Background: Due to maternal and fetal physiologic demand , the rate along with amplitude of anemia is expected to rise over pregnancy. The iron and oxidative status also are expected to vary accordingly. It is thus assumed that iron supplementation will somewhat modify the profile observed in markers of iron and oxidative status of our series. Objectives : We aimed to measure variations of indices of iron and oxidative status of iron supplemented women over pregnancy. Methods : This is a prospective observational cohort of 74 pregnant women with singleton pregnancy whose baseline iron and oxidative status have been recently assessed at University Clinics of Kinshasa, DR Congo. Women with anemia (Hb < 10 g%) took iron for curative purposes (320 mg/day of ferric ammonium citrate) while the others received preventive iron supplementation (160 mg/day). Iron was associated with 15 mg folate/day. Nutritional iron intake was measured through a 24-hour recall using a questionnaire of common foods, including stuffs and habits likely to impede iron absorption. Biological parameters of iron and oxidative status included hemoglobin, hematocrit, ferritin, serum iron, transferrin, superoxide dismutase or SOD, uric acid, oxidized LDL and blood glucose. For statistical calculations we used t-test, chi-square test, ANOVAR and regression, the significance being stated at p < 0.05. Results : Trimester wise evolution of hematologic status in anemic women shows a rise in values of hemoglobin (+average 1 gr/dl) and hematocrit (+3%) throughout pregnancy, with significant change only between recruitment and 28 - 32 weeks. In non anemic women a significant decrease was observed, although levels remained normal. For ferritin (7.5 - 53 ng/mL from recruitment to term) and transferrin (107 - 157 g/L), significant rise was found in anemic women from recruitment to 28 - 32 weeks, while in non anemic notable change occurred only for transferrin (133 - 204 g/L). Serum iron significantly increased (53 - 83 μg/dL) from recruitment to 28 - 32 weeks in anemic women only. So, following supplementation, values of blood parameters tended to be similar for both goups at term. Non anemic women did not benefit from supplementation. SOD decreased and LDL values increased alongside supplementation. This represents a growing oxidant threat for both anemic and non anemic women. This could be related to iron overload and/or unabsorbed iron. Conclusion : Iron supplementation improved iron status in anemic women, not in non anemic. Differences that were significant between groups at recruitment disappeared by 28 - 32 weeks. Non anemic women did not benefit from supplementation. SOD decreased and LDL values increased alongside supplementation. This represents a growing oxidant threat for both anemic and non anemic women. This could be related to iron overload and/or unabsorbed iron. Doses of iron should be decreased (at least halved) and duration of treatment restricted to not more than 12 weeks.
Routine iron supplementation during pregnancy is a worldwide practice among strategies to prevent the burden of maternal anemia. Although some studies pointed out the risk of iron overload likely to enhance the Fenton reaction [
In a previous study [
The rate and amplitude of this situation are expected to rise over pregnancy, due to maternal and fetal physiologic demand. Indeed, ferritin that reflects total iron in the body has been found decreasing over normal pregnancy [
For routine supplementation, the quantity of iron to be given individually varies a lot from country to country: this can fluctuate from 30 mg/day [
Addressing routine (prophylactic and curative) supplementation during pregnancy, the present study aimed to assess variations of indices of iron and oxidative status, while taking in account some factors such as nutritional intake and intestinal conditions of iron absorption.
The current study was approved by the Ethics Committee of the School of Public Health of the University of Kinshasa, DR Congo, and was conducted during 10 months (from September 2017 throughout June 2018), the protocol of which was recently published [
Nutritional iron intake was measured through a 24-hour recall using a questionnaire of common foods, including stuffs and habits likely to impede iron absorption, such as pica/geophagia (proven to contain kaolinite, calcic phosphates, quartz, polyphenols with chelating properties [
Additionally to baseline measurements at recruitment (±15 weeks of gestation) blood sampling and analysis were carried out at 28 - 32 weeks and at term in conditions previously described [
Data were registered using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA, 2007) and after transfer to SPSS (version 18.0; SPSS Inc., Chicago, IL, USA). For statistical calculations we used t-test and chi-square test to compare means and proportions, respectively, ANOVAR to assess differences of means between periods of pregnancy and odds ratio to check associations between anemia/oxidative stress and factors related to iron absorption. Univariate analysis (odds ratios [ORs]) were stratified in a dichotomous way (with or without anemia, with and without oxidative stress, with and without iron/oxidative status variations) to seek significant association with iron supplements. Multivariate calculations (regression) used various durations of supplementation to seek the lowest one at which an OR ≥ 1.5 with 95 % confidence intervals (CIs) and p-value < 0.05 could be found for oxidative status.
