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ORIGINAL ARTICLE
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Epidemiology of myelomeningocoele in Africa: An experience in a Regional Neurosurgical Center in Northern Nigeria


1 Department of Surgery, College of Medical Sciences, University of Calabar, Calabar, Nigeria
2 Regional Centre for Neurosurgery
3 Department of Surgery, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria
4 Department of Surgery, University of Abuja Teaching Hospital, Sokoto, Nigeria

Date of Submission03-Nov-2020
Date of Acceptance11-Feb-2021
Date of Web Publication11-Oct-2021

Correspondence Address:
Henry Olayere Obanife,
Division of Neurosurgery, Department of Surgery, College of Medical Sciences, University of Calabar, Calabar.
Nigeria
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpn.JPN_291_20

 

   Abstract 

Background: Myelomeningocoele is a common birth defect with strong associations with folate deficiency and maternal illiteracy. The aim of this study is to describe the distribution and pattern of myelomeningocoele in a resource-poor community and determine the factors responsible for the rising incidence in Africa. Patients and Methods: Prospective cohort study of 90 patients with myelomeningocoele who were treated at the Regional Centre for Neurosurgery (RCNS), Sokoto between September 2015 and December 2016. Data were collected through a structured questionnaire and analyzed by using SPSS 21 version. Results: Ninety patients were recruited into this study with a male: female ratio of 1:1 and a mean age of 102±213 days at presentation. The majority of patients’ mothers were between 19 and 35 years of age, with 70% having no formal education; however, most of the patients’ fathers were either unskilled casual workers or subsistent farmers (56.7%). Of the 36.7% of the patients’ mothers who had antenatal care, only 35.6% of them took a folic acid supplement mostly after the first trimester. More than 90% of the mothers had persistent sources of heat irradiation during pregnancy, majorly from firewood cooking. Most of the myelomeningocoele (MMC) sacs (72.9%) were located in the lumbar and sacral regions. Wound infection was the most common complication (50.0%), whereas trans-fontanelle ultrasound scan (TFUSS) showed hydrocephalus in 45.6% of patients. Conclusion: Myelomeningocoele is a common medical problem with increased incidence in poor countries. Poverty and illiteracy play major roles in its occurrence, and challenges are faced with its prevention and management. Long-time exposure to heat from firewood cooking and multiparity were identified as significant risk factors for myelomeningocoele.


Keywords: Africa, epidemiology, myelomeningocoele



How to cite this URL:
Obanife HO, Nasiru IJ, Lagbo J, Otorkpa EJ, Shehu BB. Epidemiology of myelomeningocoele in Africa: An experience in a Regional Neurosurgical Center in Northern Nigeria. J Pediatr Neurosci [Epub ahead of print] [cited 2021 Dec 9]. Available from: https://www.pediatricneurosciences.com/preprintarticle.asp?id=327906





   Introduction Top


Myelomeningocoele is one of the most common neural tube defects.[1] It occurs as a result of a teratogenic process, leading to failure of closure and abnormal differentiation of the embryonic neural tube during the first 28 days of gestation.[2],[3]

Myelomeningocoele is the most common major birth defect, with a prevalence at birth of between 4.4 and 4.6 cases per 10,000 live births from 1983 to 1990.[4] Internationally, the incidence of myelomeningocoele varies widely from country to country and from one geographical region to another within countries. Racial and ethnicity-specific prevalence estimates of myelomeningocoele with five years of a population-based study found that Hispanic women had the highest overall rates, followed by whites, Blacks, and Asians.[5] Lower socioeconomic status is associated with higher risk in many populations.[6],[7],[8] Mortality rate reported for infants who are untreated for myelomeningocoele ranges from 90% to 100% based on several series of studies dating from the turn of the century through recent years.[6],[7],[8],[9] Most patients with myelomeningocoele are born to mothers with no previous affected children or family history. However, certain genetic, racial, and environmental risk factors are strongly associated with the occurrence of myelomeningocoele.[10],[11] Siblings in a family with one affected child have an increased risk of an myelomeningocoele (MMC) than children born to families without a history of MMC.[12] Twin studies showed a concordance rate of 7.7% for monozygotic twins and 4.0% for dizygotic twins, respectively, and these are consistent with genetic contributions to the risk of MMC.[12] Maternal risk factors include insulin-dependent diabetes mellitus and hypothermia.[6] Intrauterine fetal exposure to drugs such as valproic acid, carbamazepine, and drugs used to induce ovulation are identified as risk factors for MMC.[8] A study of the association of low maternal education with neural tube defects revealed that the single strongest predictor of having a child with a neural tube defect was low maternal education.[13] This study recommended that to further reduce the incidence of neural tube defects, interventions should target women of low educational status.[13] Various studies have shown that up to 50% of cases of neural tube defects are related to a nutritional deficiency of folic acid and thus, are preventable.[8]

Aim

  • To describe the distribution and pattern of myelomeningocoele in the study population.


