Trial Outcomes & Findings for High Dose Folic Acid Supplementation Throughout Pregnancy for Preeclampsia Prevention (NCT NCT01355159)

Last Updated: 2020-07-07

Results Overview

PE is defined as diastolic blood pressure ≥90 mmHg on two occasions ≥4 hours apart and proteinuria developed in women greater than 20+0 weeks of gestation. Proteinuria is defined as: urinary protein ≥300mg in 24 hour urine collection OR in the absence of 24 hour collection, ≥2+ dipstick proteinuria, OR random protein-creatinine ratio ≥30mg protein/mmol. OR HELLP (Haemolysis, Elevated, Liver Enzymes, Low Platelets) syndrome defined as: Haemolysis (characteristic peripheral blood smear), Serum LDH ≥ 600U/L, Serum AST ≥ 70U/L, and Platelet count \<100 x109/L OR Superimposed pre-eclampsia, defined as history of pre-existing hypertension (diagnosed pre-pregnancy or before 20+0 weeks' gestation) with new proteinuria.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2464 participants

Primary outcome timeframe

Participants will be followed from 20+0 weeks of gestational age until 42 days postpartum (after delivery)

Results posted on

2020-07-07

Participant Flow

High risk pregnant women were recruited in Canada and internationally.

Participant milestones

Participant milestones
Measure	Folic Acid 4 mg Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Overall Study STARTED	1228	1236
Overall Study COMPLETED	1144	1157
Overall Study NOT COMPLETED	84	79

Reasons for withdrawal

Reasons for withdrawal
Measure	Folic Acid 4 mg Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Overall Study Withdrew consent	39	47
Overall Study No primary outcome data	17	11
Overall Study Spontaneous abortion (<20 weeks)	22	15
Overall Study Early intrauterine fetal death	6	6

