Clinicians should consider “trade-offs” in prevention strategies for birth defects, say researchers

By Nicola Gordon-Seymour

- Last updated on GMT

getty | prostock studio
getty | prostock studio

Related tags maternal health Research Vitamin a Vitamin d Zinc Iron

Advice on maternal supplementation to prevent birth defects (BDs) should consider the teratogenic effects of multivitamins (MVs) and adverse effects of excess folic acid (FA), according to Chinese research.

MVs contain high dose vitamin A (1.2mg), vitamin D (12.5ug), iron (60mg), and zinc (7.5mg) and are recommended during pregnancy, along with FA, to prevent obstetric complications and birth defects (BDs).

However, over-exposure is associated with increased incidence of cleft palates, limb defects, and congenital heart defects (CHD), suggesting a trade-off is needed when developing prevention strategies, say the authors of a recent study.

“Maternal exposure to only MV was associated with an increased risk of offspring genitourinary defects and abnormal chromosomes with statistical significance,” ​they write in Nutrients.

Furthermore, research supports the “deleterious effects of maternal excessive folate intake” ​on BD risks and, along with findings from the current study, suggest more attention should be directed to “the effect of disparities of FA on different subtypes of BDs,”​ they say.

Defect assessment

Birth defects are defined as “a series of structural, functional, or metabolic disorders that occur during embryonic or foetal development​”, with incidence generally higher in low-income and developing countries.

Although rates in China are comparable to developed countries, BD is currently a major cause of death among Chinese children aged 0 to 5 years due to inadequate maternal micronutrient intake.

While maternal FA supplementation is known to prevent neural tube defects (NTDs), there are conflicting results on risks for other types of BD. Equally, evidence on subtype risk with MV supplements is limited.

Clinical approach

The current study analysed the impact of FA and/or MV supplements on different types of BDs based on a Chinese cohort of 120,652 pregnant women, of which 3,390 infants were born with defects.

Eligible participants were interviewed and completed questionnaires at intervals during pregnancy. A total of 40,204 were exposed to only FA supplements; 5,567 only took MVs; 71,538 administered both, while 3,343 participants received neither supplement.

Clinical data was collected at follow-up visits, along with additional information where BD was detected.

Risk factors

CHDs were cited as the most common BD subtype, followed by abnormal chromosome, the genitourinary system, nervous system, limb, ear, face and neck, and oral clefts, although risk rates (RR) varied. BDs were also more common in individuals from north China.

Incidence of genitourinary defects, abnormal chromosome, and oral clefts were higher in the group exposed to FA and MV, but RRs were lower for the remaining defects, compared with no supplement exposure - although figures were not statistically significant.

The negative impact of FA on zinc absorption in MV was postulated as one explanation, as it inhibits the synthesis of a variety of enzymes, nucleic acids and proteins that have an important role in embryonic growth and development.

Maternal zinc deficiency may cause foetal NTDs, low birth weight, and intrauterine growth retardation. In our study, when FA and MV are supplemented simultaneously in the first trimester of pregnancy, FA may interact with zinc in MV and demonstrate inconsistent effects for different subtypes of BDs,” ​the authors explain.

Disparate results

On the other hand, they note the RR of genitourinary defect and abnormal chromosomal in the maternal FA and MV group decreased compared to the group taking only the MV supplement.

This disparity could be attributed to excessive accumulation of fat-soluble vitamins from MV, leading to increases risk of some subtypes of BDs, they say: “The MV products sold in China contain vitamin A, which was easy to accumulate in the body and reached a higher concentration. Exposure to high doses of vitamin A might affect foetal palatogenesis by interfering with cell proliferation.​”

Recommendations about MV use for mothers in early pregnancy should therefore be “treated with caution”​, they add.

Analyses also suggest that FA in the daily diet of pregnant women plus FA and MV supplements is likely to exceed upper intake levels (UL) and put individuals “at high risk of FA overexposure”.

Source: Nutrients

Published online, January 5, 2023:

‘Is the Trade-off between Folic Acid or/and Multivitamin Supplementation against Birth Defects in Early Pregnancy Reconsidered? Evidence Based on a Chinese Birth Cohort Study’

Authors: Jian Su, Shen Gao, Ruohua Yan, Ruixia Liu, Shaofei Su, Xiaolu Nie, Xiaohang Liu, Enjie Zhang, Shuanghua Xie, Jianhui Liu, Yue Zhang, Wentao Yue, Chenghong Yin and Xiaoxia Peng

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