Plant-Based and Plant-Rich Diet Patterns during Gestation: Beneficial Effects and Possible Shortcomings^,

Abstract

Environmental and lifestyle factors are known to play an important role during gestation, determining newborns’ health status and influencing their risk of being subject to certain noncommunicable diseases later in life. In particular, maternal nutritional patterns characterized by a low intake of plant-derived foods could increase the risk of gestation-related issues, such as preeclampsia and pregravid obesity, increase genotoxicant susceptibility, and contribute to the onset of pediatric diseases. In particular, the risk of pediatric wheeze, diabetes, neural tube defects, orofacial clefts, and some pediatric tumors seems to be reduced by maternal intake of adequate amounts of vegetables, fruits, and selected antioxidants. Nevertheless, plant-based diets, like any other diet, if improperly balanced, could be deficient in some specific nutrients that are particularly relevant during gestation, such as n–3 (ω-3) fatty acids, vitamin B-12, iron, zinc, and iodine, possibly affecting the offspring’s health state. Here we review the scientific literature in this field, focusing specifically on observational studies in humans, and highlight protective effects elicited by maternal diets enriched in plant-derived foods and possible issues related to maternal plant-based diets.

Introduction

Several epidemiologic studies have shown that nonfavorable environmental and lifestyle factors play an important role during pregnancy, determining newborns’ health state and possibly affecting offsprings’ risk of developing certain chronic and degenerative diseases later in life, a phenomenon commonly defined as “early life programming.” Among these factors, maternal nutrition (e.g., high-energy and high-fat diets), sleep quality, a low level of physical activity, smoking, and exposure to pollutants can negatively influence fetal development and health status later in life (1, 2). For instance, it is known that both maternal malnutrition and overnutrition are associated with a higher risk of diabetes in the offspring. For this reason, pregnancy represents a relevant window of opportunity for health care providers to modify diet toward habits that will be healthier for both mothers and their offspring (3).

In this regard, vegan and vegetarian dietary patterns are currently considered beneficial for the prevention of several chronic and degenerative ailments (4–6) and appropriate during all life cycle stages, including pregnancy, lactation, infancy, childhood, and adolescence (6). It has been reported that well-balanced vegan and vegetarian diets can be considered safe and beneficial during pregnancy. Vegan pregnant women have a lower-than-average rate of cesarean delivery, less postpartum depression, and lower neonatal and maternal mortality, with no complications or negative outcomes that are higher than average (7–9). Generally, vegans weigh less than omnivores and seem to experience fewer weight-related complications, and plant-based maternal diets could prevent gestational diabetes by providing greater amounts of fiber (10). In addition, the incidence of preeclampsia appears to be lower among vegan mothers (8). This could be related to the theory that the risk of preeclampsia is directly associated with a high consumption of fat and sugar and a low intake of fiber, and plant-based dietary patterns generally provide low amounts of fat and sugar and higher quantities of fiber (11). Despite these beneficial outcomes, some studies reported that mothers following vegetarian diets could give birth to infants with lower birth weights, whereas other studies reported higher birth weights; in addition, some heterogeneous studies reported that vegan/vegetarian women could be at risk of vitamin B-12 and iron deficiencies during gestation, as recently described (12).

Here we review the scientific literature in this field, focusing specifically on observational studies in humans, and address the protective effects elicited by gestational dietary patterns enriched in plant-derived foods and their health-related outcomes for mothers and their offspring. We also discuss the possible risks linked to poorly balanced or deficient plant-based (i.e., vegan) diets.

Plant-Based or Plant-Rich Diets during Pregnancy and the Risk of Gestation-Related Issues

Recent studies indicate that nutritional patterns enriched with plant-derived foods might be protective during pregnancy, conferring beneficial effects to both mothers and their offspring. In this regard, it has been reported that low-glycemic, Mediterranean diet–type patterns, characterized by high intakes of vegetables, fruits, and grains, together with adequate consumption of n–3 FAs may improve ovulatory infertility, decrease preterm birth, and lower the risk of gestational diabetes mellitus (GDM)⁹ (13). Below we summarize observational and intervention studies describing the beneficial effects of maternal diets enriched in plant-derived foods in reducing the risk of common gestation-related issues.

Preeclampsia.

Diets characterized by a high consumption of plant-derived foods, with at least 3 daily servings of vegetables, combined with physical activity seem to reduce the risk of pregnancy-induced hypertension (or preeclampsia) (8, 14). A longitudinal study conducted in 238 black pregnant women in the Congo showed that the incidence of arterial hypertension was 4.6% overall (2.9% of whom had preeclampsia and 1.7% of whom showed transient hypertension). Hypertensive mothers presented lower parity and infant birth weights, with higher rates of edema. Preeclampsia occurred more frequently among women who rarely consumed daily servings of vegetables during pregnancy (33.3%) than among women consuming ≥3 servings of vegetables per day (3.7%) (14).

Similarly, diets high in fiber and potassium seem to be associated with a reduced risk of hypertension and preeclampsia, as reported in a case-control study in 172 preeclamptic pregnant women and 339 normotensive controls. The foods that were found to be more beneficial in reducing the risk of preeclampsia in this study were fruits, vegetables, cereals, dark bread, and low-fat dairy products (11).

GDM.