Baseline Characteristics

Remaining participants did not return study treatment and so the mean could not be calculated.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Folic Acid 4 mg n=1227 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1236 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.	Total n=2463 Participants Total of all reporting groups
Age, Continuous	31 years STANDARD_DEVIATION 5.4 • n=1227 Participants	31 years STANDARD_DEVIATION 5.4 • n=1236 Participants	31 years STANDARD_DEVIATION 5.4 • n=2463 Participants
Age, Customized Maternal age (years) · <20	10 Participants n=1227 Participants	10 Participants n=1236 Participants	20 Participants n=2463 Participants
Age, Customized Maternal age (years) · 20-29	439 Participants n=1227 Participants	447 Participants n=1236 Participants	886 Participants n=2463 Participants
Age, Customized Maternal age (years) · 30-34	411 Participants n=1227 Participants	441 Participants n=1236 Participants	852 Participants n=2463 Participants
Age, Customized Maternal age (years) · >=35	367 Participants n=1227 Participants	338 Participants n=1236 Participants	705 Participants n=2463 Participants
Sex: Female, Male Female	1227 Participants n=1227 Participants	1236 Participants n=1236 Participants	2463 Participants n=2463 Participants
Sex: Female, Male Male	0 Participants n=1227 Participants	0 Participants n=1236 Participants	0 Participants n=2463 Participants
Race/Ethnicity, Customized Maternal Background · Native/Aboriginal	35 Participants n=1227 Participants	24 Participants n=1236 Participants	59 Participants n=2463 Participants
Race/Ethnicity, Customized Maternal Background · Caucasian	970 Participants n=1227 Participants	987 Participants n=1236 Participants	1957 Participants n=2463 Participants
Race/Ethnicity, Customized Maternal Background · Black	93 Participants n=1227 Participants	107 Participants n=1236 Participants	200 Participants n=2463 Participants
Race/Ethnicity, Customized Maternal Background · Asian	45 Participants n=1227 Participants	50 Participants n=1236 Participants	95 Participants n=2463 Participants
Race/Ethnicity, Customized Maternal Background · Latino/Hispanic	31 Participants n=1227 Participants	22 Participants n=1236 Participants	53 Participants n=2463 Participants
Race/Ethnicity, Customized Maternal Background · Indian/South Asian	45 Participants n=1227 Participants	36 Participants n=1236 Participants	81 Participants n=2463 Participants
Race/Ethnicity, Customized Maternal Background · Declined to answer	8 Participants n=1227 Participants	10 Participants n=1236 Participants	18 Participants n=2463 Participants
Region of Enrollment Canada	600 participants n=1227 Participants	607 participants n=1236 Participants	1207 participants n=2463 Participants
Region of Enrollment Argentina	157 participants n=1227 Participants	153 participants n=1236 Participants	310 participants n=2463 Participants
Region of Enrollment United Kingdom	61 participants n=1227 Participants	61 participants n=1236 Participants	122 participants n=2463 Participants
Region of Enrollment Australia	29 participants n=1227 Participants	32 participants n=1236 Participants	61 participants n=2463 Participants
Region of Enrollment Jamaica	380 participants n=1227 Participants	383 participants n=1236 Participants	763 participants n=2463 Participants
Parity 0	413 Participants n=1227 Participants	420 Participants n=1236 Participants	833 Participants n=2463 Participants
Parity 1	498 Participants n=1227 Participants	499 Participants n=1236 Participants	997 Participants n=2463 Participants
Parity >=2	316 Participants n=1227 Participants	317 Participants n=1236 Participants	633 Participants n=2463 Participants
Pre-pregnancy BMI (kg/m2) <18.5	15 Participants n=1227 Participants	11 Participants n=1236 Participants	26 Participants n=2463 Participants
Pre-pregnancy BMI (kg/m2) 18.5 to <25	230 Participants n=1227 Participants	225 Participants n=1236 Participants	455 Participants n=2463 Participants
Pre-pregnancy BMI (kg/m2) 25 to <30	211 Participants n=1227 Participants	199 Participants n=1236 Participants	410 Participants n=2463 Participants
Pre-pregnancy BMI (kg/m2) 30 to <35	164 Participants n=1227 Participants	146 Participants n=1236 Participants	310 Participants n=2463 Participants
Pre-pregnancy BMI (kg/m2) >=35	607 Participants n=1227 Participants	655 Participants n=1236 Participants	1262 Participants n=2463 Participants
Education level High school and below	353 Participants n=1227 Participants	348 Participants n=1236 Participants	701 Participants n=2463 Participants
Education level College/University not complete	198 Participants n=1227 Participants	197 Participants n=1236 Participants	395 Participants n=2463 Participants
Education level College/University completed	675 Participants n=1227 Participants	689 Participants n=1236 Participants	1364 Participants n=2463 Participants
Gestational age (weeks) at recruitment 8-12	386 Participants n=1227 Participants	433 Participants n=1236 Participants	819 Participants n=2463 Participants
Gestational age (weeks) at recruitment 13-16	841 Participants n=1227 Participants	803 Participants n=1236 Participants	1644 Participants n=2463 Participants
Smoking during pregnancy Yes	98 Participants n=1227 Participants	95 Participants n=1236 Participants	193 Participants n=2463 Participants
