8.1.12 Nutrition and reproduction

Reproductive function is closely related to nutritional status. In the animal kingdom reproduction often takes place when food and climatic conditions are favourable towards optimal nutrition to maximize the survival of the offspring. This is sensible considering pregnancy and lactation are times of greatest nutritional needs in the life of female mammals. In humans, under- and over-nutrition as reflected in body weight and body composition significantly impact fertility. Aside from the mother’s energy status, her micronutrient adequacy throughout the pregnancy and lactation period also influences the development of the offspring.

It has long been known that either nutritional deprivation or excessive body weight are associated with reduced fecundity. Women exposed to the Dutch Famine 1944–45 at the ages of 3–13 had a 1.9-fold increased risk (95% CI 1.3 to 1.8) of having fewer than the desired number of children (1). On the other hand, it was also recognized over half a century ago that 43% of women suffering from menstrual disorders, infertility, or recurrent miscarriages were overweight or obese. The prevalence of anovulatory cycles, irregular menses, hirsutism, and infertility are also higher among obese women compared with normal weight women.

Undernutrition remains a significant public health problem in many developing countries. About 50% of children in India, Bangladesh, and Nepal are malnourished. In subSaharan Africa, more than 30% of children are underweight and 40% are stunted. About 67 million children worldwide weigh less than they should for their height and 183 million weigh less than they should for their age.

In developed countries, undernutrition is more commonly seen among patients with eating disorders or in female athletes. About 1% of young women suffer from bulimia nervosa and 1–5% from anorexia nervosa. Anorexia nervosa is defined as having body weight of less than 85% of expected weight with intense fear of weight gain and distorted body image. Bulimic behaviour patterns include binge eating, purging, excessive exercise or fasting, and excessive concern about bodyweight or shape.

Undernutrition reduces fertility. A European multicentre study found that having BMI under 20 kg/m² is associated with delayed conception, defined as time to pregnancy exceeding 9.5 months of unprotected intercourse. Similarly, the Nurses’ Health Study II found that 12% of ovulatory infertility in the US could be due to underweight (BMI lower than 20 kg/m²) (2). A 10–15% reduction in body weight could result in amenorrhoea. This may explain the higher prevalence of amenorrhoea among anorexia nervosa patients, athletes, or dancers with very low body mass.

The relationship between energy status and reproductive function is mediated via several hypothalamic pathways. The GnRH neurons in the hypothalamus control the secretion of pituitary luteinizing hormone through the pulsatile release of GnRH. The GnRH neurons are very sensitive to energy states. Dynamic changes in energy states resulting from food restriction, temperature changes, or changes in physical activity levels could affect GnRH pulse frequency. When the stressors have been alleviated, GnRH pulsatility resumes its usual state within 1–2 h. Leptin is one of the adiposity signals that relay information on energy state to the hypothalamus. Sufficient level of leptin is essential for ovulation. In women with exercise or anorexia-induced amenorrhoea, leptin administration increases the level and frequency of luteinizing hormone, ovarian volume, number of dominant follicles, and oestradiol levels. However, leptin-signalling pathways in the hypothalamus is not fully understood. Although leptin appears to have a potent effect on GnRH release, GnRH neurons do not express leptin receptors (3). Further studies are needed to elucidate the signalling pathways of leptin in the hypothalamus.

In addition to reducing fecundity, undernutrition may also adversely affect pregnancy outcomes. Low pre-pregnancy BMI (less than 18.5) is associated with increased risk of early miscarriage (Odds ratio 1.72, 95% CI 1.17 to 2.53) after adjusting for year of conception, maternal age, previous miscarriage, and previous livebirth (4). Those with BMI<20 kg/m² are 4 times more likely to have pre-term labour (Odds ratio 3.96, 95% CI 2.61 to 7.09) (1). Underweight women are also more likely to deliver infants with lower birthweight compared with normal weight women (3233 vs. 3516 g) (1). Women with anorexia are at higher risk of caesarean delivery, postnatal complications, and postpartum depression. Women with eating disorders should be in remission prior to conception to ensure optimal maternal and fetal outcomes.

