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Vitamin supplements and the risk for congenital anomalies other than neural tube defects.
Am J Med Genet C Semin Med Genet. 2004 Feb 15; 125C(1):12-21.AJ

Abstract

Randomized trials, supported by many observational studies, have shown that periconceptional use of folic acid, alone or in multivitamin supplements, is effective for the primary prevention of neural tube defects (NTDs). Whether this is true also for other congenital anomalies is a complex issue and the focus of this review. It is useful to consider the evidence not only for specific birth defects separately but, importantly, also for all birth defects combined. For the latter, the Hungarian randomized clinical trial indicated, for periconceptional multivitamin use, a reduction in the risk for all birth defects (odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.35-0.70), even after excluding NTDs (OR = 0.53, 95% CI = 0.38-0.75). The Atlanta population-based case-control study, the only large observational study to date on all major birth defects, also found a significant risk reduction for all birth defects (OR = 0.80, 95% CI = 0.69-0.93) even after excluding NTDs (OR = 0.84, 95% CI = 0.72-0.97). These and other studies also evaluated specific anomalies, including those of the heart, limb, and urinary tract, as well as orofacial clefts, omphalocele, and imperforate anus. For cardiovascular anomalies, two studies were negative, whereas three, including the randomized clinical trial, suggest a possible 25-50% overall risk reduction, more marked for some conotruncal and septal defects. For orofacial clefts, six of seven case-control studies suggest an apparent reduced risk, which could vary by cleft type and perhaps, according to some investigators, by pill dosage. For limb deficiencies, three case-control studies and the randomized trial estimated approximately a 50% reduced risk. For urinary tract defects, three case-control studies and the randomized trial reported reduced risks, as did one study of nonsyndromic omphalocele. All these studies examined multivitamin supplement use. With respect to folic acid alone, a reduced rate of imperforate anus was observed among folic acid users in China. We discuss key gaps in knowledge, possible avenues for future research, and counseling issues for families concerned about occurrence or recurrence of these birth defects.

Authors+Show Affiliations

Botto LD
National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. LBotto@cdc.gov
Olney RS
No affiliation info available
Erickson JD
No affiliation info available

MeSH

AdultCase-Control StudiesClinical Trials as TopicCongenital AbnormalitiesDietary SupplementsEpidemiologic StudiesFemaleHumansInfant, NewbornOdds RatioPregnancyRisk FactorsVitamins

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

14755429

Clinical Trial Links

Folic Acid Dosage and Malformations Reduction

Citation

Botto, Lorenzo D., et al. "Vitamin Supplements and the Risk for Congenital Anomalies Other Than Neural Tube Defects." American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, vol. 125C, no. 1, 2004, pp. 12-21.
Botto LD, Olney RS, Erickson JD. Vitamin supplements and the risk for congenital anomalies other than neural tube defects. Am J Med Genet C Semin Med Genet. 2004;125C(1):12-21.
Botto, L. D., Olney, R. S., & Erickson, J. D. (2004). Vitamin supplements and the risk for congenital anomalies other than neural tube defects. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, 125C(1), 12-21.
Botto LD, Olney RS, Erickson JD. Vitamin Supplements and the Risk for Congenital Anomalies Other Than Neural Tube Defects. Am J Med Genet C Semin Med Genet. 2004 Feb 15;125C(1):12-21. PubMed PMID: 14755429.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin supplements and the risk for congenital anomalies other than neural tube defects. AU - Botto,Lorenzo D, AU - Olney,Richard S, AU - Erickson,J David, PY - 2004/2/3/pubmed PY - 2004/8/19/medline PY - 2004/2/3/entrez SP - 12 EP - 21 JF - American journal of medical genetics. Part C, Seminars in medical genetics JO - Am J Med Genet C Semin Med Genet VL - 125C IS - 1 N2 - Randomized trials, supported by many observational studies, have shown that periconceptional use of folic acid, alone or in multivitamin supplements, is effective for the primary prevention of neural tube defects (NTDs). Whether this is true also for other congenital anomalies is a complex issue and the focus of this review. It is useful to consider the evidence not only for specific birth defects separately but, importantly, also for all birth defects combined. For the latter, the Hungarian randomized clinical trial indicated, for periconceptional multivitamin use, a reduction in the risk for all birth defects (odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.35-0.70), even after excluding NTDs (OR = 0.53, 95% CI = 0.38-0.75). The Atlanta population-based case-control study, the only large observational study to date on all major birth defects, also found a significant risk reduction for all birth defects (OR = 0.80, 95% CI = 0.69-0.93) even after excluding NTDs (OR = 0.84, 95% CI = 0.72-0.97). These and other studies also evaluated specific anomalies, including those of the heart, limb, and urinary tract, as well as orofacial clefts, omphalocele, and imperforate anus. For cardiovascular anomalies, two studies were negative, whereas three, including the randomized clinical trial, suggest a possible 25-50% overall risk reduction, more marked for some conotruncal and septal defects. For orofacial clefts, six of seven case-control studies suggest an apparent reduced risk, which could vary by cleft type and perhaps, according to some investigators, by pill dosage. For limb deficiencies, three case-control studies and the randomized trial estimated approximately a 50% reduced risk. For urinary tract defects, three case-control studies and the randomized trial reported reduced risks, as did one study of nonsyndromic omphalocele. All these studies examined multivitamin supplement use. With respect to folic acid alone, a reduced rate of imperforate anus was observed among folic acid users in China. We discuss key gaps in knowledge, possible avenues for future research, and counseling issues for families concerned about occurrence or recurrence of these birth defects. SN - 1552-4868 UR - https://www.unboundmedicine.com/medline/citation/14755429/Vitamin_supplements_and_the_risk_for_congenital_anomalies_other_than_neural_tube_defects_ DB - PRIME DP - Unbound Medicine ER -