Journal of Womens Health, Issues and Care ISSN: 2325-9795

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Review Article, J Womens Health Issues Care Vol: 5 Issue: 3

Long-Term Effects of Maternal Nutrition and Childhood Growth on Later Health

Mohammadreza Vafa1,2 and Salma Mahmoodianfard3*
1Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
2Endocrine Research Center (Firouzgar), Institute of Endocrinology and Metabolism (Hemmat Campus), Iran University of Medical Sciences, Iran
3Department of Clinical Nutrition, School of Nutritional Sciences & Dietetics, Tehran University of Medical Sciences, Iran
Corresponding author :Salma Mahmoodianfard
Department of Clinical Nutrition, School of Nutritional Sciences & Dietetics, Tehran University of Medical Sciences, Iran
E-mail: [email protected]
Received: October 02, 2015 Accepted: April 14, 2016 Published: April 18, 2016
Citation: Vafa M, Mahmoodianfard S (2016) Long-Term Effects of Maternal Nutrition and Childhood Growth on Later Health. J Womens Health, Issues Care 5:3. doi:10.4172/2325-9795.1000230


Objectives: This paper reviews the importance of maternal nutrition and weight gain with birthweigh and neonatal/childhood growth, and highlights the r isk of chronic diseases in later life.
Methods: The data was sourced based on the result of original and review articles relating to the life exposures, pregnancy weight gain, birth weight, childhood growth and the risk of chronic diseases in adult life.
Findings: Experimental studies have suggested that both maternal undernutrition and overnutrition are involved in later disease risk. Maternal macronutrient deficiency leads to LBW and subsequently insulin resistance and adiposity in later life. It seems that micronutrient deficiencies contribute to long-term negative effects such as metabolic syndrome and related disorders. As well as fetal life, early infancy, the adiposity rebound period and puberty also account as critical periods for the development of obesity in adulthood.
Conclusion: It is now widely accepted that the risks of adult chronic diseases may have their developmental origins in fetal life. Maternal under-nutrition or over-nutrition affect the infant’s health . Both macro- and micro-nutrients are critical for appropriate pregnancy outcomes. Understanding their precise patho-physiological mechanism are critical to apply new strategies to prevent the adverse effects of maternal dietary restriction and environmental factors in early stages of life.

Keywords: Maternal nutrition; Obesity; LBW; Chronic diseases


Maternal nutrition; Obesity; LBW; Chronic diseases


Low birth weight (LBW) has been defined as weight of less than 2500 grams in a given time period by the World Health Organization (WHO). LBW is closely related to fetal and neonatal mortality and morbidity, growth retardation and cognitive developmental disorders, and greater risk of chronic diseases later in life. More than 20 million LBW infants are born each year in the world, 95.6 percent of them are concentrated in two regions of the developing world: Asia and Africa. Half of all LBW infants are born in South-central Asia [1].
In 1986, Barker et al. [2,3] were the first to published the concept that an adverse intrauterine environment contributed to the onset of the diseases later in life. They reported a correlation between low birth weight and a greater risk of coronary heart disease in later life. Severe inrauterine growth retardation (IUGR) contributes to reduced endocrine pancreatic tissue and dysfunction of β-cells [4,5] which might restrict the function of β-cells in future and lead to the increased incidence of non-insulin-dependent diabetes mellitus. Furthermore, several studies have been mentioned to some of the chronic disorders such as hypertension [6], increasing rate of cardiovascular mortality, insulin resistance, impaired glucose tolerance and type 2 diabetes mellitus as the consequences of IUGR and LBW during the fetal and neonatal life [7]. Also, by increasing birth weight, this trend reduced progressively [8]. Moreover, an association was found between low birth weight and the presence of metabolic syndrome [9]. metabolic syndrome defines as central obesity, plus any two of the following criteria including raised blood pressure, raised fasting plasma glucose, raised triglycerides and reduced high- density lipoprotein (HDL) cholesterol [10].
It is shown that both those born small and those born large have higher incidence of diseases, thus reflecting a U-shaped curve [10]. Several factors affect the duration of gestation and fetal growth and consequently the neonate birthweight. These factors are related to the infant, the mother, or the physical environment and have a major role in prediction of the birthweight and the future health of the newborn. LBW mainly results from poor maternal nutrition before and during pregnancy. Insufficient maternal weight gain is the most important cause of fetal growth retardation [1]. In addition, heavy physical activity during pregnancy may also associated with lower birth weight and pregnancy weight gain [11].
The term Developmental Origins of Adult Health and Diseases (DOHaD) is focused on the relationship between fetal and postnatal growth, and adult metabolic diseases [12]. Studies worldwide have shown a consistent association between low birthweight and diabetes type 2 in adult life that has been corrolated to a programmed response to intrauterine malnutrition [13]. The etiology of type 2 diabetes is multifactorial, including strong contributions from adult obesity and lifestyle as well as genetic factors and would be prevented by reduction of several critical exposures. In a systematic review of 31 studies from different populations , an inverse birth weight-type 2 diabetes associations was found in in 23 populations (9 of which were statistically significant). Populationwide birth weight increasing interventions such as changing maternal nutrition or smoking habits could generally increase birth weight up to 100 g, with larger increases (up to 200 g) in populations with marginal nutrition status. Such interventions could reduce the risk of type 2 diabetes 5% to 10% [14]. Fetal insulin hypothesis proposed that as well as gene variants can cause differences in insulin resistance or secretion in normal population, may also have effects on birth weight through having an impact on insulin-mediated fetal growth. The fetal insulin hypothesis offers an alternative explanation for the consistent association between impaired fetal growth and insulin resistance during life and the link with hypertension and vascular disease [13].
Several studies have reported that early life exposures play a critical role in development of obesity in adult life. Some critical periods including early infancy, 5–7 years of age (the period of adiposity rebound), and adolescence consider to have influence on the development of obesity in later life [15]. In order to prevent obesity, it is necessary to consider both the risk factors and developmental critical periods of obesity (including fetal life, early infancy, the adiposity rebound period and puberty) [16]. Increasing the importance of the life critical periods for promoting of obesity and its outcomes may lead to perform interventions in order to prevent or treat such consequences. Nutrition in the first postnatal weeks of life may play an important role for attenuating the risk associated with fetal overnutrition[17]. Experimental animal studies have concluded that both maternal undernutrition and overnutrition leading to obesity, insulin resistance and diabetes in adult life [18].
The most important mechanisms for explaining the fetal origins of the disease in later life include; hypothalamic pituitary axis alteration, epigenetic regulation of gene expression and oxidative stress which all of these mechanisms may be activated at different stage of gestation and involved in metabolic syndrome development in adult life [12]. The obejective of this paper is to briefly review how maternal nutrition correlates with birthweight and neonatal/childhood growth and risk of later life diseases.