Despite the risks of undernutrition in normal fertility, many studies found that undernutrition does not affect fertility treatment outcomes (5). Livebirth rates and delivery rates do not differ between those who are underweight and those with normal body weight (Box 8.1.12.1).

There are more than 1 billion adults worldwide who are overweight and 300 million are obese. More than half of all adults are overweight or obese in Western countries, such as Australia and USA. Overweight is defined as having a BMI between 25 and 29.9 kg/m², while obese is defined as having a BMI of 30 kg/m² and above. The prevalence of obesity has increased dramatically in developing countries. For example, about one in four adults in China are now overweight or obese. The global epidemic of obesity is likely to be due to changes in dietary patterns towards greater consumption of energy-dense food, and decreased physical activities associated with work, home, transport, or leisure. Obesity contributes significantly to the development of chronic diseases, such as diabetes, cardiovascular diseases, certain types of cancers (e.g. endometrial, ovary, cervix, and postmenopausal breast cancer) and reproductive disorders.

Overweight or obesity reduces fecundity. Twenty-five per cent of ovulatory infertility in the USA could be attributable to overweight or obesity (BMI greater than or equal to 25 kg/m²) (2). Overweight or obesity increases time-to-pregnancy regardless of menstrual regularity, parity, smoking status, and age. Body weight or body composition changes during pubertal period may have an important impact on the development of reproductive system. The onset of obesity during adolescence is associated with increased menstrual irregularities and ovulatory disorders.

PCOS is one of the most common endocrine conditions that affect women of reproductive age (5–8%). More than half of the women with PCOS in Western countries are obese, with most of them having central obesity. The Rotterdam definition of PCOS is the presence of at least two of the following, with the exclusion of abnormal thyroid function, high prolactin, and abnormal adrenal function:

Women with PCOS may be at greater risk of adverse pregnancy outcomes, including increased risk of gestational diabetes, pregnancy-induced hypertension, pre-eclampsia, premature delivery, and higher admission to neonatal intensive unit (6). When fertility treatment are sought, women with PCOS may have higher rate of cycle cancellation, but the pregnancy rates are comparable to normal healthy women (Table 8.1.12.1 and 8.1.12.2)(7).

Obesity is likely to promote hyperandrogenism and PCOS via hyperinsulinaemia, a compensatory response to insulin resistance. An increase in insulin level usually causes a concomitant increase in testosterone or androstenedione levels. The mechanisms underlying the relationship between hyperinsulinaemia and hyperandrogenism are summarized in Box 8.1.12.2.

Obesity increases the risk of complications during pregnancy and delivery. Obese women are more likely to develop hypertensive disorders or gestational diabetes during pregnancy (8). They are also at higher risk of early miscarriage (9). Higher maternal body weight also confers additional risks to the fetus, including increased risk of birth defects and stillbirth (9).

Obesity compromises the success with assisted reproductive technology. Women with BMI of 25 kg/m² and above generally require higher doses of gonadotropin (weighted mean differences 210.08, 95% CI 149.12 to 271.05), at increased risk of miscarriage (odds ratio 1.33, 95% CI 1.06 to 1.68), and have lower chance of pregnancy (odds ratio 0.71, 95% CI 0.62 to 0.81) following IVF (10). There is insufficient evidence to determine the effect of obesity on other fertility treatment outcomes including livebirth, oocyte recovery, and ovarian hyperstimulation syndrome(Tables 8.1.12.3 and 8.1.12.4).