The mean age of the study group (n = 74) was 32.2 ± 5.2 years, with 39 women diagnosed anemic (52.2%) according to local standards (hemoglobin < 10 g/dl). The majority was para 2, with average weight of 70.2 ± 14.5 Kg (P not significant between sub-groups) and BMI of 26 ± 5.2 Kg/m2 (p < 0.01). The proportion of obeses was 18.9%. Of their general characteristics already presented in a previous paper [
Additional significant differences between anemic and non anemic women were found in consumption of tannins and geophagia (more frequent in anemic women). As pregnancy progressed pairwise comparison based on the anemic state varied trimester wise (
Characteristics | |||||||
---|---|---|---|---|---|---|---|
Sociodemographic | n | 14-19 GA | n | 28-32 GA | n | At term | |
Low socioeconomic level | Anemic | 39 | 69.2%y | 44 | 54.5% | 39 | 46.2% |
Non anemic | 35 | 2.9% | 30 | 13.3% | 35 | 28.6% | |
Overall group | 74 | 37.8% | 74 | 37.8% | 74 | 37.8% | |
p | <0.001 | <0.001 | 0.094 | ||||
Iron nutritional intake (gr) | Anemic | 39 | 22.8 ± 4.9 | 44 | 36.8 ± 11.7 | 39 | 41.4 ± 11.1 |
Non anemic | 35 | 31.4 ± 9.5 | 30 | 39.8 ± 10.7 | 35 | 40.9 ± 11.9 | |
Overall group | 74 | 26.9 ± 8.6 | 74 | 38.02 ± 11.4 | 74 | 41.2 ± 11.4 | |
p | < 0.001 | 0.262 | 0.871 | ||||
Fibers and tannins consumption | Anemic | 39 | 76.9% | 44 | 50% | 39 | 59% |
Non anemic | 35 | 25.7% | 30 | 16.7% | 35 | 17.1% | |
Overall group | 74 | 52.7% | 74 | 36.5% | 74 | 39.2% | |
p | <0.001 | <0.004 | <0.001 | ||||
Geophagia | Anemic | 39 | 41% | 44 | 40.9% | 39 | 35.9% |
Non anemic | 35 | 8.6% | 30 | 16.7% | 35 | 11.4% | |
Overall group | 74 | 25.7% | 74 | 31.1% | 74 | 24.3% | |
p | <0.002 | <0.03 | <0.02 | ||||
Clinical | |||||||
BMI (Kg/m2) | Anemic | 39 | 27.8 ± 5.4 | 44 | 27.3 ± 5.7 | 39 | 26.9 ± 5.7 |
Non anemic | 35 | 24.03 ± 4.3 | 30 | 24.1 ± 3.7 | 35 | 25 ± 4.5 | |
Overall group | 74 | 26 ± 5.2 | 74 | 26 ± 5.2 | 74 | 26 ± 5.2 | |
p | <0.003 | <0.01 | 0.117 | ||||
Duration of supplementation (weeks) | Anemic | 39 | - | 44 | 12.3 ± 2.5 | 39 | 8.6 ± 2.8 |
Non anemic | 35 | - | 30 | 10.6 ± 1.8 | 35 | 8.6 ± 2.3 | |
Overall group | 74 | - | 74 | 11.6 ± 2.4 | 74 | 8.6 ± 2.5 | |
p | - | <0.003 | 0.976 | ||||
Intestinal parasitosis | Anemic | 39 | 61.5% | 44 | 79.5% | 39 | 64.1% |
Non anemic | 35 | 34.3% | 30 | 30% | 35 | 8.6% | |
Overall group | 74 | 48.6% | 74 | 59.5% | 74 | 37.8% | |
p | <0.02 | <0.001 | <0.001 |
of tannins and geophagia and intestinal parasitosis, while only till 28 - 32 weeks for low socioeconomic level and just at recruitment (14 - 19 weeks) for low nutritional iron intake.
General characteristics proven to impede intestinal iron absorption such ac pica, fibers and tannins were found significantly more consumed in the anemic group. The duration of iron replacement was significantly longer in the anemic group by 28 - 32 weeks (p < 0.003) owed to the fact that curative supplementation was started at 19 weeks of gestation while preventive supply was initiated at recruitment (15.8 weeks of gestation).
