الخلاصـة: بغية استقصاء نتائج الإصابة بالملاريا في أواخر الحمل، أجرى الباحثان دراسة مبدئية في مستشفيين في محافظة الحديدة، على 276 امرأة وَلَدْنََ ولادات مهبلية دون مضاعفات. وكانت 17 امرأة فقط من بين هؤلاء مصابات بالملاريا (المتصورة المنجلية Plasmodium falciparum)، ستٌّ منهـن وجـدت فيهن الطفيليات في الدم و11 وجدت فيهن الطفيليات في الدم إلى جانب الملاريا المشيمية. وقد مثلت العدوى العارضة اختطاراً يزيد بمقدار 9.44 ضعفاً لحدوث ولادات مبتسرة، واختطاراً يزيد بمقدار 12.2 ضعفاً لنقص وزن الجنين (<2500 غ). وقد شخصت الإصابة بفقر الدم في 46.4% من الحالات، وكانت مرتبطة بالملاريا في 11.7% منها، وكانت جميع عوامل الاختطار، كالإقامة في المناطـق الريفية (نسبة الأرجحية 5.18)، وعمـر الأم <20 سنة (نسبة الأرجحية4.39) والحمل الأول (نسبة الأرجحية 8.29) جميعها مرتبطة بشكل كبير بعدوى الملاريا.

ABSTRACT: To investigate the consequences of maternal malaria during late pregnancy, we conducted a preliminary study in the 2 hospitals in Al Hodeidah on 276 women who had uncomplicated vaginal deliveries. Only 17 women had malaria (Plasmodium falciparum), 6 with peripheral parasitaemia and 11 with both peripheral parasitaemia and placental malaria. Coincident infection carried a 9.44 times higher risk of preterm delivery and a 12.2 times greater risk of low birth weight (< 2500 g). Anaemia was diagnosed in 46.4%, associated with malaria in 11.7 % of cases. All risk factors, rural residence (OR 5.18), maternal age < 20 years (OR 4.93) and primigravidae (OR 8.29), were significantly associated with malaria infection.

Le paludisme en fin de grossesse dans le Gouvernorat d’Al Hodeidah (Yémen)

RÉSUMÉ: Afin d’examiner les conséquences du paludisme maternel durant le dernier trimestre de la grossesse, nous avons réalisé une étude préliminaire dans les deux hôpitaux de Al Hodeidah sur 276 femmes qui avaient eu un accouchement par voie basse sans complications. Seules 17 femmes avaient le paludisme (Plasmodium falciparum), 6 présentant une parasitémie périphérique et 11 ayant à la fois une parasitémie périphérique et un paludisme placentaire. La présence concomitante de ces deux paramètres d’infection comportait un risque 9,44 fois plus élevé d’accouchement prématuré et un risque 12,2 fois plus élevé de faible poids de naissance (< 2500 g). Une anémie a été diagnostiquée chez 46,4 %, en association avec le paludisme chez 11,7 % des cas. La résidence rurale (OR 5,18), l’âge de la mère inférieur à 20 ans (OR 4,93) et le statut de primigeste (OR 8,29) étaient les facteurs de risque significativement associés à l’infection paludéenne.

¹Department of Tropical Health, High Institute of Public Health, University of Alexandria, Alexandria, Egypt (Correspondence to H.K. Bassiouny: h_k_bassiouny@hotmail.com).
²Department of Medical Parasitology, Faculty of Medicine, University of Sana’a, Sana’a, Yemen

 

Introduction
 

Malaria is a priority public health problem in Yemen. The problem has become more acute with the emergence of Plasmodium falciparum strains resistant to chloroquine. About 60% of the total population of 20 million is at risk [1]. The estimated number of cases was up to 3 million in the year 2000, more than 90% of them P. falciparum malaria. Anopheles arabiensis is the main vector of transmission [2].

