Demographics: Sex, Age and Patient Characteristics of both studies
As opposed to their female counterparts, males had a relatively higher chance of being diagnosed with HCP (140 patients accounting for 57.14%). This finding is similar with published studies in other African countries which have shown that majority of pediatric patients with HCP were males; 64.6% of the population in a study from Tanzania and 53% in a study from Kenya (7); 60.5% in a study from Nigeria (8), as well as a predominance of 51.9% in a study from Uganda (9). The finding also is in agreement with a published study in Ethiopia which similarly found males to be predominant both in isolated HCP (38 male patients accounting for 66.7% of all patients with isolated HCP) and in the MMC associated HCP group (30 male patients accounting for 53.6% of the patients in that group) (6). However, the prospective study had a different finding; as it was found that females had a relatively higher chance of being diagnosed with HCP (12 patients accounting for 52.17% of all patients diagnosed with HCP). In this study, sex was not considered as one of the risk factors of HCP. As a result, the relatively higher prevalence of HCP among males in retrospective study and females in prospective studies was not further investigated. In this study, age distribution ranged from 1 to 60 months; there was a slight increment in the mean age of pediatric patients from 22.3 months to 24.9 months in the two study periods but the difference was not statistically significant. A statistically significant association between age and the development of HCP was found (P<0.05), in the retrospective study, among children aged younger than 24 months; 192 children (78.3%) out of all patients diagnosed with HCP. These children were observed to have a higher risk of developing HCP 1.9 times as opposed to those aged older than 24months. (Table 1) This is similar to an article published in the journal of the International Society for Pediatric Neurosurgery (ISPN) and the National Organization of Rare Disorders (NORD) both of which reported the majority of children who present with HCP do so before 2 years of age (10, 11). Non-communicating HCP (obstructive HCP) was predominant in both populations, 62.4% in the retrospective and 56.5% in the prospective study. This is in agreement with the Ethiopian study that also found obstructive HCP to be predominant in two of their study periods, 64.7 % during the first period, and 62.2 % in the second (6).
Prevalence of HCP
In developed countries, the incidence of congenital HCP is estimated at three to five cases per 1000 live births (3). This study had a different finding as it identified the prevalence in the population studied during the retrospective study to be 222.72 per 1,000 births (2,222.72 per 10,000 births) and the prevalence observed during the prospective study period to be 232.3 per 1,000 (2,323.2 per 10,000 births). The observed prevalence of pediatric HCP in both studies is much higher than prevalence rates of 20.3 per 10,000 births seen in northern China (12), 4.65 per 10,000 births in four European regions (13), 11 per 10,000 births in Denmark (14), 5.9 per 10,000 births for California (15), and prevalence of 28.7 per 10,000 births in a region of Nigeria (16). However, the results of this study are in agreement with the study conducted in Uganda-from CURE Children’s Hospital of Uganda (CCHU) which demonstrated infant HCP among 3,684 children. The study estimated the infant HCP prevalence rate between 1,000 and 2,000 cases every year (4). This study is also similar to research conducted here in Addis Ababa, Ethiopia that used the estimates applied in the Ugandan research and presented an estimate between 2,000 and 4,000 new cases of pediatric HCP per year (6). As described earlier, this high prevalence rate of HCP in Ethiopia has been attributed to high percentages of Aqueductal stenosis, NTDs, and a small contribution of post-infectious causes observed in both study periods. In presenting the causes and incidence rates of HCP from East Africa (6), where it served as a reference for Ethiopia, there is a contradiction concerning the cause of HCP.