Trimester wise evolution of hematologic status as presented in
For ferritin (7.5 - 53 ng/mL from recruitment to term) and transferrin (107 - 157 g/L) significant rise was found in anemic women from recruitment to 28 - 32 weeks, while in non anemic a small decline was noted at mid-pregnancy before rising again till term. Notable change (rise) occurred for transferrin throughout pregnancy for both groups. Serum iron significantly increased (53 - 83 μg/dl) from recruitment to 28 - 32 weeks in anemic women only. So, differences that were significant between groups at recruitment disappeared thereafter, and blood parameters tended to be similar for both groups at term. Non anemic women did not benefit from supplementation.
As shown in
For oxidized LDL, both in anemic and non anemic women, values significantly increased from recruitment to term. Values remained significantly higher in anemic women.
An increase was also observed in uric acid from recruitment to mid-pregnancy among anemic women and in glycemia in non anemic.
Furthering the role of iron supplementation on changes of iron and oxidative status, we also questioned changes (at 28 - 32 weeks of gestation and at term) in factors for which significant differences have been found between anemic and non anemic groups (
For oxidative stress (
The association of oxidative stress (SOD < 785 or > 1570 UI/L; oxidized LDL < 200 or > 600 UI/L) with the duration of supplementation is presented in
Markers | n | 14 - 19 GA(1) | 28 -32 SA(2) | At term(3) | p(1-2) | p(1-3) | p 2-3) | p(1-2-3) | |
---|---|---|---|---|---|---|---|---|---|
Hemoglobin (mg/dl) | Anemic | 39 | 9.01 ± 0.6 | 9.6 ± 0.6 | 9.7 ± 0.8 | <0.001 | <0.001 | 0.498 | <0.001 |
Non anemic | 35 | 11.6 ± 0.9 | 10.2 ± 0.8 | 10.3 ± 0.8 | <0.001 | <0.001 | 0.652 | <0.001 | |
Overall group | 74 | 10.3 ± 1.5 | 9.9 ± 0.8 | 9.9 ± 0.9 | 0.066 | 0.191 | 0.463 | 0.115 | |
p | <0.001 | <0.001 | 0.001 | ||||||
Hematocrit (%) | Anemic | 39 | 26.3 ± 2.2 | 29.2 ± 2.02 | 29.4 ± 2.9 | <0.001 | <0.001 | 0.715 | <0.001 |
Non anemic | 35 | 35.1 ± 2.7 | 30.5 ± 2.9 | 31 ± 2.6 | <0.001 | <0.001 | 0.411 | <0.001 | |
Overall group | 74 | 30.5 ± 5.04 | 29.8 ± 2.5 | 30.2 ± 2.8 | 0.312 | 0.656 | 0.411 | 0.540 | |
p | <0.001 | <0.03 | <0.02 | ||||||
Ferritin (ng/mL) | Anemic | 39 | 7.5 ± 3.9 | 22.5 ± 29.2 | 52.9 ± 106.8 | <0.003 | <0.02 | 0.091 | <0.01 |
Non anemic | 35 | 35.7 ± 17.1 | 25.3 ± 30.4 | 41.8 ± 71.2 | 0.080 | 0.625 | 0.210 | 0.314 | |
Overall group | 74 | 20.9 ± 18.6 | 23.8 ± 29.6 | 47.6 ± 91.1 | 0.469 | <0.02 | <0.04 | <0.01 | |
p | <0.001 | 0.697 | 0.606 | ||||||
Serum iron (μg/dl) | Anemic | 39 | 52.7 ± 38.9 | 83.4 ± 49.7 | 81.2 ± 50.2 | <0.01 | <0.01 | 0.850 | <0.01 |
Non anemic | 35 | 96.2 ± 41.9 | 80.1 ± 41.4 | 80.5 ± 37.4 | 0.109 | 0.101 | 0.967 | 0.165 | |
Overall group | 74 | 73.3 ± 45.7 | 81.8 ± 45.7 | 80.9 ± 44.3 | 0.257 | 0.306 | 0.898 | 0.454 | |
p | <0.001 | 0.759 | 0.942 | ||||||
Transferrin (g/L) | Anemic | 39 | 107.2 ± 45.9 | 166.7 ± 94.4 | 157.4 ± 89.9 | <0.01 | <0.01 | 0.657 | <0.01 |
Non anemic | 35 | 133.1 ± 91.9 | 178.3 ± 119.5 | 203.8 ± 120.4 | 0.081 | <0.01 | 0.377 | <0.04 | |
Overall group | 74 | 119.5 ± 72.2 | 172.2 ± 106.4 | 179.3 ± 107.3 | <0.01 | <0.001 | 0.685 | <0.001 | |
p | 0.125 | 0.644 | 0.063 | ||||||
CST (%) | Anemic | 39 | 2.5 ± 1.1 | 2.4 ± 1.4 | 2.3 ± 1.3 | 0.671 | 0.421 | 0.747 | 0.746 |
Non anemic | 35 | 2.8 ± 1.1 | 2.3 ± 1.1 | 2.1 ± 1.2 | 0.075 | <0.02 | 0.450 | <0.04 | |
Overall group | 74 | 2.6 ± 1.1 | 2.3 ± 1.3 | 2.2 ± 1.3 | 0.136 | <0.03 | 0.466 | 0.077 | |
p | 0.357 | 0.678 | 0.422 |
It can be seen that significant associations with oxidative stress appeared only for oxidized LDL after ≥ 20 weeks of supplementation (OR = 7.04; CI95%: 2.5 - 19.7; p < 0.001). This concerns mostly anemic women for which iron was provided earlier than non anemic.
