Research increasingly points to myriad ways in which maternal dietary intake potentially impacts the health of offspring.1-3 However, despite the large amount of information about the health effects of soyfood consumption, relatively little research on the effects of maternal soyfood intake on the developing fetus has been conducted. Recent research suggests consuming soy during pregnancy may benefit offspring.4
Asian epidemiologic studies have the potential to provide insight about maternal soy consumption because in Asian countries, soy is commonly consumed during pregnancy.5,6 For example, isoflavone intake (mean ± SD) among 194 pregnant Japanese was 21.7 ± 13.7 mg/d.7 Similarly, Miyake et al.6 reported that the genistein and daidzein intake (mean ± SD) of 1,002 pregnant Japanese women participating in the Japan Osaka Maternal and Child Health Study was 15.0 ± 10.1 mg/d and 9.0 ± 6.1 mg/d, respectively.
Most focus on maternal soy consumption has centered on the possible impact of isoflavones.8,9 It has long been established that isoflavones reach the womb.10
Concern about maternal isoflavone intake was raised in 2000 when a British prospective study, which included 7,928 boys born to mothers taking part in the Avon Longitudinal Study of Pregnancy and Childhood, found that mothers who drank soymilk (yes or no) or ate soy “meat” (≥1x/wk versus never) during pregnancy were about 3-fold more likely to give birth to boys with hypospadias.11 However, these associations were not statistically significant; furthermore, ≤2% of the >6,000 mothers enrolled in this study consumed soy during pregnancy.11
Also, although the authors speculated that isoflavones might be responsible for the apparent association with soy intake, legume (dried peas, beans, lentils, and chickpeas) intake was associated with an approximate 7-fold increased risk of hypospadias, despite non-soy legumes containing negligible amounts of isoflavones.12,13 Soy meat analogues, which are also typically low in isoflavones, were also associated with an increased risk.12
Hypospadias is a common genitourinary anomaly in which the opening of the urethra is on the underside of the penis. Springer et al.14 concluded that hypospadias may be on the rise and cited prevalence rates ranging from 5 to 50/10,000 births with high rates in European and North America and low rates in China, Japan, South-East Asia, and South America. One might expect that if isoflavone exposure increased risk of hypospadias, prevalence rates would be higher in Japan than in non-soyfood-consuming countries, but the opposite appears to be the case.15,16
The most direct examination of a possible association between isoflavone intake and risk of hypospadias is a nationwide birth cohort study, which recruited women as early in pregnancy as possible throughout Japan between 2011 and 2014.17 Among 41,578 mothers who delivered singleton live male births, 51 cases of hypospadias were identified, and the median genistein intake was 15.3 mg/d. Compared with mothers in the reference group (genistein intake 11th-89th percentiles), those in the low intake group (£10th percentile) had an elevated risk of their sons having hypospadias. Neither adverse nor beneficial effects of genistein on hypospadias were observed in the high intake group (≥90th percentile). The authors concluded that low maternal isoflavone intake in early pregnancy was associated with an elevated risk of hypospadias. Low natto and tofu intake were each associated with about a 2-fold increased risk.
Indirect evidence pointing to isoflavones not affecting the fetus comes from a comparison between in utero isoflavone and estrogen concentrations. Research indicates that in utero isoflavone concentrations in mothers who consumed soy during pregnancy are markedly lower than estrogen concentrations.18 This difference in concentration, combined with the much greater potency of estrogen in comparison to isoflavones, strongly suggests that isoflavones are unlikely to exert an estrogenic effect on the fetus.18
As noted at the onset, newly published research suggests that maternal soy intake may benefit offspring.4 Subjects of this Japanese study were 1,199 mother-child pairs. Emotional problems, conduct problems, hyperactivity problems, peer problems, and low prosocial behavior of the offspring were assessed as was maternal total soy product consumption during pregnancy. Mean 1st through 4th quartile isoflavone intake was 11.1, 19.9, 29.7, and 50.4 mg/d, respectively.
Key findings from this study are as follows:
- Maternal fermented soybean consumption during pregnancy was independently inversely associated with childhood hyperactivity problems.
- Maternal isoflavone consumption during pregnancy was independently inversely related to childhood hyperactivity problems.
