Methods

Randomisation: adequate by means of computer‐generated numbers. Allocation concealment: adequate. Blinding: adequate. Participant and care provider blinded. Loss to follow up: adequate. Less than 5%.

Participants

97 healthy women attending prenatal care at National Maternity Hospital, Dublin, Ireland with singleton pregnancy, during their first trimester of pregnancy, and with haemoglobin equal or higher than 140 g/L were assigned to the groups. Women were excluded if they had a recent blood transfusion, chronic respiratory disease, chronic hypertension, renal disease, diabetes mellitus, history of haematologic disorder and alcohol dependence.

Interventions

Women were randomly assigned to one of two groups: group 1: received iron and folic acid tablets, one tablet to be taken by mouth twice daily (each tablet contained 0.5 mg of folic acid and 60 mg elemental iron); group 2: placebo tablets also to be taken by mouth twice daily.
Supplementation started at 12 wks until delivery. No postpartum supplementation.

Outcomes

Maternal: haemoglobin, hematocrit, serum erythropoietin concentrations at baseline and at 24, 28, 32, 36 and 40 wk; serum ferritin at baseline and at 36 wk; number of hypertensive disorders, antepartum haemorrhage, cesarean delivery.
Infant: perinatal death, birthweight below 10th percentile, Apgar score, need for neonatal resuscitation and admission to neonatal intensive care unit data recorded but not reported in paper. Cord blood values of haemoglobin, hematocrit, serum ferritin, and erythropoietin concentrations.

Notes

Unsupervised.
No participants were withdrawn because of anaemia.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate by means of computer‐generated numbers.

Allocation concealment?

Low risk

Adequate.

Blinding?
All outcomes

Low risk

Adequate.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 5% lost to follow up.

Methods

Randomisation: unclear ‐ method not stated. Allocation concealment: unclear. Blinding: unclear ‐ participant blinded. Provider/assessor not stated or clear. Loss to follow up: inadequate ‐ 37 women (28%) were excluded for analysis.

Participants

133 women referred to investigators from a population of women attending an antenatal clinic for the fist time in Yangoon (also known as Rangoon), Myanmar (Burma). Women with severe anaemia were excluded from the trial during the intervention for treatment.

Interventions

Women were randomly assigned to one of four groups starting at 22‐25 wks: group 1: one ferrous sulphate tablet containing 60 mg of elemental iron, and one placebo tablets twice daily; group 2: one tablet containing 60 mg of elemental iron as ferrous sulphate, and one tablet containing 0.5 mg of folic acid twice daily; group 3: two placebo tablets twice daily; group 4: one placebo tablet and one tablet containing 0.5 mg of folic acid twice daily. Administration of the treatments was carefully supervised. Supplementation started at 22‐25 wks until term.

Outcomes

Maternal: haemoglobin concentrations at baseline, at term (38‐40th wk) and 4‐7 wk postpartum, serum iron, serum and red cell folate activity and hypersegmented polimorph count at baseline, at 38‐40th wk and postpartum.

Notes

Supervised. 32 women who had taken other supplements or whose Hb level at full term was not available were excluded from the analysis. Three women from group 3 and two from group 4 developed severe anaemia and were also withdrawn from analysis.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Unclear ‐ method not stated.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

Unclear risk

Unclear ‐ participant blinded. Provider/assessor not stated or clear.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate ‐ 37 women (28%) were excluded for analysis.

Methods

Randomisation: adequate by means of a randomised list stratified by age, parity and initial haemoglobin level. Allocation concealment: adequate. Numbered bottles of tablets and code was broken after study completed for group 1 and 2. Blinding: inadequate. Participant and provider were blinded to treatment for groups 1 and 2. The control group did not get a placebo. Loss to follow up: inadequate ‐ more than 20% were lost to follow up to the postnatal visit.

Participants

200 women before 20th week of gestation and Hb above 100 g/L attending antenatal clinic at the Maternity Hospital in Glossop Terrace, Cardiff, England, United Kingdom were studied. Exclusion criteria included urinary infection and threatened miscarriage, confusion over therapy, intercurrent illness and difficult veins, intolerant to the iron form, premature labor.

Interventions

Women were randomly allocated to three groups: group 1: received 122 mg of elemental iron as ferrous sulphate daily; group 2: received 122 mg of elemental iron as ferrous sulphate plus 3.4 mg of folic acid daily; group 3: no treatment. A group 4 was formed as some subjects (n = 38) from group 3 received iron supplements for treatment of anaemia in the course of the intervention. They are excluded for analysis. Women were supplemented from week 20 to week 40 of gestation.

Outcomes

Maternal: haemoglobin concentrations, blood and plasma volume, haematocrit (not reported), red cell volume, albumin and globulin fractions, oedema, intrapartum haemorrhage.

Notes

Unsupervised.
154 women were followed through to the postnatal visit. Only 16 women (30%) in the no treatment group remained untreated.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate by means of a randomised list stratified by age, parity and initial haemoglobin level.

Allocation concealment?

Low risk

Adequate.

Blinding?
All outcomes

High risk

Inadequate. Participant and provider were blinded to treatment for groups 1 and 2. The control group did not get a placebo.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate ‐ more than 20% were lost to follow up to the postnatal visit.

Methods

Randomisation: adequate by random table numbers. Allocation concealment: adequate by means of sealed envelopes. Blinding: inadequate. Participant nor provider blinded. No placebo used. Loss to follow‐up: adequate ‐ less than 20% lost to follow up.

Participants

45 non‐anaemic women with singleton pregnancy and no major illnesses attending the University Hospital Obstetric and Gynaecologic Clinic in Antwerp, Belgium.

Interventions

Women were randomly assigned to one of two groups:
group 1: received 105 mg of elemental iron as ferrous sulphate daily in a sustained release preparation and group 2: received no iron supplement.
Supplementation started at 14‐16th week of gestation and continued until delivery.

Outcomes

Maternal: haemoglobin, serum iron, serum transferrin and serum ferritin concentrations at 16, 28, 36 wks, delivery and 6 wks postpartum.

Notes

Unsupervised. The randomisation was made for each clinic in Antwerp, and the results are presented separately by clinic. Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate ‐ by random table numbers.

Allocation concealment?

Low risk

Adequate, by means of sealed envelopes.

Blinding?
All outcomes

High risk

Inadequate. Participant nor provider blinded. No placebo used.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 20% lost to follow up

Methods

Randomisation: unclear. method not stated. Allocation concealment: unclear. Blinding: unclear. Not specified. Loss to follow up: unclear. Not reported.

Participants

27 apparently healthy non‐anaemic pregnant women 17‐35 years of age from 4 participating obstetricians' private practice clinics from Montreal, Canada in their 1‐5th month of pregnancy with Hb 12 g/dL or higher in first trimester and 11 g/dL or higher in second trimester. Women with history of pathological blood loss or gross dietary imbalance were excluded.

Interventions

Women were randomly assigned to two groups: group 1 received 39 mg elemental iron to be taken twice daily with meals (total daily 78 mg elemental iron) or group 2 who received no iron tablets. Both groups received one tablet of multivitamin supplement daily containing: copper citrate 2 mg, magnesium stearate 6 mg, manganese carbonate 0.3 mg, vitamin A 1000 IU, vitamin D 500 IU, bone flour 130 mg, vitamin B1 1 mg, vitamin B2 1 mg, brewer yeast concentrate 50 mg, niacinamide 5 mg, vitamin C 25 mg, sodium iodide 0.2 mg and folate 0.049 ug (naturally occurring). Duration of supplementation unclear.

Outcomes

Maternal: Hb concentration, packed cell volume, reticulocyte count, sedimentation rate, total white blood cell and differential counts, serum iron, unsaturated and total iron binding capacity, serum B12, serum and RBC folate at baseline and at 32, 36, 39th wks and 7 days postpartum.

Notes

Supervision unclear.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Unclear ‐ method not stated.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

Unclear risk

Unclear.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate ‐ not reported.

Methods

Randomisation: inadequate ‐ quasi‐randomised study, assignment by sequence. Allocation concealment: inadequate. Blinding: adequate. Participant and provider blinded. Loss to follow up: adequate ‐ less than 20%.

Participants

251 women attending antenatal clinic at St Mary's Hospital, London, England, United Kingdom before 20th week of gestation.

