"Periconceptional Multivitamin and Folic Acid Supplementation Prevents Neural Tube Defects". The New England Journal of Medicine. 1992. 327(26):1832-1835. PubMed • Full text • PDF

Clinical Question

Does periconceptional multivitamin and folic acid supplementation reduce the incidence of a first occurrence of neural tube defects?

Bottom Line

Periconceptional use of a multivitamin supplement containing folic acid significantly decreases the incidence of a first occurrence of neural tube defects.

Major Points

Neural tube defects (NTDs) are serious birth defects that can lead to significant morbidity and mortality. Previous research had suggested that folic acid or multivitamin supplementation could decrease the risk of recurrent NTDs. This Hungarian randomized controlled trial aimed to determine if similar supplementation could reduce the first occurrence of NTDs.

The study randomized women planning pregnancy to receive either a periconceptional multivitamin supplement containing 0.8 mg of folic acid or a trace element supplement daily. The vitamin supplement resulted in a significant reduction in congenital malformations, specifically neural tube defects, with no cases occurring in the vitamin-supplement group compared to six cases in the trace-element supplement group.

Guidelines

No specific guidelines were established as a result of this study. However, following subsequent studies and the confirmation of the benefits of folic acid supplementation in the prevention of NTDs, various health organizations worldwide now recommend that women planning a pregnancy take daily supplements of folic acid starting before conception and continuing into pregnancy.

Design

Randomized, controlled trial.
N=4753 women planning pregnancy.
Intervention: Multivitamin supplement containing 0.8 mg folic acid.
Control: Trace-element supplement.
Periconceptional period of at least one month before conception until the second missed menstrual period or longer.

Outcomes were evaluated in women in both study groups.

Population

Women planning a pregnancy.
No delayed conception or infertility.
Not currently pregnant.
Between 18 to 35 years of age.

Interventions

Receiving a single tablet daily of either:
Multivitamin supplement - containing 12 vitamins (including 0.8 mg of folic acid), 4 minerals, and 3 trace elements.
Trace-element supplement - containing copper, manganese, zinc, and a low dose of vitamin C.

Outcomes

Primary Outcome: Incidence of neural tube defects.
No cases in the vitamin-supplement group.
Six cases in the trace-element supplement group (P=0.029).

Secondary Outcomes: Prevalence of congenital malformations.
Congenital malformations were significantly more prevalent in the trace-element supplement group (22.9 per 1000) compared to the vitamin-supplement group (13.3 per 1000, P=0.02).

Criticisms

The study was specifically conducted in Hungary, so results may be different in populations with varying nutritional statuses.
The small number of NTD cases in the study limits the ability to make broad generalizations based on the findings.
Vitamin A content in the multivitamin was adjusted during the study which could have introduced variability in the treatment effect.

Funding

The study was supported by Hoffmann—La Roche who supplied the supplements.

Further Reading

Refer to studies and recommendations of the CDC, WHO, and public health bodies regarding folic acid supplementation during preconception and pregnancy.