The data was sourced based on the result of original and review articles relating to the life exposures, pregnancy weight gain, birth weight, childhood growth and the risk of chronic diseases in adult life. For this purpose, we mainly used the online database PubMed search engine. The following keywords were searched: “pregnancy”,“Maternal Nutrition”, “Obesity”, “LBW”, “offspring” and “Chronic Diseases” . Then we selected, the relevant free-access full texts and reviewed the suitable articles. We consider appropriate published articles in the English language with no restrictions according to the dates of articles. Our review was included both animal and human studies. Further, we searched manually and considered some of the references of the selected articles to clarify the related topics better. We summerised the information of the some of most important papers in Tables 1 and 2.
Table 1: Results from studies of associations between maternal macronutrients intake and birth outcomes.
Table 2: Results from studies of associations between maternal micronutrients intake and birth outcome.
Underlying mechanisms
The fetal programming hypothesis believes that early events in life contribute to susceptibility to chronic diseases including type 2 diabetes in adult life. Low birth weight results from growth restriction in the uterus which may associate to poorly developed pancreatic β-cell mass and functionality, retardation in development of skeletal muscle, alteration in set point of the hypothalamic-pituitary-adrenal axis, or epigenetic alterations including methylation of DNA [19]. All above mentioned changes may subsequently influence on insulin secretion or insulin resistance. These alterations may overlap with genetic trajectory relating to the onset of type 2 diabetes [20]. Also, presence of the interactions between low birth weight and genetic factors are possible. It has been shown that genetic variants of obesity, which are more linked to insulin resistance, are more regulated by weight at birth than the genetic variants of type 2 diabetes, which are more closely associated to insulin secretion [21]. Epigenetic modifications may consider as a mechanism by which exposure to an alteration of the intrauterine environment or metabolic disorder may affect the organism phenotype in later life. In the IUGR animal model, it has been clearly considered that epigenetic regulation has a critical role in gene expression of β-cells and muscles (Figure 1). Theoretically, the animal model of IUGR could explain the crucial appropriate epigenetic mechanisms of gene regulation in the adipocyte and determine specific epigenetic modifications that concern to the manifestation of adiposity and obesity phenotype [15].
Figure 1: Schematic representation of the relationship between maternal nutrition and predisposition to disease risk.
Excessive reactive oxygen species may result in modulation of gene expression and/or detrimental effects on membrane of the cells and other molecules [10]. Many believe that oxidative stress which accounts as a common factor relating to several disorders, is the primary link between undernutrition and increasing risk of chronic diseases in adult life. Known sources of oxidative stress including smoking, gestational hypertension, inflammation, infection, obesity, and malnutrition are associated with low birth weight [22]. Proteins are needed for antioxidant synthesis, such as glutathione, also some micronutrients such as vitamins A, C, and E are antioxidants [23]. A human study [24] reported significant higher levels of vitamin A, C, and E in term babies compared to preterm ones. Thus preterm babies were more susceptible to oxidative stress. But only neonatal levels of vitamin A and E were dependent on maternal levels. Reactive oxygen species are also detrimental for sensitive pancreatic β-cells due to low levels of enzymatic antioxidant defense [25]. Higher susceptibility of pancreatic β-cells to oxidative stress could contribute to metabolic syndrome and related disorders [22]. Protein and micronutrient deficiency during the fetal development can result in a pro-oxidant state which relating to elevated risks of the metabolic syndrome [23]. Elevation in levels of oxidative stress has been observed in infants born small for gestational age as compared to those appropriate for gestational age [26].
Pre-pregnacy weight, maternal weight gain and obesity in the offspring
Overweight and obese women are more suceptible to several pregnancy cosequences, including gestational diabetes mellitus, hypertension, preeclampsia, cesarean delivery, and postpartum weight retention. Also, fetuses of these women have higher risk of prematurity, stillbirth, congenital anomalies, macrosomia with possible birth injury, and childhood obesity. Furthermore, obese women have difficulty for initiation and maintenance of breastfeeding.
Obesity in pregnancy is associated to an increased maternal and perinatal morbidity and mortality [27]. Maternal over nutrition and obesity and gestational diabetes lead to fetal over nutrition and overgrowth. These conditions have deleterious effects on the offspring including obesity, insulin resistance and type 2 diabetes, metabolic syndrome and cardiovascular diseases [28]. Maternal pre-pregnancy weight and adiposity, and weight gain during pregnancy are contributed to the offspring weight. Studies reported an association between mother’s pre-pregnancy obesity, excessive gestational weight gain, and higher childhood weight and risk of obesity in later life [29].
The institute of medicine (IOM) released a report in 1990, that included BMI-specific weight gain guidelines during pregnancy. The 2009 institute of medicine (IOM) revised report, included new weight gain guidelines for weight gain of obese pregnant women. Average pregnancy weight gain varies by pre-pregnancy weight, with obese women gaining less weight than normal and underweight women [30].
A comprehensive systematic review and meta-analysis [31] indicated that, in comparison with mothers with a normal BMI, pre-pregnancy underweight increased the risk of SGA and LBW. In contrast, pre-pregnancy overweight or obesity increased the risk of large for gestational age, high birth weight, macrosomia, subsequent offspring overweight/obesity in compared to normal BMI mothers.
In a prospective cohort study [32], Oken et al. studied 1,044 mother–child pairs at age 3. In this study, higher gestation weight gain was related to a higher offspring BMI z-score (0.13 units per 5 kg of weight gain). Further, the odds of child obesity (BMI ≥ 95th percentile) increased 4-fold in women with adequate or excessive weight gain during pregnancy (according to the 1990 IOM guidelines) compared to women gaining below the IOM guidelines. In an other study, Olson et al. [33] examined 208 mother–child pairs in rural upstate New York. Overweight women, gaining above IOM guidelines had 2.5-fold elevated odds of child obesity. In obese women, excessive gastation weight gain was related to 6-fold increase in odds of child obesity. In a random sample of 5,125 children at the age of 8, the odds for being overweight/obese was 1.01 (95%CI: 1.00, 1.0) for 1 kg gestational weight gain. Further analysis showed that offspring of women who gain excessive weight above the IOM maternal weight gain guidlines were at an increased risk of obesity (OR: 1.45; 95%CI, 1.26, 1.67) in comparison to offspring of women with gestation weight gain within the recommended range [34]. Oken et al. [35] also examined gestation weight gain and obesity in older children/adolescents aged 9–14 years. They discovered that weight gain above the IOM guidelines was associated with an adjusted odds ratio of 1.42 (95% CI 1.19–1.70) for obesity. But, In this study, maternal pre-pregnancy BMI did not modify the association between GWG and child obesity.
