OJHAS Vol. 8, Issue 4: (2009
|Impact of Maternal Helicobacter pylori
Infection on Trace Elements (Copper, Iron and Zinc) and Pregnancy
of Chemical Pathology, Faculty of Clinical Medicine, Ebonyi State
P.M.B. 053 Abakaliki, Nigeria,
of Biochemistry, Abia State University, Uturu, Nigeria
Address For Correspondence
of Chemical Pathology,
Faculty of Clinical Medicine,
P.M.B. 053 Abakaliki, Nigeria
Ugwuja EI, Akubugwo EI. Impact of Maternal Helicobacter pylori
Infection on Trace Elements (copper Iron and Zinc) and Pregnancy
Outcomes. Online J Health Allied Scs.
Submitted: Dec 12, 2009; Accepted:
Apr 2, 2010; Published: Apr 30, 2010
H. pylori infection has been suggested to interfere with
metabolism and influence pregnancy outcomes. Objectives:
This study therefore seeks to document the prevalence of H. pylori
seroposivity among pregnant women and to determine its impact on some
trace element status and pregnancy outcomes. Materials and methods:
Three hundred and forty nine consenting pregnant women aged 15-40 years
(mean; 27. 04 ± 4. 75 years) and gestational age ≤ 25 weeks (mean
21.77 ± 3.14 wks) attending antenatal clinic at Federal Medical Centre,
Abakaliki, between July 2007 and September 2008 participated in the
study. H. Pylori antibody (IgG) was determined by a new
ELISA method. Plasma copper, iron and zinc were analysed using flame
atomic absorption spectrophotometer (Bulk Scientific AVG 210 Model)
while haemoglobin and albumin were analysed using standard
and biochemical techniques. Both maternal sociodemographic and
parameters were recorded at recruitment. The women were followed-up
till delivery after which neonatal anthropometrics and other birth
were recorded. Results: H. pylori seroprevalence of 24.1%
(84/349) was recorded with higher prevalence in multiparous and older
women. H. pylori infected women had significantly higher BMI
(29.00 ± 3.89 vs. 26.86 ± 4.10, p = 0.020) and lower (p > 0.05)
plasma levels of Cu, Fe, Zn, albumin, and haemoglobin when compared
to non-infected women. Also H. pylori infected women had
(p < 0.05) higher rates of convulsion and concomitant illnesses than
their non-infected counterparts, although there was no difference in
the two groups for other pregnancy outcomes. Conclusion:
H. pylori infection during pregnancy seems to interfere with
trace element metabolism and contribute significantly to increased
morbidity. Prior to confirmation of these findings in a well controlled
randomised trial, it is suggested that pregnant women be screened for
H. pylori infection to reduce H. pylori associated
H. pylori, Pregnancy, Trace elements, Copper, Iron, Zinc, Nigeria
in 1982, H. pylori infection has been recognised to occur
the world, with seroprevalence significantly higher in developing than
the developed countries.(1,2) Current evidence showed that H.
is acquired in early childhood through family members by oral-oral,
gastric-oral, or oral-faecal routes and persist till adulthood.(3, 4)
In Nigeria, like other developing countries, the prevalence of H.
pylori is alarmingly high (5) and this has been attributed to poor
personal and public hygiene. Infection with Helicobacter pylori
has been associated with both gastric and extragastric clinical
For example, H. pylori infection has been associated with
peptic ulcer, gastric adenocarcinoma, and type B low-grade mucosa
lymphoid tissue lymphoma (6) as well as diabetes mellitus,
insulin resistance, some autoimmune diseases (7-9) and iron deficiency
anaemia refractory to iron supplementation.(10) Except for IDA, the
role of H. pylori in some of these extragastric associations
has been of intense debate as data have been conflicting. Recently,
there has been controversy of the association between infection with
H. pylori and intra-uterine growth restriction. For instance, while
McKenna et al. (11) and Bromberg et al. (12) in Ireland
and Francisco respectively, reported lack of association between
H. pylori and outcomes of pregnancy such as preterm delivery, non
reassuring foetal status during labour or both and its presence not
associated with obesity or parity, Eslick and his colleagues (13)
that intrauterine growth restriction was more common in H. pylori-seropositive
women than in H. pylori-seronegative women. Deficiencies of some
micronutrients such as copper, zinc manganese, vitamins A, B12,
C, and E have been suggested to occur concomitantly in H. pylori
H. pylori and pregnancy have some symptoms, such as, epigastric
pain/dyspepsia, flatulence, nausea, fullness, vomiting in common,
have shown that H. pylori infection is neither associated with
dyspeptic symptoms in pregnancy nor is it related to the severity of
dyspeptic symptoms.(12,15) In H. pylori endemic population
as evidenced in Abakaliki, pregnant women may be harbouring asymptomatic
H.pylori infection, with its attendant deficiencies of essential
micronutrients which may affect the course and outcomes of pregnancy.
