REVIEW

Plant-Based and Plant-Rich Diet Patterns during

Gestation: Beneficial Effects and Possible
Shortcomings1,2
Francesca Pistollato,3 Sandra Sumalla Cano,3–5 Iñaki Elio,3–5 Manuel Masias Vergara,3,6 Francesca Giampieri,7,8*
and Maurizio Battino3,8*
3
Center for Nutrition and Health, European University of the Atlantic, Santander, Spain; 4International Ibero-American University, Campeche,
Mexico; 5Ibero-American University Foundation, Barcelona, Spain; 6International Ibero-American University, Arecibo, Puerto Rico; 7Umberto Veronesi
Foundation, Milan, Italy; and 8Department of Specialized Clinical Sciences and Dentistry, Marche Polytechnic University, Ancona, Italy

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 (v-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. Adv Nutr
2015;6:581–91.

Keywords: plant-based diets, human, gestation, preeclampsia, diabetes, pediatric tumors, pediatric diseases

Introduction modify diet toward habits that will be healthier for both
Several epidemiologic studies have shown that nonfavorable mothers and their offspring (3).
environmental and lifestyle factors play an important role In this regard, vegan and vegetarian dietary patterns are
during pregnancy, determining newborns’ health state and currently considered beneficial for the prevention of several
possibly affecting offsprings’ risk of developing certain chronic and degenerative ailments (4–6) and appropriate
chronic and degenerative diseases later in life, a phenome- during all life cycle stages, including pregnancy, lactation,
non commonly defined as “early life programming.” Among infancy, childhood, and adolescence (6). It has been re-
these factors, maternal nutrition (e.g., high-energy and ported that well-balanced vegan and vegetarian diets can
high-fat diets), sleep quality, a low level of physical activity, be considered safe and beneficial during pregnancy. Vegan
smoking, and exposure to pollutants can negatively influ- pregnant women have a lower-than-average rate of cesarean
ence fetal development and health status later in life (1, 2). delivery, less postpartum depression, and lower neonatal
For instance, it is known that both maternal malnutrition and maternal mortality, with no complications or negative
and overnutrition are associated with a higher risk of diabe- outcomes that are higher than average (7–9). Generally,
tes in the offspring. For this reason, pregnancy represents a vegans weigh less than omnivores and seem to experience
relevant window of opportunity for health care providers to fewer weight-related complications, and plant-based mater-
nal diets could prevent gestational diabetes by providing
1
Supported by a grant from the Fondazione Umberto Veronesi, Milan, Italy (to FG). greater amounts of fiber (10). In addition, the incidence of
2
Author disclosures: F Pistollato, S Sumalla Cano, I Elio, M Masias Vergara, F Giampieri, and M preeclampsia appears to be lower among vegan mothers (8).
Battino, no conflicts of interest.
* To whom correspondence should be addressed. E-mail: [Link]@[Link] (M Battino), This could be related to the theory that the risk of pre-
[Link]@[Link] (F Giampieri). eclampsia is directly associated with a high consumption of