A high intake of fiber during pregnancy seems to be particularly beneficial in preventing GDM. Indeed, maternal diets characterized by low intakes of fiber and a high glycemic load seem to be associated with an increased risk of GDM, as shown in a prospective cohort study in 13,110 eligible women in the Nurses’ Health Study II (10). In particular, an increment of 10 g/d in total fiber intake was found to be associated with a 26% risk reduction in GDM and an increment of 5 g/d in cereal or fruit fiber intake was associated with a 23% or 26% reduction in GDM, respectively. On the contrary, dietary glycemic load was directly associated with GDM risk (10).

Another randomized controlled clinical trial enrolled 52 women diagnosed with GDM; participants were randomly assigned to consume for 4 wk either a control diet (n = 26) or the DASH (Dietary Approaches to Stop Hypertension) diet (n = 26) (15). The DASH diet was enriched in fruits, vegetables, whole grains, and low-fat dairy products, with low amounts of saturated fats, cholesterol, and refined grains, and a total of 2.4 g sodium/d. Fewer women following the DASH diet underwent cesarean delivery (46.2% vs. 80.8% of the control group) and started insulin therapy after intervention (23% vs. 73% of the control group). In addition, offspring born to DASH group participants presented lower weight, head circumference, and ponderal index values compared with children born to mothers who consumed the control diet (15).

Pregravid obesity and gestational weight gain.

Pregravid obesity in pregnant women, defined as a BMI (in kg/m²) >29, has been found to be correlated with inadequate dietary intakes of grains, vegetables, iron, and folate (both of plant and animal origin), as shown in 2394 women recruited for a clinic-based population study (16). Moreover, a systematic review of observational studies on gestational weight gain (GWG) showed that both intake of carbohydrates and vegetarian diets were associated with lower GWG, contrary to dietary patterns characterized by higher intakes of proteins, animal fats, and energy-dense foods and more servings of food per day (17), suggesting that plant-based dietary regimens could be beneficial in preventing GWG. Accordingly, first-trimester vegetarian diets (i.e., diets excluding certain animal products), together with walking during midpregnancy and vigorous physical activity (30 min/d for both), were inversely associated with excessive GWG (defined as a “gain greater than the upper limit for each woman’s prepregnancy BMI category” (18) (e.g., women with a BMI >29.0 who gained at least 6.8 kg but not more than 11.5 kg) contrary to diets high in total energy, dairy, and fried foods, which were directly associated with high GWG, as shown in 1388 women (19).

Calf cramps.

A German study comprising 108 healthy pregnant women (i.e., not taking any medical drug interacting with magnesium absorption, free of any metabolic disease, and not using magnesium supplements) who were following either a long-term (>3 y) plant-based/vegetarian diet [either lactoovovegetarian (n = 27) or including a low amount of meat (n = 43)] or an average Western diet (n = 38) showed that vegetarian diets, by providing a high intake of magnesium (assessed by higher urinary magnesium excretion), reduced the frequency of calf cramps, particularly during the third trimester of pregnancy, compared with an average Western diet (20). In particular, lactoovovegetarian regimens were found to be characterized by both the highest magnesium intake and the highest urinary magnesium excretion (20). It should be noted that authors of this study applied the term “vegetarian” to diets that also included low amounts of meat, which should be taken into account when disaggregating the effects specifically elicited by strict vegetarian regimens (i.e., lactoovovegetarian) vs. health-conscious omnivorous diets.

Chronic kidney disease.

Gestation time can be particularly challenging for women affected by chronic kidney disease (CKD), especially considering the scarcity of therapeutic drugs suitable during pregnancy. In this regard, low-protein vegetarian diets (i.e., 0.6 g protein/(kg · d), supplemented with a commercial keto acid preparation and 1–2 free choice meals/wk) were reported to be beneficial for the management of pregnant patients with CKD, as shown in a prospective cohort study in 168 pregnant women undergoing monthly measurements of renal function, urine protein, uric acid, serum electrolytes, coagulation variables, and blood cell counts and urinalysis and urinary culture (21).

This evidence was later confirmed in a nutritional intervention study by the same group in pregnant women with stages 3–5 CKD, which reported a positive correlation among low-protein vegan/vegetarian diets during gestation [i.e., 0.6–0.8 g protein/(kg · d), with keto acid supplementation and 1–3 free meals/wk, allowing small quantities of milk and yogurt (100–150 mL/d)], a reduced likelihood of small-for-gestational-age offspring, and the absence of detrimental effects on both kidney function and urine protein concentrations in the mothers (22).

Fetal growth variables.

Maternal plant-rich diets also seem to be beneficial in supporting fetal growth. Small-for-gestational-age weight and body length measurements were inversely associated particularly with a high consumption of vegetables, but not fruits, in a Spanish mother-infant cohort (n = 787 infant-mother pairs) (23). Accordingly, 2 previous studies, one from India and another from Denmark, both showed that a high intake of fruits and vegetables seems to be positively associated with birth weight and size (24, 25). In particular, the Indian study reported that the consumption of milk at gestational week 18 and of green leafy vegetables/fruits at gestational week 28, by providing adequate intakes of folate and other micronutrients, was positively associated with birth size (24). The Danish study highlighted strong associations between high intakes of both green leafy vegetables and fruits during pregnancy and birth weight in 43,585 well-nourished women (25). Overall, these studies suggest that increasing maternal intakes of plant-derived foods (i.e., vegetables and fruits) and, as reported in some studies, of milk products could be beneficial in preventing gestation-related problems and improving fetal growth.

Plant-Based or Plant-Rich Diets during Pregnancy and the Risk of Genotoxicant Exposure

Pregnant women following a plant-based diet could also be better protected against genotoxicants.

Bulky DNA adducts.