At recruitment, significant association was found under 26 mg/day for SOD (OR = 1.7; CI95%: 1.2 - 2.5; p < 0.001) and oxidized LDL (OR = 1.8; CI 95%: 1.01 - 3.2; p < 0.04). Considering oxidative status at 28 - 32 weeks of gestation and at
Markers | n | 14 - 19 GA(1) | 28 - 32 GA(2) | At term(3) | p(1-2) | p(1-3) | p(2-3) | p(1-2-3) | |
---|---|---|---|---|---|---|---|---|---|
SOD (UI/L) | Anemic | 39 | 1056.4 ± 762.1 | 917.3 ± 629.1 | 808.8 ± 560.3 | 0.382 | 0.106 | 0.424 | 0.252 |
Non anemic | 35 | 682.6 ± 543.9 | 635.4 ± 483.2 | 777.4 ± 508.7 | 0.702 | 0.454 | 0.235 | 0.501 | |
Overall group | 74 | 879.6 ± 689.5 | 783.9 ± 578.7 | 793.9 ± 533.1 | 0.362 | 0.399 | 0.913 | 0.572 | |
p | <0.02 | <0.04 | 0.802 | ||||||
Oxidized LDL (UI/L) | Anemic | 39 | 439.6 ± 209.5 | 512.1 ± 253.7 | 684.1 ± 222.1 | 0.147 | <0.001 | <0.01 | <0.001 |
Non anemic | 35 | 192.8 ± 136.3 | 352.1 ± 214.6 | 360.2 ± 215.4 | <0.01 | <0.001 | 0.852 | <0.01 | |
Overall group | 74 | 322.9 ± 216.5 | 436.4 ± 247.8 | 530.9 ± 271.7 | <0.01 | <0.001 | <0.03 | <0.001 | |
p | <0.001 | <0.01 | <0.001 | ||||||
Uric acid (mg/L) | Anemic | 39 | 2.6 ± 1.03 | 3.6 ± 1.7 | 1.9 ± 1.3 | <0.01 | <0.001 | 0.248 | <0.01 |
Non anemic | 35 | 3.03 ± 0.9 | 5.3 ± 11.01 | 6.02 ± 2.4 | 0.078 | 0.005 | 0.361 | 0.028 | |
Overall group | 74 | 2.8 ± 1.01 | 4.4 ± 7.7 | 4.4 ± 1.3 | <0.01 | <0.001 | 0.138 | <0.01 | |
p | 0.088 | 0.326 | 0.356 | ||||||
Fasting glycemia (g/L) | Anemic | 39 | 75.3 ± 15.9 | 80.3 ± 21.9 | 81.4 ± 17.9 | 0.256 | 0.115 | 0.799 | 0.313 |
Non anemic | 35 | 73.4 ± 15.9 | 82.6 ± 18,4 | 82 ± 20.4 | <0.04 | 0.055 | 0.903 | 0.071 | |
Overall group | 74 | 74.4 ± 15.8 | 81.4 ± 20.2 | 81.7 ± 18.9 | <0.03 | <0.02 | 0.917 | <0.03 | |
p | 0.614 | 0.626 | 0.895 |
Factors | Anemia | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
14 - 19 gestational weeks | 28 - 32 gestational weeks | At term | ||||||||||
Frequency (n = 39) | OR | CI (95%) | p | Frequency (n = 44) | OR | CI (95%) | p | Frequency (n = 39) | OR | CI (95%) | p | |
Low socioeconomic level | 27 (69.2%) | 20.7 | 2.9 - 142.9 | <0.001 | 24 (54.5%) | 7.8 | 2.3 - 26.1 | <0.001 | 18 (46.2%) | 2.1 | 0.8 - 5.6 | 0.094 |
Intestinal parasitosis | 24 (61.5%) | 3.1 | 1.2 - 7.9 | <0.02 | 22 (50%) | 1.1 | 0.5 - 2.9 | 0.482 | 18 (46.2%) | 0.8 | 0.3 - 2.02 | 0.413 |
Geophagia | 16 (41%) | 7.4 | 1.9 - 28.5 | <0.01 | 14 (31.8%) | 2.3 | 0.7 - 7.4 | 0.115 | 13 (33.3%) | 2.4 | 0.8 - 7.3 | 0.092 |
Tanins and fibers | 30 (76.9%) | 9.6 | 3.3 - 27.9 | <0.001 | 29 (65.9%) | 3.9 | 1.5 - 10.3 | <0.01 | 25 (64.1%) | 2.7 | 1.1 - 6.9 | <0.04 |
term the association appeared significant for oxidized LDL at 19 mg/day (OR = 2.2; CI 95%: 1.7 - 2.8; p < 0.01 and OR= 1.9; CI 95%: 1.5 - 2.4; p < 0.02, respectively).