Interventions

Women were allocated by sequence to one of five groups: group 1: oral dose of 30 mg of elemental iron daily; group 2: oral dose of 60 mg of elemental iron daily; group 3: oral dose of 120 mg of elemental iron daily; group 4: placebo; group 5: 1 g of iron (Imferon, 4 x 250 mg) intravenously before week 20, and thereafter oral 60 mg of elemental iron as ferrous fumarate daily (not included in this review). Oral elemental iron provided as ferrous fumarate.
Supplementation started at 20th week until 37th week. Only the data related to comparisons of group 1: oral dose of 30 mg of elemental iron daily with group 4: placebo are used in this review given that no data for the other groups could be desegregated.

Outcomes

Maternal: full blood count, serum iron at 20, 25, 30 and 37th week. Sternal marrow aspiration at 37 wks; antepartum haemorrhage, threatened abortion, urinary tract infection, fetal abnormalities, pregnancy hypertension, premature delivery and puerperal infection measured but not reported by groups.
Infant: birthweight (not reported by groups).

Notes

Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

High risk

Inadequate ‐ quasi‐randomised study, assignment by sequence.

Allocation concealment?

High risk

Inadequate.

Blinding?
All outcomes

Low risk

Adequate. Participant and provider blinded.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 20%.

Methods

Randomisation: adequate, using a set of random tables. Allocation concealment: unclear. Blinding: unclear ‐ participant and outcome assessor blinded. Provider blinding unclear. Loss to follow up: adequate. Ranged from 10%‐15%.

Participants

325 pregnant women with Hb (AA) and 232 pregnant women with Hb (AE) attending midwife centres in 80 villages from the Varin Chamrab district of Ubon Province, Thailand. Chronic illness, complicated pregnancy, severe anaemia (Hb < 80 g/L), haemoglobinopathies Hb (EE) and (EF), and unwillingness to cooperate were reason for exclusion. Individuals with Hb (AA) have normal hemoglobin genes. Individuals with Hb (AE) have a heterozygous Hb E trait with normal Hb gene (A‐adults) and an abnormal Hb gene (E). This is usually a clinically insignificant condition.

Interventions

Women were divided into two groups according to Hb (AA) and Hb (AE) and studied separately. Women from each group were randomly assigned to one of the following interventions: group 1: placebo, supervised; group 2, 120 mg of elemental iron and 5 mg folic acid daily supervised; group 3, 240 mg of elemental iron daily supervised; group 4: 240 mg of elemental iron daily supervised; group 5: 120 mg elemental iron and 5 mg of folic acid, motivated but unsupervised; and group 6: 240 mg of elemental iron and 5 mg of folic acid daily, motivated but unsupervised. For the Hb (AE) group, women were randomly assigned to one of the following groups: group 7: placebo, supervised; group 8: 240 mg elemental iron and 5 mg of folic acid daily, supervised; group 9: 240 mg of elemental iron daily, supervised; group 10: 120 mg of elemental iron and 5 mg of folic acid daily, motivated but unsupervised, and group 11: 240 mg of elemental iron and 5 mg of folic acid daily, motivated but unsupervised. Elemental iron was given as ferrous sulphate.
Starting and ending time of supplementation not stated.

Outcomes

Maternal: haemoglobin, serum ferritin after 10 and 15 wks of supplementation, and side effects.

Notes

Groups 1, 2, 3, 4, 7, 8, 9 supervised. Groups 5, 6, 10 and 11 motivated but unsupervised. For purposes of analysis, the groups were merged by iron alone or iron‐folic acid, and included as daily higher doses in both cases.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate, using a set of random tables.

Allocation concealment?

Unclear risk

Unclear

Blinding?
All outcomes

Low risk

Unclear ‐ participant and outcome assessor blinded. Provider blinding unclear.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate. Ranged from 10%‐15%.

Methods

Randomisation: adequate ‐ by computerised random numbers. Allocation concealment: adequate by sealed envelopes. Blinding: inadequate ‐ participant, care provider and outcome assessor not blinded. Loss to follow up: inadequate ‐ more than 20% lost to follow up.

Participants

256 clinically healthy pregnant women from low socio‐economic status attending one antenatal care clinic in Guatemala City, Guatemala and Hb > 80 g/L were recruited. City of Guatemala is at 1500 m above sea level, so values were adjusted by altitude subtracting 5 g/L in Hb.

Interventions

Women were randomly assigned to one of two groups: group 1: daily supervised intake of 60 mg elemental iron and 500 ug folic acid; group 2: weekly supervised intake of 180 mg of elemental iron and 3.5 mg of folic acid in one intake once a week. Iron given as ferrous sulphate.
Supplementation started at different gestational age for each participant. Average gestational age at start was 20.5 wks until 38th wk.

Outcomes

Maternal: haemoglobin concentration at baseline and at term (38th week of gestation); side effects and total iron intake.
Infant: birthweight.

Notes

Supervised.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate ‐ by computerised random numbers.

Allocation concealment?

Low risk

Adequate, by sealed envelopes.

Blinding?
All outcomes

High risk

Inadequate ‐participant, care provider and outcome assessor not blinded.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate ‐ more than 20% lost to follow up.

Methods

Randomisation: adequate by computerised random numbers. Allocation concealment: adequate by sealed envelopes. Blinding: inadequate. Participant and provider not blinded. Outcome assessor for laboratory blinded to groups. Loss to follow up: inadequate.

Participants

120 clinically healthy pregnant women attending one antenatal care clinic in Guatemala City, Guatemala with Hb >80 g/L were recruited. Women were from low SES. City of Guatemala is 1500 m above sea level, so values were adjusted by altitude subtracting 5 g/L in Hb.

Interventions

Women from low SES were randomly assigned to one of two groups: group 3: daily unsupervised intake of 60 mg elemental iron as ferrous sulphate and 500 ug folic acid; or group 4: weekly unsupervised intake of 180 mg of elemental iron as ferrous sulphate and 3.5 mg of folic acid in one intake once a week.
Supplementation started at an average of 20.5 wks of gestation until 38th wk.

Outcomes

Maternal: haemoglobin concentration at baseline and at term (38th week of gestation); side effects and total iron intake.
Infant: birthweight.

Notes

Unsupervised.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate, by computerised random numbers.

Allocation concealment?

Low risk

Adequate, by sealed envelopes.

Blinding?
All outcomes

High risk

Inadequate. Participant and provider not blinded.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate

Methods

Randomisation: method unclear. Allocation concealment: adequate. Bottles containing the tablets had been numbered by random selection at source and the code was unknown during trial. Blinding: adequate. participant and provider blinded. Loss to follow up: adequate. No losses to follow up.

Participants

360 non‐anaemic women attending antenatal clinic at Ridcliffe Infirmary, Oxford, England United Kingdom before 28th week of gestation, who had not taken iron supplements in the preceding 8 wks and with Hb >= 102 g/L or a normal serum iron reading. Exclusion criteria: Hb < 110 g/L and serum iron less than 60 ug/L.

Interventions

Women were randomly assigned to one of various combinations of elemental iron as ferrous gluconate and folic acid, as follows:
group 1: 900 mg elemental iron alone daily; group 2: 900 mg elemental iron and 500 ug folic acid daily; group 3: 900 mg elemental iron and 5 mg folic acid daily; group 4: placebo; group 5: 500 ug folic acid daily; group 6: 5 mg of folic acid daily. Iron and folic acid placebos were used.
Supplementation started at 28th week until 40th week.

Outcomes

Maternal: haemoglobin, haematocrit, serum iron, serum folic acid activity, serum vitamin B12 estimation at 28 wks of gestation and predelivery.

Notes

Unsupervised.
For purposes of this review, placebo group was the group who received neither iron nor folic acid. Groups 2 and 3 were merged for iron‐folic acid comparisons.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Method unclear.

Allocation concealment?

Low risk

Adequate. Bottles containing the tablets had been numbered by random selection at source and the code was unknown during trial.

Blinding?
All outcomes

Low risk

Adequate. Participant and provider blinded.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate. No losses to follow up.

Methods

Randomisation: adequate. Cluster randomisation. Allocation concealment: adequate. Coded. Blinding: adequate. Participant, provider and outcome assessors blinded. Loss to follow up: inadequate. More than 20% losses to follow up.

Participants

4998 married pregnant women (with positive pregnancy test) living in the south eastern plains district of Sarlahi, Nepal. Widows were excluded.