It has been shown that the presence of bulky DNA adducts in cord blood is a sensitive indicator of a biologically effective dose of genotoxic agents at the prenatal stage, including polycyclic aromatic hydrocarbons, which may contribute to reduced fetal growth (26). A recent multicenter study comprising 229 mothers and 612 newborns estimated the association between the amounts of bulky DNA adducts in cord blood (measured by the ³²P-postlabeling technique in white blood cells), birth weight, and maternal intake of fruits and vegetables during pregnancy (27). Data indicate that women who more frequently consume fruits and vegetables were better protected against the accumulation of bulky DNA adducts, and the weights of their newborns were greater than the weights of offspring born to women consuming fewer fruits and vegetables (27).

Nitrate, nitrite, and N-nitroso compounds.

Maternal exposure to nitrate, nitrite, and N-nitroso compounds (NOCs) from drinking water or diet has been associated with a higher risk of developing neural tube defects (NTDs) and pediatric brain tumors. It is conceivable that plant-based/vegetarian diets, characterized by a high consumption of fruits and vegetables and low or no intakes of cured meat and smoked fish, which represent the main exogenous dietary sources of NOCs (28), could prevent NOC exposure, thus decreasing the risk of congenital malformations and childhood brain tumors (29–31).

However, it should be noted that pickled vegetables also contain relatively large amounts of nitrite and NOCs. In this regard, a 2011 study examined the possible association between maternal periconceptional consumption of pickled vegetables and NTDs in 4 Chinese counties, and the data indicated that >6 pickled vegetable meals/wk increased the risk of NTDs, compared with less frequent (i.e., <1 meal/wk) consumption (32). In addition, the authors of this study showed that maternal intake (≥1 meal/wk) of meat, eggs, or milk elicited a protective effect against the risk of NTDs (32).

Plant-Based or Plant-Rich Diets during Pregnancy and the Risk of Pediatric Diseases

Plant-based diets and a high intake of fruits and vegetables during pregnancy may prevent the risk of developing certain diseases in infants.

Pediatric wheeze, asthma, and eczema.

Maternal intakes of vegetables, fruits, and selected antioxidants during pregnancy were reported to reduce the risk of wheeze and eczema in infants aged 16–24 mo, as shown in 763 Japanese mother-child pairs (33). In particular, a higher maternal intake of green and yellow vegetables, citrus fruit, and β-carotene during pregnancy significantly reduced the risk of eczema, but not wheeze, in the offspring, whereas the consumption of vitamin E during pregnancy lowered the risk of infantile wheeze but not eczema (33).

Conversely, the same research group later reported that a Western nutritional pattern during pregnancy, characterized by a high intake of vegetable oil, salt-containing seasonings, beef, pork, processed meats, eggs, chicken, and white vegetables, seems to confer protection against wheeze, whereas neither a healthy maternal dietary pattern (i.e., high intakes of green and yellow vegetables, seaweed, mushrooms, white vegetables, pulses, potatoes, fish, seafood, fruits, and shellfish) or the Japanese pattern (i.e., high intakes of rice, miso soup, seafood, and fish) during pregnancy was directly related to higher childhood wheeze or eczema risk (34). However, in this study both the “healthy” and “Japanese” maternal dietary patterns were characterized by a high intake of fish, fish products, and shellfish, which have been shown in other studies to possibly increase the risk of infant wheeze and food allergy (35, 36). In addition, a maternal Mediterranean diet and diets including fruits and vegetables and providing high intakes of vitamins A, D, and E and zinc also seem to prevent asthma, allergic outcomes, and atopic dermatitis in the offspring, as reported in a 2011 meta-analysis comprising 21 cohort, 15 case-control, and 26 cross-sectional studies (37).

Diabetes.

Several maternal factors during pregnancy could increase the risk of type 2 diabetes in the offspring later in life. Among these risk factors, malnutrition, hyperglycemia, obesity, smoking, drinking, junk food diets, hormone use, and stress seem to play a relevant role (3, 38).

In particular, a family history of type 2 diabetes (the transmission of type 2 diabetes to the next generation) seems to be stronger for maternal than for paternal diabetes and this difference seems to be determined by the larger contribution of diet, adiposity, and other lifestyle factors to maternal diabetes, as shown in a Dutch study comprising 35,174 participants (aged 20–70 y) (39). Nevertheless, studies addressing the possible protective role of plant-based diets during gestation in relation to the onset of type 2 diabetes in the offspring have not been published previously.

Interestingly, prenatal nutritional exposures could be correlated with the risk of developing type 1 diabetes in children. The Diabetes Autoimmunity Study in the Young analyzed the association between mothers’ diet, assessed via a FFQ, during the third trimester and islet autoantibody production at 9 mo, 15 mo, and 2 y of age and annually thereafter in 642 infants (40). A child was considered diabetic if tests were positive for islet autoantibodies at 2 consecutive blood draws and remained positive at the last follow-up. Among the foods taken into account for possible correlations (e.g., potatoes and other root vegetables, gluten-containing foods, nongluten cereal grains, cow milk and cow-milk products, fruits, vegetables, meat and poultry, and fish), only a higher maternal intake of potatoes was found to be correlated with the delayed onset of islet autoantibodies (40).

In addition, dietary vitamin D intake and/or supplementation with vitamin D during pregnancy was found to be possibly protective against islet autoantibody appearance in the offspring (41, 42). Maternal intake of n–3 and n–6 FAs was also not associated with the appearance of islet autoantibodies in their offspring (41).

