There were four famine periods in recent past where data were available to assess differential effect of maternal malnutrition. Three of these occur during the Second World War in certain areas of Netherlands (Smith, 1947a,b; Lumey and Stein, 1997), Germany (Dean, 1946) and Leningrad (Antonov, 1947; Koupil et al., 2007) and fourth one in China (Huang et al., 2010b; Song, 2013). The famine during World War II were of relatively short duration causing acute malnutrition in otherwise healthy populations while in China famine was prolonged (3 years) and occurred in a population with high baseline prevalence of chronic malnutrition. There were about 30–50 million deaths during famine in China (Huang et al., 2010b).

During Dutch famine, there was an acute shortage of food and official rations fell as low as 590 calories a day; resulting in maternal weight loss of as much as 2.5 kg from prefamine levels. This resulted in increased incidence of LBW and inflated perinatal mortality. Interesting to note was that the greatest effects on birth weight were among infants conceived before the onset of famine, but delivered during, the famine (Smith, 1947a,b). Maternal undernutrition had the highest impact during second and third trimester of pregnancy, however the infants who were conceived during famine and whose mothers were exposed through the second trimester but then received adequate nutrition during the third trimester, had normal size at birth. Intrauterine exposure was thought to be associated with increased risk of development of hypertension, obesity, and diabetes mellitus in middle age in offspring (Koupil et al., 2007; Huang et al., 2010a; Stein et al., 2006; Hult et al., 2010; Ross and Desai, 2005). Similar observations of adverse effects of acute maternal malnutrition were reported from Leningrad and Germany.

Chinese famine was prolonged and had exposure windows that included prenatal as well as postnatal life and negative effects were reported during adult life (Huang et al., 2010a). A study by Huang et al. (2010b) compared birth size of infants born to who were conceived prior to the famine, during the famine and after the famine, and compared with those of women who were never exposed to the famine. Results showed that in rural areas, exposure to famine was associated with increases in offspring weight [71 g, (95% CI 30, 113)], length [0.3 cm, (95% CI 0.0, 0.6 cm)] and BMI [0.1 kg/m², (95% CI 0.0, 0.2)] at birth, compared to those in prefamine and famine cohorts. In urban areas, however, there was no difference in offspring birth size. The authors proposed that markedly increased mortality in rural areas may have resulted in the selection of hardier mothers with greater growth potential, which becomes expressed in their offspring (Huang et al., 2010b) however other authors speculated that mortality was related to severity of famine and nutritional status of the mother at the time of conception (Song, 2010,  2013).

In summary, acute severe maternal malnutrition may adversely affect the birth weight of the fetus especially when the exposure is during the third trimester of the pregnancy. All together, there is an increase risk of perinatal mortality when there is exposure to intrauterine famine and the risk may be as high as 6 times compared to normal, as seen in Dutch famine (Smith, 1947a,b).

The exact mechanisms, by which maternal obesity adversely affects the health of offspring, are not clear. Several metabolic pathways are likely to influence fetal development and neonatal outcomes and may include altered placental nutrient transport, glucose metabolism, excessive fetal exposure to insulin, and state of inflammation (Poston et al., 2011). In terms of long-term effects, “programming” must include permanent changes in cellular structure or function in the offspring in response to the metabolic consequences of maternal obesity (Poston et al., 2011). This may involve hormone dysregulation, hyperinsulinemia, fat deposit during fetal life, and epigenetic modification of DNA (Zambrano and Nathanielsz, 2013; Zhang et al., 2011; Symonds et al., 2009). The human data in this regard are relatively scarce; however, animal studies had helped explain some of the above listed mechanism (Zambrano and Nathanielsz, 2013). More research is needed to discover the mechanisms in humans and ultimately develop interventions to target these mechanisms to avoid the adverse consequence of maternal obesity.

Four of the ten studies described above showed that MMN had a positive effect on growth outcomes during childhood. Rest of the studies did not show an overall effect for growth; however, some author reported positive effects for those with better compliance and whose mothers were malnourished at the start of the study (Ramakrishnan et al., 2009). Six randomized trial described effect of MMN during pregnancy on neurodevelopment outcomes during childhood (Prado et al., 2012; McGrath et al., 2006; Hanieh et al., 2013; Tofail et al., 2008; Christian et al., 2010; Li et al., 2009) and these studies had mixed results. Some of the studies showed positive effects on neurodevelopment, such as motor and cognitive abilities of children; however, the results were not consistent across the studies (Leung et al., 2011). A recent meta-analysis assessed effect of MMN supplements during pregnancy and its effects on growth during childhood. It included nine trials and showed that antenatal MMN supplementation increased child head circumference (effect size = 0.08, 95% CI: 0.00–0.15) compared with supplementation with two micronutrient or less (Lu et al., 2014). There was no evidence of benefits on weight (P = 0.11), height (P = 0.66), weight-for-age z scores (P = 0.34), height-for-age z scores (P = 0.81), and weight-for-height z scores (P = 0.22). This review however only analyzed continuous data and no categorical outcomes like stunting or underweight were analyzed. MMN supplements may not affect average weight or height but may decrease the prevalence of stunting or underweight. Stewart et al. (2009b) reported data from Nepal for effect of micronutrient supplements on blood pressure, BMI, waist circumference, glycated hemoglobin, cholesterol, triglycerides, glucose, insulin, and the urinary microalbumin:creatinine ratio in children 6–8 years. No combination of micronutrient supplement produced differential effect on blood pressure, cholesterol, triglycerides, glucose, and insulin. There was however a reduced risk of microalbuminuria in the folic acid and folic acid + iron + zinc groups and a reduced risk of metabolic syndrome in the folic acid group. There was no effect of MMN on reduction of obesity in children 6–8 years (Stewart et al., 2009a). Another study from Nepal by Devakumar and coworkers reported data on obesity, blood pressure, and lung function of children whose mothers were supplemented with MMN compared to iron-folate at an average age of 8.5 years (Devakumar et al., 2014,  2015). There was no differential effect on blood pressure, obesity, or lung function (based on spirometry) between the two groups.

