Low intake of vitamin A in early pregnancy associated with birth defects: Japan cohort study reveals

By Guan Yu Lim contact

- Last updated on GMT

Vitamin A is known to play a role in diaphragm development ©Getty Images
Vitamin A is known to play a role in diaphragm development ©Getty Images

Related tags: Vitamin a, Pregnancy, Birth defects, Japan

Vitamin A dietary intake during pregnancy has been found to be inversely associated with the risk of congenital diaphragmatic hernia (CDH).

CDH is the incomplete formation of the diaphragm that occurs before birth. Although the pathogenesis of CDH is unknown, vitamin A is known to play a role in diaphragm development.

Previous case-control studies have investigated the association between maternal intake of vitamin A and CDH occurrence but researchers believed this is the first cohort study.

They published the findings on the British Journal of Nutrition​.

Data collection

The study analysed 89,658 mothers from the Japan nationwide birth cohort study from 2011 to 2014, who delivered singleton live births. A total of 40 CDH cases were documented.

Validated food frequency questionnaire was used to assess estimated daily intakes of total vitamin A (retinol activity equivalents), retinol, provitamin A carotenoids, and vegetables.

Researchers said that the main source of vitamin A intake in Japan is provitamin A carotenoids that come from vegetables, particularly green and yellow vegetables.

Data on frequency and amount of consumption were collected twice, during the first trimester and second/third trimester (27th​ week of gestation).

A logistic regression analysis was performed to assess the association.

Vitamin A in early pregnancy

The study revealed that with higher intake of total vitamin A in the first trimester (median intake = 468 μg/day), the OR was 0.6 for CDH occurrence, compared to lower intake of total vitamin A (median intake = 230 μg/day).

The risk reduction was also observed with higher intakes of αand β-carotenes, total vegetables, and green and yellow vegetables.

Researchers found no association between total vitamin A intake and CDH on dietary intakes in mid-late pregnancy.

They explained the biological mechanism may be due to the retinoic acid signalling pathway which is known to play an important role in diaphragmatic morphogenesis.

Retinoic acid is likely to regulate the gene expressions, such as Wilm’s tumour 1 and Chicken Ovalbumin Upstream Promotor Transcription Factor II, that are related to the development of the diaphragm​,” they said.


The researchers acknowledged a few limitations of the study: “Although our study focused on vitamin A, the National Birth Defects Prevention Study in US (NBDPS) reported that choline, methionine, and cysteine, which are involved in DNA methylation pathway, were associated with CDH​.”

Additional studies are required to explore the contribution of DNA methylation to the diaphragm development​.”

Another limitation was that participants were not asked on their dietary habits during the diaphragm development period (4-8 weeks), which were likely to lead to a non-differential misclassification based on measurement errors in the assessment of vitamin A intake, “and let us underestimate the association between vitamin A and CDH​.”

In summary, low dietary intake of vitamin A in early pregnancy was associated with the occurrence of CDH.

Although we acknowledge the limitation represented by the small number of outcomes, the results would appear to support our hypothesis that low vitamin A intake is a risk factor for CDH​,” they concluded.


Source: British Journal of Nutrition


“Maternal dietary intake of vitamin A during pregnancy was inversely associated with congenital diaphragmatic hernia: the Japan Environment and Children’s Study”

Authors: Takehiro Michikawa, et al​.

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