However, it is difficult to measure the effects of confounding variables such as infant feeding practices, lifestyle and behavioral factors in human studies. In animal studies the diet and physical activity can be controlled. The rsults of these studies show that overnutrition during pregnancy and early postnatal life have important long-term effects on the weight and metabolism of the offspring. Overall, the majority of data suggests that gestational weight gain independently leads to childhood obesity [28].
It is discussed in recent IOM workshop that “Obesity begets obesity”. Data from animal and human studies demonstrating that exposure to maternal obesity during prenatal and postnatal period, predispose offspring to early onset metabolic disease and childhood obesity. Studies carried on obese pregnant mothers show that prepregnancy BMI of the mothers, not infant BMI, is associated to higher infant liver fat at 2 months of age. It is explained that, maternal fuels cross the placenta and shift into the fetal liver. It is suggested that this fatty liver trans-generational effect of maternal obesity may be mediated by epigenetic changes in offspring liver cells. Moreover, evidence from breastfeeding mothers show that maternal obesity may increase infant adiposity via epigenetic mechanisms by imposing effects on the infant microbiome. Furthermore, an overview of the role of sperm in early development was discussed. It was described that, sperm deliver many different types of RNA molecules to the oocyte which several of them have indications for paternally induced epigenetic-mediated transgenerational inheritance effects of the paternal nutrition [36].
Academy of Nutrition and Dietetics emphasizes that women of childbearing age should follow a lifestyle promoting health and minimizing risk of birth defects, sub-optimal fetal development, and chronic health problems in both mother and infant. Prepregnancy BMI accounts as an independent predictor of many adverse pregnancy outcomes. Over-nutrition and over-weight during the reproductive cycle are related to short- and long-term maternal health complications, including obesity, diabetes, dyslipidemia, and cardiovascular disease. Receiving excess caloric intake does not guarantee adequqte nutriental status for optimal pregnancy outcomes. In addition to health risks, gestational weight gain higher than the IOM recommendations, increases risk of excess weight retention in obese women at 1 year postpartum [37]. Excessive gestational weight gain may be preventable through the frequency of prenatal visits and encouraging women to make healthful changes in their lifestyle. Such interventions may be helpful to reduce obesity in the next generation, as well as reduce the long-term risk of weight gain in the mother [29].
Birth weight, rapid weight gain and obesity in adult life
There is also increasing evidence of the effects of prenatal stage as well as influence of early life exposures. This period is critical as a time of rapid growth, cellular replication and differentiation, and functional maturation of organ systems. These actions are very sensitive to the alterations of maternal nutrition and metabolic environment. Obesity in pregnancy can lead the promoting of obesity and diabetes in the offspring in long time [15]. Recent estimates of obesity between adults, adolescents, and children in the United States showed that more than one-third of adults and approximately 17% of children and adolescents were obese in 2009–2010 [38]. A crosssectional study that was carried in 2009, reported the prevalence of overweight and obesity among Iranian children aged 7-18 years old, 9.27% and 3.22% respectively [39]. The obesity related conditions such as heart disease and type 2 diabetes account as common causes of morbidity and contribute to a large part of leading cause of preventable deaths and medical costs in the United States. Therefore, in addition to treatment, prevention of obesity has become a global public health priority [40]. Rapid weight gain during early life stages has been contributed to childhood obesity. Childhood obesity often associated with adulthood obesity, especially in children with obese parents [16]. An earlier study [41] showed that the children with obese and overweight parents, especially children of two obese parents, had an increased obesity risk throughout childhood and early adult life and also manifestede a stronger pattern of tracking from childhood to adulthood. Although it has shown in animal models [42,43] that rapid weight gain during early life periods contributes to obesity in adult life, this pattern is uncertain in humans. Stettler et al. [16], in a cohort sttudy, for the first time followed 300 full term African Americans from birth to 20 years of age. They found that rapid rate of weight gain in early infancy (an increase in weight-for-age ≥ 1 SD between birth and 4 month), as catch-up growth, was associated with not only childhood obesity but also with one-third of the obesity at 20 years of age. This study supported this hypothesis that, as well as fetal life, early infancy, the adiposity rebound period and puberty also account as critical periods for the development of obesity in adulthood. This study also suggested a new hypothesis of the life-long outcomes of early growth patterns on obesity and related chronic health complications. Studies have found life lasting alterations in the regulation of appetite centers and in the secretion of insulin in rats who overfed in early infancy periods [42,44]. Childhood obesity is associated to maternal pre-pregnancy weight. It has been shown that, inducing obesity in the rat with an obesogenic diet before pregnancy was correlated to insulin resistance and an abnormal glucose tolerance. Offspring of these pregnant diet-induced obese rats were obese in their later life and had insulin resistance . Maternal obesity induce a trans-generational effect leading to obesity increase in the offspring [28]. Formula feeding infants have shown more rapid rate of weight gain than breastfeeding ones [45] and also have elevated risk of obesity in both childhood and adolescence [46], but no data showed the continuance of this association into adulthood clearly . Rapid rate of weight gain during infancy rather than a causal connection, may also constitute a peattern regarding an early expression reflection of a genetic susceptibility to excessive weight [16]. Data from animal and human studies suggest that, not just maternal over-nutrition but also maternal under-nutrition are related to increasing the risk of childhood obesity and can cause long-term metabolic changes in offspring. These changes are contributed to altered DNA methylation patterns that extend into the early postnatal life. In the future, DNA methylation differences at birth may be used as predictive biomarkers of later adiposity [36].
High birth weight and obesity
Observational studies that found association of higher birth weight with higher achieved BMI, suggested the programing hypothesis of utero determinants of birth weight responsible for elevated risk of obesity later in life. Altered metabolism of maternal glucose and hyperglycemia contribute to excess fetal insulin as a growth hormone for the fetus [47]. So, gestational diabetes mellitus (GDM) mothers would have offsprings with higher birth weights . Moreover, animal studies suggest fetal hyperinsulinemia can cause alteration in hypothalamic neurotransmitters expression which leads to hyperphagia and increased weight of offsprings [48]. Maternal diabetes is associated with higher risk of overweight and obesity in neonates later in life. It seems that this effect is related to intrauterine programming. It is necessary to understand the extent of these longterm effects in order to assess in which groups intervention can promote the next generation health [49].