Notably, fish are known to provide the highest amount of vitamin D, although this source mainly derives from microalgae, which represent their main food supply. The presence of both vitamin D₃ and provitamin D₃ in microalgae confirms that vitamin D₃ exists in the plant kingdom, as found in several plant species (43). In addition to sunlight exposure to increase the amount of vitamin D synthesis, many vitamin D–fortified foods (e.g., soy milk, breakfast cereal, orange juice, and meal replacement bars) (9) could be consumed especially during gestation to increase vitamin D intake.

Moreover, a high maternal intake of retinol (mainly from meat and milk products), β-carotene (from roots), vitamin C (from juice, fruits, vegetables, and citrus fruits), vitamin E (from vegetable oils and cereal products), selenium and zinc (both from meat and milk), or manganese (from cereal products), assessed postnatally via a self-administered FFQ, was found to confer no relevant protection against advanced β cell autoimmunity in early childhood in a Finnish prospective population-based cohort study comprising 4297 children with increased genetic susceptibility to type 1 diabetes (44). Another Swedish study analyzed 5724 mother-child pairs and showed that the low consumption of vegetables (i.e., <3–5 times/wk) during pregnancy (assessed postnatally by an FFQ) was associated with an increased risk of islet autoantibody production in children (45), suggesting that the daily consumption of vegetables by pregnant mothers could decrease the risk of type 1 diabetes in the offspring.

Further large-scale studies would be helpful in elucidating the correlations between specific nutritional patterns (i.e., vegan, vegetarian, or omnivorous) and/or specific foods (i.e., plant-derived, eggs, dairy products, meat, and fish) and the risk of type 1 diabetes in the offspring.

NTDs and orofacial clefts.

A high periconceptional intake of folic acid, in addition to preventing NTDs, is also known to prevent orofacial clefts (OFCs) in the offspring; and lactoovovegetarian pregnant women, compared with low meat eaters and Western diet controls, seem to present the highest concentrations in both plasma and RBCs, as shown in a prospective study in 109 pregnant women (46). Both NTDs and OFCs are caused by aberrant neural crest cell–related mechanisms and for this reason might possibly share common pathogenic pathways (47). An analysis of 182 mothers of children with OFCs and 173 control mothers revealed that mothers whose preconceptional intake of macronutrients, vitamins, minerals (i.e., protein, fat, carbohydrate, fiber, cholesterol, vitamin A, retinol, β-carotene, ascorbic acid, α-tocopherol, calcium, phosphorus, iron, magnesium, and zinc), and specific food groups (vegetables, eggs, fruits, grain products, bread, herbs, cheese, and soy products) was lower were more prone to have offspring with OFCs. Also in this study, dietary intake was assessed ∼14 mo after delivery via an FFQ. Importantly, increasing intakes of vegetable protein, fiber, ascorbic acid, iron, and magnesium were found to reduce the risk of OFCs (47). Similarly, a case-control study in 203 mothers of children with OFCs and 178 control mothers showed that a maternal “prudent” dietary pattern (assessed 14 mo after delivery), characterized by high intakes of garlic, nuts, vegetables, and fish, together with increased serum vitamin B-12 and folate concentrations, was not associated with OFC risk, unlike a Western diet (i.e., high intakes of meat, pizza, legumes, and potatoes and a low intake of fruits), which was shown to increase by ∼2-fold the risk of offspring with OFCs (48).

Pediatric tumors.

There is currently a growing body of evidence suggesting that prolonged and frequent breastfeeding and dietary and vitamin intakes during pregnancy could contribute to reducing the risk of childhood cancers. Therefore, dietary choices starting early in life deserve attention (49). Particularly, a high intake of fruits, vegetables, and whole grains; a favorable n–6 to n–3 PUFA ratio; and the consumption of fish may reduce cancer risk in children (49). Nevertheless, children and pregnant women should avoid consuming large fish, such as shark, swordfish, king mackerel, and tilefish, because they may contain high concentrations of heavy metals (e.g., mercury), polychlorinated biphenyls, dioxins, and other contaminants (49, 50).

It has been suggested that maternal supplementation of folic acid/folate, which is naturally found in green leafy vegetables, fruits, and legumes (51), may reduce the risk of pediatric acute lymphoblastic leukemia (ALL) (52), Wilms tumor, and primitive neuroectodermal tumors (53). Accordingly, maternal dietary patterns, assessed 12 mo before pregnancy, characterized by a high intake of vegetables, protein sources (both plant and animal derived), and fruits, and particularly of provitamin A carotenoids and the antioxidant glutathione, were found to be inversely associated with childhood ALL, as shown in a population-based case-control study comprising 138 ALL cases and 138 controls matched on sex, date of birth, mother’s race, and county of residence at birth (54).

Accordingly, a case-control study including 240 incident cases of infant acute leukemia and 255 controls reported that maternal consumption of fresh vegetables and fruits during pregnancy seems to be associated with a reduced risk of infant leukemia, especially the form that presents mixed-lineage leukemia gene (MLL) translocations (MLL+) (55). However, the risk of one specific form of leukemia [i.e., MLL+ acute myeloid leukemia, or AML (MLL+)] could be increased by maternal consumption of certain plant-derived foods that are known to be natural sources of DNA topoisomerase II (DNAt2) inhibitors (55). According to this study, foods containing DNAt2 inhibitors were as follows: canned or dried legumes, apples, onions, berries, soy products, coffee, black and green tea, cocoa, red wine, and coffee and other caffeinated beverages (55). Acute myeloid leukemia AML (MLL+) is known to possibly arise upon chemotherapy with DNAt2 inhibitors, which can naturally occur in foods, such as quercetin (a flavonoid present in some fruits and vegetables), genistein (in soy), catechins (present in green and black tea), cocoa, and red wine (56–58). Further large-scale clinical and epidemiologic studies are needed to confirm these observations.