ã2015 American Society for Nutrition. Adv Nutr 2015;6:581–91; doi:10.3945/an.115.009126. 581
fat and sugar and a low intake of fiber, and plant-based di- pregnant women and 339 normotensive controls. The foods
etary patterns generally provide low amounts of fat and that were found to be more beneficial in reducing the risk of
sugar and higher quantities of fiber (11). Despite these ben- preeclampsia in this study were fruits, vegetables, cereals,
eficial outcomes, some studies reported that mothers follow- dark bread, and low-fat dairy products (11).
ing vegetarian diets could give birth to infants with lower
birth weights, whereas other studies reported higher birth GDM. A high intake of fiber during pregnancy seems to be
weights; in addition, some heterogeneous studies reported particularly beneficial in preventing GDM. Indeed, maternal
that vegan/vegetarian women could be at risk of vitamin diets characterized by low intakes of fiber and a high glyce-
B-12 and iron deficiencies during gestation, as recently de- mic load seem to be associated with an increased risk of
scribed (12). GDM, as shown in a prospective cohort study in 13,110 el-
Here we review the scientific literature in this field, focus- igible women in the Nurses’ Health Study II (10). In partic-
ing specifically on observational studies in humans, and ad- ular, an increment of 10 g/d in total fiber intake was found to
dress the protective effects elicited by gestational dietary be associated with a 26% risk reduction in GDM and an in-
patterns enriched in plant-derived foods and their health- crement of 5 g/d in cereal or fruit fiber intake was associated
related outcomes for mothers and their offspring. We also with a 23% or 26% reduction in GDM, respectively. On the
discuss the possible risks linked to poorly balanced or defi- contrary, dietary glycemic load was directly associated with
cient plant-based (i.e., vegan) diets. GDM risk (10).
Another randomized controlled clinical trial enrolled 52
women diagnosed with GDM; participants were randomly
Plant-Based or Plant-Rich Diets during Preg- assigned to consume for 4 wk either a control diet (n =
nancy and the Risk of Gestation-Related Issues 26) or the DASH (Dietary Approaches to Stop Hyperten-
Recent studies indicate that nutritional patterns enriched sion) diet (n = 26) (15). The DASH diet was enriched in
with plant-derived foods might be protective during preg- fruits, vegetables, whole grains, and low-fat dairy products,
nancy, conferring beneficial effects to both mothers and with low amounts of saturated fats, cholesterol, and refined
their offspring. In this regard, it has been reported that grains, and a total of 2.4 g sodium/d. Fewer women follow-
low-glycemic, Mediterranean diet–type patterns, character- ing the DASH diet underwent cesarean delivery (46.2% vs.
ized by high intakes of vegetables, fruits, and grains, together 80.8% of the control group) and started insulin therapy after
with adequate consumption of n–3 FAs may improve ovula- intervention (23% vs. 73% of the control group). In addi-
tory infertility, decrease preterm birth, and lower the risk of tion, offspring born to DASH group participants presented
gestational diabetes mellitus (GDM)9 (13). Below we sum- lower weight, head circumference, and ponderal index
marize observational and intervention studies describing values compared with children born to mothers who con-
the beneficial effects of maternal diets enriched in plant- sumed the control diet (15).
derived foods in reducing the risk of common gestation-
related issues. Pregravid obesity and gestational weight gain. Pregravid
obesity in pregnant women, defined as a BMI (in kg/m2)
Preeclampsia. Diets characterized by a high consumption >29, has been found to be correlated with inadequate di-
of plant-derived foods, with at least 3 daily servings of veg- etary intakes of grains, vegetables, iron, and folate (both
etables, combined with physical activity seem to reduce the of plant and animal origin), as shown in 2394 women re-
risk of pregnancy-induced hypertension (or preeclampsia) cruited for a clinic-based population study (16). More-
(8, 14). A longitudinal study conducted in 238 black preg- over, a systematic review of observational studies on
nant women in the Congo showed that the incidence of ar- gestational weight gain (GWG) showed that both intake
terial hypertension was 4.6% overall (2.9% of whom had of carbohydrates and vegetarian diets were associated
preeclampsia and 1.7% of whom showed transient hyper- with lower GWG, contrary to dietary patterns charac-
tension). Hypertensive mothers presented lower parity and terized by higher intakes of proteins, animal fats, and
infant birth weights, with higher rates of edema. Preeclamp- energy-dense foods and more servings of food per day
sia occurred more frequently among women who rarely (17), suggesting that plant-based dietary regimens could be
consumed daily servings of vegetables during pregnancy beneficial in preventing GWG. Accordingly, first-trimester
(33.3%) than among women consuming $3 servings of veg- vegetarian diets (i.e., diets excluding certain animal pro-
etables per day (3.7%) (14). ducts), together with walking during midpregnancy and
Similarly, diets high in fiber and potassium seem to be as- vigorous physical activity (30 min/d for both), were in-
sociated with a reduced risk of hypertension and preeclamp- versely associated with excessive GWG (defined as a “gain
sia, as reported in a case-control study in 172 preeclamptic greater than the upper limit for each woman’s prepregnancy
BMI category” (18) (e.g., women with a BMI >29.0 who
9
Abbreviations used: ALA, a-linolenic acid; ALL, acute lymphoblastic leukemia; CKD, chronic gained at least 6.8 kg but not more than 11.5 kg) contrary
kidney disease; DASH, Dietary Approaches to Stop Hypertension; DNAt2, DNA to diets high in total energy, dairy, and fried foods, which
topoisomerase II; GDM, gestational diabetes mellitus; GWG, gestational weight gain; MLL,
mixed-lineage leukemia gene; NOC, N-nitroso compound; NTD, neural tube defect; OFC, were directly associated with high GWG, as shown in 1388
orofacial cleft; PPD, postpartum depression. women (19).

