Intermittent Preventive Treatment and Malaria of Parturient Women in Southeastern Gabon.

Background: Evaluating malaria control strategies for pregnant women is essential. The objective of this study was to determine the factors inuencing the frequency of prenatal consultations (PNC), the adherence to intermittent preventive treatment with sulfadoxine-pyrimethamine (IPT-SP) and its impact on the health of parturient women and their newborn babies living in semi-urban and rural areas of southeastern Gabon. Methods: This transversal study was performed at the Centre Hospitalier Régional Paul Moukambi de Koula-Moutou (CHRPMK). Information regarding age, frequency of prenatal consultations, obstetric history, use of malaria control measures, use of IPT-SP, malaria diagnostic of parturient women and their newborns, were collected with a questionnaire and from birth registers from January 1 st 2018 to December 31 st 2019. Results: In total, 2174 parturient women were included in the study. The mean age was 26.2 ± 6.99 years and 81.4% of parturient women attended at least four CPN. The proper attendance of PNC (at least 4 prenatal consultations) was linked with age (p< 0.001) and profession (aOR= 1.72 [1.27 - 2.37]; p< 0.001). The coverage rate of IPT-SP was 90% with a good adherence rate (at least three doses of IPT-SP) of 58.87%. The good adherence rate to IPT-SP was linked to profession (aOR= 1.65 [1.20 - 2.29]; p< 0.01) and age (p< 0.001). The mean weight of newborns was higher for babies whose mothers had received three doses of IPT-SP (p< 0,001) but the APGAR score was not inuenced by the use of IPT-SP by the mother (p= 0.47). The prevalence of plasmodial infection was 3.10% (IC 95% = [1.21 - 5]) and Plasmodium falciparum was responsible for 100% of infections. The prevalence of plasmodial infection was the same for all age groups (p>


Background
Malaria is a public health issue and approximately half of the population in the world is exposed. Malaria is particularly severe in tropical areas where Plasmodium falciparum is found. Plasmodial infection essentially results in severe and sometimes lethal febrile symptoms. Pregnant women are one of the most vulnerable populations because of their compromised immune system due to pregnancy. In order to ght malaria in pregnant women, the World Health Organization (WHO) recommends a threefold approach: vector control through the use of long-lasting insecticidal nets (LLINs), the use of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPT-SP) which has a protective effect in the mother and fetus, and nally, the early diagnostic of all suspect cases in order to initiate care [WHO, 2020].
In Gabon, malaria transmission is perennial due to its warm and humid equatorial climate which favors the proliferation of mosquitos. In order to ght malaria, the country has adopted WHO recommendations since 2003. These measures have led to a signi cant decrease of infection, especially in the most vulnerable subjects (children aged less than ve years old and pregnant women) [1,2].
Previous studies on malaria in pregnant women in Gabon have shown that malaria prevalence in the capital Libreville and its surrounding areas was 34.4%, 53.6% and 18.2% in maternal peripheral blood, placenta and umbilical cord, respectively. In addition, adherence to IPT-SP was associated with the decrease of plasmodial infection in pregnant women, and to the prevention of premature birth and low birth weight [3]. The adherence of pregnant women to IPT-SP reaches 80% in urban areas, with a good adherence rate of 57.4% (at least three doses of IPT-SP) [4].
Furthermore, a recent study in Fougamou [5], a semi-urban area in central Gabon, showed that 94.4% and 47.9% of parturients received one and at least three doses of IPT-SP, respectively, during pregnancy and that the prevalence of P. falciparum infection was 11.7%. In the same study, Fleuramie et al. showed that prevalence of plasmodial infection was the same whatever the number of doses of IPT-SP received by pregnant women. However, no data are available for semi-urban and rural areas in southeastern Gabon Thus, the objective of this study is to determine the frequency of prenatal consultations (PNC), the adherence to IPT-SP and its impact on the health of newborn babies in semi-urban and rural areas in southeastern Gabon.