Weight loss through energy restriction, with or without exercise, improves reproductive function in overweight or obese women. In women with PCOS, about half of them had significant improvements in menstrual cyclicity or ovulation following weight loss through lifestyle modification (11). Among those who have lost at least 5% of weight loss, up to 80% experienced improvements in reproductive function (11). Improvement in reproductive function has been observed shortly after energy restriction (2 weeks) before weight loss occurs. This is consistent with the current understanding of reproductive function being influenced by energy balance instead of adiposity.

A number of dietary factors were found to affect ovulatory infertility in a prospective cohort study involving 18 555 premenopausal women (12). Replacing 5% energy intake from animal protein with vegetable protein is associated with more than 50% reduced risk of ovulatory infertility (p = 0.007). Higher dietary glycaemic load is also associated with higher risk of ovulatory infertility (multivariable-adjusted risk ratio 1.92, 95% CI 1.26 to 2.92). The risk of ovulatory infertility is increased when transunsaturated fatty acids is consumed in place of carbohydrate, polyunsaturated fats, or monounsaturated fats. Consumption of iron supplements and other sources of nonhaem iron is associated with decreased risk of ovulatory infertility. The effects of these dietary factors on fertility have not been investigated in intervention trials.

Due to the role of hyperinsulinaemia in anovulatory infertility, insulin-sensitizing agents, such as metformin has been used to improve reproductive functions. A recent systematic review in women with PCOS reported that metformin achieved livebirths comparable with clomiphene citrate in therapy naïve women (relative risks 0.73, 95% CI 0.51 to 1.1) (13). In clomiphene citrate resistant women, the addition of metformin resulted in higher livebirth rates compared with laparoscopic ovarian drilling (relative risks 1.6, 95% CI 1.1 to 2.5). The use of metformin in women receiving IVF also led to fewer cases of ovarian hyperstimulation syndrome (relative risks 0.33, 95% CI 0.13 to 0.8) (13).

A recent review reported that bariatric surgery in women of reproductive age result in improved fertility and reduced risk of pregnancy complications including gestational diabetes, macrosomia, and hypertensive disorders (14). However, these benefits were counterbalanced by increased incidence of intrauterine growth restriction and small-for-gestational-age births. Pregnancies within the first postoperative year are associated with increased risk of miscarriage and preterm delivery. Other operative complications include intestinal obstruction, band migration during pregnancy, and nutritional deficiencies. The nutritional status of young women who underwent bariatric surgery needs to be monitored closely. Preconceptional supplemention of folic acid, vitamin B12, and iron are recommended. Attention should also be given to the status of calcium and fat-soluble vitamins (i.e. vitamin A, D, E, and K) in these women.

Besides body weight and energy status, maternal dietary intakes before conception or during pregnancy could also affect pregnancy outcomes. The section below summarizes the effect of various macronutrients and micronutrients on pregnancy outcomes.

In a meta-analysis involving 3 trials (n = 384), energy restriction during pregnancy in women with high BMI or high gestational weight gain resulted in reduced gestational weight gain compared with control groups with the possible effect of reducing birthweight (15). Considering that macrosomia is one of the risks of maternal obesity, appropriate reduction in birthweight and gestational weight gain may be desirable in women with high BMI or excessive gestational weight gain.

Observational studies suggest that energy intake from protein during pregnancy is positively associated with birthweight, independent of prepregnancy weight or weight gain during pregnancy. However, the effect is modest, with 1% increase in energy derived from protein associated with 16–18 g increase in birthweight. Balanced energy/protein supplementation (<25% energy from protein) increases gestational weight gain (20 g) and birthweight (40 g), while decreasing the incidence of small-for-gestational-age (SGA) births (Relative risk 0.68, 95% CI 0.56 to 0.84) (15). This effect may be more prominent in undernourished women. (15). On the other hand, energy/protein restriction is associated with lower gestational weight gain, but its effect on birth weight was inconsistent.

