Exposure to a diabetic intrauterine environment is associated with an earlier age at diagnosis of type 2 diabetes in offspring, according to findings from the SEARCH for Diabetes in Youth Study - a survey of ethnically diverse people diagnosed with diabetes before age 20 years.
"This study helps explain why other studies have found higher age-specific rates of type 2 diabetes among offspring of women with diabetes," note Dr. David J. Pettitt from the Sansum Diabetes Research Institute, Santa Barbara, California, and colleagues in the November issue of Diabetes Care.
The study sample included 2,342 young patients with type 1 diabetes and 331 with type 2 diabetes. A total of 269 subjects with type 1 diabetes and 174 with type 2 diabetes had a family history of diabetes.
Dr. Pettitt and colleagues observed that individuals with type 2 diabetes were significantly more likely than subjects with type 1 diabetes to have a parent with diabetes (type 1 or type 2).
They also discovered that type 2 diabetes was diagnosed 1.68 years earlier among the 174 young patients exposed to diabetes in utero than among those whose mothers' diabetes was not diagnosed until after the offspring's birth.
"The significance of this finding persisted when analyses were controlled for the age at which the mothers' diabetes was diagnosed," the investigators note.
Among youth with type 1 diabetes, the effect of intrauterine exposure was not significant when controlled for the mother's age at diagnosis. Father's diabetes before birth was not associated with age at diagnosis of type 1 or type 2 diabetes.
These findings, note Dr. Pettitt and colleagues, "suggest that the hyperglycemic intrauterine environment predisposes to an earlier onset of type 2 diabetes, whereas the age of onset of type 1 diabetes is largely familial, is possibly genetic, and is influenced very little by the intrauterine milieu."
As rates of obesity and type 2 diabetes increase, more young women will be exposing their unborn children to hyperglycemia. "Thus, children exposed at this early stage of life to abnormal nutrients from their diabetic mothers need to be followed carefully, and known risk factors, such as obesity, hypertension, and hyperlipidemia, need early treatment," the investigators conclude.
Diabetes Care 2008;31:2126-2130.
From Reuters Health Information
In Utero Diabetes Exposure May Predispose to Type 2 Diabetes at Earlier Age
NEW YORK (Reuters Health) Nov 27
23 May 2009
Is Gardasil Recommended for Young Women Already Exposed to HPV?
Question:
Should Gardasil® (human papillomavirus [HPV] quadrivalent [types 6, 11, 16, and 18] vaccine) be administered to young women who test positive for oncogenic-risk HPV strains, or to those who have abnormal Papanicolaou ("Pap") smear results?
Response:
Genital human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, with an estimated 20 million people already infected and over 6 million people infected annually. Although most infections prove to be self-limiting or asymptomatic, persistent infection with oncogenic strains (such as types 16 and 18) can lead to cervical cancer. Seventy percent of cervical cancers are attributed to HPV types 16 and 18; HPV types 6 and 11 contribute to 90% of cases of genital warts.
The HPV quadrivalent (types 6, 11, 16, and 18) vaccine (Gardasil®) was approved by the US Food and Drug Administration in 2006 and is indicated for use in 9- to 26-year-old females for the prevention of diseases caused by those 4 virus strains. These diseases include cervical, vulvar, and vaginal cancer caused by HPV types 16 and 18; cervical, vaginal, and vulvar cancer precursor and dysplastic lesions; and genital warts caused by HPV types 6 and 11. Clinical trials indicate that the vaccine is effective in preventing HPV infection and precancerous lesions in females who have not already been infected with the respective HPV type. Thus, the goal is to administer the vaccine series to females prior to their sexual activity debut, with the recommended age being 11-12 years.
Vaccination is also recommended for 13- to 26-year-old females who have not been vaccinated, or who have not completed the vaccination series, even if the female is already sexually active and could have contracted HPV infection. No evidence exists of protection against vaccine HPV types that have already infected the female at the time of vaccination. However, females infected with fewer than all 4 of the vaccine HPV types before vaccination would likely receive protection and partial benefit against the other vaccine types upon vaccination.
Vaccination is recommended for females with an abnormal Pap test in order to impart partial benefit from vaccine type(s) to which the female has not already been infected. As Pap test results increase in severity, risk for infection with HPV 16 or 18 increases, potentially decreasing the benefit of vaccination.