- Maternal consumption of total soy products, fermented soybean and isoflavones during pregnancy may be protective against hyperactivity problems in Japanese children.
The authors of this study suggested that isoflavones may have been at least partially responsible for the observed benefits, but also noted that isoflavone intake was correlated with a healthy dietary pattern. Therefore, the healthy dietary pattern might have confounded the observed inverse relationships with soy and isoflavones.
Overall, there is a need for more research into the health effects of maternal soy consumption on the mother as well as the offspring. The historical precedent of Asian women consuming soy during pregnancy helps allay concerns about adverse effects, but future research should evaluate benefits as well as concerns. Given that sample size may need to be quite large to see significant effects in offspring, it is likely that epidemiologic studies involving soyfood-consuming populations, such as Asians and vegetarians, will produce the most informative results.
- Habibi N, Bianco-Miotto T, Phoi YY, et al. Maternal diet and offspring telomere length: a systematic review. Nutr Rev. 2021;79:148-59.
- Al Rubaye H, Adamson CC, Jadavji NM. The role of maternal diet on offspring gut microbiota development: A review. J Neurosci Res. 2021;99:284-93.
- Mirpuri J. Evidence for maternal diet-mediated effects on the offspring microbiome and immunity: implications for public health initiatives. Pediatr Res. 2021;89:301-6.
- Miyake Y, Tanaka K, Okubo H, et al. Maternal consumption of soy and isoflavones during pregnancy and risk of childhood behavioural problems: the Kyushu Okinawa Maternal and Child Health Study. Int J Food Sci Nutr. 2021:1-10.
- Li J, Teng X, Wang W, et al. Effects of dietary soy intake on maternal thyroid functions and serum anti-thyroperoxidase antibody level during early pregnancy. J Med Food. 2011;14:543-50.
- Miyake Y, Sasaki S, Ohya Y, et al. Soy, isoflavones, and prevalence of allergic rhinitis in Japanese women: the Osaka Maternal and Child Health Study. J Allergy Clin Immunol. 2005;115:1176-83.
- Nagata C, Iwasa S, Shiraki M, et al. Associations among maternal soy intake, isoflavone levels in urine and blood samples, and maternal and umbilical hormone concentrations (Japan). Cancer Causes Control. 2006;17:1107-13.
- Yang J, Nakagawa H, Tsuta K, et al. Influence of perinatal genistein exposure on the development of MNU- induced mammary carcinoma in female Sprague-Dawley rats. Cancer Lett. 2000;149:171-9.
- Shibayama T, Fukata H, Sakurai K, et al. Neonatal exposure to genistein reduces expression of estrogen receptor alpha and androgen receptor in testes of adult mice. Endocr J. 2001;48:655-63.
- Foster WG, Chan S, Platt L, et al. Detection of phytoestrogens in samples of second trimester human amniotic fluid. Toxicol Lett. 2002;129:199-205.
- North K, Golding J. A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. BJU Int. 2000;85:107-13.
- Murphy PA, Song T, Buseman G, et al. Isoflavones in retail and institutional soy foods. J Agric Food Chem. 1999;47:2697-704.
- Franke AA, Custer LJ, Wang W, et al. HPLC analysis of isoflavonoids and other phenolic agents from foods and from human fluids. Proc Soc Exp Biol Med. 1998;217:263-73.
- Springer A, van den Heijkant M, Baumann S. Worldwide prevalence of hypospadias. Journal of pediatric urology. 2016;12:152 e1-7.
- Paulozzi LJ. International trends in rates of hypospadias and cryptorchidism. Environ Health Perspect. 1999;107:297-302.
- Kurahashi N, Murakumo M, Kakizaki H, et al. The estimated prevalence of hypospadias in Hokkaido, Japan. J Epidemiol. 2004;14:73-7.
- Michikawa T, Yamazaki S, Ono M, et al. Isoflavone intake in early pregnancy and hypospadias in the Japan Environment and Children’s Study. Urology. 2019;124:229-36.
- Messina M, Mejia SB, Cassidy A, et al. Neither soyfoods nor isoflavones warrant classification as endocrine disruptors: a technical review of the observational and clinical data. Crit Rev Food Sci Nutr. 2021:1-57.