In addition, low gestational maternal intake of fruits and vegetables may contribute to the development of sporadic (noninherited) retinoblastoma. In this regard, a Mexican hospital–based case-control study assessed maternal dietary intake of vegetables and fruits in a cohort study comprising the mothers of 101 children with retinoblastoma compared with 172 control cases. Data showed that mothers who consumed <2 daily servings of vegetables, and consequently lower quantities of folate and lutein/zeaxanthin derived from fruits and vegetables, had a higher risk of having children affected by sporadic retinoblastoma (59).

Furthermore, a 2009 case-control study assessed possible correlations between maternal diet habits (measured by an FFQ) and the risk of childhood brain tumors in 9 study centers from 7 different countries, contributing to a total of 1218 cases and 2223 controls. This study highlighted that dietary patterns that included cured meats, eggs/dairy, and oil products resulted in being generally associated with a higher incidence of brain tumors (31). On the contrary, diets that included yellow-orange vegetables, grains, and fresh fish seemed to decrease this risk. Specifically, the consumption of cured meat was associated with astrocytomas and ependymomas and high intake of oil products was associated with medulloblastoma. Conversely, the consumption of cruciferous vegetables reduced the risk of anaplastic astrocytomas, whereas the consumption of fresh fish decreased the risk of astroglial tumors (31). Studies describing the effects elicited by plant-based and plant-rich diet patterns during gestation are summarized in Table 1.

TABLE 1.

Summary of the effects elicited by plant-based and plant-rich dietary patterns during gestation¹

Plant-based and plant-rich diets in relation to	Described effects (reference)	Do studies also account for animal-derived foods?
Pregnancy-related issues	Lower-than-average cesarean delivery rate, lower postpartum depression, lower neonatal mortality, lower maternal mortality, lower risk of preeclampsia (7–9, 11, 14)	In reference 11, beneficial effects of low-fat dairy products are reported
	High-fiber, low-glycemic-load or DASH diets reduce GDM (10, 15)	In reference 15, DASH diet includes low-fat dairy products
	Mediterranean-like diets improve ovulatory infertility, decrease preterm birth, lower gestational diabetes risk (13)	Mediterranean diet generally includes fish, dairy, and/or other animal products
	Prevention of pregravid obesity (16)	Iron and folate are both of plant and animal origin
	Reduction in gestational weight gain (17, 19)	In reference 17, beneficial effects of vegetarian diet are reported; in reference 19, certain animal products are included
	Reduced frequency of calf cramps (20)	Beneficial effects of (lactoovo) vegetarian diets are reported
	Amelioration of chronic kidney disease (21, 22)	Beneficial effects of low-protein vegan and vegetarian diets (including milk and yogurt) are reported
	Support of fetal growth (22–25)	In reference 24, beneficial effects of milk are reported
Genotoxicant exposure	Increased protection against bulky DNA adduct accumulations; improved newborn weights (27)	No
	Prevention of NOC exposure, decreased risk of congenital malformations and childhood brain tumors (29–31)	In reference 31, consumption of fresh fish seems beneficial in reducing the risk of astroglial tumors
	Pickled vegetables rich in NOCs might increase neural tube defects (32)	Intake of meat (≥1 meal/wk) and of eggs or milk (≥1 meal/wk) is considered protective
Pediatric diseases	Possible reduced risk of wheeze and eczema (33, 34)	In reference 34, fish, fish products and shellfish are included
	Meta-analysis report (i.e., 21 cohort, 15 case-control, and 26 cross-sectional studies): Mediterranean diet and diets enriched in fruits/vegetables prevent asthma, allergy, and atopic dermatitis (37)	Mediterranean diet generally includes fish, dairy, and/or other animal products
	Possible reduced risk of islet autoantibody production and of type 1 diabetes (40, 44, 45)	In reference 44, meat and milk products represent the major sources of retinol, selenium, and zinc
	Lactoovovegetarian pregnant women compared with low meat eaters and Western diet controls have lower risk of folate deficiency (46), which correlates with a reduced risk of orofacial clefts (47, 48)	In references 46 and 47, eggs and cheese are included; in reference 48, fish is included
	Possible reduced risk of the following tumors: pediatric ALL, Wilms tumor, primitive neuroectodermal tumors, AML (MLL+), sporadic retinoblastoma, anaplastic astrocytomas (31, 49, 54, 55, 59)	In reference 31, consumption of fresh fish seems beneficial in reducing the risk of astroglial tumors; in reference 49, the protective effects of fish are considered; in reference 54, protein sources are also of animal origin

¹ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; DASH, Dietary Approaches to Stop Hypertension; GDM, gestational diabetes mellitus; MLL, mixed-lineage leukemia gene; NOC, N-nitroso compound.

Possible Shortcomings Associated with Plant-Based Diets during Pregnancy

n–3 PUFAs.

