Helicobacter pylori and anemia with pregnancy
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Subjects and methods
Study was conducted in Ain Shams University hospitals on 100 pregnant women with iron-deficiency anemia (IDA), including 50 cases infected with Helicobacter pylori (H. pylori) and 50 cases negative for H. pylori infection. Cases with symptomatic gastritis or hyperemesis gravidarum were not included in the study, obstetric history, sociodemographic and dietary variables were also assessed. Hemoglobin level, serum iron, serum ferritin, total iron binding capacity (TIBC), H. pylori serum antibody, stool analysis to exclude parasitic infection causing IDA, occult blood in stool and ultrasound for the fetus to ensure its cardiac pulsations and to exclude any associated abnormality were all done for all patients. Iron therapy in a fixed dose was given to all patients for 1 month. Response was estimated and statistical comparison was done between both groups. Eradication of H. pylori was done in positive cases by triple therapy in the second trimester and iron therapy was given after treatment in the same dose for another month. Their response to treatment after eradication was compared to their response to iron therapy prior to H. pylori eradication.
Hb levels, serum iron, serum ferritin were lower and TIBC was higher in H. pylori-infected cases than negative ones. The average rise of Hb in cases negative to H. pylori was higher than those positive to H. pylori. After comparing response of cases infected with H. pylori to iron therapy before and after eradication of H. pylori, it was found that rise of Hb was higher after treatment than before eradication of H. pylori.
Response to iron therapy in cases of iron deficiency anemia in patients without H. pylori infection was better than those infected with H. pylori. H. pylori eradication in the infected cases increased their response to iron therapy.
KeywordsPregnancy Helicobacter pylori infection Iron-deficiency anemia Hemoglobin Serum ferritin TIBC
Iron deficiency is the most common nutritional deficiency in the world and affects immune, cognitive and reproductive functions, as well as work performance. Iron-deficiency anemia (IDA) affects more than a billion people worldwide and contributes to up to 40 % of maternal deaths in the developing countries. [1, 2, 3]. Recent studies have suggested an association between Helicobacter pylori infection and iron deficiency. [4, 5, 6, 7, 8, 9, 10, 11, 12]. Various mechanisms have been hypothesized for the development of IDA in H. pylori infection; some of which are low gastric pH, low vitamin C levels in stomach, sequestration of serum iron and ferritin by gastric H. pylori [13, 14, 15].
H. pylori may cause microbleeding and/or affect iron uptake and thus deplete iron stores in persons with iron deficiency and IDA, independently of ulcer disease. The associations between H. pylori infection and IDA seem to be stronger among persons with a history of peptic ulcer, suggesting that ulcers may play a role in that small subpopulation. [16, 17, 18]. Helicobacter pylori in pregnant women has been found to be associated with low initial hemoglobin (Hb), and IDA is associated with high chance of fetal growth retardation and H. pylori infection in children of these mothers [12, 19]. The aim of this study was to investigate the effect of eradication of H. pylori on response to iron therapy in cases of IDA associating H. pylori infection during pregnancy.
Patients and methods
One hundred pregnant women with IDA including 50 cases infected with H. pylori (group A) and 50 cases negative for H. pylori infection (group B) were included in the study. Pregnant women were 10–14 weeks gestation. A power analysis revealed that a sample size of 100 (50 in each group) would enable detection of mean difference in Hb of 1.6 and 3.3 standard deviation between the groups with 90 % power at the 5 % significance level. Cases were recruited from Ain Shams university hospitals in the period from January 2010 to January 2012. IDA was diagnosed during their routine lab investigations in their antenatal care. All women confirmed their participation by signing a written informed consent and approval of the ethical committee was obtained.
Complete blood count, hemoglobin level, Serum ferritin, serum iron, and total iron binding capacity (TIBC) were done for all cases. Stool analysis was done to exclude parasitic infection causing iron deficiency anemia as hook worm infection, whip worm infection and schistosomiasis. Cases with symptomatic gastritis in the form of epigastric dull, vague, burning, aching, gnawing, sore or sharp pain or upper abdominal discomfort, either associated or not with nausea, vomiting, belching and/or bloating, were excluded from the study . Patients with history of gastric ulcer—previously diagnosed by upper endoscopy—were excluded from the study. Patients with history of parasitic worm infection causing IDA were not included in the study.
