Birth defects can be defined as structural or functional abnormalities, including metabolic disorders, which are present from birth [
Neural tube defect are the second most serious leading cause of neonatal mortality next to prematurity and birth asphyxia worldwide [
Studies conducted across the globe have identified different factors of NTDs. These include low socioeconomic status, maternal exposure to certain environmental factors (i.e., chemicals and pesticides), tobacco use during pregnancy, genetic factors, pregnancy in the late maternal age, poor intake of folic acid prior or during pregnancy, sex of the neonate, and no antenatal care [
Different programs, strategies, and policies at global, regional, and national levels have been tried in the past to address the burden of congenital abnormalities at large and neural tube defects in particular. These strategies include folic acid and/or multivitamins supplementation before or during pregnancy periods [
The study was conducted from December 15, 2018, to January 01, 2019, among newborns in the four randomly selected public hospitals (namely, Debre Birhan, Dessie, Woldia, and Felege-Hiwot referral hospitals) those located in the Amhara Regional State, Ethiopia. The region has a total of seven referral hospitals, which serve an estimated more than 25 million populations in the region.
A hospital-based unmatched case-control study design was conducted to identify the determinants of neural tube defects (NTDs) among newborns. Neonates born after the age of viability (after 28 weeks of gestation) with a confirmed diagnosis of NTD during the study period were included as cases and those neonates born without any form NTDs during the study period were included as controls. However, pregnancies terminated before 28 weeks of gestation and neonates whose mothers were seriously ill during the study period were not included in this study.
To determine the sample size, various factors significantly associated with the outcome variable were considered, and the larger sample size was used for this study.
The required sample size was determined using the double population proportion formula with the assumptions of 95% CI, 80% power, case to control ratio of 1 : 2, and 5% contingency was allowed to compensate nonresponses. Moreover, the percent of cases exposed (
Based on the prestudy chart review, an estimated 6,480 neonates with NTDs were born in the randomly selected four public hospitals in the previous year (from December 2017 to 30 October 2018). Then, the cases were proportionally allocated into the randomly selected public hospitals (i.e.,
The dependent variable was neural tube defects (NTDs) (
Independent variables are as follows: (1) sociodemographic characteristics of the mother, (2) obstetric and medical conditions of the mother, (3) substance use during pregnancy, and (3) newborn-related factors.
The questionnaire used was adapted and modified from previous literature conducted in Ethiopia and other developing regions of Africa [
The data were collected using face-to-face interviews guided by structured and pretested interviewer-administered questionnaire. Besides, the maternal and neonatal medical chart review was done. The same interviewer was used to interview both cases and the consecutive two controls. The outcome variable was attributed to newborns whose medical records indicated a physician or midwife diagnosis of neonates with NTD or free of NTDs. Mothers were interviewed in private rooms to ensure their privacy and to encourage participation.
Three days of training was provided for data collectors and supervisors. Eight trained midwives or nurses who work in the labor wards of each of the selected hospitals collected the data. An independent translator translated the English language into the local language (Amharic), then back to English the measurement tool. A pretest of the questionnaire was conducted with 5% (21 participants) of samples newborns delivered other than the selected public hospitals. The mothers of newborns were interviewed within four to six hours of delivery.
The data were checked for completeness and were entered into the Epi data version 3.1. Then, the data were exported and analyzed using Stata version 14.0. The collected data were checked for normality and other assumptions. Model fitness was assessed using the Pearson or Hosmer-Lemeshow goodness-of-fit test. In addition, the correlation between the independent variables was checked.
Texts, frequency tables, graphs, mean, and standard deviations were applied to present the descriptive statistics.
Binary logistic regression analysis was done to evaluate the association of NTD with each predictor variable, and variables with a
In this study, a total of 127 cases and 254 controls were included with a response rate of 95.3%. The mean age of the participants was
A higher proportion of mothers in the case groups resided in rural areas compared to mothers in the control groups (59.1% and 36.2%, respectively). When comparing the highest completed educational level by mothers, a higher proportion of mothers of the cases did not attend any formal education (41.7% compared to the mother of the controls (11.4%) (Table
Sociodemographic characteristics of participants who gave birth at public referral hospitals, Amhara Region, Ethiopia, 2019.
