An ounce of prevention: The evidence supporting periconception health care

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Applied Evidence

An ounce of prevention: The evidence supporting periconception health care

J Fam Pract. 2004 February;53(2):126-134

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References

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15. Li D, Daling JR, Mueller BA, Hickok DE, Fantel AG, Weiss NS. Periconceptional multivitamin use in relation to the risk of congenital urinary tract anomalies. Epidemiology 1995;6:212-218.

16. Shaw GM, Lammer EJ, Wasserman CR, O’Malley CD, Tolarova MM. Risks of orofacial clefts in children born to women using multivitamins containing folic acid periconceptionally. Lancet 1995;345:393-396.

17. Itikala PR, Watkins M, Mulinare J, Moore CA, Liu Y. Maternal multivitamin use and orofacial clefts in offspring. Teratology 2001;63:79-86.

18. Olshan AF, Smith JC, Bondy ML, Neglia JP, Pollock BH. Maternal vitamin use and reduced risk of neuroblastoma. Epidemiology 2002;13:575-580.

19. Brouwer IA, van Dusseldorp M, West CE, et al. Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial. J Nutr 1999;129:1135-1139.

20. Cuskelly GJ, McNulty H, Scott JM. Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects. Lancet 1996;347:657-659.

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22. March of Dimes Birth Defects Foundation. Folic acid and the prevention of birth defects: a national survey of pre-pregnancy awareness and behavior among women of childbearing age, 1995-2002. Conducted by the Gallup Organization. White Plains, NY: March of Dimes Foundation; 2002. Publication no. 31-1677-02.

23. Folic acid campaign and evaluation—southwestern Virginia, 1997-1999. MMWR Morb Mortal Wkly Rep 1999;48:914-917.

24. Canfield MA, Anderson JL, Waller DK, Palmer SE, Kaye CI. Folic acid awareness and use among women with a history of a neural tube defect pregnancy—Texas, 2000-2001. MMWR Recomm Rep 2002;51(RR-13):16-19.

25. de Weerd S, Thomas CM, Cikot RJ, Steegers-Theunissen RF, DeBoo TM, Steegers EA. Preconception counseling improves folate status of women planning pregnancy. Obstet Gynecol 2002;99:45-50.

26. Green NS. Folic acid supplementation and prevention of birth defects. J Nutr 2002;123(8 Suppl):2356S-2360S.

27. Rader JI, Yetley EA. Nationwide folate fortification has complex ramifications and requires careful monitoring over time. Arch Intern Med 2002;162:608-609.

28. Honein MA, Paulozzi LJ, Matthews TJ, Erickson JD, Wong LY. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA 2001;285:2981-2986.

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30. CDC. Third National Health and Nutrition Examination Survey (NHANES III). Hyattsville, Md: National Center for Health Statistics, Division of Data Services, 1998.

31. Combs CA, Kitzmiller JL. Spontaneous abortion and congenital malformations in diabetes. Baillieres Clin Obstet Gynecol 1991;5:315-331.

32. Dicker D, Feldberg D, Samuel N, et al. Spontaneous abortion in patients with insulin-dependent diabetes mellitus: the effect of preconceptional diabetic control. Am J Obstet Gynecol 1988;158:1161-1164.

33. Ray JG, O’Brien TE, Chan WS. Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus. Q J Med 2001;94:435-444.

34. Elixhauser A, Weschler JM, Kitzmiller JL, et al. Cost-benefit analysis of preconception care for women with established diabetes mellitus. Diabetes Care 1993;16:1146-1157.

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Applying the evidence

Because of the proven reduction in neonatal morbidity, smoking cessation counseling may be the most effective part of periconception care. Advise smoking cessation to all women who smoke, before and during pregnancy (strength of recommendation [SOR]: A).

