and funnel plot analyses where data allowed. MAIN RESULTS: We included 24 studies comprising three parallel-group RCTs (n = 1054 randomised) and 21 prospective analytical cohort studies (about 25,059 children completed). Twenty-three were conducted in high-income countries. No meta-analyses were possible, since only one RCT reported the same outcome at each time point range for all outcomes, and cohort studies were too heterogeneous.For the RCTs, concerns about imprecision and poor reporting limited our confidence in our findings. In addition, the inclusion of hypercholesteraemic children in two trials raised concerns about applicability. Lower versus usual or modified total fat intake may have made little or no difference to weight over a six- to twelve month period (mean difference (MD) -0.50 kg, 95% confidence interval (CI) -1.78 to 0.78; 1 RCT; n = 620; low-quality evidence), nor a two- to five-year period (MD -0.60 kg, 95% CI -2.39 to 1.19; 1 RCT; n = 612; low-quality evidence). Compared to controls, lower total fat intake (30% or less TE) probably decreased BMI in children over a one- to two-year period (MD -1.5 kg/m2, 95% CI -2.45 to -0.55; 1 RCT; n = 191; moderate-quality evidence), with no other differences evident across the other time points (two to five years: MD 0.00 kg/m2, 95% CI -0.63 to 0.63; 1 RCT; n = 541; greater than five years; MD -0.10 kg/m2, 95% CI -0.75 to 0.55; 1 RCT; n = 576; low-quality evidence). Lower fat intake probably slightly reduced total cholesterol over six to 12 months compared to controls (MD -0.15 mmol/L, 95% CI -0.24 to -0.06; 1 RCT; n = 618; moderate-quality evidence), but may make little or no difference over longer time periods. Lower fat intake probably slightly decreased low-density lipoprotein (LDL) cholesterol over six to 12 months (MD -0.12 mmol/L, 95% CI -0.20 to -0.04; 1 RCT; n = 618, moderate-quality evidence) and over two to five years (MD -0.09, 95% CI -0.17 to -0.01; 1 RCT; n = 623; moderate-quality evidence), compared to controls. However, lower total fat intake probably made little or no difference to HDL-C over a six- to 12-month period (MD -0.03 mmol/L, 95% CI -0.08 to 0.02; 1 RCT; n = 618; moderate-quality evidence), nor a two- to five-year period (MD -0.01 mmol/L, 95% CI -0.06 to 0.04; 1 RCT; n = 522; moderate-quality evidence). Likewise, lower total fat intake probably made little or no difference to triglycerides in children over a six- to 12-month period (MD -0.01 mmol/L, 95% CI -0.08 to 0.06; 1 RCT; n = 618; moderate-quality evidence). Lower versus usual or modified fat intake may make little or no difference to height over more than five years (MD -0.60 cm, 95% CI -2.06 to 0.86; 1 RCT; n = 577; low-quality evidence).Over half the cohort analyses that reported on primary outcomes suggested that as total fat intake increases, body fatness measures may move in the same direction. However, heterogeneous methods and reporting across cohort studies, and predominantly very low-quality evidence, made it difficult to draw firm conclusions and true relationships may be substantially different. AUTHORS' CONCLUSIONS: We were unable to reach firm conclusions. Limited evidence from three trials that randomised children to a lower total fat intake (30% or less TE) versus usual or modified fat intake, but with no intention to reduce weight, showed small reductions in body mass index, total- and LDL-cholesterol at some time points with lower fat intake compared to controls, and no consistent differences in effects on weight, high-density lipoprotein (HDL) cholesterol or height. Associations in cohort studies that related total fat intake to later measures of body fatness in children were inconsistent and the quality of this evidence was mostly very low. Twenty-three out of 24 included studies were conducted in high-income countries, and may not be applicable in low- and middle-income settings. High-quality, longer-term studies are needed, that include low- and middle-income settings and look at both possible benefits and risks.

Scope and quality of Cochrane reviews of nutrition interventions: a cross-sectional study.