Prevalence of Congenital and Acquired HCP
Aqueductal stenosis and Neural tube defects (NTDs)
This study has identified Aqueductal stenosis (17.9%) as the most prevalent type of congenital HCP. Aqueductal stenosis is a narrowing of the aqueduct of Sylvius which blocks the flow of CSF in the ventricular system. The aqueduct of Sylvius, a channel that connects the third to the fourth ventricle, because of its small size, is the most likely place for a blockage of CSF in the ventricular system (17). Reports that aqueductal stenosis causes the majority of the Obstructive HCP (17), have been reviewed by this study and it similarly has attributed the non-communicating HCP (Obstructive HCP) predominance in both populations, i.e. 62.4% in the retrospective and 56.5% in the prospective study to Aqueductal stenosis. Following this, NTDs have been identified as the second most prevalent type of congenital HCP. NTDs compiled within the retrospective data were Chari II malformation, Dandy-Walker malformation, and MMC. This result is in agreement with a study conducted in three African countries; Zambia, Zimbabwe, and Malawi, that stated the most common cause of HCP to be congenital, associated with Aqueductal stenosis and NTDs (18). A similar distribution was also found when compiling the prospective data, Aqueductal stenosis accounting for 26.1%, followed by NTDs (Dandy walker malformation, MMC and Chari II malformation). In contrast, this study differed from the study in Uganda which indicated HCP secondary to CNS infection to be the single most common cause of infant HCP accounting for 60% of cases (19). The results of this study may be explained by the diagnosis of typical characteristics of NTDs and level of obstruction of the cerebral aqueduct on MR neuroimaging of the children’s brain and clinical history acquired during the interview process that was able to show the classic features of HCP, that is, increase in head size, sun-setting eyes, vomiting, and seizures in the patients. This study also found HCP associated with MMC accounting for 0.81% retrospectively and 8.69% prospectively. This result is different from the Ugandan study which found MMC associated HCP to account for 14% (4). This finding is also contrary to the study conducted here in Ethiopia that found MMC associated HCP among children aged under 5 years to account for 44.5% (6). This study also differed from the study in Kenya which found MMC (Spinal Bifida) associated HCP to account for 43.4% (20), south-western Saudi Arabian study that found Spinal Bifida Cystica accounting for (95.8%) (21), and the Tanzanian study that reported MMC to account for 16% of their cases (22). MMC cases were not encountered as much as expected in this study because it was conducted within diagnostic centers and these patients had better chances of being treated in public hospitals since they were detected early and diagnosed clinically; not a lot of imaging investigations were referred out to diagnostic centers. Besides, there is no centrally managed database of the patient’s clinical history in public and private health institutes.
Post-infectious HCP (PIH)
Studies in Uganda (4), Tanzania (22), and Kenya (20); have reported PIH prevalence of 57%, 22.4%, and 27.7%. In our study, however, a prevalence of only 10.1% and 8.69% have been observed in the retrospective and prospective study periods respectively. This discrepancy may be explained by differences in methodology. In the Ugandan study, for example, PIH was defined in terms of the absence of HCP at birth, history of febrile illness or seizure preceding the onset of HCP, and convincing evidence of prior ventriculitis based on imaging or ventriculoscopic findings if the history was unclear (4). In this study, however, PIH was defined in terms of the patient’s clinical history and post-natal CT and MRI imaging investigations only; thus defining PIH in terms of post-natal diagnosis. This study has identified PIH related post-meningitis complications due to Pyogenic and Tuberculous causes accounting for 6.9% and 8.69% within the retrospective and prospective data respectively. In contrast, this study had a lower percentage when compared with the south-western Saudi Arabia study that found post-meningitis causes accounting for 14.8% (21). This study however agrees with the study conducted in three African countries; Zambia, Zimbabwe, and Malawi, that identified post-meningitic HCP as the most frequent cause next to NTDs and aqueductal stenosis (18). A similar study in Kenya was observed to show the same finding where it classified post-meningitis HCP within the PIH group which was again identified as the second most common cause of HCP following Spinal Bifida (20).
The Risk Factors Associated with Pediatric HCP
Prenatal care given to mothers and HCP
This prospective study identified that 82.4% of the interviewed mothers attended their antenatal visits. Statistical significance was not reached among those mothers that did not attend their visits (17.6%). This study hypothesized that those mothers that said they went to their visits may not have attended all the visits they were supposed to go to. This may be explained by poor antenatal follow-ups and this could have resulted in NTDs, which in turn lead to HCP. This study is supported by a study conducted in Atlanta that has suggested that getting adequate prenatal care might help prevent birth defects, HCP being one of them (23). In this study, no association was found with the onset of prenatal care given to the mother and HCP development (P>0.05). This finding is supported by the study from Mississippi that similarly studied potential risk factors of congenital HCP, which similarly did not find any association among prenatal care given to mothers and HCP occurrence (24).