Patients should be counseled that the vaccine will not have any therapeutic benefit on existing HPV infection or lesions based on clinical trial data.[2] It is important to note that patients who receive Gardasil® should continue to undergo routine cervical cancer screenings by Pap test as recommended by their physicians.
From Medscape Pharmacists
Is Gardasil® Recommended for Young Women Already Exposed to HPV?
Laurie L. Briceland, PharmD
Published: 04/01/2009
Should Gardasil® (human papillomavirus [HPV] quadrivalent [types 6, 11, 16, and 18] vaccine) be administered to young women who test positive for oncogenic-risk HPV strains, or to those who have abnormal Papanicolaou ("Pap") smear results?
Response:
Genital human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, with an estimated 20 million people already infected and over 6 million people infected annually. Although most infections prove to be self-limiting or asymptomatic, persistent infection with oncogenic strains (such as types 16 and 18) can lead to cervical cancer. Seventy percent of cervical cancers are attributed to HPV types 16 and 18; HPV types 6 and 11 contribute to 90% of cases of genital warts.
The HPV quadrivalent (types 6, 11, 16, and 18) vaccine (Gardasil®) was approved by the US Food and Drug Administration in 2006 and is indicated for use in 9- to 26-year-old females for the prevention of diseases caused by those 4 virus strains. These diseases include cervical, vulvar, and vaginal cancer caused by HPV types 16 and 18; cervical, vaginal, and vulvar cancer precursor and dysplastic lesions; and genital warts caused by HPV types 6 and 11. Clinical trials indicate that the vaccine is effective in preventing HPV infection and precancerous lesions in females who have not already been infected with the respective HPV type. Thus, the goal is to administer the vaccine series to females prior to their sexual activity debut, with the recommended age being 11-12 years.
Vaccination is also recommended for 13- to 26-year-old females who have not been vaccinated, or who have not completed the vaccination series, even if the female is already sexually active and could have contracted HPV infection. No evidence exists of protection against vaccine HPV types that have already infected the female at the time of vaccination. However, females infected with fewer than all 4 of the vaccine HPV types before vaccination would likely receive protection and partial benefit against the other vaccine types upon vaccination.
Vaccination is recommended for females with an abnormal Pap test in order to impart partial benefit from vaccine type(s) to which the female has not already been infected. As Pap test results increase in severity, risk for infection with HPV 16 or 18 increases, potentially decreasing the benefit of vaccination.
Patients should be counseled that the vaccine will not have any therapeutic benefit on existing HPV infection or lesions based on clinical trial data.[2] It is important to note that patients who receive Gardasil® should continue to undergo routine cervical cancer screenings by Pap test as recommended by their physicians.
From Medscape Pharmacists
Is Gardasil® Recommended for Young Women Already Exposed to HPV?
Laurie L. Briceland, PharmD
Published: 04/01/2009
ACOG Issues Recommendations on Routine Pelvic Exam, Cervical Cytology Screening
The recommendations of ACOG Committee Opinion Number 431 come with the caveat that the document "reflects emerging clinical and scientific advances as of the date issued and is subject to change," writes ACOG's Committee on Gynecologic Practice. "The information should not be construed as dictating an exclusive course of treatment or procedure to be followed."
ACOG decided to issue the guidelines because the advent of the human papillomavirus vaccine has given rise to some confusion about when, and in whom, to perform periodic health assessments in women.
The recommendations on when to start screening, how often to continue screening, and when to stop routine pelvic examination and cervical cytology are based on age.
- For women younger than 21 years who have never been sexually active, no routine pelvic examination, cervical cytology, or testing for sexually transmitted disease (STD) is needed. If the women have ever been sexually active, however, ACOG recommends cervical cytology be performed 3 years after the onset of sexual activity, and annually thereafter. Routine pelvic examination should be performed only when indicated by the patient's medical history.
- For women aged 21 to 29 years, ACOG recommends an annual pelvic examination and cervical cytology.
- Sexually active women aged 25 years or younger should be screened for chlamydia, and all sexually active adolescents should be screened for gonorrhea. Urine-based screening without a speculum examination is sufficient for such screening, according to ACOG.
- ACOG also says that all adolescents and women aged 19 to 64 years who are sexually active should be screened for HIV.
- For women aged 30 to 64 years, the recommendation is for annual pelvic examination plus cervical cytology. However, screening can be decreased to every 2 to 3 years after 3 normal test results if the patient has no history of cervical intraepithelial neoplasia (CIN) 2 or CIN3, is not immunosuppressed, is not HIV-positive, and was not exposed to diethylstilbestrol (DES) in utero.
