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ABSTRACT |
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES |
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2 =42.5, P < 0.0001). Similarly, 27 (40.9%) of 66 babies with FM compared with 40 (16.8%) among 238 babies without FM had malaria parasites in the cord blood (2 =17.5, P < 0.001). The means of birth weight, ponderal index, and placenta weight were significantly lower among the babies of mothers with malaria-infected placentae than those without (P < 0.05 in all cases). Lack of antenatal care, primiparity, and failure to have chemoprophylaxis against malaria were the maternal factors found to be associated with placental malaria infection. Placental malaria is a major factor in the etiology of FM in Nigeria. |
INTRODUCTION |
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES |
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The evidence for malaria infection in pregnancy can be obtained from either the density of peripheral parasitemia during pregnancy or placental infection at the time of delivery.1 Parasite densities in placental infections are sometimes difficult to assess with accuracy because there seems to be no correlation between parasite density in peripheral blood and in the placenta in pregnant women with well-developed immunity in malaria-holoendemic regions.1 Thus, the placenta may contain large numbers of infected red blood cells (as many as 65%), whereas the peripheral blood is free from parasites.1 Placental histology alone or in addition to blood films from the placenta could therefore be useful in diagnosing placental malaria.1
FM means failure of a fetus to acquire and/or maintain the normal quantum of fat and muscle mass during intrauterine growth. In FM, the subcutaneous tissues and underlying muscles are diminished and the skin of arms, legs, elbows, knees, and interscapular regions is very loose. These changes may be mainly caused by a disturbance of fetal growth at a later stage and result in asymmetric intrauterine growth retardation/restriction. FM is common in Nigeria and other developing countries,13 and it has been shown to affect body composition and impair brain development and behavior in experimental animals.14–16 It is therefore important to evaluate the factors responsible for FM in any community so that preventive strategies can be mapped out to mitigate the documented associated adverse neurologic effects.14–16 This study to determine the role of malaria in the etiology of FM was conducted in Wesley Guild Hospital, Ilesa, which provides general and specialist care to communities of an ~40-km radius around its Western Nigeria location.
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MATERIALS AND METHODS |
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
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Anthropometric data, birth weight, length, chest circumference, and mid upper arm circumference, of each baby were measured using standard methods.
The nutritional status of each baby was assessed by one of us (OJA) using the Clinical Assessment of Fetal Nutritional Status (CANS) and the score (CANSCORE) as described by Metcoff.16 CANSCORE consists of nine superficial readily detectable signs of FM. This was based on inspection and hands-on estimates of loss of subcutaneous tissue and muscles. Hair, cheeks, neck and chin, arms, back, buttocks, legs, chest, and abdomen were examined and scored. The range of score for each varied between 1 and 4. A maximum score of 4 was awarded to each parameter with no evidence of malnutrition, and the lowest score of 1 was awarded to parameters with the worst evidence of malnutrition. The total rating of the nine CANS signs is the CANSCORE for the subject. The CANSCORE ranges between 9 (lowest) and 36 (highest). Babies with a CANSCORE < 25 were diagnosed as having FM. Babies with a CANSCORE of 
25 were regarded as normal. This assessment of nutritional status was done as soon after birth as possible (usually within 24 hours) and at a time when the clinician was blinded to the malaria status on the blood film and placenta.
The placentae were weighed in grams to the nearest 10 g. Each placenta was held by the cord under running water to wash off blood smears and clots.
From the fresh placenta, multiple aspirations5 were made on the maternal half of the placenta, just below halfway between the maternal and fetal surfaces using a 19-gauge needle attached to a 2-mL syringe. From the aspirates, duplicate thick and thin films were made on clean microscopic slides.
Three biopsies with dimensions of 1 cm3 were also taken from the placentae, from the fetal and maternal surfaces of the placenta in an off-center position, one quarter of the distance from the center to the edge of the placenta. Previous reports have shown that placental pathology in malaria infection is most marked in the middle and lower placental zones.18,19 The biopsies were fixed in 20 mL neutral-buffered formalin and transported to the histopathologic unit of the teaching hospital in Ile-Ife (~35 km away) within a week for processing. The placenta tissues were fixed for 2 months before processing.