Falciparum malaria is known to adversely affect the feto-placental unit, especially during the last trimester, and LBW babies born to mothers with malaria infection are probably the product of a pathological process [3]. Malaria infection affects birth weight through placental hyperparasitism [4] or indirectly through malaria-   induced maternal anaemia [5].

In Yemen, mothers and children constitute a priority group. Together they form nearly two thirds of the total population [6]. Yemen is experiencing very rapid population growth compared with other developing countries: women marry by 15 years of age and conceive during their teenage years [7]. Maternity care is still minimal. High maternal (100/10 000 live births, 1991) and infant (78.8/1000 live births, 1998) mortality rates have been recorded [8].

In neonates, the mortality rate of Yemeni infants considered by their mothers to be smaller than average at birth was nearly 3 times that of infants estimated to be normal sized at birth. In early childhood, it was still 1.5 times that of infants considered normal sized at birth [7]. The overall rate of low-birth-weight infants (birth weight < 2500 g) in Yemen was 47% in 1994 [8].

Malaria infection in pregnancy has not previously been studied in Yemen. In particular, there is no data in terms of its impact on the health of both mother and baby. Clinical observations have indicated that symptoms are more severe in mothers, but little is known about the effect of placental malaria on the newborn baby.

We conducted a preliminary study in Al Hodeidah governorate in order to investigate the consequences of maternal malaria during late pregnancy and the effect of placental malaria on survival and morbidity of neonates. This information will help in the formulation and implementation of a malaria control strategy for pregnant women in Yemen.

Methods
 

The study area was Al Hodeidah governorate in western Yemen. According to the 1998 census, this area is inhabited by 10% of the total Yemeni population.

We conducted a cross-sectional descriptive study on all women who had uncomplicated vaginal deliveries in the labour wards of the 2 hospitals in the study area, Al Thawra (n = 227) and Asalakhana (n = 49), during March–August 2001. After consent was obtained from the mothers, they were interviewed by the supervising physician in the labour ward. Data concerning personal and obstetric history, the current pregnancy and pregnancy outcome were collected.

A peripheral maternal blood smear was made by finger prick. A cord smear was prepared from the blood of the umbilical stump. A placental smear was taken from the blood on the maternal side of the placenta after an incision had been made. Duplicate thin and thick blood films were stained with Giemsa stain and examined microscopically for malaria parasites. Parasites were counted against 200 leukocytes and expressed as number of parasites/µL blood, assuming a standard leukocyte count of 8000/µL blood [9]. A second investigator, blind to the initial results, rechecked all positive and 10% of randomly chosen negative slides. Maternal haemoglobin (Hb) level was measured using the cyanmethaemoglobin photometric method [10]. Haemoglobin concentration ≥ 10g/dL was considered normal [11]. Packed cell volume was estimated by the microhaemocrit centrifugation method. The red blood cell count (× 106/µL) was also done by automated blood counting and blood indices calculated [10].

Birth weight was measured soon after birth using digital scales.

All questionnaires were reviewed prior to computer data entry. Data were analysed using SPSS, version 9.0. Proportion was used to present qualitative data. Geometric mean and standard deviation were used for calculating quantitative data such as parasite density and blood parameters and indices. To compare proportions and to estimate the difference in risk between groups, odds ratios and 95% confidence intervals were calculated. For comparison of mean blood parameters and indices of malaria infection, analysis of variance was applied followed by least significant difference. P-value < 0.05 was used as indicator of statistical significance.

Results
 

Table 1 shows some demographic and medical data about the mothers and neonates in this study. Of the 276 pregnant women who participated in the study, 23.9% were from rural areas, 29.7% were under 20 years old at the time of the study, 46.0% had given birth before the age of 20 years and 80.8% were married when they were under 20 years old. Most of the study participants (85.5%) were housewives, 29.0% were primigravidae and 90.2% had full term deliveries (> 37 weeks).
 