582 Pistollato et al.

Calf cramps. A German study comprising 108 healthy preg- associated with birth size (24). The Danish study highlighted
nant women (i.e., not taking any medical drug interacting strong associations between high intakes of both green leafy
with magnesium absorption, free of any metabolic disease, vegetables and fruits during pregnancy and birth weight in
and not using magnesium supplements) who were following 43,585 well-nourished women (25). Overall, these studies
either a long-term (>3 y) plant-based/vegetarian diet [either suggest that increasing maternal intakes of plant-derived
lactoovovegetarian (n = 27) or including a low amount of foods (i.e., vegetables and fruits) and, as reported in some
meat (n = 43)] or an average Western diet (n = 38) showed studies, of milk products could be beneficial in preventing
that vegetarian diets, by providing a high intake of magne- gestation-related problems and improving fetal growth.
sium (assessed by higher urinary magnesium excretion), re-
duced the frequency of calf cramps, particularly during the Plant-Based or Plant-Rich Diets during Preg-
third trimester of pregnancy, compared with an average nancy and the Risk of Genotoxicant Exposure
Western diet (20). In particular, lactoovovegetarian regi- Pregnant women following a plant-based diet could also be
mens were found to be characterized by both the highest better protected against genotoxicants.
magnesium intake and the highest urinary magnesium ex-
cretion (20). It should be noted that authors of this study ap- Bulky DNA adducts. It has been shown that the presence of
plied the term “vegetarian” to diets that also included low bulky DNA adducts in cord blood is a sensitive indicator of a
amounts of meat, which should be taken into account biologically effective dose of genotoxic agents at the prenatal
when disaggregating the effects specifically elicited by strict stage, including polycyclic aromatic hydrocarbons, which
vegetarian regimens (i.e., lactoovovegetarian) vs. health- may contribute to reduced fetal growth (26). A recent mul-
conscious omnivorous diets. ticenter study comprising 229 mothers and 612 newborns
estimated the association between the amounts of bulky DNA
Chronic kidney disease. Gestation time can be particularly adducts in cord blood (measured by the 32P-postlabeling
challenging for women affected by chronic kidney disease technique in white blood cells), birth weight, and maternal
(CKD), especially considering the scarcity of therapeutic intake of fruits and vegetables during pregnancy (27). Data
drugs suitable during pregnancy. In this regard, low-protein indicate that women who more frequently consume fruits
vegetarian diets (i.e., 0.6 g protein/(kg $ d), supplemented and vegetables were better protected against the accumula-
with a commercial keto acid preparation and 1–2 free choice tion of bulky DNA adducts, and the weights of their new-
meals/wk) were reported to be beneficial for the manage- borns were greater than the weights of offspring born to
ment of pregnant patients with CKD, as shown in a pros- women consuming fewer fruits and vegetables (27).
pective cohort study in 168 pregnant women undergoing
monthly measurements of renal function, urine protein, Nitrate, nitrite, and N-nitroso compounds. Maternal ex-
uric acid, serum electrolytes, coagulation variables, and blood posure to nitrate, nitrite, and N-nitroso compounds
cell counts and urinalysis and urinary culture (21). (NOCs) from drinking water or diet has been associated
This evidence was later confirmed in a nutritional inter- with a higher risk of developing neural tube defects
vention study by the same group in pregnant women with (NTDs) and pediatric brain tumors. It is conceivable that
stages 3–5 CKD, which reported a positive correlation plant-based/vegetarian diets, characterized by a high con-
among low-protein vegan/vegetarian diets during gestation sumption of fruits and vegetables and low or no intakes of
[i.e., 0.6–0.8 g protein/(kg $ d), with keto acid supplemen- cured meat and smoked fish, which represent the main ex-
tation and 1–3 free meals/wk, allowing small quantities of ogenous dietary sources of NOCs (28), could prevent NOC
milk and yogurt (100–150 mL/d)], a reduced likelihood of exposure, thus decreasing the risk of congenital malforma-
small-for-gestational-age offspring, and the absence of detri- tions and childhood brain tumors (29–31).
mental effects on both kidney function and urine protein However, it should be noted that pickled vegetables also
concentrations in the mothers (22). contain relatively large amounts of nitrite and NOCs. In
this regard, a 2011 study examined the possible association
Fetal growth variables. Maternal plant-rich diets also seem to between maternal periconceptional consumption of pickled
be beneficial in supporting fetal growth. Small-for-gestational- vegetables and NTDs in 4 Chinese counties, and the data in-
age weight and body length measurements were inversely dicated that >6 pickled vegetable meals/wk increased the risk
associated particularly with a high consumption of veg- of NTDs, compared with less frequent (i.e., <1 meal/wk)
etables, but not fruits, in a Spanish mother-infant cohort consumption (32). In addition, the authors of this study showed
(n = 787 infant-mother pairs) (23). Accordingly, 2 previous that maternal intake ($1 meal/wk) of meat, eggs, or milk
studies, one from India and another from Denmark, both elicited a protective effect against the risk of NTDs (32).
showed that a high intake of fruits and vegetables seems to
be positively associated with birth weight and size (24, 25). Plant-Based or Plant-Rich Diets during
In particular, the Indian study reported that the consump- Pregnancy and the Risk of Pediatric Diseases
tion of milk at gestational week 18 and of green leafy vege- Plant-based diets and a high intake of fruits and vegetables
tables/fruits at gestational week 28, by providing adequate during pregnancy may prevent the risk of developing certain
intakes of folate and other micronutrients, was positively diseases in infants.