BACKGROUND: All countries face significant challenges from complex manifestations of malnutrition, which affects one in three people globally. Systematic reviews provide ready-to-use syntheses of quality-appraised evidence to inform decision-making for actions. To enhance the utility and quality of future Cochrane nutrition evidence, we described the scope and quality of all nutrition systematic reviews in the Cochrane Database of Systematic Reviews (CDSR). METHODS: We screened all active CDSR records (31 July 2015) to identify reviews and protocols using pre-specified eligibility criteria and definitions. Duplicate, independent data extraction included criteria for inclusion of studies in completed reviews (PICOS). We assessed methodological quality (AMSTAR), use of GRADE, mapped reviews against 2013 Global Burden of Disease data, and categorised the paradigm (medical, lifestyle and socio-ecological) of the review question. We analysed our results using descriptive statistics. RESULTS: We screened 8484 records, and included 470 (8%) completed reviews (in 45 Cochrane Review Groups (CRGs)) and 169 (7%) protocols (in 41 CRGs) published by 47 of 53 CRGs with reviews. Most completed reviews were produced by the Pregnancy and Childbirth (n = 73), Neonatal (n = 64), Metabolic and Endocrine Disorders (n = 33), Developmental, Psychosocial and Learning Problems (n = 26), Kidney and Transplant (n = 18) and Heart (n = 18) CRGs. Only 27% (n = 129) of reviews had searches for new studies in 2013 or thereafter. Supplementation/supplement interventions were most common (50%; n = 235; majority with micronutrients; 73%, n = 173), followed by food interventions (20%; n = 95). All reviews included randomised controlled trials; about 5% included other designs; 25% used GRADE; the median AMSTAR score was 9 (interquartile range: 7 to 10), 51% were high (AMSTAR 9-11) and 49% moderate (AMSTAR 5-8) quality. More than 80% framed questions using a medical paradigm. For top causes of years-of-life-lost, most reviews addressed preterm birth, diabetes and ischaemic heart disease; for leading risk factors for disability-adjusted-life-years, most targeted childhood undernutrition and high body mass index. CONCLUSIONS: Nutrition reviews comprised 8% of active CDSR records, were widely distributed across nearly all CRGs and reflected the double nutrition burden. This analysis presents a comprehensive description of the scope and quality of Cochrane nutrition reviews, and identifies gaps for future activities to support actions to address the nutrition burden, in line with the current nutrition agenda and impetus.

Research evidence and policy: qualitative study in selected provinces in South Africa and Cameroon.

BACKGROUND: The translation of research into policy and practice is enhanced by policymakers who can recognise and articulate their information needs and researchers that understand the policymakers' environment. As researchers, we sought to understand the policymaking process and how research evidence may contribute in South Africa and Cameroon. METHODS: We conducted qualitative in-depth interviews in South Africa and focus group discussions in Cameroon with purposively sampled subnational (provincial and regional) government health programme managers. Audio recorded interviews were transcribed, thematically coded and analysed. RESULTS: Participants in both countries described the complex, often lengthy nature of policymaking processes, which often include back-and-forth consultations with many diverse stakeholder groups. These processes may be influenced by political structures, relationships between national and subnational levels, funding and international stakeholder agendas. Research is not a main driver of policy, but rather current contextual realities, costs, logistics and people (clinicians, NGOs, funders) influence the policy, and research plays a part. Research evidence is frequently perceived as unavailable, inaccessible, ill-timed or not applicable. The reliability of research on the internet was questioned. Evidence-informed health decision-making (EIDM) is regarded as necessary in South Africa but is less well understood in Cameroon. Insufficient time and capacity were hindrances to EIDM in both countries. Good relationships between researchers and policymakers may facilitate EIDM. Researchers should have a good understanding of the policymaking environment if they want to influence it. Greater interaction between policymakers and researchers is perceived as beneficial when formulating research and policy questions as it raises researchers' awareness of implementation challenges and enables the design of tailored and focused strategies to respond to policymakers' needs. CONCLUSIONS: Policymaking is complicated, lengthy and mostly done at national level. Provinces/regions are tasked with implementation, with more room for adaptation in South Africa than in Cameroon. Research evidence plays a role in policy but does not drive it and is seen as mostly unavailable. Researchers need a thorough understanding of the policy process and environment, how the health system operates, as well as the priorities of policymakers. This can inform effective dialogue between researchers and policymakers, and contribute to enhancing use of research evidence in decision-making.