Poorly planned, monotonous plant-based diets may lead to nutritional deficiencies that could have relevant consequences in prenatal and postnatal life. A 2011 study that analyzed 13 low- and middle-income countries reported that the content of DHA in breast milk is very low in populations living mainly on plant-based diets but higher in fish-eating countries (60). In addition, the supply of fat and n–3 FAs is higher in countries with higher gross domestic product, and 70–80% of PUFA intake comes from cereals and vegetable oils, some of which are characterized by low contents of α-linolenic acid (ALA; 18:3n−3). These data suggest that increasing the intake of vegetable oils with higher ALA content, such as soybean or rapeseed oil, and of fish would be beneficial for enriching the n–3 FA supply (60).

It should be noted that high amounts of the n–6 FA linoleic acid (18:2n−6) in the diet, as a result of replacement of saturated fats with plant-based PUFAs, generally result in low n–3 long-chain PUFA endogenous status. Because the FA supply is particularly critical during both pregnancy and infancy, it is important to ensure an adequate intake of n–3 PUFAs in order to avoid brain developmental defects and to reduce the risk of a range of growth, metabolic, and immune childhood outcomes (61). Even at the pregestational level, an intake of adequate amounts of n–3 PUFAs and DHA plays a major role; indeed, small variations in the habitual maternal dietary composition before pregnancy are likely to be more effective in improving the delivery of long-chain PUFAs to the fetus than are large dietary changes in the late stages of pregnancy, as reported (62).

Vitamin B-12.

Strict or poorly balanced vegan diets could result in vitamin B-12 deficiencies and vitamin B-12 is essential for the synthesis of nucleic acids and erythrocytes and in the maintenance of myelin. A recent review reported that deficiency of vitamin B-12 among pregnant women following vegetarian diets was found to range from 17% to 39%, depending on the trimester; and in general, higher deficiency was reported in vegans than in vegetarians (63).

Vitamin B-12 deficiency in developed countries usually occurs in children who are exclusively breastfed by vegetarian/vegan mothers, and possible symptoms of this deficiency often appear during the second trimester of life, as reported in a 6-mo-old infant whose mother followed a strict vegetarian diet and significantly prolonged breastfeeding (64). Symptoms can include lethargy, hypotonia, arrest or regression of developmental skills, and megaloblastic anemia; if left untreated, children could undergo lasting neurodisability (65). In addition, low intakes of both vitamin B-12 and protein during pregnancy are associated with increased NTD risk, less lean mass, higher adiposity, insulin resistance, impaired neurodevelopment, and altered cancer risk in the offspring (66). For these reasons, vitamin B-12 supplementation is often recommended, especially for pregnant women following a strict vegan diet (64, 67), for children presenting failure to thrive and delayed development (65), and to avoid hyperhomocysteinemia, which plays a critical role in the pathogenesis of NTDs and preeclampsia (68).

Dietary minerals.

Unvaried plant-based diets could result in low intake of dietary iron. Iron deficiency is correlated with poor pregnancy outcome but also impaired school performance and decreased productivity (69). Supplementing iron by means of iron supplements or iron-fortified foods can counteract iron deficiency, despite limitations of iron compound bioavailability (69). Interestingly, a 2011 British study conducted in a cohort of 1274 pregnant women, aged 18–45 y, showed that vegetarians were more likely to have adequate dietary iron intake and to take supplements during the first and second trimesters of pregnancy than nonvegetarians (70). Adequate iron intake, either from foods or supplements, was positively associated with birth weight (70).

Another micronutrient that could possibly be deficient in vegan diets is zinc, which is provided by animal tissue sources and might be further decreased by the intake of inhibitors of zinc absorption, such as phytic acid, which is present in cereals and grains. A recent review commented on the fact that adult vegetarians, compared with nonvegetarian control groups, seem to present lower dietary zinc intakes and lower serum zinc concentrations. However, given the lack of sufficient evidence, this has not been clearly proven in pregnant and lactating women, in the elderly, and in children (71).

In addition, vegan diets might provide a low intake of iodine, which could represent an issue during gestation, although iodine deficiencies are quite uncommon in Western countries. Nevertheless, a British single case study reported on a 10-d-old female infant and her vegan mother with goiter and abnormal thyroid function tests; the mother’s dietary iodine intake was found to be extremely low and reliably causative of the health complications in her daughter. In cases such as this one, iodine supplements could help to avoid possible risks (72), as recently suggested (73).

Strictly vegan pregnant women might possibly experience calcium deficiency (74), although calcium absorption is normally increased during pregnancy and calcium-fortified plant-based foods, such as soy/nut/rice/hemp milk, juice, cereals, calcium-set tofu, beans, sesame seeds, figs, nuts, and leafy greens, are currently widely available (9). A 2011 study in 797 pregnant rural Indian women sought to establish possible relations between bone mass in Indian children and maternal nutritional status during pregnancy. The women’s nutritional status was measured at the 18th and 28th gestational weeks and accounted for anthropometric measurements, dietary intakes (assessed via a 24-h recall and FFQ), a physical workload questionnaire, and analysis of circulating micronutrients (i.e., RBC folate, plasma ferritin, and vitamins B-12 and C). Total spine and total body bone mineral content and bone mineral density were measured 6 y postnatally by using DXA absorptiometry in 698 children (of 762 live births) and their parents (75). Data indicated that the higher maternal intake of calcium-rich foods during pregnancy (i.e., milk, milk products, pulses, nonvegetarian foods, green leafy vegetables, and fruits) was correlated with higher total body and total spine bone mineral content in children (75). To our knowledge, there are no other studies providing clear evidence of causal correlation between possible calcium deficit in vegan pregnant women and possible adverse outcomes.

Vitamin D.