Plant-based diets during pregnancy 583

Pediatric wheeze, asthma, and eczema. Maternal intakes root vegetables, gluten-containing foods, nongluten cereal
of vegetables, fruits, and selected antioxidants during preg- grains, cow milk and cow-milk products, fruits, vegetables,
nancy were reported to reduce the risk of wheeze and ec- meat and poultry, and fish), only a higher maternal intake
zema in infants aged 16–24 mo, as shown in 763 Japanese of potatoes was found to be correlated with the delayed onset
mother-child pairs (33). In particular, a higher mater- of islet autoantibodies (40).
nal intake of green and yellow vegetables, citrus fruit, and In addition, dietary vitamin D intake and/or supplemen-
b-carotene during pregnancy significantly reduced the risk tation with vitamin D during pregnancy was found to be
of eczema, but not wheeze, in the offspring, whereas the possibly protective against islet autoantibody appearance
consumption of vitamin E during pregnancy lowered the in the offspring (41, 42). Maternal intake of n–3 and n–6
risk of infantile wheeze but not eczema (33). FAs was also not associated with the appearance of islet au-
Conversely, the same research group later reported that a toantibodies in their offspring (41).
Western nutritional pattern during pregnancy, characterized Notably, fish are known to provide the highest amount of
by a high intake of vegetable oil, salt-containing seasonings, vitamin D, although this source mainly derives from microal-
beef, pork, processed meats, eggs, chicken, and white vegeta- gae, which represent their main food supply. The presence of
bles, seems to confer protection against wheeze, whereas nei- both vitamin D3 and provitamin D3 in microalgae confirms
ther a healthy maternal dietary pattern (i.e., high intakes of that vitamin D3 exists in the plant kingdom, as found in
green and yellow vegetables, seaweed, mushrooms, white veg- several plant species (43). In addition to sunlight exposure
etables, pulses, potatoes, fish, seafood, fruits, and shellfish) or to increase the amount of vitamin D synthesis, many vita-
the Japanese pattern (i.e., high intakes of rice, miso soup, sea- min D–fortified foods (e.g., soy milk, breakfast cereal, orange
food, and fish) during pregnancy was directly related to juice, and meal replacement bars) (9) could be consumed es-
higher childhood wheeze or eczema risk (34). However, in pecially during gestation to increase vitamin D intake.
this study both the “healthy” and “Japanese” maternal dietary Moreover, a high maternal intake of retinol (mainly from
patterns were characterized by a high intake of fish, fish pro- meat and milk products), b-carotene (from roots), vitamin C
ducts, and shellfish, which have been shown in other studies (from juice, fruits, vegetables, and citrus fruits), vitamin E
to possibly increase the risk of infant wheeze and food allergy (from vegetable oils and cereal products), selenium and zinc
(35, 36). In addition, a maternal Mediterranean diet and diets (both from meat and milk), or manganese (from cereal pro-
including fruits and vegetables and providing high intakes of ducts), assessed postnatally via a self-administered FFQ, was
vitamins A, D, and E and zinc also seem to prevent asthma, found to confer no relevant protection against advanced b
allergic outcomes, and atopic dermatitis in the offspring, as cell autoimmunity in early childhood in a Finnish prospective
reported in a 2011 meta-analysis comprising 21 cohort, 15 population-based cohort study comprising 4297 children
case-control, and 26 cross-sectional studies (37). with increased genetic susceptibility to type 1 diabetes (44).
Another Swedish study analyzed 5724 mother-child pairs
Diabetes. Several maternal factors during pregnancy could and showed that the low consumption of vegetables (i.e.,
increase the risk of type 2 diabetes in the offspring later in <3–5 times/wk) during pregnancy (assessed postnatally by
life. Among these risk factors, malnutrition, hyperglycemia, an FFQ) was associated with an increased risk of islet autoan-
obesity, smoking, drinking, junk food diets, hormone use, tibody production in children (45), suggesting that the daily
and stress seem to play a relevant role (3, 38). consumption of vegetables by pregnant mothers could de-
In particular, a family history of type 2 diabetes (the crease the risk of type 1 diabetes in the offspring.
transmission of type 2 diabetes to the next generation) Further large-scale studies would be helpful in elucidat-
seems to be stronger for maternal than for paternal diabetes ing the correlations between specific nutritional patterns
and this difference seems to be determined by the larger (i.e., vegan, vegetarian, or omnivorous) and/or specific
contribution of diet, adiposity, and other lifestyle factors foods (i.e., plant-derived, eggs, dairy products, meat, and
to maternal diabetes, as shown in a Dutch study comprising fish) and the risk of type 1 diabetes in the offspring.
35,174 participants (aged 20–70 y) (39). Nevertheless, stud-
ies addressing the possible protective role of plant-based NTDs and orofacial clefts. A high periconceptional intake
diets during gestation in relation to the onset of type 2 dia- of folic acid, in addition to preventing NTDs, is also known
betes in the offspring have not been published previously. to prevent orofacial clefts (OFCs) in the offspring; and lac-
Interestingly, prenatal nutritional exposures could be cor- toovovegetarian pregnant women, compared with low
related with the risk of developing type 1 diabetes in children. meat eaters and Western diet controls, seem to present the
The Diabetes Autoimmunity Study in the Young analyzed the highest concentrations in both plasma and RBCs, as shown
association between mothers’ diet, assessed via a FFQ, during in a prospective study in 109 pregnant women (46). Both
the third trimester and islet autoantibody production at 9 mo, NTDs and OFCs are caused by aberrant neural crest cell–
15 mo, and 2 y of age and annually thereafter in 642 infants related mechanisms and for this reason might possibly share
(40). A child was considered diabetic if tests were positive for common pathogenic pathways (47). An analysis of 182
islet autoantibodies at 2 consecutive blood draws and re- mothers of children with OFCs and 173 control mothers re-
mained positive at the last follow-up. Among the foods taken vealed that mothers whose preconceptional intake of macro-
into account for possible correlations (e.g., potatoes and other nutrients, vitamins, minerals (i.e., protein, fat, carbohydrate,

