Anemia is a globally prevalent medical condition that often complicates pregnancy. In 2019, 30.5% of non-pregnant women and 35.5% of pregnant women within the reproductive age group were affected by anemia1. In 2016 a population-based survey was held in India which showed that 50% of women in India were anaemic2.

Anaemia is a condition characterized by a lower-than-normal number of red blood cells or reduced hemoglobin levels within the body. Imbalance in the utilization of iron and deficiency of iron stores is the main pathology behind the development of anaemia during pregnancy3. During pregnancy, WHO has defined anemia as a hemoglobin level <11gm/dl in the first trimester, < 10.5gm/dl in the second trimester, and < 11gm/dl in the third trimester4.  Iron deficiency anemia is common in pregnancy due to increased demand for iron, required to support maternal hemoglobin mass expansion as well as the growing fetus and placenta. Iron deficiency anemia is further aggravated by gastrointestinal effects of pregnancy like nausea, vomiting, indigestion and constipation. The symptoms of iron deficiency anemia (IDA) can vary widely. Reduced oxygen levels in the blood may lead to shortness of breath, fatigue, palpitations, tachycardia, and angina. The resulting hypoxemia can trigger a compensatory reduction in intestinal blood flow, which may cause motility disorders, malabsorption, nausea, weight loss, and abdominal pain5.

To prevent adverse iron deficiency pregnancy outcome effective iron supplimentation is needed. Timely correction of iron deficiency helps in preventing blood transfusion and its related adverse effects. It helps women to replenish the iron stores during antenatal period and increase the hemoglobin6. As a part of global strategy to prevent anemia, it has been put forward by WHO that all pregnant women be given 60mg of elemental iron with 400 microgram of folic acid everyday prophylactically7. However, many undesirable side effects causing poor compliance to iron has been observed by pregnant females due to daily intake of iron. The probable cause is that there is oxidative stress due to high doses of iron which leads to gastrointestinal intolerance8. There has been lot of research in iron metabolism. It is found that the protein hepcidin regulates the iron absorption. The mucosal turnover time is said to occur in 3 to 5 days and thus after a given dose, further supplementation with iron until turnover time is completed, leads to impaired absorption since the cells are already saturated and therefore excess iron causes oxidative stress and other side effects9. Therefore, periodic iron supplementation may let mucosa heal up and get better iron absorption.

A randomized control study was done in Department of Obstetrics and Gynecology in collaboration with Department of Pathology & Pediatrics Jawaharlal Nehru Medical College and Hospital, AMU Aligarh, U.P. from year 2022 to year 2024. Two hundred twenty pregnant women with gestational age between 12-16 weeks coming to the antenatal clinic (ANC), outpatient clinic were included in the study after taking informed consent from the pregnant women and ethical clearance from the institutional ethical committee. Sample size was calculated using online sample size calculator tool. The women were divided into two equal groups after randomization.

Group 1 – One hundred and ten pregnant women at 12-16 weeks of gestation were offered sixty mg of elemental iron daily till they delivered

Group 2 – One hundred and ten pregnant women pregnant women at 12-16 weeks of gestation were offered sixty mg of elemental iron on day 1 and 4 twice a day till they delivered.

Both groups were followed at each ANC visits for compliance to therapy, maternal side effects and haemoglobin. Haematological parameters including haemoglobin, haematocrit, red cell distribution width were studied and compared between the two groups before the iron supplementation and after 20 weeks of iron supplementation during the antenatal period. Fetomaternal outcome in both the groups were also studied.

Inclusion criteria-

Pregnant women without and with mild anaemia (WHO)

Exclusion criteria -

Pregnant women with moderate or severe anaemia (WHO)

Pregnant women with diseases like pre-eclampsia, diabetes mellitus, chronic haematological diseases like thalassemia Multi foetal pregnancies.

Statistics

Statistical analysis Data was entered in MS Excel, Cleared and inputed to IBM SPSS version 23.0 for analysis. Chi square was applied for studying association between categorical variables (compare intervention between two groups) and independent T test was applied to see significant differences between continuous variables of the two groups.

Eight cases in group 1 and five cases in group 2 were lost to follow up at the end of the study. Both the groups (Continuous and Intermittent) had similar age distributions, with more cases aged 21 to 30 years (Table-1).

