Effects of prenatal micronutrients supplementation timing on pregnancy-induced hypertension: Secondary analysis of a double-blind randomized controlled trial.

In this secondary analysis of data from a double-blind randomized controlled trial (clinicaltrials.gov identifier: NCT00133744) of micronutrient supplementation (multiple micronutrients [MMN], iron-folic acid [IFA] and folic acid [FA] alone), we examined the potential modifying effect of gestational age at enrolment on the association of antenatal supplementation and pregnancy-induced hypertension (PIH). We included 18,775 nulliparous pregnant women with mild or no anaemia who were enrolled at 20 weeks of gestation or earlier from five counties of northern China. Women were randomly assigned to receive daily FA, IFA or MMN from enrolment until delivery. We used logistic regression to evaluate the association between PIH and timing of micronutrient supplementation. The incidence of PIH was statistically significantly lower among women who began MMN supplementation before 12 gestational weeks compared with women who began MMN supplementation at 12 weeks or later (RR = 0.74, 95% CI: 0.60-0.91). A similar protective effect was observed for both early-onset (<28 weeks, RR 0.45, 0.21-0.96) and late-onset of PIH (≥28 weeks, RR 0.77, 0.63-0.96). No statistically significant association was observed between PIH occurrence and timing of supplementation for FA or IFA. Maternal MMN supplementation and antenatal enrolment during the first trimester of pregnancy appeared to be of importance in preventing both early- and late-onset of PIH.

Combined infant and young child feeding with small-quantity lipid-based nutrient supplementation is associated with a reduction in anemia but no changes in anthropometric status of young children from Katanga Province of the Democratic Republic of Congo: a quasi-experimental effectiveness study.

BACKGROUND: Small-quantity lipid-based nutrient supplements (SQ-LNS) are efficacious in controlled settings; data are scarce on the effectiveness utilizing health care delivery platforms. OBJECTIVE: We evaluated the impact of an infant young child feeding (IYCF)-SQ-LNS intervention on anemia and growth in children aged 6-18 mo in the Democratic Republic of Congo following a quasi-experimental effectiveness design. METHODS: An intervention health zone (HZ) received enhanced IYCF including improved counseling on IYCF during pregnancy until 12 mo after birth and daily use of SQ-LNS for infants 6-12 mo; the control HZ received the standard IYCF package. We analyzed data from 2995 children, collected in repeated cross-sectional surveys. We used adjusted difference-in-difference analyses to calculate changes in anemia, iron and vitamin A deficiencies, stunting, wasting, and underweight. RESULTS: Of mothers, 70.5% received SQ-LNS at least once in the intervention HZ, with 99.6% of their children consuming SQ-LNS at least once. The mean number of batches of SQ-LNS (28 sachets per batch, 6 batches total) received was 2.3 ± 0.8 (i.e., 64.4 ± 22.4 d of SQ-LNS). The enhanced program was associated with an 11.0% point (95% CI: -18.1, -3.8; P < 0.01) adjusted relative reduction in anemia prevalence and a mean +0.26-g/dL (95% CI: 0.04, 0.48; P = 0.02) increase in hemoglobin but no effect on anthropometry or iron or vitamin A deficiencies. At endline in the intervention HZ, children aged 8-13 mo who received ≥3 monthly SQ-LNS batch distributions had higher anthropometry z scores [length-for-age z score (LAZ): +0.40, P = 0.04; weight-for-age z score (WAZ): +0.37, P = 0.04] and hemoglobin (+0.65 g/dL, P = 0.007) and a lower adjusted prevalence difference of stunting (-16.7%, P = 0.03) compared with those who received none. CONCLUSIONS: The enhanced IYCF-SQ-LNS intervention using the existing health care delivery platform was associated with a reduction in prevalence of anemia and improvement in mean hemoglobin. At endline among the subpopulation receiving ≥3 mo of SQ-LNS, their LAZ, WAZ, and hemoglobin improved. Future research could explore contextual tools to maximize coverage and intake adherence in programs using SQ-LNS.

Predictors of micronutrient powder (MNP) knowledge, coverage, and consumption during the scale-up of an integrated infant and young child feeding (IYCF-MNP) programme in Nepal.