Interventions

Women were randomly assigned to one of five groups: group 1 received 1000 ug retinol equivalents vitamin A (control) daily; group 2 received 1000 ug retinol equivalents vitamin A and 400 ug folic acid daily; group 3 received 1000 ug retinol equivalents vitamin A, 400 ug folic acid and 60 mg elemental iron as ferrous fumarate daily; group 4 received 1000 ug retinol equivalents vitamin A, 400 ug folic acid, 60 mg of elemental iron as ferrous fumarate and 30 mg of zinc sulphate daily; and group 5 received 1000 ug retinol equivalents vitamin A, 400 ug folic acid, 60 mg elemental iron as ferrous fumarate, 30 mg of zinc, 10 ug vitamin D, 10 mg vitamin E, 1.6 mg thiamine, 1.8 mg riboflavin, 20 mg niacin, 2.2 mg vitamin B6, 2.6 ug vitamin B12, 100 mg vitamin C, 65 ug vitamin K, 2 mg cooper, and 100 mg magnesium daily. Only groups 1 and three are considered in this review. Supplementation started at recruitment and continued until 3 month post‐partum in the case of live births of 5 wks or more after a miscarriage or stillbirth. All participating women were offered deworming treatment (albendazole 400 mg single dose) in the second and third trimester.
Supplementation lasted 257.5 days in group 1 (control) and 251.7 days in the group 3 receiving vitamin A, iron and folic acid.
Comparisons: group 3 vs group 1: effect of iron supplementation with folic acid; group 3 vs group 2: effect of iron supplementation alone.

Outcomes

Maternal: premature delivery, Hb and iron status at baseline in the third trimester and Hb at 6 wk postpartum, prevalence of anemia in third trimester and at 6 wk postpartum, severe anemia postpartum, moderate anaemia during third trimester, moderate anaemia postpartum, moderate haemoconcentration during third trimester
Infant: birth weight, prevalence of low birth weight, perinatal mortality, neonatal mortality, infant deaths, small for gestational age.

Notes

Unsupervised but trial personnel visited women twice each week to monitor supplement intake.
Compliance during pregnancy measured by pill count was high (median 88%) and did not vary by groups.
98% of the women accepted the albendazole treatment at both times (second and third trimesters)

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate. Cluster randomisation.

Allocation concealment?

Low risk

Adequate. Coded.

Blinding?
All outcomes

Low risk

Adequate ‐ participant, provider and outcome assessors blinded.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate. More than 20% losses to follow up.

Methods

Randomisation: adequate by computerised random numbers. Allocation concealment: adequate. Blinding: adequate ‐ participant and care provider blinded. Outcome assessor unclear. Loss to follow up: inadequate ‐ more than 20% lost to follow up.

Participants

275 legally competent, non‐imprisoned, non‐anaemic, low‐income pregnant women at < 20 wks of gestation with ferritin levels above 20 ug/L enrolled at the Cuyahoga County, MetroHealth Center, Supplemental Nutrition Program for Women, Infants and Children in Cleveland, Ohio, USA.

Interventions

Women were randomly assigned to one of two groups: group 1 received 1 gelatin capsule containing 30 mg of elemental iron as ferrous sulphate daily; group 2 received 1 placebo soft gelatin capsule daily for 119 days.
Supplementation started at an average of 11 wks of gestation until delivery.

Outcomes

Maternal: prevalence of anaemia at 28 and 38 wks, side effects, compliance to treatment, maternal weight gain, iron status (mean cell volume, haemoglobin concentration, serum ferritin, erythrocyte protoporphyrin concentrations at 28 and 38 wks.
Infant: birthweight, birth length, proportion of low birthweight, low birthweight and premature, small‐for‐gestational age.

Notes

Unsupervised. Women were re‐evaluated at 28 wks of gestation, and according to haemoglobin concentrations at that time were prescribed treatment following the Institute of Medicine guidelines for iron supplementation during pregnancy.
Compliance was 63.4% and 65.2% in groups 1 and 2 respectively.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate, by computerised random numbers.

Allocation concealment?

Low risk

Adequate

Blinding?
All outcomes

Low risk

Adequate ‐ participant and care provider blinded. Outcome assessor unclear.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate ‐ more than 20% lost to follow up.

Methods

Randomisation: unclear ‐ randomised but method used unclear. Allocation concealment: adequate. Blinding: adequate. Participant and provider blinded. Loss to follow up: adequate ‐ less than 20%.

Participants

191 non‐anaemic pregnant women with 12‐18 wks of gestation attending antenatal care clinic at the Maternity at Poissy Hospital, Paris, France. Exclusion criteria included women who had taken iron or folate supplements in the prior 6 months and those with language barriers for proper communication.
Supplementation started at 12‐18 wks until delivery.

Interventions

Women were randomly allocated to one of 2 groups: group 1: daily intake of 45 mg of elemental iron as ferrous betainate hydrochloride (15 mg elemental iron per tablet) and group 2: placebo tablets.

Outcomes

Maternal: haemoglobin, MCV, serum iron, total iron binding capacity, transferrin saturation, serum ferritin at baseline, at 5 months, at 7 months, at delivery and 2 months postpartum.

Notes

Unsupervised.
Serum ferritin values presented as arithmetic and geometric means. No standard deviation in transformed ferritin values is presented. Women in the placebo group were prescribed treatment after delivery thus not allowing comparisons at 2 months postpartum among the groups.
Compliance reported as good.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Unclear ‐ randomised but method used unclear.

Allocation concealment?

Low risk

Adequate.

Blinding?
All outcomes

Low risk

Adequate. Participant and provider blinded.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate, less than 20%.

Methods

Randomisation: adequate by cluster. Allocation concealment: inadequate ‐ not used. Blinding: inadequate ‐ neither participant nor provider blinded. Outcome assessor unclear. Loss to follow up: inadequate ‐ more than 20% loss to follow up.

Participants

209 apparently healthy women attending antenatal care clinics in rural areas of Mymemsingh thana, Bangladesh, with fundal height of 14‐22 cm (18‐24 wks of gestation), who had not used iron supplements prior to the study. Exclusion criteria: women with haemoglobin concentrations < 80 g/L.

Interventions

Each clinic was randomly assigned to one of two interventions: 60 mg of elemental iron as ferrous sulphate and 250 ug folic acid given in one tablet daily, or 120 mg of elemental iron as ferrous sulphate and 500 ug folic acid once a week (given in two tablets one day of the week). Supplementation continued until 6 wks postpartum.
Supplementation started at baseline for 12 wks.

Outcomes

Maternal: haemoglobin concentration at baseline and after 12 wks of supplementation. Compliance, side‐effects, serum ferritin and serum transferrin receptors at 6 wks postpartum.

Notes

Unsupervised.
Cluster randomisation used among 52 antenatal clinics: n = 25 to daily supplementation and n = 25 to weekly supplementation. Two antenatal care units ceased operation during the trial period.
Compliance was 104% and 68% for weekly and daily groups respectively. The compliance above 100% for the weekly means that more tablets that were indicated to be taken were ingested in the period of time.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate by cluster.

Allocation concealment?

High risk

Not used.

Blinding?
All outcomes

High risk

Inadequate ‐ neither participant nor provider blinded. Outcome assessor unclear.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate ‐ more than 20% loss to follow up.

Methods

Randomisation: adequate ‐ computer generated. Allocation concealment: adequate ‐ central allocation at trials office, sequentially numbered. Blinding: adequate ‐ participant and care provider blinded. Loss to follow up: inadequate. 23% and 21% in groups included.

Participants

90 healthy non‐anaemic pregnant women with singleton pregnancy of less than 13 wks, attending an inner city maternity centre in Bergen, Norway and willing to participate. Exclusion criteria: uncertain gestational age according to menstrual history, haemoglobin concentration < 110 g/L, chronic disease or pregnancy complications (hypertension, diabetes, bleeding), multiple pregnancy, liver enzymes out of normal range and logistic difficulties foreseen at baseline (moving out of area).

Interventions

Women were randomly allocated to one of the following: group 1: three tablets containing 1.2 mg heme iron from porcine blood and 9 mg of elemental iron as ferrous fumarate (Hemofer^®) and one placebo tablet (total 27 mg elemental iron a day); group 2: one tablet containing 27 mg elemental iron as iron fumarate with 100 mg vitamin C (Collet^®) and three placebo tablets; or group 3: four placebo tablets.
Supplementation started at 20th week until 38‐40th week.

Outcomes

Maternal: haemoglobin, erythrocytes count, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, reticulocytes, serum iron, total iron binding capacity, serum transferrin, erythrocyte protoporphyrin at baseline and at 20, 28, 38 wks, 8 wks postpartum, and 6 months postpartum; pregnancy complications: hypertension, pre‐eclampsia, forceps, postpartum haemorrhage, maternal wellbeing and breastfeeding duration.
Infant: birthweight and length.

