Janet M. Peerson

Preventive Zinc Supplementation among Infants, Preschoolers, and Older Prepubertal Children

Zinc supplementation trials carried out among children have produced variable results, depending on the specific outcomes considered and the initial characteristics of the children who were enrolled. We completed a series of meta-analyses to examine the impact of preventive zinc supplementation on morbidity; mortality; physical growth; biochemical indicators of zinc, iron, and copper status; and indicators of behavioral development, along with possible modifying effects of the intervention results. Zinc supplementation reduced the incidence of diarrhea by ∼20%, but the impact was limited to studies that enrolled children with a mean initial age greater than 12 months. Among the subset of studies that enrolled children with mean initial age greater than 12 months, the relative risk of diarrhea was reduced by 27%. Zinc supplementation reduced the incidence of acute lower respiratory tract infections by ∼15%. Zinc supplementation yielded inconsistent impacts on malaria incidence, and too few trials are currently available to allow definitive conclusions to be drawn. Zinc supplementation had a marginal 6% impact on overall child mortality, but there was an 18% reduction in deaths among zinc-supplemented children older than 12 months of age. Zinc supplementation increased linear growth and weight gain by a small, but highly significant, amount. The interventions yielded a consistent, moderately large increase in mean serum zinc concentrations, and they had no significant adverse effects on indicators of iron and copper status. There were no significant effects on childrens behavioral development, although the number of available studies is relatively small. The available evidence supports the need for intervention programs to enhance zinc status to reduce child morbidity and mortality and to enhance child growth. Possible strategies for delivering preventive zinc supplements are discussed.

Use of Serum Zinc Concentration as an Indicator of Population Zinc Status

Assessing the prevalence and severity of zinc deficiency in populations is critical to determine the need for and appropriate targeting of zinc intervention programs and to assess their effectiveness for improving the health and well-being of high-risk populations. However, there is very little information on the zinc status of populations worldwide due to the lack of consensus on appropriate biochemical indicators of zinc status. The objective of this review was to evaluate the use of serum zinc concentration as an indicator of population zinc status. We have reviewed the response of serum zinc concentration to dietary zinc restriction and zinc supplementation. In addition, we completed pooled analyses of nine zinc intervention trials in young children to assess the relations between serum zinc concentration of individuals before treatment and their responses to zinc supplementation. Also, in updated combined analyses of previously published data, we investigated the relation between the mean initial serum zinc concentration of a study population and their mean growth responses to zinc supplementation in randomized intervention trials among children. The results from depletion/repletion studies indicate that serum zinc concentrations respond appreciably to severe dietary zinc restriction, although there is considerable interindividual variation in these responses. There is also clear evidence that both individual and population mean serum zinc concentrations increase consistently during zinc supplementation, regardless of the initial level of serum zinc concentration. By contrast, an individuals serum zinc concentration does not reliably predict that persons response to zinc supplementation. Serum zinc concentration can be considered a useful biomarker of a populations risk of zinc deficiency and response to zinc interventions, although it may not be a reliable indicator of individual zinc status.

Use of national food balance data to estimate the adequacy of zinc in national food supplies: methodology and regional estimates

OBJECTIVES Adequate zinc nutriture is critically important for human health, but the development of programmes to control zinc deficiency is limited by the lack of reliable information on population zinc status. The present analyses were conducted to: (1) estimate the absorbable zinc content of national food supplies; (2) compare this information with theoretical population requirements for zinc; and (3) use these results to predict national risks of inadequate zinc intake. SETTING AND DESIGN National food balance data were obtained for 176 countries from the Food and Agriculture Organization of the United Nations. The amount of absorbable zinc in these foods was estimated from food composition data, and zinc absorption was predicted using a model developed by the International Zinc Nutrition Consultative Group (IZiNCG). Demographic data were obtained from United Nations estimates, and age- and sex-specific physiological requirements for absorbable zinc were estimated using IZiNCG recommendations. RESULTS AND CONCLUSIONS The mean per capita absorbable zinc content of national food supplies ranged from 2.98-3.01 mg day(-1) in Western Europe and USA & Canada to 2.09 mg day(-1) in Southeast Asia. The estimated percentage of individuals at risk of inadequate zinc intake ranged from 9.3-9.5% in the regions of North Africa & Eastern Mediterranean and USA & Canada to 33.1% in Southeast Asia. Overall, approximately 20.5% of the worlds population is estimated to be at risk of inadequate zinc intake. Data on the absorbable zinc content of national food supplies can be used to determine whether further assessments of population zinc status and development of intervention programmes are warranted.