Study Site And Patients
This study was conducted at the maternity ward of the Centre Hospitalier Régional Paul Moukambi de Koula-Moutou (CHRPMK) in the Ogooué-Lolo province, Gabon. This cross-sectional descriptive study involved all pregnant womenwho gave birth at the hospital.

Sampling
Socio-demographic, clinical and paraclinical data of all parturient women, as well as the birth information of their newborn babies were collected: (i) from birth registries dated from January 1st, 2018 to December 31st, 2019; (ii) with a questionnaire from January 1st to April 30, 2020, lled and signed by the investigator and the parturient woman or the parent/legal guardian for minors, after informed consent. Additional information such as knowledge of parturient women on malaria, the presence or absence of window screens in their homes, the use of insecticide, ventilation means and the use of long-lasting insecticidal nets (LLINs) were collected via the questionnaires. The mosquito net was considered treated with insecticide when it was obtained less than 6 months ago. Malaria diagnosis was performed for all parturient women who came to the hospital from January 1st to April 30, 2020 using the Lambaréné method [7].
In accordance with WHO recommendations, were considered as "bad attendance" and "good attendance" of antenatal care if parturients had consulted "less than four times" and "at least four times" respectively during pregnancy. Also, was considered "bad adherence" and "good adherence" to IPT-PS, parturients who had taken "less than three (<3) doses" and "at least three (≥3) doses" of IPT-PS, respectively. APGAR score and neonatal birth weight were described as elsewhere [8][9][10].

Statistical Analyses
Data of parturient women were recorded in Excel 2013 spreadsheets. Statistical analysis was performed using the Epi-Info 6 and R version 4.0.5 (2021-03-31) software. Proportion and mean of qualitative variables, standard deviation, median and inter-quartile range (IQR) were recorded. The proportions of qualitative variables were compared using the Chi-square test. Fisher's exact test was used for numbers below 5. Mean values were compared with Student's t test, with the ANOVA test to compare more than two means or the nonparametric Kruskal-Wallis test when numbers were insu cient. The Crude (OR) and adjusted odds ratios (aOR) are presented, the con dence interval was set at 95 % (IC 95% ). Statistical signi cance was set at α = 5%.

Sampling description
In total, the data of 2174 parturient women was collected: 1851 from birth registries and 323 from pregnant women enrolled in the survey carried out from January 1st to April 30, 2020. The proportion of Gabonese women or women of foreign nationality were, respectively, 95.58% (IC 95% = [94.87 -96.57]) and 4.42% (IC 95% = [3.45 -5.15]). Ninety-percent (90%, 1953 women) of parturient women were unemployed and ten percent (10%, 223 women) had an occupation or income-generating activities. The majority of women (97.70%) lived in the semi-urban regions of Koula-Moutou and Lastourville. The remainder (1.8%) lived in rural villages. The mean age was 26.2 ± 6.99 years, the median was 25 years (IQ = [20 -31]). The rate of parturient women with health insurance (National Health Insurance Fund) was 80.31%. were primiparous. The average gestation period was 38.4 ± 2.04 weeks. The percentage of parturient women according to their obstetric history (gravidity and parity) are presented in Table 1.

Prenatal Consultations And Intermittent Preventive Treatment
Parturient women attended on average 3.63 ± 1.46 PNC with a median of 4 PNC (IQ= [3 -5]), a minimum of 0 and a maximum of 8 ( Figure 2). The rate of attendance to prenatal care was 40% for parturient women aged 12 to 17 years and 57.55% for women aged more than 18 years. Proper attendance to prenatal care (at least 4 PNC) was observed in 55.11% (1198/2174) of pregnant women. The rate of proper attendance to prenatal care was 53.46% for unemployed women and 66.09% for those with an occupation. In primigravida, multigravida, and grand multigravida women, the rate of prenatal care attendance was 53.30%, 59.41% and 52.87, respectively.  Impact of obstetric history on PNC attendance and adherence to IPT-SP. Univariate analysis showed that proper PNC attendance (p= 0.03) and good adherence to IPT-SP (p< 0.01) were linked to the obstetric history of pregnant women (gravidity).
Impact of residence on PNC attendance and adherence to IPT-SP. Parturient women living in semi-urban and rural areas both had the same attendance rate to PNC (p> 0.05) and the same adherence rate to IPT-SP (p> 0.05). The mean weight of newborns signi cantly evolves depending on the number of IPT-SP doses received by the mother ( Table 3). The mean weight was statistically higher in babies whose mothers had received three (3) doses of IPT-SP (p< 0.001). More than 80% of newborns had an excellent APGAR score at birth regardless of the number of IPT-SP doses received by the mother (Table 3). No statistical link was found between the number of IPT-SP doses and the APGAR score of newborns (p= 0.47).  No statistical link was found between the different control measures and plasmodial infection in parturient women (Table 4).