This study therefore seeks to document, for the first time, the
of H. pylori seroposivity among pregnant women and to determine
the impact of H. pylori infection on some trace element status and
was part of a larger study that evaluated the impact of maternal trace
element (copper, iron and zinc) status on pregnancy outcomes in
South Eastern Nigeria. It was a longitudinal study that recruited 349
consenting pregnant women, aged 15-40 years, gestational age ≤25
weeks between July 2007 and September 2008. Gestational age was
by date of last menstruation and confirmed by ultrasonography and where
there is disagreement between the two methods that of ultrasonography
was used. Exclusion criteria include suffering from chronic disease,
HIV-seropositivity and multiple pregnancies. Women who were on proton
pump inhibitors or on H. pylori eradication therapies were also
excluded. The protocol for this study was approved by the Ethics and
Research Committee of the Federal Medical Centre Abakaliki. The
of the participants were collected by structured questionnaires.
anthropometry; height and weight were measured with the subject in light
clothes without shoes, and BMI (Kg/m2) calculated. Seven millilitres
(7.0 ml) of non-fasting venous blood collected between 08.00-10.00 hours
were dispensed into trace element-free heparinised plastic bottles (3.0
ml), plain bottles (2.0 ml) and EDTA bottle (2.0 ml) for analysis of
biochemical, haematological parameters and for H. pylori
serology respectively. The blood samples in the trace element-free and
plain bottles were centrifuged at 2000g for five minute for the
of plasma and serum respectively. The plasma samples were frozen until
they were analysed. Participants were followed-up weekly till delivery.
At every follow-up, participants were evaluated by the attending
for concomitant illness such as diabetes and hypertension. At
delivery baby’s birth outcomes such as weight, length, head
as well as still birth, mode of delivery, gestation age at delivery
were recorded by the attending midwives. Birth weight was determined
using electronic weighing balance and recorded to the nearest 0.05Kg
with the scale checked periodically throughout the study for accuracy
while birth length and head circumference was determined by a measuring
tape to the nearest 0.1cm. Plasma copper, iron and zinc were determined
in duplicates using atomic absorption spectrophotometer and the mean
recorded as the absolute value. Haemoglobin concentration was determined
using Cyanmethaemoglobin method as described previously.(16) Anaemia
was defined as haemoglobin concentration <11.0 g/dl (17) while
iron and zinc deficiencies were defined plasma levels <8.0 µmol/l,
< 10.0 µmol/l and < 5.0 µmol/l respectively.(18) Plasma albumin
was determined as described previously (19) Determination of
G (IgG) to Helicobacter pylori
was done by enzyme-linked immunosorbent assay (20) using a third
commercial ELISA kit.
were analysed using statistical package for social science (SPSS version
10). Percentage prevalence rates were calculated with their respective
95% confidence intervals. Differences between proportions were evaluated
using the chi-square tests while differences in means were evaluated
using one-way analysis of variance (ANOVA). Statistical significance
were achieved at p <0.05.