Gillman et al. [47] conducted a survey on participants of Growing Up Today Study, consists of 7981 girls and 6900 boys, 9 to 14 years of age. They evaluated the independent associations of birth weight and GDM with adolescent BMI and considered the influence of maternal GDM on birth weight. Birth weight showed a direct relationship with risk of overweight 9 to 14 years later. This study, also showed a relationship between GDM and increased risk of overweight in adolescence, but much of this relationship was contributed to the influence of maternal BMI as a counfonder, so a combination of pre/post-natal environmental factors as well as genetic inheritance might be involved. Thus, GDM as a risk factor contributs to obesity in offsprings, but the extent of such causal influence needs further research. Some animal studies has suggested that exposure to overnutrition in the critical rapid growth periods such as fetal or neonatal periods contributes to lasting alteration in body composition including fat mass and hypothalamic neuronal rsponses for appetite regulation in the adult brain.
Majority of women with GDM can be effectively managed by dietary and lifestyle changes and also glucose monitoring alone. These interventions in most women with GDM are relatively noninvasive and have effect on maternal weight gain during pregnancy and neonatal birth weight. However, 7–20% of women can not be successful to achieve adequate glycaemic control only with diet and exercise activity. In these patients, oral hypoglycaemic agents or insulin injection will be effective for controling their gestational diabetes [49].
Intrauterine environment and fuel mediated teratogenesis
The concept of “fuel-mediated teratogenesis” introduced by Norbert Freinkel in 1980, as a causal relationship between exposure to a metabolic damage during fetal development and its long-term postnatal consequences. Evidence from animal models, human clinical research, and epidemiological studies has supported this hypothesis in the previous three decades. It is possible that intrauterine exposure to maternal diabetes could play a role in insreasing risk of obesity and related metabolic consequences in later life. The mechanisms of shared genetic susceptibility, shared postnatal lifestyles, and specific intrauterine effects of fetal overnutrition have been suggested as explanations for these associations [17]. The exact mechanism how overnutrition during intrauterine period contributes to increased risk of obesity and related metabolic consequences is currently uncertain. Exposure of fetus to a diabetic intrauterine environment contribute to excessive growth. While maternal glucose would transport easily to the fetus across the placenta, maternal insulin could not [30]. An unsuitable intrauterine environment has consequences for diseases in the offspring in later life. Genetic potential of the fetus determine the fetal growth and development. However, environmental factors exert stimulatory or inhibitory effects on the genetically predetermined growth and development pattern. These alterations in fetal growth and development may have consequences in offspring life in the future. Developmental programming which is a process related to intrauterine and early postnatal life can induce a permanent response in the fetus and newborn. These responses enhanced susceptibility of diseases later in life [28]. Intrauterine environment alterations exert some effects on fetal growth and development. In most diabetic pregnant women with no vasculopathy complication, hyperinsulinemia and macrosomia appear in fetus. Fetal B cells are hyperactive for insulin producing. Peripheral vasculopathy and nephropathy are in association with intrauterine growth restriction and hypoinsulinism are common findings. Data from human and animal studies have clearly shown that fetal hyperinsulinemia is associated to loss of capacity for insulin secretion in later life. If offspring become obese, insulin resistance also worsen the condition. These effects are transgenerational. It is imprtant to give special attention to fetal growth in the care of the diabetic pregnant woman [28]. In diabetes women, it is critical to maintain precise glycemic control during pregnancy through diet or drug therapy. Intensive glycemic control of women with GDM lead to reduced weight gain during pregnancy and lower incidence of macrosomia and fetal overgrowth [50]. Enzi et al. [51] reported that the infants of controlled diabetes mothers with normal birthweight did not showed increase in fat mass by the 1 year of age. They found that intrauterine overnutrition, such as it happens with maternal diabetes, does not have long-lasting effects on adiposity if the birthweight is normal and infant overfeeding early in life is prevented.
However, It is currently uncertain whether strict glycemic control and reducing excessive weight gain during pregnancy would attenuate the increased risks of obesity and diabetes in the neonates of GDM women later in life.
Relationship between breastfeeding and obesity in childhood
Breast-feeding has shown protective effects on the risk of obesity in long-term. So, it considers as an important preventive strategy due to considerable public health benefits [17]. Earlier studies [46,52] have reported a protective effects of breast-feeding on risk of overweight and lower prevalence of overweight among adolescents, an effect that became more apparent by increasing the duration and exclusive breast-feeding. Finding of these studies also were controlled for maternal overweight and diabetes during pregnancy. American Academy of Pediatrics recommends encouraging breastfeeding through the first year of life. It is possible that breast-feeding may offer an opportunity to break the cycle of overweight and diabetes that occurs among offspring of diabetic mothers [17]. In a cross-sectional study in Tehran, Iran, [53] the introduction time of complementary feeding (CF) showed a significant inverse association with childhood BMI (aged 7 years). Children with the timing of introduction of CF at >4-6 months and >6 months had significantly lower BMI than children having early CF timing (≤ 4 months). Breastfed children had lower prevalence of being overweight than formula or mixed-fed children but this trend was not statistically significant. In an other cross-sectional study that was conducted on the students aged 6-14 years in Sao Paulo [54] the children that had never been breastfed showed twice higher risk of obesity compared to other children, but no dose-response effect of duration of breastfeeding was seen on the prevalence of obesity in children. There is evidence that the correlation between BF and BMI may vary with age. Some studies [55-57] has shown that the inverse correlation between breastfeeding and BMI at the 1 year of age reduced at the 7 years of age or even vanished in later childhood or adul life. Thus, it seems that genetic and environmental factors including; dietary patterns, socioeconomic status, and parental characteristics, diminish or undo the preventive effects of breastfeeding on childhood BMI after 1 year of age [53].
Birth weight and type 2 diabetes