Predictor variables | Category of variables | Cases | Controls | |
---|---|---|---|---|
Age | ||||
18-27 | 40 (31.5) | 96 (37.8) | 3.15, | |
28-34 | 60 (47.2) | 96 (37.8) | ||
≥35 | 27 (21.3) | 62 (24.4) | ||
Residence | ||||
Rural | 75 (59.1) | 92 (36.2) | 17.93, | |
Urban | 52 (40.9) | 162 (63.8) | ||
Education level of mother | ||||
Illiterate | 53 (41.7) | 29 (11.4) | 59.16, | |
Primary | 23 (18.1) | 112 (44.1) | ||
Secondary | 32 (25.2) | 92 (36.2) | ||
Tertiary | 19 (15.0) | 21 (8.3) | ||
Marital status | ||||
Single | 8 (6.3) | 13 (5.1) | 0.23, | |
Married | 119 (93.7) | 241 (94.9) | ||
Sex of the newborn | ||||
Male | 38 (29.9) | 120 (47.2) | 10.47, | |
Female | 89 (70.1) | 134 (52.8) |
In this study, a higher proportion of mothers of cases had no antenatal care follow-up (15.5%) compared to mothers of controls (5.5%). Moreover, a higher percent of mothers with cases were not supplemented with folic acid (77.9%) compared to mothers of controls (49.2%). Furthermore, mothers with cases had twice-higher exposure history of previous NTDs compared to mothers with controls (62.2% and 28.38%, respectively). Finally, a higher proportion of mothers of cases used substances (drugs, alcohol, khat, and cigarette) during pregnancy (29.1%) compared to the mothers of controls (9.1%) (Table
The maternal obstetric, behavioral, and newborn-related conditions, Amhara Region, Ethiopia, 2019.
Predictor variables | Category of variables | Cases | Controls | |
---|---|---|---|---|
Parity | ||||
Multipara | 82 (64.6) | 163 (64.2) | 0.015, | |
Primipara | 45 (35.4) | 91 (35.8) | ||
ANC follow-up for this index pregnancy | ||||
Yes | 108 (85.0) | 240 (94.5) | 9.56, | |
No | 19 (15.0) | 14 (5.5) | ||
Gestational age at birth | ||||
<37 weeks | 11 (8.7) | 21 (8.3) | 0.017, | |
≥37 weeks | 116 (91.3) | 233 (91.7) | ||
Folic acid supplemented prior to or during pregnancy | ||||
No | 99 (77.9) | 125 (49.2) | 28.87, | |
Yes | 28 (22.1) | 129 (50.8) | ||
Planned pregnancy | ||||
Yes | 51 (40.2) | 93 (36.6) | 0.45, | |
No | 76 (59.8) | 161 (63.4) | ||
Previous history of NTDs | ||||
No | 48 (37.8) | 182 (71.7) | 40.57, | |
Yes | 79 (62.2) | 72 (28.3) | ||
Medical problems during this pregnancy (PROM, DM, HTN, HIV, UTI, etc.) | ||||
Yes | 18 (14.2) | 19 (7.5) | 4.33, | |
No | 109 (85.8) | 235 (92.5) | ||
Previous adverse birth outcomes (stillbirth, PTB, LBW, abortion, and SGA) | ||||
Yes | 25 (19.7) | 32 (12.6) | 3.34, | |
No | 102 (80.3) | 222 (87.4) | ||
Substance use during pregnancy (drugs, alcohol, khat, and cigarette) | ||||
Yes | 27 (29.1) | 23 (9.1) | 25.73, | |
No | 90 (70.9) | 231 (90.9) | ||
Onset of labor | ||||
Spontaneous | 115 (90.6) | 238 (93.7) | 1.23, | |
Induced | 12 (9.4) | 16 (6.3) | ||
Mode of delivery | ||||
SVD | 105 (82.7) | 224 (88.2) | 2.23, | |
C-section | 14 (11.0) | 19 (7.5) | ||
Instrumental assisted delivery | 8 (6.3) | 11 (4.3) | ||
Weight of the newborn | ||||
<2500 | 87 (68.5) | 9 (3.5) | 189.56, | |
≥2500 | 40 (31.5) | 245 (96.5) |
Key: DM, diabetes mellitus; HTN, hypertension; HIV, human immune virus; UTI, urinary tract infection; PROM, premature rupture of membrane; PTB, preterm birth; LBW, low birth weight; SGA, small for gestational age; ANC, antenatal care; NTD, neural tube defects.
