Effects of Maternal Plasmodium Falciparum Malaria, Anemia and HIV Infection on Fetal Hemoglobin Levels in Nigeria
C Uneke, F Iyare, I Sunday-Adeoye, O Asiegu, K Nwosu, J Ajayi
C Uneke, F Iyare, I Sunday-Adeoye, O Asiegu, K Nwosu, J Ajayi. Effects of Maternal Plasmodium Falciparum Malaria, Anemia and HIV Infection on Fetal Hemoglobin Levels in Nigeria. The Internet Journal of Gynecology and Obstetrics. 2008 Volume 12 Number 1.
Fetal anemia has been described as an important public health issue because it is one of the major risk factors for infant anemia which is a life threatening condition and an important cause of hospital admission in many developing countries. In this study, apparently healthy pregnant women were enrolled at child birth. Maternal malaria parasite microscopy, hemoglobin concentration (HbC), HIV infection and cord HbC were determined using standard techniques. Prevalence rates of maternal peripheral malaria, HIV infection and maternal anemia (HbC<11g/dl) were 16.0%, 3.1% and 17.2% respectively. Prevalence of fetal anemia (FA) (cord HbC<12.5g/dl) was 65.6%. Babies of malaria infected mothers had a higher proportion of FA (72.2%) compared to those of the uninfected mothers (64.2%). The prevalence of FA was higher among babies born by HIV-positive women (83.3%) than those of HIV-negative women (65.0%), and higher among babies born by anemic women (82.6%) than those of the non-anemic women (63.5%), but differences were not statistically significant (
Despite considerable improvement in maternal and infant health care delivery services in many parts of African, making motherhood safer which is one of several child survival strategies applied through antenatal care continues to be particularly challenging. Malaria during pregnancy has been described as one of the most complex and severe medical challenges facing humanity particularly in sub-Saharan Africa, affecting an estimated 24 million pregnant women . Each year between 75,000 and 200,000 infant deaths are attributed to malaria infection in pregnancy globally [1,2]. It has been estimated that about 90% of all deaths attributable to malaria in the world today occur in the sub-Saharan Africa and this is because majority of infections are caused by
The sub-Saharan Africa remains by far the worst-affected region by the global HIV/AIDS epidemic, with 25.4 million people living with HIV (Just under two thirds, i.e. 64% of all people living with HIV) . In the malaria-endemic regions of the sub-Saharan Africa, the effects of HIV on maternal health have been superimposed on that of malaria . Each year in the sub-region, approximately 25 million women become pregnant and are at increased risk of infection with
Beside malaria and HIV infection, anemia in pregnancy is another major public health problem in Africa and has been described as an important factor associated with increased risk for poor pregnancy outcomes in developing countries . Even though malaria and HIV infection are recognized as major causes of anemia in pregnancy in the sub-region [9,10], it is however pertinent to state that the etiology of anemia in pregnancy in the sub-Saharan Africa is complex and multifactorial, being also caused by an iron- and folate deficient diet and infections such as hookworm,
Although documented evidence abound on the impacts of maternal malaria, HIV and anemia on pregnancy outcome in the sub-Saharan Africa, there is however paucity of information on their relationship with fetal anemia. Fetal anemia has been described as common in women with chronic moderate-to-severe iron deficiency anemia; also a severe degree of fetal anemia is reported in several areas where malaria in pregnancy is common . Thus the prevalence of infants born with low cord hemoglobin (fetal anemia) is high in areas where malaria and iron deficiency anemia in pregnancy are common as in the sub-Saharan Africa , and the high rate of maternal infection with HIV in this region further increases the risk of fetal anemia . Fetal anemia has been described as an important public health issue because it is one of the major risk factors for infant anemia which is a life threatening condition and an important cause of hospital admission in many developing countries [15,16,17].
The objective of this study therefore was to evaluate the effects of maternal malaria, HIV infection and anemia on fetal anemia with the view to providing scientific information that is relevant to policy development and control program implementation as it relates to the overall maternal, fetal and infant wellbeing in Nigeria and other developing tropical nations threaten by both malaria and HIV infection.