Table 1: Baseline characteristics of both the groups

Figure 1: Distribution of cases as per gravidity

Table 2: Effect of iron supplementation on blood indices in the groups

Figure2: Box Whisker plot for haemoglobin before and after iron supplementation

Table 3: Comparison between the Groups depending on blood
indices

Figure3: Box-Whisker plot for Haematocrit before and after iron supplementation

Table4: GI complaints (maternal complications) in both the Groups

Figure4: Gastrointestinal Complications in both the groups

Table5:  Fetal weight in the Groups

Figure5: Mode of delivery in both the groups

Table 6: Apgar score in the groups

Both the groups were comparable in gravidity and other sociodemographic factors (Table -1, Figure-1). In present study mean Hb levels before iron supplementation was 10.980g/dL± 0.9004 after iron supplementation was 12.149g/dL±0.9689 in group1 as compared to mean Hb before supplementation was 11.044g/dL±0.8693 and after supplementation was 12.321g/dL±0.9517 in group2. Mean haematocrit before supplementation was 34.402% and after supplementation it was 38.186% in group1 whereas mean haematocrit before supplementation was 34.194% and after supplementation was 37.590% in group2. Mean RDW before supplementation was14.532% and after supplementation it was 15.592% in group1whereas mean RDW before supplementation was 13.520% and after supplementation was 14.180% in group2. Both supplementation methods significantly increase haemoglobin, haematocrit levels and RDW after iron supplementation (Table-2). There was no significant difference in the blood indices on comparing the two groups (Table-3; figure2,3). Maternal complications in form of gastrointestinal complaints were found 45.1% in group 1 and 26.7% in group 2 (Table-4; figure-4). The result was stastically significant (p=0.006). The mode of delivery is similar between the groups, with no statistically significant differences (Figure-5). The mean weeks of gestation at delivery in group 1 was 37.8 weeks while in case of group 2 was 37.9 weeks. Fetal weight was comparable in both the groups with no significant difference (Table-5). Majority of neonates in both the groups had no complications with no significant difference when the groups were compared (Table-6).

Anemia is a prevalent medical disorder that complicates pregnancy, particularly affecting pregnant women, postpartum women, and menstruating females in developing nations. About 32.4 million women globally are anemic during pregnancy, with 95% residing in developing countries. In India, a survey revealed that 50% of women are anemic, largely due to iron deficiency, which is the primary cause of anemia in non-malaria areas10. Iron deficiency anemia significantly contributes to maternal morbidity and mortality, causing adverse fetal and infant health outcomes.

Iron doses at weekly intervals is expected to increase iron absorption and reduce gastrointestinal (GI) exposure due to unabsorbed elemental iron. This is supported by the fact that enterocytes become refractive to absorbing additional iron until they are replaced by new enterocytes after 5–6 days11. To mitigate these issues, administering iron supplements weekly may enhance its absorption and reduce gastrointestinal discomfort thus improving overall iron levels in pregnant women.

Haemoglobin levels in both the group continuous and intermittent showed increase in their serial measurements thus indicating improvement. The increase in haemoglobin level in both the groups was statistically significant(p<0.001). The dosage of iron was higher in group 1 (continuous) than in group 2 (intermittent), but it did not result in greater improvement of mean corpuscular haemoglobin in group1(continuous) suggesting inadequate acquisition of iron by RBC in the group. The result in present study was consistent with study done by Abelgawad etal (2017)12, Chitra etal(2020)13, Yaznil etal (2020)14, Khangura etal (2021)15.

Haematocrit and Red Cell Distribution Width showed increase trend in their mean values after the supplementation in both the groups which was statistically significant(p<0.001). The mean haematocrit levels increased from 34.402% to 38.186% in continuous group whereas it increased from 34.194% to 37.590% in intermittent group. But there was no significant difference when the two groups were compared. Despite haemodilution in pregnancy there was significant increase in haematocrit due to iron supplementation. Similar results were observed by Goonewardene etal (2017)16, Khangura etal (2021)15, Asif etal (2023)17.

Maternal outcomes, including gestational age at delivery, mode of delivery were similar in both the groups with no significant difference. However, gastrointestinal complications including nausea, vomiting, diarrhoea, bloating, gastritis were significantly more in group1 (continuous) as compared to in group2 (intermittent). Similar results were observed by Goonewardene etal (2017)16, Chitra etal (2020)13, Abelgawad etal (2021)12having more gastrointestinal side effects in continuous iron supplemented groups as compared to weekly iron supplemented group. Fetal outcome was similar in both the groups. Apgar scores of neonate at 1 minute and 5 minute of birth were comparable in both the groups with no significant difference.

In present study no significant difference was observed with respect to foetal weight at birth in both the groups. Similar results were observed in the study done by Hanieh etal. (2015)18 .

 During antenatal period, both continuous and intermittent iron therapy effectively improved hemoglobin levels and were comparable in terms of blood indices. However, continuous iron therapy was associated with a higher incidence of gastrointestinal complications as compared to intermittent iron therapy. No significant differences were observed in maternal outcomes, fetal outcomes, or modes of delivery between the two groups. The study showed during antenatal period intermittent iron therapy was as good as continuous iron therapy with less gastrointestinal side effects. However, small sample size, absence of variation with respect to geographical parameters were the limitation in the study. Therefore, more research with larger sample size needed to been done to compare effectiveness of continuous verses intermittent iron therapy.

DECLARATIONS

Conflict of interest – No conflict of interest.

Informed consent – It was a randomized control trial and all the participants were included in the study after informed consent

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