Provision of Multiple Rather Than Two or Fewer Micronutrients More Effectively Improves Growth and Other Outcomes in Micronutrient-Deficient Children and Adults

Deficiencies of multiple micronutrients (MMN) usually coexist in developing countries, but supplements have usually provided only 1 or 2 micronutrients (MN). To inform policy, in this article we compared the relative benefits of supplying MMN vs. a placebo or 1 or 2 MN on the following: childrens growth, health, and development; pregnancy outcome; nutritional status; and HIV/AIDS mortality and morbidity in adults. Sufficient data were available to perform random-effects meta-analyses of randomized controlled trials (RCT) for the effects of MMN on child growth and nutritional status. Results for other outcomes are presented as effect sizes (ES) when available. In children, MMN interventions resulted in small but significantly greater improvements in length or height (ES = 0.13; 95% CI: 0.055, 0.21) and weight (ES = 0.14; 95% CI: 0.029, 0.25), hemoglobin (ES = 0.39; 95% CI: 0.25, 0.53), serum zinc (ES = 0.23; 95% CI: 0.18, 0.43), serum retinol (ES = 0.33; 95% CI: 0.050, 0.61), and motor development. A Cochrane review reported that compared with no supplementation or a placebo, MMN supplementation during pregnancy reduced the relative risk of low birth weight (0.83), small-for-gestational age (0.92), and anemia (0.61); however, MMN were not more effective than iron + folic acid alone. There is some evidence that MMN supplementation improves CD4 counts and HIV-related morbidity and mortality in adults. The efficacy of MMN varies across trials, but overall there is evidence that outcomes are better than when providing < or =2 MN. The policy implications of these studies are discussed.

Intake and growth of breast‐fed and formula‐fed infants in relation to the timing of introduction of complementary foods: the DARLING study

We examined if the timing of introduction of solid foods was related to growth, intake, morbidity, activity or motor development among infants either breast fed or formula fed until 12 months of age. Breast‐fed infants given solids before 6 months of age (earlysol) consumed less breast milk at 6 and 9 months of age than those given solids 6 months (latesol); thus total energy intake did not differ between groups. Z scores for weight, length and weight‐for‐length at 1–18 months did not differ between groups. Latesol infants gained less weight from 6 to 9 months but not during any other interval. Neither activity level nor morbidity differed between groups, but several developmental milestones occurred earlier in the earlysol versus the latesol group, probably due to reverse causation. Among formula‐fed infants, timing of introduction of solid foods was not related to intake, growth, activity or morbidity. We conclude that solid foods given before 6 months of age generally replace the milk source among breast‐fed but not formula‐fed infants.

In-hospital formula use increases early breastfeeding cessation among first-time mothers intending to exclusively breastfeed.

OBJECTIVE To evaluate in-hospital formula supplementation among first-time mothers who intended to exclusively breastfeed and determined if in-hospital formula supplementation shortens breastfeeding duration after adjusting for breastfeeding intention. STUDY DESIGN We assessed strength of breastfeeding intentions prenatally in a diverse cohort of expectant primiparae and followed infant feeding practices through day 60. Among mothers planning to exclusively breastfeed their healthy term infants for ≥1 week, we determined predictors, reasons, and characteristics of in-hospital formula supplementation, and calculated the intention-adjusted relative risk (ARR) of not fully breastfeeding days 30-60 and breastfeeding cessation by day 60 with in-hospital formula supplementation (n = 393). RESULTS Two hundred ten (53%) infants were exclusively breastfed during the maternity stay and 183 (47%) received in-hospital formula supplementation. The most prevalent reasons mothers cited for in-hospital formula supplementation were: perceived insufficient milk supply (18%), signs of inadequate intake (16%), and poor latch or breastfeeding (14%). Prevalence of not fully breastfeeding days 30-60 was 67.8% vs. 36.7%, ARR 1.8 (95% CI, 1.4-2.3), in-hospital formula supplementation vs exclusively breastfed groups, respectively, and breastfeeding cessation by day 60 was 32.8% vs. 10.5%, ARR 2.7 (95% CI, 1.7-4.5). Odds of both adverse outcomes increased with more in-hospital formula supplementation feeds (not fully breastfeeding days 30-60, P = .003 and breastfeeding cessation, P = .011). CONCLUSIONS Among women intending to exclusively breastfeed, in-hospital formula supplementation was associated with a nearly 2-fold greater risk of not fully breastfeeding days 30-60 and a nearly 3-fold risk of breastfeeding cessation by day 60, even after adjusting for strength of breastfeeding intentions. Strategies should be sought to avoid unnecessary in-hospital formula supplementation and to support breastfeeding when in-hospital formula supplementation is unavoidable.