Coincident infection was found in 8/11 women from rural areas (72.7%) and 3/11 women from urban areas (27.3%). Prevalence of primigravidae was 54.5% in the women from rural areas and 9.1% in those from urban areas (data not shown in tables).

No anti-malarial drugs had been given for 73.6% of the women, either for treatment or prophylaxis, and 34.4% had not visited antenatal care clinics during the current pregnancy.

All babies were live singleton deliveries. Twenty-nine of them were of low birth weight (LBW) (< 2500 g). Only 17 (6.2%) of the women had malaria, 6 with peripheral parasitaemia alone and 11 with both peripheral parasitaemia and placental malaria. Cord parasitaemia was not detected. P.  falciparum was the only recorded parasite species. Anaemia (Hb < 10 g/dL) was diagnosed in 46.4% of the women in the study.

Analysis of potential risk factors predisposing to malaria infection among pregnant women revealed that all were significantly associated with malaria infection in the study participants (Table 2). Malaria was significantly more prevalent among participants from rural areas and they were at a 5.18 times greater risk than those from urban areas (P < 0.05). Participants in the age group < 20 years showed a 4.93 times higher estimated risk of infection than those in the age group 20–34 years (P < 0.05). Primigravidae had an 8.3 times greater risk of infection than secundigravidae (P < 0.05).
 

Malaria infection and parasite density were associated with maternal anaemia. Pregnant women with coincident infection (both peripheral parasitaemia and placental malaria) had a 28.42 times higher risk of maternal anaemia and a 9.44 times greater risk of preterm delivery. They also had a 12.15 times greater risk of having LBW babies than aparasitaemic women (Table 3) (P < 0.05).
 

Similarly, a high parasite density  (≥ 1000 parasites/µL blood) carried a 22.27 times higher estimated risk of maternal anaemia, a 14.17 times greater risk of preterm delivery and a 9.45 times higher estimated risk of having LBW babies than women who were aparasitaemic (Table 4) (P < 0.05).


 

Of the 276 women who participated in the study, 128 (46.4%) were anaemic (Hb < 10 g/dL), 15 of whom (11.7%) also had malaria parasitaemia. There were 148 (53.6%) non-anaemic women, 2 (1.4%) of whom were parasitaemic (Table 5). Anaemia and parasitaemia in mothers had an effect on gestational age at birth and on birth weight.

Of the 27 women who had preterm deliveries, 22.2% were parasitaemic and anaemic. They had a 3.30 times higher risk of preterm delivery than the women who were aparasitaemic but anaemic (P > 0.05). Similarly, women who were parasitaemic but non-anaemic had an 18.00 times higher risk of preterm delivery than those who were aparasitaemic and non-anaemic (P > 0.05).

Of 80 women who had LBW babies, 11.2% were parasitaemic and anaemic and had a 3.08 times higher risk of delivering LBW babies than the women who were aparasitaemic but anaemic (P > 0.05). Similarly, women who were parasitaemic but non-anaemic had a 3.42 times higher risk of having LBW babies than those who were aparasitaemic and non-anaemic (P < 0.05) (Table 5).
 

The effect of malaria infection on blood parameters and indices is shown in Table 6. Microcytic hypochromic anaemia was the predominant type of anaemia among the women infected with malaria. Those with peripheral parasitaemia alone had a mean haemoglobin level of 9.8 g/dL. This was only 6.4 g/dL in women who had peripheral parasitaemia associated with placental malaria, significantly lower than that observed among the aparasitaemic group (11.2 g/dL) (F = 63.3; P > 0.05). All other blood parameters followed the same pattern. The mean red blood cell count for women with coincident infection (2.9 × 106/µL) was much lower than in those who had peripheral parasitaemia alone or were aparasitaemic.
 