As opposed to the results of balanced energy/protein supplementation, high protein supplementation (≥25% energy from protein) in African American women at risk of having low birthweight baby results in nonsignificant reduction in birth size and nonsignificant increase in neonatal death (16). Isocaloric protein supplementation (replacing other macronutrients with protein without changing the overall energy intake) was similarly associated with potential adverse effects, with a nonsignificant increase in SGA births (15). It is unclear if high protein supplementation results in a reduction in overall energy intake, as usually seen in high protein ad libitum weight loss trials. Until further research demonstrates the safety of high protein supplementations or dietary pattern during pregnancy, these should be approached with caution for pregnant women.

The glycaemic index (GI) is a measure of the effect of dietary carbohydrate on blood glucose levels. High GI foods cause a greater increase in blood glucose level within 2-h of consumption. Maternal dietary GI may influence birthweight. Women with higher GI diets during pregnancy had higher risks of having large-for-gestational-age (LGA) babies compared with women with lower GI diets (3.1 vs. 33.3%, p < 0.01) in the absence of differences in maternal weight gain and energy intake.

Prepregnancy dietary glycaemic load and dietary fibre intake may also affect the risk of gestational diabetes. The Nurses Health Study II (n = 13 110) reported that dietary glycaemic load is positively associated with the risk of gestational diabetes (RR = 1.61, p = 0.03) (17). Each 10 g/day increment in total fibre in prepregnancy diet is associated with 26% reduced risk of developing gestational diabetes mellitus while each 5 g/day increment in cereal fibre or fruit fibre reduced the risk by 23 or 26%, respectively (17). Low glycaemic load and high fibre diets could be recommended preconceptionally to women at risk of developing gestational diabetes.

N-3 long chain polyunsaturated fatty acids such as docosahexaenoic acid (DHA) may be involved in neural or visual development of infants. Eicosapentaenoic (EPA) may reduce the synthesis of thromboxane A2 from arachidonic acid and thus was expected to be effective in preventing pre-eclampsia. However, a meta-analysis involving 6 trials (n = 2783) found that supplementation of these prostaglandin precursors had no effect on gestational hypertension, pre-eclampsia (gestational hypertension with proteinuria), or eclampsia (18). The effect of n-3 fatty acids intakes on birth weight and the duration of gestation is inconsistent. In summary, evidence to date does not support the supplementation of n-3 fatty acids to prevent pregnancy hypertensive disorders or to improve fetal outcomes.

The requirements for most micronutrients increase during pregnancy. While some of these could be met by increased absorption during pregnancy, certain populations may be at risk of developing micronutrient deficiencies during pregnancy. Deficiency in one or more micronutrients could have long-term consequences for the offspring.

Folate is present in many green leafy vegetables and fruits. Folate is essential for DNA and RNA synthesis, amino acid metabolism, and formate oxidation. Folic acid also removes oxidizing free radicals, thus is also considered to be an antioxidant. Folate is particularly important during phases of rapid cell division and growth, e.g. during embryonic and fetal periods. Circulating folate concentrations usually decreases during pregnancy in women not supplemented with folic acid. This could be due to increased folate demand resulting from fetus and uteroplacental organ development, increased blood volume, increased folate catabolism or clearance, decreased folate absorption or hormonal influence during pregnancy. Women from developing countries may be at high risk of folate inadequacy during pregnancy. About 40–60% of pregnant women in India and Sri Lanka have serum folic acid levels below 3 ng/ml. Low levels of maternal folic acid increases the risk of fetal abnormalities. It was estimated that about half of all birth deficits can be prevented if maternal folic acid status was adequate. Peri-conceptional supplementation containing folate can prevent neural tube defects, cardiovascular defects, limb defects, cleft palate, oral clefts, urinary tract anomalies, and congenital hydrocephalus. Supplementation of folic acid does not completely abolish the increased risk of neural tube defects associated with obesity. The benefit of folic acid on preventing neural tube defects is smaller in obese patients compared with nonobese patients.