  • To determine the etiology or risk factors responsible for the increasing incidence of myelomeningocoele in the African continent.



  •    Patients and Methods Top


    This study was carried out at the Regional Centre for Neurosurgery, Usmanu Danfodiyo University Teaching Hospital, Sokoto. All patients with myelomeningocoele treated during the study period from September 2015 to December 2016 were recruited into the study. Sociodemographic features, clinical features, radiological findings, perioperative details, and postoperative clinical outcomes during hospital admission up to one year follow-ups were obtained from patients, caregivers, theater records, and case files by using a structured proforma.

    Inclusion criterion

    Patients with established diagnosis of myelomeningocoele and who had undergone surgery during the study period.

    Exclusion criteria

    Patients who defaulted from care or follow-up clinics, all patients who refused consent, and all cases of lipoma, dermoid cysts, or meningocoeles were excluded from the study.

    The study was conducted as a hospital-based prospective cohort study. The sample size was calculated by using the Fisher’s formula as follows: n = (Z2 pq/d2) and a total of 90 patients were recruited into the study. Data were analyzed by using the statistical packages for the social sciences (SPSS) version 21 for windows. Data collected on proforma (Appendix II) were entered by using numerical codes. Comparisons of proportions between the two groups were made by using chi-square analysis or Fischer’s exact tests for means or Mann-Whitney test for medians where appropriate.


       Results Top


    Sociodemographic characteristics

    A total of 90 patients certified the inclusion criteria. The mean age at presentation was 101.9 days with a standard deviation of 213.32. Forty-three patients (47.8%) were aged 28 days or less, 41 patients (45.6%) were between the ages of 29 and 364 days, and eight patients were 365 days old or older. There was no sex dominance with a male to female ratio of 1:1. However, most of the female patients presented during the neonatal period (60.5%) whereas the male patients presented predominantly during infancy (58.5%) and early childhood (66.7%), respectively [Figure 1]. More than half of the patients’ mothers {51 (56.7%)} were in the ages of 19 to 35 years, 23 (25.6%) of the patients’ mothers were older than 35 years, and the remaining 16 (17.8%) of the mothers were adolescents [Figure 2]. Sixty-three (70.0%) of the patients’ mothers lacked formal education whereas 17 (18.9%) and 10 (11.1%) had primary and secondary or postsecondary level of education, respectively [Figure 3]. Most of the patients’ fathers {64 (71.2%)} were either unskilled casual workers or subsistent farmers whereas 19 (21%) were gainfully employed (having jobs that can sustain a standard of living above poverty level) [Figure 4].
    Figure 1: Comparison of patients’ age and sex distribution

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    Figure 2: Mothers’ age group

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    Figure 3: Mothers’ level of education

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    Figure 4: Fathers’ occupation

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    Mothers’ obstetric history

    More than a third {33 (36.7%)} of the patients’ mothers had antenatal care services in the hospitals: Among them, 21 (63.6%) commenced these services from the first trimester and 10 (30.3%) started them in the second trimester. Thirty-two (35.6%) were compliant with folic acid and other routine antenatal drugs, though they mostly commenced them in the second trimester of pregnancy. Four mothers (4.4%) had a history of epilepsy and use of antiepilepsy medications. The majority of the patients’ mothers (92.2%) had persistent and/or intense heat exposures, 67 (74.4%)} of whom were exposed to heat through routine firewood cooking, 10 (11.1%) had high-grade fever especially during the first trimester, and 6 (6.7%) had multiple risk exposures in the form of firewood cooking, high-grade fevers, and/or radiation exposure during medical investigations in the hospital. More than half {46 (51.1%)} of the patients’ mothers had more than two deliveries, whereas 29 (32.2%) were grand multipara. There was a second-degree family history of myelomeningocoele in six (6.7%) patients. Majority of the patients {74 (82.2%)} were delivered at home, whereas only 16 (17.8%) were delivered in the hospital. Eighty (88.9%) patients were products of full-term pregnancies, whereas eight (8.9%) were delivered preterm. Seventy-nine (87.8%) patients gave birth via spontaneous vaginal delivery, whereas 11 (12.2%) delivered via Cesarean section. Birth weights for 63 (70%) of the patients were not known, because they were delivered at home. However, 26 (27.8%) of the patients had normal birth weight whereas 2 (2.2%) had low birth weight [Table 1].
    Table 1: Relevant obstetric features