Discussion
 

Of the 276 women investigated in our study, 17 (6.2%) had the malaria parasite (P. falciparum) in their peripheral blood. This low prevalence could be an outcome of many interacting factors. Anti-malarial drugs, mostly chloroquine, had been given to 26.4% of the women during the current pregnancy. Also, 34.4% had not visited antenatal care clinics during their pregnancy. Thus they missed out on antenatal care, which has a beneficial impact on mothers and their babies, either through the diagnosis and treatment of malaria infection and other complications of pregnancy or by reducing the modifiable risk factors associated with pregnancy. The low prevalence could also be related to the fact that our study was conducted on a select group of women with uncomplicated vaginal deliveries. Finally, the sample size was relatively small (276 participants) as most Yemeni women prefer to have their babies either at home, supervised by trained midwives, or in private hospitals [12].

Our findings indicate that primigravidae, maternal age less than 20 years and rural residence are potential risk factors predisposing to malaria infection. The risk of malaria infection decreased as gravidity increased, prevalence was highest in primigravidae, who had an 8.3 times greater risk of infection than secundigravidae, confirming the high vulnerability of this group in malaria endemic regions [13]. Maternal malaria has the most evident impact during first pregnancies, becoming less severe during second and subsequent ones [14]. The increased susceptibility of primigravidae to malaria has been attributed to immunosuppression [15] or sequestration of infected red blood cells in the placenta through binding to chondroitin sulfate A in the placenta syncytiotrophoblast [16]. Conversely, several mechanisms underlying increased resistance of multigravid women to the severe effects of malaria have been proposed. These include the presence of agglutinating antibodies against a wide range of placental parasite isolates in sera of multigravid women [17] and the existence of a sub-population of P. falciparum parasites that specifically bind placental chondroitin sulfate A with development of antibodies against the chondroitin sulfate A-binding parasites in multigravid women [18].

Maternal age was the second risk factor examined in our study. Pregnant women under 20 years of age had a 4.93 times higher estimated risk of malaria infection than those in the age group 20–34 years. This finding confirms the observation of the World Health Organization which reported that those who get pregnant before the age of 18 years may have a 5-fold higher risk of pregnancy-related complications than women who get pregnant when aged 20–25 years [19].

We also investigated the effect of residential area. Rural areas have environmental conditions more favourable to trans- mission of the disease than urban areas. We found that malaria was more prevalent among pregnant women from rural areas and they were at a 5.18 times greater risk than those from urban areas.

Cord parasitaemia was not recorded in our study, in agreement with the view that congenital malaria is rare, even in malaria-endemic areas such as sub-Saharan Africa, where prevalence varies from 0% to 23% [20].

Coincident infection of peripheral parasitaemia and placenta malaria occurred in 64.7% of malaria-infected women in the study area, compared to 75.5% recorded in Tanzania [21]. On the other hand, a lower percentage (18.5%) was reported in Sierra Leone [4]. Moreover, the prevalence of coincident infection from rural areas was greater than that reported from the urban area. Prevalence of primigravidae in women from rural areas was greater than in those from urban areas. This could indicate hyperendemicity in the rural areas and mesoendemicity in the urban areas.

Our study shows a strong association between coincident infection and both preterm delivery and LBW babies. The risk for preterm delivery was 9.44 times greater and for having a LBW baby risk was 12.2 times greater. This is in agreement with the observation of Morgan who reported that placental infection affects fetoplacental function, which in turn, affects fetal growth and/or prematurity [4].

The impact of placental malaria-related changes on gestational age and birth weight has also been studied by Menendez et al. [21] in Tanzania and Sullivan et al. [22] in Malawi. They reported that birth weight may be affected via placental insufficiency, which leads to intrauterine growth retardation. They observed that massive mononuclear intervillous inflammatory infiltration was associated with increased risk of LBW. Parasitized maternal red blood cells and perivillous fibrin deposition were independently associated with increased risk of premature delivery.