As mentioned above, extending sunlight exposure and consuming vitamin D–fortified foods (9) might be appropriate strategies to increase vitamin D intake and to avoid possible vitamin D deficiencies, especially during pregnancy. Nevertheless, despite the abundant sunshine, vitamin D deficiency has been reported to be prevalent in India (76), Greece (77), and Iran (78) and these deficiencies might be related to poorly varied plant-based dietary patterns (79, 80). In this regard, a 2012 Indian study assessed in 50 pregnant women aged 20–40 y whether vegetarian diet together with dietary calcium intake, multivitamin supplementation, the extent of sun exposure, and the use of sunscreen were associated with their vitamin D status (i.e., measurement of 25-hydroxyvitamin D concentration by RIA) during pregnancy (81). Although neither multivitamin supplementation nor dietary calcium intake was associated with vitamin D concentration, the extent of sun exposure, the use of sunscreen, and a vegetarian dietary pattern were found to be directly associated with 25-hydroxyvitamin D concentrations (81).

Phytoestrogens.

A high consumption of soy products normally provides a high intake of phytoestrogens, which might be associated with an increased risk of hypospadias, as reported in some animal models (82, 83). Hypospadias is a congenital malformation in which the penile urethra opening occurs on the ventral side of the penis. A recent meta-analysis assessed whether hypospadias was associated with maternal intake of phytoestrogens, which are often high in vegetarian and vegan diets. Data analysis of 1250 hypospadias cases and 3118 controls revealed that high intakes of phytoestrogens (i.e., daidzein, genistein, glycetin, secoisolariciresinol, total isoflavones, total lignans, and total phytoestrogens) during pregnancy and in the year before the beginning of gestation (as assessed via FFQ) resulted in a reduced risk of hypospadias (84) and, in general, that a vegetarian diet or worse diet quality did not seem to be associated with hypospadias (85). Nevertheless, it was also shown that a diet lacking both fish and meat during pregnancy might be associated with a >4-fold increased risk of hypospadias, as shown in a case-control Swedish/Danish study assessing maternal diet via a self-administered FFQ in mothers of children with hypospadias and matched controls (86). Similarly, mothers who were vegetarian during pregnancy had an adjusted OR of 4.99 of giving birth to a son affected by hypospadias compared with omnivores who took iron supplements, as reported in a British longitudinal study comprising 51 hypospadias cases (of 7928 boys who were analyzed) (87).

Other possible health-related issues.

Another major issue that often occurs in the first months after delivery is postpartum depression (PPD), which is characterized by depressive episodes beginning within 1 mo after delivery and experienced by ∼13% of mothers (88). A recent study in 400 Austrian participants showed that depression was found to be more prevalent among vegetarians (47.4%) than among nonvegetarians (19.4%), and subjects with self-reported depression described nutritional support during pregnancy as inadequate (88). However, this is the only study showing a direct correlation between vegetarian diet and PPD. In addition, thus far there is no clear evidence for recommending selenium, DHA, EPA, or any other dietary supplements to prevent PPD in vegan pregnant women (or in pregnant women following a vegan diet) (89).

Furthermore, Down syndrome is often screened at midtrimester gestation by screening maternal serum free β-human chorionic gonadotropin and α-fetoprotein concentrations. Notably, concentrations of these serum biomarkers often are higher in vegetarian pregnant women than in omnivores, leading to a higher false-positive rate of Down syndrome screening, possibly resulting in needless invasive procedures, as reported in a Taiwanese study of 98 vegetarian and 122 omnivore singleton pregnancies (90). For this reason, establishing α-fetoprotein and β-human chorionic gonadotropin reference concentrations in vegetarian pregnant women would be required to avoid these false-positive screening results (90). Studies describing possible issues related to maternal plant-based dietary patterns are summarized in Table 2.

TABLE 2.

Summary of the possible issues related to maternal plant-based dietary patterns¹

Possible shortcomings	Possible effects (reference)
Lower intake of n–3 PUFAs	Lower DHA content in breast milk, especially in countries with lower gross domestic product; possible negative growth, metabolic, and immune childhood outcomes; lower PUFA delivery to the fetus (60–62)
Lower intake of vitamin B-12	Vegan/vegetarian mothers might have vitamin B-12 deficiencies during gestation (12); possible lethargy, hypotonia, arrest/regression of developmental skills, megaloblastic anemia, neurodisability; increased NTD risk, lower lean mass, higher adiposity, insulin resistance, impaired neurodevelopment, higher cancer risk, hyperhomocysteinemia (63–68)
Lower intake of dietary minerals	Iron deficiencies during gestation in vegan/vegetarian mothers (12) correlate with lower birth weight, poor pregnancy outcome, impaired school performance, decreased productivity (69, 70); in reference 70, vegetarian mothers seemed to have adequate dietary iron intake vs. nonvegetarian mothers
	Zinc deficiency (but insufficient evidence of possible effects during pregnancy) (71)
	Iodine deficiency: possible transient neonatal hypothyroidism (72, 73)
	Calcium deficiency: lower total body and total spine bone mineral content in children, possible risk of childhood rickets (74, 75)
Lower vitamin D concentrations	Vegetarian diet might cause reduction in 25(OH)D concentrations, risk of hypovitaminosis D, and rickets in offspring (79–81)
Higher intake of phytoestrogens	Increased risk of hypospadias in rodents (82, 83); possible risk of hypospadias (conflicting data) (84–87)
Lower intake of specific micronutrients (e.g., selenium, DHA, EPA)	Vegetarian diet seems to be associated with postpartum depression (88, 89)
Higher maternal serum free β-human chorionic gonadotropin and α-fetoprotein concentrations	Higher false-positive rate of Down syndrome screening (as assessed in mothers following a vegetarian diet) (90)

¹NTD, neural tube defect; 25(OH)D, 25-hydroxyvitamin D.