Lipid-based nutrient supplements (LNS) include multiple micronutrient (MMN) fortified semisolid pastes usually prepared from vegetable oil, groundnut paste, milk, sugar, and different concentrations of micronutrients depending on the type of product and the specific nutritional conditions in the target population. The existing evidence base on the impact of LNS during pregnancy is limited. When compared to multiple micronutrient supplementations, the provision of LNS to pregnant women in Burkina Faso resulted in higher birth length. Supplemented women were found to have elevated leptin concentrations and could be attributable to the higher neonatal fat mass (Huybregts et al., 2013). However, the positive effect of prenatal LNS on birth length was not sustained during the postnatal phase suggesting lack of long term impact on child linear growth (Lanou et al., 2014).

The study from Bangladesh did not show an overall effect; however, early prenatal food supplementation lead to reduce prevalence of stunting among boys (Khan et al., 2011). The study by Stein et al. from Guatemala showed that children born to women who received the balanced protein energy supplementation were taller (age-adjusted difference: 0.80 cm; 95% CI: 0.16, 1.44 cm), and this effect was more pronounced in boys than in girls. There was a positive effect on neurodevelopment outcomes during childhood as described in three studies (Tofail et al., 2008; Waber et al., 1981; Freeman et al., 1980). A study from Gambia reported effect of balanced protein energy supplementation during pregnancy on blood pressure, body composition, fasting blood glucose, and cholesterol of children aged 11–17 years (Hawkesworth et al., 2009). There was no difference between the two study groups except that fasting blood sugars in protein supplementation group were slightly lower than control. Webb et al. (2005) reported data for protein energy supplementation during pregnancy from Guatemala and showed that there was no differential effect between high versus low energy supplements on blood pressure for adults 21–29 years old. A cohort study from India reported follow up data for offspring aged 13–18 years of mothers who were given balanced protein energy supplements during pregnancy compared to control (Kinra et al., 2008). The results showed that adolescents from intervention villages had more favorable measures of insulin resistance and arterial stiffness: lower HOMA (homoeostasis model assessment) score and lower augmentation index (measure of arterial stiffness). There was no evidence of differences in blood pressures and serum lipids.

It is important to note that there was significant heterogeneity in above-mentioned studies in terms of study site, participants, type and duration of supplements, type of comparison, and combined supplementation for mothers and children. This means that study results may not applicable from one site to the other site. In summary, balanced protein energy supplementation during pregnancy has variable effects on growth and development during childhood and might modify risk of chronic disease during adulthood.

A review evaluating the impact of LCPUFA supplementation during pregnancy on head circumference of newborn suggests that supplementation was associated with significantly greater head circumference of the infants in the intervention group (Deng et al., 2012). However, the difference was no longer significant according to the sensitivity analysis. Another review suggests significantly greater length of pregnancy, increase in head circumference, and a modest increase in birth weight associated with n-3 LCPUFA supplementation during pregnancy for women with low-risk pregnancies (Szajewska et al., 2006; Imhoff-Kunsch et al., 2012).

Existing evidence on the effect of prenatal supplementation of LCPUFAs on long-term growth and development is very limited. An existing review evaluating the effect of n-3 LCPUFAs during the perinatal period on later body composition suggests inconclusive evidence. Two of the included studies in the review showed inverse associations between maternal n-3 LCPUFA intake and children’s later body composition [including lower adiposity, body mass index (BMI) or body weight]; two studies showed direct associations while no effects were observed in the remaining two studies (Rodriguez et al., 2012). Another review suggests no effect of maternal n-3 LCPUFA supplementation during pregnancy and/or lactation on BMI in preschool and school-aged children (Stratakis et al., 2014; Muhlhausler et al., 2010). There is no consistent data on the effect of LCPUFA supplementation during pregnancy and/or lactation on neurodevelopment and visual function in children (Dziechciarz et al., 2010). Most of the existing data on LCPUFA supplementation comes from high-income countries. More studies in low- and middle-income country settings are needed to determine any effect of supplementation in resource-poor settings, where intake is likely to be low. Further studies are required in which the intervention is confined to the perinatal period and that are sufficiently powered.

Preconception iron deficiency anemia is associated with fetal growth restriction and reduced birth weight. (Ronnenberg et al., 2004). There is currently no evidence for long-term effects of iron folate supplementation to the women of reproductive age; however, there is an ongoing study in Vietnam that addresses this question (Nguyen et al., 2012).