Large-scale programmes using micronutrient powders (MNPs) may not achieve maximum impact due to limited/inappropriate MNP coverage, consumption, and use. We identify predictors of MNP coverage, maternal knowledge of appropriate use, and child MNP consumption in Nepal. A cross-sectional survey was conducted in 2,578 mother-child pairs representative of children 6-23 months in two districts that were part of the post-pilot, scale-up of an integrated infant and young child feeding-MNP (IYCF-MNP) programme. Children aged 6-23 months were expected to receive 60 MNP sachets every 6 months from a female community health volunteer (FCHV) or health centre. Outcomes of interest were MNP coverage (ever received), maternal knowledge of appropriate use (correct response to seven questions), repeat coverage (receipt ≥ twice; among children 12-23 months who had received MNP at least once, n = 1342), and high intake (child consumed ≥75% of last distribution, excluding those with recent receipt/insufficient time to use 75% at recommended one-sachet-per-day dose, n = 1422). Multivariable log-binomial regression models were used to identify predictors of the four outcomes. Coverage, knowledge of appropriate use, and repeat coverage were 61.3%, 33.5%, and 45.9%, respectively. Among MNP receivers, 97.9% consumed MNP at least once and 38.9% of eligible children consumed ≥75% of last distribution. FCHV IYCF-MNP counselling was positively associated with knowledge, coverage, repeat coverage, and high intake; health worker counselling with knowledge and coverage indicators; and radio messages with coverage indicators only. FCHV counselling had the strongest association with knowledge, coverage, and high intake. Community-based counselling may play a vital role in improving coverage and intake in MNP programmes.

Changes in growth, anaemia, and iron deficiency among children aged 6-23 months in two districts in Nepal that were part of the post-pilot scale-up of an integrated infant and young child feeding and micronutrient powder intervention.

There is limited research on integrated infant and young child feeding (IYCF) and micronutrient powders (MNPs) programmes operating at scale, despite widespread implementation. This study uses cross-sectional baseline (n = 2,542) and endline (n = 2,578) surveys representative of children 6-23 months in two districts in Nepal that were part of a post-pilot scale-up of a IYCF-MNP programme. Multivariable log-binomial regression models were used to estimate prevalence ratios (PRs) for stunting (length-for-age z-score <-2), wasting (weight-for-length z-score <-2), underweight (weight-for-age z-score <-2), anaemia (altitude-adjusted haemoglobin <110 µg/L), moderate or severe anaemia (altitude-adjusted haemoglobin <100 g/L), iron deficiency (inflammation-adjusted ferritin <12 µg/L), and iron deficiency anaemia (iron deficiency + anaemia [IDA]) at endline versus baseline and also to compare children in the endline survey based on frequency of mothers' interactions with female community health volunteers (FCHVs; >1× per month or monthly vs. <1× per month) and MNP coverage (1 or ≥2 distributions vs. none among children 12-23 months). Endline children were significantly less likely to be stunted than baseline children in both districts (multivariable-adjusted PR [95% CI]: 0.77 [0.69, 0.85], P < 0.001 and 0.82 [0.75, 0.91], P < 0.001 in Kapilvastu and Achham, respectively); however, only Achham had significantly lower prevalences of underweight, moderate/severe anaemia, iron deficiency, and IDA at endline. At endline, 53.5% and 71.4% of children had tried MNP in Kapilvastu and Achham districts, respectively, consuming an average of 24 sachets from the last distribution. Frequent maternal-FCHV interactions were associated with a reduced risk of stunting and underweight at endline, whereas repeat MNP coverage was associated with reduced risk of anaemia and IDA. Future research using experimental designs should verify the potential of integrated IYCF-MNP programmes to improve children's nutritional status.

Micronutrient supplementation during pregnancy and the risk of pregnancy-induced hypertension: A randomized clinical trial.

BACKGROUND & AIMS: Increasing evidence suggests that iron-containing multiple micronutrient may reduce the risk of pregnancy-induced hypertension including gestational hypertension or preeclampsia. We aimed to examine whether 30 mg iron plus folic acid or multiple micronutrients during pregnancy reduces the risk of pregnancy-induced hypertension. METHODS: We conducted a secondary data analysis by the dataset from a double-blind randomized controlled trial in China from 2006 to 2009 that was conducted to investigate the effects of multiple micronutrient supplements on adverse pregnancy outcomes when provided to pregnant women with no/mild anemia. We used logistic regression to estimate the adjusted odds ratio and 95% confidence interval and test for effect modification. RESULTS: The incidence of pregnancy-induced hypertension was 7.1% (423/5923), 6.3% (374/5933) and 6.3% (372/5914) among the pregnant women who took folic acid only, iron-folic acid and multiple micronutrient supplements, respectively. The adjusted odds ratios associated with iron-folic acid supplements and multiple micronutrient supplements for pregnancy-induced hypertension were both nearly 0.88 (95% confidence interval, 0.76-1.02), compared with folic acid supplements only. Among pregnant women aged 20-24 years, iron-folic acid (adjusted odds ratios: 0.81, 95% confidence interval: 0.67-0.96) or multiple micronutrient supplementation (adjusted odds ratios: 0.83, 95% confidence interval: 0.70-0.99) can significantly reduce the risk of pregnancy-induced hypertension compared to folic acid supplementation. CONCLUSIONS: Overall, there were no significant differences in pregnancy-induced hypertension across supplement groups. However, among pregnant women aged 20-24 years, iron-containing multiple micronutrient supplementation was associated with a reduced risk of pregnancy-induced hypertension compared with folic acid supplements only. TRIAL REGISTRATION: ClinicalTrials.gov NCT00133744.