Further Considerations

Diet is one of the most critical lifestyle-related factors in determining health state and the risk of most noncommunicable diseases. In light of the finding that maternal diet can affect “early life programming,” thus predisposing the offspring to develop (or not) several types of diseases later in life (1, 2), specific dietary interventions before, during, and after gestation that are aimed at improving diet quality and setting appropriate intakes of macro- and micronutrients should be considered. In this regard, well-planned plant-based diets seem to be beneficial at all life stages, including pregnancy, as recommended by the Academy of Nutrition and Dietetics and the Dietitians of Canada (6, 91). Compared with omnivores, vegetarians and vegans, in particular, tend to be thinner, with lower serum cholesterol concentrations and lower blood pressure and consequently less at risk of heart disease. Overall, plant-based diets seem to confer protection to both mothers and newborns by reducing the risk of several pregnancy-related issues (8, 13, 14, 16, 19, 21), conferring protection against genotoxicant exposure (27, 29–31), and decreasing the risk of developing pediatric diseases (31, 33, 45, 47, 49, 54, 55, 59). However, populations in developing countries, despite having overall access to plant-based foods, often show a higher prevalence of micronutrient deficiencies (92), which might also be determined by inappropriate cooking and food-processing methods (93). Importantly, these deficiencies might have a special impact during pregnancy. For this reason, in resource-poor countries, it would be desirable to implement guidelines aimed at correcting possible pathogenic dietary patterns and to establish long-term participatory interventions to promote the adoption of traditional food-processing and preparation methods (e.g., thermal and mechanical processing, soaking, fermentation, germination, and malting) (92, 93).

Nevertheless, the risk of specific nutritional deficiencies might occur, especially during gestation, given the higher demand (94). In particular, because concentrations of vitamin D and folate are often low during pregnancy in developed countries, recommending a diet enriched in folate and calcium and adequate amounts of vitamin D through sun exposure or supplements might be advisable (13). This has special relevance in low-income or developing Mediterranean, tropical, and subtropical countries where, despite abundant sunlight, hypovitaminosis D together with low calcium intake are highly prevalent (76–78); and these deficiencies seem to be due to poorly varied plant-based dietary patterns (79–81).

In addition, during pregnancy, especially when strictly adhering to a vegan regimen, it is essential to provide adequate intakes of other nutrients that are known to be important in preventing possible health complications in the offspring, in particular the following: n–3 FAs (even of plant origin, such as soybean or rapeseed oil) (60) to avoid brain developmental defects (61); vitamin B-12, to prevent deficiencies possibly causing offspring neurodisability (65); vitamin D, to prevent the risk of childhood rickets (79–81); and other minerals, such as dietary iron (69), zinc (71), and iodine (72, 73). In general, it is important to consume a varied diet, regardless of whether it is vegan or accounts for a moderate consumption of animal-derived products (i.e., vegetarian and omnivorous), that contains a variety of macro- and micronutrients to avoid possible nutritional deficiencies.

However, the consumption of fish during pregnancy should be carefully examined. On the one hand, the intake of fish and fish products has been considered by some authors to be beneficial in reducing the risk of cleft lip or cleft palate (48), hypospadias (86), and pediatric tumors (31, 49) and fundamental in supplying adequate amounts of n–3 FAs. On the other hand, fish is also known to be one of the main exogenous dietary sources of NOCs (28), large fish have been reported to contain high concentrations of heavy metals and other contaminants (49, 50), and maternal fish consumption has been causally linked to an increased risk of infant wheeze and food allergy (35, 36). As a consequence, a precautionary approach should be generally followed with regard to fish intake, especially during pregnancy, and possible alternative plant-derived sources of n–3 PUFAs should be considered, such as soybean or rapeseed oil, that are enriched in ALA, the natural precursor of n–3 FAs. Despite the reported low bioconversion rate of ALA into n–3 PUFAs, it has been found that the endogenous synthesis of DHA from both ALA and EPA appears to be greater in women than in men, which may partly be due to a lower utilization of ALA for β-oxidation and to a possible estrogen-mediated enhancement of δ-6 desaturase activity (95). This more efficient bioconversion capacity in women is particularly relevant in providing an adequate supply of DHA during pregnancy (95).

Last, some of the studies cited in this review provide conflicting data (33, 34, 44, 45, 84, 85, 87), which partially limits inferring clear correlations between specific nutritional patterns or nutrients and the risk of developing certain diseases in the offspring. These discrepancies are mainly due to different study periods, different food groupings [e.g., vegetarian diets accounting (or not) for the intake of fish products, milk, and dairy], and different sizes of analyzed cohorts. In addition, the majority of cited studies assessed maternal dietary intake postnatally by using FFQs, which might substantially differ between studies. Values reported from FFQs are often subject to substantial systematic and random errors that can significantly affect the design, analysis, and interpretation of nutritional epidemiologic studies (96–98). Moreover, the majority of these studies generally do not provide detailed information on maternal nutritional status. Taking these possible flaws into account, and considering that conducting randomized controlled trials and nutritional interventions in pregnant women might be ethically questionable, further large-scale observational studies would help to define correlations between consolidated diets, gestation, and health and might be suitable to design pregestational nutrition intervention strategies.