- For women older than 65 years, ACOG recommends an annual pelvic examination. However, cervical cytology may be discontinued if the woman has had 3 or more normal test results in a row, no abnormal test results in 10 years, no history of cervical cancer, no DES exposure in utero, is HIV-negative and immunocompetent, and does not have other risk factors for STDs. The need to begin screening again should be evaluated at each annual examination.
- The pelvic examination is not a routine part of the annual health examination in girls aged 13 to 18 years, unless it is medically indicated. It should be performed when it is likely to yield information about amenorrhea, abnormal bleeding, vaginitis, pelvic pain, an STD, a pelvic mass, or other conditions.
- It is also reasonable to stop speculum and bimanual pelvic examinations in asymptomatic women who have had a total hysterectomy and bilateral oophorectomy for benign indications, although annual examination of the external genitalia should continue.
- It would also be reasonable to stop pelvic examination when a woman's age or other health issues reach a point where the woman would not choose to treat conditions detected during the routine examination.
Such a decision should be discussed between the patient and her physician, ACOG recommends.
From Medscape Medical News
Fran Lowry
April 22, 2009 — The American College of Obstetricians and Gynecologists (ACOG) has issued a committee opinion on routine pelvic examination and cervical cytology screening that will be published in the May issue of Obstetrics and Gynecology. (Obstet Gynecol. 2009;113:1190–1193.)
17 May 2009
Probiotics cut bellly fat after pregnancy
New research suggests that probiotics - widely viewed as "friendly" bacteria that improve digestion and gut health - may help women keep belly fat under control after pregnancy.
Researchers from the University of Turku in Finland enrolled 256 pregnant women in a study on weight gain, dividing them into three groups during their first trimesters. Women in two of the groups received dietary counseling consistent with what doctors recommend for healthy weight gain and optimal fetal development. They also were sent home with foods such as spreads and salad dressings with monounsaturated and polyunsaturated fatty acids, as well as fiber-enriched pasta and breakfast cereal. Women in one of those two groups also received daily capsules containing lactobacillus and bifidobacterium, the most commonly used probiotics - bacteria that help maintain a healthy bacterial balance in the gut. The other group received dummy capsules along with counseling. A third group received dummy capsules and got no dietary counseling. All of the women were weighed at the start of the study. They were weighed again at 12 months after childbirth; researchers then measured each woman's waist circumference and skin fold thickness.
Central obesity -- defined as a body mass index of 30 or more and a waist circumference over 80 centimeters (31.5 inches) -- was found in 25% of the women who had been given the probiotics as well as advice on what to eat.
Those not given probiotics didn't do as well. Central obesity was found in 43% of the women who got dietary counseling alone and 40% of the women who got neither probiotics nor dietary advice.
The average body fat percentage in the probiotics group was 28%, compared with 29% in the diet-advice-only group and 30% in the third set of women. "The women who got the probiotics fared best," says Kirsi Laitinen, a nutritionist and senior lecturer at Turku. "One year after childbirth, they had the lowest levels of central obesity as well as the lowest body fat percentage."
Central obesity combined with a "particularly fat belly is considered especially unhealthy," Laitinen says. She adds that more research is needed to confirm the potential positive role of probiotics on belly fat. Also, she says her team of researchers will continue to track the women and their babies to determine whether giving probiotics during pregnancy has any influence on the health of the children.
The findings were released during the 17th European Congress on Obesity in Amsterdam, Netherlands.
SOURCES:
News release, 17th European Congress on Obesity.
17th European Congress on Obesity meeting, Amsterdam, Netherlands, May 6-9, 2009.
May 8, 2009
from WebMD — a health information Web site for patients
Bill Hendrick
Researchers from the University of Turku in Finland enrolled 256 pregnant women in a study on weight gain, dividing them into three groups during their first trimesters. Women in two of the groups received dietary counseling consistent with what doctors recommend for healthy weight gain and optimal fetal development. They also were sent home with foods such as spreads and salad dressings with monounsaturated and polyunsaturated fatty acids, as well as fiber-enriched pasta and breakfast cereal. Women in one of those two groups also received daily capsules containing lactobacillus and bifidobacterium, the most commonly used probiotics - bacteria that help maintain a healthy bacterial balance in the gut. The other group received dummy capsules along with counseling. A third group received dummy capsules and got no dietary counseling. All of the women were weighed at the start of the study. They were weighed again at 12 months after childbirth; researchers then measured each woman's waist circumference and skin fold thickness.
