Journal Reading

The Impact of Folic Acid Intake on The Association Among Diabetes Mellitus, Obesity, and Spina Bifida By: dr. Anton
September 2013, American journal of obstetrics and gynecology

BACKGROUND

 Folic acid intake in the periconceptuional period

reduce the risk of spina bifida in offspring The US public Health Service, Intitute of Medicine, and Preventive Service Task Force reccomended that women of childbearing age consume at least 400g of folic acid daily through supplements and fortified food products . Pre existing diabetes millitus and obesity have been indentified as 2 such risk factors for spina bifida.

Materials and Methods

 Case of birth defects are ascertained from birth

hospitals, tertiary care centers, and birth defects registries in Massachusets (1976+); Philadelpia, PA (1976+); San Diego CA (2001+); Toronto, ON, Canada (1976-2005) selected countries in Iowa (1983-1985); and parts of New York State (2004+).
The present study includes case of spina bifida

and control subjects that were ascertained in 19762011.

 Information

on preexisting and gestational diabetes milllitus was collected throughout the study. Data on body mass index were available from 1993 onward,when information on maternal height was incorporated into the interview. Folic acid intake in the periconceptional period, defined as the month before the last menstrual period through the first lunar month of pregnancy, was calculated by totalling aerage daily folic acid in take from supplements and fortified foods

TABLE Foloc acid , dia betes millitus, and risk of spina bifida,1976-2011

Preexixting diabetes millitus

Folic acid <400 g

Cases/control subjects

Adjusted OR(95%Cl)

No

No

242/3827

1.0(reference)

No

Yes

803/4798

1.99(1.69-2.34)

Yes

No

1/15

1.31 (0.17-10.30)

Yes

Yes

7/24

3.95 (1.56-10.00)

Relative excess risk due to interaction,1.65: 95% Cl, -2.87 to 6.18 Cl ,confidence interval: OR,odds ratio. Adjusted for maternal age, education, race/ethnicity,and study center. Parker , Folic acid,diabetes millitus,obesity,and spina bifida.Am J Obstet Gynecol 2013

CLINICAL IMPLICATION : Offspring of women with preexisting diabetes melitus and of those whose are obese before pregnancy are increased risk for spina bifida. Folic acid intake <400g per day whose associated with increased risk of spina bifida with or without pre exsisting diabetes millitus or prepregnancy obesity. Folic acid intake <400g per day coupled with preexisting diabetes millitus increases the risk for spina bifida synergistically, although when coupled with obesity Future research should focus on understanding whether the risk of spina bifida would be reduced in offspring of obese woman if women ingested higher levels of folic acid than are recommended currently.

RESULT

 The diabetes millitus analysis included

1154 cases of spina bifida and 9439 control subjects that were ascertained from 1976-2011.
The join effect of low folic acid intake and

preexisting diabetes militus resulted in 4fold increasted risk of spina bifida relative to mothers without diabetes milllitus and with higher daily folic acid intake,which was greater than expected given the individual additive effects of low folic accid intake and preexisting diabetes millitus

 Among case mothers , 19.0% were obese

compared with 10.0% of control mothers. The aOR for spina bifida among overweight women was 1.24(95% Cl,0.931.63) and for obese women was 1.97(95% Cl,1.46-2.65).
There did not appear to be joint effect

between obesity and folic acid intake (relative excess risk due interaction, 0.14; 95% Cl,- 1.08 t0 1.35)

DISCUSSION

 Failure of achieve the recomendded intake of folic

acid during the periconceptional period is suggestive of a further increase in the risk of spina bifida among mothers with preexisting diabetes millitus. researcher observed a 2-fold increased risk for spina bifida among women with preexisting diabetes millitus, but the estimate was unstable because of a small number of diabetic cases. Although other studies have considered the relationship between preexisting diabetes millitus and the combined group of all neural tube defect(including spina bifida and annencephaly),few have quantified the association between diabetes millitus and spina bifida.

 The mechanism by which folic acid may reduce the

risk of spina bifida because of diabetic embryopathy is not well understood.

It has been proposed that the antioxidant properties of

folic acid may mitigate the effect of reactive oxygen species and abnormal apoptosis the result from diabetes millitus.
A potential explanation of our findings involves the

ability of folic acid to reduce oxidative stress in the embryo that is caused by increased levels of glucose.
The risk of spina bifida among obese women was

comparable between those consuming vs not

 Strenghts of this study include its large sample size ,

more diabetes millitus cases than in previous studies, and the short interval between delivery and interview.
Furthermore, dietary data were available from a

validate food frequence quetionare. The slone Epidemiology Center has a comprehensive database of information on supplements in which the amount of folic acid in specific supplement products is available.
Among limitations of the study is that data on

preexisting diabetes mellitus and obesity were collected by maternal self-report, which may have resulted in misclassification.

 In summary , the achievement of the daily

recomanded intake of 400g of folic acid reduce the risk for spina bifida because of diabetes millitus than because of obesity.
An understanding of the mechanism by

which diabetes millitus appears to increase the risk of spina bifida and how folic acid more reduce its teratogenic qualities would provide more insight into wheth higher levels of folic acid intake , might further attenuate the risk for spina bifida because of obesity.

Conclusion

 General Description 1. Design : a retrospective cohort 2. Target Population: mothers with preexisting

diabetes mellitus (collected 1976-2011) and obesity (collected 1993-2011) with cases of spina bifida 3. Exclusion criteria were: maternal age, race, education and study center 4. Sample : control partisipans (9439), spina bifida (1154) 5. Periode : Between 1976-2011

What question did the study ask ?

P : mothers with preexisting diabetes mellitus (collected 1976-2011) and obesity (collected 1993-2011) with cases of spina bifida I : folic acid intake

C : The join effect of low folic acid intake and preexisting diabetes militus with increasted risk of spina bifida relative to mothers without diabetes milllitus and with higher daily folic acid intake
O : giving folic acid further attenuates reduce the possibility of spina bifida although does not elliminate the risk of spina bifida

Are the result of this prognosis study valid ?

Questions 1. Was a defined, representative sample of patients assembled at a common point in the course of their disease ? 2. Was patient follow-up sufficiently long and complete ? 3. Were objective outcome criteria applied in a blind fashion ? Answer yes

Yes blind

4. If subgroups with different prognosis are identified, was there adjustment for important prognostic factors ? 5. Was there validation in an independent group of patients ?

Yes

Yes

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Are the valid results of this prognosis study important ?

Questions Answer

1. How precise are the prognostic estimates ?

2. Were the study patients similar to your own ?

Yes
Yes

3.Will this evidence make a clinically yes important impact on your conclusions about what to offer or tell your patient ?
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 CONCLUSION

VALID, IMPORTANT, APPLICABLE

Thanks you