The tissue was embedded in paraffin wax and processed using standard techniques. Paraffin sections, 5 µm thick, were stained with hematoxylin and eosin (H&E), Giemsa stain, and the periodic acid-Schiff technique for malaria parasites and pigments. Sections were examined by light microscopy. All placentae were examined by an experienced consultant histopathologist (OEGO) with no prior knowledge of the results of placenta and cord blood smears for malaria parasite and FM status (CANSCORE). Malaria pigment was recognized by its deep brown coarse granular appearance. The intensity of malaria parasitization of the placenta tissue was graded as adapted from Bulmer and others20: 0 =no evidence of malaria parasites or pigments; I, active infection (parasites and pigments in maternal erythrocytes in the intervillous space but no pigment in fibrin or cells within fibrin; II =active–chronic infection (parasites and pigments in maternal erythrocytes in the intervillous space and pigment in fibrin or cells within fibrin); III =past-chronic infection (parasites not present but pigments confined to fibrin or cells within the fibrin).
Thick and thin blood films were also made from the cord blood after the cord was cleaned with 70% alcohol to avoid maternal blood contamination and incised at ~15 cm from its attachment to placenta with a fresh blade. The slides were identified with the identification sample number. All the slides from the placenta blood aspirate and cord blood were made to dry before being stained with Giemsa by the technologists. Microscopic examination was done under a x100 oil-immersion objective by different experienced technologists who were also blind to the outcome of the placenta histology report and the CANSCORE result. Asexual malaria parasites were counted concomitantly with white blood cells (WBC) in each field, and parasites counts were recorded as the ratio of asexual forms per 200 WBC. Parasites densities were calculated by multiplying the number of asexual parasites per 200 WBCs by the average WBC count of the maternal population (for placenta counts) or neonatal population (for cord counts) or where these are not available, by assuming a total leukocyte count of 8,000/µL.5 A minimum of 200 fields were examined for each negative thick and thin smear. The intensity of malaria parasitization in the placenta and the cord blood smear were also graded, as adapted by Sowunmi and others5: I, 1–10 parasites per 100 high power fields (HPFs); II, 11–100 parasites per 100 HPFs; III, 1–10 parasites per HPF; IV, > 10 parasites per HPF.
Data obtained were fed into a computer using EPI Info 6 version 6.02 (1994) software and exported to and analyzed using SPSS for Windows version 11. Means and SDs were determined for continuous variables such as weight, and these were compared between the babies of mothers with evidence of malaria in the placenta with those of the babies of mothers without malaria using analysis of variance and Student t tests. Proportions and percentages were compared using the 2 test. P < 0.05 was taken as statistically significant. Multiple linear regression analysis was also used to determine the (independent) effects of each of the maternal factors of parity, babies anthropometrics measurements, placental parasitemia, placenta malaria, and cord blood malaria on FM.
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RESULTS |
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
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There were 167 (54.9%) boys and 137 (45.1%) girls, giving a male:female ratio of 1.2:1. There were 104 primigravidae and 200 multigravidae. On the whole, 244 (80.3%) of the mothers had antenatal care in various health units. One hundred forty-two (46.7%) mothers regularly (every week) took and 82 (27.0%) occasionally took pyrimethamine antimalaria prophylaxis. Eighty (26.3%) mothers did not take any prophylaxis against malaria.
Malaria parasitemia of samples. One hundred one (33.2%) of the 304 placental blood films and 67 (22.0%) of the 304 cord blood samples were positive for malaria parasites, with the thin blood films showing Plasmodium falciparum infection. Of the 101 positive for placental parasitemia, 72 (71.3%), 24 (23.8%), and 5 (4.9%), respectively, had Grades I, II, and III parasitemia. There was no placenta with Grade IV malaria parasitemia. Similarly, of the 67 cord blood samples that were positive for malaria parasite 63 (94.0%) and 4 (6.0%) had Grades I and II, respectively. None of the cord blood samples had malaria parasite in Grades III and IV. Forty-two (41.6%) of the 101 babies of mothers with placental blood malaria did not have malarial parasites in their cord blood. On the other hand, 8 (3.9%) of 203 babies without placental blood malaria parasite had Grade I cord blood parasitemia.
Fifty-nine (58.4%) of the 101 babies of mothers with placental parasitemia also had cord blood malaria compared with 8 (3.9%) of the 203 babies of mothers without placental blood malaria (2 =116.5, df =1, P < 0.001). Thus, 59 (88.1%) of 67 babies with cord blood malaria were delivered by 101 mothers with placental parasitemia, whereas 8 (11.9%) were delivered by the 203 mothers without.
Factors associated with malaria parasitization.
