Intermittent oral iron supplementation during pregnancy
Juan Pablo Peña-Rosas, Luz Maria De-Regil, Heber Gomez Malave, Monica C Flores-Urrutia, Therese Dowswell, Juan Pablo Peña-Rosas, Luz Maria De-Regil, Heber Gomez Malave, Monica C Flores-Urrutia, Therese Dowswell
Abstract
Background: Anaemia is a frequent condition during pregnancy, particularly among women in low- and middle-income countries. Traditionally, gestational anaemia has been prevented with daily iron supplements throughout pregnancy, but adherence to this regimen due to side effects, interrupted supply of the supplements, and concerns about safety among women with an adequate iron intake, have limited the use of this intervention. Intermittent (i.e. two or three times a week on non-consecutive days) supplementation has been proposed as an alternative to daily supplementation.
Objectives: To assess the benefits and harms of intermittent supplementation with iron alone or in combination with folic acid or other vitamins and minerals to pregnant women on neonatal and pregnancy outcomes.
Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2015), the WHO International Clinical Trials Registry Platform (ICTRP) (31 July 2015) and contacted relevant organisations for the identification of ongoing and unpublished studies (31 July 2015).
Selection criteria: Randomised or quasi-randomised trials.
Data collection and analysis: We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy.
Main results: This review includes 27 trials from 15 countries, but only 21 trials (with 5490 women) contributed data to the review. All studies compared daily versus intermittent iron supplementation. The methodological quality of included studies was mixed and most had high levels of attrition.The overall assessment of the quality of the evidence for primary infant outcomes was low and for maternal outcomes very low.Of the 21 trials contributing data, three studies provided intermittent iron alone, 14 intermittent iron + folic acid and four intermittent iron plus multiple vitamins and minerals in comparison with the same composition of supplements provided in a daily regimen.Overall, for women receiving any intermittent iron regimen (with or without other vitamins and minerals) compared with a daily regimen there was no clear evidence of differences between groups for any infant primary outcomes: low birthweight (average risk ratio (RR) 0.82; 95% confidence interval (CI) 0.55 to 1.22; participants = 1898; studies = eight; low quality evidence), infant birthweight (mean difference (MD) 5.13 g; 95% CI -29.46 to 39.72; participants = 1939; studies = nine; low quality evidence), premature birth (average RR 1.03; 95% CI 0.76 to 1.39; participants = 1177; studies = five; low quality evidence), or neonatal death (average RR 0.49; 95% CI 0.04 to 5.42; participants = 795; studies = one; very low quality). None of the studies reported congenital anomalies.For maternal outcomes, there was no clear evidence of differences between groups for anaemia at term (average RR 1.22; 95% CI 0.84 to 1.80; participants = 676; studies = four; I² = 10%; very low quality). Women receiving intermittent supplementation had fewer side effects (average RR 0.56; 95% CI 0.37 to 0.84; participants = 1777; studies = 11; I² = 87%; very low quality) and were at lower risk of having high haemoglobin (Hb) concentrations (greater than 130 g/L) during the second or third trimester of pregnancy (average RR 0.53; 95% CI 0.38 to 0.74; participants = 2616; studies = 15; I² = 52%; (this was not a primary outcome)) compared with women receiving daily supplements. There were no significant differences in iron-deficiency anaemia at term between women receiving intermittent or daily iron + folic acid supplementation (average RR 0.71; 95% CI 0.08 to 6.63; participants = 156; studies = one). There were no maternal deaths (six studies) or women with severe anaemia in pregnancy (six studies). None of the studies reported on iron deficiency at term or infections during pregnancy.Most of the studies included in the review (14/21 contributing data) compared intermittent oral iron + folic acid supplementation compared with daily oral iron + folic acid supplementation (4653 women) and findings for this comparison broadly reflect findings for the main comparison (any intermittent versus any daily regimen).Three studies with 464 women examined supplementation with intermittent oral iron alone compared with daily oral iron alone. There were no clear differences between groups for mean birthweight, preterm birth, maternal anaemia or maternal side effects. Other primary outcomes were not reported.Four studies with a combined sample size of 412 women compared intermittent oral iron + vitamins and minerals supplementation with daily oral iron + vitamins and minerals supplementation. Results were not reported for any of the review's infant primary outcomes. One study reported fewer maternal side effects in the intermittent iron group, and two studies that more women were anaemic at term compared with those receiving daily supplementation.Where sufficient data were available for primary outcomes, we set up subgroups to look for possible differences between studies in terms of earlier or later supplementation; women's anaemia status at the start of supplementation; higher and lower weekly doses of iron; and the malarial status of the region in which the trials were conducted. There was no clear effect of these variables on results.