In this study, the commonest type of neural tube defects among newborns is anencephaly, which accounts for 48.1% of total cases. The second and the third common types of NTDs are spinal bifida and encephalon that account for 36.2% and 11.8% of total cases, respectively. Besides, the rest 3.9% of cases were other forms of NTDs (craniorachischisis and lipomas) (Figure
Types of NTDs among the cases of the neonates born in the hospitals, Amhara Region, Ethiopia, 2019.
The predictor variables with a
After controlling the covariates; women who resided in rural areas had 78% higher odds of newborns with neural tube defects (NTDs) compared to women who resided in urban residence (
Determinants of NTDs among neonates born at public hospitals, Amhara Region, Ethiopia, 2019.
Predictor variables | Birth outcomes | COR (95% CI) | AOR (95% CI) | ||
---|---|---|---|---|---|
Cases | Controls | ||||
Residence | Rural | 75 (59.1) | 92 (36.2) | 2.54 (1.64, 3.93) | 1.78 (1.02, 3.11) |
Urban | 52 (40.9) | 162 (63.8) | 1.00 | 1.00 | |
Mothers’ age (in completed years) | 18-27 | 40 (31.5) | 96 (37.8) | 1.00 | 1.00 |
28-34 | 60 (47.2) | 96 (37.8) | 1.50 (0.92, 2.44) | 1.74 (0.92, 3.30) | |
≥35 | 27 (21.3) | 62 (24.4) | 1.04 (0.58, 1.87) | 0.78 (0.36, 1.69) | |
Mothers’ completed educational level | Illiterate | 53 (41.7) | 29 (11.4) | 2.02 (0.93, 4.53) | 1.81 (1.07, 4.61) |
Primary | 23 (18.1) | 112 (44.1) | 0.23 (0.11, 0.48) | 0.13 (0.05, 0.35) | |
Secondary | 32 (25.2) | 92 (36.2) | 0.38 (0.18, 0.81) | 0.30 (0.12, 0.75) | |
Tertiary | 19 (15.0) | 21 (8.3) | 1.00 | 1.00 | |
Sex of the newborn | Male | 38 (29.9) | 120 (47.2) | 1.00 | 1.00 |
Female | 89 (70.1) | 134 (52.8) | 2.09 (1.34, 3.29) | 1.95 (1.09, 3.50) | |
ANC follow-up | Yes | 108 (85.0) | 240 (94.5) | 1.00 | 1.00 |
No | 19 (15.0) | 14 (5.5) | 3.02 (1.46, 6.23) | 1.93 (1.17, 5.04) | |
Folic acid supplemented prior to or during pregnancy | No | 99 (77.9) | 125 (49.2) | 1.00 | 1.00 |
Yes | 28 (22.1) | 129 (50.8) | 0.27 (0.17, 0.44) | 0.37 (0.21, 0.65) | |
Pregnancy was planned | Yes | 51 (40.2) | 93 (36.6) | 1.00 | 1.00 |
No | 76 (59.8) | 161 (63.4) | 0.86 (0.55, 1.33) | 0.94 (0.54, 1.66) | |
Previous history of NTD(s) | No | 48 (37.8) | 182 (71.7) | 1.00 | 1.00 |
Yes | 79 (62.2) | 72 (28.3) | 4.16 (2.65, 6.53) | 4.39 (2.42, 7.96) | |
Substance use during pregnancy (alcohol, khat, cigarette, and drugs | Yes | 27 (29.1) | 23 (9.1) | 1.00 | 1.00 |
No | 90 (70.9) | 231 (90.9) | 0.24 (0.14, 0.43) | 0.42 (0.21, 0.88) | |
Previous adverse birth outcomes (stillbirth, PTB, LBW, abortion, and SGA) | Yes | 25 (19.7) | 32 (12.6) | 1.00 | 1.00 |
No | 102 (80.3) | 222 (87.4) | 0.59 (0.33, 1.05) | 0.61 (0.28, 1.29) | |
Medical problems during this pregnancy (PROM, DM, HTN, HIV, UTI, etc.) | Yes | 18 (14.2) | 19 (7.5) | 1.00 | 1.00 |
No | 109 (85.8) | 235 (92.5) | 0.49 (0.25, 0.96) | 0.27 (0.11, 0.69) | |
Mode of delivery | SVD | 105 (82.7) | 224 (88.2) | 1.00 | 1.00 |
C-section | 14 (11.0) | 19 (7.5) | 1.57 (0.76, 3.25) | 2.23 (0.84, 5.91) | |
Instrumental delivery | 8 (6.3) | 11 (4.3) | 1.55 (0.61, 3.97) | 2.05 (0.63, 6.59) |
Key: AOR, adjusted odds ratio; COR, crude odds ratio; CI, confidence interval;
Defects of the neural tube involve the imperfect development of the neuropore during embryogenesis and the subsequent maldevelopment of the adjacent bone and mesenchymal structures [