Significantly higher proportions of the infected placentae and malaria-positive cord blood samples belong to primigravida mothers. Thus, the positive placentae for parasites (active and active-chronic infections) consisted of 53 (51.0%) of 104 primigravidae versus 48 (24.0%) of the 200 multigravidae (2 =22.4, P < 0.001). Also, 35 (33.7%) of the 104 babies of primigravidae had malaria parasites in the cord blood compared with 32 (16.0%) of the 200 babies of multigravidae (2 =12.4, P < 0.001). Seventy-two (29.5%) of the 244 mothers who had antenatal care compared with 29 (48.3%) of the 60 mothers without antenatal care had infected placentae (2 =7.7 P < 0.01). Also, 64 (28.6%) of the mothers who took regular weekly antimalaria prophylaxis compared with 37 (46.3%) of the 80 mothers without routine antimalaria prophylaxis had infected placentae (2 =8.3 P < 0.005). Nineteen (28.8%) of the 66 mothers in higher socioeconomic classes 1and 2 had placental parasitemia compared with 83 (34.9%) of 238 mothers in lower socioeconomic classes 3–5 (2 =0.9 P > 0.25). The mean BMI of the 101 mothers with placental parasitemia was 25.546 ± 4.794 kg/m2 compared with 26.230 ± 4.688 kg/m2 of 203 mothers without placental parasitemia (t =1.19, P > 0.2).
Fetal malnutrition and malaria parasitization.
The frequencies of the presence or absence of placental tissue malaria and parasitemia in mothers of babies with or without FM are shown in Table 1
. The frequency of fetal malnutrition was significantly associated with the presence of infected placentae. For example, 44 (66.7%) and 53 (80.3%) of the 66 babies with FM were delivered by mothers with placental blood film malaria (placental parasitemia) and placental tissue malaria, respectively, compared with 57 (23.9%) and 126 (52.9%) of the 238 without FM (2 =42.5, P < 0.001 and 2 =16.0, P < 0.001, respectively). The frequencies of the grade of placental infections among the mothers with babies with fetal malnutrition are also shown in Table 2. Twenty-six (36.1%) of the 72 babies of mothers with placental blood film malaria with Grade I, 15 (62.5%) of the 24 with Grade II, and 3 (60.0%) of the 5 with Grade III had FM. The corresponding values among babies without FM were 46 (63.1%) of the 72 placental blood film malaria with Grade I, 9 (24.0%) of the 24 with Grade II, and 2 (40.0%) of the 5 with Grade III. Thus, higher proportions of babies with FM were babies of mothers with Grades II and III placenta parasitemia. Also, 39 (59.1%) of the 66 babies with FM had placenta in of active-chronic and past-chronic categories compared with 100 (42.0%) of the 238 babies without FM (2 =6.1, df =1, P < 0.05).
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2 =17.5, df =1, P < 0.001). There were 63 and 4 babies with Grades I and II parasitemia in the cord blood, respectively. Twenty-four (38.1%) of the 63 and 3 (75.0%) of the 4 babies with Grades I and II cord malaria, respectively, had FM, whereas the corresponding figures among babies without FM were 39 (63.1%) and 1 (25.0%). The numbers involved are small, but they indicate that higher proportions of babies with FM had Grade II cord blood malaria.
Measurements and relationship with FM.
Table 3 shows the comparison of the mean anthropometrics and placental weight among the babies with respect to the placenta infection. The means of birth weight, chest circumference, ponderal index, and placenta weight were significantly lower among the babies of mothers with malaria-infected placentae than those without (P < 0.05 in all cases). Multivariate analysis of the data as shown in Table 4 also suggested that parity and presence of malaria have independent significant roles in the etiology of FM, and also in turn, have effects on the anthropometrics data of the babies affected.