Prenatal iron containing supplements provided to Chinese women with no or mild anemia had no effect on hemoglobin concentration in post-partum women or their infants at 6 and 12 months of age.

BACKGROUND: Although prenatal iron-containing supplements have been associated with lower anemia prevalence in later pregnancy, few trials have examined the effect of supplements on the anemia status of post-partum women and their infants. OBJECTIVE: We compared the effects of folic acid alone (FA), iron-folic acid (IFA) and multiple micronutrients (MMN) when provided to pregnant women with no or mild anemia on the hemoglobin levels of post-partum women and their infants at 6 and 12 months of age. We also examined the potential modifying effect of maternal hemoglobin concentration at enrollment. METHODS: A double-blind randomized controlled trial was conducted in China; 18,775 nulliparous women with a hemoglobin concentration > 100 g/L were randomly assigned to receive daily FA (400 µg); IFA (FA, Fe 30 mg), or MMN (FA, Fe and 13 micronutrients) from before 20 gestational weeks until delivery. RESULTS: Compared with daily prenatal FA, supplementation with IFA or MMN did not affect the prevalence of anemia at 4-6 weeks post-partum (27.2%, 26.8%, and 26.3%, respectively). At 6 months of age, the anemia prevalence in infants was 6.9%, 6.7%, and 6.7%, respectively. Findings were similar at 12 months of age. Among both post-partum women and infants, findings were similar across all levels of hemoglobin at enrollment. CONCLUSIONS: Compared to FA alone, prenatal IFA and MMN provided to women with no or mild anemia did not affect anemia in women post-partum or their infants regardless of baseline maternal hemoglobin concentration at enrollment.

Infant and Young Child Feeding (IYCF) Practices Improved in 2 Districts in Nepal during the Scale-Up of an Integrated IYCF and Micronutrient Powder Program.

BACKGROUND: Three-quarters of the ≥50 programs that use micronutrient powders (MNPs) integrate MNPs into infant and young child feeding (IYCF) programs, with limited research on impacts on IYCF practices. OBJECTIVE: This study assessed changes in IYCF practices in 2 districts in Nepal that were part of a post-pilot scale-up of an integrated IYCF-MNP program. METHODS: This analysis used cross-sectional surveys (n = 2543 and 2578 for baseline and endline) representative of children aged 6-23 mo and their mothers in 2 districts where an IYCF program added MNP distributions through female community health volunteers (FCHVs) and health workers (HWs). Multivariable log-binomial models estimated prevalence ratios comparing reported IYCF at endline with baseline and at endline on the basis of exposure to different sources of IYCF information. Mothers who received FCHV-IYCF counseling with infrequent (≤1 time/mo) and frequent (>1 time/mo) interactions were compared with mothers who never received FCHV-IYCF counseling. The receipt of HW-IYCF counseling and receipt of MNPs from an FCHV (both yes or no) were also compared. RESULTS: The prevalence of minimum dietary diversity (MDD) and minimum acceptable diet (MAD) was significantly higher at endline than at baseline. In analyses from endline, compared with mothers who never received FCHV counseling, only mothers in the frequent FCHV-IYCF counseling group were more likely to report feeding the minimum meal frequency (MMF) and MAD, with no difference for the infrequent FCHV-IYCF counseling group in these indicators. HW-IYCF counseling was not associated with these indicators. Mothers who received MNPs from their FCHV were more likely to report initiating solid foods at 6 mo and feeding the child the MDD, MMF, and MAD compared with mothers who did not, adjusting for HW- and FCHV-IYCF counseling and demographic covariates. CONCLUSIONS: Incorporating MNPs into the Nepal IYCF program did not harm IYCF and may have contributed to improvements in select practices. Research that uses experimental designs should verify whether integrated IYCF-MNP programs can improve IYCF practices.

