Malaria in pregnancy in sub-Saharan Africa: Relationships with mothers

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Malaria in pregnancy in sub-Saharan Africa
Relationships with mothers anemia and their
infants birth weightMohamed Ag Ayoya, MD, PhD
CandidateCornell University, Ithaca, NY 14850
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Introduction Malaria is the
worlds most important parasitic infection,
ranking among the major health and developmental
challenges for the poor countries of the world
(Sachs et al., 2002). More than a third of the
worlds population (about 2 billion people) lives
in malaria-endemic areas. In Africa alone there
are an estimated 200-450 million cases each year
(Philippe et al., 2002). In sub-Saharan Africa
countries, where stable transmission is common,
Plasmodium falciparum malaria is the most
important parasitic disease (Marchant et al.,
2002).
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The main objective of this paper is to describe
the relationships between malaria infection
during pregnancy, and womens anemia and their
infants weight at birth in sub-Saharan
Africa.The hypotheses to be tested are that
1) pregnant women with
malaria infection have a poorer iron status
compared to those without malaria 2) children
born to women who have had malaria infection have
a lower birth weight compared to those born to
women who have not had malaria.
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Background1. Definition of
malariaMalaria is an infectious disease caused
by protozoan organisms of the genus Plasmodium
(falciparum, ovale, vivax, malariae). It is
characterized by high fever and erythrocytic
infection resulting in anemia. In pregnant women,
it causes a placental infection that impacts the
fetus development.
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2. Definition of anemiaAnemia is defined as
hemoglobin (Hb) concentration below 2 standard
deviations of the age- and sex- specific
reference. The most commonly used cut-off for
anemia is Hb lt 110 g/L for pregnant women (Yip,
2001). Unless stated otherwise, anemia in this
paper will be referred to a Hb level less than
110 g/L and iron deficiency will be referred to a
serum ferritin level lt 12 µg/l.
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3. Definition of LBWThe World Health
Organization (WHO) defines LBW as a birth weight
lt 2500g (WHO,1970). LBW infants include both
those who are preterm (lt37 weeks gestational age)
and those who are small for their gestational age
(lt 10th percentile for gestational age)
(Rasmussen, 2001). This paper will consider both
definitions.
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4. Malaria, iron deficiency, anemia and LBW The
major consequences of malaria during pregnancy
are maternal anemia and reduced birth weight of
the newborn. It has been postulated that malaria
might contribute to iron depletion through
decreasing intake during malaria-induced
anorexia, reducing absorption and causing iron
loss through haemoglobinura, but these factors
have never been quantified (Menendez et al.,
2000). Iron deficiency and malaria both coincide
in several anemic subjects, and anemia is also
taught to be associated with LBW. It has been
postulated that malaria might contribute to iron
depletion (Menendez et al., 2000), and iron
depletion contributes to anemia.
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Conceptual framework to analyze the literature
findingsThe conceptual framework (malaria - iron
deficiency anemia - LBW) used in this review is
adapted from Rasmussen (Rasmussen, 2001) and
Elder (Elder, 2000) and is presented in the annex
(figure 1). It shows that malaria during
pregnancy could lead to anemia either directly or
via iron deficiency. Malaria could also lead to
LBW through placental infection or through
malaria-related anemia. In the discussion
section, I will look at other possible
determinants of iron deficiency, anemia and LBW
in sub-Saharan Africa other than malaria, and
assess if these have been taken into account in
the design and analysis of the studies described.
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Methodology used to collect informationTo
identify articles for this paper, Index Medicus
was searched electronically using Medline
citations in English. Malaria, pregnancy and,
sub-Saharan Africa were used as search terms
along with the following outcomes of interest
iron deficiency, anemia and LBW.The articles
obtained were grouped into four categories those
establishing an association between maternal
malaria infection and iron deficiency, and/or
anemia those establishing an association between
anemia and LBW those establishing an association
between malaria infection and LBW and those
establishing a causal association between any of
these factors.
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ResultsThere is a
large literature that reviews the impact of
malaria in pregnancy on maternal and birth
outcomes (Brabin, 1983 and 1991 Steketee et al.,
1996a). The parity pattern of malaria
susceptibility in highly endemic areas (whereby
primigravidae and, to a lesser extent,
secundigravidae are more affected than other
parities) has been well established (McGregor et
al., 1983). The tendency of Plasmodium falciparum
parasites to invade the placenta in semi-immune
women has been described also (Bray et al.,
1979). Regardless of the level of endemicity, the
main effects of malaria during pregnancy are
maternal anemia and reduced birth weight of the
newborn (McGregor, 1987 Meuris et al., 1993).
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1. Malaria and iron deficiency or anemia during
pregnancyIron deficiency affects mostly young
children and pregnant women, the same populations
who suffer the bulk of the morbidity due to
malaria (Shankar, 2000). During acute malaria,
iron is mobilized in haemazoin complexes and
intestinal iron absorption is reduced (Brabin,
1992) resulting in iron deficiency and then in
anemia.
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In contrast with the studies above, Matteelli et
al. (1994) in a cross-sectional study conducted
in an urban area of Zanzibar, Tanzania found that
the proportion of women with anemia was similar
in those with (85) and without (80) malaria
infection. But, when primigravidae were
considered alone, malaria infection was
significantly more frequent among anemic women
(65.2) than in those with normal Hb values
(40), and malaria was significantly associated
with anemia in this group with an odds ratio of
3.2 (95 confidence interval1.1-9.6 Plt0.05).
In the same country, but in a different
municipality, anemia was found in 95 of pregnant
women and was predominantly due to iron, folate
and B12 deficiencies (Msolla et al., 1997).