Plasmodial infection and impact on newborns.
Among parturients infected by P. falciparum (

Discussion
Pregnant women are one of the most vulnerable populations to malaria. Indeed, pregnant women are more susceptible to plasmodial infections even though these are often asymptomatic [11]. This susceptibility is in part due to the depression of the immune system during pregnancy which allows women to tolerate the fetus [12]. The effectiveness of IPT-SP has been demonstrated in sub-Saharan Africa [13][14][15] and in a few localities in Gabon [1,3]. However, no data regarding the semi-urban and rural regions in southeastern Gabon have been published to date. The objective of this study was, on one hand, to evaluate the level of attendance to prenatal counselling services, and on the other hand, to assess the adherence rate of parturient women to IPT-SP and its impact on newborns, in rural and semiurban areas in southeastern Gabon.
The mean age of parturient women was the same as the one found in urban regions in Gabon (the capital Libreville and its surroundings) [4]. Moreover, the same trends were observed in several countries of sub-Saharan Africa such as Benin, Burkina-Faso and Senegal [13,14,16].
The PNC attendance rate (Figure 1) is signi cantly higher than the one observed in Libreville and its surroundings (urban area) in 2011 [4] and in other countries in Africa such as Kenya [17] and Benin [18]. These results show a signi cant improvement in the monitoring of pregnant women in Gabon, probably due to multiple awareness campaigns and free childbirth care since 2017 (for any woman attending a PNC in a health structure recognized by the National Health Insurance Fund in Gabon). In total, 90% of parturient women received at least one dose of IPT-SP and 58.87% received at least three doses, as recommended by the WHO for good adherence. Indeed, since 2003, Gabon has adopted WHO recommendations [19] for prenatal care and led extensive awareness campaigns on the necessity of using IPT-SP. Our results show a good adherence rate of pregnant women to this new malaria control measure in southeastern Gabon, as is the case in other regions of the country. Indeed, studies led in the capital Libreville and its surrounding areas, Lambaréné and Fougamou have shown that the adherence rate to IPT-SP is good, and has led to a signi cant decrease in malaria prevalence in pregnant women [1,3,4,6,20]. Similar results were noted in other African countries such as Kenya or Burkina Faso [21,22] though a low adherence rate to IPT-SP was reported in an urban area in the south of Benin in 2017 [13]. However, it should be noted that the rate of women receiving at least three doses of IPT-SP during their pregnancy has not changed much since 2007 [3,4]. These data support the fact that in urban centers, certain categories of women do not have access to socio-economic development. In Gabon, it is therefore urgent to explore new factors which may limit an excellent coverage of IPT-SP.
Moreover, our study showed that parturient women aged less than 18 years old were those with the lowest adherence rate to IPT-SP (Table 2). This could be explained by the fact that these pregnant women were also those who attended PNC the least during their pregnancy (p < 0.001), given that prophylaxis with SP is administered to pregnant women during PNC. Indeed, a study performed in Libreville showed that the adherence to IPT-SP was statically linked to the attendance of prenatal counselling services [4].
Our results are also consistent with those of studies in the Democratic Republic of the Congo and in Burkina Faso, which showed that teenagers were less likely to attend PNC during pregnancy [15] and less likely to adhere to IPT-SP. These results could be due to several factors such as nancial and geographical constraints, the lack of knowledge on pregnancy risks and the lack of education on the importance of prenatal care. The low attendance to PNC could also be due to socio-cultural aspects such as the shame of being seen by relations, or beliefs according to which a pregnancy can be cursed or unsuccessful if it is revealed too early [23][24][25]. In contrast to parturient women aged less than 18 years, the 30 -35 age group had the