Iodised salt and iodine supplements for prenatal and postnatal growth: a rapid scoping of existing systematic reviews.

BACKGROUND: Iodine deficiency can adversely affect child development including stunted growth. However, the effect of iodine supplementation or fortification on prenatal and postnatal growth in children (<18 years) is unclear. We identified the potential need for a systematic review to contribute to the evidence base in this area. To avoid duplication and inform the need for a new systematic review and its protocol, we undertook a rapid scoping review of existing systematic reviews investigating the effect of iodised salt and iodine supplements on growth and other iodine-related outcomes. METHODS: We searched TRIP and Epistemokinos (latest search date 15 December 2014). All English language systematic reviews reporting on the effect of iodine supplementation or fortification in any form, dose or regimen on any iodine-related health outcomes (including but not limited to growth) were included. Eligible systematic reviews could include experimental or observational studies in pregnant or lactating women or children to age 18. We tabulated the extracted data to capture the scope of questions addressed, including: author, publication year, most recent search date, participants, pre-specified treatment/exposure and comparator, pre-specified outcomes, outcomes relevant to our question and number and type of studies included. Methodological quality of included reviews was assessed using AMSTAR. RESULTS: Nine hundred and seventy-six records were screened and 10 reviews included. Most studies were of moderate methodological quality. Outcomes included assessments of thyroid function, iodine deficiency disorders, mental development and growth. Populations studied included pregnant women, preterm infants and children into adulthood. Most reviews looked at direct iodine supplementation or fortification, though some reviews considered iodine status, including the relationship between iodine intake and iodine biomarkers. Although five reviews pre-specified inclusion of growth outcomes, none provided synthesised evidence on the effects of iodine supplementation or fortification on prenatal and postnatal somatic growth. CONCLUSIONS: Our rapid scoping review demonstrates a gap in the evidence base with no existing, up-to-date systematic reviews on the effects of all forms of iodine supplementation/fortification in all of the relevant population groups on relevant growth and growth-related outcomes. A new systematic review examining this question will assist in addressing this gap.

High-dose vitamin D3 reduces deficiency caused by low UVB exposure and limits HIV-1 replication in urban Southern Africans.

Cape Town, South Africa, has a seasonal pattern of UVB radiation and a predominantly dark-skinned urban population who suffer high HIV-1 prevalence. This coexistent environmental and phenotypic scenario puts residents at risk for vitamin D deficiency, which may potentiate HIV-1 disease progression. We conducted a longitudinal study in two ethnically distinct groups of healthy young adults in Cape Town, supplemented with vitamin D3 in winter, to determine whether vitamin D status modifies the response to HIV-1 infection and to identify the major determinants of vitamin D status (UVB exposure, diet, pigmentation, and genetics). Vitamin D deficiency was observed in the majority of subjects in winter and in a proportion of individuals in summer, was highly correlated with UVB exposure, and was associated with greater HIV-1 replication in peripheral blood cells. High-dosage oral vitamin D3 supplementation attenuated HIV-1 replication, increased circulating leukocytes, and reversed winter-associated anemia. Vitamin D3 therefore presents as a low-cost supplementation to improve HIV-associated immunity.

Systematic review of the effects of iodised salt and iodine supplements on prenatal and postnatal growth: study protocol.