584 Pistollato et al.

fiber, cholesterol, vitamin A, retinol, b-carotene, ascorbic legumes, apples, onions, berries, soy products, coffee, black
acid, a-tocopherol, calcium, phosphorus, iron, magnesium, and green tea, cocoa, red wine, and coffee and other caffein-
and zinc), and specific food groups (vegetables, eggs, fruits, ated beverages (55). Acute myeloid leukemia AML (MLL+) is
grain products, bread, herbs, cheese, and soy products) was known to possibly arise upon chemotherapy with DNAt2 in-
lower were more prone to have offspring with OFCs. Also in hibitors, which can naturally occur in foods, such as quercetin
this study, dietary intake was assessed ;14 mo after delivery (a flavonoid present in some fruits and vegetables), genistein
via an FFQ. Importantly, increasing intakes of vegetable pro- (in soy), catechins (present in green and black tea), cocoa, and
tein, fiber, ascorbic acid, iron, and magnesium were found to red wine (56–58). Further large-scale clinical and epidemio-
reduce the risk of OFCs (47). Similarly, a case-control study logic studies are needed to confirm these observations.
in 203 mothers of children with OFCs and 178 control In addition, low gestational maternal intake of fruits and
mothers showed that a maternal “prudent” dietary pattern vegetables may contribute to the development of sporadic
(assessed 14 mo after delivery), characterized by high intakes (noninherited) retinoblastoma. In this regard, a Mexican
of garlic, nuts, vegetables, and fish, together with increased hospital–based case-control study assessed maternal dietary
serum vitamin B-12 and folate concentrations, was not asso- intake of vegetables and fruits in a cohort study comprising
ciated with OFC risk, unlike a Western diet (i.e., high intakes the mothers of 101 children with retinoblastoma compared
of meat, pizza, legumes, and potatoes and a low intake of with 172 control cases. Data showed that mothers who con-
fruits), which was shown to increase by ;2-fold the risk sumed <2 daily servings of vegetables, and consequently
of offspring with OFCs (48). lower quantities of folate and lutein/zeaxanthin derived
from fruits and vegetables, had a higher risk of having chil-
Pediatric tumors. There is currently a growing body of evi- dren affected by sporadic retinoblastoma (59).
dence suggesting that prolonged and frequent breastfeeding Furthermore, a 2009 case-control study assessed possible
and dietary and vitamin intakes during pregnancy could correlations between maternal diet habits (measured by an
contribute to reducing the risk of childhood cancers. There- FFQ) and the risk of childhood brain tumors in 9 study cen-
fore, dietary choices starting early in life deserve attention ters from 7 different countries, contributing to a total of
(49). Particularly, a high intake of fruits, vegetables, and 1218 cases and 2223 controls. This study highlighted that di-
whole grains; a favorable n–6 to n–3 PUFA ratio; and the etary patterns that included cured meats, eggs/dairy, and oil
consumption of fish may reduce cancer risk in children products resulted in being generally associated with a higher
(49). Nevertheless, children and pregnant women should incidence of brain tumors (31). On the contrary, diets that
avoid consuming large fish, such as shark, swordfish, king included yellow-orange vegetables, grains, and fresh fish
mackerel, and tilefish, because they may contain high con- seemed to decrease this risk. Specifically, the consumption
centrations of heavy metals (e.g., mercury), polychlorinated of cured meat was associated with astrocytomas and ependy-
biphenyls, dioxins, and other contaminants (49, 50). momas and high intake of oil products was associated with
It has been suggested that maternal supplementation of medulloblastoma. Conversely, the consumption of crucifer-
folic acid/folate, which is naturally found in green leafy vege- ous vegetables reduced the risk of anaplastic astrocytomas,
tables, fruits, and legumes (51), may reduce the risk of pedi- whereas the consumption of fresh fish decreased the risk
atric acute lymphoblastic leukemia (ALL) (52), Wilms tumor, of astroglial tumors (31). Studies describing the effects eli-
and primitive neuroectodermal tumors (53). Accordingly, cited by plant-based and plant-rich diet patterns during ges-
maternal dietary patterns, assessed 12 mo before pregnancy, tation are summarized in Table 1.
characterized by a high intake of vegetables, protein sources
(both plant and animal derived), and fruits, and particularly Possible Shortcomings Associated with
of provitamin A carotenoids and the antioxidant glutathione, Plant-Based Diets during Pregnancy
were found to be inversely associated with childhood ALL, as n–3 PUFAs. Poorly planned, monotonous plant-based diets
shown in a population-based case-control study comprising may lead to nutritional deficiencies that could have relevant
138 ALL cases and 138 controls matched on sex, date of birth, consequences in prenatal and postnatal life. A 2011 study
mother’s race, and county of residence at birth (54). that analyzed 13 low- and middle-income countries re-
Accordingly, a case-control study including 240 incident ported that the content of DHA in breast milk is very low
cases of infant acute leukemia and 255 controls reported in populations living mainly on plant-based diets but higher
that maternal consumption of fresh vegetables and fruits dur- in fish-eating countries (60). In addition, the supply of fat
ing pregnancy seems to be associated with a reduced risk of in- and n–3 FAs is higher in countries with higher gross domes-
fant leukemia, especially the form that presents mixed-lineage tic product, and 70–80% of PUFA intake comes from cereals
leukemia gene (MLL) translocations (MLL+) (55). How- and vegetable oils, some of which are characterized by low
ever, the risk of one specific form of leukemia [i.e., MLL+ contents of a-linolenic acid (ALA; 18:3n23). These data
acute myeloid leukemia, or AML (MLL+)] could be increased suggest that increasing the intake of vegetable oils with
by maternal consumption of certain plant-derived foods that higher ALA content, such as soybean or rapeseed oil, and of
are known to be natural sources of DNA topoisomerase II fish would be beneficial for enriching the n–3 FA supply (60).
(DNAt2) inhibitors (55). According to this study, foods con- It should be noted that high amounts of the n–6 FA lino-
taining DNAt2 inhibitors were as follows: canned or dried leic acid (18:2n26) in the diet, as a result of replacement of

Plant-based diets during pregnancy 585

TABLE 1 Summary of the effects elicited by plant-based and plant-rich dietary patterns during gestation1
Plant-based and plant-rich Do studies also account for
diets in relation to Described effects (reference) animal-derived foods?
Pregnancy-related issues Lower-than-average cesarean delivery rate, lower post- In reference 11, beneficial effects of low-fat dairy pro-
partum depression, lower neonatal mortality, lower ducts are reported
maternal mortality, lower risk of preeclampsia (7–9, 11,
14)
High-fiber, low-glycemic-load or DASH diets reduce GDM In reference 15, DASH diet includes low-fat dairy products
(10, 15)
Mediterranean-like diets improve ovulatory infertility, Mediterranean diet generally includes fish, dairy, and/or
decrease preterm birth, lower gestational diabetes risk other animal products
(13)
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 accu- No
mulations; improved newborn weights (27)
Prevention of NOC exposure, decreased risk of congenital In reference 31, consumption of fresh fish seems bene-
malformations and childhood brain tumors (29–31) ficial in reducing the risk of astroglial tumors
Pickled vegetables rich in NOCs might increase neural Intake of meat ($1 meal/wk) and of eggs or milk ($1
tube defects (32) 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 Mediterranean diet generally includes fish, dairy, and/or
26 cross-sectional studies): Mediterranean diet and other animal products
diets enriched in fruits/vegetables prevent asthma, al-
lergy, and atopic dermatitis (37)
Possible reduced risk of islet autoantibody production In reference 44, meat and milk products represent the
and of type 1 diabetes (40, 44, 45) major sources of retinol, selenium, and zinc
Lactoovovegetarian pregnant women compared with In references 46 and 47, eggs and cheese are included; in
low meat eaters and Western diet controls have lower reference 48, fish is included
risk of folate deficiency (46), which correlates with a
reduced risk of orofacial clefts (47, 48)
Possible reduced risk of the following tumors: pediatric In reference 31, consumption of fresh fish seems bene-
ALL, Wilms tumor, primitive neuroectodermal tumors, ficial in reducing the risk of astroglial tumors; in refer-
AML (MLL+), sporadic retinoblastoma, anaplastic as- ence 49, the protective effects of fish are considered; in
trocytomas (31, 49, 54, 55, 59) reference 54, protein sources are also of animal origin
1
ALL, 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.