Our study aimed to assess variations of iron and oxidative status of routinely supplemented women during pregnancy. In anemic women of our series, evolution of hematologic parameters showed an increase in hemoglobin and hematocrit values (+average 1 gr/dl and +3%, respectively) throughout pregnancy, with significant change only between recruitment and 28 - 32 weeks. Nutrition was an important factor in the generation of anemia found in our series, as it can be derived from significant associations of anemia with nutritional iron intake (under 47 mg/day at recruitment, under 35 mg/day at 28 - 32 weeks and not thereafter).
Factors | 14 - 19 weeks | 28 - 32 weeks | At term | ||||||
---|---|---|---|---|---|---|---|---|---|
Frequency | OR (CI 95%) | p | Frequency | OR (CI 95%) | p | Frequency | OR (CI 95%) | p | |
Pathologic SOD | |||||||||
Anemia | 38/60 (63.3%) | 22.5 (2.8 - 183.5) | <0.001 | 26/52 (50%) | 0.7 (0.3 - 1.9) | 0.323 | 26/48 (54.2%) | 1.2 (0.5 - 3.1) | 0.460 |
Low socioeconomic level | 27/60 (45%) | 10.6 (1.3 - 86.6) | <0.01 | 20/52 (38.5%) | 1.1 (0.4 - 3.1) | 0.540 | 20/48 (41.7%) | 1.6 (0.6 - 4.4) | 0.252 |
Intestinal parasitosis | 32/60 (53.3%) | 2.9 (0.8 - 10.1) | 0.084 | 23/52 (44.2%) | 0.6 (0.2 - 1.5) | 0.180 | 23/48 (47.9%) | 0.9 (0.4 - 2.4) | 0.529 |
Geophagia | 18/60 (30%) | 5.6 (0.7 - 45.8) | 0.070 | 14/52 (26.9%) | 1.3 (0.4 - 4.04) | 0.473 | 14/48 (29.2%) | 1,7 (0.5 - 5.5) | 0.259 |
Tannins and fibers | 35/60 (58.3%) | 3.5 (1.9 - 12.4) | <0.05 | 30/52 (57.7%) | 1.9 (0.7 - 5.4) | 0.143 | 26/48 (54.2%) | 1.2 (0.5 - 3.1) | 0.460 |
Patholologic oxidized LDL | |||||||||
Anemia | 35/41 (85.4%) | 42.3 (10.9 - 164.4) | <0.001 | 28/38 (73.7%) | 6.4 (2.3 - 17.5) | <0.001 | 35/42 (83.3) | 35 (9.3 - 131.7) | <0.001 |
Low socioeconomic level | 25/41 (61%) | 15.6 (4.1 - 59.8) | <0.001 | 21/38 (55.3) | 5.1 (1.8 - 14.5) | <0.01 | 25/42 (59.5%) | 14.2 (3.7 - 54.2) | <0.001 |
Intestinal parasitosis | 25/41 (61%) | 3.1 (1.2 - 8.1) | <0.02 | 22/38 (57.9%) | 2.2 (0.9 - 5.5) | 0.080 | 26/42 (61.9%) | 3.6 (14 - 9.5) | <0.01 |
Geophagia | 14/41 (34.1%) | 2.9 (1.9 - 9.2) | <0.05 | 12/38 (31.6%) | 1.9 (0.7 - 5.6) | 0.177 | 15/42 (35.7%) | 3.9 (1.2 - 13.2) | <0.03 |
Tannins and fibers | 27/41 (65.9%) | 3.4 (1.3 - 8.8) | <0.02 | 26/38 (68.4%) | 3.8 (1.5 - 10.1) | <0.01 | 30/42 (71.4%) | 6.4 (2.3 - 17.7) | <0.001 |
Duration of supplementation (weeks) | Frequency | OR (CI 95%) | p |
---|---|---|---|
Pathologic SOD | |||
≥24 | 3/48 (6.3%) | 2.1 (0.8 - 5.3) | <0.05 |
≥23 | 7/48 (14.6%) | 1.4 (0.8 - 2.4) | 0.163 |
≥22 | 11/48 (22.9%) | 1,2 (0.8 - 1.8) | 0.319 |
≥21 | 18/48 (37.5%) | 1,1 (0.8 - 1.6) | 0.316 |