Smoking during pregnancy No	1046 Participants n=1227 Participants	1035 Participants n=1236 Participants	2081 Participants n=2463 Participants
Smoking during pregnancy Quit during pregnancy	83 Participants n=1227 Participants	106 Participants n=1236 Participants	189 Participants n=2463 Participants
Alcohol during pregnancy Yes	23 Participants n=1227 Participants	27 Participants n=1236 Participants	50 Participants n=2463 Participants
Alcohol during pregnancy No	977 Participants n=1227 Participants	955 Participants n=1236 Participants	1932 Participants n=2463 Participants
Alcohol during pregnancy Quit during pregnancy	227 Participants n=1227 Participants	254 Participants n=1236 Participants	481 Participants n=2463 Participants
Supplementation of FA at randomisation (yes)	989 Participants n=1227 Participants	1016 Participants n=1236 Participants	2005 Participants n=2463 Participants
Supplementation of high dose FA at randomisation (yes)	346 Participants n=1227 Participants	335 Participants n=1236 Participants	681 Participants n=2463 Participants
Aspirin supplementation at randomisation	358 Participants n=1227 Participants	340 Participants n=1236 Participants	698 Participants n=2463 Participants
Calcium supplementation at randomisation	97 Participants n=1227 Participants	109 Participants n=1236 Participants	206 Participants n=2463 Participants
Dietary Folate (µg) (Mean, SD) VIsit 1 (8-16 completed weeks' gestation)	494 µg STANDARD_DEVIATION 209 • n=1215 Participants • Remaining participants did not return study treatment and so the mean could not be calculated.	504 µg STANDARD_DEVIATION 222 • n=1225 Participants • Remaining participants did not return study treatment and so the mean could not be calculated.	499 µg STANDARD_DEVIATION 216 • n=2440 Participants • Remaining participants did not return study treatment and so the mean could not be calculated.
Dietary Folate (µg) (Mean, SD) Visit 2 (24-26 weeks' completed gestation)	494 µg STANDARD_DEVIATION 209 • n=1008 Participants • Remaining participants did not return study treatment and so the mean could not be calculated.	500 µg STANDARD_DEVIATION 213 • n=1023 Participants • Remaining participants did not return study treatment and so the mean could not be calculated.	497 µg STANDARD_DEVIATION 211 • n=2031 Participants • Remaining participants did not return study treatment and so the mean could not be calculated.
Visit 2 Compliance ≤50%	108 Participants n=964 Participants • Calculated on returned study treatment (n=1941). Remaining participants did not return any study treatment and compliance could not be calculated (n=522).	106 Participants n=977 Participants • Calculated on returned study treatment (n=1941). Remaining participants did not return any study treatment and compliance could not be calculated (n=522).	214 Participants n=1941 Participants • Calculated on returned study treatment (n=1941). Remaining participants did not return any study treatment and compliance could not be calculated (n=522).
Visit 2 Compliance 50-75%	140 Participants n=964 Participants • Calculated on returned study treatment (n=1941). Remaining participants did not return any study treatment and compliance could not be calculated (n=522).	122 Participants n=977 Participants • Calculated on returned study treatment (n=1941). Remaining participants did not return any study treatment and compliance could not be calculated (n=522).	262 Participants n=1941 Participants • Calculated on returned study treatment (n=1941). Remaining participants did not return any study treatment and compliance could not be calculated (n=522).
Visit 2 Compliance ≥75%	716 Participants n=964 Participants • Calculated on returned study treatment (n=1941). Remaining participants did not return any study treatment and compliance could not be calculated (n=522).	749 Participants n=977 Participants • Calculated on returned study treatment (n=1941). Remaining participants did not return any study treatment and compliance could not be calculated (n=522).	1465 Participants n=1941 Participants • Calculated on returned study treatment (n=1941). Remaining participants did not return any study treatment and compliance could not be calculated (n=522).
History of Pre-eclampsia	308 Participants n=1227 Participants	303 Participants n=1236 Participants	611 Participants n=2463 Participants
Chronic Hypertension	203 Participants n=1227 Participants	241 Participants n=1236 Participants	444 Participants n=2463 Participants
Type 1 Diabetes	84 Participants n=1227 Participants	72 Participants n=1236 Participants	156 Participants n=2463 Participants
Type 2 Diabetes	98 Participants n=1227 Participants	84 Participants n=1236 Participants	182 Participants n=2463 Participants
Twin Pregnancy	233 Participants n=1227 Participants	229 Participants n=1236 Participants	462 Participants n=2463 Participants
Body mass index >=35	606 Participants n=1227 Participants	656 Participants n=1236 Participants	1262 Participants n=2463 Participants
Prepregnancy Body Mass Index	34 kg/m^2 STANDARD_DEVIATION 8.6 • n=1227 Participants	34 kg/m^2 STANDARD_DEVIATION 13 • n=1236 Participants	34 kg/m^2 STANDARD_DEVIATION 11 • n=2463 Participants
Gestational age at recruitment	14 weeks STANDARD_DEVIATION 1.9 • n=1227 Participants	14 weeks STANDARD_DEVIATION 1.9 • n=1236 Participants	14 weeks STANDARD_DEVIATION 1.9 • n=2463 Participants