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In Ghana, Mockenhaupt et al. (2000) found out of
530 pregnant women that 54 were anemic (Hb lt 110
g/L) and 63 harboured malaria parasites at
predominantly low numbers. Ferritin levels were
considerably influenced by malaria and
inflammatory processes (CRP gt 0.6
multigravidae/dL). The prevalence of iron
deficiency, depending on the definition applied,
ranged between 5 and 46.
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2. Anemia and LBWTo identify risks
associated with teenage pregnancy, 704 teenagers
out of 4,649pregnant women were followed in an
antenatal clinic of Ibadan, Nigeria (Onadeko et
al., 1996). The investigators observed a
significantly higher proportion of LBW infants
and anemia (51 with Hb lt 11g/L) in teenage
mothers compared with those with normal levels
(35.5 with Hb gt 11 g/L).
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3. Placental malaria and LBW The
studies, whose results are presented below,
covered a range of malaria endemicities and both
rural and urban areas. A study conducted in
Malawi (Steketee et al., 1996b) found a
difference in the incidence of LBW between women
with and without placental malaria (diagnosed by
placenta smear) of 7.6 in primigravidae, 10.1
in secundigravidae and 7.4 in women of gravidity
3 or more.A prospective study of primigravidae
women attending an antenatal clinic in Malawi
found that among 178 singleton deliveries, 35 of
infants were preterm or had IUGR (Sullivan et
al., 1999).
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A study in Tanzania (Menendez et al., 2000)
assessed the effects of placental malaria-related
changes on birth weight and gestational age in
1,177 mothers and their newborns. The authors
found that massive mononuclear intervillous
inflammatory infiltration was associated with
increased risk of LBW (OR 4.0), whereas
maternal parasitized red blood cells and
perivillous fibrin deposition both were
associated independently with increased risk of
preterm delivery (OR 3.2 OR 2.1
respectively).
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In Kenya, the effects of malaria on pregnancy
outcomes were measured among 912 women who
delivered in Kilifi district hospital (Shulman et
al., 2001). The authors performed placental
histology to assess the prevalence of active or
past malaria and its association with anemia and
LBW. They found a high prevalence of active or
past malaria in all gravidities, ranging from 64
in primigravidae to 30 in gravidities 5 and
above. In gravidities 1-4, active malaria
infection was associated with severe maternal
anemia, adjusted OR 2.21 (95 CI, 1.36-3.61).
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The possible impact of placental malaria
infection on infant mortality through reduced
birthweight was modeled by analyzing several
studies (Guyatt et al., 2001). The authors found
that the proportion of LBW associated with
infected and uninfected placentas for
all-parities (primigravidae and multigravidae)
was higher in those with infected placenta than
in those without. The overall proportions with
LBW were higher for primigravidae than
all-parities, but a similar relative difference
was observed in the median values between
infected (0.320, 0.280-0.360) and uninfected
(0.160, 0.065-0.235) placentas (P 0.001).
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4. Impact of malaria prevention interventions on
the adverse consequences of malaria in pregnancy
(causal inferences)The main interventions aimed
at the prevention of malaria and its consequences
in pregnancy have been anti-malarial
chemoprophylaxis taken during pregnancy and the
use of insecticide-treated bednets (ITBN).
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The studies that looked at the effect of
placental malaria on LBW suffer more or less from
the same weaknesses. In some of them, the
investigators either did not control for any
confounding factors (Menendez et al., 2000) or
did for few of them such as seasons (Sullivan et
al., 1999 Moormann et al., 1999) HIV (Stekettee
et al., 1996a Verhoeff et al., 2001 Shulman et
al., 2001) hypertension, socio-economic status,
education and maternal height and weight (Shulman
et al., 2001) maternal weight and maternal
syphilis infection (Stekettee et al., 1996a).
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Evidence for the importance of malaria as a
contributor to LBW, iron deficiency, and anemia
comes from randomized controlled trials of
interventions directed against malaria such as
antimalarial drug chemoprophylaxis and ITBNs
studies. While those conducted on
chemoprophylaxis (Steketee et al., 1996a
Steketee et al., 1996a Mutabingwa et al., 1993
Parise et al., 1998 Fleming et al., 1986,
Shulman et al., 1999 Salihu et al., 2000) seem
to agree on the impact on malaria infection,
those on ITBNs findings (DAlessandro et al.,
1996 Browne, 1997 Shulman et al., 1998
Marchant et al., 2002) are contradictory.
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Most of the data on malaria, LBW, iron deficiency
and anemia presented in this paper are
facility-based (clinics or hospitals), therefore
it is unclear whether the probability of the
infections outcomes at facilities would be
higher than within communities. As those who
attend these facilities might be more
privileged, the prevalence of malaria and LBW
may not be representative of the community as a
whole.
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VII. Conclusions Malaria during
pregnancy is highly prevalent in sub-Saharan
Africa. Its main cause is Plasmodium falciparum.
Iron deficiency and anemia related to malaria are
shown to be prevalent in several countries. Low
birth weight, maternal iron deficiency and anemia
during pregnancy are associated with malaria but
these associations (though shown significant in
several studies) should not be interpreted as
always causal given the other factors that could
impact these outcomes.
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Malaria still remains an important public health
problem in the region and negatively impacts
childrens and pregnant womens health. A
multifaceted approach directed both towards
prevention and treatment of malaria and other
socio-economic and political factors (education,
poverty, health infrastructures, political
commitment and collaboration between scientists
and policy-makers etc.) would be more efficient
in the control of the disease and its adverse
effects on maternal and child health. Therefore,
there is a need to explore new other control
strategies to prevent malaria in these high risk
groups.
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