Central obesity -- defined as a body mass index of 30 or more and a waist circumference over 80 centimeters (31.5 inches) -- was found in 25% of the women who had been given the probiotics as well as advice on what to eat.
Those not given probiotics didn't do as well. Central obesity was found in 43% of the women who got dietary counseling alone and 40% of the women who got neither probiotics nor dietary advice.
The average body fat percentage in the probiotics group was 28%, compared with 29% in the diet-advice-only group and 30% in the third set of women. "The women who got the probiotics fared best," says Kirsi Laitinen, a nutritionist and senior lecturer at Turku. "One year after childbirth, they had the lowest levels of central obesity as well as the lowest body fat percentage."
Central obesity combined with a "particularly fat belly is considered especially unhealthy," Laitinen says. She adds that more research is needed to confirm the potential positive role of probiotics on belly fat. Also, she says her team of researchers will continue to track the women and their babies to determine whether giving probiotics during pregnancy has any influence on the health of the children.
The findings were released during the 17th European Congress on Obesity in Amsterdam, Netherlands.
SOURCES:
News release, 17th European Congress on Obesity.
17th European Congress on Obesity meeting, Amsterdam, Netherlands, May 6-9, 2009.
May 8, 2009
from WebMD — a health information Web site for patients
Bill Hendrick
Folic acid supplements for women of child-bearing age
USPSTF Recommends Folic Acid Supplements for Women of Child-Bearing Age
Laurie Barclay, MD
Released: 05/12/2009
New observational evidence supports previous evidence from a randomized controlled trial that folic acid–containing supplements lower the risk for pregnancies affected by neural tube defects, according to a US Preventive Services Task Force (USPSTF) statement and review of evidence reported in the May 5 issue of theAnnals of Internal Medicine. The review suggests that the previously noted association of folic acid use with twin gestation may be confounded by fertility interventions. Based on the evidence, the USPSTF has issued a grade A recommendation that all women planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400 - 800 µg) of folic acid.
Regarding benefits of this preventive measure, the USPSTF found convincing evidence that taking supplements containing 0.4 to 0.8 mg (400 - 800 µg) of folic acid during the periconceptional period lowers the risk for neural tube defects. Regarding potential harms, adequate evidence suggests that folic acid from supplementation at usual doses is not associated with serious harms. For women who are planning or are capable of pregnancy, the USPSTF therefore concludes that there is high certainty that the net benefit of folic acid supplementation during pregnancy is substantial.
Tracy Wolff, MD, MPH, and colleagues from the USPSTF write, "Neural tube defects (NTDs) are among the most common birth defects in the United States,...In 1996, the...USPSTF recommended that all women planning a pregnancy or capable of conception take a supplement containing folic acid to reduce the risk for NTDs."
USPSTF Review Process
The goal of the review was to provide a basis for an updated USPSTF recommendation by searching for new evidence published since 1996 regarding the benefits and harms of folic acid supplementation for women of childbearing age, with the aim of preventing neural tube defects in offspring. The reviewers searched MEDLINE and Cochrane Central Register of Controlled Trials from January 1995 through December 2008, as well as recent systematic reviews and bibliographies cited in identified articles. Experts were also contacted for any pertinent suggestions.
Inclusion criteria for the studies were English-language articles describing the benefits and harms of folic acid supplementation in women of childbearing age to reduce neural tube defects in offspring. These included randomized controlled trials, cohort studies, case-control studies, systematic reviews, and meta-analyses. The investigators reviewed, abstracted, and rated the identified studies for methodologic quality using predefined USPSTF criteria.
The reviewers identified 4 observational studies that showed a benefit of reduction of the risk for neural tube defects associated with use of folic acid–containing supplements. However, a summary of the reduction in risk could not be calculated because of differences in study type and methods. There was only 1 included study on harms, which reported that the apparent association of twin pregnancies with folic acid intake disappeared after adjusting for in vitro fertilization and underreporting of folic acid intake.
Limitations of the review include studies with limited evidence on dose. Also, none of the studies that discussed B12 supported or refuted the potential harm of masking vitamin B12 deficiency in women of childbearing potential. The review did not provide a comprehensive review of the effects of folic acid on all possible outcomes or of the effects of dietary intake of folic acid.