Authors' conclusions: This review is the most comprehensive summary of the evidence assessing the benefits and harms of intermittent iron supplementation in pregnant women on haematological and pregnancy outcomes. Findings suggest that intermittent regimens produced similar maternal and infant outcomes as daily supplementation but were associated with fewer side effects and reduced the risk of high levels of Hb in mid and late pregnancy, although the risk of mild anaemia near term was increased. While the quality of the evidence was assessed as low or very low, intermittent may be a feasible alternative to daily iron supplementation among those pregnant women who are not anaemic and have adequate antenatal care.
Conflict of interest statement
We certify that we have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of the review (e.g. employment, consultancy, stock ownership, honoraria, expert testimony).
Juan Pablo Peña‐Rosas was author of an excluded study on iron and folic acid intermittent supplementation (Pena‐Rosas 2003). Juan Pablo Peña‐Rosas and Luz Maria De‐Regil provided technical input in the development of the protocol of one included study (Hanieh 2013 (C)). Neither of these authors was involved in assessing study eligibility.
Juan Pablo Peña‐Rosas is currently a staff member of the World Health Organization. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy or views of the World Health Organization.
Monica C Flores‐Urrutia worked on the review during an internship at the World Health Organization and was financially supported by the International Life Sciences Institute (ILSI).
Figures
Study flow diagram for 2015 update
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 1 Low birthweight (less than 2500 g) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 2 Low birthweight (less than 2500 g) SUBGROUP ANALYSIS by weekly dose of iron.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 3 Low birthweight (less than 2500 g) SUBGROUP ANALYSIS by anaemia status.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 4 Low birthweight (less than 2500 g) SUBGROUP ANALYSIS by gestational age.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 5 Low birthweight (less than 2500 g) SUBGROUP ANALYSIS by intermittent regimen.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 6 Birthweight (g) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 7 Birthweight (g) SUBGROUP ANALYSIS by gestational age.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 8 Birthweight (g) SUBGROUP ANALYSIS by anaemia status.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 9 Birthweight (g) SUBGROUP ANALYSIS by weekly dose of iron.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 10 Birthweight (g) SUBGROUP ANALYSIS by intermittent regimen.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 11 Premature birth (less than 37 weeks of gestation) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 12 Premature birth (less than 37 weeks' gestation) SUBGROUP ANALYSIS by gestational age.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 13 Premature birth (less than 37 weeks' gestation) SUBGROUP ANALYSIS by anaemia status.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 14 Premature birth (less than 37 weeks' gestation) SUBGROUP ANALYSIS by weekly dose of iron.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 15 Premature birth (less than 37 weeks' gestation) SUBGROUP ANALYSIS by intermittent regimen.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 16 Neonatal death (within 28 days after delivery) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 18 Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 19 Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) SUBGROUP ANALYSIS by gestational age.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 20 Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) SUBGROUP ANALYSIS by anaemia status.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 21 Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) SUBGROUP ANALYSIS by weekly dose of iron.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 22 Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) SUBGROUP ANALYSIS by intermittent regimen.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 24 Maternal iron deficiency anaemia at term (Hb less than 110 g/L and at least one additional laboratory indicators at 37 weeks gestation or more) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 26 Side effects (any reported throughout intervention period) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 27 Side effects (any reported throughout intervention period) SUBGROUP ANALYSIS by gestational age.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 28 Side effects (any reported throughout intervention period) SUBGROUP ANALYSIS by anaemia status.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 29 Side effects (any reported throughout intervention period)SUBGROUP ANALYSIS by weekly dose of iron.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 30 Side effects (any reported throughout intervention period) SUBGROUP ANALYSIS by intermittent regimen.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 31 Severe anaemia at any time during second and third trimester (Hb less than 70 g/L) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 32 Severe anaemia at any time during the 2nd and 3rd trimesters SUBGROUP ANALYSIS by gestational age.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 33 Severe anaemia at any time during the 2nd and 3rd trimesters SUBGROUP ANALYSIS by anaemia status.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 34 Severe anaemia at any time during the 2nd and 3rd trimesters SUBGROUP ANALYSIS by weekly dose of iron.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 35 Severe anaemia at any time during the 2nd and 3rd trimesters SUBGROUP ANALYSIS by intermittent regimen.
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 38 Very low birthweight (less than 1500 g) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 39 Very premature birth (less than 34 weeks of gestation) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 40 Infant Hb concentration within the first six months (in g/L, counting the last reported measure after birth within this period)..