PRIMARY outcome

Timeframe: Participants will be followed from 20+0 weeks of gestational age until 42 days postpartum (after delivery)

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1144 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1157 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Preeclampsia	169 Participants	156 Participants

SECONDARY outcome

Timeframe: Time Frame: Participants will be followed from 20+0 weeks of gestation until 42 days postpartum (after delivery)

Population: Participants who completed study and were analyzed for primary outcome

According to the World Health Organization, "A maternal death is defined as the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1144 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1157 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Maternal Death	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Participants will be followed from randomization until 20+0 weeks of gestation

Population: Not all participants had secondary outcome data. Numbers above reflect those that had information available for this secondary outcome.

Spontaneous abortion or miscarriage defined as death of a fetus \<500g or \<20 weeks of gestation

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1172 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1180 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Spontaneous Abortion	27 Participants	21 Participants

SECONDARY outcome

Timeframe: Participants will be followed from 20+0 weeks of gestation until delivery

Population: Not all participants had secondary outcome data. Numbers above reflect those that had information available for this secondary outcome.

Placental abruption (abruptio placentae) is the premature detachment of a normally positioned placenta from the wall of the uterus.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1169 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1179 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Placenta Abruption	12 Participants	19 Participants

SECONDARY outcome

Timeframe: Participants will be followed from randomization (8-16 weeks' completed gestation) until the onset of labor

Rupture of the membranes (rupture of the amniotic sac) before the onset of labor.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1169 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1180 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Premature Rupture of Membranes	215 Participants	224 Participants

SECONDARY outcome

Timeframe: Participants will be followed from 20+0 weeks to 36+6 weeks of gestation

Population: Not all participants had secondary outcome data. Numbers above reflect those that had information available for this secondary outcome.

Birth that occur earlier than 37+0 weeks of gestational age.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1150 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1164 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Preterm Birth	297 Participants	304 Participants

SECONDARY outcome

Timeframe: Participants will be followed from 20+0 weeks of gestation until delivery

Population: Not all participants had secondary outcome data. Numbers above reflect those that had information available for this secondary outcome.

Haemolysis (characteristic peripheral blood smear), Serum LDH \>=600U/L, Serum AST \>=70U/L, Platelet count \<100 x109/L

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1144 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1156 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
HELLP (Hemolysis, Elevated Liver Enzyme Levels & Low Platelet Count)	6 Participants	5 Participants

SECONDARY outcome

Timeframe: Participants will be followed from 20+0 weeks of gestation until delivery.

Population: Not all participants had secondary outcome data. Numbers above reflect those that had information available for this secondary outcome.

Severe PE: Defined as PE with convulsion or HELLP or delivery \<34 weeks.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1144 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1156 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Severe Preeclampsia	24 Participants	16 Participants

SECONDARY outcome

Timeframe: Participants will be followed from date of randomization (8-16 weeks' completed gestation) until admission for delivery

Population: Not all participants had secondary outcome data. Numbers above reflect those that had information available for this secondary outcome.

Length of inpatient stay before admission for delivery in days

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=221 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=232 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Antenatal Inpatient Length of Stay	5.6 days Standard Deviation 7.7	5.2 days Standard Deviation 6.2

SECONDARY outcome

Timeframe: Participants will be followed from 20+0 weeks of gestation up to delivery.

Population: A total of 2738 infants were born to women recruited into the trial (1364 in folic acid group and 1374 in placebo group). This is an infant outcome.