Folic acid Supplementation and HCP
Folate deficiency has a recognized teratogenic effect, resulting in an increased risk of NTDs (16). This study argues that the incidence of these NTDs that eventually lead to HCP and other CNS anomalies could have resulted due to the inadequate consumption of folic acid. In this study, mothers who did not take folic acid nutritional supplements were significantly associated with HCP occurrence (P<0.05). (Table2) During early development, folic acid helps form the neural tube hence, it plays an important role in the prevention of some major birth defects of an infant’s brain i.e. (Anencephaly) and spine (Spinal Bifida) (25). Although the majority (67.8%) of the interviewed mothers in this study did take their folic acid supplement, it was discovered that they took their supplements once they had found out they had conceived and within their late first trimester period and about 32.2 % of these mothers did not take their supplements at all. This study also found that mothers who took their supplements after they had conceived (58.6%) were significantly associated with HCP development (P<0.05). This study has gathered from this that these mothers did not plan their pregnancy and early consumption of folic acid was not considered. The fact that these mothers did not take their supplements before pregnancy and during their early pregnancy periods could explain the high prevalence of NTDs identified during both study periods. This study is also in agreement with the study from the Enugu region of Nigeria that similarly suggested that the high incidence of NTDs among the study cohort attributed to the lack of use of folic acid by the majority of the mothers studied, 57 (79.2%) of the affected children (16). This study is also similar to another study that suggested the consumption of adequate amounts of folic acid by women before pregnancy and during early pregnancy decreases their risk for having a pregnancy affected by NTDs (26). This study again goes following the study conducted in Northern China that found the supplementation of folic acid reduced the incidence of HCP and NTDs in their study population (12). This study supports the findings above. Nevertheless, multivariate analysis of this study was not able to show the inadequate consumption of folic acid as the predictor of HCP occurrence. This has been attributed to the small sample size in the studied population. However, bivariate analysis of this study has found that mothers who did not take the folic acid nutritional supplement were significantly associated with HCP occurrence. As Ethiopia is one of the largest producers of Wheat in Sub-Saharan Africa (27), and most Ethiopian’s diet commonly use Wheat in bread, fortification of wheat flour is an effective, and simple strategy for supplying folic acid and iron to its population (28), thereby reducing the incidence of NTDs that have the potential to lead to HCP.
Advanced maternal age and HCP
Although an association was expected between advanced maternal age and occurrence of HCP, this study did not find a significant relationship between the two (P>0.05). It was difficult to find association as the number of interviewed mothers aged above 35 accounted for only 12.4% and these mother’s risk of having a child with HCP was not found to have increased; whereby only 8.6% of these mothers had an infant with HCP. This is in agreement with the study conducted in Mississippi that similarly did not find any association with advanced maternal age and HCP occurrence (P=0.976) (24). This study has however found that the majority of mothers (46.4%) were aged 24-29; of these mothers (60.8%) were found to have a child with HCP. This finding among the young mother's age group goes following the study from Atlanta which has also identified HCP without NTDs among young mothers and has reported 1.56 times increased risk among this sect of the population. It was suggested that the most likely explanation for the increased risk for birth defects observed in these young mothers may be due to different lifestyle factors like inadequate prenatal care, lower intake of vitamins, lowest awareness of folic acid, unhealthy diet, exposure to alcohol, smoking and/or drugs (23). Young maternal age and advanced maternal age are both associated with increased risks for some types of non-chromosomal birth defects and mothers under 20 and over 35 have a higher risk of giving birth to an infant with a birth defect (23). However, this study was not designed to determine the mechanism by which birth defects occur among different age groups of mothers but further investigation is needed to understand the effects of maternal age on HCP and other birth defects.
Familial Association and HCP
This study was able to show an association between the history of HCP among family members and the development of congenital HCP with a statistical significance of (P<0.05) (Table 2); when performing the bivariate analysis. However, the multivariate analysis was not able to show this as a predictor of HCP development and this as mentioned before has been attributed to the small number of study participants. History of HCP among family members was found to account for 73.9% of all the diagnosed cases of HCP. This is similar to a study conducted in Mississippi which reported 72 of 596 congenital HCP cases (12.1%) had at least one additional family member with HCP (24). Although in this study significant association among different degrees of relatives and the development of HCP was not found, it was identified that of the children with HCP, 8.69% had a first degree relative with congenital HCP. This result is in agreement with a study conducted in Denmark that also found a significant association of HCP among individuals with first- or second relatives with congenital HCP. The Denmark study suggested that familial aggregation and both the genetic and the maternal effects play important roles in congenital HCP pathogenesis (29). This study was unable to adequately analyze genetic sequences due to the lack of genetic laboratories and clinics. Though this study did not investigate genetic agents as a risk factor for HCP, it does recognize its significance and recommends further exploration into the topic for future researches.
Trauma during Pregnancy
In this study, trauma to the mother during the pregnancy period was not significantly associated with pediatric HCP. This study, however, indicated that 17.3% of mothers of children with HCP suffered from trauma during their gestation. Nonetheless, this did not show statistical significance. This is in agreement with a similar study conducted in Mississippi that identified trauma to the mother during her gestation (3%) and traumatic birth (19.5%) as risk factors for the development of HCP; this study from Mississippi nevertheless did not find this to be statistically significant (24). In this prospective study, vaginal delivery (78%) and caesarian section delivery (20.9%) accounted for the total number of modes of deliveries questioned. Instrumental delivery was considered a traumatic birth that could have the potential to cause brain injury leading to HCP. Falling accidents during the gestational period were also considered to be causes of fetal brain damage. This goes following a study in Washington State, USA, that reported brain injury as one of the severe birth traumas observed among hospital singleton live births (30). However, this study was not able to acquire sufficient information from mothers about the details of delivery and only a few of the mothers interviewed were able to recall falling during their pregnancy time. This made it difficult to assess the association; thus making it hard to conclude that birth traumas and accidents were exactly the causes that lead to HCP development. Nonetheless, it hypothesizes that post-hemorrhagic complications that resulted from these traumas could have the potential to lead to HCP. Even though the etiologies of acquired infant HCP associated with post-hemorrhagic HCP of prematurity were reported to be the most common cause of HCP in more economically developed countries (4), this study has described earlier the contribution of post-hemorrhagic HCP i.e. hypoxic-ischemic cerebral injury, perinatal ischemic insult, subdural hematoma, IVH and cystic encephalomalacia here in Addis Ababa, Ethiopia, a low-income country. Following the initial hypothesis, this study has attributed the occurrence of these post-hemorrhagic complications of acquired HCP to post-traumatic reasons.