Barkersʼ hypothesis has been noted in associations of many diseases including the relationship between low birth weight and type 2 diabetes in adult life [10]. In most of the populations examined, birth weight was inversely associated to risk of type 2 diabetes later in life [58]. These associations were independent of adjusting for adult body size or socioeconomic status. Data has shown that per 1-kg increase in birth weight the reduction of type 2 diabetes risk would be about one-fifth. Numerous human cohort studies have also established that birth weight was inversely related to type 2 diabetes later in life and this association would be strengthened after adjusting for BMI in adulthood [14]. Despite all these associations that has been seen in human and animal studies, the underlying cause is still unknown . Fetal insulin hypothesis has proposed that the association between low birthweight and insulin resistance in adultlife is mainly due to genetic. Genetically determined insulin resistance is related to low utero growth of fetal mediated by insulin. Fetal insulin hypothesis researchers have proposed that low birth weight, insulin resistance in adult life, glucose intolerance and diabetes all may be phenotypes of the same insulin-resistant genotype. The main concept of this fetal insulin hypothesis is that fetal genetic factors influenced on the growth of fetal, mediated by insulin that contribute to the regulation of either fetal insulin secretion or the sensitivity of fetal tissues to the insulin effects [13]. Some studies concluded that prevalent variants in the genome of human are related to the development of type 2 diabetes. These genetic variants may influenc on β-cell function or insulin resistance and thus associated to the risk of diseases. Studies showed that some risk alleles of type 2 diabetes are related to reduced while some others are related to increased birth weight . Those results suggest that both genetic variants and birth weight may affect the disease risk via different mechanisms. Thus, it is proposed that the interaction of these two risk factors would determine risk of type 2 diabetes [19]. There are studies from high-income countries that shown the association of rapid weight gain in early childhood or adult life with an increment in incidence of DM and insulin resistance [59]. A cohort study [60] that examined the corrolation of birth weight and gaining weight in infancy and early childhood and risk of type 2 diabetes in five low and middle income count ries also showed low birth weight and acceleration of gaining weigh after 48 month as predictable risk factors of glucose intolerance. Further, gaining weigh between 0 and 24 month reported as a predictor of higher insulin resistance in adultlife. Hales et al. [8] also reported that fetal undernutrition might play an important role in the etiology of type 2 diabetes. The association between birth weight and risk of type 2 diabetes has been examined in a large number of studies [14]. Studies has shown that intrauterine exposure to environmental stress including malnutrition is related to increased risk of type 2 diabetes in adult life [8], which may contribute to fundamental alterations of poor developed pancreatic β-cell mass and function [61] or insulin resistance [62]. As prevalence of adult over-weight and obesity in many countries is increasing, the risks of type 2 diabetes and prevalence of abnormal glucose tolerance during gestation would increase. Both GDM and minor degrees of hyperglycemia contribute to higher birth weight and increasing risk of type 2 diabetes in offsprings.
In some populations with higher prevalence of maternal diabetes, obesity and type 2 diabetes, a strong positive U-shaped association of birth weight with type 2 diabetes has seen and it seems that this common pattern is increasing. It has been suggested that high, rather than low, birth weight could also play an important increasing role on the risk of type 2 diabetes risk in future [14].
Birthweight and hypertention
Alteration in circulating glucocorticoids may contribute to early programming of disease in adulthood. Several studies have suggested that reduced fetal growth leads to a longlasting effects on the set-point of the hypothalamic-pituitary-adrenal (HPA) axis [10]. Exposure to a diversity of stressors such as specific nutrient restriction in pregnant animal models, contribute to an increase in secretion of basal or stress-induced glucocorticoids in the neonates. Thus, exposure to stressors during pregnancy subsequently results in excessive fetal exposure to glucocorticoids leading persistent alterations in the activity of HPA axis [63]. Animal Studies have shown that maternal exposure to administered steroids throughout gestation, specially at certain developmental stages can reduce offspring birth weight and result hypertension in adult life [64]. Another animal study showed that severe gestational undernutrishment can change the HPA axis function of offspring in adult life, including an incresae in response of adrenocorticotropic hormone (ACTH) [65]. Philips et al. [66] in a study of over 300 men from 3 populations found that low birth weight predicts elevated plasma cortisol concentrations in adults and concluded that low birth weigh may contribute to elevated HPA axis activity and higher blood pressure later in life. A human epidemiological study, also showed significant correlation between elevated levels of cortisol and higher blood pressure, plasma glucose levels and insulin resistance. The investigators found that independence of age and body mass index of adults, plasma cortisol levels decline dramatically with increasing birth weight, suggesting that the probable mechanism explaining the correlation of low birth weight and the metabolic syndrome in adult life, is the HPA axis programming [67].
Maternal malnutrition and risk of diseases
A number of epidemiological and experimental studies have discussed the importance of nutrition status in fetal and early infant period and the development of metabolic disorders later in life [12]. Maternal nutrition before and during pregnancy is responsible for healthy outcomes of pregnancy [68]. It is essenitial to provide adequate nutrient supply during pregnancy and lactation in order to support the growth and development of fetal or infant [69]. Maternal malnutrition is an important determinant of poor fetal growth, low birth weight and in short- and long-term is a leading cause of infant morbidity and mortality and contribute to long-term, inalterable and damaging cognitive, motor and health impairments. Poor socioeconomic and nutritional status of the mother during pregnancy has been associated with damaging pregnancy outcomes [68]. Maternal Macronutrient deficiency; protein and carbohydrates, leads to lower birth of weight, a marker relating to fetal growth and subsequently insulin resistance, glucose intolerance, hypertension and adiposity in later in life [12]. Both macro- and micronutrients are critical for appropriate pregnancy outcomes as well as growth of the fetus. While the macronutrients are involved in providing enough energy and proteins for fetal growth, micronutrients are essential for the appropriate macronutrients metabolism, structural and cellular metabolism of the fetus [69]. Worldwide micronutrient deficiency prevalence is estimated to be in around 2 billion people [70] but the long-term effects of micronutrient deficiency during gestation and their consequences on offspring health has not been well established. Data on the importance of micronutrients in developmental origin of adult diseases are also limited. Several of the micronutrients play critical role in fetal growth, so they might be associated with susceptibility to the development of adult diseases [12]. Restriction of multiple vitamins in experimental animals led to increased body fat %, reduced lean body mass, elevation in expression of adiposity related genes, alteration in function of adipose tissue and lipid metabolism in offspring which may implicate the role of vitamins in developmental origins of diseases in adult life [71]. Although there is some evidance of the important role of epigenetic in regulation of adiposity by maternal macronutrient restriction, the role of epigenetics in maternal micronutrient deficiency in predisposing adiposity has not been investigated yet. It seems that micronutrient deficiency may contribute to long lasting effects such as metabolic syndrome and related diseases [69]. This section will review the association between maternal nutrition and birth outcomes (Tables 1 and 2).