Furthermore, the review did not include a comprehensive picture of how folic acid–containing supplements may prevent other congenital abnormalities, consideration of the evidence on counseling to increase dietary intake of folic acid, or comparison of the effect of folic acid on neural tube defects among different ethnic groups or among groups with genetic differences that may affect folic acid metabolism.
"New observational evidence supports previous evidence from a randomized, controlled trial that folic acid–containing supplements reduce the risk for NTD-affected pregnancies," the review authors write. "The association of folic acid use with twin gestation may be confounded by fertility interventions."
Updates to 1996 Recommendation
The accompanying USPSTF statement is an update of the 1996 USPSTF recommendation that all women planning or capable of pregnancy take a multivitamin supplement containing folic acid to prevent neural tube defects. The statement is based on the evidence regarding folic acid supplementation in women of childbearing age published since the 1996 USPSTF recommendation, without review of evidence regarding food fortification with folic acid, counseling to increase dietary intake, or screening for neural tube defects.
"Approximately 1 in every 1000 pregnancies is affected by a neural tube defect," write USPSTF chair Ned Calonge, MD, MPH, from the Colorado Department of Public Health and Environment in Denver, and colleagues. "Although a personal or family history of a pregnancy affected by a neural tube defect is associated with an increased risk for having an affected pregnancy, most cases occur in the absence of any positive history."
Recommendations From Other Associations
This USPSTF recommendation is consistent with published guidelines of other specialty professional organizations. In 2003, the American College of Obstetrics and Gynecology recommended periconceptual use of a multivitamin supplement containing 0.4 mg of folic acid for most women of childbearing potential.
The American Academy of Family Physicians strongly recommends prescribing folic acid supplementation of 0.4 to 0.8 mg/day for women planning to become pregnant and without a history of neural tube defects, and 0.4 mg/day of folate supplementation to women of childbearing age who are not planning pregnancy.
"The American College of Obstetrics and Gynecology, AAFP [American Academy of Family Physicians], and most other organizations recommend 4 mg/d for women with a history of neural tube defects," the statement authors conclude.
"The American Academy of Pediatrics endorses the U.S. Public Health Service recommendation that all women capable of becoming pregnant consume 400 mcg of folic acid daily to prevent neural tube defects,' particularly for adolescent, ''sexually active women who do not plan to use effective contraception or abstain from sexual intercourse.' Because of teratogenesis and impaired folate metabolism associated with certain antiepileptic drugs, the American Academy of Neurology recommends folic acid supplementation of no less than 0.4 mg/d for women of childbearing age with epilepsy."
Ann Intern Med. 2009;150:626-631, 632-639.
Clinical Context
Neural tube defects affect approximately 0.1% of pregnancies in the United States, with spina bifida and anencephaly being the most common of these defects. Personal and family history play significant roles in the risk for neural tube defects. A history of a previous child with a neural tube defect or a history of a first-, second-, or third-degree relative with a neural tube defect increases this risk, as does Hispanic or non-Hispanic white race. Other risk factors for neural tube defects include diabetes, obesity, and the treatment of epilepsy with medications such as valproic acid or carbamazepine.
In 1996, the USPSTF recommended treatment with folic acid in young women to prevent neural tube defects. The current review updates this recommendation.
Study Highlights
Researchers found observational data published since 1996 that supported the use of folic acid supplements to prevent neural tube defects. In 1 study involving more than 6000 women, the rate of neural tube defects was 0.0032% in women who received folic acid and 0.029% in women who did not. In a meta-analysis, the use of folic acid was associated with an odds ratio of neural tube defects of 0.67 in case-control studies, and the odds ratio was 0.52 in the sum of data from randomized controlled trials.
Researchers considered potential harms associated with the use of folic acid, including possible masking of vitamin B12 deficiency and a higher rate of twin pregnancy. However, they found no significant harms associated with folic acid supplementation. In some research, the use of folic acid appeared to increase the rate of twin pregnancy by nearly 60%. However, this result was rendered insignificant after adjusting for underreporting of folic acid use and rates of in vitro fertilization. In the United States, less than 1% of the total population between the ages of 4 and 50 years had a significant risk for vitamin B12 deficiency. In addition, 1 study found no association between folic acid supplementation and reduced serum levels of vitamin B12.
The USPSTF now gives a grade A recommendation to treat all women planning or capable of pregnancy to receive a daily supplement containing folic acid. This recommendation involves a broad population of women because of the fact that half of pregnancies are unplanned.
