|Year : 2015 | Volume
| Issue : 3 | Page : 105-109
The prevalence of neural tube defects in live born neonates in Kano, North-Western Nigeria
Lofty-John Chukwuemeka Anyanwu1, Barnabas Danborno2, Wilson Oliver Hamman2
1 Department of Human Anatomy, Faculty of Medicine, Ahmadu Bello University, Zaria; Department of Surgery, Paediatric Surgery Unit, Aminu Kano Teaching Hospital, Bayero University, Kano, Nigeria
2 Department of Human Anatomy, Faculty of Medicine, Ahmadu Bello University, Zaria, Nigeria
|Date of Submission||17-Apr-2015|
|Date of Acceptance||08-Jul-2015|
|Date of Web Publication||3-Sep-2015|
Lofty-John Chukwuemeka Anyanwu
Department of Surgery, Aminu Kano Teaching Hospital, Kano
Background: Neural tube defects (NTDs) are congenital malformations of the cranium, spine, and nervous system. About 350,000 infants are born with NTDs yearly worldwide. This study aimed to determine the prevalence and spectrum of NTDs in live-born neonates in the Kano Metropolis of North-western Nigeria. Materials and Methods: This is a prospective study of all live-born neonates in three selected hospitals in the Kano metropolis between April 2013 and December 2013. A descriptive study design was employed. Neonates delivered at gestational ages 28 weeks or more were examined within 48 h of birth for external congenital anomalies. Detailed family history and clinical data were recorded for each child. Data were analyzed using SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, USA). Results: Of the 1456 neonates recruited into the study, there were 757 (52%) boys and 699 (48%) girls. Of these, 4 neonates (2 boys and 2 girls) had NTDs (male:female ratio = 1:1), giving a birth prevalence of NTDs (2 spina bifida cystic, 1 anencephaly, and 1 encephalocele) of 2.75/1000 live births. The mean gestational age for the neonates with NTDs was 38 weeks (standard deviation [SD] 2.16 weeks) while their mean birth weight was 2.93 kg (SD 0.51 kg). Only 5.03% of the mothers in this study began the use of folic acid-containing multivitamin supplement at least 1-month before or in the 1 st month of the index pregnancy. Conclusion: Given the high prevalence of NTDs in this study, public health measures aimed at the prevention of this anomaly should be encouraged.
Keywords: Congenital malformation, folic acid, multivitamin supplement, neural tube defects, spine
|How to cite this article:|
Anyanwu LJC, Danborno B, Hamman WO. The prevalence of neural tube defects in live born neonates in Kano, North-Western Nigeria
. Sub-Saharan Afr J Med 2015;2:105-9
|How to cite this URL:|
Anyanwu LJC, Danborno B, Hamman WO. The prevalence of neural tube defects in live born neonates in Kano, North-Western Nigeria
. Sub-Saharan Afr J Med [serial online] 2015 [cited 2020 Apr 10];2:105-9. Available from: http://www.ssajm.org/text.asp?2015/2/3/105/164417
| Introduction|| |
Neural tube defects (NTDs) are a major cause of morbidity and mortality in neonates worldwide, affecting an estimated 0.5-8/1000 live births.  The prevalence of NTDs is however believed to vary significantly with geography and ethnicity.  In North America, NTDs occur in about 1 in 1000 pregnancies annually.  The prevalence of NTDs in Sub-Saharan African is not known, although it has been estimated that among 1000 newly born African babies in 2006, between one and three may have spina bifida.  Annually, about 350,000 children are born with NTDs worldwide. ,
NTDs result from the failure of the neural tube to close spontaneously between the 3 rd and 4 th week of intrauterine life. ,,, The failure of closure may lead to anencephaly or encephalocele (in the cranial region), spina bifida (in the low spine), or craniorachischisis in which almost the entire neural tube remains open, from midbrain to low spine. ,, The exposure of the open neural tube to the amniotic fluid environment in NTDs leads to neuroepithelial degeneration, with massive loss of neural tissue by the end of pregnancy. , Most individuals who survive with NTDs have a limited life expectancy and often have multiple system handicaps.  Neurological impairment below the lesion leads to lack of sensation, inability to walk, and incontinence.  Children with spina bifida also do not grow at a normal rate. 