Notes

Unsupervised.
Only groups 1 and 3 (placebo) were included in this review.
Compliance was 81% and 82% in groups 1 and 3 respectively.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate, computer generated.

Allocation concealment?

Low risk

Adequate

Blinding?
All outcomes

Low risk

Adequate ‐ participant and care provider blinded.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate. 23% and 21% in groups included.

Methods

Randomisation: inadequate ‐ alternate by day of the week. Allocation concealment: inadequate. Blinding: inadequate. Open. Loss to follow up: adequate. Less than 5% excluded.

Participants

174 primigravidae or secundigravidae at their first visit at the antenatal Clinic of Queen Elizabeth Hospital in Woodville, Australia with ability to write and speak English.

Interventions

Women were divided into a supplemented group receiving a daily dose of 100 mg of elemental iron as ferrous gluconate or a control group that was unsupplemented.
Supplementation started during 2nd trimester and ending time is unclear.

Outcomes

Maternal: haemoglobin and haematocrit at 20‐30 wk, 30‐40 wk, at 5 days, at 6 wk and at 3 months postpartum.
Infant: haemoglobin from umbilical cord, at 6 wk, at 3 months and at 6 months of age (not reported).

Notes

Unsupervised.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

High risk

Inadequate ‐ quasi‐randomised, alternate by day of the week.

Allocation concealment?

High risk

Inadequate.

Blinding?
All outcomes

High risk

Inadequate. Open.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate. Less than 5% excluded.

Methods

Randomisation: adequate. Allocation concealment: adequate ‐ supplied in coded opaque bottles. Blinding: inadequate ‐ participant blinded. Care provider and outcome assessor unblinded. Loss to follow up: adequate. No losses to follow up.

Participants

13 apparently healthy non‐anemic non‐smokers pregnant women aged 18‐40 years and < 14 wks of gestation with singleton pregnancy recruited through local medical practitioners and the Maternity Department of the Norfolk and Norwich University Hospital, England, United Kingdom.

Interventions

Women were randomly assigned to one of two groups: group 1 received 100 mg elemental iron as ferrous gluconate daily after food and group 2 received a placebo. Supplementation started at 16th week of gestation until delivery.

Outcomes

Maternal: haemoglobin, serum ferritin, transferrin receptor, plasma zinc, exchangeable zinc pool, zinc excretion and zinc absorption at 16, 24 and 34 wks of gestation.
Infant: birth weight (not reported).

Notes

Unsupervised.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate.

Allocation concealment?

Low risk

Adequate, supplied in coded opaque bottles.

Blinding?
All outcomes

High risk

Inadequate ‐ participant blinded. Care provider and outcome assessor unblinded.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ no losses to follow up.

Methods

Randomisation: adequate. Random codes created by computer in blocks of ten by maternity centre. Allocation concealment: adequate. Sealed numbered envelopes stored in containers from which midwives were asked to take them in order. Blinding: inadequate ‐ neither participants nor provider blinded. Outcome assessor blinded. Loss to follow up: adequate ‐ less than 5% lost to follow up.

Participants

2994 pregnant women with less than 16 wks of gestation attending 15 communal maternity centres and 12 centres in five neighbouring communities in Tampere, Finland who consented to participate. Exclusion criteria included: chronic illness, anemia (hematocrit under 0.32 or Hb <110 g/L), late arrival, likelihood of moving away from the area before child birth, or twin pregnancies.

Interventions

Women were randomly assigned to one of two policy groups: group 1 (routine) were recommended to take 100 mg elemental iron alone (iron compounds and dosage varied as per midwife recommendation) daily after the 16th week gestation; or group 2 (selective) who received no iron supplements. Women in the selective group who had a haematocrit of < 0.30 (Hb < 100 g/L) on two consecutive visits were provided 100 mg elemental iron (as ferrous sulphate) to be taken one tablet (50 mg) twice a day for two months or until haematocrit increased to 0.31 (Hb 100 g/L)

Outcomes

Maternal: Haematocrit at 28th and 36th week gestation, weight increase (kg), systolic and systolic blood pressure at 36^th wk, proteinuria, haematocrit at 28^th and 36^th wk gestation,  overall estimation of health, symptoms of tiredness, sick days, fever, adverse effects from iron supplements, symptoms related to iron supplements, duration of first stage of labor, C‐section, blood transfusion, fever I hospital, postpartum stay in hospital for more than 7 days, not breastfeeding in postpartum check up, spontaneous abortions, length of gestation in wk, proportion of premature births.

Infant: birth weight, low birth weight, death, perinatal mortality, 1 min Apgar score < 7, special care unit, malformations, infections, hiperviscosity as a discharge diagnosis, weight gain, overall health.

Notes

Average iron intake in the routine group was 124 mg elemental iron a day. 32 women were excluded: 20 twin pregnancies, 4 discovered not to be pregnant, and 8 for other (unintentional) reasons. Of the remaining 2912, 218 participants miscarried. Final samples were therefore 2694: 1336 women in the routine iron group and 1358 women in the selective group.

The limit to prescribe treatment on the selective group was changed in the middle of the study to haematocrit <0.31 (Hb < 105 g/L) after the 33^rd wk of gestation.

Compliance assessed daily through self reporting. Women in the routine group who reported not having taken the iron supplements during the preceding two wks was only 8.2% at 28^th week gestation and 14% at 36 wks.

It is reported that 7.4% of mothers in the selective group (i.e. no iron unless anaemic) reported having taken iron either regularly or "every now and then" in the preceding two wks, at 28^th wk gestation, while this proportion increased to 14% in the 36^th wk.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate. Random codes created by computer in blocks of ten by maternity centre.

Allocation concealment?

Low risk

Adequate ‐ sealed numbered envelopes stored in containers from which midwives were asked to take them in order.

Blinding?
All outcomes

High risk

Inadequate ‐ neither participants nor provider blinded. Outcome assessor blinded.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 5% lost to follow up.

Free of selective reporting?

Low risk

Methods

Randomisation: unclear. Allocation concealment: unclear. Blinding: inadequate ‐ neither participants nor provider blinded. Outcome assessor unclear. Loss to follow up: unclear.

Participants

207 pregnant women with less than 26 wks of gestation and Hb > 100 g/L attending antenatal care clinic in Nebraska, USA.

Interventions

Women were randomly assigned to one of 3 groups: group 1 received 1 g of an iron salt daily; group 2 received 0.8‐1.2 g of ferrous sulphate and 60‐90 mg of cobalt chloride daily, and group 3 received no treatment.
Supplementation started at various times before 26th week of gestation for each of the subjects until delivery.

Outcomes

Maternal: haemoglobin, haematocrit, serum iron, erythrocyte protoporphyrin at 3‐6 months and pre‐delivery.

Notes

Unsupervised.
Three iron salts (n = 94) were used: ferrous gluconate (n = 40), ferrous sulphate (n = 32) and Mol‐Iron^® (n = 22). The iron treated groups with different iron salts were merged together by the author as iron treated group since the results were comparable. The iron and cobalt treatment group is not included in this review.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Unclear.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

High risk

Inadequate ‐ neither participants nor provider blinded.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Unclear.

Methods

Randomisation: unclear. Allocation concealment: unclear. Blinding: inadequate ‐ neither participant nor provider blinded. Outcome assessor unclear. Loss to follow up: adequate. Less than 20%.

Participants

75 consecutive apparently healthy pregnant women with 32‐34 wks of gestation attending the maternity clinic at St Anthony's Hospital, Oklahoma City, Oklahoma, USA.

Interventions

Women were randomly divided in three groups: group 1 served as control and received no treatment; group 2 received 220 mg elemental iron as ferrous sulphate daily; and group 3 received 55 mg elemental iron as sustained release ferrous sulphate daily.
Supplementation started at 32‐34 week of gestation until delivery.

Outcomes

Maternal: haemoglobin, haematocrit, incidence and severity of side effects on a weekly basis until delivery.

Notes

Unsupervised.
Group 2 is recorded as higher daily dose and group 3 as low daily dose. For any iron versus no treatment comparison groups were merged.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Unclear.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

High risk

Inadequate ‐ neither participant nor provider blinded. Outcome assessor unclear.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate. Less than 20% losses to follow up.