The dose of folic acid should be 0.4 to 0.8 mg daily. Higher doses of 4 mg/day may be used in women with a higher risk for neural tube defects.
Most women do not derive adequate amounts of folate from diet alone to protect against neural tube defects. Most studies indicate that folic acid supplementation should begin at least 1 month before conception of a planned pregnancy.
Clinical Implications
Risk factors for a neural tube defect include a previous child with neural tube defect, a family history of neural tube defects among close or distant relatives, Hispanic or non-Hispanic white race, diabetes, and treatment of epilepsy with valproic acid and carbamazepine. The current guidelines from the USPSTF recommend daily supplementation with 0.4 to 0.8 mg of folic acid for all women planning or capable of pregnancy.
Laurie Barclay, MD
Released: 05/12/2009
New observational evidence supports previous evidence from a randomized controlled trial that folic acid–containing supplements lower the risk for pregnancies affected by neural tube defects, according to a US Preventive Services Task Force (USPSTF) statement and review of evidence reported in the May 5 issue of theAnnals of Internal Medicine. The review suggests that the previously noted association of folic acid use with twin gestation may be confounded by fertility interventions. Based on the evidence, the USPSTF has issued a grade A recommendation that all women planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400 - 800 µg) of folic acid.
Regarding benefits of this preventive measure, the USPSTF found convincing evidence that taking supplements containing 0.4 to 0.8 mg (400 - 800 µg) of folic acid during the periconceptional period lowers the risk for neural tube defects. Regarding potential harms, adequate evidence suggests that folic acid from supplementation at usual doses is not associated with serious harms. For women who are planning or are capable of pregnancy, the USPSTF therefore concludes that there is high certainty that the net benefit of folic acid supplementation during pregnancy is substantial.
Tracy Wolff, MD, MPH, and colleagues from the USPSTF write, "Neural tube defects (NTDs) are among the most common birth defects in the United States,...In 1996, the...USPSTF recommended that all women planning a pregnancy or capable of conception take a supplement containing folic acid to reduce the risk for NTDs."
USPSTF Review Process
The goal of the review was to provide a basis for an updated USPSTF recommendation by searching for new evidence published since 1996 regarding the benefits and harms of folic acid supplementation for women of childbearing age, with the aim of preventing neural tube defects in offspring. The reviewers searched MEDLINE and Cochrane Central Register of Controlled Trials from January 1995 through December 2008, as well as recent systematic reviews and bibliographies cited in identified articles. Experts were also contacted for any pertinent suggestions.
Inclusion criteria for the studies were English-language articles describing the benefits and harms of folic acid supplementation in women of childbearing age to reduce neural tube defects in offspring. These included randomized controlled trials, cohort studies, case-control studies, systematic reviews, and meta-analyses. The investigators reviewed, abstracted, and rated the identified studies for methodologic quality using predefined USPSTF criteria.
The reviewers identified 4 observational studies that showed a benefit of reduction of the risk for neural tube defects associated with use of folic acid–containing supplements. However, a summary of the reduction in risk could not be calculated because of differences in study type and methods. There was only 1 included study on harms, which reported that the apparent association of twin pregnancies with folic acid intake disappeared after adjusting for in vitro fertilization and underreporting of folic acid intake.
Limitations of the review include studies with limited evidence on dose. Also, none of the studies that discussed B12 supported or refuted the potential harm of masking vitamin B12 deficiency in women of childbearing potential. The review did not provide a comprehensive review of the effects of folic acid on all possible outcomes or of the effects of dietary intake of folic acid.
Furthermore, the review did not include a comprehensive picture of how folic acid–containing supplements may prevent other congenital abnormalities, consideration of the evidence on counseling to increase dietary intake of folic acid, or comparison of the effect of folic acid on neural tube defects among different ethnic groups or among groups with genetic differences that may affect folic acid metabolism.
"New observational evidence supports previous evidence from a randomized, controlled trial that folic acid–containing supplements reduce the risk for NTD-affected pregnancies," the review authors write. "The association of folic acid use with twin gestation may be confounded by fertility interventions."
Updates to 1996 Recommendation
The accompanying USPSTF statement is an update of the 1996 USPSTF recommendation that all women planning or capable of pregnancy take a multivitamin supplement containing folic acid to prevent neural tube defects. The statement is based on the evidence regarding folic acid supplementation in women of childbearing age published since the 1996 USPSTF recommendation, without review of evidence regarding food fortification with folic acid, counseling to increase dietary intake, or screening for neural tube defects.