≥20 | 25/48 (52.1%) | 1,2 (0.9 - 1.7) | 0.196 |
≥19 | 37/48 (77.1%) | 1.2 (0.8 - 1.7) | 0.326 |
Pathologic oxidized LDL | |||
≥24 | 8/42 (19%) | 7.3 (0.9 - 61.7) | <0.04 |
≥ 23 | 13/42 (31%) | 13.9 (1.7 - 113.03) | <0.01 |
≥22 | 18/42 (42.9%) | 23.3 (2.9 - 186.7) | <0.01 |
≥21 | 24/42 (57.1%) | 5.8 (1.9 - 16.9) | <0.01 |
≥20 | 32/42 (76.2%) | 7.04 (2.5 - 19.7) | <0.001 |
≥19 | 34/42 (81%) | 1.2 (0.4 - 3.7) | 0.494 |
General characteristics proven to impede intestinal iron absorption such as pica, fibers and tannins significantly more frequent in the anemic group could be accounted for among factors influencing the responsiveness of supplemented women. The effect of intestinal parasitosis was probably offset by treatment at recruitment. Finally, the proportion of anemic women decreased following
Nutritonal iron intake (mg/day) | Period (weeks of gestation) | Frequency of anemia | OR | CI 95% | p |
---|---|---|---|---|---|
14 - 19 | 39/39 (100%) | 2.2 | 1.7 - 2.9 | 0.101 | |
<48 | 28 - 32 | 43/44 (97.7%) | 3.1 | 0.3 - 35.5 | 0.358 |
At term | 38/39 (97.4%) | 2.3 | 0.2 - 26.6 | 0.459 | |
14 - 19 | 39/39 (100%) | 2.3 | 1.7 - 2.9 | <0.05 | |
<47 | 28 - 32 | 43/44 (97.7%) | 4.8 | 0.5 - 48.3 | 0.179 |
A term | 38/39 (97.4%) | 3.6 | 0.4 - 35.9 | 0.267 | |
14 - 19 | 38/39 (97.4%) | 15.2 | 1.8 - 126.2 | <0.01 | |
<35 | 28 - 32 | 41/44 (93.2%) | 4.9 | 1.2 - 20.7 | <0.03 |
A term | 35/39 (89.7%) | 2.2 | 0.6 - 8.2 | 0.198 | |
14 - 19 | 11/39 (28.2%) | 13.4 | 1.6 - 109.9 | <0.01 | |
<21 | 28 - 32 | 11/44 (25%) | 9.7 | 1.2 - 79.5 | <0.02 |
At term | 8/39 (20.5%) | 2 | 0.6 - 7.3 | 0.230 | |
14 - 19 | 7/39 (17.9%) | 0.5 | 0.4 - 0.6 | <0.01 | |
<19 | 28 - 32 | 7/44 (15.9%) | 0.6 | 0.5 - 0.7 | <0.03 |
At term | 5/39 (12.8%) | 2.4 | 0.4 - 13.4 | 0.262 | |
14 - 19 | 4/39 (10.3%) | 0.5 | 0.4 - 0.6 | 0.071 | |
<18 | 28 - 32 | 4/44 (9.1%) | 0.6 | 0.5 - 0.7 | 0.118 |
At term | 3/39 (7.7%) | 2.8 | 0.3 - 28.6 | 0.349 |
supplementation. In non anemic group, however, no significant change was observed in hemoglobin and hematocrit, meaning that they did not benefit from supplementation.
As of ferritin and transferrin of anemic women, they significantly increased (from 7.5 at recruitment to 53 ng/mL at term and from 107 to 157 g/L at 208 - 32 weeks, respectively). In non anemic women notable change occurred only for transferrin (133 - 204 g/L). Serum iron significantly increased (53 - 83 μg/dl) from recruitment to 28 - 32 weeks in anemic women only. So, differences that were significant between groups at recruitment disappeared thereafter. On this basis too, non anemic women did not benefit from supplementation.