Methods

Randomisation: adequate by cards shuffle. Allocation concealment: unclear. Blinding: inadequate ‐ participant blinded. Provider blinded to treatments but not to controls. Outcome assessor unclear. Loss to follow up: inadequate. 23% of participants were lost to follow up.

Participants

430 apparently healthy women with 24‐25 wks of singleton pregnancy and Hb equal or above 104 g/L attending antenatal clinic at Simpson Memorial Maternity Pavillion, Edinburgh, Scotland, United Kingdom.

Interventions

Women were randomly allocated to one of 4 groups: group 1 received 35 mg of elemental iron as ferrous sulphate three times a day; group 2 received 35 mg of elemental iron as ferrous gluconate three times a day; group 3 received 35 mg of elemental iron as ferrous gluconate with 25 mg of ascorbic acid, three times a day; group 4 received placebo.
Supplementation started at 24‐25th week of gestation until term.

Outcomes

Maternal: haemoglobin, red cell count, haematocrit at baseline and at 37th week.

Notes

Unsupervised.
Groups 1 and 2 were merged for analysis. Group 3 was not used in this review.
Compliance not measured.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate by cards shuffle.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

High risk

Inadequate ‐ participant blinded. Provider blinded to treatments but not to controls. Outcome assessor unclear.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate. 23% of participants were lost to follow up.

Methods

Randomisation: adequate. Allocation concealment: unclear. Blinding: inadequate: subject, provider and outcome assessor unclear. Loss to follow up: adequate: more than 80% of participants were included in the analysis. 16.2% of participants were lost to follow up.

Participants

154 apparently healthy pregnant women seeking prenatal care in Gwangju, South Korea during first trimester of pregnancy who did not receive other supplements or medications throughout pregnancy and who were willing to participate.

Interventions

Women were randomly allocated to one of 5 groups: group 1 received 30 mg elemental iron and 175 ug folic acid daily from first trimester until delivery; group 2 received 60 mg of elemental iron with 350 ug of folic acid from first trimester until delivery; group 3 received 30 mg elemental iron and 175 ug of folic acid from 20th week of gestation until delivery; group 4 received 60 mg elemental iron and 350 ug of folic acid from 20th week of gestation until delivery; or control group with no supplement. Elemental iron was given as ferrous sulphate.

Outcomes

Maternal: haemoglobin, haematocrit, serum ferritin, serum soluble transferrin receptor concentrations at baseline and during first, second, third trimester of pregnancy and at delivery.

Notes

Unsupervised.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

High risk

Unclear: subject, provider and outcome assessor blinding unclear.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 20% lost to follow up.

Methods

Randomisation: method unclear. Non‐supplemented group was self‐selected.
Allocation concealment: adequate by sealed closed envelopes. Blinding: inadequate. Neither participant nor provider blinded. Outcome assessor blinded. Follow up: adequate ‐ less than 20% lost to follow up.

Participants

395 healthy, anaemic and non anaemic, pregnant women attending prenatal care at 2 outpatient clinics at Changji Hospital and Shihezi Maternal and Child Health Station in Xianjiang, China. Women with Hb < 80 g/L were excluded. Maternal age was 25.15 ± 2.28 years.

Interventions

Women were randomly assigned to one of 3 groups: group 1: 60 mg elemental iron as ferrous sulphate and 0.25 mg of folic acid daily; group 2: 120 mg of elemental iron as ferrous sulphate and 0.5 mg of folic acid daily; group 3: 120 mg elemental iron as ferrous sulphate and 0.5 mg of folic acid once weekly. A control group that received no iron was composed of women who did not want to participate in the study and did not receive any iron supplements.

Outcomes

Maternal: haemoglobin concentration at 3, 5, 8 months and at term; serum ferritin concentrations at 3 months and at term in a subgroup; side effects.
Weight at entry and at term (not used in the review).

Notes

Unsupervised.
Iron supplementation is not mandatory for women in China, if they have a Hb concentration > 80 g/L.
Compliance for group 1 (daily 60 mg Fe), group 2 (daily 120 mg Fe) and group 3 (weekly 20 mg Fe) were 77%, 75% and 86% respectively.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

High risk

Method unclear. Non‐supplemented group was self‐selected.

Allocation concealment?

Low risk

Adequate by sealed closed envelopes.

Blinding?
All outcomes

High risk

Inadequate. Neither participant nor provider blinded. Outcome assessor blinded.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 20% lost to follow up.

Methods

Randomisation: adequate by means of computer generated with balanced blocks and stratified for parity. Allocation concealment:adequate ‐ opaque bottles marked with sequential numerical code prepared by the Pharmacy Department of Women's & Children's Hospital. Blinding: adequate ‐ participant and care provider blinded. Loss to follow up: adequate. Less than 20% lost to follow up.

Participants

430 non‐anaemic pregnant women attending antenatal clinics at Women's and Children's Hospital in Adelaide, Australia with singleton or twin pregnancies and informed consent. Exclusion criteria: diagnosis of thalassaemia, history of drug or alcohol abuse and history of vitamin and mineral preparations containing iron prior to enrolment in study.

Interventions

Women were randomly assigned to receive one tablet containing 20 mg of elemental iron daily between meals from week 20 until delivery or a placebo tablet.

Outcomes

Maternal: haemoglobin concentration at 28 wk, at delivery, and at 6 months postpartum; ferritin concentration at delivery and at 6 months postpartum; maternal gastrointestinal side effects at 24 and 36 wk of gestation; serum zinc at delivery and at 6 month postpartum; maternal well being at 36 wk of gestation, at 6 wk and at 6 months postpartum; pregnancy outcomes: type of birth, blood loss at delivery, gestational age. At 4 years postpartum: general health of mothers using the SF‐36, a self administered questionnaire that assesses 8 concepts of health.
Infant: birthweight, birth length, birth head circumference, Apgar scores, and level of nursery care. Follow up at 4 years: intelligence quotient (IQ) using Stanford‐Binet Intelligence Scale, child behaviour using Strength and Difficulties Questionnaire parent report form.

Notes

Unsupervised but monthly phone calls to encourage compliance.
If anaemia was detected in the routine 28 wk blood sample or if the clinician considered her Hb too low the woman was advised to purchase and take a high‐dose iron supplement (containing > 80 mg elemental iron per tablet) until the end of pregnancy.
Compliance was 86% and 85% in the iron and placebo groups respectively.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate by means of computer generated with balanced blocks and stratified for parity.

Allocation concealment?

Low risk

Aadequate, opaque bottles marked with sequential numerical code prepared by the Pharmacy Department of Women's & Children's Hospital.

Blinding?
All outcomes

Low risk

Adequate ‐ participant and care provider blinded.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate. Less than 20% lost to follow up.

Methods

Randomisation: adequate stratified by age group. Allocation concealment: unclear. Blinding: adequate. Participant and provider blinded. Outcome assessor unclear. Loss to follow up: inadequate. More than 20% lost to follow up.

Participants

144 non‐iron deficient adolescents 15‐18 years old in their first pregnancy and adult women 19 or older in their first or greater pregnancy attending prenatal care at Marshfield Clinic, Wisconsin, USA.

Interventions

Women were randomly assigned to receive once daily 60 mg of elemental iron as ferrous sulphate or a placebo. All women received 1 mg of folic acid daily.

Outcomes

Maternal: prevalence of iron deficiency anaemia, compliance to treatment, side effects, vomiting, nausea, constipation, diarrhoea, C‐section, serum ferritin and haemoglobin concentrations at 24‐28 wk gestation and at 36‐40 wk gestation.
infant: perinatal morbidity and mortality, birth weight, birth length, Apgar scores at 1 and 5 minutes, admission to neonatal unit, prevalence of birthweight.

Notes

Unsupervised.
All adolescents and adult pregnant women who developed iron deficiency anaemia at 24‐28 wk gestation were offered 60 mg elemental iron three times a day.
Compliance was assessed through pill counts and ranged from 32% to 124% (median 95.5% in iron supplemented group and 87.4% in placebo group.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate stratified by age group.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

Low risk

Adequate. Participant and provider blinded. Outcome assessor unclear.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate. More than 20% lost to follow up.

Methods

Randomisation: unclear ‐ randomised but method unclear. Allocation concealment: inadequate. Blinding: inadequate. Participant and provider not blinded. Outcome assessor blinded. Loss to follow up: inadequate. More than 20% lost to follow up.

Participants

550 multi gravidae pregnant women with less than 34 wks of gestation attending antenatal care clinics in 18 villages near the town of Farafenni, in North Bank Division, Gambia where malaria is endemic with high transmission during 4‐5 months a year.