Monitoring and surveillance for multiple micronutrient supplements in pregnancy.

The World Health Organization (WHO) recommends iron-folic acid (IFA) supplementation during pregnancy to improve maternal and infant health outcomes. Multiple micronutrient (MMN) supplementation in pregnancy has been implemented in select countries and emerging evidence suggests that MMN supplementation in pregnancy may provide additional benefits compared to IFA alone. In 2015, WHO, the United Nations Children's Fund (UNICEF), and the Micronutrient Initiative held a "Technical Consultation on MMN supplements in pregnancy: implementation considerations for successful incorporation into existing programmemes," which included a call for indicators needed for monitoring, evaluation, and surveillance of MMN supplementation programmes. Currently, global surveillance and monitoring data show that overall IFA supplementation programmes suffer from low coverage and intake adherence, despite inclusion in national policies. Common barriers that limit the effectiveness of IFA-which also apply to MMN programmes-include weak supply chains, low access to antenatal care services, low-quality behaviour change interventions to support and motivate women, and weak or non-existent monitoring systems used for programme improvement. The causes of these barriers in a given country need careful review to resolve them. As countries heighten their focus on supplementation during pregnancy, or if they decide to initiate or transition into MMN supplementation, a priority is to identify key monitoring indicators to address these issues and support effective programmes. National and global monitoring and surveillance data on IFA supplementation during pregnancy are primarily derived from cross-sectional surveys and, on a more routine basis, through health and logistics management information systems. Indicators for IFA supplementation exist; however, the new indicators for MMN supplementation need to be incorporated. We reviewed practice-based evidence, guided by the WHO/Centers for Disease Control and Prevention logic model for vitamin and mineral interventions in public health programmes, and used existing manuals, published literature, country reports, and the opinion of experts, to identify monitoring, evaluation, and surveillance indicators for MMN supplementation programmes. We also considered cross-cutting indicators that could be used across programme settings, as well as those specific to common delivery models, such as antenatal care services. We then described mechanisms for collecting these data, including integration within existing government monitoring systems, as well as other existing or proposed systems. Monitoring data needs at all stages of the programme lifecycle were considered, as well as the feasibility and cost of data collection. We also propose revisions to global-, national-, and subnational-surveillance indicators based on these reviews.

Effects of Prenatal Micronutrient Supplementation on Spontaneous Preterm Birth: A Double-Blind Randomized Controlled Trial in China.

In this secondary analysis of data from a double-blind randomized controlled trial carried out in northern China, we aimed to assess the effect of prenatal supplementation with multiple micronutrients (MMN) or iron + folic acid (IFA), versus folic acid (FA) alone, on risk of spontaneous preterm birth (SPB) and the impact of supplementation timing on SPB. A total of 18,775 nulliparous pregnant women enrolled between 2006 and 2009 were randomly assigned to receive daily FA, IFA, or MMN from the period before 20 weeks' gestation to delivery. The incidences of SPB for women consuming FA, IFA, and MMN were 5.7%, 5.6% and 5.1%, respectively. Compared with women given FA, the relative risks of SPB for those using MMN and IFA were 0.99 (95% confidence interval: 0.85, 1.16) and 0.89 (95% confidence interval: 0.79, 1.05), respectively. SPB incidence in women who started consuming FA, IFA, and MMN before the 12th week of gestation (4.6%, 4.2%, and 3.9%, respectively) was significantly reduced compared with starting supplement use on or after the 12th gestational week (6.9%, 7.2%, and 6.4%, respectively). Starting use of FA, IFA, or MMN supplements before the 12th week of gestation produced a 41%-45% reduction in risk of SPB. Early prenatal enrollment and micronutrient use during the first trimester of pregnancy appeared to be of particular importance for prevention of SPB, regardless of supplement group.

C-reactive protein increases with gestational age during pregnancy among Chinese women.