Human NTDs are considered to exhibit a multifactorial etiology involving multiple interacting genes and environmental factors. , Women who previously have had a child with an NTD, have about 2-5% risk of recurrence, which is approximately 50-fold more than in the general population, and they also have an additional increase in risk after two or more affected pregnancies. ,
The burden of NTDs in Kano is not well characterized. In response to this concern, this study was undertaken to establish the prevalence and spectrum of NTDs in live births in the Kano Metropolis in North-western Nigeria.
| Materials and methods|| |
Between April 2013 and December 2013, 1456 consecutive live-born neonates at three major Hospitals in the Kano metropolis of North-western Nigeria were prospectively studied.
Approval was obtained from the Aminu Kano Teaching Hospital's and Kano State Hospitals' Management Board's Ethical Committees for this study. All babies were routinely examined within 48 h of delivery.  The diagnosis of a congenital malformation was based only on clinical examination and assessment by trained research assistants who were either medically qualified or medical students. Only overt anomalies were documented. There was no effort made to detect occult anomalies. A description of other congenital anomalies observed in this study population has been published elsewhere by our group.  For each neonate, a detailed pregnancy and family history, including the presence of consanguinity, was obtained by interviewing the mother. , Only consenting mothers were interviewed at the same time as the neonatal examination was conducted. Ages of the mothers were grouped into three (teenagers, young mothers <35 years, and mothers older than 35 years), to observe the distribution of NTDs among the groups [Table 1].
|Table 1: Sociodemographic characteristics of the mothers of neonates with and without NTDs|
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Data were recorded on a pretested structured questionnaire for each child. Data were analyzed using SPSS 15.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics were computed for continuous variables while proportions were used for categorical characteristics of the study subject.
| Results|| |
There were or a total of 1456 live-born neonates who were recruited into the study over the study period. Only babies born in the study hospitals were included in the study. Of these, 757 were boys and 699 girls. The neonates who had NTDs were 4 in number (2 boys and 2 girls; male:female ratio = 1:1), giving a birth prevalence of NTDs of 2.75/1000 live births. The types of NTDs seen in the study (2 spina bifida cystic, 1 anencephaly, and 1 encephalocele) are shown in [Figure 1]a-c. The basic characteristics of the study neonates and their mothers are depicted in [Table 1], [Table 2], [Table 3]. Three neonates with NTDs were born to mothers in the 20-34 year age group [Table 1]. Only 5.03% of the mothers began the use of folic acid-containing multivitamin supplement at least 1-month before or in the 1 st month of the index pregnancy as shown in [Table 2], while [Table 3] shows that about 7.4% of the study neonates were of low birth weight (birth weight <2.5 kg). The mean gestational age for the neonates with NTDs was 38 weeks (standard deviation [SD] 2.16 weeks) while their mean birth weight was 2.93 kg (SD 0.15 kg). Hydrocephalous was seen in both neonates (100%) with spina bifida.
|Figure 1: (a) A female child with anencephaly, (b) A female child with encephalocele, (c) A male child with spina bifi da cystica on the lower spine|
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|Table 2: Peri-pregnancy characteristics of the mothers of the neonates with and without NTDs|
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| Discussion|| |
NTDs which are the most common (38.6%) types of central nervous system (CNS) malformations, result when the neural tube, the embryonic precursor of the brain and spinal cord, fails to fuse during neurulation, which occurs between the 3 rd and 4 th weeks of intrauterine life. ,,, In humans, isolated NTDs have a multifactorial origin, with most NTDs resulting from a complex interaction between several genes and poorly understood environmental factors. , NTDs are among the most common congenital abnormalities, with their prevalence varying between countries and races.  Data from this study have established a birth prevalence of NTDs of 2.75/1000 live births in the Kano metropolis. This is in agreement with the findings of Miles (2006) working in East Africa, who documented that NTDs occurred in between 1 and 3 neonates per 1000 live births in the region. 
It is commonly believed that up to 70% of the variance in NTDs prevalence may be due to genetic factors.  To date, few specific environmental causes of NTDs have been recognized, and include maternal diabetes, maternal use of some antiepileptic drugs such as valproic acid, fever, hyperthermia in early pregnancy, maternal obesity, maternal age over 35 years, fetal alcohol syndrome, multiple pregnancy, maternal under nutrition, and stressful life events. ,,,, Our data also showed that 50% of the NTDs in the study were seen in grand multiparous (parity 5+) women. This may point to the contribution of maternal depletion in the etiology of NTDs in this study population. Our data, however, did not show an increase in NTDs among offspring of mothers aged 35 years and above, which has been shown to be a risk factor for the development of CNS malformations. 