Maternal Macronutrient Malnutrition

Maternal calorie restriction
Pre-pregnancy weight and gestational weight gain both have effects on fetal growth. Pregnant women with current or past anorexia nervosa or bulimia nervosa show poorer obstetric consequences. In mothers with eating disorders, low pre-pregnancy BMI is related to higher risk of having a low birth weight infant. Women who attend fertility clinics have higher risk of eating disorders. Treatment of these woman can help them conceive even with low BMI. Although, pregnancy is contributed to symptom reduction or remission of pre-existing eating disorders, new onset of eating disorders may occur. Pregnant women with eating disorders show eating behaviour alteration including undernutrition and/or bingeing, purging and restriction. Low pre-pregnancy body weight is related to increased risk of poor obstetric outcomes. Both pre-pregnancy weight and gestational weight gain exert effects on foetal growth. Maternal eating disorders increase the risk of having a neonate with LBW. Since women with eating disorders feed their offspring in different ways, some of these deletrious effects may continue postpartum [72].
Data from famine studies [68] carried out during the World War II reported that maternal malnutrition associated with birth outcomes. During the Dutch famine in 1944–45 that lasted 6 months, the food intake of mothers was significantly decreased as low as 590 calories a day. This calorie restriction led to average 2.5 kg maternal weight loss compared to pre-famine levels. Maternal weigh loss resulted in major (approximately 300 g) reductions in mean birthweight at the height of the famine. Offspring birthweight was affected the most if maternal exposure to famine was during the latter stages of gestation and there was little difference between the mothers who exposed to the famine only during the third trimester and those exposed during both the second and the third trimesters [73]. Those exposed to the famine in utero, showed an average of 8 kg higher weight in adulthood than those not exposed. Early maternal exposure to famine was related to higher rate of adult obesity and heart diseases. Prenatal exposure to famine, especially during the late gestation, was associated to alteration in insulin-glucose metabolism and impaired glucose tolerance in adult offspring [72].
During the height of exposure to intrauterine famine, the risk of perinatal mortality increased sixfold. Prolonged malnutrition until weaning was associated with decreased β-cell development in rat offspring which was not fully restored by subsequent renutrition [74]. In a rat model, offspring from undernurished mothers were significantly smaller at birth than control group. Maternal calorie restriction also led to increased systolic blood pressure and a significant increase in fasting plasma insulin [75]. An other study that exposed pregnant rats to food restriction to produce IUGR newborns suggested that timing of IUGR newborn catch-up growth may determine the programming of offspring obesity [76].
Studies relating maternal protein restriction and birth outcome are largely besed on rodent models. Maternal low protein diet during gestation and lactation was associated to offspring growth retardation [12]. Low protein diet during gestation and lactation have been shown to result in impaired pancreatic development and reducing β-cell mass and consequently reduced insulin secretion later in life [77]. Protein restriction was also associated to insulin resistance, hyperinsulinemia and reduced insulin-signaling protein expression [12]. Weanling rats exposed to protein restriction in utero weighed less and had increased serum glucose, serum triglycerides, and hepatic triglyceride concentrations. Furthermore, low protein diet could result in increased hepatic gene expression of enzymes favoring fat synthesis in offspring which may be in consistent with the increased triglyceride concentrations. Such increase may predispose the offspring to accumulation of fat and insulin resistance later in life [78]. Exposure to a maternal protein restriction in rat offspring was associated to a preference for high fat foods consumption which suggested that low protein diet may be associated with food preference programming. This study suggested that maternal undernutrition may involve the offspring by controlling the appetite pathways or the perception of palatability [79]. Maternal protein restriction, also causes small neonate with reduced numbers of nephorons which may predispose the offspring to hypertention development in adult life. This reduction in number of nephrons account as an immediate adaptation in order to conserve energy and resource but it has no advantages in long-time [80]. Consumption of a low protein diet during pregnancy and later catch-up growth in early childhood in rats caused alteration in adipocytes and impairment in expression of insulin-signalling proteins which may be involved in predisposing insulin resistance and metabolic diseses later in life [81].
Few studies have investigated the importance of protein restriction on diseases susceptabolity in adult life. A study in Scotland [82] investigated that how the relationship between maternal protein intake and the offspring’s blood pressure 40 years later is complex. This study concluded that maternal intakes of animal protein and carbohydrate in late pregnancy may affect on the offspring s’ blood pressure in adult life and that was associated with decreased placental growth. When the daily animal protein intake of mothers during pregnancy was lower than 50 g, a higher intake of carbohydrate was associated with higher blood pressure. Inversely, when maternal protein intake was higher than 50 g, a lower carbohydrate diet was associated with higher blood pressure in adult life. Another study [83] assessed maternal 24 h food recall and food frequency of twenty year old young adults. This study showed that lower protein intake during first trimester of pregnancy may increase Carotid Media Intima thickness in twenty- years-old offspring. The result of this study demonstrated this hypothesis that atherosclerosis is the mechanism in the relationship between intrauterine food restriction and vascular disease.
Maternal protein-energy supplementation
Additional energy is essential during pregnancy for the growth and development of the fetus, placenta and different maternal tissues, such as in the uterus, breast and the fat stores [68]. All these process need amino acids for protein accretion. Maternal protein supplementation in order to improve fetal growth and treat IUGR accounts as an attractive therapeutic option, especially in fetal growth failure situation. However, perinatal outcomes was worse when mothersʼ amounts of protein supplementation was higher than mothers who had recieved balanced energy supplementation. It seems that, high protein supplementation is associated with increased risk of small for gestational age, preterm delivery and fetal death [84] although the mechanisms responsible for explaining this are uncertain and future investigations must be carried out to support this observation. But it is obvious that providing supplemental dietary protein to pregnant women who are at risk for bearing an IUGR infant, would promote growth of the fetus. Moreover, it was found that decreased fetal growth during protein malnutrition is not related only to protein restriction and other confounding variables such as micronutrient deficiencies and the environmental factors are involved [85]. However maternal calori malnutrition is obviously related to IUGR. The findings of a review study on energy and protein intake in pregnancy suggested thet nutritional advice to pregnant women and balanced energy/protein supplementation appears to be effective and may reduce the risk of fetal and neonatal death but that high-protein or balanced-protin supplementation alone is not beneficial and may be detrimental to the fetal growth [86].
Due to all mentioned above, it seems that providing a balanced protein-energy supplemented diet especially to undernourished pregnant women, is a suitable preventive option in order to decrease the rate of IUGR and its later consequences.
Observation from animal studies showed that dietary sugar intake during pregnancy can affect pregnancy outcomes. Since puberty is a period associated with hyperinsulinemia and insulin resistance and also increasing blood pressure , consuming a high sugar diet may impose adverse effects especially on pregnant adolscents. In a study that carried out to determine the relationship between adolescent pregnancy outcomes and dietary sugar intake, the authors reported that the pregnant adolscents who were consuming high sugar diets showed twofold higher risk of delivering small for gestational age infants [87]. Both animal and human studies showed that intrauterine exposure to high sugar diets and/or hyperglycemia could increase the risk of the metabolic syndrome [10]. Exposure to a sucroserich diet (70% calories as sucrose) in early stage of life starting 1 wk before breeding, during pregnancy, at birth, and after weaning of the offspring led to long-time postnatal matabolic responses including higher adiposity and a significant increase in triglyceride liver content together with unfavorable alteration in LDL concentrations in offspring. On the contrary, an increase was found in insulin sensitivity of skeletal muscle together with higher concentrations of adiponectin in offspring of the sucrose-fed mothers in comparison to control group [88].
High intake of dietary fat, especially of SFA, is associated with an elevation in cardiovascular disease risk. A few animal studies suggested that high consumption of fat during gestation may predispose the appearance of the metabolic syndrome in offspring in adult life; Moreover, population studies have shown that different kinds of dietary fats impose different affects on cardiovascular health; a high intake of saturated fatty acids (SFA) have detrimental effects, conversely polyunsaturated fatty acids (PUFA) show protective effects . The data from an animal study suggested that high maternal fat consumption during pregnancy lead to lipid metabolism alteration and hypercholesterolemia in adult offspring. Although, it was seen that the offspring’s own diet was also critical for maintaining the regulation of lipid metabolism [89]. An other study reported hyperphagia, adiposity, hypertension and insulin resistance in offspring of obese mice that had exposed to a high fat diet throughout pregnancy and lactation compared with offspring of control dams [90]. Perinatal exposure to a high fat diet in mice was related to programing of deleterious response to a high fat diet and more susceptibility to development of metabolic syndrome later in life after being reexposed to the high fat diet despite recieving a standard diet after weaning [91]. Another study in rats, [92] showed that exposure to maternal high fat intake during pregnancy was associated with a decreased liver mtDNA copy number, abnormal liver and abdominal fat accumulation. Also, a significant reduction in liver abundance of Ppargc1a mRNA was found which inversely was correlated to insulin resistance in adult life. Detrimental effects of high fat diet result from higher oxidative stress due to an imbalance between oxidants/antioxidants status. Human observational studies have also demonstrated the relation between recieving a high fat diet during pregnancy and birth consequences as well as offspring health in adult life [10]. A case-control study reported that consumption of a diet rich in fat but poor in several dietary factors such as vegetables and fruits, milk and dairy products may be associated to higher risk of spontaneous abortion [93]. Another study showed that total calorie per day, intake of dietary fat and SFA was higher and intake of PUFA was lower in GDM women compared with normal pregnant women [94].