saturated fats with plant-based PUFAs, generally result in and in the maintenance of myelin. A recent review reported
low n–3 long-chain PUFA endogenous status. Because the that deficiency of vitamin B-12 among pregnant women fol-
FA supply is particularly critical during both pregnancy lowing vegetarian diets was found to range from 17% to
and infancy, it is important to ensure an adequate intake 39%, depending on the trimester; and in general, higher de-
of n–3 PUFAs in order to avoid brain developmental defects ficiency was reported in vegans than in vegetarians (63).
and to reduce the risk of a range of growth, metabolic, and Vitamin B-12 deficiency in developed countries usually
immune childhood outcomes (61). Even at the pregesta- occurs in children who are exclusively breastfed by vegetar-
tional level, an intake of adequate amounts of n–3 PUFAs ian/vegan mothers, and possible symptoms of this deficiency
and DHA plays a major role; indeed, small variations in often appear during the second trimester of life, as reported
the habitual maternal dietary composition before pregnancy in a 6-mo-old infant whose mother followed a strict vege-
are likely to be more effective in improving the delivery of tarian diet and significantly prolonged breastfeeding (64).
long-chain PUFAs to the fetus than are large dietary changes Symptoms can include lethargy, hypotonia, arrest or regres-
in the late stages of pregnancy, as reported (62). sion of developmental skills, and megaloblastic anemia; if
left untreated, children could undergo lasting neurodisabil-
Vitamin B-12. Strict or poorly balanced vegan diets could ity (65). In addition, low intakes of both vitamin B-12 and
result in vitamin B-12 deficiencies and vitamin B-12 is es- protein during pregnancy are associated with increased
sential for the synthesis of nucleic acids and erythrocytes NTD risk, less lean mass, higher adiposity, insulin resistance,