Interventions

Women were allocated randomly by compound of residence to receive 60 mg of elemental iron as ferrous sulphate or placebo. All pregnant women received a weekly tablet of 5 mg of folic acid but no antimalarial chemoprophylaxis.
Supplementation started at 23‐24 wks until delivery.

Outcomes

Maternal: haemoglobin concentrations at baseline, 4‐6 wks before delivery and one week postpartum; plasma iron, total iron binding capacity, transferrin saturation, deposition of malaria pigment in placenta.
Infant: birthweight within 7 days of delivery.

Notes

Unsupervised.
Malaria prophylaxis is provided to primigravidae in The Gambia. Thirty women with PCV less than 25% after enrolment (17 in iron group and 13 in placebo) were treated and withdrawn from study and analysis. Additionally 29 women (7 in iron and 22 in placebo group) had PCV below 25% at the second visit and were also withdrawn from study.
Compliance: estimated tablet consumption was 81.1 and 81.7 tablets in the iron and placebo groups respectively.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Unclear ‐ randomised but method unclear.

Allocation concealment?

High risk

Inadequate.

Blinding?
All outcomes

High risk

Inadequate. Participant and provider not blinded. Outcome assessor blinded.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate. More than 20% lost to follow up.

Methods

Randomisation: method unclear. Allocation concealment: unclear. Blinding: adequate. Participant and provider blinded. Outcome assessor unclear. Loss to follow up: adequate. Less than 20% lost to follow up.

Participants

248 healthy Caucasian Danish women attending Birth Clinic in Copenhagen, Denmark within 9‐18 wks of gestation and normal pregnancy. Exclusion criteria: complicated delivery, excessive smoking (> 9 cigarettes/day).

Interventions

Women were randomly assigned to receive 66 mg of elemental iron as ferrous fumarate daily (n = 121) or placebo (n = 127) until delivery.
Supplementation started at 8‐9th week until delivery.

Outcomes

Maternal: haemoglobin, haematocrit, erythrocyte indices, iron status, serum ferritin, serum transferrin saturation, serum erythropoietin at baseline and every 4th week until delivery, and 1‐8 wks after delivery in sub sample; pregnancy complications.
Infant: birthweight, serum ferritin, transferrin saturation and serum erythropoietin in umbilical cord.

Notes

Unsupervised.
Of the 248 women, 20 placebo and 21 iron treated were excluded by the authors in some of the analysis for the following reasons: withdrawn consent, 10; uterine bleeding episodes, 5; placental insufficiency, placenta praevia and abruptio placentae, 7; pre‐eclampsia, 3; partus prematurus, 5; excessive smoking, 3. Sample size has been adjusted for intention to treat ITT.
Compliance: number of tablets consumed was 159 +/‐ 38 and 93 +/‐43 tablets in the iron treated and placebo groups respectively.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Method unclear.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

Low risk

Adequate. Participant and provider blinded. Outcome assessor unclear.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate. Less than 20% lost to follow up.

Methods

Randomisation: adequate. computer generated random numbers. Block randomisation (block size = 10). Allocation concealment: inadequate ‐ not used. Blinding: inadequate. Open to participants, care providers and outcome assessor. Loss to follow up: inadequate. More than 20% excluded.

Participants

111 apparently healthy pregnant women with less than 20 wks and no prior intake of iron supplements during this pregnancy with Hb equal or higher than 100 g/L and singleton pregnancy in New Delhi, India. Women who were taking anti‐epileptics or anti‐thyroid medications, had history of menorrhagia, bleeding disorders, chronic peptic ulcers, bleeding piles, thalassaemia or other haemoglobinopathies, or history of haemorrhage in present or past pregnancies were excluded.

Interventions

Women were randomly assigned to one of two groups: group 1 received two tablets of 100 mg elemental iron and 500 ug folic acid each (total 200 mg iron and 1000 ug folic acid), to be taken only once a week, one tablet before lunch and another tablet before dinner; group 2 received one tablet of 100 mg elemental iron and 500 ug folic acid daily. Women were advised to take the supplements 30 minutes before the meals and not with tea, coffee or milk. Also, women were advised to take calcium supplements after meals (500 mg elemental calcium twice daily). Iron supplementation started between 14 and 20 wks until delivery. Deworming, if required, was carried out with Mebendazole 100 mg twice a day for 3 days in the second trimester.

Outcomes

Maternal: Hb, serum ferritin concentrations at baseline and at 32‐34 wks, prevalence of anaemia, compliance to treatment, presence of intestinal parasites.
Infant: birth weight.

Notes

Unsupervised.
Compliance measured by pill count and interview. compliance was 85% in group 1 (intermittent) and 40% in group 2 (daily).

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate. computer generated random numbers. Block randomisation (block size=10).

Allocation concealment?

High risk

Not used.

Blinding?
All outcomes

High risk

Inadequate ‐ open to participants, care providers and outcome assessor.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate. More than 20% excluded.

Methods

Randomisation: method unclear. Allocation concealment: adequate ‐ sequentially numbered. Blinding: adequate ‐ participant and provider blinded. Loss to follow up: adequate ‐ less than 5%.

Participants

180 primigravidae women with less than 20 wk gestation and Hb > 100 g/L attending antenatal clinic in Aberdeen Maternity Hospital, Scotland, United Kingdom.

Interventions

Women were randomly assigned to one of three groups: group 1 received 3 tablets containing 4 mg elemental iron each (total 12 mg daily); group 2 received 3 tablets containing 35 mg elemental iron (total 105 mg elemental iron daily) and group 3 received placebo. Intervention was from week 20 to week 36 of gestation.

Outcomes

Maternal: haemoglobin, haematocrit at baseline, and at wks 20, 30, 36 of gestation and 7‐13 days postpartum; plasma volume at 30 wks, total red cell volume, serum iron and total iron binding capacity at 30 wks, subjective health and side effects at 30 wks.

Notes

Unsupervised.
Compliance estimated by measuring tablets returned. Authors report good compliance.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Method unclear.

Allocation concealment?

Low risk

Adequate, sequentially numbered.

Blinding?
All outcomes

Low risk

Adequate ‐ participant and provider blinded.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 5%.

Methods

Randomisation: inadequate ‐ quasi randomised. Allocation concealment: not used. Blinding: inadequate ‐ neither participant nor provider blinded. Outcome assessor blinded. Loss to follow up: inadequate. More than 20% lost to follow up.

Participants

203 healthy pregnant women with normal blood pressure at first visit, attending antenatal care clinic at Diego Paroissien Hospital in the Province of Buenos Aires, Argentina.

Interventions

Women were assigned to one of three groups: group 1 received 60 mg of elemental iron as ferrous fumarate daily; group 2 received 60 mg elemental iron every three days; and group 3 received no treatment. Supplementation started at 8‐28 wks until 34‐37 wks of gestation.

Outcomes

Maternal: Hb, haematocrit, erythroporphyrin, serum ferritin concentration at baseline and at 34‐37wk gestation, premature delivery.
Infant: birthweight.

Notes

Unsupervised.
Women from control group (group 3) were not assigned randomly. These women were recruited but due to delays in the acquisition of the iron tablets and the progression of their pregnancies without supplementation they were left as controls in the study.
This study is used only for comparison between intermittent and daily iron supplementation (group 2 vs group 1).
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

High risk

Inadequate ‐ quasi randomised.

Allocation concealment?

High risk

Not used

Blinding?
All outcomes

High risk

Inadequate ‐ neither participant nor provider blinded. Outcome assessor blinded.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate. More than 20% lost to follow up.

Free of selective reporting?

High risk

Free of other bias?

High risk

Methods

Randomisation: adequate ‐ by random numbers. Allocation concealment: adequate ‐ packages of tablets numbered by manufacturer. Blinding: adequate ‐ participant and provider blinded. Outcome assessor blinded. Loss to follow up: unclear.

Participants

197 healthy pregnant women 17‐40 years of age, with 28 +/‐ 3 wks of gestation attending antenatal care clinic in a Mother‐Child Health Center in Niamey, Niger.

Interventions

Women were randomly assigned to one of two groups: group 1 received 100 mg of elemental iron as ferrous betainate daily; group 2 received placebo.
Supplementation was from 28 +/‐ 3 wks of gestation until delivery.