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DISCUSSION |
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
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Factors found in this study to be significantly associated with increased placental infection include primigravidarity and failure of mothers to have antenatal care and antimalaria prophylaxis. Also, mothers with placental infections had lower BMI and belonged to lower socioeconomic groups compared with mothers without, although not at a statistically significant level. We, however, noted the higher prevalence of placenta parasitemia among the primigravidae group in this study, a finding consistent with reports of previous studies.1–3,8 The reasons for this are mainly immunity-related factors.1 Non-specific immunosuppression may result from the increased production of steroids in pregnancy. On the other hand, acquisition of a placenta-specific immunity and/or previous exposure to different malaria phenotypes in earlier pregnancies may probably explain the decreased susceptibility to infection in multigravidae compared with primi-gravidae.1,20,25
It is striking that two thirds of the babies of mothers with malaria-infected placentae had FM, which has been shown to have adverse neurologic effects in experimental animals.15 Circulating parasitemia has been said to be uncommon in the newborn. However, the reason for the poor fetal outcomes often encountered has been unclear.26 Reductions in interleukin (IL)-10 concentrations and increases in interferon (IFN)-
, IL-2, and tumor necrosis factor (TNF)-
in the placenta, shifting the balance toward type 1 cytokines, have been implicated.26 Perinatal problems such as hypoglycemia, asphyxia, and/or central nervous system sequelae are known to occur primarily in babies with FM whether appropriate for gestational age (AGA) or SGA but not among those who are simply SGA but not malnourished.16 The long-term effect of FM among babies of mothers with infected placentae may therefore not be immediately known.16 This needs further studies of affected babies.
However, the fact that FM was also found among babies of mothers without infected placentae attests to its multifactorial etiology, which may include factors such as pregnancy-induced hypertension, antepartum hemorrhage, and some maternal infections previously implicated in the etiology of FM.13,27 In this study, even though the mean BMI of mothers with malaria-infected placentae was lower and the mothers also belonged to the lower socioeconomic groups, the difference was not statistically different from mothers with negative placenta blood films.
How may one explain the link clearly established in this study between placental malaria parasitemia and FM? We see that significantly greater percentage of mothers of babies with FM had infected placentae compared with the percentages of mothers of babies without FM (2 =42.5, P < 0.001). Depression of placental function as an organ of fetal nutrition has been hypothesized.1 It is known that mean birth weight of infants born with infected placentae are depressed.5 The reduction of the anthropometric measurements found in this study may thus indicate severe effect of chronic malaria infection on the newborn through the reduction of placental perfusion. The disturbance of intrauterine growth noted in these babies may be caused by both early and late intrauter-ine growth failure. Our findings are similar to the finding of Sowumi and others5 in Ibadan, which may also be similarly explained.
The high prevalence rates of placental malaria and cord blood malaria parasitemia in this study indicate that malaria is a major problem during pregnancy, especially among the primigravidae group. The strong association of FM with in- fected placentae and cord blood malaria parasitemia may imply that malaria infection is a major factor in the etiology of FM in Nigeria. It would seem that it is responsible for both symmetric and asymmetric intrauterine growth retardation/ restriction. The reduction of anthropometric measurements indicates the former, whereas the low CANSCORE recorded in the babies indicates the latter.
Giving the magnitude of the problem of FM and its possible long-term sequelae, efforts must made to reduce FM through provision of antenatal care to all pregnant women to reduce perinatal problems and malaria infections during pregnancy. Antenatal care and regular malaria prophylaxis should be made affordable and accessible to all pregnant mothers. More importantly, consistent global efforts at controlling malaria infection should be pursued.
Received August 4, 2006. Accepted for publication April 30, 2007.
Acknowledgments: We thank Mr. Adeyemi and Ms. Dupe Adediran and all nurses, resident doctors, and consultants in the Paediatrics Department, Wesley Guild Hospital Ilesa unit of Obafemi Awolowo University Teaching Hospital Complex, for various roles in carrying out this research work. The American Society of Tropical Medicine and Hygiene (ASTMH) assisted with publication expenses.
* Address correspondence to O. Joseph Adebami, Department of Paediatrics and Child Health, Ladoke Akintola University of Technology Teaching Hospital, Osogbo 23401, Nigeria. E-mail: segunadebami{at}yahoo.com or ojadebami{at}lautech.edu.ng 
Authors’ addresses: O. Joseph Adebami, Department of Paediatrics and Child Health, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Nigeria. J. Aderinsola Owa, G. Ademola Oyedeji, and O. Akibu Oyelami, Department of Paediatrics and Child Health, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, 220005, Nigeria. G. Olutoyin Omoniyi-Esan, Department of Morbid Anatomy and Forensic Medicine, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, 220005, Nigeria.
Reprint requests: O. Joseph Adebami, Department of Paediatrics and Child Health, Ladoke Akintola University of Technology Teaching Hospital, Osogbo 23401, Nigeria. E-mail: segunadebami{at}yahoo.com.
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
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and TNF-associated with pregnancy outcomes. J Immunol 160: 2523–2530.
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