highest attendance rate to PNC and the best adherence rate to IPT-SP (. This can be explained by the fact that it is in this age group that are found wanted pregnancies, due to marital status or age, and these women carefully seek and follow prenatal care. Our study showed that the professional status of women impacted the attendance rate of PNC as well as the adherence rate to IPT-SP. Indeed, several Gabonese women declared that in the case of IPT-SP stock shortage in prenatal counselling services, pregnant women are often asked to buy their dose of IPT-SP themselves in drugstores, which is often very di cult for this underprivileged population. This was demonstrated in Burkina Faso in a study by Sinare-Ousmane in which 71% of parturient women did not take enough doses of IPT-SP because they were required to pay for treatment [26]. have highlighted a decrease in low birth weight with the adoption of IPT-SP [28][29][30]. In our study, we shown that birth weight was statistically linked with IPT-SP (Table 5). Indeed, we noted a signi cant birth weight gain for newborns whose mothers took three doses of IPT-SP. These data con rm those previously reported in Libreville and Lambaréné [1,3] and in several countries of sub-Saharan Africa [31]. Despite the high prevalence of genotypes associated with resistance to SP in some rural areas in Gabon [32], the three-dose IPT-SP policy must be maintained and improved in order to make it accessible to all pregnant women for effective malaria control.
The a good adherence rate to IPT-SP (58.87%), we found no link between infection and prevention measures such as the use of LLINs, knowledge on malaria or window screens (Table 4). Furthermore, the prevalence of malaria in peripheral blood in pregnant women found in this study is lower than those reported in 1995 (25%), in 2005 (12%) and in 2011 (6%) [33]. However, parasitic sequestration and submicroscopic infections support an overestimation of this prevalence. Indeed, a study showed that malaria diagnosis by polymerase chain reaction (PCR) leads to a better estimate of malaria prevalence after treatment with SP, since the parasite load decreases in populations after the implementation of new disease control strategies [34]. These infections are a part of plasmodial reservoir. In this study, P. falciparum infection was associated with low birth weight and premature births (Table 5). Similar results were found in Libreville [3] and in several other studies [31,35]. Indeed, the presence of parasite in placenta disrupts exchanges between the mother and the fetus, thus limiting its development. We found no link between plasmodial infection, age and obstetric history (gravidity and parity) of parturient women, unlike previous studies [20,32,[36][37][38]]. Indeed, it was shown that the decrease in malaria prevalence in pregnant women thanks to prevention means cancels the effect of age and obstetric history on infection [39][40][41]. The low prevalence of plasmodial infection observed in our study corroborates these observations Our study has a few limitations. The data gathered on the attendance of PNC and the adherence to IPT-SP were largely based on hospital birth registries (CHRPMK). The data of several parturient women were missing and could not be included in our analyses. In addition, during data collection from January 1st to April 30, 2020, several parturient women were reluctant to answer the questions while others forgot some of their medical information. Finally, the parasitological examination of the umbilical cord and placenta could not be performed especially as P. falciparum is often sequestered there, and placental infection is considered as one indicator of malaria in pregnant women [3].

Conclusion
Several years after Gabon implemented WHO monitoring recommendations for pregnant women, our study showed the good attendance of parturient women to prenatal counselling services in southeastern Gabon. However, the adherence rate to IPT-SP in still insu cient. Awareness campaigns to educate on the importance of antenatal care are essential to improve the monitoring of pregnant women in Gabon. Distribution of parturient women according to age group.

Figure 2
Attendance to PNC and treatment with IPT-SP.