Materials and Methods
This study was conducted in Abakaliki the capital of Ebonyi State in South Eastern Nigeria, from June 2006 to December 2006 at the Ebonyi State University Teaching Hospital (EBSUTH), Abakaliki, which is the largest health facility in this region. The climatic condition of the area is characterized by two distinct seasons, the wet and the dry seasons, the former takes place between April and October, while the latter occurs from November to March. Malaria transmission in the area is perennial but usually at the peak towards the end of the rainy season.
The study protocol was approved by Department of Medical Microbiology/Parasitology, Faculty of Clinical Medicine, Ebonyi State University, Abakaliki, Nigeria. Ethical approval was obtained from the Ethical Committee of the EBSUTH, Abakaliki. All work was performed according to the international guidelines for human experimentation in clinical research .
Study Population/Sampling Technique
Pregnant women who fulfilled the following study inclusion criteria were enrolled into the study: (i) attended the antenatal clinic at EBSUTH, (ii) had an uncomplicated pregnancy greater than 32 weeks’ gestation (based on the fundal height estimation), (iii) reside in Abakaliki or neighbouring local government areas, (iv) had no obvious clinical evidence of malaria (asymptomatic), and (v) had no known underlying chronic illness. Shortly before child birth informed consent was obtained from each participant and about 5ml of the maternal peripheral blood, was obtained from each participant by venepuncture technique into sterile EDTA container for laboratory analysis. Immediately after childbirth, about 5ml of cord blood was obtained technique into sterile EDTA container for laboratory analysis.
Each maternal blood sample was analyzed for malaria parasite infection by performing the microscopy of Giemsa-stained thick and thin blood films. The Plus System was used for the determination of parasite density as previously outlined . All the films were double checked blindly by experienced parasitologists and if there were differences an additional assessment was made by another observer, and the average of the two agreeing counts using the Plus System was recorded. Parasitaemia was graded as 1-10 parasites per 100 thick film fields (‘+’ or 4-40 parasites per mm3), 11-100 parasites per 100 thick film fields (‘++’ or 41-400 parasites per mm3), 1-10 parasites per single thick film fields (‘+++’ or 41-400 parasites per mm3) .
The HIV Tri Line Test kits, commercially available (Biosystem INC, Vienna Austria) were first used to screen each maternal serum sample which was separated from the blood, to detect antibodies to HIV-1 and HIV-2. Thereafter the HIV-seropositive samples were confirmed by immunoblot analysis using the BIORAD New Lav Blot kits, commercially available (Bio-Rad Novapath Diagnostic Group US, Oxnard CA.). Manufacturer’s instructions were strictly followed to determine the sero-status of the samples.
The haemoglobin concentration (HbC) was determined to assess maternal and fetal anemia using the cyanmethaemoglobin method described previously ; reading was done using a spectrophotometer (Bayer RA 50). The WHO definition of anemia in pregnancy i.e., haemoglobin concentration Hb<11g/dl , and fetal anemia defined by Hb<12.5 g/dl [13,17] were adopted in this investigation.
All the analysis was done at the Research Laboratories of Departments of Medical Microbiology and Chemical Pathology of Ebonyi State University, Abakaliki.
Percentage prevalence rates were calculated with their respective 95% confidence intervals. Difference between proportions were evaluated using the chi-square tests. Statistical significance were achieved at
A total of 300 women at full pregnancy term, comprising of 89(29.7%) primigravidae and 211(70.3%) multigravidae were studied and of these, 48(16.0%) had malaria parasite in their peripheral blood.