Randomized, community-based trial of the effect of zinc supplementation, with and without other micronutrients, on the duration of persistent childhood diarrhea in Lima, Peru

OBJECTIVE To determine whether supplemental zinc, with or without additional micronutrients, affects the severity and duration of persistent childhood diarrhea and the rate of nutritional recovery. DESIGN The study was a community-based, double-blind, randomized trial implemented in a shanty town in Lima, Peru. Children aged 6 to 36 months with persistent (>/=14 days) diarrhea received daily, for 2 weeks, a placebo (group P, n = 136) or a supplement of 20 mg of zinc, either with (group Z+VM, n = 137) or without (group Z, n = 139) additional vitamins and minerals. Symptoms of illness were recorded daily, and biochemical and anthropometric assessments were completed at baseline and on day 15. RESULTS The treatment groups were similar at baseline with regard to the characteristics of the presenting episode, anthropometric data, and plasma zinc concentration. The children consumed, on average, 95% (group P), 94% (group Z), or 88% (group Z+VM) of the supplement (P <.001). The plasma zinc concentration did not change significantly from baseline to day 15 in group P (4 microg/dL) but increased by 38 microg/dL in group Z and 14 microg/dL in group Z+VM. The median duration of diarrhea after starting treatment was 1 day; among children who continued to have diarrhea, there was a significant effect of treatment on diarrheal duration (P =.04, analysis of covariance). Specifically, the duration of illness was significantly reduced by 28% in children in group Z (P =.01) and by 33% in girls in group Z+VM (P =.04). There were no differences in the severity of the episode by treatment group. CONCLUSION There was a significant reduction in the duration of persistent diarrhea in selected subgroups of zinc-supplemented ambulatory patients in this population.

Epidemiology of altered intestinal permeability to lactulose and mannitol in Guatemalan infants

BACKGROUND Subclinical alterations of small intestinal function have been reported frequently in tropical countries. Studies of small intestinal permeability to lactulose and mannitol were therefore completed in Guatemalan infants from a low-income, periurban community to assess the prevalence of altered intestinal function and the factors associated with this condition. METHODS Two hundred studies were successfully completed in 158 infants who had been free of diarrhea for at least 1 week before the day of study. Urinary concentrations of lactulose and mannitol during the 5-hour period after ingestion of 400 mg/kg body weight of lactulose and 100 mg/kg body weight of mannitol were measured by gas-liquid chromatography and compared by age group, feeding practices, anthropometric indexes, and serum iron and zinc concentrations. RESULTS The overall prevalence of altered intestinal permeability (defined as a ratio of urinary recovery of lactulose to mannitol [L/M] > or =0.07) was 30%. The urinary L/M recovery ratio was positively associated with age; low weight for age; and, in infants less than 6 months of age, non-breast-feeding. Children with serum iron concentrations less than 7.16 microM/l (40 [microg/dl) had higher median L/M ratios (L/M = 0.068; 95% confidence interval [CI], 0.054, 0.085) than those with iron levels higher than this cutoff (L/M = 0.052; CI = 0.046, 0.058; p = 0.038). The median urinary L/M recovery ratio in 10 currently asymptomatic infants who had diarrhea during the week before testing (0.087; CI = 0.49, 0.154) was higher than that in children who had been free from diarrhea for at least 1 week (0.052; CI = 0.048, 0.056; p = 0.01). CONCLUSION Age, feeding practices, low weight-for-age, low serum iron concentration, and recent diarrhea were all associated with altered intestinal function in this group of Guatemalan infants.