Maternal pregestational diabetes mellitus which is an important risk factor for the development of CNS malformations, has been found to cause a 2-fold to 10-fold increase in risk of CNS malformations (including NTDs) among the offspring of affected women, relative to the general population. , The teratogenic effect of maternal diabetes may be due to embryonic exposure to elevated glucose concentrations.  Hyperglycemia has been shown to inhibit the uptake of myo-inositol, which is essential for embryonic development during gastrulation and neurulation stages of embryogenesis.  It is estimated that diabetes mellitus complicates between 2% and 6% of all pregnancies.  Data from our study show that about 1.6% (23/1454) of the mothers gave a history of pregestational diabetes mellitus. NTDs were, however, not seen in the offspring of diabetic mothers in this study. Optimal glycemic control in these women may explain this finding. Given that the pathogenesis of diabetic embryopathy is heterogeneous, the maintenance of glucose homeostasis is an important for the prevention of diabetic embryopathy. 
Among environmental factors, folate status plays a key role in determining the risk of NTDs.  The term folate is typically used as a generic name for the group of chemically related compounds based on the structure of folic acid, which is a synthetic dietary supplement.  Folates are integral to intracellular one-carbon metabolism, which produces pyrimidines and purines for DNA synthesis and s-adenosyl methionine, the universal methyl group donor for all macromolecules. , Both folate and folic acid must be reduced to participate in cellular metabolism.  The micronutrient form of folate 5-methyltetrahydrofolate (MTHF) which circulates in plasma, is the physiologically active form of folate that serves as a cofactor for enzymatic reactions that involve the transfer of one-carbon moieties necessary for purine and pyrimidine synthesis. , Demands for folate increase during pregnancy because it is also required for growth and development of the fetus.  Maternal folate status is involved in the pathogenesis of NTDs, and although the exact mechanism is not clear, a nutritional or genetic defect in homocysteine metabolism through methionine synthase appears likely.  Maternal supplementation with folic acid during pregnancy reduces NTD frequency whereas reduced serum folate and/or elevated homocysteine (an inverse indicator of folate status) is observed in some mothers of NTD fetuses, and is considered risk factors for NTDs. ,, In humans, dietary supplementation with supraphysiologic doses of folic acid, before and during pregnancy, reduces the incidence of NTDs by up to 70%. ,,[ 3] A common mutation in the gene for 5, 10-MTHF reductase (MTHFR) (an enzyme critical for almost all biologic processes that involve the metabolism of folate and methionine) has been identified which produces a thermolabile variant of 5, 10-MTHFR with reduced enzyme activity, and folic acid is believed to act to increase the activity of the variant MTHFR thereby reducing plasma homocysteine levels. , It has been shown that maternal folate levels in most human NTD - affected pregnancies are in the "normal" range, suggesting that low folate status may increase susceptibility but is not directly causative.  Folic acid which is the synthetic and most stable form of folate is the form most often used in supplements and food fortification, and has a bioavailability of 70-85% compared to 50% for folates occurring naturally in foods. ,
Since the neural tube develops and closes within 28 days of conception, before many women become aware that they are pregnant, public health services in many countries recommend that all women capable of becoming pregnant should consume at least 400 mcg of supplemental synthetic folic acid daily in addition to a folate-rich diet. ,, If continuous supplementation is not possible, experts suggest that women begin folate supplementation at least 1-month before becoming pregnant.  Our data show that only about 5.03% (73/1452) of the mothers in this study began the use of folic acid-containing multivitamin supplement at least 1-month before or in the 1 st month of the index pregnancy, while about 10.90% (158/1452) reported no use at all. One NTD was observed in each of these groups. Although multifactorial inheritance is the most common cause of NTDs, recent evidence suggests that several of the many known NTD risk factors have immune features and/or associations, including diabetes mellitus, exposure to pharmaceutical compounds such as valproic acid, and induction of high titers of folate receptor autoantibodies. 
This study shows that a high prevalence of NTDs (2.75/1000 live births) exists in the study population. Furthermore, since only about 5% of the mothers in the study showed knowledge of appropriate use of folic acid supplementation, a missed opportunity for education on the appropriate use of periconceptional folic acid containing multivitamin supplements thus exists in the study population. Given that children with severe birth defects such as NTDs have a 15-fold increased risk of death during the 1 st year of life, with 9-10% of such children dying during this period,  a concerted public health effort to reduce the prevalence of NTDs by promoting awareness and consumption of folic acid among women of childbearing age in the community, will help improve their preconception health and combat infant mortality.
Financial Support and Sponsorship
Conflicts of Interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]