The prevalence of fetal anemia was 65.6%. The primigravidae had slightly higher proportion of babies with fetal anemia (67.5%) than the multigravidae (65.0%), the difference was also not statistically significant (Chi-square =0.09, df=1,
A high level of fetal anemia (65.6%) defined by cord blood Hb<12.5g/dl, was observed in this study. This was consistent with an earlier report which indicated that the prevalence of fetal anemia was high in developing countries particularly in malarious areas . In two separate studies conducted in Southern Malawi, a fetal anemia prevalence of 23.4%  and 23.3%  were recorded, while in Maputo Mozambique, up to 93% of newborns were found to have fetal anemia . These findings were contrary to those obtained from developed countries where it was shown that anemia in newborns is rare, regardless of maternal status . In most parts of the sub-Saharan Africa where malaria is endemic, cord hemoglobin levels have been described as lower-than-expected, and it was hypothesized to result from fetal immune activation to maternal malarial antigens . Thus it was suggested that exposure of the fetus to malaria antigens due to damage of the placental barrier may make the newborn more susceptible to immunologically mediated hemolysis or to dyserythropoiesis .
In this study, the prevalence of fetal anemia was higher among babies born by malaria infected mothers compared to those of the uninfected mothers, although the difference was not statistically significant (
Maternal anemia was not significantly associated with fetal anemia (
Furthermore it was argued that the maintenance of cord hemoglobin levels despite the presence of maternal anemia appeared to suggest that the fetus has developed mechanisms to preferentially obtain sufficient iron and produce adequate amounts of red cells, since it was long shown that iron is transported unidirectionally from mother to foetus across a concentration gradient , and thus stores should be preferentially preserved in the fetus . However, mounting evidence indicates that maternal iron deficiency in pregnancy reduces fetal iron stores, perhaps well into the first year of life and this deserves further exploration because of the tendency of infants to develop iron deficiency anemia and because of the documented adverse consequences of this condition on infant development . Therefore because of a wide range of unanswered questions about the mechanisms involved in the relationship between maternal anemia and fetal anemia, further studies using molecular biological tools are urgently needed to properly elucidate this in the sub-Saharan Africa.
In this present study, the prevalence of fetal anemia was considerably higher among babies born by the HIV-positive mothers compared to those of the HIV-negative mothers. Although there is paucity of published data on the relationship between maternal HIV infection and fetal anemia in sub-Saharan Africa, an available report from Western Kenya, indicated that maternal infection with HIV was a major risk factor to fetal and infant anemia not only directly, through mother-to-child transmission of HIV, but also indirectly, as suggested by the finding that infant anemia was worse in HIV-uninfected infants when born to HIV-seropositive mothers compared with those born to HIV-seronegative mothers .
In conclusion it is imperative to state that a major limitation to this study was our inability to evaluate other potential causes of fetal anemia including blood loss (through obstetrical causes and internal hemorrhage) and red blood cell destruction (through intrinsic and extrinsic causes). This may have affected adequate assessment of the effects of maternal malaria, HIV infection and anemia on the fetal anemia. The inclusion of these factors in future studies is advocated. Another limitation worth mentioning was the use of microscopy technique for the screening of maternal malaria. Although this method is arguably the “gold standard”, it is important to note that the possibility of under-diagnosis cannot be completely ruled out. However, because of the public health significance of fetal anemia and other adverse perinatal outcomes associated with maternal malaria, anemia and HIV infection in pregnancy, the importance of effective interventional effort cannot be overstated. Interventions should aim to reduce fetal anemia by improving malaria, HIV infection and anemia control and treatment in pregnancy and by addressing the determinants of pre-term delivery as this may also affect fetal haemoglobin levels .
It has been suggested that improving antimalarial control and iron supplementation throughout pregnancy should have direct effects on reducing fetal and infant anemia and improving child development and survival . Antiretroviral regimens can also improve the health of HIV-positive pregnant women and reduce fetal anemia. The WHO guidelines currently recommend highly active antiretroviral therapy (HAART) using the combination of nevirapine, lamivudine,and either stavudine or zidovudine for HIV-infected pregnant women with clinical or laboratory evidence of immunosuppression . There is the need for the integration of the delivery of malaria, anemia and HIV interventions within existing health services in the sub-Saharan Africa, particularly through the antenatal care services as this may permit effective utilization of human resources and address serious resource constraints.
Authors are grateful to the Management of the Ebonyi State University Teaching Hospital for logistic support.