Seroprevalence of H. pylori
in relation to maternal sociodemographic and Obstetrics data (percentage
H. pylori positive (n/%)
|< = 19
prevalence of 24.1% (84/349) was recorded. Although no specific trend
was observed, H. pylori infection was higher in women who live
in flat than other living accommodation (table 1). Similarly, without
a particular trend, higher prevalence of H. pylori was observed
in women who were educated up to tertiary level and women without formal
education compared with women with either primary or secondary
As for maternal occupation, highest H. pylori infection was found
among women whose occupation was farming (2/5, 95% CI: -2.9-28.9) when
compared to other occupations, with least prevalence of 12/61, 95% CI:
5.3-28.1) recorded among women who were student. Maternal H. pylori
infection was found to increase with parity, with multiparous women
having the highest prevalence while least prevalence was found among
women with parity 1 (11/66, 95% CI: 7.6-25.8). However, maternal age
group 30-35 years had the highest prevalence of H. pylori infection, with
age groups < = 19 and 10-24 years having least prevalence of 18.8% each (table
Comparison of maternal anthropometrics, haematological and biochemical
parameters between H. pylori infected and non-infected pregnant
(n = 84)
seronegative (n = 265)
| Age (yrs)
||28.19 ± 4.89
||26. 70 ± 4.65
||29.00 ± 3.89
||26.86 ± 4.10
||1.54 ± 1. 57
||1.37 ± 1. 43
||10.04 ± 1.22
||10.27 ± 1.27
||8.64 ± 7.10
||9.90 ± 10.03
||10.00 ± 7.27
||10.33 ± 7.83
||8.79 ± 9.93
||9.31 ± 8.92
||3.41 ± 0.82
||3.47 ± 0.79
*P < 0.05 is considered statistically significant.
2, although women who were infected with H. pylori were
older (p < 0.05), and have significantly higher BMI than non infected
women, no difference was observed between the two groups in term of
parity p > 0.05). Also no significant difference was found in the
haemoglobin concentration (HBC) between women who were infected with
H. pylori and those without infection, although H. pylori
infected women had slightly higher value. For trace elements Cu, Fe,
and Zn, although women who were seropositive for H. pylori had
slightly lower values than their seronegative counterparts, these were not
statistically significant (p > 0.05). The two groups also showed comparable
plasma albumin concentration (p > 0.05).
3: Maternal and foetal outcomes in relation to Maternal
H. pylori serostatus (proportions; n/%)
H. pylori serostatus
(n = 239)
||Positive (n = 79)|
HBC < 11.0 g/dl
§(Malaria, Urinary tract infection, upper respiratory tract infection,
p-values < 0.05.
3, maternal anaemia was comparable between H. pylori infected
and non infected women. The proportions of women with diabetes and
were higher in H. pylori infected women than in non infected
women, although not statistically significant, with an association
between H. pylori infection and maternal D/M (RR 1.9 (1.6-2.0).
However, both maternal convulsion and concomitant illnesses were
higher in women with H. pylori
infection when compared to their non infected counterparts.
strong positive associations were observed between the two co-morbid
conditions and H. pylori (RR: 9.5 and 2.4 for convulsion and
concomitant illnesses respectively). Although all the pregnancy
outcomes (instrumental delivery, C/S, preterm delivery, LBW, male sex
and still births) were lower in women infected with H. pylori
than non infected women, these were not up to statistical significant
level. However, while no association was found between male sex and
H. pylori, all other outcomes showed negative associations.
has documented H. pylori seroprevalence of 24.1% among pregnant
women which was associated with poor socioeconomic status. It also
that H. pylori infection during pregnancy is associated with
increased BMI, convulsion and concomitant illness such as malaria,
tract infections, upper respiratory tract infections and dyspeptic
H. pylori prevalence of 24.1% is comparable to the value obtained
in an earlier study (26.3%) of uninvestigated dyspeptic individuals
in the same population. It is also comparable to H. pylori
of 20% reported by Eslick et al. (13) among pregnant women in Australia.