Cases with hyperemesis gravidarum—characterized by severe nausea and vomiting associated with weight loss, ketonemia, electrolyte imbalance (hyponatremia and hypokalemia), metabolic hypochloremic alkalosis and elevated liver enzymes in pregnancy— were excluded from the study. Cases that developed attacks of hematemesis were not included in the study. Patients who received any recent antibiotics or previous medications for H. pylori or antacids were not included also in the study. Obstetric history, sociodemographic and dietary variables were also assessed for all patients. Tests commonly used to detect H. pylori are either invasive or non-invasive investigations. Endoscopic biopsy is an invasive method and it was not preferred during pregnancy in the current study. Non-invasive tests include serological test, urea breath test and stool antigen tests . Although 13 C and 14 C urea breath tests are inexpensive and non-invasive but low-dose irradiation in 14 C test considers it not the investigation of choice during pregnancy.
The stool-specific antigen test, although a simple, inexpensive assay, but was mentioned to be slightly less accurate in some comparative studies and mainly used for follow-up after treatment . The simplest tests for ascertaining H. pylori status are serologic assays measuring specific IgG levels in serum by enzyme-linked immunosorbant assay or immunoblot. It is considered the best of these tests and as accurate as other diagnostic methods . Serum H. pylori IgG antibody titer using commercial (ELISA) method was measured for all patients in the current study. IgG antibody titer < 13 AU/mL (which corresponds to optical density ratio < 0.9) was considered negative, IgG titer > 16.5 AU/mL (which corresponds to optical density ratio > 1.1) was regarded as positive and IgG level 13–16.5 AU/mL (which corresponds to optical density ratio 0.9–1.1) was regarded as suspicious requiring repetition after 2–4 weeks .
Iron therapy in the from of ferrous–glycine–sulfate complex 567.7 mg capsules (equivalent to 100 mg elemental iron) twice daily in a fixed dose was given to all patients for 1 month and response was obtained in both groups. Statistical comparison between both groups was done.
The patients in the two groups did not have significant differences in terms of age, job, education, husband’s education, husband’s job, number of pregnancies and economic status. There were 50 negative cases included in the study and 50 positive cases for H. pylori infection. Serum iron ranged from 18 to 51 μg/dL with a mean of 23 ± 1.03 μg/dL, in the anemic patients infected with H. pylori (group A), and was 24–56 (45 ± 2.64) μg/dL in group B.
Serum ferritin ranged from 3.4 to 18.6 ng/mL with a mean of 7 ± 2.23 ng/mL in group A and range of 17.2–24.3 ng/mL with a mean of (19 ± 3.67) ng/mL in group B. TIBC ranged from 381 to 428 μg/dL with a mean of 410 ± 3.56 μg/dL in group A and range of 353–379 μg/dL with a mean of 360 ± 2.34 μg/dL in group B, with a significant difference between both groups regarding serum iron, serum ferritin and TIBC (p < 0. 001). Serum Hb ranged from (7.3–9.4) gm/dL with a mean of 8 ± 0.23 gm/dL in group A, and from (9.1–10.9) 10.1 ± 0.4 gm/dL in group B. Hb level was significantly lower in group A than in group B (p < 0.001).
Values of serum iron, ferritin, TIBC and Hb in both groups
Group A (anemic pregnant infected with H. pylori) no = 50
Group B (anemic pregnant non-infected with H. pylori) no = 50
Serum iron in μg/dL
18–51 (23 ± 1.03)
24–56 (45 ± 2.64)
Serum ferritin in ng/mL
3.4–18.6 (7 ± 2.23)
17.2–24.3 (19 ± 3.67)
TIBC in μg/dL
381–428 (410 ± 3.56)
353–379 (360 ± 2.34)
Hb in gm/dL
7.3–9.4 (8 ± 0.23)
9.1–10.9 (10.1 ± 0.4)
Hb after 1 month of iron treatment in gm/dL
7.9–9.9 (8.4 ± 0.34)
10–11.7 (11.1 ± 1.26)
Hb after eradication of H. pylori in positive group in gm/dL
8.7–11 (10.1 ± 0.04)
Iron deficiency anemia is the most common cause of anemia during pregnancy. The WHO estimated that 35–75 % of pregnant women in developing countries and approximately 20 % of industrialized countries are anemic during pregnancy . Moderate-to-severe maternal anemia has been associated with an increased risk of poor reproductive outcomes, including low birth weight and preterm birth deliveries . 600 mg of iron is needed for a singleton pregnancy, which amounts to 4–6 mg per day of absorbed iron. Dietary intake is mostly insufficient, so additional supplementation is needed .