586 Pistollato et al.

impaired neurodevelopment, and altered cancer risk in the bone mineral content and bone mineral density were mea-
offspring (66). For these reasons, vitamin B-12 supplemen- sured 6 y postnatally by using DXA absorptiometry in 698
tation is often recommended, especially for pregnant children (of 762 live births) and their parents (75). Data
women following a strict vegan diet (64, 67), for children indicated that the higher maternal intake of calcium-rich
presenting failure to thrive and delayed development (65), foods during pregnancy (i.e., milk, milk products, pulses,
and to avoid hyperhomocysteinemia, which plays a critical nonvegetarian foods, green leafy vegetables, and fruits) was
role in the pathogenesis of NTDs and preeclampsia (68). correlated with higher total body and total spine bone min-
eral content in children (75). To our knowledge, there are no
Dietary minerals. Unvaried plant-based diets could result in other studies providing clear evidence of causal correlation
low intake of dietary iron. Iron deficiency is correlated with between possible calcium deficit in vegan pregnant women
poor pregnancy outcome but also impaired school perfor- and possible adverse outcomes.
mance and decreased productivity (69). Supplementing iron
by means of iron supplements or iron-fortified foods can Vitamin D. As mentioned above, extending sunlight expo-
counteract iron deficiency, despite limitations of iron com- sure and consuming vitamin D–fortified foods (9) might be
pound bioavailability (69). Interestingly, a 2011 British study appropriate strategies to increase vitamin D intake and to
conducted in a cohort of 1274 pregnant women, aged 18–45 y, avoid possible vitamin D deficiencies, especially during
showed that vegetarians were more likely to have adequate pregnancy. Nevertheless, despite the abundant sunshine, vi-
dietary iron intake and to take supplements during the first tamin D deficiency has been reported to be prevalent in In-
and second trimesters of pregnancy than nonvegetarians dia (76), Greece (77), and Iran (78) and these deficiencies
(70). Adequate iron intake, either from foods or supplements, might be related to poorly varied plant-based dietary pat-
was positively associated with birth weight (70). terns (79, 80). In this regard, a 2012 Indian study assessed
Another micronutrient that could possibly be deficient in in 50 pregnant women aged 20–40 y whether vegetarian
vegan diets is zinc, which is provided by animal tissue diet together with dietary calcium intake, multivitamin sup-
sources and might be further decreased by the intake of plementation, the extent of sun exposure, and the use of
inhibitors of zinc absorption, such as phytic acid, which is sunscreen were associated with their vitamin D status (i.e.,
present in cereals and grains. A recent review commented measurement of 25-hydroxyvitamin D concentration by
on the fact that adult vegetarians, compared with nonvege- RIA) during pregnancy (81). Although neither multivitamin
tarian control groups, seem to present lower dietary zinc in- supplementation nor dietary calcium intake was associated
takes and lower serum zinc concentrations. However, given with vitamin D concentration, the extent of sun exposure,
the lack of sufficient evidence, this has not been clearly the use of sunscreen, and a vegetarian dietary pattern were
proven in pregnant and lactating women, in the elderly, found to be directly associated with 25-hydroxyvitamin D
and in children (71). concentrations (81).
In addition, vegan diets might provide a low intake of io-
dine, which could represent an issue during gestation, al- Phytoestrogens. A high consumption of soy products nor-
though iodine deficiencies are quite uncommon in Western mally provides a high intake of phytoestrogens, which might
countries. Nevertheless, a British single case study reported be associated with an increased risk of hypospadias, as re-
on a 10-d-old female infant and her vegan mother with goiter ported in some animal models (82, 83). Hypospadias is a
and abnormal thyroid function tests; the mother’s dietary io- congenital malformation in which the penile urethra open-
dine intake was found to be extremely low and reliably caus- ing occurs on the ventral side of the penis. A recent meta-
ative of the health complications in her daughter. In cases analysis assessed whether hypospadias was associated with
such as this one, iodine supplements could help to avoid pos- maternal intake of phytoestrogens, which are often high in
sible risks (72), as recently suggested (73). vegetarian and vegan diets. Data analysis of 1250 hypospa-
Strictly vegan pregnant women might possibly experience dias cases and 3118 controls revealed that high intakes of
calcium deficiency (74), although calcium absorption is nor- phytoestrogens (i.e., daidzein, genistein, glycetin, secoisolar-
mally increased during pregnancy and calcium-fortified iciresinol, total isoflavones, total lignans, and total phytoes-
plant-based foods, such as soy/nut/rice/hemp milk, juice, ce- trogens) during pregnancy and in the year before the
reals, calcium-set tofu, beans, sesame seeds, figs, nuts, and beginning of gestation (as assessed via FFQ) resulted in a re-
leafy greens, are currently widely available (9). A 2011 study duced risk of hypospadias (84) and, in general, that a vege-
in 797 pregnant rural Indian women sought to establish tarian diet or worse diet quality did not seem to be
possible relations between bone mass in Indian children and associated with hypospadias (85). Nevertheless, it was also
maternal nutritional status during pregnancy. The women’s shown that a diet lacking both fish and meat during preg-
nutritional status was measured at the 18th and 28th gesta- nancy might be associated with a >4-fold increased risk of
tional weeks and accounted for anthropometric measure- hypospadias, as shown in a case-control Swedish/Danish
ments, dietary intakes (assessed via a 24-h recall and FFQ), study assessing maternal diet via a self-administered FFQ
a physical workload questionnaire, and analysis of cir- in mothers of children with hypospadias and matched con-
culating micronutrients (i.e., RBC folate, plasma ferritin, trols (86). Similarly, mothers who were vegetarian during
and vitamins B-12 and C). Total spine and total body pregnancy had an adjusted OR of 4.99 of giving birth to a