"Approximately 1 in every 1000 pregnancies is affected by a neural tube defect," write USPSTF chair Ned Calonge, MD, MPH, from the Colorado Department of Public Health and Environment in Denver, and colleagues. "Although a personal or family history of a pregnancy affected by a neural tube defect is associated with an increased risk for having an affected pregnancy, most cases occur in the absence of any positive history."
Recommendations From Other Associations
This USPSTF recommendation is consistent with published guidelines of other specialty professional organizations. In 2003, the American College of Obstetrics and Gynecology recommended periconceptual use of a multivitamin supplement containing 0.4 mg of folic acid for most women of childbearing potential.
The American Academy of Family Physicians strongly recommends prescribing folic acid supplementation of 0.4 to 0.8 mg/day for women planning to become pregnant and without a history of neural tube defects, and 0.4 mg/day of folate supplementation to women of childbearing age who are not planning pregnancy.
"The American College of Obstetrics and Gynecology, AAFP [American Academy of Family Physicians], and most other organizations recommend 4 mg/d for women with a history of neural tube defects," the statement authors conclude.
"The American Academy of Pediatrics endorses the U.S. Public Health Service recommendation that all women capable of becoming pregnant consume 400 mcg of folic acid daily to prevent neural tube defects,' particularly for adolescent, ''sexually active women who do not plan to use effective contraception or abstain from sexual intercourse.' Because of teratogenesis and impaired folate metabolism associated with certain antiepileptic drugs, the American Academy of Neurology recommends folic acid supplementation of no less than 0.4 mg/d for women of childbearing age with epilepsy."
Ann Intern Med. 2009;150:626-631, 632-639.
Clinical Context
Neural tube defects affect approximately 0.1% of pregnancies in the United States, with spina bifida and anencephaly being the most common of these defects. Personal and family history play significant roles in the risk for neural tube defects. A history of a previous child with a neural tube defect or a history of a first-, second-, or third-degree relative with a neural tube defect increases this risk, as does Hispanic or non-Hispanic white race. Other risk factors for neural tube defects include diabetes, obesity, and the treatment of epilepsy with medications such as valproic acid or carbamazepine.
In 1996, the USPSTF recommended treatment with folic acid in young women to prevent neural tube defects. The current review updates this recommendation.
Study Highlights
Researchers found observational data published since 1996 that supported the use of folic acid supplements to prevent neural tube defects. In 1 study involving more than 6000 women, the rate of neural tube defects was 0.0032% in women who received folic acid and 0.029% in women who did not. In a meta-analysis, the use of folic acid was associated with an odds ratio of neural tube defects of 0.67 in case-control studies, and the odds ratio was 0.52 in the sum of data from randomized controlled trials.
Researchers considered potential harms associated with the use of folic acid, including possible masking of vitamin B12 deficiency and a higher rate of twin pregnancy. However, they found no significant harms associated with folic acid supplementation. In some research, the use of folic acid appeared to increase the rate of twin pregnancy by nearly 60%. However, this result was rendered insignificant after adjusting for underreporting of folic acid use and rates of in vitro fertilization. In the United States, less than 1% of the total population between the ages of 4 and 50 years had a significant risk for vitamin B12 deficiency. In addition, 1 study found no association between folic acid supplementation and reduced serum levels of vitamin B12.
The USPSTF now gives a grade A recommendation to treat all women planning or capable of pregnancy to receive a daily supplement containing folic acid. This recommendation involves a broad population of women because of the fact that half of pregnancies are unplanned.
The dose of folic acid should be 0.4 to 0.8 mg daily. Higher doses of 4 mg/day may be used in women with a higher risk for neural tube defects.
Most women do not derive adequate amounts of folate from diet alone to protect against neural tube defects. Most studies indicate that folic acid supplementation should begin at least 1 month before conception of a planned pregnancy.
Clinical Implications
Risk factors for a neural tube defect include a previous child with neural tube defect, a family history of neural tube defects among close or distant relatives, Hispanic or non-Hispanic white race, diabetes, and treatment of epilepsy with valproic acid and carbamazepine. The current guidelines from the USPSTF recommend daily supplementation with 0.4 to 0.8 mg of folic acid for all women planning or capable of pregnancy.
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