Excess Weight Loss in First-Born Breastfed Newborns Relates to Maternal Intrapartum Fluid Balance

OBJECTIVES: The objectives were to describe weight loss in a multiethnic population of first-born, predominantly breastfed, term infants and to identify potentially modifiable risk factors for excess weight loss (EWL). METHODS: Data on prenatal breastfeeding intentions, demographic characteristics, labor and delivery interventions and outcomes, breastfeeding behaviors, formula and pacifier use, onset of lactogenesis, and nipple type and pain were collected prospectively. Logistic regression analyses identified independent predictors of EWL (≥10% of birth weight) by using a preplanned theoretical model. RESULTS: EWL occurred for 18% of infants who received no or minimal (≤60 mL total since birth) formula (n = 229), including 19% of exclusively breastfed infants (n = 134) and 16% of infants who received minimal formula (n = 95). In bivariate analyses, EWL was associated (P < .05) with higher maternal age, education, and income levels, hourly intrapartum fluid balance, postpartum edema, delayed lactogenesis (>72 hours), fewer infant stools, and infant birth weight. In multivariate logistic regression analysis, only 2 variables predicted EWL significantly, namely, intrapartum fluid balance (adjusted relative risk for EWL of 3.18 [95% confidence interval [CI]: 1.35–13.29] and 2.80 [95% CI: 1.17–11.68] with net intrapartum fluid balance of >200 and 100–200 mL/hour, respectively, compared with <100 mL/hour) and delayed lactogenesis (adjusted relative risk: 3.35 [95% CI: 1.74–8.10]). CONCLUSIONS: EWL was more common in this population than reported previously and was independently related to intrapartum fluid balance. This suggests that intrapartum fluid administration can cause fetal volume expansion and greater fluid loss after birth, although other mechanisms are possible.

Lipid-based nutrient supplement increases the birth size of infants of primiparous women in Ghana

BACKGROUND The International Lipid-Based Nutrient Supplements Project developed a small-quantity (20 g/d) lipid-based nutrient supplement (LNS) for pregnant and lactating women. OBJECTIVE We evaluated the effects of prenatal LNS supplementation on fetal growth. DESIGN In a community-based, partially double-blind, individually randomized controlled trial, 1320 women ≤20 wk pregnant received 60 mg Fe/400 μg folic acid (IFA), or 1-2 Recommended Dietary Allowances of 18 micronutrients, including 20 mg Fe (MMN), or LNS with the same micronutrients as the MMN group, plus 4 minerals and macronutrients contributing 118 kcal (LNS) daily until delivery. Fetal growth was compared across groups by using intention-to-treat analysis. The primary outcome was birth length. RESULTS This analysis included 1057 women (IFA = 349, MMN = 354, LNS = 354). Groups did not differ significantly in mean birth length, length-for-age z score (LAZ), head circumference, or percentage low birth length but differed in mean birth weight (P = 0.044), weight-for-age z score (WAZ; P = 0.046), and BMI-for-age z score (BMIZ; P = 0.040), with a trend toward differences in low birth weight (P = 0.069). In pairwise comparisons, the LNS group had greater mean birth weight (+85 g; P = 0.040), WAZ (+0.19; P = 0.045), and BMIZ (+0.21; P = 0.035) and a lower risk of low birth weight (RR: 0.61, 95% CI: 0.39, 0.96; P = 0.032) than did the IFA group. The other group differences were not significant. The effect of intervention was modified by mothers parity, age, height, baseline hemoglobin, household food insecurity, and child sex, with parity being the most consistent modifier. Among primiparous women (IFA = 131; MMN = 110; LNS = 128), the LNS group had greater mean birth length (+0.91 cm; P = 0.001), LAZ (+0.47; P = 0.001), weight (+237 g; P < 0.001), WAZ (+0.56; P < 0.001), BMIZ (+0.52; P < 0.001), head circumference (0.50 cm; P = 0.017), and head circumference-for-age z score (+0.40; P = 0.022) than did the IFA group; similar differences were found when comparing the LNS and MMN groups among primiparous women, and no group differences were found among multiparous women. CONCLUSION Prenatal LNS supplementation can improve fetal growth among vulnerable women in Ghana, particularly primiparous women. This trial was registered at clinicaltrials.gov as NCT00970866.