|Year : 2016 | Volume
| Issue : 3 | Page : 126-132
Epidemiology of congenital anomalies of the central nervous system in children in Enugu, Nigeria: A retrospective study
Christopher Bismarck Eke1, Enoch Ogbonnaya Uche2, Josephat Maduabuchi Chinawa1, Ikechukwu Emmanuel Obi3, Herbert Anayo Obu1, Roland Chidi Ibekwe1
1 Department of Paediatrics, University of Nigeria/University of Nigeria Teaching Hospital, Enugu, Nigeria
2 Department of Surgery, Neurosurgical Unit, University of Nigeria/University of Nigeria Teaching Hospital, Enugu, Nigeria
3 Department of Community Medicine, College of Medicine, University of Nigeria/University of Nigeria Teaching Hospital, Enugu, Nigeria
|Date of Web Publication||23-Aug-2016|
Christopher Bismarck Eke
Department of Paediatrics, College of Medicine, University of Nigeria, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu 400001
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Congenital anomalies, including those of the central nervous system (CNS), are among the leading causes of morbidity, mortality, and fetal loss.
Objective: To determine the prevalence and associated factors of CNS congenital anomalies in children.
Methods: A cross-sectional retrospective study of children managed with CNS anomalies was undertaken. Relevant clinical data of identified cases based on standard case definitions were retrieved from their case record files. Data were analyzed using SPSS 20.0 while the level of statistical significance was set at P < 0.05.
Results: Seventy-two cases of CNS anomalies were identified over the period under review; out of 7329 total pediatric admissions giving a prevalence of 0.98%. Spina bifida cystica, 49 (68.0%) was the most common of the five anomalies seen followed by congenital hydrocephalus 11 (15.3%). Fifty-seven (79.2%) of the mothers did not take periconceptional folic acid supplementation (P < 0.05) whereas 25 (34.7%), 6 (8.3%), and 1 (1.4%) reported history of febrile illness in the first trimester of pregnancy, alcohol use, and diabetes mellitus in pregnancy, respectively. Majority of the cases of spina bifida cystica (30 [61.2%]) seen had corrective surgeries while the overall case fatality rate was 1 (1.4%).
Conclusions: Spina bifida cystica was the most common anomaly of the CNS seen in this study and majority of the mothers of affected children did not take periconceptional folic acid supplementation (P < 0.05). Efforts should be made to create awareness and apply adequate preventive health education models including the use of periconceptional folic acid supplementation as well as the provision of access to standard prenatal care to at risk mothers.
| Abstract in French|| |
Arrière-plan: Les anomalies congénitales, y compris celles du système nerveux central (CNS), sont parmi les causes principales de la morbidité, de la mortalité, et de perte fœtale.
Objectif: Pour déterminer la prédominance et les facteurs associés aux anomalies congénitales du CNS chez les enfants.
Méthodes: Une étude rétrospective en coupe transversale des enfants contrôlés avec des anomalies du CNS a été entreprise. Les données cliniques appropriées des cas identifiés basés sur des définitions standares des cas ont été recherchées à partir de leurs dossiers de fiche individuelle. Des données ont été analysées utilisant SPSS 20,0 tandis que le niveau d'importance statistique était à P < 0.05.
Résultats: Soixante-douze cas d'anomalies du CNS ont été identifiés au cours de l'exercice écoulé ; sur 7329 admissions pédiatriques totales donnant une prédominance de 0,98%. Le cystica despina bifida, 49(68,0%) était la plus commue des cinq anomalies identifiées suivies de l' hydrocephalus congénital 11(15,3%. Cinquante-sept (79,2%) des mères qui n'ont pas pris le supplément d'acide folique périconceptionel (P < 0.05) tandis que 25(34,7%), 6(8,3%, et 1(1,4%) ont présenté des antécédents de la maladie fébrile dans le premier trimestre de la grossesse, de l'utilisation d'alcool, et du diabète dans la grossesse, respectivement. La majorité des cas du cystica bifida de la colonne vertébrale (30[61,2%]) ont subit des chirurgies correctives tandis que la fatalité des cas globaux était de 1 (1,4).
Conclusions: Le cytica despina bifida était l'anomalie la plus commune du CNS identifié dans cette étude et la majorité des mères des enfants affectés n'a pas pris de supplément d'acide folique périconceptionel (P < 0.05).On doit faire des efforts qui visent à sensibiliser et à appliquer des modèles préventifs appropriés d'éducation à la sante comprenant l'utilisation du supplément d'acide folique périconceptionel aussi bien que l'accès aux soins prénatals standars aux mères en danger.
