September 3, 2026, 4:08 pm | Read time: 5 minutes
Adequate folic acid intake around the start of pregnancy can reduce the risk of certain birth defects in the unborn child. But what role do other nutrients play–and could the father’s diet also be significant? A large cohort study published in 2026 in the renowned journal “Annals of Internal Medicine” by the Children’s Hospital of Fudan University in Shanghai examined how the vitamin B12 and folate levels of both parents are related to the occurrence of birth defects. The finding: Not only the nutrient supply of expectant mothers but also that of fathers is important.
Vitamin B12 Before Conception Shows Clear Connection
The study suggests that the vitamin B12 level of both parents before conception could be important. Both fathers and mothers with very low B12 levels before conception statistically had children with birth defects more often than parents with high levels. It’s intriguing how the fathers’ levels affected outcomes. While fathers with less than 148 picomoles per liter (pmol/L)–a very low vitamin B12 level–had 55.5 birth defects per 1,000 pregnancies, those with high levels of 590 pmol/L or more had only about 24 cases.1
How the Study Was Conducted
Folate is important for DNA formation and cell growth. Women are therefore advised to take folic acid before and at the beginning of pregnancy. Vitamin B12 also plays a crucial role in these processes. However, little research has been done on how the vitamin B12 and folate supply of both parents around conception relates to birth defects. The role of fathers, in particular, is not yet well understood.
The researchers analyzed data from the Shanghai Preconception Cohort. In an initial analysis, they examined 3,032 couples who had blood drawn within four months before conception. In this group, 73 cases of birth defects were recorded. A second analysis included 17,765 women who had blood drawn up to the fourth month of pregnancy. Here, 327 cases of birth defects were recorded.
The researchers determined the vitamin B12 levels in the blood and the folate concentration in the red blood cells. The latter indicates how well a person is supplied with folate over a longer period. The researchers then calculated how frequently birth defects were statistically expected at different vitamin B12 and folate levels.
Fewer Birth Defects at Higher Vitamin B12 and Folate Levels
More than half of the recorded birth defects affected the cardiovascular system, accounting for 55.9 percent of the cases. Among the couples examined before conception, the proportion was 52.1 percent, while among the women whose blood values were determined early in pregnancy, it was 59.6 percent. Neural tube defects, such as spina bifida, which are often associated with folic acid supply, played only a minor role: About 98 percent of the recorded birth defects were not neural tube defects.
Higher folate levels before conception also tended to be associated with fewer birth defects. However, according to the researchers, these results were associated with greater uncertainty.
After conception, the mother’s folate levels showed a more nuanced picture with a clear saturation effect: At levels between 906 and 1,131 nmol/L, about 17 cases per 1,000 pregnancies were predicted. At low levels below 453 nmol/L, there were about 26 cases. Even higher folate levels, however, were hardly associated with a further decrease.
Before conception, a clear trend was observed in mothers. At very low B12 levels below 148 pmol/L, the predicted frequency was about 50 cases per 1,000 pregnancies, at 148 to 294 pmol/L about 31, and at levels of 590 pmol/L or more about 16. After conception, the pattern was less clear: The lower B12 categories differed little, while at high levels of 590 pmol/L or more, a lower predicted frequency of about 12 cases per 1,000 pregnancies was calculated.
What the Results Mean for Couples Planning to Have Children
The results do not mean that women or men planning to have children should take high-dose vitamin B12 supplements as a precaution. The researchers examined the vitamin B12 and folate levels in the blood–not whether taking supplements can prevent birth defects.
Additionally, in fathers, the observed correlation flattened at higher vitamin B12 levels. The results therefore do not suggest that the highest possible levels are automatically associated with an ever-decreasing risk.
Also interesting: Study shows link between what fathers eat and baby’s birth weight
Study Shows Link Between What Fathers Eat and Baby’s Birth Weight
Sperm Abnormalities–Men Hoping to Have Children Should Avoid Alcohol
Strengths and Weaknesses of the Study
A strength of the study is that the blood values were determined before or early in pregnancy–before the outcome of the pregnancy was known. Additionally, the researchers examined not only the mothers’ values but also the fathers’. The analysis of women in early pregnancy also included a large number of participants.
In recording birth defects, the researchers considered not only live births but also stillbirths and pregnancy terminations due to fetal malformations.
An important limitation is that other factors, not or not fully recorded, could have influenced the observed correlations. Since this is an observational study, it cannot be proven that higher vitamin B12 or folate levels were actually the cause of the lower frequency of birth defects.
Furthermore, the available documents do not indicate how well the results of the Chinese cohort can be transferred to other populations.
What Previous Studies Show
The observation that very high levels do not provide additional benefits aligns with previous research. A Chinese case-control study from Guangdong compared 129 children with congenital heart defects with 516 controls and found a U-shaped relationship.2 Both low and particularly high folate levels in maternal blood were associated with an increased risk. At low levels, the probability was about three times higher. At very high levels, it was about 1.8 times higher than in the middle range. An additional vitamin B12 deficiency amplified this effect.
For the question of whether the correlations actually involve a cause-and-effect relationship, an analysis of the same Shanghai cohort from 2022 is insightful.3 The researchers used a genetic variant that affects folate metabolism as a kind of natural experiment. Even with this approach, a higher folate level was associated with a lower risk of heart defects. However, since it is the same cohort, this is not an independent confirmation.