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 41 Infant ferritin concentration in the first 6 months (μg/L, counting the last reported measure after birth within this period) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 42 Development and motor skills (cognitive score at 6 months).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 43 Development and motor skills (language at 6 months).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 44 Development and motor skills (motor at 6 months).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 45 Development and motor skills (socioemotional at 6 months).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 46 Development and motor skills (adaptive behaviour at 6 months).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 47 Maternal anaemia at or near term (Hb less than 110 g/L at 34 weeks gestation or more) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 48 Maternal iron deficiency at or near term (based on any indicator of iron status at 34 weeks' gestation or more) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 49 Maternal iron deficiency anaemia at or near term (Hb less than 110 g/L and at least one additional laboratory indicators at 34 weeks gestation or more) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 50 Maternal haemoglobin concentration at or near term (in g/L at 34 weeks' gestation or more) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 51 Maternal high haemoglobin concentrations during second or third trimester (Hb more than 130 g/L) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 52 Moderate anaemia at any time during second or third trimester (Hb between 70 and 99 g/L)(ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 53 Severe anaemia at term (Hb less than 70 g/L at 37 weeks' gestation or more) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 54 Severe anaemia at or near term (Hb less than 70 g/L at 34 weeks' gestation or more) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 55 Severe anaemia at postpartum (Hb less than 80 g/L) (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 56 Antepartum haemorrhage (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 57 Diarrhoea (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 58 Constipation (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 59 Nausea (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 60 Heartburn (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 61 Vomiting (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 62 Placental abruption (ALL).
Comparison 2 Any intermittent iron regimen (with or without other vitamins and minerals) compared with daily regimen (with same vitamins and minerals), Outcome 63 Premature rupture of membranes (ALL).
Comparison 6 Intermittent oral iron alone supplementation versus daily iron alone supplementation, Outcome 1 Low birthweight (less than 2500 g) (ALL).
Comparison 6 Intermittent oral iron alone supplementation versus daily iron alone supplementation, Outcome 2 Birthweight (g) (ALL).
Comparison 6 Intermittent oral iron alone supplementation versus daily iron alone supplementation, Outcome 3 Premature birth (less than 37 weeks of gestation) (ALL).
Comparison 6 Intermittent oral iron alone supplementation versus daily iron alone supplementation, Outcome 6 Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) (ALL).
Comparison 6 Intermittent oral iron alone supplementation versus daily iron alone supplementation, Outcome 10 Side effects (any reported throughout intervention period) (ALL).
Comparison 6 Intermittent oral iron alone supplementation versus daily iron alone supplementation, Outcome 11 Maternal severe anaemia at any time during second and third trimester (Hb less than 70 g/L) (ALL).
Comparison 6 Intermittent oral iron alone supplementation versus daily iron alone supplementation, Outcome 14 Maternal anaemia at or near term (Hb less than 110 g/L at 34 weeks' gestation or more) (ALL).
Comparison 6 Intermittent oral iron alone supplementation versus daily iron alone supplementation, Outcome 15 Maternal haemoglobin concentration at or near term (in g/L at 34 weeks' gestation or more) (ALL).
Comparison 6 Intermittent oral iron alone supplementation versus daily iron alone supplementation, Outcome 16 Maternal high haemoglobin concentrations during second or third trimester (Hb more than 130 g/L) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 1 Low birthweight (less than 2500 g) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 2 Low birthweight (less than 2500 g) SUBGROUP ANALYSIS by gestational age.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 3 Low birthweight (less than 2500 g) SUBGROUP ANALYSIS by anaemia status.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 4 Low birthweight (less than 2500 g) SUBGROUP ANALYSIS by weekly dose of iron.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 5 Low birthweight (less than 2500 g) SUBGROUP ANALYSIS by intermittent regimen.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 6 Birthweight (g) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 7 Birthweight (g) SUBGROUP ANALYSIS by gestational age.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 8 Birthweight (g) SUBGROUP ANALYSIS by anaemia status.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 9 Birthweight (g) SUBGROUP ANALYSIS by weekly dose of iron.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 10 Birthweight (g) SUBGROUP ANALYSIS by intermittent regimen.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 11 Premature birth (less than 37 weeks of gestation) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 12 Neonatal death (within 28 days after delivery) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 14 Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 15 Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) SUBGROUP ANALYSIS by gestational age.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 16 Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) SUBGROUP ANALYSIS by anaemia status.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 17 Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) SUBGROUP ANALYSIS by weekly dose of iron.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 18 Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) SUBGROUP ANALYSIS by intermittent regimen.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 20 Maternal iron deficiency anaemia at term (Hb less than 110 g/L and at least one additional laboratory indicator at 37 weeks' gestation or more (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 22 Side effects (any reported throughout intervention period) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 23 Side effects (any reported throughout intervention period) SUBGROUP ANALYSIS by gestational age.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 24 Side effects (any reported throughout intervention period) SUBGROUP ANALYSIS by anaemia status.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 25 Side effects (any reported throughout intervention period) SUBGROUP ANALYSIS by weekly dose of iron.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 26 Side effects (any reported throughout intervention period) SUBGROUP ANALYSIS by intermittent regimen.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 27 Severe anaemia at any time during second and third trimester (Hb less than 70 g/L) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 28 Severe anaemia at any time during the 2nd and 3rd trimesters (Hb less than 70 g/L) SUBGROUP ANALYSIS by gestational age.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 29 Severe anaemia at any time during the 2nd and 3rd trimesters (Hb less than 70 g/L) SUBGROUP ANALYSIS by anaemia status.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 30 Severe anaemia at any time during the 2nd and 3rd trimesters (Hb less than 70 g/L) SUBGROUP ANALYSIS by intermittent regimen.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 31 Severe anaemia at any time during the 2nd and 3rd trimesters (Hb less than 70 g/L) SUBGROUP ANALYSIS by weekly dose of iron.