Anaemia in pregnancy has become a common clinical problem in many developing countries [23]. It has been reported to contribute significantly to maternal mortality [24] and to both maternal and fetal morbidity [25]. In our study, coincident infection had a significantly higher risk of inducing maternal anaemia by reducing the haemoglobin concentration. Also, the parasitaemic, anaemic women had a 3.3 times higher risk of preterm delivery compared to those who were anaemic but aparasitaemic. Similarly, the women who were parasitaemic but non-anaemic had an 11.6 times higher risk of preterm delivery than those belonging to aparasitaemic non-anaemia group. The same pattern is true with LBW babies. The women who were parasitaemic and anaemic and those who were parasitaemic but non-anaemic had a 3.1 times higher risk of having LBW babies than those who were aparasitaemic anaemic and a 3.4 times higher risk than those who were aparasitaemic but non-anaemic. Thus, we can conclude that in malaria-endemic areas  such as Al Hodeidah governorate, malaria infection is a more important risk factor for both preterm delivery and LBW babies than anaemia, and indirectly influences neonatal mortality. Our findings support the observation of Brabin and Piper, who concluded that malaria infection was a more important risk factor for LBW than maternal anaemia [26].

The causes of maternal malarial parasitic anaemia are multifactorial and cannot be explained simply by the direct destruction of parasitized red blood cells at the time of release of merozoites [27], but include inhibition of erythropoiesis [28], loss of infected red blood cells in the spleen [29] and elevated levels of tumour necrosis factor α in the placenta [18]. In addition persistent low-grade parasitaemia leads to persistent haemolysis, reticulocytosis and megaloblastosis because of folic acid deficiency [30].

We found that maternal anaemia in general was extremely common; 46.4% of the participants were anaemic. In 11.7% of these, the anaemia was associated with malaria parasitaemia, indicating that P. falciparum infection is an important cause of anaemia in pregnant women.

The findings also revealed that microcytic hypochromic anaemia was the predominant type of anaemia among pregnant women infected with malaria. The severity of anaemia increased when peripheral parasitaemia was associated with placental malaria, indicating that anaemia during pregnancy is most often believed to result from nutritional deficiencies, especially iron deficiency [31]. However, folate deficiency, vitamin A deficiency and vitamin B12 deficiency have all been found to contribute to anaemia [32–34]. Thus, the etiological factors responsible for anaemia in pregnancy are multiple and their relative contributions can be expected to vary by geographical area. Knowledge of the relative importance of the different causes should form the basis for intervention strategies to control anaemia in pregnancy [35].

A very low red blood cell count was observed in pregnant women with coincident infection. This may be an outcome of haemolytic anaemia associated with malaria infection [36]. Immunological factors play an important role in the etiology of haemolytic anaemia associated with malaria and the reduction in the life span of the red blood cells persists for several weeks after acute infection [37].

In conclusion, this work represents a preliminary study of malaria during pregnancy in Yemen. The results confirm that P. falciparum infection in pregnancy is significantly associated with maternal anaemia of the microcytic hypochromic type, besides the haemolytic anaemia which accompanied malaria infection. Young primigravidae are the most vulnerable group affected and they have more preterm deliveries and LBW babies.

Effective measures aimed at preventing malaria in primigravidae would scientifically reduce anaemia attributable to P. falciparum infection and the deleterious effects on both mother and baby. Motivating pregnant women of all parities to utilize antenatal care services is a must, especially since most of the pregnant women in this study were illiterate (71.0%), and the vast majority were housewives (85.5%). In addition, about 80.8% of them were married before they were 20. About one third of the women in our study did not visit the antenatal care services at all.

It has been shown that intermittent treatment in the second and third trimesters of pregnancy with sulphadoxine– pyrimethamine can reduce severe maternal anaemia in primigravidae [38] and significantly improve birth weight in primigravidae and secundigravidae [39]. The introduction of a policy incorporating this strategy would be appropriate for rural Al Hodeidah governorate, where malaria is hyperendemic.

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