The recommended folate requirement is 400 µg for women of reproductive age, 600 µg for pregnant women, and 500 µg for lactating women. It is recommended that women with a balanced diet containing folate-rich food should be supplemented with 0.4–1.0 mg/day folic acid from several months prior to conception till breastfeeding ceases. In patients with history of poor compliance to medication and poor lifestyle behaviours including poor dietary habits and substance use, such as smoking and alcohol, a higher dose of folic acid (5 mg) should be used to compensate for irregular folic acid intake. Increasing folate intake through supplementation or folate-rich diets is associated with reduced risk of facial clefts (odds ratio 0.61, 95% CI 0.39 to 0.96 and odds ratio 0.75, 95% CI 0.1 to 1.11, respectively). The greatest risk reduction, however, is achieved by a combination of both supplements and folate-rich diet (odds ratio 0.36, 95% CI 0.17 to 0.77) (19). Thus, women supplemented with folic acid should be recommended to consume a folate-rich diet for optimal outcomes. One possible adverse effect with high folate intake is twin births. Multiple gestation is considered undesirable due to greater risk of infant morbidity and mortality. On the balance of benefit and risk, women contemplating pregnancy should be prescribed with folate supplementation and advised to increase the intake of folate-rich foods.

Vitamin A is present in carrots, sweet potatoes, and green leafy vegetables, such as kale. Vitamin A is involved in the physiological functions of vision, immunity, reproduction, and growth. As vitamin A is also involved in cell proliferation, adequate levels during the gestation period are essential (20). In a region in Nepal with endemic vitamin A deficiency, vitamin A supplementation reduced maternal mortality by 40%, while supplementations with β-carotene reduced mortality by 49%. The upper limit for retinol supplements is 10 000 IU (3000 µg RE) per day, as excess doses could have teratogenic effects. Supplementation with β-carotene is not known to be associated with adverse effects. Due to the potential risks of toxicity, supplementation should only be initiated after careful assessment of the women’s current intake. In most developed countries where hypovitaminosis A is rare, there is no need for supplementation.

Vitamin B₁ (thiamine), vitamin B₂ (riboflavin), vitamin B₃ (niacin), vitamin B₆ (pyridoxine) are involved energy production, and the metabolism of protein, fat, and carbohydrate. Greater energy and protein requirements during pregnancy increase the requirement for these vitamins. Thiamine deficiency could impair fetal brain development due to the role of thiamine-dependant enzymes in lipid and nucleotide synthesis in the brain. Deficiency in riboflavin may be associated with low birth weight, and possibly pre-eclampsia. The effect of supplementing these vitamins during pregnancy is not known.

Vitamin B₁₂ is involved in the conversion of homocysteine to methionine and of methyl malonyl CoS to succinyl CoA. As vitamin B12 is mainly derived from animal sources, those with restricted meat intake are at higher risk of deficiency. A high prevalence of low plasma vitamin B₁₂ concentrations has been found in Latin American, Indian, and Nepalese women. Low plasma vitamin B₁₂ is associated with high plasma homocysteine levels. High maternal homocysteine levels have been associated with various adverse pregnancy outcomes including placental abruption, still-births, low birthweight, and preterm deliveries. Low maternal vitamin B₁₂ levels have also been associated with increased risk of neural tube defects and spina bifida. The effect of vitamin B₁₂ supplementation during pregnancy is currently unknown.

Ascorbic acid and vitamin E are important antioxidants, which inhibit free radical formation. Increased oxidative stress by free radicals has been implicated in the pathogenesis of pre-eclampsia. It was expected that antioxidants, such as vitamin C and E will prevent the development of pre-eclampsia. However, a Cochrane Review in 2008 (ten trials; n = 6533) concluded that combined vitamin C and E therapy does not reduce the risk of pre-eclampsia or improve any other pregnancy outcomes.

