In this large randomized MINIMat trial in Bangladesh, children born to mothers receiving an early invitation to food supplementation were less likely to be stunted during the first five years of life. Children born to mothers who received multiple micronutrients rather than the standard iron-folate program, however, had a higher occurrence of stunting during the first five years of life: these effects were primarily in boys.
In MINIMat trial, the interviewers were unaware of the intervention groups and the mothers were unaware of their micronutrient supplement. By design, there was a difference in the number of food supplements of 18,000 kcal (30 packets) between the early and usual invitation groups. Allocation to food and micronutrient supplementation was according to MINIMat protocol, and masking was maintained for the micronutrient supplementation groups until the completion of intention-to-treat analysis. There was no difference among the groups in loss to follow-up, although there were minor differences in the number of capsules consumed across the groups. The pregnant mothers received almost 4 months of daily micronutrient supplements.
Sex differences in fetal growth are reported , but the underlying mechanisms are poorly understood and may reflect both genetic (cell division among male embryos occurs more rapidly than in female embryos ) and environmental factors (boys are often given preference in food allocation within the family in Bangladesh ). These observations suggest males may be more responsive to growth-promoting influences. The differences in stunting persisted until the last follow-up assessment at 54 months. Nevertheless, there was a trend of better linear growth in the infants in the early food group throughout the follow-up until the fifth year of life. The results indicate that early invitation of prenatal food supplementation had a positive effect on post- natal infant/child growth.
Early food supplementation had an effect on early child growth. In Indonesia, maternal nutrition during pregnancy influenced the growth of offspring in early childhood, and high-energy supplementation produced less stunting throughout the first five years . In this study, there were more stunted children in the MMS group than in the iron+folic acid supplementation group. The reason prenatal MMS increased the risk of stunting is unclear, as a non-randomized, non-blinded trial in Vietnam found MMS during pregnancy to be an important intervention for reducing stunting in children . In this Bangladeshi sample, MMS (rather than 30 mg or 60 mg iron) did not appear to benefit child growth, and this could have perinatal causes, such as potential interactions among nutrients producing adverse outcomes . In Indonesian infants , single supplementation with either iron or zinc improved growth, yet combined supplementation with iron and zinc had no effect on child growth or development. Other possible reasons for prenatal MMS to increase the risk of stunting could include low doses of micronutrients (i.e, recommended daily dietary allowance) being insufficient for influencing fetal development ; the effects of the endocrine system on uterine sensitivity on long-term child growth [28, 29]; and post natal causes, such as feeding practices, specifically breast feeding and complementary feeding, and morbidity. In a meta-analysis  comparing MMS with a placebo or no supplementation groups, there were reductions in anemia in pregnant women, low birth weight, and small-for-gestational age, but there was no greater response when MMS was compared to iron+folic acid.
The causes of stunting are complex and involve poor quality diet, breastfeeding practices, long-term burden of infectious disease morbidity, and chronic adverse environmental exposure; these factors are difficult to measure. The biological basis for the effects of multiple micronutrient supplements and the role of specific micronutrients in human biology is a complex mechanism [31, 32]. Multiple micronutrients are needed for gene regulation, embryogenesis, and fetal development, and influence birth and infancy [31, 33]. Thus, adequate availability of many micronutrients and improvement in body storage could affect the physiological and anatomical development of the fetus and be associated with the homoeostasis needed in infants to withstand adversity during birth and early infancy. A deeper understanding of the mechanisms is clearly needed. Thus, amelioration of multiple micronutrient deficiencies in women with insufficient macronutrient intake could enhance physiological, endocrine, or metabolic processes in infants, or optimize the anatomical structures that promote survival without changing total body mass; sufficient macronutrient intake along with improved MMS status could improve body mass, and therefore, survival.
The World Health Organization (WHO) recommends iron and folic acid supplementation to women during pregnancy as part of routine antenatal care. The effect of multiple-micronutrient supplementation with iron and folic acid supplementation was assessed, and we observed no significant added benefit of multiple-micronutrient supplements over iron and folic acid supplementation for post-natal growth. There is a lack published data presenting similar findings of more stunted children in a maternal MMS group than in iron+folic acid supplementation groups. This study was conducted in a low-income country, and further studies in different populations are needed to assess the consistency of the findings. The study was not designed to examine the potential risks of excess micronutrient supplementation or to examine potential adverse interactions between the micronutrients, which need addressing in future studies. As an early start to supplementation during pregnancy is beneficial for early child growth, future food supplementation during pregnancy should be implemented at the beginning of pregnancy. The randomized, double-blind design was a major strength of this study. As a placebo group could not be added due to ethical reasons, it is not appropriate to conclude micronutrient supplementation does not have any beneficial effect on birth outcome or early child growth.
It may be pertinent to ask the effect size of different nutrition interventions that improve child growth, particularly stunting. Our data suggest that early food supplementation during pregnancy had a positive impact on preventing stunting. Effects of nutrition-related interventions on stunting in 36 country analysis showed that nutrition education and counseling of complementary feeding and other supportive strategies could reduce stunting by 19.8% at 12 months, 17.2% at 24 months, and 15.0% at 36 months . In our study, we did not have any interventions on complementary feeding education or counseling. Earlier study done in Matlab in the specific population has shown that the overall rate of stunting was 63% in 2002 . In our study stunting was reduced by 13% (difference: 35.3-30.8 = 4.5 unit, reduce stunting by 12.7%) when food supplementation could start during early stage of pregnancy compare to late start and could be of major public health importance. This study provided evidence of the potential benefit of the government-supported nutrition program even it targeting to women with BMI < 18.5 may be questioned. Community facilitators educate the pregnant women and encourage them to visit the community nutrition centers to obtain the supplements. Due to the novel design of the MINIMat study, and the use of the existing health system supported by non-governmental organizations, the results are relevant for public-health planners and policymakers. In addition, more attention should be given to the issues of optimal delivery vehicles (including supplements, fortified foods), program efficacy and effectiveness, and the target (i.e., whether stunted children should be targeted). For sustainable solutions, efforts should continue to adopt and improve locally available and affordable food-based approaches.