|- candidate number||10567|
|- NTR Number||NTR3161|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||22-nov-2011|
|- Secondary IDs||2011-003325-10 EudraCT number|
|- Public Title||Het Foliumzuur-Extra bij kinderwens en zwangerschap onderzoek Noord-Nederland.|
|- Scientific Title||A randomized controlled trail on the effects of periconceptional and prenatal folic acid supplementation on congenital anomalies and preterm birth.|
|- hypothesis||1. What is the effect of a high (4.0 mg) versus low (0.4 mg) dose of folic acid supplementation from 4 weeks before conception to 12 weeks after conception on the prevalence of folic acid related congenital anomalies?|
2. What is the effect of 0.8 mg folic acid supplementation versus 0.2 mg folic acid supplementation from 12 weeks after conception to the end of pregnancy on the prevalence of preterm birth and preeclampsia?
|- Healt Condition(s) or Problem(s) studied||Pre-eclampsia, Neural tube defect, Preterm birth, Folic acid, Congenital anomalies|
|- Inclusion criteria||All women living in the Northern region of the Netherlands of 18 to 45 years old who want to become pregnant within 12 months are eligible for participation in the study. Women followed by an assisted reproduction centre are not excluded.|
|- Exclusion criteria||1. No informed consent given;|
2. Not understanding Dutch;
3. Already pregnant at time of inclusion or within 4 weeks after start intervention;
4. Planning to move to an area where the study is not implemented;
5. Recently or at present using folic acid antagonists or antifolates or other drugs influencing the folic acid metabolism (anti-epileptica, methotrexaat, pyrimethamine, trimethoprim);
6. Being affected by diabetes, megaloblastic anaemia and/or cancer (previous cancer or abnormal PAP smears);
7. Being allergic to folic acid or any other ingredient of the pills used in this study;
8. Take defined dosages of folic acid for directions other than those listed in the above exclusion criteria.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jan-2012|
|- planned closingdate||31-dec-2016|
|- Target number of participants||5000|
|- Interventions||Women in all intervention groups will receive identical pills, containing two different doses of folic acid (0.4 or 4.0 mg). Women will start taking the pills after randomisation, but at least 4 weeks before conception, and will receive new pills from their pharmacy every 16 weeks.|
Fourteen weeks after the first day of the last menstruation (12 weeks after conception), all women will receive a new set of pills, half of them will receive 0.2 mg supplements and half will receive 0.8 mg of FA.
|- Primary outcome||The primary outcome measures are: FA related congenital anomalies and preterm birth.
Information on all congenital anomalies of live births, stillbirths and terminations of pregnancy following prenatal diagnosis will be derived from the database of EUROCAT, where virtually all congenital anomalies are registered. Data about the diagnosis and the medical history are collected in a standardized procedure of high quality. FA related congenital anomalies are neural tube defects, heart anomalies, limb defects, urinary tract malformations, oral cleft and Down syndrome. The congenital anomalies will be classified according to the guidelines for case classification by Rasmussen et al (2003).
Preterm birth is defined as a gestational age < 37 weeks. Gestational age will be assessed from the medical records. Medical terminations will also be included, to avoid bias toward the null hypothesis.|
|- Secondary outcome||1. Birth weight, obtained from medical records;|
2. Preeclampsia (defined as a systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg after 20 weeks of gestation among women with previously normal blood pressure, combined with proteinuria (> 300 mg/24 hours)), obtained from medical records;
3. Compliance with intervention.
|- Timepoints||After randomisation, women will collect new pills every 16 weeks at the pharmacy, until a period of 12 months has gone by without them getting pregnant or until the end of their pregnancy (live birth, stillbirth, spontaneous abortion, or termination). At each collection date, they fill in a short questionnaire.|
|- Trial web site||www.foliumzuurextra.nl|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| Fenneke Blom|
|- CONTACT for SCIENTIFIC QUERIES|| Fenneke Blom|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|ZON-MW, The Netherlands Organization for Health Research and Development|
|- Brief summary||N/A|
|- Main changes (audit trail)|
|- RECORD||22-nov-2011 - 24-jul-2014|