Plant-based diets during pregnancy 587

son affected by hypospadias compared with omnivores who TABLE 2 Summary of the possible issues related to maternal
took iron supplements, as reported in a British longitudinal plant-based dietary patterns1
study comprising 51 hypospadias cases (of 7928 boys who Possible shortcomings Possible effects (reference)
were analyzed) (87). Lower intake of n–3 PUFAs Lower DHA content in breast milk,
especially in countries with lower
gross domestic product; possible
Other possible health-related issues. Another major issue negative growth, metabolic, and
that often occurs in the first months after delivery is postpar- immune childhood outcomes;
tum depression (PPD), which is characterized by depressive lower PUFA delivery to the fetus
episodes beginning within 1 mo after delivery and experi- (60–62)
enced by ;13% of mothers (88). A recent study in 400 Aus- Lower intake of vitamin B-12 Vegan/vegetarian mothers might
have vitamin B-12 deficiencies
trian participants showed that depression was found to be during gestation (12);
more prevalent among vegetarians (47.4%) than among possible lethargy, hypotonia, arrest/
nonvegetarians (19.4%), and subjects with self-reported de- regression of developmental skills,
pression described nutritional support during pregnancy as megaloblastic anemia, neurodis-
inadequate (88). However, this is the only study showing a ability; increased NTD risk, lower
lean mass, higher adiposity, insulin
direct correlation between vegetarian diet and PPD. In addi- resistance, impaired neurodevel-
tion, thus far there is no clear evidence for recommending opment, higher cancer risk, hyper-
selenium, DHA, EPA, or any other dietary supplements to homocysteinemia (63–68)
prevent PPD in vegan pregnant women (or in pregnant Lower intake of dietary Iron deficiencies during gestation in
women following a vegan diet) (89). minerals vegan/vegetarian mothers (12)
correlate with lower birth weight,
Furthermore, Down syndrome is often screened at poor pregnancy outcome, im-
midtrimester gestation by screening maternal serum free paired school performance, de-
b-human chorionic gonadotropin and a-fetoprotein con- creased productivity (69, 70); in
centrations. Notably, concentrations of these serum bio- reference 70, vegetarian mothers
markers often are higher in vegetarian pregnant women seemed to have adequate dietary
iron intake vs. nonvegetarian
than in omnivores, leading to a higher false-positive rate mothers
of Down syndrome screening, possibly resulting in needless Zinc deficiency (but insufficient evi-
invasive procedures, as reported in a Taiwanese study of 98 dence of possible effects during
vegetarian and 122 omnivore singleton pregnancies (90). pregnancy) (71)
For this reason, establishing a-fetoprotein and b-human Iodine deficiency: possible transient
neonatal hypothyroidism (72, 73)
chorionic gonadotropin reference concentrations in vegetar- Calcium deficiency: lower total body
ian pregnant women would be required to avoid these false- and total spine bone mineral con-
positive screening results (90). Studies describing possible tent in children, possible risk of
issues related to maternal plant-based dietary patterns are childhood rickets (74, 75)
summarized in Table 2. Lower vitamin D Vegetarian diet might cause reduc-
concentrations tion in 25(OH)D concentrations, risk
of hypovitaminosis D, and rickets in
Further Considerations offspring (79–81)
Diet is one of the most critical lifestyle-related factors in de- Higher intake of Increased risk of hypospadias in ro-
termining health state and the risk of most noncommunica- phytoestrogens dents (82, 83); possible risk of hy-
pospadias (conflicting data) (84–87)
ble diseases. In light of the finding that maternal diet can
Lower intake of specific mi- Vegetarian diet seems to be associ-
affect “early life programming,” thus predisposing the off- cronutrients (e.g., selenium, ated with postpartum depression
spring to develop (or not) several types of diseases later in DHA, EPA) (88, 89)
life (1, 2), specific dietary interventions before, during, Higher maternal serum free Higher false-positive rate of Down
and after gestation that are aimed at improving diet quality β-human chorionic gonad- syndrome screening (as assessed in
otropin and a-fetoprotein mothers following a vegetarian
and setting appropriate intakes of macro- and micronutri-
concentrations diet) (90)
ents should be considered. In this regard, well-planned 1
NTD, neural tube defect; 25(OH)D, 25-hydroxyvitamin D.
plant-based diets seem to be beneficial at all life stages, in-
cluding pregnancy, as recommended by the Academy of Nu-
trition and Dietetics and the Dietitians of Canada (6, 91). pediatric diseases (31, 33, 45, 47, 49, 54, 55, 59). However,
Compared with omnivores, vegetarians and vegans, in par- populations in developing countries, despite having overall ac-
ticular, tend to be thinner, with lower serum cholesterol cess to plant-based foods, often show a higher prevalence of
concentrations and lower blood pressure and consequently micronutrient deficiencies (92), which might also be deter-
less at risk of heart disease. Overall, plant-based diets seem mined by inappropriate cooking and food-processing methods
to confer protection to both mothers and newborns by re- (93). Importantly, these deficiencies might have a special im-
ducing the risk of several pregnancy-related issues (8, 13, pact during pregnancy. For this reason, in resource-poor coun-
14, 16, 19, 21), conferring protection against genotoxicant tries, it would be desirable to implement guidelines aimed at
exposure (27, 29–31), and decreasing the risk of developing correcting possible pathogenic dietary patterns and to establish

588 Pistollato et al.

long-term participatory interventions to promote the adoption Last, some of the studies cited in this review provide con-
of traditional food-processing and preparation methods (e.g., flicting data (33, 34, 44, 45, 84, 85, 87), which partially limits
thermal and mechanical processing, soaking, fermentation, inferring clear correlations between specific nutritional pat-
germination, and malting) (92, 93). terns or nutrients and the risk of developing certain diseases
Nevertheless, the risk of specific nutritional deficiencies in the offspring. These discrepancies are mainly due to dif-
might occur, especially during gestation, given the higher ferent study periods, different food groupings [e.g., vegetar-
demand (94). In particular, because concentrations of vita- ian diets accounting (or not) for the intake of fish products,
min D and folate are often low during pregnancy in devel- milk, and dairy], and different sizes of analyzed cohorts. In
oped countries, recommending a diet enriched in folate addition, the majority of cited studies assessed maternal di-
and calcium and adequate amounts of vitamin D through etary intake postnatally by using FFQs, which might sub-
sun exposure or supplements might be advisable (13). stantially differ between studies. Values reported from
This has special relevance in low-income or developing FFQs are often subject to substantial systematic and random
Mediterranean, tropical, and subtropical countries where, errors that can significantly affect the design, analysis, and
despite abundant sunlight, hypovitaminosis D together interpretation of nutritional epidemiologic studies (96–
with low calcium intake are highly prevalent (76–78); and 98). Moreover, the majority of these studies generally do
these deficiencies seem to be due to poorly varied plant- not provide detailed information on maternal nutritional
based dietary patterns (79–81). status. Taking these possible flaws into account, and consid-
In addition, during pregnancy, especially when strictly ering that conducting randomized controlled trials and nu-
adhering to a vegan regimen, it is essential to provide ade- tritional interventions in pregnant women might be ethically
quate intakes of other nutrients that are known to be impor- questionable, further large-scale observational studies would
tant in preventing possible health complications in the help to define correlations between consolidated diets, gesta-
offspring, in particular the following: n–3 FAs (even of plant tion, and health and might be suitable to design pregestational
origin, such as soybean or rapeseed oil) (60) to avoid brain nutrition intervention strategies.
developmental defects (61); vitamin B-12, to prevent defi-
ciencies possibly causing offspring neurodisability (65); vita- Acknowledgments
min D, to prevent the risk of childhood rickets (79–81); and All authors read and approved the final version of the
other minerals, such as dietary iron (69), zinc (71), and io- manuscript.
dine (72, 73). In general, it is important to consume a varied
diet, regardless of whether it is vegan or accounts for a mod-
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