Fetal death defined as death of fetus of at least 500 grams birth weight or, if birth weight is unavailable, a gestational age of at least 20+0 weeks of gestation.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1364 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1374 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Stillbirth	15 Participants	26 Participants

SECONDARY outcome

Timeframe: Participants will be followed from 20+0 weeks of gestation until delivery

Population: A total of 2738 infants were born to women recruited into the trial (1364 in folic acid group and 1374 in placebo group). This is an infant outcome. Some participants had missing data for this outcome and therefore were excluded from this analysis.

Intrauterine growth restriction is defined as a birth weight less than the 3rd percentile of the population, adjusted for sex and gestational age, based on the current population-based Canadian reference standard.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1347 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1348 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Intrauterine Growth Restriction (<3rd Percentile)	20 Participants	25 Participants

SECONDARY outcome

Timeframe: Participants will be followed from 20+0 weeks of gestation until delivery

Intrauterine growth restriction is defined as a birth weight less than the 10th percentile of the population, adjusted for sex and gestational age, based on the current population-based Canadian reference standard.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1347 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1348 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Intrauterine Growth Restriction (<10th Percentile)	151 Participants	144 Participants

SECONDARY outcome

Timeframe: Participants will be followed from birth until 28 days of life

Neonatal death defined as death of a baby that occurred during first 28 days of life.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1343 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1347 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Neonatal Death	8 Participants	11 Participants

SECONDARY outcome

Timeframe: Participants will be followed from 20+0 weeks of gestation until 28 days of life.

The perinatal mortality is defined as the number of deaths (fetal deaths and neonatal deaths) of babies ≥ 500 grams birth weight or, if birth weight is unavailable, a gestational age ≥ 20+0 weeks, up to 28 completed days after birth.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1364 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1374 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Perinatal Mortality	23 Participants	37 Participants

SECONDARY outcome

Timeframe: Infants born to the participant will be followed for the duration of hospital stay, or up to 6 weeks

Retinopathy of prematurity a retinopathy typically occurring in premature infants treated with high concentrations of oxygen, characterized by vascular dilatation, proliferation, tortuosity, edema, retinal detachment, and fibrous tissue behind the lens confirmed by retinal examination according to an International Committee for the Classification of Retinopathy of Prematurity.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1342 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1347 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Retinopathy of Prematurity	21 Participants	13 Participants

SECONDARY outcome

Timeframe: Infants born to the participants will be followed first 48 hours of life.

Within first 48hr of life, confirmed by positive blood or cerebrospinal fluid cultures

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1342 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1347 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Early Onset Sepsis	3 Participants	9 Participants

SECONDARY outcome

Timeframe: Infants borm to the participants will be followed for the duration of hospital stay, or up to 6 weeks.

Necrotizing enterocolitis (NEC) according to modified Bell's criteria stage 2 or higher (grossly bloody stool, plus absent bowel sounds with or without abdominal tenderness and radiographic findings such as intestinal dilation, ileus, pneumatosis intestinalis), excluding isolated spontaneous intestinal perforations.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1343 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1347 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Necrotising Enterocolitis	8 Participants	3 Participants

SECONDARY outcome

Timeframe: Time Frame: Infants born to the participants will be followed for the duration of hospital stay, or up to 6 weeks

* IVH Grade 1(Blood in germinal matrix) * IVH Grade 2 (Blood in germinal matrix and extending into the ventricles) * IVH Grade 3 (Ventricular enlargement) * IVH Grade 4 (Intraparenchymal lesion)

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1343 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1347 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Intraventricular Hemorrhage (IVH)	18 Participants	19 Participants

SECONDARY outcome

Timeframe: Infants born to the participants will be followed for the duration of hospital stay, or up to 6 weeks.