Vitamin D is a fat-soluble vitamin synthesized by the skin during exposure to sunlight (20). It can also be obtained from dietary sources such as fortified dairy products. Vitamin D is essential for calcium metabolism. Vitamin D deficiency could lead to rickets in infants and osteomalacia in adults (20). Poor vitamin D status can also occur in developed countries, possibly resulting from low intake of fortified cereals and milk products, highly pigmented skin, and minimal sunlight exposure due to clothing. The National Health and Nutrition Examination Survey III (1988–1994) in the USA found that 42% of African American and 4% of Caucasian-non-Hispanic women has low plasma concentration of 25-hydroxyvitamin D. Low maternal plasma 25-hydroxyvitamin D concentrations have been associated with poor mineralization in bones and teeth of developing fetus and excessive skeletal loss in the mother. The potential benefit and harm of vitamin D supplementation during pregnancy has not been investigated.

Calcium is required for fetal skeletal development. Neonates to mothers with very low calcium intakes may have lower bone mass. In individuals who consume less than 600 mg calcium or less than 2 dairy serves per day, calcium supplementation may increase infants bone mass or fetal bone growth (21). This effect may be limited to mothers with inadequate calcium intakes as maternal calcium supplementation does not improve newborn bone mineral mass in women with adequate baseline intakes.

In addition to its pivotal role in bone and teeth formation, calcium may also be involved in the regulation of blood pressure. However, a review by the US Food and Drug Administration concluded that it is highly unlikely that supplemental calcium would have any benefit in preventing pregnancy-induced hypertension or pre-eclampsia (22).

Iodine is a non-metallic trace element essential for the synthesis of thyroid hormones. Dietary sources of iodine include kelp, seafood, and plants from iodine-rich soil. About two-thirds of the population in Western and Central Europe live in regions of mild-to-severe iodine deficiency (23). Populations in mountainous and flooded areas are also at increased risk of iodine deficiency. Adequate iodine supply to the fetus is particularly important during early pregnancy. Even mild or sub-clinical maternal hypothyroidism can have significant influence on the mental development of the fetus. The fetus depends on maternal iodine to synthesis its own thyroid hormone. Physical and mental growth could be affected if mother is iodine deficient during pregnancy or lactation. Iodine-deficiency disorders (IDD) is one of the most common cause of preventable brain damage. The characteristics of IDD include mental retardation, hypothyroidism, goitre, and growth abnormalities. Due to the critical need for adequate iodine status in early pregnancy, periconceptional iodine supplementation should be considered for women at risk of iodine deficiency.

The most important role of iron is oxygen transport, although it is also involved in growth, reproduction, and healing. WHO estimated that globally 50% of pregnant women are anaemic. Iron-deficiency anaemia contributed to 20% postbirth maternal death in Africa and Asia (1). The prevalence of anaemia among pregnant women in South Asia ranges from 60 to 90% (24). It is difficult to meet the increased iron requirements during pregnancy with food sources alone, even with the increase in iron absorption during second and third trimester. As iron stores at conception is an important predictor of maternal iron status and the risk of anaemia in later pregnancy, iron supplementations may have its greatest benefit if started at conception or in early pregnancy. Adequate iron status during pregnancy can also prevent postpartum anaemia, which is associated with postpartum depression. A Cochrane review has found that iron supplementation in developed countries reduces maternal anaemia without significant effect on fetal survival or birthweight. There is currently insufficient evidence available from developing countries.

Zinc is present in meat and seafood. It is a cofactor in over 80 metallo-enzymes involved in DNA transcription and protein synthesis. Zinc is also involved in wound healing, neurological function, immunity, folate utilization, vision, and other important reactions in the body. Zinc also has antioxidant properties. It binds the sulphydryl groups in proteins, and displaces iron or copper, while preventing them from binding to lipids, proteins, and DNA. As there is no single definitive test for measuring zinc status, the prevalence of zinc deficiency is unclear. Zinc status could be ascertained by measuring plasma or serum zinc levels, zinc-dependant enzyme levels or 24-h urinary zinc excretion. Women who are strict vegetarians, or those who have chronic diseases or infections are at increased risk of zinc deficiency. Some data from developing countries suggest that low zinc status is associated with low birthweight (25). The effect of zinc supplementation during pregnancy on birth weight is inconsistent.

