A Shanghai cohort measured fathers' B12 too. It tracked with birth defects.

Preconception nutrition advice is almost entirely addressed to women, and almost entirely about folic acid. A prospective cohort study published in Annals of Internal Medicine on 1 September examines two departures from that: vitamin B12 alongside folate, and fathers alongside mothers [s1].

The cohort

The analysis draws on the Shanghai Preconception Cohort in China [s1]. Two samples were used: 3,032 couples with biomarkers measured within four months before conception, containing 73 birth-defect cases; and 17,765 women sampled at four months' gestation or earlier, containing 327 cases [s1].

Birth defects were ascertained among live births, stillbirths and abortions due to fetal abnormalities — a broader ascertainment than live-birth-only studies, which systematically undercount the most severe defects [s1]. Standardised predicted prevalences were estimated using weighted logistic regression [s1].

The starting point the authors state is that maternal folic acid prevents neural tube defects, but that associations of parental folate and vitamin B12 with birth defects remain unclear [s1].

What it found

The B12 findings are the substantive ones.

For preconception maternal vitamin B12, moving from the lowest category (below 148 pmol/L) to the highest (590 pmol/L or above), predicted birth-defect prevalence fell from 49.6 to 16.2 cases per 1,000 pregnancies [s1]. Paternal vitamin B12 showed a similar but attenuated pattern — 55.5 down to 24.0 cases per 1,000 pregnancies [s1]. Both were dose-response.

Folate behaved differently depending on timing. Preconception parental red blood cell folate showed imprecise patterns of lower predicted prevalence [s1] — that is, the direction was there and the estimates were not stable. Postconception maternal red blood cell folate did show an effect, with predicted prevalence lower at levels of 906 to 1,131 nmol/L than below 453 nmol/L (16.5 vs 25.7 cases per 1,000 pregnancies), and little further reduction at higher levels [s1].

That plateau matters. It is evidence against the assumption, common in supplement marketing, that more folate is monotonically better.

Postconception maternal B12 changed little across the lower categories but was lower at the top: 11.8 versus 20.4 cases per 1,000 pregnancies at 590 pmol/L or above versus 148 to 294 pmol/L [s1].

The authors' stated limitation is residual confounding [s1], and it is the right one to lead with.

The paternal finding, in proportion

An accompanying editorial in the same issue is titled "Both Paternal and Maternal Nutrition Status Matter: An Exemplar From Folate and Vitamin B12 in Association With Risks for Birth Defects" [s2], which is a fair reading of the direction of the data and a stronger claim than the data can carry on its own.

The reason for caution is straightforward. Within couples, nutritional status is correlated: partners eat similar food, share socioeconomic circumstances and often supplement together. A paternal association that is weaker than the maternal one, in a study of 3,032 couples with 73 cases [s1], is exactly what would be produced by maternal effect alone plus within-couple correlation. Separating the two requires either a design that breaks the correlation or a mechanism, and this study has neither.

The paternal result is worth reporting because nobody measures fathers. It is not yet worth acting on.

Where B12 already had a case

The B12 hypothesis did not originate here. A study of three independent nested case-control groups of Irish women, sampled at an average of 15 weeks' gestation at a time when supplementation and fortification were rare, found that mothers of children affected by neural tube defects had significantly lower B12 status [s3]. In all three groups, women in the lowest B12 quartile had between two- and threefold higher adjusted odds of an affected pregnancy compared with the highest, and pregnancy blood B12 concentrations below 250 ng/L carried the highest risks [s3].

Those authors suggested women have B12 levels above 300 ng/L (221 pmol/L) before becoming pregnant, while noting that whether improving status beyond that level reduces risk further is uncertain [s3]. They also framed the search explicitly: folic acid fortification has reduced neural tube defect prevalence by 50% to 70%, and since fortification levels are unlikely to rise further, other modifiable risk factors need identifying [s3].

The Shanghai cohort extends that logic from neural tube defects to birth defects generally, in a population and at a life stage where preconception measurement is rare [s1].

What it does not license

This is an observational cohort. It reports associations between measured biomarkers and outcomes, not the effect of supplementing. No trial has randomised preconception B12 in either parent to a birth-defect endpoint, and nothing here tells a reader what to take.

The two numbers that would matter most for policy — whether raising a low B12 level before conception changes outcomes, and whether the paternal signal is real — are both untested.

Sources

• [s1] "Periconception Parental Red Blood Cell Folate, Vitamin B12, and Birth Defects in Offspring: A Prospective Cohort Study," Annals of Internal Medicine, 1 September 2026. https://doi.org/10.7326/ANNALS-25-05243
• [s2] "Both Paternal and Maternal Nutrition Status Matter: An Exemplar From Folate and Vitamin B12 in Association With Risks for Birth Defects," Annals of Internal Medicine, 1 September 2026. https://doi.org/10.7326/ANNALS-26-03045
• [s3] "Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic Acid fortification," Pediatrics, 1 March 2009. https://doi.org/10.1542/peds.2008-1173