Ventilatory support after initial resuscitation, with/without intubation.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1346 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1348 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Ventilation	49 Participants	30 Participants

SECONDARY outcome

Timeframe: Infants to the participants will be followed for 28 days after birth.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1220 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1227 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Need for Oxygen at 28 Days	9 Participants	3 Participants

SECONDARY outcome

Timeframe: Outcomes included in the composite outcome were measured for each of their respective time frames, up to 6-weeks after birth

Composite outcome included any of retinopathy of prematurity, periventricular leukomacia, early onset sepsis, necrotizing enterocolitis, intraventricular haemorrhage, ventilation. Need for O2at 28 days, NICU admission

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1349 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1348 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Composite Severe Adverse Fetal/Neonatal Outcome	63 Participants	51 Participants

SECONDARY outcome

Timeframe: Infants to the participants will be followed for the duration of hospital stay, or up to 6 weeks.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=299 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=263 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Length of Stay in 'High Level' Neonatal Care Unit	16 days Standard Deviation 27	17 days Standard Deviation 23

SECONDARY outcome

Timeframe: Infants to the participants will be followed for 28 days after birth.

Neonatal death defined as death of the infant occurred before 28 days of life

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1343 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1347 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Neonatal Death	151 Participants	144 Participants

SECONDARY outcome

Timeframe: Infants to the participants were followed for 28 days after birth.

One of the two outcomes used to measure neonatal morbidity.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1343 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1347 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Periventricular Leukomalacia	4 Participants	2 Participants

SECONDARY outcome

Timeframe: Infants to the participants will be followed for the duration of hospital stay, or up to 6 weeks.

This outcome measured whether or not the infant was admitted into the NICU.

Outcome measures

Outcome measures
Measure	Folic Acid 4 mg n=1346 Participants Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1348 Participants Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Neonatal Intensive Care Unit (NICU) Admission	299 Participants	267 Participants

Adverse Events

Folic Acid 4 mg

Serious events: 227 serious events

Other events: 961 other events

Deaths: 0 deaths

Placebo

Serious events: 195 serious events

Other events: 968 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Folic Acid 4 mg n=1227 participants at risk Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1236 participants at risk Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Pregnancy, puerperium and perinatal conditions Prematurity	2.4% 29/1227 One participant (in the Folic Acid group) withdrew consent on the same day of randomization; participants is excluded from being considered "at risk" for AE/SAEs.	1.6% 20/1236 One participant (in the Folic Acid group) withdrew consent on the same day of randomization; participants is excluded from being considered "at risk" for AE/SAEs.
Pregnancy, puerperium and perinatal conditions Hypertension	2.5% 31/1227 One participant (in the Folic Acid group) withdrew consent on the same day of randomization; participants is excluded from being considered "at risk" for AE/SAEs.	2.0% 25/1236 One participant (in the Folic Acid group) withdrew consent on the same day of randomization; participants is excluded from being considered "at risk" for AE/SAEs.
Pregnancy, puerperium and perinatal conditions Other SAE	13.6% 167/1227 One participant (in the Folic Acid group) withdrew consent on the same day of randomization; participants is excluded from being considered "at risk" for AE/SAEs.	12.1% 150/1236 One participant (in the Folic Acid group) withdrew consent on the same day of randomization; participants is excluded from being considered "at risk" for AE/SAEs.

Other adverse events

Other adverse events
Measure	Folic Acid 4 mg n=1227 participants at risk Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid Folic Acid 4 mg: Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid	Placebo n=1236 participants at risk Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo Placebo: Placebo x 4 tablets will be taken daily by oral administration.
Pregnancy, puerperium and perinatal conditions Other AE	78.3% 961/1227 One participant (in the Folic Acid group) withdrew consent on the same day of randomization; participants is excluded from being considered "at risk" for AE/SAEs.	78.3% 968/1236 One participant (in the Folic Acid group) withdrew consent on the same day of randomization; participants is excluded from being considered "at risk" for AE/SAEs.

Additional Information

Dr. Mark Walker

Ottawa Hospital Research Institute

Phone: 6137378899

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place