Maternal Micro-nutrient Deficiency

Maternal intak of micronutrients are related to fetal exposure to glucocorticoids. The importance of early life stages of the micronutrient deficiency in association with adult diseases have been investigated only in few human studies [10]. Dietary maternal restriction of copper, zinc, and vitamin E in a mouse model exhibited a reduction in the activity of placental 11β-hydroxysteroiddehyd rogenase-2, an enzyme that contributes to protection of fetus from overexposure to maternal glucocorticoids [95]. As discussed before, fetal overexposure to glucocorticoids is related to smaller size of newborn, insulin resistance and hypertension later in life. Signiicant reduction has seen in newborn body weight, increased blood pressure and insulin levels in offspring exposed to the micronutrient restricted diet in comparison to those exposed to a control diet [10]. Some of the micronutrients contributing to the the fetal programming, have been reviewed below.
Vitamin D and vitamin A deficiency
Some evidence showed that the rate of body fat accumulation accelerates during neonatal period which might be in association with insulin resistance [69]. It seems that vitamin D deficiency during pregnancy may be related to increased risk of preeclampsia, insulin resistance and gestational diabetes mellitus. Also, evidance suggest that vitamin D sufficiency is important for fetal development [96]. Maternal vitamin D deficiency was associated with lower myofibrillar protein and thus retardation in metabolic and contractile development of heart in rat offspring [97], but human studies could not find any effect of maternal vitamin D status on the child’s body size or the function of cardiovascular system [98]. Vitamin D deficiency was inversely contributed to anthropometric indicators of adiposity in school-age children and adiposity was prevalent among vitamin D deficient adolescents [69]. Randomised trials showed little evidence regarding the effect of vitamin D supplementation during pregnancy on fetal or infant health consequences. Meta-analysis of trials suggested protective effects of supplementation on reducing the risk of low birthweight and non-significant protective effects of daily supplementation on small-for-gestational age [99].
Animal models have also shown the development of hypertension in adult life exposed to Vitamin A deficiency in utero. Mild vitamin A deficiency in the rat utero led to inherent deficiency in nephron numbers which may predispose to hypertention consequences [12]. Marginal maternal vitamin A deficiency of rats reduced β-cell mass in fetus that may cause glucose intolerance in adult life [100]. Humans studies did not report conclusive evidence. A study in a rural in South Asia with a high incidence of LBW and preterm birth showed that vitamin A or β-carotene supplementation to mothers could not not affect these consequences. Also, in a study in Nepal, maternal vitamin A supplementation during pregnancy did not affect on blood pressure in pre-adolescent children [12].
Vitamin B12 and folate deficiency
Vitamin B12 and folate are essential nutrients involved in synthesis of nucleic acid, DNA methy lation and growth and differentiation of the cells [18]. A study which assessed 30 weeks of gestation in Asian Indians, found that low vitamin B12 concentrations during pregnancy was associated with GDM, increased adiposity and insulin resistance, especially if the concentrations of folate was high. This study suggested that the status of vitamin B12 might be a predictor of obesity and type 2 diabetes mellitus [101]. Maternal GDM considered as an important factor in prediction of the children’s adiposity and insulin resistance at 9.5 years of age [102]. Also, an Indian birth cohort study showed that lower maternal vitamin B12 and higher folate concentrations during pregnancy were correlated with higher rate of insulin resistance in offsprings as well as higher maternal homocysteine concentrations were inreversly associated with offsprings birthweight [103]. But, in another cohort study of urban Indian children [18], no correlation of maternal vitamin B12 concentration with newborn size or with insulin resistance and other cardiometabolic risk markers were found, although higher insulin resistance at 9.5 and 13.5 years was shown in children with higher maternal folate concentration. The importance of maternal folate for the prevention of neural tube defects is well known [18]. In the observational studies conducted in UK, dietary folate intakes of mothers were associated with higher bone mineral content in their children [104], in consistence with these results, some other studies showed higher bone mineral content and density, better cognitive function and taller height in children of mothers with higher folate status in pregnancy [105,106].
Iron deficiency
Young obese women have reduced iron absorption and iron deficiency is more common in obese children with a reduced response to iron fortification [107]. Thus, rapid increasing rate of over-weight seen in countries in transition may impair the programs in association to control micronutrient deficiency in these target groups [69]. It has found in adult offspring of guinea pigs that moderate maternal iron deficiency during pregnancy and lactating period can cause altered brain fatty acid and eicosanoid metabolism [108]. Studies have reported that maternal dietary iron restriction during pregnancy was associated to fetal growth retardation , reducing birth weight , and offspring lipid metabolism alteration. Also, a study showed that maternal dietary iron restriction during pregnancy modulate hepatic lipid metabolism in the fetuses through an increase in hepatic cholesterol and reduce triglyceride concentrations which were in accordance to genesʼ down regulation involved in the synthesis of bile acid and fatty acids in fetuses. Moreover, iron deficiency in early stages of life caused permanent alteration in brain biochemistry and irreversible developmental consequences. It seems that maternal micronutrient restriction both affects on adipose tissue and different organs such as liver and brain [69]. Perinatal iron deficiency (PID) will be common in developing countries which can also predispose to adult chronic diseases. PID in rodents (before and during pregnancy) was associated with higher blood pressure in comparison to controls were fed an iron enriched diet. This study confirmed that PID adversely affects blood pressure control, which might be in accordance with altered intrarenal hemodynamic properties [109]. In an other study by Bourque et al. [110], rats feeding iron deficient diet combined with a high-fat diet during pregnancy caused adiposity and higher mean arterial pressure in rats offspring.
Zinc deficiency
Zinc has a critical role in growth, development and reproduction and zinc deficiency during gestation and lactation could negatively affect animal models, including congenital malformations, fetal death and intrauterine growth retardation [69]. Studies in rats found that maternal dietary zinc restriction during intrauterine and postnatal growth periods can cause an increase in arterial blood pressure and renal lesions in adult life. These studies showed that zinc deiciency in early stages of life caused reduced glomerular filtration rate which was in accordance with a reduction in the number and size of nephrons. These studies also reported proteinuria, higher lipid peroxidation end products, and increased renal apoptosis and fibrosis manifestations in animal models [111,112]. Some other studies found that zincdeficient rats had impaired lipid intestinal absorption and maternal restriction of zinc was associated with decreased cholesterol and triglycerides in rat offspring [69].
Maternal calcium intake
The positive effects of calcium intake on blood pressure may start in utero [113]. An animal study [114] also reported that deficient maternal calcium intake during pregnancy could elevate blood pressure of the rat offspring later in adult life. Calcium restriction in rats led to an increase in body fat and insulin resistance of the offsprings [115]. A cross sectional study was performed on nutritional status of five hundred healthy pregnant women in Zahedan city of Iran. This study reported that maternal calcium intake in the third trimester were significantly correlated with birth weight of neonates [116]. A review study evaluated the preventive effect of calcium supplementation during pregnancy on pregnancy outcomes. The result of this study confirmed the efficacy of calcium supplementation in reducing gestational hypertensive disorders, preterm birth and an increase in birthweight in populations with low calcium intake [117]. However, no benefits was seen by consumption of dietary calcium much higher than recommended levels [113].