OBJECTIVE: To examine the concentration of C-reactive protein (CRP) in relation to gestational weeks during pregnancy among Chinese women. METHODS: From a randomized control trial of prenatal supplementation with folic acid, iron-folic acid, and multiple micronutrients in China, we examined 834 pregnant women with CRP measured initially between 5 and 20 weeks and at follow-up between 28 and 32 weeks gestation. We calculated and plotted CRP geometric means by gestational weeks. The same analysis was repeated for women who had normal pregnancies (624 women) by excluding women with stillbirth, preterm, small for gestational age, body mass index <18.5 kg/m(2) or >30 kg/m(2) at enrollment, and hypertension or anemia during pregnancy. RESULTS: We observed a significant positive trend between log-transformed CRP and gestational age from 5 to 20 weeks and from 28 to 32 weeks both in the full sample and in the subset of women who had normal pregnancies. CRP geometric mean was 0.81 mg/l at 5-7 weeks of gestation, 2.85 mg/l at 19-20 weeks of gestation, and 3.89 mg/l at 32 weeks of gestation. A similar increasing trend in the CRP median or percentage of elevated CRP were also observed. CONCLUSION: We concluded that CRP increased with gestational age among healthy Chinese women who delivered healthy infants. Am. J. Hum. Biol. 28:574-579, 2016. © 2016 Wiley Periodicals, Inc.

Modifying effects of maternal Hb concentration on infant birth weight in women receiving prenatal iron-containing supplements: a randomised controlled trial.

Concerns have been raised about the benefits of Fe-containing supplements on infant birth weight among women with normal/high Hb levels at baseline. Thus far, no clinical trials have examined whether the effects of prenatal Fe-containing supplements on birth weight vary by maternal Hb levels. We compared the effects of Fe-folic acid (IFA) or multiple micronutrients (MMN) with folic acid (FA) supplements on birth weight among pregnant women with mild/no anaemia or high Hb levels. A double-blind randomised controlled trial was conducted in 2006-2009. In total, 18 775 pregnant women with mild/no anaemia (145 g/l) baseline Hb levels, IFA and MMN supplements increased birth weight by 91·44 (95% CI 3·37, 179·51) g and 107·63 (95% CI 21·98, 193·28) g (P<0·05), respectively, compared with the FA group. No differences were found between the IFA and the MMN group, regardless of maternal Hb concentration. In conclusion, the effects of Fe-containing supplements on birth weight depended on baseline Hb concentrations. The Fe-containing supplements improved birth weight in women with very high Hb levels before 20 weeks of gestation.

Evidence of the effectiveness of flour fortification programs on iron status and anemia: a systematic review.

CONTEXT: More than 80 countries fortify flour, yet the public health impact of this intervention on iron and anemia outcomes has not been reviewed. OBJECTIVE: The objective of this systematic review was to review published and gray literature pertaining to the impact of flour fortification on iron and anemia. DATA SOURCES: A systematic review was conducted by searching 17 databases and appealing for unpublished reports, yielding 1881 documents. STUDY SELECTION: Only studies of government-supported, widely implemented fortification programs in which anemia or iron status was measured prior to and ≥12 months after initiation of fortification were included. DATA EXTRACTION: Details about the design, coverage, compliance with national standards, and evaluation (e.g., anemia prevalence before and after fortification) of flour fortification programs were extracted from the reports. DATA SYNTHESIS: Thirteen studies describing 26 subgroups (n = 14 for children ≤15 y, n = 12 for women of reproductive age) were included. During the period from pre- to postfortification (and as difference-in-difference for those studies that included a control group), there were statistically significant decreases in the prevalence of anemia in 4 of 13 subgroups of children and in 4 of 12 subgroups of women of reproductive age as well as significant decreases in the prevalence of low ferritin in 1 of 6 subgroups of children and in 3 of 3 subgroups of women of reproductive age. CONCLUSIONS: . Evidence of the effectiveness of flour fortification for reducing the prevalence of anemia is limited; however, evidence of effectiveness for reducing the prevalence of low ferritin in women is more consistent.

Iron-containing micronutrient supplementation of Chinese women with no or mild anemia during pregnancy improved iron status but did not affect perinatal anemia.

