Journal of Pregnancy and Child Health
Open Access

ANC: Antenatal Care; AOD: Adjusted Odds Ratio; CNS: Central Nervous System; CI: Confidence Interval; EPHI: Ethiopian Public Health Institute; ETB: Ethiopian Birr; IFA: Iron Folic Acid; LBW: Low Birth Weight; LMIC: Low and Middle Income Countries; MMWR: Morbidity and Mortality Weekly Report; NNP: National Nutritional Program; NTD: Neural Tube Defect; OR: Odds Ratio; PPIP: Perinatal Problem Identification Program

Neural tube defect (NTD) is related to failure of neural tube closure between 3^rd and 4^th weeks of embryo development [1]. The cause of NTDs is not clearly stated, however, many factors like radiation, drugs, malnutrition, chemicals, genetic, maternal age, previous history of still birth, lack of Antenatal Care (ANC), consanguinity and any febrile illness during pregnancy were identified as contributors for development of NTDs [2-4].

Anatomically, NTD can be classified into cranial and spinal defects. Cranial defects comprised anencephaly, encephalocele, and iniencephaly. On the other hand, spinal defects include meningocele, myelomeningocele and spina bifida occulta [5]. The spina bifida occulta could be due to vertebral column defects while the neural tube is normal in development [6].

Depending on the surface exposure or skin covering, the NTDs can be categorized as opened or closed defects [2]. Opened NTD is characterized by communication of brain and spinal cord or its meningeal covering with the external environment which includes anencephaly, spina bifida, iniencephaly and encephalocele. Nonetheless, in closed NTD there is no communication with external environment which includes spina bifida occulta, lipoma, diastematomyelia, diplomyelia [2,7].

Neural tube defects are characterized by incomplete closure of the spinal column and cranium. When newborns with NTDs survive, they will end up in lifelong disability as well as medical expense for their families [8]. For instance, study done in Florida revealed that about 70 cases of newborn with spina bifida were identified each year with an estimated cost of $44.5 million [9]. Besides, study done in United States the lifetime medical costs involved for each child with spina bifida is estimated at approximately $294,000.00 [10].

People born with spina bifida usually lacks acceptance in their communities. In Kenya stigmatization of neural tube defects has been documented affecting the quality of life of caring families [11].

A severe birth defect that has scientifically been shown to be avoidable is NTD [12]. A considerable number of NTDs occur as a result of insufficient intake of folic acid around the time of conception [9]. Recent study showed that only about 10% of NTDs are being prevented through folic acid fortification worldwide [13]. Despite this fact, nearly two-thirds of Ethiopian women are victim of folic acid deficiency [14].

Worldwide, more than 300,000 babies are born with NTDs each year, serious birth defects of the brain and spine are a significant cause of infant death and lifelong disability [13]. In Africa, it is said to affect approximately 1-3 per 1000 births annually [15]. According to study done in Tanzania NTDs was the highest prevalence form of birth defect (1/1000 births) among the selected external major structural defects [16].

In Ethiopia the prevalence of birth defect is 19 per 1000 births from which 30.87% is attributable to NTDs, which is the second common cause of birth defect [3,17]. According to study done in two teaching hospitals in Addis Ababa, Ethiopia, the prevalence of neural tube defect is higher (6.1/1000 births) than reports from different studies in African countries [15,16,18].

In Ethiopia there are limited studies done on factors associated with NTDs, studies indicated regional variation on the occurrence of NTDs and folic acid deficiency [19,20]. Therefore this study was undertaken to identify factors associated with NTDs and provide baseline for future studies.

Study design

A case control study design was used conducted among newborn in four public hospitals, in Bale Zone.

Sample size

The total sample size was 462 ( 42 cases and 420 controls) determined with Epi info version 7.1 using prevalence of exposure (alcohol intake of mothers) among control 9.8% OR=3.15 [4]. Convenience sampling method was employed to include all newborns with neural tube defect and ten consecutive newborns without NTDs delivered after each case.