Despite this, many cases remain anemic . Hence it was necessary to review other factors affecting gastric absorption and utilization of dietary or supplemental iron. H pylori has been shown to be associated with IDA [27, 28, 29, 30]. The current study aimed to compare pregnant cases with IDA with H. pylori infection with non-infected cases as regard Hb levels, serum iron, serum ferritin and TIBC, and to compare the response of both groups to fixed dose of iron therapy and to compare response of infected cases to iron therapy before and after eradication of H. pylori. In the current study, the anemic patients infected with H. pylori had lower Hb level, serum ferritin, and serum iron levels and higher TIBC than the anemic non-infected cases. Their response to iron therapy was less than the non-infected group.
The infected group revealed better response to iron therapy after eradication of H. pylori by triple therapy. Though interventional studies conducted in pediatric population have shown improvement in IDA with H. pylori eradication, even without iron replacement [27, 28, 29, 30], there is paucity of such clinical trials in pregnant women. Several investigators have evaluated the safety of individual drugs, including proton pump inhibitors used in the anti H. pylori triple drug therapy in pregnant women and the meta-analysis reports no increased risk for spontaneous abortion, preterm delivery or major congenital birth defects. The treatment of H. pylori in the current study was given after the first trimester in all cases [23, 31].
Weyermann and others found that pregnant women infected with H. pylori had lower mean hemoglobin level at the beginning of pregnancy and a greater decrease in the mean hemoglobin level at the end of pregnancy with higher chance of fetal growth retardation . Their study plan was different from the current study but agrees with results of this study regarding the lower Hb levels in infected cases than non-infected ones. Valiyaveetil et al.  found a high prevalence (61.5 %) in their study of H. pylori infection in adults with IDA in south India. The high prevalence of H. pylori infection in developing countries is well established. However, we have no statistical data for the prevalence of H. pylori in Egyptian women. In the current study, we did not assess the prevalence of H. pylori infection among cases with IDA, but the aim was to compare cases of IDA infected with H. pylori and the non-infected ones, regarding Hb, serum iron, serum ferritin, TIBC, response to iron treatment.
Mulayim et al. tried to determine whether there is a relationship between H. pylori infection and iron deficiency anemia and thrombocytopenia in pregnant women measuring hemoglobin and ferritin levels and platelet counts during the third trimester of pregnancy. They found 27 of 117 pregnant women had anemia, and all them were in the H. pylori-positive group. Serum hemoglobin and ferritin levels and neonatal body weight were found to be lower in the anemic group compared with the non-anemic group among H. pylori-infected women . Clinical trials of H. pylori eradication and/or iron supplementation found an effect on anemia in the H. pylori eradication treatment group that was comparable to the effect in persons who received only iron supplementation. Their results agree with the results of the current study . Other clinical studies stated that H. pylori eradication would enhance the response to iron therapy in IDA [35, 36, 37].
Results of Malik et al. showed a high occurrence of H. pylori infection in pregnant women with IDA. Eradication therapy resulted in significantly better response to oral iron supplementation among H. pylori-infected pregnant women with IDA, results that agree with the results in the current study . Malik et al.  compared treated cases with cases who received placebo. Placebo was not preferred in the current study to give all patients the same chance of therapy. Another large cross-sectional study conducted in Alaska  found that H. pylori infection was associated with decreasing levels of serum ferritin and that this association seemed stronger among adolescents and women of childbearing age. A recent study of pregnant women in Germany reported an association between current H. pylori infection and hemoglobin levels .
Farag et al. also reported higher odds of H. pylori infection in women with severe anemia . Iron-deficiency anemia can also be due to bleeding lesions of the gastrointestinal tract and that is why exclusion was elicited in the current study by history taking of peptic ulcer or gastritis and by occult blood in stool. Also, patients who received any recent antibiotics or previous medications for H. pylori or antacids were excluded from the current study to be sure that there was no recent eradication of the organism. The current study augments the relation of H. pylori and IDA in pregnant women, and that it may be a cause for lowering the Hb, and that eradication of H. pylori is important for better response to iron therapy.
Iron deficiency anemia during pregnancy may be worse with H. pylori infection. Eradication of H. pylori accelerates response to iron therapy during pregnancy, therefore it is suggested that tests for H. pylori infection should be included in pre-conception consultations, especially for women who have a history of anemia or persistent anemia. Eradication of H. pylori in infected cases of IDA would accelerate the response to iron therapy. Further studies on a large number of women are needed to corroborate the current findings.
Conflict of interest
Authors state that there was no funding specifically designated for this study and there is no conflict of interest.
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