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 34 Very low birthweight (less than 1500 g) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 35 Very premature birth (less than 34 weeks of gestation) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 36 Infant Hb concentration within the first six months (in g/L, counting the last reported measure after birth within this period)..
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 37 Infant ferritin concentration in the first 6 months (μg/L, counting the last reported measured after birth within this period) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 38 Development and motor skills (cognitive score at 6 months).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 39 Development and motor skills (language at 6 months).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 40 Development and motor skills (motor at 6 months).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 41 Development and motor skills (socioemotional at 6 months).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 42 Development and motor skills (adaptive behaviour at 6 months).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 43 Maternal anaemia at or near term (Hb less than 110 g/L at 34 weeks' gestation or more) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 44 Maternal iron deficiency anaemia at or near term (Hb less than 110 g/L and at least one additional laboratory indicators at 34 weeks gestation or more) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 45 Maternal haemoglobin concentration at or near term (g/L, at 34 weeks' gestation or more) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 46 Maternal high haemoglobin concentrations during second or third trimester (Hb more than 130 g/L) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 47 Moderate anaemia at any time during second or third trimester (Hb between 70 and 99 g/L)(ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 48 Moderate anaemia at postpartum (Hb between 80 and 109 g/L) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 49 Severe anaemia at term (Hb less than 70 g/L at 37 weeks' gestation or more) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 50 Severe anaemia at postpartum (Hb less than 80 g/L) (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 51 Antepartum haemorrhage (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 52 Diarrhoea (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 53 Constipation (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 54 Nausea (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 55 Heartburn (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 56 Vomiting (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 57 Placental abruption (ALL).
Comparison 7 Intermittent oral iron+folic acid supplementation versus daily iron+folic acid supplementation, Outcome 58 Premature rupture of membranes (ALL).
Comparison 8 Intermittent oral iron+vitamins and minerals supplementation versus daily iron+vitamins and minerals supplementation, Outcome 6 Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) (ALL).
Comparison 8 Intermittent oral iron+vitamins and minerals supplementation versus daily iron+vitamins and minerals supplementation, Outcome 10 Side effects (any reported throughout intervention period) (ALL).
Comparison 8 Intermittent oral iron+vitamins and minerals supplementation versus daily iron+vitamins and minerals supplementation, Outcome 13 Very premature birth (less than 34 weeks of gestation) (ALL).
Comparison 8 Intermittent oral iron+vitamins and minerals supplementation versus daily iron+vitamins and minerals supplementation, Outcome 14 Maternal anaemia at or near term (Hb less than 110 g/L at 34 weeks' gestation or more) (ALL).
Comparison 8 Intermittent oral iron+vitamins and minerals supplementation versus daily iron+vitamins and minerals supplementation, Outcome 15 Maternal iron deficiency at or near term (based on any indicator of iron status at 34 weeks' gestation or more) (ALL).
Comparison 8 Intermittent oral iron+vitamins and minerals supplementation versus daily iron+vitamins and minerals supplementation, Outcome 16 Maternal haemoglobin concentration at or near term (g/L, at 34 weeks' gestation or more) (ALL).
Comparison 8 Intermittent oral iron+vitamins and minerals supplementation versus daily iron+vitamins and minerals supplementation, Outcome 17 Maternal high haemoglobin concentrations during second or third trimester (Hb more than 130 g/L) (ALL).
Comparison 8 Intermittent oral iron+vitamins and minerals supplementation versus daily iron+vitamins and minerals supplementation, Outcome 18 Severe anaemia at term (Hb less than 70 g/L at 37 weeks' gestation or more) (ALL).
Comparison 8 Intermittent oral iron+vitamins and minerals supplementation versus daily iron+vitamins and minerals supplementation, Outcome 19 Severe anaemia at any time during second and third trimester (Hb less than 70 g/L) (ALL).
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