Data collection procedure

Data were collected using structured questionnaire from relevant related studies, which include questions of socio-demographic, obstetric, medical, alcohol intake and smoking history and folic acid supplementation [21-23]. The questionnaire was prepared in English then translated into Amharic and Afan Oromo then back to English for consistence of translation.

Four data collectors (midwives) and four supervisors (head nurses of Maternity and labor ward) were recruited. The supervisors and data collectors were trained for two days on basic principles of data collection and on the questionnaire by the principal investigator [24]. Accordingly, the supervisors continuously followed the data collection process. Moreover, supervisors and investigators reviewed and cross collected data before analysis [25,26]. Finally, it was reported and discussed with the investigator on a daily basis throughout the data collection period.

Data quality assurance

To maintain data quality, data collectors were selected by their educational level and experience of data collection. They were trained about data collection tool and purpose of the study for two days. The questionnaire was developed by the investigator based on questions used in previous peer reviewed published studies [26,27]. Pretest study was conducted at nearby health center to see for the accuracy of responses, language clarity, and appropriateness of the tools. The collected data had been cleared by the investigator and supervisor on daily basis during data collection.

Data management and data analysis

The collected data were coded, manually checked and entered by using Epi-data version 3.1 prior to analysis, the data were exported from Epi-data to SPSS Version 21 and was checked for missing values. Descriptive statistics and numerical summary measures were presented by using frequencies distribution tables and graphs (diagrams). Univariate analysis was employed to examine the relationship between the outcome variable and independent variable. Those variables with (p ≤ 0.2) in the univariate analysis was entered into multivariable logistic regression model by using adjusted odds ratio (AOR) and Confidence Intervals (CI). This helps to identify important determinants by controlling possible confounding effect [28,29]. Variables with p-value<0.05 were considered as statistically significant. Hosmer- Lemeshow goodness of-fit test was used to test the fitness of model.

Ethical consideration

Ethical clearance was obtained from Ethical Review Committee of University of Gondar. Ethical clearance obtained from University of Gondar submitted to Bale Zone Health Office. Bale Zone Health Office was informed about the objectives and support letter from Bale Zone Health Office was submitted to the respective hospital CEOs. Written consent was obtained from each selected mothers to confirm willingness. Each respondent was informed about the aim of the study. They were also informed that all data obtained from them will be kept confidential by using codes instead of any personal identifiers and is meant only for the purpose of the study.

In the present study, a total of 462 newborns delivered from October 2017 to February 2018 in Bale Zone were included. Out of them 42 were newborns with NTD and 420 newborns without NTDs. Maternal age ranges from 16 to 45 years with mean age of 30.29 ± 7.27 year. The mean age of mothers in the control group was 30.83 ± 7.22 year and in case group was 29.86 ± 5.32 year.

Socio-demographic predictors

Univariate analysis of maternal socio-demographic characteristics revealed that, maternal age between 15-24 year of age was significantly associated with increased risk of NTDs (OR=4.78, 95%CI, 1.10-20.66) [30-32]. Attending secondary school was identified to be protective for NTDs both in mothers and their husbands (OR=0.228, 95%CI, 0.096- 0.547) and (OR=0.171, 95%CI, 0.07-0.41), respectively. Regardless of the statistically non-significant difference, the number of mothers attending college and above was slightly higher among controls 118 (28.1%) than mothers of newborns with NTDs 7(16.7%) [33-35]. Marital status, occupational status, monthly family income, religion and ethnicity were not significantly associated with NTDs (Table 1).

Table 1: Socio-demographic characteristics of mothers of newborn with NTDs and controls in Bale Zone Hospitals, Southeast Ethiopia, 2018.

Patterns of neural tube defects

Occurrence patterns of NTDs identified were anencephaly, myelomeningocele, meningocele and spina bifida occulta accounts for (32 (76.2%), 5(11.9%), 4(9.5%) and 1 (2.4%)), respectively (Figure 1).