Regular alcohol intake (at least once a week) or high alcohol consumption (more than 14 units a week or more than 3 units a day) increases the risk of first trimester miscarriage and SGA births (4, 26). The effect of moderate or occasional alcohol consumption on pregnancy outcomes is less clear. Low to moderate level of alcohol consumption (less than 12 g/day) was found in some studies to increase the risk of miscarriage, stillbirth, impaired growth, low birthweight, preterm birth, and malformations (27). However, many of these studies had methodological limitations, such as not adjusting for potential confounders in estimating risks. Pregnant women should limit or avoid alcohol intake.

The effect of caffeine on pregnancy outcomes is inconsistent. Maternal caffeine intake appears to have no effect on cardiovascular malformations, oral clefts, or early miscarriage (4, 28). However, a prospective cohort study in the US (n = 1063) reported that high caffeine intake (more than 200 mg/day) is associated with increased risk of miscarriage after adjusting for age, income, education, smoking, alcohol, and other confounders (adjusted hazard ratio 2.23, 95% CI 1.34 to 3.69) (29). Women should be advised to minimize or avoid caffeine intake during pregnancy until safety limits could be established.

Compared with the literature in women, there is relatively limited information on nutrition and reproduction in men. Obesity is a risk factor for infertility in males, as it is in females. There is a dose-response relationship between BMI and infertility in men. High BMI is associated with low sperm density, low sperm count, low number of normal-motile sperm, and greater number of sperm cells with chromatic damage measured using DNA fragmentation index (30). In contrast to women, body weight corresponds negatively to testosterone levels and to testosterone/oestradiol ratio in men. High oestrogen levels, insulin resistance, and sleep apnoea contributes to hypoandrogenaemia in obese men. The risk of erectile dysfunction also increases with BMI.

Zinc is also important for male fertility. It is present at high concentrations in male genital organs such as prostate gland. Some of the suggested functions of zinc in male reproduction include testicular steroidogenesis, testicular development, nuclear chromatin condensation, acrosome reaction, acrosin activity, and testosterone synthesis. There are some evidence that zinc supplementation may improve sperm count, motility, and morphology (Table 8.1.12.5).

Aside from periconceptional folic acid supplementation to prevent birth defects and possibly iron supplementation to treat iron-deficiency anaemia in pregnant women, there is insufficient evidence to support recommendations for other micronutrient supplementations to improve pregnancy outcomes. For many micronutrients, the association between deficient states and adverse pregnancy outcomes is known but the effect of supplementation has not been investigated. As micronutrient deficiencies are more prevalent in developing countries, specific information from these regions are also needed.

Despite the numerous food products claiming to have fertility-enhancing properties, there are surprisingly few nutrients found to have an effect on fertility. The most significant link between nutrition and reproduction is energy states, i.e. being underweight or overweight. Thus, currently the best nutritional advice for optimal fertility is maintaining a healthy body weight. In addition, zinc may also have a role in determining male fertility.

There are increasing evidence suggesting that exposure to certain stimulus during critical windows of embryo or fetal development can have life-long implications for the offspring. This hypothesis suggests that changes in the intrauterine environment will incur permanent changes in organs and systems of the developing fetus, which in turn produce long-term consequences for adult health. For example, animal studies have shown that maternal nutrient restriction could increase the risk of metabolic and cardiovascular diseases in adulthood of the offspring. Findings in this area will help to prevent not only the known adverse consequences of micronutrient deficiencies discussed above, but also to prevent chronic diseases in adulthood by creating the optimal intrauterine environment for this purpose.