Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid: community-based randomized clinical trial in Italy and the Netherlands.

Publisher: BioMed Central Country of Publication: England NLM ID: 100967799 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2393 (Electronic) Linking ISSN: 14712393 NLM ISO Abbreviation: BMC Pregnancy Childbirth Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Congenital Abnormalities/*prevention & control ; Folic Acid/*administration & dosage ; Pregnancy Complications/*prevention & control ; Vitamin B Complex/*administration & dosage; Adolescent ; Adult ; Community Health Services ; Counseling ; Dietary Supplements ; Female ; Folic Acid/adverse effects ; Humans ; Italy ; Middle Aged ; Netherlands ; Preconception Care ; Pregnancy ; Pregnancy Outcome ; Prenatal Care ; Research Design ; Severity of Illness Index ; Vitamin B Complex/adverse effects ; Young Adult

Background: In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear.Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open.The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae.
Methods/design: This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information.We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis.
Discussion: The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes.
Trial Registration: Italian trial: ClinicalTrials.gov Identifier: NCT01244347.Dutch trial: Dutch Trial Register ID: NTR3161.

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Investigator: R Bortolus; F Filippini; A Compagni; E Rigotti; A Noya di Lannoy; P Mastroiacovo; E Leoncini; M Coati; S Manfrè; R Barbazza; G Zanconato; MT Zenorini; V Travagliati; E Mantovani; A Angeli; E Cavaliere; G Cherubini; A Negretto; E Lavarini; M Ozzi; N Papadopoulos; E Di Mambro; M Vessella; G Ettore; S Bianca; C Barone; G Nesima; E Cosmi; S Visentin; M Camerin; P Lanza; S Marinangeli; G Negrini; A Ottaviani; L Zivelonghi; A Baffoni; M Bertezzolo; M Pistolato; E Ioverno; E Somigliana; C Scarduelli; F Alagna; G Santi; E Cesari; P Zanini; A Morandini; I Cetin; A Laoreti; C Tresso; MG Salviato; M Matterazzo; C Failli; M Marzolini; A Casaro; D Balestreri; E Benassi; E Caloi; FL Giorgino; A Schiavo; GP Piazza; R Ruffini; G Jorizzo; G Cirelli; F Arcidiacono; A De Toni; S Rusconi; C Guaraldi; L Valotto; A Guido; G Zanni; C Vernier; A Sandri; N Minisci; M Cornel; M van Poppel; F Blom; T Kruit; D de Smit; H de Walle

NTR NTR3161
ClinicalTrials.gov NCT01244347

12001-76-2 (Vitamin B Complex)
935E97BOY8 (Folic Acid)

Date Created: 20140603 Date Completed: 20150221 Latest Revision: 20240506

20250114

PMC4045958

10.1186/1471-2393-14-166

24884885