Figure 1: Bar chart showing patterns of NTDs in Bale Zone Hospitals, Southeast Ethiopia, 2018.

Anatomically, the locations of spina bifida were lumbosacral 6 (60%), thoracolumbar 3 (30%) and lumbar 1 (10%) (Figure 2).

Figure 2: Pie chart showing anatomical locations of spinal bifida in Bale Zone Hospitals, Southeast Ethiopia, 2018.

Obstetric history of mothers

This study revealed that higher number of primigravidas give birth to NTD newborns compared to control (35%, 21%, p=0.028), respectively. Primiparous were significantly higher among mothers of newborn with NTD as compared to controls (62.9% and 23.1% p=0.000), respectively [37,38]. There was no significant difference between cases and control mothers on the history of still birth, previous history of child with NTDs and a family history of NTDs (Table 2).

Our finding indicated that mothers between the ages of 15-24 years were 4.9 times more likely to give birth of newborns with NTDs as compared with those older than or equal to 35 years of age. Similarly study done in Sudan revealed that mothers age less than 25 years were higher among cases of NTDs [5].

Consanguineous marriage found to be significantly associated with NTDs. The finding of this study, was mothers who had history of consanguinity were 6 times more likely to give birth to newborn with NTDs, this finding has agreement with study done in Egyptian, Sudan, Kashmir and Mosul city reported significant association between the consanguinity and NTDs [5,11,20,36]. The possible reason is that consanguinity is associated with genetic mutation caused by inbreeding and cause NTDs.

The result that we found revealed mothers who have previous history of abortion were 93% less likely to give birth of newborn with NTDs, is in contrast with study done in Iran revealed that mothers history of abortion were 5 times more likely to give birth to newborn with NTDs [4].

Folic acid supplementation was found to be protective for NTDs. The finding in the present study revealed mothers who were supplemented with folic acid was 91% less likely to give birth of newborn with NTDs. This in inline with the study conducted in United State and Geneva, Switzerland that reported folic acid supplement taken periconceptionally reduces the risk of NTDs by at least 50% [34,35]. The present study is also in agreement with the study done in Northern Iran revealed that folic acid consumption prior to pregnancy and during early pregnancy reduce risk of NTDs by 70 percent [24].

The finding of Present study indicated that mothers who were exposed to smoker (passive smoking) were 11 times more likely to give birth of child with NTDs as compared with mothers who were not exposed. Which is similar with study done in Italy that showed smoking were significantly associated with NTDs [4].

Patterns of NTDs tend towards more severe and lethal forms with highest being anencephaly 32(76.2%), followed by myelomeningocele 5(11.9). On the other hands, study done in Sudan and Nigeria reported myelomeningocele account (47.7%, 76.9%), followed by anencephaly (17.5% , 15.5%), respectively [41,42]. This difference is probable explained by geographical variation which affects NTD patterns.

This study revealed that consanguinity, maternal age between 15-24 years and passive smoker were risk factors associated NTDs. Therefore health education is mandatory for reproductive age group women on the risks of consanguinity and passive smoking.

Folic acid supplementation was identified to be protective for NTDs, since health facilities needs to consider folic acid supplementation for reproductive age groups women and encourage reproductive age women to have medical consultation prior to pregnancy.

The patterns of NTDs were identified with the majority being of the lethal type anencephaly followed by myelomeningocele.

Availability of data and materials: The dataset analyzed during the current study available from the corresponding author on reasonable request.

Competing interests: We have no competing interests.

Acknowledgements: We would like to be grateful to midwifes and nurses working at Madda Walabu University Goba Referral Hospital, Robe Hospital, Delo Mena Hospital and Gindhir Hospital for their support during data collection period. We would like to thanks medical directors and managers of respective hospitals for their support. We would also like to extend our thanks to all respondents for agreeing to participate in the study. Finally, we want to thanks Madda Walabu University and University of Gondar for their supported.