Mots-clés: Système nerveux central, enfants, anomalies congénitales, épidémiologie
Keywords: Central nervous system, children, congenital anomalies, epidemiology
|How to cite this article:|
Eke CB, Uche EO, Chinawa JM, Obi IE, Obu HA, Ibekwe RC. Epidemiology of congenital anomalies of the central nervous system in children in Enugu, Nigeria: A retrospective study. Ann Afr Med 2016;15:126-32
|How to cite this URL:|
Eke CB, Uche EO, Chinawa JM, Obi IE, Obu HA, Ibekwe RC. Epidemiology of congenital anomalies of the central nervous system in children in Enugu, Nigeria: A retrospective study. Ann Afr Med [serial online] 2016 [cited 2022 Aug 10];15:126-32. Available from: https://www.annalsafrmed.org/text.asp?2016/15/3/126/188892
| Introduction|| |
Recent advances in medical genetics and molecular biology have revolutionized the understanding of central nervous system (CNS) development enabling precise classification of its congenital anomalies based on the stage of development at which each occurred. 
Generally, CNS anomalies could be grouped into several entities including neural tube defects and associated spinal cord malformations (myelomeningocele, meningocele, encephalocele), disorders of structural specifications, disorders of posterior fossa, brain stem, and cerebellum, disorders of brain growth and size, and disorders of skull growth and shape. 
In addition, other systemic anomalies have been shown to occur together with CNS anomalies with some studies reporting up to 7% in children diagnosed with congenital heart defects,  and most of such children have increased risks of morbidity and mortality.
Globally, the incidence of congenital anomalies has been shown to vary from one geographical region to another, affecting about 3-7% of all newborns. In most series reported, CNS anomalies appear to be the most common systemic congenital anomalies. ,,,,
Majority of the causes of congenital anomalies is uncertain.  However, evidence suggests that in about 25% of cases where the causes are known they appear to be multifactorial involving a complex interaction between genetic and environmental factors. 
Equally, errors of morphogenesis resulting in congenital malformations have been linked to some recognized genetic causes including specific single gene mutations, chromosome imbalances, and the action of teratogens. 
Folate deficiency has a recognized teratogenic effect, resulting in an increasing risk of neural tube defects. , Observational and interventional studies equally have all pointed to a 50-70% protective effect on women who consume adequate amounts of folates on neural tube defects. 
Further evidence has also shown association with some genetic determinants (such as mutations in folate-responsive or folate-dependent pathways) which could affect the CNS development adversely from conception. 
Some environmental factors including hyperthermia, certain drugs (particularly folic acid antagonists), chemicals, high doses of irradiation during the periconceptional period, cigarette smoking among others ,, have equally been implicated. Other factors such as parental consanguinity, advanced maternal and paternal age, increasing birth order and prematurity, low birth weight, and maternal metabolic diseases have also been linked as possible risk factors. ,
Prenatal diagnosis of CNS anomalies as well as classification and determination of cases have improved its prognosis.  Most children born with congenital anomalies who survived infancy are affected physically, mentally, or socially and can be at increased risk of morbidity. ,
However, it has been reported that the global annual neonatal mortality involve over 270,000 newborns,  whereas about 2-3% of all newborns have recognizable malformations. Most of the data on congenital anomalies are from registries from developed world. In our setting, hospital data are the only source of the burden of the disease owing to the absence of birth defect registries and limited diagnostic capabilities.
In Nigeria, UNICEF has alarmed about increasing rates of under-five and infant mortality and that Nigeria alongside other nations in the sub-Sahara Africa may not meet the millennium development goal number 4 aimed at reducing childhood mortality by 2015. ,
However, as Nigeria is an economy currently in transition with rapid urbanization as well as globalization, changing lifestyles, and improving health seeking behavior, it is, therefore, pertinent to review the trend of CNS congenital anomalies in our setting so that appropriate recommendation could be made to save lives and improve infant morbidity outcomes and reduce infant mortality rates in our region. A similar study was done by Ohaegbulam and Saddeqi in Enugu about three decades ago.  It, therefore, becomes necessary to find out if there is any changing trend. Hence, this study was aimed at determining the prevalence and factors associated with CNS congenital anomalies in children presenting to University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla, Enugu, South East Nigeria.
| Methods|| |
This was a cross sectional retrospective study in which a review of the records of all newborns admitted in the newborn special care unit (NBSCU) and neurosurgical ward of the UNTH, Enugu, over a 42-month (3 years 6 months) period (January 1, 2011 and June 30, 2014) was undertaken. The case files of these babies were retrieved from the hospital records department and examined individually by the investigators.