Universal prenatal daily iron-folic acid (IFA) and multiple micronutrient (MM) supplements are recommended to reduce the risk of low birth weight, maternal anemia, and iron deficiency (ID) during pregnancy, but the evidence of their effect on iron status among women with mild or no anemia is limited. The aim of this study was to describe the iron status [serum ferritin (SF), serum soluble transferrin receptor (sTfR), and body iron (BI)] before and after micronutrient supplementation during pregnancy. We examined 834 pregnant women with hemoglobin > 100 g/L at enrollment before 20 wk of gestation and with iron measurement data from a subset of a randomized, double-blind trial in China. Women were randomly assigned to take daily 400 µg of folic acid (FA) (control), FA plus 30 mg of iron, or FA, iron, plus 13 additional MMs provided before 20 wk of gestation to delivery. Venous blood was collected in this subset during study enrollment (before 20 wk of gestation) and 28-32 wk of gestation. We found that, at 28-32 wk of gestation, compared with the FA group, both the IFA and MM groups had significantly lower prevalence of ID regardless of which indicator (SF, sTfR, or BI) was used for defining ID. The prevalence of ID at 28-32 wk of gestation for IFA, MM, and FA were 35.3%, 42.7%, and 59.6% by using low SF, 53.6%, 59.9%, and 69.9% by using high sTfR, and 34.5%, 41.2%, and 59.6% by using low BI, respectively. However, there was no difference in anemia prevalence (hemoglobin < 110 g/L) between FA and IFA or MM groups. We concluded that, compared with FA alone, prenatal IFA and MM supplements provided to women with no or mild anemia improved iron status later during pregnancy but did not affect perinatal anemia. This trial was registered at clinicaltrials.gov as NCT00137744.

Micronutrient supplementation and pregnancy outcomes: double-blind randomized controlled trial in China.

BACKGROUND: Beyond perinatal folic acid supplementation, the need for additional prenatal prophylaxis of iron with or without other micronutrients remains unclear. We aim to investigate the maternal and infant health effects of iron plus folic acid and multiple micronutrient supplements vs folic acid alone when provided to pregnant women with no or mild anemia. METHODS: In this randomized double-blind controlled trial, 18,775 nulliparous pregnant women with mild or no anemia were enrolled from 5 counties of northern China from May 2006 through April 2009. Women were randomly assigned to daily folic acid (400 µg) (control), folic acid-iron (30 mg), or folic acid, iron, and 13 additional vitamins and minerals provided before 20 weeks gestation to delivery. Primary outcome was perinatal mortality. Secondary outcomes included neonatal and infant mortality, preterm delivery, birth weight, birth length, gestational duration, and maternal hemoglobin concentration and anemia. RESULTS: A total of 92.7% of women consumed 80% to 100% of supplements as instructed. On average, women consumed 177 supplements. Compared with daily prenatal folic acid, supplementation with iron-folic acid with or without other micronutrients did not affect the rate of perinatal mortality (8.8, 8.7, and 8.3, respectively) per 1000 births, and relative risks (RRs) were 1.00 (95% CI, 0.68-1.46; P = .99) and 0.94 (95% CI, 0.64-1.39; P = .76), respectively. Risk of other adverse maternal and infant outcomes also did not differ, except that RRs for third-trimester maternal anemia were 0.72 (95% CI, 0.63-0.83; P < .001) and 0.71 (95% CI, 0.62-0.82; P < .001), respectively. CONCLUSION: Prenatal iron-folic acid and other micronutrient supplements provided to Chinese women with no or mild anemia prevented later pregnancy anemia beyond any benefit conferred by folic acid alone but did not affect perinatal mortality or other infant outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00133744.

Hemoglobin and ferritin are currently the most efficient indicators of population response to iron interventions: an analysis of nine randomized controlled trials.

Governments and donor agencies have implemented pilot and large-scale iron fortification programs, but there has been no consensus on the best choice of indicators to monitor population response to these interventions. We analyzed data from 9 randomized iron intervention trials to determine which of the following indicator(s) of iron status show the largest response in a population: hemoglobin (Hb), ferritin, transferrin receptor (TfR), zinc protoporphyrin (ZPP), mean cell volume (MCV), transferrin saturation (TS), and total body-iron store. We expressed the change in each indicator in response to the iron intervention in SD units (SDU) for the intervention group compared with the control group. Ferritin increased by > or =0.2 SDU in all trials and was significant in 7. Hb changed by > or =0.2 SDU in 6 and was significant in 5. TfR increased by > or =0.2 SDU in 5 of 8 interventions in which it was measured and was significant in 4. ZPP increased by > or =0.2 SDU and was significant in 3 of 6 interventions. Excluding Hb, the indicator with the largest change in SDU was ferritin in 4 trials, TS in 2 trials, body-iron store in 2 trials, and TfR in 1. In the 2 cases in which body-iron stores showed the largest change, the change in ferritin was nearly as large. Our results suggest that with currently available technologies, ferritin shows larger and more consistent response to iron interventions than ZPP or TfR. We cannot make confident inference about MCV or TS, which were included in only 4 and 2 trials, respectively. It is possible that the optimal indicator(s) may differ with age, sex, and pregnancy. There were too few trials in each age and sex group to allow us to explore this question.