The Educational Level of the Mother
Ethiopia has been grouped as one of the nations with a low literacy rate of 49.1% along with Liberia (literacy rate of 47.6%), Chad (literacy rate of 40.2%), and Mali (literacy rate of 38.7%) (31). By the year 2017 the literacy rate of male and female adults in Ethiopia, was 59.24% and 44.2% respectively which puts Ethiopia’s literacy rate the lowest in the world (32, 33). It was presumed in this study that the low level of literacy Ethiopia faces especially in its female population particularly among rural communities would be one factor for the limited knowledge of these mothers regarding the health of their child. Going in line with this presumption, we found 49.5% of the interviewed mothers to be from the rural population, and 81.3% to be housewives. The findings of this study could be attributed to sociocultural factors, for example, gender violence, early marriage, and the burden of housework that affects women and girls to not pursue and complete their education. Of the mothers from the rural side, 16.16% of them had a child diagnosed with HCP. In this study, 87.9% of the mothers interviewed did not have any awareness about HCP and had never even heard about it. This study is in line with the article published by Indiana University that reported low health literacy negatively affects a woman's health knowledge, ability to navigate the health care system, and ability to care for her children (34). Despite not being able to establish a statistically significant association between the mother’s educational level and HCP occurrence, different works of literature this study has reviewed has explained its assumptions about the fact that mother’s education is important not only to empower these women but to have a better awareness about their child’s health. In this study, mothers with an educational level of diploma and above had a reduced rate of children with HCP, about 3.29% were identified. This study is in line with another study conducted where parental occupation was examined as a risk factor for HCP. This study found that engineers’ and architects’ infants had a reduced risk as compared to janitors who showed a higher risk of HCP among their infants (35).
Maternal Pathologies and Infections
Maternal chronic hypertension, pre-eclampsia, and maternal diabetes (pre-gestational and gestational) were investigated as risk factors of HCP development, these associations had no statistical significance. This goes in line with reports from the study that similarly did not find statistical significance between maternal diabetes and preeclampsia with HCP development (36). Reports of the prevalence of diabetes and preeclampsia are limited in the developing country setting as opposed to the Western world. For example, a study from Mississippi has identified maternal hypertension during pregnancy to be significantly associated with HCP (24). Unlike this, a study conducted within the eastern zone of Tigray, in Ethiopia has reported the prevalence rate of gestational diabetes mellitus to be only 3.7% (37). In this study, intrauterine infections, for example, TORCH infections were identified among 9.9% of the mothers. These infections were diagnosed while CT and MRI imaging of the child’s brain was performed and HCP was diagnosed. This is in agreement with the study conducted at the University of Athens which also reported an association between maternal infections of toxoplasmosis and cytomegalovirus with congenital HCP but was not able to establish a statistical significance (36). This study found it difficult to reach a statistical significance as the mothers were neither able to explain the type of infection they were diagnosed with nor were they able to know whether they had an infection in the first place. This study has attributed this to the fact that the majority of these mothers were not educated, as previously reported, only 19.8% of the interviewed mothers had a diploma and above. Besides, as some of the viral infections stayed dormant with no clinical signs, this study did not find it surprising these mothers were unaware of the infections. In this study, sexually transmitted infections during pregnancy were identified among 4.4% of mothers. These identified infections were not confirmed by laboratory investigations in this study rather they were gathered from mothers during the interview process. Though this did not reach statistical significance, it goes following the study from Mississippi that similarly reported sexually transmitted infections at the time of delivery were 1.2% but this was not statistically significant (24).
STRENGTHS AND LIMITATIONS OF THE STUDY
- The strength of this study was; cross-sectional facility-based study design employed across the four selected diagnostic centers allowed this study to be representative of the study population and the limitation of this study was; the limited amount of time and resource the prospective study had and failure of the MRI machine to work during this data collection period, as a result, has decreased the total studied population.