Ethical approval for this study was sought from the Health Ethics Research Committee of the UNTH, Ituku-Ozalla, Enugu, Nigeria.
Data collection was done using a semi-structured questionnaire designed for the study. The diagnoses of the CNS anomalies were based on clinical evaluations and ultrasound findings and meeting the standard (International Classification of Diseases-10) case definitions. 
Patient's history including antenatal history, history of exposure to teratogens, and family history of consanguinity (first cousins) and birth defects (up to second and in some few cases third generation pedigree) were obtained from these folders. Further information obtained included maternal age, paternal age, type of delivery, gestational age, and type of CNS congenital and other associated anomalies. The prevalence rate was estimated as a percent of the total number of babies admitted in the units within the period of the study (number of babies with CNS congenital abnormalities/total number of babies admitted in the hospital for the duration of study).
Data were analyzed using SPSS 20.0 (Armonk, NY: IBM Corp). Rates and proportions were calculated with 95% confidence intervals. The proportions were compared using Chi-square with the level of significance set at P < 0.05.
Limitation of the study
Inability to use a control group for actual comparison of the findings.
| Results|| |
The most common age of presentation was <1 month in 64 (88.9%) while 1-<12 months were 3 (4.2%) and those aged more than 12 months old were 5 (6.9%) as shown in [Table 1]. The male to female ratio of children with CNS anomaly was 1.6:1 showing a male preponderance.
|Table 1: Demographic characteristics of study population and their caregivers |
Click here to view
Children with CNS anomaly were mainly delivered by mothers who were <35 years 53 (73.6%) and their fathers were mainly <45 years, 31 (43.1%). Majority of mothers of children with CNS anomalies attended secondary schools 23 (31.9%) while 11 (15.3%) had University education.
A total of about 7329 pediatric admissions were recorded over the study period. Seventy-two of these were found to have CNS anomaly of various types, giving a prevalence of 0.98%.
The most common CNS anomaly was spina bifida cystica accounting for 49 (68.1%) cases. Closed myelomeningocele was the most common form of the spina bifida cystica accounting for 39 (79.6%) of the cases and co-existed with hydrocephalus in 10 (20.4%) of them. Other anomalies in order of frequency were congenital hydrocephalous 11 (15.3%), made up of (aqueductal stenosis 6 [54.5%], Dandy-Walker syndrome 1 [9.1%], and others 4 [36.4%]); while encephalocele 9 (12.5%); microcephaly 2 (2.8%); and anencephaly 1 (1.4%) were as highlighted in [Table 2].
Of the 49 children with spina bifida cystica, 30 (61.2%) made up of 7 and 23 cases, respectively, of meningococele and closed myelomeningocele had surgery for their conditions. One child with ruptured sac on admission demised accounting for a case fatality rate of 1 (1.4%).
Majority of the children, i.e., 61 (84.7%) with CNS anomaly were delivered vaginally (spontaneous vertex) whereas 10 (13.9%) were delivered by cesarean section. Only 1 (1.4%) mother smoked cigarette and 1 (1.4%) had diabetic mellitus. Fifty-seven (79.2%) mothers of children with CNS anomalies did not take folic acid throughout pregnancy, and the difference was statistically significant (P < 0.05).
Mothers who used alcohol; had febrile illness and used local concoctions were 6 (8.3%), 25 (34.7%), 8 (11.1%), respectively, are shown in [Table 3].
| Discussion|| |
The prevalence of the CNS congenital anomalies in the present study is 0.98%. This is lower than the 2-3% reported in the general population  but compares favorably well with similar hospital based studies in Nigeria. ,,
CNS anomalies have been shown to either occur singly (isolated) or as part of syndromes. , From the current study, musculoskeletal anomalies (talipes equinovarus) particularly were found to be the most common associated systemic anomaly. A male preponderance was observed in the study population similar to previous reports , whereas other workers have reported equal sex distribution.  However, the probable reason for the higher male predilection in the present study appears uncertain. It may be due to the importance attached to male gender in this part of the world (succession/propagation of the family name) such that parents are more likely to report any problem or sickness in their male children to the hospital faster than their female folk.