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    Preoperative evaluation

    Less than half {43 (47.8%)} of the myelomeningocoele sacs were located in the lumbosacral region, whereas 22 (24.4%) and 15 (16.7%) were located in the lumbar regions respectively. Rarely, a few MMC sacs were seen in the cervical and thoracic regions {7 (7.8%) and 3 (3.3%)}, respectively. More than half {46 (51.1%)} of the MMC sacs were greater than 5cm2 in size. Fifty-six (62.2%) of the patients had ulcerations of the MMC sacs at presentation. Thirty-nine (43.3%) of the patients had ruptured MMC sacs with cerebrospinal fluid (CSF) leaks at presentation, whereas 45 (50.0%) had infected sacs, and 22 (24.4%) had meningitis (with both clinical and laboratory confirmations). Forty-eight (53.3%) had failure to thrive. Forty-nine (54.4%) patients had a normal TFUSS, whereas 25 (27.8%) had communicating hydrocephalus [Table 2].
    Table 2: Preoperative assessment features

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    Perioperative management features

    Seventy-four patients (82.2%) had elective surgeries, whereas 16 (17.8%) had emergency surgeries. Fifty-two (57.8%) had excision only, whereas 38 (42.2%) had excision and repair with VP shunt done. However, 15 (16.7%) had revision surgeries [Table 3].
    Table 3: Perioperative features

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       Discussion Top


    Sociodemographic characteristics

    In Nigeria and other developing countries, sick people often experience a delay in accessing health facilities for treatment. A study in Lagos reported harsh socioeconomic realities as the factors responsible for late presentation of myelomeningocoele in sub-Saharan Africa, and a study in Zambia showed that majority (56%) of the patients were aged between one and six months at presentation with P < 0.001.[14],[15] Similarly, a majority of the patients presented in this study had delayed presentation notably after the first 72 hours of life when early repair of MMC is no longer possible with a mean age of 101.86 ± 213.32 days at presentation. In our experience, the sociocultural background of the affected families is the major factor leading to late presentation of our patients. Most of the parents are either subsistent farmers or casual laborers residing in the villages that are far remote from the Regional Centre for Neurosurgery (RCNS) where MMC patients can be treated. The process of sourcing for funds, initial attempts of unorthodox septic treatment, and eventual transportation of patients to the RCNS usually comprise the bulk of the useful time, thereby leading to a primary delay in presentation. The sex distribution among patients with MMC varies globally. In Nigeria, most recent studies in North Western, Nigeria and in South South, Nigeria showed no significant sex dominance congruous with our finding of a male-to-female ratio of 1.[16],[17]

    Most of the patients’ mothers (74.5%) were ≤ 35 years of age, which was consistent with the median maternal age of 26 to 30 years in a study in Southern Nigeria.[17] However, these are at variance with the results of studies with a strong link between older maternal age (>35) and non-chromosomal birth defects such as neural tube defects, cleft lip or palate, congenital inguinal hernia, and cardiac defects.[18],[19],[20] However, elucidating the likely risks of MMC with the maternal age ≤ 35 years, we noted that most of our patients’ mothers ≤ 35 years of age (51.1%) were having their third or fourth child and given the traditional birth spacing of two to three years in most parts of Nigeria, a cumulative effect of the risk factors, especially nutritional deficiency of folic acid occasioned by poverty, has had sufficient time to manifest; this probably explains a previous research finding that MMC is more common among the third siblings in a family.[21]

    Poverty and low socioeconomic status are known risk factors for MMC.[19] Consistent with these associations, we found that 88.9% of the patients’ mothers were either uneducated or had attained just primary level education; however, 56.7% of the patients’ fathers were either subsistent farmers or unskilled casual workers with multiple wives who were mostly kept back at home to do domestic chores. Similar studies showed that the single strongest predictor of having a child with a neural tube defect was low maternal education.[8],[9],[10],[11],[12],[13]

    Relevant obstetric characteristics

    Overall, 36.7% of patients’ mothers attended routine antenatal clinics: 63.6% of them started from the first trimester of pregnancy whereas the remaining 35.4% attended antenatal clinics in either the second or third trimesters, respectively, during which therapeutic abortion of fetus with MMC detected via the obstetric ultrasound is no longer possible. The incidence of MMC has remained high in Africa despite the global decline, and this is majorly linked to nutritional deficiency of folic acid.[15] Previous studies have shown that up to 50% of neural tube defects are related to nutritional deficiency of folic acid.[22] Similarly, 64.4% of the patients’ mothers in this study did not use folic acid supplements before or during pregnancy. A study in Zaria also found that none of the patients’ mothers took folic acid in their first trimester of pregnancy whereas only 44% had taken folic acid starting from the second trimester onward.[23] In this study, most of the patients’ mothers who had taken a folic acid supplement started it after the first trimester and were prescribed it by obstetricians as a component of routine obstetric hematinics for the purpose of preventing anemia in pregnancy. This inconsistency in the use of folic acid seen even among pregnancies that had antenatal care were due to poor knowledge of the periconception use of folic acid among women of child-bearing ages and health workers involved in antenatal care services in primary and secondary health-care facilities. This is corroborated by findings from a study on the knowledge and uptake of folic acid among pregnant women attending a secondary health facility, which showed that only 11.8% of the women knew that folic acid can prevent birth defects and only 22.7% knew the best time to start using folic acid.[24]

