Anaemia is a frequent condition during pregnancy, particularly among women from developing countries who have insufficient iron intake to meet increased iron needs of both the mother and the fetus.Traditionally, gestational anaemia has been prevented with the provision of 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. one, two or three times a week on non-consecutive days) supplementation with iron alone or in combination with folic acid or other vitamins and minerals has recently been proposed as an alternative to daily supplementation.
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.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 March 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) for ongoing studies and contacted relevant organisations for the identification of ongoing and unpublished studies (23 March 2012).
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.
This review includes 21 trials from 13 different countries, but only 18 trials (with 4072 women) reported on our outcomes of interest and contributed data to the review. All of these studies compared daily versus intermittent iron supplementation.
Three studies provided iron alone, 12 iron+folic acid and three more iron plus multiple vitamins and minerals. Their methodological quality was mixed and most had high levels of attrition. Overall, there was no clear evidence of differences between groups for infant primary outcomes: low birthweight (average risk ratio (RR) 0.96; 95% confidence interval (CI) 0.61 to 1.52, seven studies), infant birthweight (mean difference MD -8.62 g; 95% CI -52.76 g to 35.52 g, eight studies), premature birth (average RR 1.82; 95% CI 0.75 to 4.40, four studies). None of the studies reported neonatal deaths or 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, four studies) and women receiving intermittent supplementation had less side effects (average RR 0.56; 95% CI 0.37 to 0.84, 11 studies) than those receiving daily supplements. Women receiving intermittent supplements were also at lower risk of having high haemoglobin (Hb) concentrations (greater than 130 g/L) during the second or third trimester of pregnancy (average RR 0.48; 95% CI 0.35 to 0.67, 13 studies). There were no significant differences in iron-deficiency anaemia between women receiving intermittent or daily iron+folic acid supplementation (average RR 0.71; 95% CI 0.08 to 6.63, 1 study). 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.
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 the results of the review.
The present systematic review is the most comprehensive summary of the evidence assessing the benefits and harms of intermittent iron supplementation regimens in pregnant women on haematological and pregnancy outcomes. The findings suggest that intermittent iron+folic acid regimens produce similar maternal and infant outcomes at birth as daily supplementation but are associated with fewer side effects. Women receiving daily supplements had increased risk of developing high levels of Hb in mid and late pregnancy but were less likely to present mild anaemia near term. Although the evidence is limited and the quality of the trials was 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.
三個研究提供了單獨補充鐵質、12鐵質+葉酸以及另外三種鐵質加上多種維生素與礦物質。它們的方法論品質是混合的，且大多數皆有高度的消耗水準。整體而言，就嬰兒的重要成果而言，各組間並沒有明確的差異證據: 低出生體重(平均風險比 (RR) 0.96; 95% 信賴區間(CI) 0.61到1.52，7個研究)，嬰兒出生體重 (平均數差異 MD -8.62 g; 95% CI -52.76 g到35.52 g，8個研究)，早產 (平均RR 1.82; 95% CI 0.75 到4.40，4個研究)。這些研究都沒有報告新生兒死亡或先天性畸形。
就母親的結果而言，各組間沒有明確差異可證實在懷孕達足月時的貧血問題(平均RR 1.22; 95% CI 0.84到1.80，4個研究)，且週期性接受補充品的婦女較每天接受補充品的婦女產生的副作用較少(平均RR 0.56; 95% CI 0.37到0.84，11個研究)。週期性接受補充品的婦女在第二或第三個孕期時產生高血紅素(Hb)濃度(大於130 g/L)的風險也較低(平均RR 0.48; 95% CI 0.35到0.67，13個研究)。接受週期性鐵+葉酸補充或每日鐵+葉酸補充的婦女間在缺鐵貧血上並沒有顯著的差異(平均RR 0.71; 95% CI 0.08到6.63，1個研究)。沒有母親死亡(6個研究)或孕期中貧血嚴重的婦女(6個研究)。沒有研究報告在孕期達足月後有缺鐵或感染的情形。
於可取得重要結果的充分數據之處，我們設定子群組以尋找研究間的可能差異：包括(1)於較早或稍晚進行補充鐵劑異; (2)補充初期的婦女貧血狀況; (3)每周較高或較低劑量之鐵劑;(4)以及執行試驗區域的瘧疾狀況。 這些變數在審閱結果上沒有明確的影響。