Healthy Lifestyle Changes to Optimize Pregnancy Outcomes

Obese women should be aware of the associated fetal risks, including prematurity, stillbirth, congenital abnormalities like neural tube defects, macrosomia, and higher risk of obesity during childhood and adolescence. Thus, obese women should encourage to undertake a preconception weight-reduction program. Weight and height should be recorded for all women at the prenatal visit and BMI should be calculted. Appropriate weight gain should be considered based on IOM recommendations at the initial visit and periodically throughout pregnancy. Nutrition and exercise counseling should be offered to all overweight or obese women preconception, during pregnancy, postpartum and before attempting another pregnancy [27]. Individualized care and clinical judgment are necessary in the management of the overweight or obese woman who is gaining (or wishes to gain) less weight than recommended but has an appropriately growing fetus. Balancing the risks of fetal growth (in the large-for-gestational-age fetus and the small-for-gestational-age fetus), obstetric complications, and maternal weight retention is essential but will remain challenging until research provides evidence to further refine the recommendations for gestational weight gain, especially among women with high degrees of obesity [118]. In a prospective multicenter study on more than 16000 obese women with prepregnancy BMI between 30 to 39.9, the risk of gestational diabetes, gestational hypertension, preeclampsia, and fetal macrosomia, was higher in obese mothers in comparison to mothers with a BMI of less than 30. Similarly, other studies have showed thet obesity is associated with higher rates of preeclampsia, gestational diabetes mellitus, and cesarean delivery compared to having normal prepregnancy BMI [27].
Evidence showes that maternal diet and lifestyle affect the health of the child later in life. Following a healthful dietary patterns before pregnancy, including the alternate Mediterranean Diet, Dietary Approaches to Stop Hypertension (DASH), and alternate Healthy Eating Index, have been contributed to a lower risk of GDM between 24% to 46%. Eating a variety of foods and consuming sufficient calories help pregnant women to meet nutrient needs and provide ranges of recommended weight gain. Population-based research date showes that maternal weight gain beyond the recommended range is associated with increased risk to maternal and child health [37].
As recommended in the Royal College of Obstetricians and Gynaecologists (RCOG) Statement “Exercise in Pregnancy” [119], exercise seems to be safe for both mother and fetus during pregnancy and women should be encouraged to initiate an exercise program or maintain their fitness levels. RCOG recommends pregnant women to engage in 30 minutes of aerobic activity per day. It is equal to 210 minutes or three and a half hours per week [120].
Before advising exercise to pregnant women, it is necessary to consider fitness status, current exercise activities and individual goals of exercise. Careful attention should be paid to the type and intensity of exercise, similarly to the duration and frequency of exercise sessions in order to make a balace between potential benefits and harmful effects. Most guidelines recommend a maximal heart rate of 60–70% for women with prepregnancy sedentary activity and the upper range of 60–90% of maximal heart rate for women tend to sustain their fitness during pregnancy. Maternal physical activity affects on pregnant women s’ overall health during pregnancy [37].
Exercise improves glycaemic control in women with GDM and may prevent developing of gestational diabetes [120]. Following a moderately intense activity does not increase risk of LBW, preterm delivery, or miscarriage in a low-risk pregnancy. Having a recreational moderate and vigorous physical activity during pregnancy is considered to be beneficial to decrease risk of hyperglycemia, in particular in women of normal prepregnant BMI. It has been shown that prenatal nutrition and exercise program, regardless of the intensity of the exercise will cause reduction in excessive gestational weight gain and decrease weight retention at 2 months after delivery among women with prepregnancy BMI less than 25 [37].


Fetal programming of certain chronic diseases in adult life, is now strongely accepted. Rapid weight gain during early stages of life has been associated to childhood obesity which often is contributed to obesity in adult life. DOHaD imply the relationship between fetal and postnatal growth, and metabolic diseases in adult life. Hypothalamic pituitary axis alteration, epigenetic regulation of gene expression and oxidative stress account as the most important mechanisms relating to the fetal origins of the disease in adult life which all of them may be activated at different stage of gestation and contributed to metabolic syndrome development in adult life. Evidence from studies have shown a consistent relationship between LBW and diabetes type 2 later in life that has been contributed to a programmed response to intrauterine malnutrition. Uterus growth retardation may associate to poorly developed pancreatic β-cell mass and its functionality which may subsequently affect on insulin secretion or insulin resistance. It has been suggested that low birth weight, insulin resistance, glucose intolerance and diabetes in adult life, all may be phenotypes of the same insulin-resistant genotype. Pancreatic β-cells have higher susceptibility to oxidative stress which may contribute to metabolic syndrome and related disorders. Protein and micronutrient deficiency during the fetal development can result in a pro-oxidant state. Further, an alteration in the set point of the hypothalamic - pituitary -adrenal axis is possible in LBW infants which contributes to excessive fetal exposure to glucocorticoids, leading persistent alterations in the activity of HPA axis. A significant correlation have found between elevated levels of cortisol and higher blood pressure, plasma glucose levels and insulin resistance in LBW infants. It seems necessary to apply for interventions in order to increase birth weight including changing maternal nutrition that could generally increase birth weight especially in populations with marginal nutrition status. Several studies have reported that early life exposures may play a critical role in development of obesity and its consequences in adulthood. In populations with higher prevalence of maternal diabetes, obesity and type 2 diabetes, a strong positive U-shaped association has seen between birth weight and type 2 diabetes and it seems that this common pattern is increasing. Understanding the importance of the life critical periods may lead to perform interventions in order to prevent such consequences.
Both animal experiments and epidemiological studies have showed that protein and calorie restriction during pregnancy contribute with development of metabolic diseases in adulthood.
Maternal macronutrient deficiency leads to lower birth of weight and subsequently insulin resistance, glucose intolerance, hypertension and adiposity in later in life. In contrast, consuming diets high in fat and sugar during pregnancy are showed to be related to increasing risk of metabolic syndrom. Evidance of the role of maternal micronutrient deficiencies in programming of chronic diseases in adulthood is less clear. It has been suggested that, micronutrient deficiencies are related to long-term negative effects such as metabolic syndrome and related offspring disorders. For instance, it seems that maternal vitamin A & D deficiency contribute to hypertention and impaired glucose tolerance in later life. Moreover, deficiencies of calcium or vitamin B12 during pregnancy were related to higher rate of insulin resistance in offsprings. Maternal restriction of iron consumption was corrolate to lower birth weight of offspring and growth retadtaion. Future studies are necessary in order to determine the exact role of maternal micronutrient deficiencies on early programming of chronic diseases. Understanding their precise patho-physiological mechanism are critical to establish new procedures to prevent the adverse effects of maternal dietary restriction and environmental factors in early stages of life.


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