INTRODUCTION: Iodine is an essential micronutrient and component of the thyroid hormones. Sufficient ingestion of iodine is necessary for normal growth and development. If iodine requirements are not met, growth can be impaired. Salt iodisation and supplementation with iodine can prevent iodine deficiency disorders and stunted growth. No systematic review has yet collated the evidence linking iodine to growth. With an increased emphasis on stunting within the WHO Global Nutrition Targets for 2025, we propose a systematic review to address this question. METHODS AND ANALYSIS: We will undertake a systematic review, and if appropriate, meta-analyses, evaluating the effects of iodised salt or iodine supplements on prenatal and postnatal somatic growth, until age 18. We will search a number of databases, including MEDLINE, EMBASE, Web of Science, CINAHL, PsychINFO, the Cochrane Library, including the CENTRAL register of Controlled Trials and also the WHO library and ICTRP (International Clinical Trials Registry Platform), which includes the Clinicaltrials.gov repository. We will also search Wanfang Data and the China Knowledge Resource Integrated Database. Included studies must have compared exposure to iodised salt, iodine supplements or iodised oil, to placebo, non-iodised salt or no intervention. Primary outcomes will be continuous and categorical markers of prenatal and postnatal somatic growth. Secondary outcomes will cover further measures of growth, including growth rates and indirect markers of growth such as insulin-like growth factor-1 (IGF-1). ETHICS AND DISSEMINATION: The systematic review will be published in a peer-reviewed journal, and will be sent directly to the WHO, United Nations Children's Fund, International Council for the Control of Iodine Deficiency Disorders and other stakeholders. The results generated from this systematic review will provide evidence to support future programme recommendations regarding iodine fortification or supplementation and child growth. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014012940.

Low carbohydrate versus isoenergetic balanced diets for reducing weight and cardiovascular risk: a systematic review and meta-analysis.

BACKGROUND: Some popular weight loss diets restricting carbohydrates (CHO) claim to be more effective, and have additional health benefits in preventing cardiovascular disease compared to balanced weight loss diets. METHODS AND FINDINGS: We compared the effects of low CHO and isoenergetic balanced weight loss diets in overweight and obese adults assessed in randomised controlled trials (minimum follow-up of 12 weeks), and summarised the effects on weight, as well as cardiovascular and diabetes risk. Dietary criteria were derived from existing macronutrient recommendations. We searched Medline, EMBASE and CENTRAL (19 March 2014). Analysis was stratified by outcomes at 3-6 months and 1-2 years, and participants with diabetes were analysed separately. We evaluated dietary adherence and used GRADE to assess the quality of evidence. We calculated mean differences (MD) and performed random-effects meta-analysis. Nineteen trials were included (n = 3209); 3 had adequate allocation concealment. In non-diabetic participants, our analysis showed little or no difference in mean weight loss in the two groups at 3-6 months (MD 0.74 kg, 95%CI -1.49 to 0.01 kg; I2 = 53%; n = 1745, 14 trials; moderate quality evidence) and 1-2 years (MD 0.48 kg, 95%CI -1.44 kg to 0.49 kg; I2 = 12%; n = 1025; 7 trials, moderate quality evidence). Furthermore, little or no difference was detected at 3-6 months and 1-2 years for blood pressure, LDL, HDL and total cholesterol, triglycerides and fasting blood glucose (>914 participants). In diabetic participants, findings showed a similar pattern. CONCLUSIONS: Trials show weight loss in the short-term irrespective of whether the diet is low CHO or balanced. There is probably little or no difference in weight loss and changes in cardiovascular risk factors up to two years of follow-up when overweight and obese adults, with or without type 2 diabetes, are randomised to low CHO diets and isoenergetic balanced weight loss diets.

Vitamin D and calcium status in South African adolescents with alcohol use disorders.