Outcomes

Maternal: haemoglobin concentration, mean corpuscular volume, haematocrit, erythrocyte protoporphyrin, serum iron, transferrin, total iron binding capacity, serum ferritin concentrations, at baseline and at the first stage of labor and at 3 and 6 months postpartum, prevalence of iron deficiency and iron deficiency anaemia.
Infant: birthweight and length, haemoglobin concentration, mean corpuscular volume, erythrocyte protoporphyrin, serum iron, transferrin saturation, serum ferritin concentrations at birth and at 3 and 6 months; Apgar scores.

Notes

Supervised by physicians who recorded tablet consumption.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate ‐ by random numbers.

Allocation concealment?

Low risk

Adequate, packages of tablets numbered by manufacturer.

Blinding?
All outcomes

Low risk

Adequate ‐ participant and provider blinded. Outcome assessor blinded.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Unclear.

Methods

Randomisation: method unclear. Allocation concealment: unclear. Blinding: inadequate. Neither participant nor provider blinded. Outcome assessor not blinded. Loss to follow up: unclear.

Participants

172 pregnant women believed to be in the second trimester of pregnancy by date of last menstrual period attending antenatal care clinic in Parland Memorial Hospital, Dallas, Texas, USA.

Interventions

Women were randomly assigned to one of three interventions: group 1 received 1000 mg of iron intramuscularly as iron‐dextran; group 2 received 112 mg of elemental iron as ferrous gluconate daily in 3 tablets; group 3 received placebo tablets.
Supplementation started during 2nd trimester until delivery.

Outcomes

Maternal: haemoglobin concentration at baseline and at delivery.

Notes

Unsupervised.
Only groups 2 (oral iron) and 3 (placebo) were included in this review.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Method unclear.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

High risk

Inadequate. Neither participant no provider blinded. Outcome assessor not blinded.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Unclear.

Free of other bias?

High risk

Methods

Randomisation: method unclear. Allocation concealment: unclear. Blinding: inadequate ‐ open. Loss to follow up: adequate ‐ less than 20% lost to follow up.

Participants

32 healthy non‐anaemic pregnant women attending antenatal care at maternity centres of Oulu University Central Hospital, Finland with uncomplicated pregnancy of less than 16 wks, and no earlier haematological problems.

Interventions

Women were randomly assigned to one of two groups: group 1 received 200 mg of elemental iron as ferrous sulphate daily; group 2 received no treatment.
Supplementation started at 16th week of gestation until one month postpartum.

Outcomes

Maternal: haemoglobin, haematocrit, red cell count, leucocyte count, reticulocytes, mean corpuscular volume, mean corpuscular haemoglobin concentration, mean corpuscular haemoglobin, serum iron, total iron binding capacity, transferrin, vitamin B12, whole folate, and serum ferritin concentration at baseline, and at wks, 16, 20, 24, 28, 32, 36, 40 and 5 days, 1, 2, and 6 months postpartum. Bone marrow aspirates at 16th and 32nd week and at 2 months postpartum.
Infant: birthweight, Apgar scores at 5 minutes.

Notes

Unsupervised.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Method unclear.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

High risk

Inadequate ‐ open.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 20% lost to follow up.

Methods

Randomisation: adequate ‐ block randomised by randomised numbers table. Allocation concealment: not used. Blinding: inadequate ‐ participant and care provider not blinded. Outcome assessor blinded. Loss to follow up: inadequate. More than 20% lost to follow up.

Participants

176 pregnant women with 8‐24 wks of gestation attending antenatal care at six health centres in West Java, Indonesia.

Interventions

Health centres were randomised to one of two interventions: weekly regimen, where women received 120 mg of elemental iron as ferrous sulphate with 0.50 mg of folic acid; or daily regimen where women received 60 mg of elemental iron as ferrous sulphate with 0.25 mg of folic acid daily until week 28‐32 of gestation.
Supplementation started at 8‐24 wks until 28‐32 wks of gestation.

Outcomes

Maternal: haemoglobin concentration, serum ferritin, weight at baseline and at 28‐32 wks of gestation; compliance to treatment and prevalence of parasitic infections.

Notes

Unsupervised but frequent contact with participants.
Randomisation was made by health centres.
Compliance measured by stool tests was 54.3% in the daily group and 62.2% in the weekly group.
Adjustment by intra class correlation coefficient to show effective sample size taking into account cluster randomisation and unit of analysis.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate ‐ block randomised by randomised numbers table.

Allocation concealment?

High risk

Not used.

Blinding?
All outcomes

High risk

Inadequate ‐ participant and care provider not blinded. Outcome assessor blinded.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate. More than 20% lost to follow up.

Methods

Randomisation: inadequate ‐ by alternating numbers. Allocation concealment: unclear. Blinding: inadequate ‐ participant and provider not blinded. Outcome assessor blinded. Loss to follow up: inadequate ‐ more than 20% lost to follow up.

Participants

680 pregnant women served by 11 health centres from five sub districts on or near the western end of the island of Seram in the Province of Maluku, Indonesia.

Interventions

Women were assigned to one of two interventions: group 1 received 60 mg of elemental iron as ferrous sulphate with 0.25 mg of folic acid daily by a traditional birth attendant; group 2 received 120 mg of elemental iron as ferrous sulphate with 0.5 mg of folic acid once a week by the traditional home visiting birth attendants. A control group was formed by participants receiving traditional iron supplements (60 mg elemental iron) with folic acid from health centres, self administered without incentive.

Outcomes

Maternal: haemoglobin concentration at baseline and after 12 and 20 wks of supplementation; serum ferritin at baseline and after 12 wks of supplementation; compliance.

Notes

Daily group and control unsupervised. Weekly group supervised.
Each group was further assigned alternatively by registration number to receive 500 mg of mebendazole or a placebo at the second trimester of pregnancy.
Only groups 1 and 2 are used in this analysis. Compliance was 69.6%, 96.2% and 46.9% for groups 1, 2 and control respectively. The study area is endemic to malaria.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

High risk

Inadequate ‐ quasi‐randomised, by alternating numbers.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

High risk

Inadequate ‐ participant and provider not blinded. Outcome assessor blinded.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate ‐ more than 20% lost to follow up.

Methods

Randomisation: method unclear. Allocation concealment: unclear. Blinding: inadequate ‐ participant blinded. Provider and outcome assessor unclear. Loss to follow up: adequate ‐ less than 20%.

Participants

52 healthy pregnant women attending outpatient Women's clinic at Haukeland Hospital, Bergen, Norway within first 10 wks of a normal singleton pregnancy with uncomplicated delivery at 37‐42 wks.

Interventions

Women were randomly assigned to one of two groups: group 1 received 200 mg of elemental iron as ferrous sulphate daily; group 2 received placebo.
Supplementation started at 10 wks of gestation.

Outcomes

Maternal: haemoglobin, haematocrit, plasma cell volume, erythrocyte count, leucocyte count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, serum iron, iron binding capacity, erythrocyte protoporphyrin, serum ferritin at baseline and every month during 2nd trimester and every 2 wks until delivery.
Infant: birthweight and Apgar scores.

Notes

Unsupervised.
Compliance measured by tablet count was 55% in the iron‐treated group.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Method unclear.

Allocation concealment?

Unclear risk

Unclear

Blinding?
All outcomes

High risk

Inadequate ‐ participant blinded. Provider and outcome assessor unclear.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 20%.

Methods

Randomisation: adequate ‐ by using random number generator. Allocation concealment: adequate. Blinding: adequate ‐ participant, provider and outcome assessor blinded to treatment. Loss to follow up: inadequate. More than 20% lost to follow up.

Participants

429 non anaemic iron replete women with less than 20 wks of gestation attending who had not taken supplements containing iron in the last month, with a singleton pregnancy attending the prenatal clinic at the Wake County Human services in Raleigh, North Carolina, USA.

Interventions

Women were randomly assigned to one of two groups: group 1 received multivitamin/mineral supplements containing 30 mg of iron as ferrous sulphate daily or group 2 received multivitamin/mineral supplements containing 0 mg of iron (no iron) until 29 wks of gestation. Supplementation started on average at 12 wks. The multivitamin/mineral supplement contained the following: vitamin A 4000 IU; vitamin D 400 IU; vitamin C 70 mg; folic acid 0.5 mg; thiamine 1.5 mg; riboflavin 1.6 mg; niacin 17 mg; vitamin B₆ 2.6 mg; vitamin B₁₂ 2.5 ?g; calcium 200 mg; magnesium 100 mg; copper 1.5 mg; zinc 15 mg. Folic acid supplements were prescribed for all women who had received the positive pregnancy test until the first prenatal visit.