Physiologically, hematologic parameters decrease during pregnancy [
Nutritional iron intake (mg/day) | Period (weeks of gestation) | SOD | Oxidized LDL | ||||||
---|---|---|---|---|---|---|---|---|---|
Frequency | OR | CI 95% | p | Frequency | OR | CI 95% | p | ||
14 - 19 | 56/60 (93.3%) | 1.3 | 1.1 - 1.4 | 0.424 | 39/41 (95.1%) | 1.3 | 0.2 - 9.5 | 0.606 | |
≥18 | 28 - 32 | 48/52 (92.3%) | 1.5 | 1.2 - 1.7 | 0.235 | 34/38 (89.5%) | 2.1 | 1.6 - 2.6 | 0.064 |
At term | 44/48 (91.7%) | 1.6 | 1.3 - 1.9 | 0.169 | 38/42 (90.5%) | 1.8 | 1.5 - 2.3 | 0.097 | |
14 - 19 | 54/60 (90%) | 0.7 | 0.1 - 6.3 | 0.604 | 36/41 (87.8%) | 0.5 | 0.1 - 2.6 | 0.31 | |
≥19 | 28 - 32 | 46/52 (88.5%) | 0.4 | 0.04 - 3.2 | 0.323 | 31/38 (81.6%) | 2.2 | 1.7 - 2.8 | <0.01 |
At term | 42/48 (87.5%) | 0.3 | 0.03 - 2.5 | 0.218 | 35/42 (83.3%) | 1.9 | 1.5 - 2.4 | <0.02 | |
14 - 19 | 12/60 (20%) | 1.7 | 1.2 - 2.5 | 0.000 | 8/41 (19.5%) | 1.8 | 1.01 - 3.2 | <0.04 | |
≥26 | 28 - 32 | 13/52 (25%) | 1.3 | 0.9 - 1.9 | 0.138 | 8/38 (21.1%) | 1.6 | 1.01 - 2.9 | <0.05 |
At term | 11/48 (22.9%) | 1.4 | 0.9 - 2.2 | 0.071 | 7/42 (16.7%) | 2.1 | 1.1 - 4.01 | <0.01 | |
14 - 19 | 11/60 (18.3%) | 1.8 | 1.2 - 2.7 | 0.000 | 7/41 (17.1%) | 1.9 | 1.02 - 3.6 | <0.02 | |
≥27 | 28 - 32 | 12/52 (23.1%) | 1.3 | 0.9 - 1.9 | 0.103 | 7/38 (18.4%) | 1.8 | 1.01 - 3.4 | <0.05 |
At term | 11/48 (22.9%) | 1.3 | 0.9 - 2.1 | 0.126 | 6/42 (14.3%) | 2.4 | 1.2 - 4.8 | <0.01 | |
14 - 19 | 7/60 (11.7%) | 1.9 | 1.1 - 3.3 | 0.001 | 4/41 (9.8%) | 2.4 | 1.01 - 5.6 | <0.02 | |
≥30 | 28 - 32 | 10/52 (19.2%) | 1.1 | 0.7 - 1.6 | 0.479 | 3/38 (7.9%) | 3 | 1.1 - 8.3 | <0.01 |
At term | 8/48 (16.7%) | 1.3 | 0.8 - 2.1 | 0.226 | 4/42 (9.5%) | 2.4 | 1.02 - 5.7 | <0.02 | |
14 - 19 | 5/60 (8.3%) | 1.9 | 1.01 - 3.7 | 0.004 | 1/41 (2.4%) | 6.9 | 1.1 - 45.7 | <0.01 | |
≥35 | 28 - 32 | 8/52 (15.4%) | 1.2 | 0.3 - 4.8 | 0.578 | 2/38 (5.3%) | 3.1 | 1.01 - 11.2 | <0.02 |
At term | 8/48 (16.7%) | 1.5 | 0.4 - 6.4 | 0.411 | 2/42 (4.8%) | 3.5 | 1.01 - 12.4 | <0.01 | |
14 - 19 | 5/60 (8.3%) | 1.5 | 0.8 - 2.8 | 0.059 | 1/41 (2.4%) | 5.5 | 0.9 - 35.5 | <0.01 | |
≥36 | 28 - 32 | 7/52 (13.5%) | 1.6 | 0.3 - 8.2 | 0.463 | 2/38 (5.3%) | 2.5 | 0.7 - 8.6 | 0.064 |
At term | 7/48 (14.6%) | 2.1 | 0.4 - 10.7 | 0.320 | 2/42 (4.8%) | 2.8 | 0.8 - 9.5 | <0.04 |
women obviously means that routine administration is useless for non anemic women and might be harmful for them. This aspect is rarely addressed in the literature.