Adequate vitamin D and calcium are essential for optimal adolescent skeletal development. Adolescent vitamin D insufficiency/deficiency and poor calcium intake have been reported worldwide. Heavy alcohol use impacts negatively on skeletal health, which is concerning since heavy adolescent drinking is a rising public health problem. This study aimed to examine biochemical vitamin D status and dietary intakes of calcium and vitamin D in 12-16 year-old adolescents with alcohol use disorders (AUD), but without co-morbid substance use disorders, compared to adolescents without AUD. Substance use, serum 25-hydroxyvitamin D (s-25(OH)D) concentrations, energy, calcium and vitamin D intakes were assessed in heavy drinkers (meeting DSM-IV criteria for AUD) (n = 81) and in light/non-drinkers without AUD (non-AUD) (n = 81), matched for age, gender, language, socio-economic status and education. Lifetime alcohol dose was orders of magnitude higher in AUD adolescents compared to non-AUD adolescents. AUD adolescents had a binge drinking pattern and "weekends-only" style of alcohol consumption. Significantly lower (p = 0.038) s-25(OH)D (adjusted for gender, smoking, vitamin D intake) were evident in AUD adolescents compared to non-AUD adolescents. High levels of vitamin D insufficiency/deficiency (s-25(OH)D < 29.9 ng/mL) were prevalent in both groups, but was significantly higher (p = 0.013) in the AUD group (90%) compared to the non-AUD group (70%). All participants were at risk of inadequate calcium and vitamin D intakes (Estimated Average Requirement cut-point method). Both groups were at risk of inadequate calcium intake and had poor biochemical vitamin D status, with binge drinking potentially increasing the risk of the latter. This may have negative implications for peak bone mass accrual and future osteoporosis risk, particularly with protracted binge drinking.

Growth and weight status in treatment-naïve 12-16 year old adolescents with alcohol use disorders in Cape Town, South Africa.

BACKGROUND: Heavy alcohol consumption during adolescence has many known harmful health and social consequences and is strongly associated with numerous health risk behaviours. The consequences of heavy alcohol use during adolescence on nutritional status, specifically growth and weight status are largely unknown at this time. METHODS: Substance use, anthropometric indices of growth and weight, dietary energy intake and physical activity in heavy drinking adolescents (meeting DSM-IV criteria for alcohol use disorders) and matched light/non-drinking control adolescents were assessed. RESULTS: Lifetime alcohol dose, measured in standard drinks of alcohol, was orders of magnitude higher in adolescents with alcohol use disorders (AUDs) compared to controls. The AUDs group was selected to represent relatively 'pure' AUDs, with minimal other drug use and no psychiatric diagnoses. The growth and weight status of adolescents with AUDs were generally comparable to that of controls, and is in line with the growth and weight status of the South African adolescent population. A greater proportion of overweight/obese females was found in both groups, with this percentage tending to be greater, although not significantly so, in the AUDs group. Adolescent females with AUDs had increased odds of being overweight/obese compared to controls, after adjustment for smoking, physical activity and energy intake. CONCLUSION: Anthropometric indices of growth and weight status of participants in the Control and AUD groups were generally comparable. Female adolescents with AUDs may have an increased risk of being overweight/obese compared to adolescent females without AUDs. The presence of an AUD in our adolescent sample was associated with higher energy intake. Longitudinal studies are needed to elucidate the effects of heavy alcohol use on energy balance, growth and weight status in adolescents as they age. Nonetheless, the current study contributes to our understanding of the impacts of heavy alcohol consumption on important aspects of adolescent development.

Lymphocyte measures in treatment-naïve 13-15-year old adolescents with alcohol use disorders.

Many adolescents have chronic exposure to hazardous levels of alcohol. This is likely to be a significant predictor of health outcomes, including those related to immunity. We assessed substance use and biochemical immunological parameters in heavy drinking adolescents (meeting DSM-IV criteria for alcohol dependence) and light/nondrinking control adolescents in Cape Town. Lifetime alcohol dose, measured in standard units of alcohol, was orders of magnitude higher in alcohol-dependent (AD) participants than controls. All adolescent AD had a "weekends-only" style of alcohol consumption. The AD group was chosen to represent relatively "pure" AD, with minimal other drug use and no psychiatric diagnoses. With these narrow parameters in place, we found that AD adolescents were lymphopenic compared with controls, with significantly lower mean numbers of absolute circulating CD3+, CD4+, and CD8+ T-lymphocytes. On conclusion, we found that adolescent AD individuals with excessive alcohol intake, in a weekend binge-drinking style but without comorbid drug or psychiatric disorders, may be at increased risk of lymphopenia. This alcohol misuse may increase infectious disease susceptibility (including TB and HIV) by reducing immune system capabilities. Complex interactions of alcohol with other documented high-risk activities may further compound health risks.