However, it is lower than 41.8% and 65.7% reported among pregnant women
in Northern Ireland and Francisco respectively.(11,12) The lower seroprevalence of H. pylori in the present study may be due to
study populations. While theirs were done on pregnant women with
symptoms specifically, the present study was conducted among pregnant
women generally, irrespective of dyspeptic complaint. Data have been
however conflicting on the association between H. pylori infection
and dyspeptic symptoms.(5,12,15) The higher prevalence of H. pylori
seropositivity in women without formal education and women who were
educated to tertiary level represents two extreme cases. For the former,
it could be attributable to poor personal hygiene associated with low
socioeconomic status. Poor personal hygiene has been shown to enhance
the acquisition and the spread of the bacteria.(5,21) These
factors may also have accounted for the higher prevalence of the
in multiparous women and in women whose occupation was farming in
to nulliparous or other occupational groups. However, in the
it could be due to persistency of earlier acquired infection during
childhood (22) as evidenced by higher seroprevalence in older age groups
in the present study. In the present study, H. pylori infection
was not found to be associated with maternal parity in corroboration
with the findings of Bromberg et al.(12) However the higher BMI in
women infected with H. pylori when compared with women who were
not infected with the bacteria contrasts earlier findings.(12) In an
earlier study in this population, higher BMI and dyslipidaemia was
with H. pylori infection (23), a phenomenon that has been
to be due to enhanced response to insulin leading to reduced plasma
glucose levels (24) and consequent alteration in lipid metabolism. The
lack of significant effects of H. pylori infection on maternal
haemoglobin concentration (HBC) in the present study is in contrast
with previous findings.(10,25-27) Although the reason for this
is obscure, it may be due to the effect of bacterial load, as only
H. pylori infection with low bacterial load was associated with
lower maternal haemoglobin concentration.(25) However, this study did
not assess H. pylori bacterial load. Difference in subjects may
be another reason. With the exception of the study by Farag and
(25), other studies were carried out on non pregnant subjects.(10,27)
The non-significantly (p > 0.05) lower concentrations of Cu, Fe and
Zn in H. pylori-infected when compared with non-infected women
indicate that H. pylori infection may have effect on trace
metabolism. Data on the impact of H. pylori infection on
trace element status in pregnant women is scarce but few studies have
shown that H. pylori affects iron metabolism.(10,28) Possible
mechanism by which H. pylori affects iron metabolism include
(1) decreased absorption from hypo-or achlorhydria resulting from
gastritis (29), (2) decreased gastric juice ascorbic acid concentration
which is known to facilitate iron absorption by reduction of iron III
to iron II (30), (3) increased hepcidine production associated with
H. pylori gastritis (31), (4) uptake of iron by H. pylori
for growth (32), and (5) decreased availability of iron by sequestration
of iron in lactoferin in the gastric mucosa through a receptor-mediated
process.(33) In addition to iron, a gene, copA, associated with copper
transport, has been isolated from H. pylori strains. Again,
metalloenzymes, superoxide dismutase involved in scavenging reactive
oxygen molecules (ROMs) have been found to be affected by H. pylori
infection.(34) Although, the exact mechanism by which H. pylori
affect copper and zinc nutriture during pregnancy is yet to be
it may be through its effect on BMI as studies have shown that plasma
zinc decreases with higher maternal BMI. Zinc metabolism, transport
and/or tissue distribution has been suggested to be related to BMI
a yet-to be identified mechanism.(35) However, it has been established
that plasma volume correlates significantly with BMI.(36) Thus, the
lower plasma copper and zinc concentration observed in H. pylori
infected pregnant women when compared to non-infected women in the
study may be attributable in part, to higher plasma expansion in the
former than in the latter as evidenced by non-significantly lower plasma
albumin in H. pylori infected women. However, the extent by which
H. pylori affect plasma volume expansion is yet unknown. This study
shows that H. pylori infection during pregnancy is associated
with increased risk of maternal convulsion and concomitant illnesses,
such as malaria, dyspepsia, UTI and URTI. This is in contrast with the
findings of Bromberg et al. (12) and Mckenna et al.(11) However,
recent meta-analyses indicated that eradication of H. pylori
is effective in resolving symptoms in H. pylori
positive non-ulcer dyspepsia.(37,38) The lack of association between
H. pylori infection and pregnancy outcomes as recorded in the
study is corroboration with some earlier studies (11,12) but contrast
the findings of Eslick et al. (13) where H. pylori seropositivity
was found to be an independent risk factor for intrauterine growth
(OR=2.59; 95% CI, 1.12–5.95; P=0.025). Our patients were from
H. pylori endemic population and must have had long tern adjustment
which probably may have accounted for the lack of effect on pregnancy
outcomes. It seems H. pylori infection during pregnancy may
with trace element metabolism and contribute significantly to increased
maternal morbidity. This findings need to be confirmed in a well
randomised trial. However, it is suggested that H. pylori
be part of antenatal care to reduce maternal morbidities associated
with H. pylori infection during pregnancy.
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