In their review addressing the effects of iron supplementation on hematologic status in pregnancy, Sloan et al. [
Despite iron supplementation (dosage and duration of supplementation not specified), Mpawenimana’s series In Morocco [
In the Seychelles series (dosage of one tablet containing 200 mg FeSO4 and 0・25 mg folic acid per day) [
Following 8 weeks (20th-36th gestational weeks) of iron supplementation in an Egyptian series of 50 anemic pregnant women (100 mg of ferrous sulfate twice a day in 25 women and 200 mg ferric hydroxide-IPC once a day in 25 others), Aly et al. [
Kumar et al [
This effect of iron supplement is more likely to occur in the presence of iron deficiency. So, the rise is related to initial hematologic status [
The effect of iron supplementation has been found dose (more than 91 mg/day) along with duration (11 - 13 weeks) dependent. With 60 mg of iron (ferrous sulfate)/day, Falahi et al. [
Eskeland et al. [
In our series, women with anemia (Hb < 10 g%) received 320 mg/day of ferric ammonium citrate for curative while the others received 160 mg/day for preventive purposes. These huge dosages in comparison with the above references are still common in our country without obvious scientific basis. To support them, one could advocate limiting conditions of iron absorption in our setting such as the predominantly non-heminic nature of alimentary iron, intestinal parasitosis and chelating substances contained in food (phytates, phosphates, tannins, fibers and calcium salts) [
With respect to oxidative status during pregnancy with or without any supplementation, very few studies addressed its own potential variation throughout normal gestation. The evaluation is usually carried out either early [
So far, the only data available on intrinsic changes of oxidative status throughout normal pregnancy deal with the placenta and come from Basu et al. [
What about changes induced by iron supplementation on oxidative status? Given that iron deficiency is associated with oxidative stress [
In Estonia, Rehema et al. [
In the Egyptian study, Aly et al. [
Kurtoglu et al. [
So, while oxidative stress decreases itself as pregnancy progresses [
Actually, after correcting anemia by achieving optimal hemoglobin levels and building up iron stores (ferritin levels), such as we got it in our study, total antioxidant capacity might be boosted. In our series, this probably occurred at 28 - 32 weeks, after 11 - 12 weeks of supplementation (
So, it can be suggested that additional oral iron in so replete patients remains unabsorbed. Its pro-oxidant properties are likely to induce production of free radical oxygen species and thereby impact oxidative status that was observed till term. Iron supplement is to be considered together with nutritional intake mostly providing non-heminic iron and whose significant association with oxidative stress was found at 26 mg/day for SOD (OR = 1.7; CI 95%: 1.2 - 2.5; p < 0.001) and oxidized LDL (OR = 1.8; CI 95%: 1.01 - 3.2; p < 0.04) at recruitment and even at 19 mg/day by 28 - 32 weeks of gestation for oxidized LDL (OR = 2.2; CI 95%: 1.7 - 2.8; p < 0.01). Lund et al. [
Iron supplementation improved iron status in anemic women, not in non anemic. Differences that were significant between groups at recruitment disappeared by 28 - 32 weeks. Non anemic women were not in need of iron supplementation. SOD decreased and LDL values increased alongside supplementation. This represents a growing oxidant threat for both anemic and non anemic women. This could be related to iron overload and/or unabsorbed iron.
Doses of iron should be decreased (at least halved) and duration of treatment restricted to not more than 12 weeks.
Study limitation mainly relates to smallness of the study sample, a factor already allegedly owed to cost of an own funded study. The strength of the study comes first from the scarcity of studies addressing both iron status and oxidative status during pregnancy in Sub-Saharan Africa, secondly from actual routine nature of the supplementation, involving preventive and curative concerns. Attention paid on this later aspect helps question harmful influence of iron supplements in women who are not in need of it. Furthermore, our study included many confounding factors such as dietary and nutritional details accountable for in understanding of some conflicting findings.
MMA is the principal investigator, participated in designing the study and was actively involved in data collection and statistical calculations. TUB generated and designed the study. He drafted the first manuscript. MMR participated in designing the study and analyzing the results. All authors contributed in preparing the final manuscript.
The authors declare no conflicts of interest regarding the publication of this paper.
Mbangama, A.M., Tandu-Umba, B. and Mbungu, R.M. (2019) Routine Iron Supplementation during Pregnancy: Its Reflection on Iron and Oxidative Status in a Cohort of Pregnant Women in Kinshasa, DR Congo. Open Journal of Obstetrics and Gynecology, 9, 98-115. https://doi.org/10.4236/ojog.2019.91011