Outcomes

Maternal: prevalence of anaemia, iron repletion andiron deficiency anaemia at 26‐29 wks, side effects, compliance to treatment, iron status (haemoglobin concentration, serum ferritin at 26‐29 wks, preterm delivery.
Infant: birthweight, proportion of low birthweight, small‐for‐gestational age.

Notes

Unsupervised.
Compliance measured by pill counts and a questionnaire and was 66% in the iron group and 63% in the control group. Compliance was also measured by the Medication Event Monitoring System (MEMS) in a sub sample of 100 women.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate, by using random number generator.

Allocation concealment?

Low risk

Adequate.

Blinding?
All outcomes

Low risk

Adequate ‐ participant, provider and outcome assessor blinded to treatment.

Incomplete outcome data addressed?
All outcomes

High risk

Inadequate. More than 20% lost to follow up.

Methods

Randomisation: unclear. Allocation concealment: unclear. Blinding: adequate. Participants blind, care provider blind and outcome assessor blinded. Loss to follow up: adequate ‐ less than 20% lost to follow up.

Participants

60 healthy primiparous women attending antenatal care clinic in Goteborg, Sweden with uncomplicated pregnancy and less than 14 wks of gestation and with Hb concentrations above 120 g/L who had not received iron supplements in the previous 6 months or parenteral iron at any previous time. Women whose Hb concentration fell below 100 g/L during the study period were excluded and received immediate therapy.

Interventions

Women were randomly allocated to receive 200 mg of elemental iron as a sustained release preparation of ferrous sulphate daily or placebo from 12 wks of gestation until 9 wks postdelivery.

Outcomes

Maternal: iron absorption measurements; haemoglobin concentration, haematocrit, bone marrow haemosiderin, mean corpuscular haemoglobin concentration, total iron binding capacity, transferrin saturation at baseline, and at wks 16, 20, 24, 28, 32, and 35; and 8‐10 wks after delivery.

Notes

Unsupervised.
Compliance measured by remaining pills count was 86 +/‐ 3%.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Method unclear.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

Low risk

Adequate. Participants blind, care provider blind and outcome assessor blinded.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 20% lost to follow up.

Methods

Randomisation: randomised but method unclear. Allocation concealment: unclear. Blinding: inadequate ‐ open. Loss to follow up: adequate ‐ less than 20% lost to follow up.

Participants

48 healthy pregnant women with no adverse medical or obstetric history attending antenatal care clinic in Newcastle, England, United Kingdom before 12 wks of gestation.

Interventions

Women were randomly allocated to one of two groups: group 1 receive 325 mg of ferrous sulphate (about 65 mg elemental iron) and 350 ug of folic acid daily from 12 wks until delivery and group 2 received no supplements.

Outcomes

Maternal: haemoglobin concentration, serum ferritin, mean cell volume at 12 wks and every 4 wks until delivery, and at 6 days, 6 wks and 6 months after delivery; plasma volume at 12 and 36 wks of gestation.
Infant: birthweight, infant death, admission to special care unit.

Notes

Unsupervised.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Method unclear.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

High risk

Inadequate ‐ open.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 20% lost to follow up.

Methods

Randomisation: adequate by random number lists. Allocation concealment: adequate, sealed envelopes progressively numerated. Blinding: inadequate ‐ open. Loss to follow up: adequate ‐ less than 20%.

Participants

254 non‐anaemic non‐iron deficient healthy pregnant women from multiple centres in Italy. Exclusion criteria: acquired or congenital anaemia, haemoglobinopathies, thalassaemia, medically or surgically treated cardiopathy, abortion, hypertension, gastric resection, metabolic or endocrine disorder, hepatic or renal disease, epilepsy or another neurological disease, previously treated for cancer, alcohol or substance dependence.

Interventions

Women were randomly assigned to receive 40 mg of elemental iron containing 250 g of ferritin in a microgranulated gastric resistant capsule daily or no treatment from 12‐16 wks of gestation until the end of puerperium.

Outcomes

Maternal: haemoglobin concentration, red cell count, mean corpuscular volume, serum iron, total transferrin, transferrin saturation, serum ferritin at 12‐16 wks, two times during pregnancy, at 38‐42 wks, and at puerperium 48‐52 wks.

Notes

Unsupervised.
The study included another sample of women who were iron deficient and received two forms of iron preparation. This sample is not used in this review.
Compliance reported as higher than 98.5%.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate by random number lists

Allocation concealment?

Low risk

Adequate, sealed envelopes progressively numerated.

Blinding?
All outcomes

High risk

Inadequate ‐ open

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 20% losses to follow up.

Methods

Randomisation: method unclear. Allocation concealment: not used. Blinding: inadequate ‐ open. Loss to follow up: adequate ‐ less than 20%.

Participants

30 pregnant women with uncomplicated pregnancies and deliveries attending antenatal care clinic at the University Hospital Obstetric Unit in Rotterdam, Netherlands.

Interventions

Women received 100 mg of elemental iron as ferrous sulphate daily or no treatment from the third month of gestation until delivery. Follow up was until 12 wks after delivery.

Outcomes

Maternal: haemoglobin concentration, serum iron, serum ferritin, transferrin concentration at baseline and every 3‐4 wks until delivery, and three months after delivery.
Infant: haemoglobin concentration, transferrin, serum iron, serum ferritin in cord blood at term.

Notes

Unsupervised.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Method unclear.

Allocation concealment?

High risk

Not used.

Blinding?
All outcomes

High risk

Inadequate ‐ open.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 20% losses to follow up.

Methods

Randomisation: adequate ‐ by random table numbers. Allocation concealment: adequate by means of sealed envelopes. Blinding: inadequate. Participant nor provider blinded. No placebo used. Loss to follow up: adequate ‐ less than 20%.

Participants

44 non‐anaemic Caucasian women with singleton pregnancy and no major illnesses attending the University Hospital Obstetrical Clinic of the Erasmus University in Rotterdam who had not received iron supplementation during their first visit.

Interventions

Women were randomly assigned to one of two groups:
group 1: received 105 mg of elemental iron as ferrous sulphate daily in a sustained release preparation and group 2: received no iron supplement.
Supplementation started at 14‐16th week of gestation until delivery.

Outcomes

Maternal: haemoglobin, serum iron, serum transferrin and serum ferritin concentrations at 16, 28, 36 wks, delivery, 6 and 12 wks postpartum.

Notes

Unsupervised.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Adequate ‐ by random table numbers.

Allocation concealment?

Low risk

Adequate, by means of sealed envelopes.

Blinding?
All outcomes

High risk

Inadequate. Participant nor provider blinded. No placebo used.

Incomplete outcome data addressed?
All outcomes

Low risk

Adequate ‐ less than 20% losses to follow up.

Methods

Randomisation: method unclear. Allocation concealment: unclear. Blinding: unclear. Loss to follow up: adequate ‐ less than 20%.

Participants

3599 pregnant women with Hb above 100 g/L at their antenatal care clinic visit at Queen's Mother's Hospital in Glasgow, Scotland, United Kingdom. Women who reported not taken the tablets regularly ere excluded as well as those diagnosed with anaemia during the study.

Interventions

Women were randomly allocated to one of five interventions: group 1 received no prophylactic supplements; group 2 received 105 mg of elemental iron daily as chelated iron aminoates; group 3 received 105 mg of elemental iron with 100 ug of folic acid; group 4 received 105 mg of elemental iron daily with 300 ug of folic acid; and group 5 received 105 mg elemental iron daily with 450 ug of folic acid.
Starting and ending time of supplementation variable.

Outcomes

Maternal: haemoglobin concentration at baseline and in every visit, at early puerperium and during postnatal visit; incidence of obstetric complications. incidence of megaloblastic anaemia.
Infant: Hb and whole blood folate levels a 6 wks of age. Incidence of neonatal complications.

Notes

Unsupervised.
Groups 3‐5 were merged for the purposes of this review.
Women were excluded from the trial and the analysis if they were diagnosed as anaemic.
Compliance not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Method unclear.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

Unclear risk

Unclear.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Adequate ‐ less than 20% losses to follow up. However, women were excluded from the trial and the analysis if they were diagnosed as anaemic.

Free of selective reporting?

High risk

Methods

Randomisation: inadequate ‐ alternate. Allocation concealment: not used. Blinding: adequate ‐ participant and care provider blinded. Outcome assessor blinded. Loss to follow up: inadequate. More than 20% lost to follow up.