No history of parental consanguinity was observed among the study population. Although consanguineous marriages are known to contribute to increased risk of congenital malformations as some rare recessive genes may easily come to manifest. However, such marriages are uncommon in our setting. ,
Social class, particularly parental educational status, has been shown to be an important determinant of acceptance or rejection of surgical intervention in some cases of CNS anomalies. In addition, low schooling and low socioeconomic class among the caregivers could be a reason for the lack of accessibility to proper antenatal care and nonimplementation of both primary and secondary preventive modalities of congenital anomalies. , In the current study, majority of the mothers of the affected children had primary or no formal education though most still opted for surgeries and other modalities of treatment as requested by the managing teams.
Maternal age is an important risk factor in the birth of a child with congenital anomaly. About 22.2% of mothers in the present study were above 35 years of age. Studies have shown that a direct relationship exists between maternal age and incidence of congenital anomalies and showing low incidence with age <20 years. ,
Current study reported myelomeningocele as the most common CNS anomaly in our study area as reported in other Nigerian hospital based studies. ,, However, earlier study in Enugu, South East Nigeria,  some three and half decades ago and in Ibadan, South West Nigeria,  respectively, reported hydrocephalus as the most common CNS anomaly. This shows a changing trend from higher incidence of hydrocephalus to neural tube defects - myelomeningocele.
Maternal febrile illness such as maternal rubella infection in early pregnancy has been associated with increased risk of birth defects. Some congenital anomalies particularly those involving the cardiovascular system including tricuspid atresia, transposition of great arteries, left obstructive defects, and ventricular septal defects  have been linked to maternal fever in the first trimester. In the current study, about a third of the mothers reported history of febrile illness in the first trimester. Majority of the cases, i.e., 61 (84.7%) were delivered vaginally compared to 10 (13.9%) delivered by cesarean section. Studies have reported similar occurrences.  The probable cause is uncertain. However, delivery by the vaginal route could result in neurological trauma and expose the neural tissue to infectious agents present in the birth canal with the possibility of causing CNS infections such as meningitis which could be complicated with hydrocephalus if not adequately managed.
Birth defects have been implicated in pregnancies complicated by hyperglycemia, and this association is most common in individuals with type I diabetes. Higher risks of CNS anomalies have been reported in mothers with maternal diabetes  as equally observed in the present study.
Majority of the mothers of the children studied reported not to have taken folic acid in pregnancy. Folate deficiency has a recognized teratogenic effect, resulting in an increasing risk of neural tube defects. , Observational and interventional studies equally have all pointed to a 50-70% protective effect on women who consume adequate amounts of folates on neural tube defects. 
Moreover, evidence has shown association with some genetic determinants (such as mutations in folate-responsive or folate-dependent pathways) which could affect the CNS development adversely from conception.  The lack of use of folic acid by majority of the mothers, 57 (79.2%) of the affected children could partly explain the high incidence of neural tube defects among the study cohort.
Potentially, almost any drug used by pregnant mothers could be teratogenic. About 8 (11.12%) of the mothers made use of herbal medications in the first, second, and/or third trimester(s) of pregnancy. In our setting, some mothers believe that the use of certain herbal concoctions could help them to give birth to "light" weight babies hence making them avert prolonged obstructed labor with resultant need for cesareans section. On the other hand, some of the prospective mothers could have been taking the herbal concoctions for treatment of one form of infertility or the other without knowing when they became pregnant and apparently exposing their fetuses to the deleterious effects of such local herbs.
It has been estimated that about 2-3% of birth defects are due to exposure to drugs.  Moreover that the timing of the exposure during embryogenesis is crucial as the fetal brain development continues well into the second and third trimesters of pregnancy.
The impact of drug exposure during pregnancy/fetal life is of concern generally. Sometimes, some of the effects may not be recognized until later in life. Other drugs such as alcohol have equally been implicated in causing congenital anomalies including mental retardation. In the current study, 6 (8.3%) mothers reported the use of alcohol. Most studies have reported chronic alcohol use; however, it is less well known the minimal levels of alcohol intake that are safe in pregnancy in different populations. 
Majority of the cases presented in the neonatal age while a few presented even beyond infancy with associated complications. The majority of the cases that presented late came with complications and accounted for majority of the morbidity as reported in current the study.
| Conclusions|| |
Neural tube defects were observed to be the most common CNS anomalies in the current study while maternal febrile illness in the first trimester, maternal age >35 years, use of herbal medications, lack of use of periconceptional folic acid supplementation were the possible risk factors.
Efforts should be made to create awareness and apply adequate health education models including use of periconceptional folic acid supplementation as well as provision of access to standard prenatal care to at risk mothers.
We wish to appreciate Mrs. Ngozi Okolo (Chief Nursing Officer, NBSCU, UNTH, Enugu, Nigeria) who helped with the listing of the cases.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]
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