Folic acid and multivitamins

Neural tube defects occur in 1 in 1000 babies delivered in the US. The Medical Research Council Vitamin Study found that mothers who had a child with neural tube defects reduced the risk of having another child with neural tube defects by 72% if they took 4 mg of folic acid a day prior to conception and during the first trimester.¹²

A large primary prevention trial in Hungary showed the risk of anomalies (including neural tube defects) in babies decreased by 46% among mothers randomized to receive folic acid.¹³ A Cochrane meta-analysis demonstrated a 3-fold decreased risk of a first neural tube defect if women took folic acid. The absolute risk of neural tube defects decreased from 10.2/1000 in the control group to 2.4/1000 in the folic acid group. The NNT to prevent 1 neural tube defect was 847.¹⁴

Studies have shown that periconception multivitamin intake confers other benefits as well: decreased risk of genitourinary malformations, cleft lip and cleft palate, and neuroectodermal tumors in offspring. In all studies, the multivitamins contained folic acid, but most studies were unable to look at folic acid independently.^15-18

Optimal dose of folic acid

Studies have attempted to determine the most beneficial dose of folic acid and how it should be consumed (ie, diet, supplementation, fortification). Study results, however, are conflicting.^19,20

In 1992, the US Preventive Services Task Force (USPSTF) recommended women of childbearing age consume 0.4 mg/d folic acid,²¹ but it did not make a recommendation on the form of folic acid.

Patient education that works

Women in the US are not fully aware of the benefits of taking multivitamins with folic acid prior to conception and during pregnancy. A 2002 survey showed that only 20% of women knew that folic acid could prevent certain birth defects. Even fewer women knew they have to take folic acid prior to conception (7% in the survey).²²

Though many studies have shown that education increases awareness about folic acid, only a few have investigated if awareness leads to changes in behavior.²³ In highly motivated women, education does appear to influence behavior changes. A study in Texas showed that women who had children with neural tube defects and had received advice about taking folic acid prior to subsequent pregnancies were more likely to use supplements than women who did not receive this advice.²⁴ Another study looked at women planning a pregnancy who had preconception counseling. Counseling about folic acid increased folic acid intake.²⁵

The USPSTF expected a 70% decrease in incidence of neural tube defects if its 1992 recommendation was followed. In 1998, the Food and Drug Administration began requiring the fortification of cereal grains at the level of 140 μg/100 g grain. This was expected to increase the intake of folate in women by 100 μg/d and decrease the incidence of neural tube defects by 20%.²⁶

Data from the Centers for Disease Control and Prevention (CDC) has shown that folate status had improved significantly in women of childbearing age,²⁷ and the incidence of neuroblastoma has decreased by 19%, from 37.8/100,000 prior to supplementation to 30.5/100,000 since fortification became mandatory.²⁸

Applying the evidence

Increased folic acid intake significantly decreases neural tube defects. Education about folic acid increases vitamin use in motivated women (SOR: A). Folic acid supplementation of food is an effective population-based intervention to reduce neural tube defects (SOR: B). Folic acid intake by women decreases genitourinary and cleft-lip malformations and neuroblastoma in their infants (SOR: B).

Diabetes mellitus

Estimates of pregestational diabetes in women of childbearing age range from 1.9% to 3.5%.^29,30 Diabetes has been associated with decreased fertility, spontaneous abortions, and congenital anomalies. Several studies have correlated spontaneous abortion rates with hemoglobin A_1c values at the time of conception (LOE: 2a).³¹

Glycemic control reduces spontaneous abortions

One prospective trial³² compared the spontaneous abortion rate in diabetic women who receive intensive preconception insulin therapy with the rate in women who receive usual care (LOE: 2b). A spontaneous abortion rate of 8.4% occurred in the preconception treatment group compared with 28% in the pregnancy care–only group (NNT=5). Limitations of this study include the small number of participants and the lack of randomization. However, given all the benefits of improved glycemic control, preconception glycemic control is recommended to reduce the spontaneous abortion rate in diabetic women (SOR: B).