Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Clinical Trial to Evaluate the Efficacy of High Dose of Folic Acid to Prevent the Occurrence of Congenital Malformations
Brief Summary: In 1991 the Medical Research Council Vitamin Study Group and in 1992 the Hungarian randomised clinical trial have shown conclusively that the risk of neural tube defects can be reduced substantially by taking folic acid during the peri-conceptional period. At present there is enough evidence to support the hypothesis that folic acid supplementation can reduce the risk of all congenital malformations or of a specific and selected group of them, namely: neural tube defects, oral clefts, cardiac defects, urinary tract anomalies except hypospadias, limb reduction defects, omphalocele, anal atresia and trisomy 21.

The hypothesis that a higher intake of folic acid is related to an higher risk reduction of neural tube defects and of other congenital malformations is the main rationale for the present study.

The present study is a randomized, double-blind, controlled trial evaluating whether supplementation with folic acid at high dose (4 mg/day) reduces the overall risk of major congenital malformations in the population more than the standard recommended dose (0.4 mg/day). At the enrolment visit all the eligible women will be interviewed to assess sociodemographic, life style and health status. After randomization, women will be interviewed every 4 months to evaluate pregnancy status. Women who have a pregnancy diagnosis during the study period will be interviewed by telephone at the expected 16, 24 and 40 weeks of gestation to evaluate the pregnancy outcome. The health status of live births will be evaluated at the child's age of 1 month, 3 months and 1 year.

The primary aim of this project is conducting a study to assess the effect of folic acid periconceptional supplementation of 4 mg/day compared to the 0.4 mg/day standard dose on reducing the occurrence of all congenital malformations. Secondary aims of this study include comparing severity of CMs in offspring of trial mothers, rates of "selected congenital malformations", rates of twinning, miscarriages, recurrent abortions, small-for-gestational age, preeclampsia and abruptio placentae. The sample size is not easy to be computed because lacking robust estimate of the size effect of the treatment. Three hypotheses of a size effect of 45%, 26% and 13% were considered. A sample size of outcomes (and women) respectively of 2,006 (5,015), 8,510 (21,275) and 30,126 (75,315) is needed. Since the sample size needed to evaluate different scenarios is large, the present study is also the pilot study to promote an international prospective meta-analysis.


Options:
A: Inclusion Criteria:

Women were eligible if they were:

* Married
* Nulliparous
* \< 40 years old
* Living in the same household as their husband

Exclusion Criteria:

Women were excluded if they were:

* Pregnant at enrollment
* Planning to move out of the region
* Using iron supplements within the previous 3 months
* Using an implant form of birth control, or had surgery to prevent pregnancy
* Women with a Hb concentration of \< 70 g/L, defined as severely anemic according to WHO definition (5), were excluded from the study and appropriately treated
B: Inclusion Criteria:

1. One neoplastic polyp removed within three months of study entry or within 16 months of study entry if over 1 cm in size or if subject has had a lifetime history of at least two polyps, with the entire large bowel seen by colonoscopy to be free of further polyps within 3 months of entry.
2. An ability and willingness to follow the study protocol, as indicated by the subject's giving informed consent to participate.
3. Good general health, with no severely debilitating diseases or active malignancy that might compromise the patient's ability to complete the study.
4. Anticipated colonoscopic follow-up three years after the qualifying colonoscopy.
5. Age between 21 and 80 years at the time of the intake colonoscopy.
6. For women of childbearing potential, agreement to use effective birth control for the duration of the study.
7. Intent not to take aspirin or aspirin-containing products, NSAIDs or folic acid for the length of the study unless required by a physician.
8. Not randomized previously or currently in a chemoprevention trial, except for the: "Nutritional Prevention of Large Bowel Polyps" Study (Polyps Prevention Study I); and brief participation in the "VA Cooperative Study" with no continuing involvement.

Exclusion Criteria:

1. Invasive carcinoma in any colonic polyp removed.
2. Familial colonic polyposis syndromes.
3. Ulcerative colitis or Crohn's disease.
4. Malabsorption syndrome (e.g. pancreatic insufficiency).
5. Large bowel resection for any reason.
6. Diagnosed narcotic or alcohol dependence
7. Contraindication to aspirin use, including:

   1. documented peptic ulcer disease in the past 20 years
   2. aspirin sensitivity
   3. bleeding diathesis, including hemorrhagic stroke
8. Likelihood of NSAID use

   1. recurring arthritis or other musculo-skeletal problems
   2. frequent NSAID use in 5 years preceding
   3. history of stroke or TIAs
   4. history of angina or myocardial infarction
   5. desire to take aspirin for the prevention of cardiovascular disease
9. Required or contraindicated folic acid use pernicious anemia or folic acid deficiency
10. Pregnancy or lactation.
C: Inclusion Criteria:

* age between 18 and 44 years
* women who intend to become pregnant (not excluded women

Exclusion Criteria:

* pregnant women
* women planning to move to an area where the study is not ongoing
* women who do not understand and speak Italian
* women who do not have a phone
* women affected by epilepsy, even not assuming anticonvulsivant drugs
* women affected by diabetes
* women who previously had a tumour or a disease relevant for the study (Crohn disease, rheumatoid arthritis, ulcerative colitis)
* women who recently assumed antifolates, like methotrexate
* women who currently abuse or previously abused alcohol
* obese women
* vegetarian women
* women who had a previous pregnancy with neural tube defect (NTD) or any other congenital structural defect
* women or partners with NTD, or one of their relatives with an NTD
* women with positive family history for breast or colorectal cancer
* women with positive family or personal history of hereditary syndrome like adenomatous polyposis, or hereditary nonpolyposis colorectal cancer
* women allergic to folic acid
* women presenting contraindications to folic acid
* women affected by megaloblastic anaemia
* assuming folic acid at defined doses for conditions other than those already mentioned
D: Inclusion Criteria:

* 18-45 year old English-speaking women

Exclusion Criteria:

* current pregnancy
* history of tubal ligation
* hysterectomy
* partner with a vasectomy
* no sex with men
* will not be able to be reached by telephone in 6 months

Answer: C