Studies indicated that supplementation of folic acid three months before or during pregnancy can decrease NTDs by 50-70% [
In this study, women who had a previous history of NTDs had 4-folds higher odds of newborns with NTDs compared to their counterparts. This finding is very consistent with a study done in Addis Ababa City Administrative and Amhara Region, Ethiopia [
Previous studies recommended women to avoid harmful substances (i.e., tobacco, illicit drugs, and alcohol) during their pregnancy period [
In this study, women who resided in rural areas had 78% higher odds of newborns with neural tube defects (NTDs) compared to women who resided in urban residences. This is similar to a study conducted in Tigray regional state of Ethiopia [
Studies revealed that women with no education gave birth with NTDs compared to literate women [
Women who had no antenatal care visits had twice-greater odds of newborns with NTDs compared to those who had antenatal care visits. This finding is similar to a study done in Northwest Ethiopia [
Women who had experienced medical illnesses during pregnancy had 73% lesser odds of neonates with NTDs compared to that experienced medical illness during pregnancy. This finding is in line with a study conducted in Northwest Ethiopia [
In this study, being female neonates was 2-folds a greater risk of NTD compared to male neonates. This is similar to studies conducted in Addis Ababa Teaching Hospitals, Ethiopia [
First, the study deals with personal and sensitive behaviors, such as substance use during pregnancy. Thus, this might introduce social desirability bias. Second, the study was facility-based, in which institutional delivery is very low, and this study may not represent as close to 74% of deliveries which take place at home in the region. Lastly, the study did not address the genetic, syndromic, and chromosomal causes of NTD that are not preventable by folic acid.
The study identified different factors associated with NTDs among newborns in the region. After controlling the effect of covariates, residence, maternal education level, sex of the newborn, antenatal care follow-ups, previous history of birth with NTDs, folic acid intake, substance use during pregnancy, and medical illnesses during pregnancy were the independent predictors of NTDs among neonates. Therefore, comprehensive preventive strategies focused on identified risk factors are needed at regional and national government levels. Further research to address the genetic factors of NTDs is recommended.
Antenatal care
Ethiopian Demographic and Health Survey
Gestational age
Neonatal intensive care unit
Neural tube defects
World Health Organization.
All materials and data related to this article are included in the main document of the manuscript. However, if anyone has interested to have raw data, he/she can contact the corresponding author.
Ethical approval was obtained from the Dream Science and Technology Institutional Health Research Ethics Review Committee with the approval letter of DSTC/DHS/031/2019. Then, a permission letter was written for selected public hospitals for cooperation and support. We avoided personal identification to ensure confidentiality and anonymity of study participants.
The authors declare that they have no competing interests.