    More than 4.4% of the patients’ mothers in this study had seizure disorders, and some were on routine antiseizure medications. Maternal epilepsy and the use of antiepilepsy medications are known risk factors for MMC, with the incidence rising from 3% without drugs to 9% with drug administration.[8],[25] The teratogenic mechanisms of the antiseizure drugs are hypothesized to involve anti-folate effect and histone deacetylase inhibitory activity, which alter the balance of protein acetylation versus de-acetylation, thereby leading to NTD.[26],[27] Even though earlier investigations on hyperthermia from fever and exposure to heat yielded inconsistent findings, 92.2% of the patients’ mothers in this study had persistent heat exposure. The most common source of persistent heat exposure was the practice of cooking food by setting dry wood (firewood) aflame; this was habitually practiced by 74.4% of the patients’ mothers. Firewood cooking is predominantly the method used by people of low socioeconomic class and people living in the rural areas where a majority of the patients come from.[25] This might be the reason why people of lower socioeconomic status and residents in neighborhoods with lower socioeconomic status have higher risks of having children with MMC.[23]

    Positive family history was shown to confer a risk of developing MMC; the mechanism for this is poorly understood but it is believed to be a multifactorial polygenic or oligogenic pattern of inheritance.[26] A study on the families in a group of MMC patients reported 8.5% family risk, and this is congruous with our finding of 6.7% positive family history.[25]

    Preoperative evaluation

    The lumbar region is the most common site for MMC occurrence, and this was seen in up to 60% of patients with P < 0.001 in a certain study.[14] Similarly, the most frequent region of occurrence in this study was the lumbar region, with only 7.8% and 3.3% of cases occurring in the thoracic and cervical regions, respectively.

    More than half (51.1%) of the patients had large defects (>5cm2). Large MMC sacs (>5cm2) were associated with a higher rupture rate compare with smaller MMC sacs (≤5cm). MMC sac ulcerations, rupture with CSF leaks, infections, and failure to thrive were the most complications seen before patients’ presentation. These complications occurred because 82.2% of the patients were delivered unsupervised at home under septic conditions. TFUSS was the initial investigation used to assess the ventricles, and this showed normal results in 54.4% of the patients. However, a previous study showed hydrocephalus in 61% of the patients studied.[14]

    Perioperative management features

    Managing patients with MMC in sub-Saharan Africa can be potentially distressing due to several socioeconomic and health-care associated factors.[14] It is often difficult for most of these patients with financial difficulties to source for funds to finance investigations and treatment, especially when CT or MRI is being requested or when there is need for an emergency surgery. This difficulty potentially leads to a secondary delay in patient care, thereby resulting in increased morbidity and mortality. More than 17% (17.8%) of the patients had emergency surgeries on account of MMC sac rupture and persistent CSF leaks.

    Only 42.2% of the patients had MMC repair with VP shunt either at the same time or on different days. More than fifty-seven percent (57.8%) of those who did not have VP shunt insertion did not develop hydrocephalus during the follow-up period.


       Conclusions Top


    Late presentation of patients with MMC at the RCNS was significant and mostly caused by poverty, illiteracy, and unhealthy cultural practices in rural communities. The chief etiological factors found were maternal persistent heat exposure mostly from firewood cooking, poverty, and maternal illiteracy. There was a lack of understanding of the need and timing of commencement of a periconception folic acid supplement.

    Financial support and sponsorship

    The authors received no external funding for the study design; data collection, analysis, and interpretation; or for writing the article.

    Conflicts of interest

    None.

    Authors’ contributions

    All authors contributed to the research idea and methodology. Henry Olayere Obanife collected, analyzed, and interpreted the data. Henry Olayere Obanife completed the first draft of the article. Bello Bala Shehu, Jacob Legbo, and Nasiru Jinjiri Ismail contributed toward drafting and revising the article. All authors read and approved the final article.

    Ethics approval and consent to participate

    Ethical approval was granted by the Institution’s Ethical and Research Committee. All patients recruited into this study provided informed written consent to participate in the study.

    Availability of data and material

    The dataset and materials used for this study are available from the corresponding author on reasonable request.



     
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        Figures

      [Figure 1], [Figure 2], [Figure 3], [Figure 4]
     
     
        Tables

      [Table 1], [Table 2], [Table 3]



     

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