Risk factors for neural tube defects in the war and siege-affected tigray regional state of ethiopia: a case-control study

Abstract

Background

Neural tube defects (NTDs) remain a significant global health concern, with varying prevalence and risk factors across regions. In Tigray, the war and siege have severely disrupted healthcare services, exacerbating pregnancy complications and increasing NTD prevalence. This study investigates the sociodemographic, obstetric, and conflict-related risk factors contributing to NTDs in Tigray during the crisis.

Methods

A case-control study was conducted between December 2023 and January 2024, including 103 NTD cases and 205 controls. Data were collected using a WHO-adapted birth defect survey and ODK/KOBO software. Statistical analysis was conducted using SPSS version 27, with descriptive statistics used for participant characteristics and logistic regression models applied to identify risk factors for neural tube defects, using a significance threshold of p < 0.05.

Result

A total of 308 participants were included (103 NTD cases and 205 controls). Stillbirths accounted for 79.7% of NTD cases, with anencephaly as the most common defect, followed by spina bifida and encephalocele. Among NTD cases, 23.3% were male, 18.4% female, and 58.3% had unidentified sex. Associated congenital anomalies were less common, including hydrocephalus (2.9%), clubfoot, omphalocele, and cleft palate (1-1.9%). Key risk factors for NTDs included younger maternal age, low education, history of abortion or stillbirth, and lack of prenatal care. Conflict-related factors, such as violence, unintended pregnancies, and limited healthcare, worsened NTD prevalence. Food insecurity was found a significant issue, with many women relying on aid or subsistence farming and consuming fewer than two meals per day.

Conclusion

The study demonstrates that neural tube defects, particularly anencephaly the most frequently observed subtype are strongly associated with increased stillbirth rates. Diagnostic challenges, including high rates of unidentified fetal sex and low detection of associated anomalies, coupled with limited prenatal care and maternal sociodemographic factors, contribute to poor prognoses. The ongoing conflict in Tigray has further worsened maternal health risks through healthcare disruptions, increased violence, unintended pregnancies, and food insecurity, potentially contributing to the higher prevalence of neural tube defects. These findings underscore the urgent need for strengthened maternal healthcare systems, targeted prevention strategies, and improved access to care, particularly in conflict-affected regions.

Background

Neural tube defects (NTDs), including spina bifida, anencephaly, and encephalocele, present a significant public health challenge worldwide. These congenital abnormalities result from the incomplete closure of the neural tube during early embryonic development and are associated with considerable morbidity and mortality, especially in low-resource settings [1]. On a global scale, the average prevalence of NTDs is approximately two cases per 1,000 births, translating to an estimated 214,000–322,000 affected pregnancies annually [2]. The incidence and related complications of NTDs are notably higher in developing countries, where access to healthcare and nutritional resources is often limited [2]. Research consistently shows that NTDs are more prevalent in regions with inadequate prenatal care and insufficient folic acid supplementation [3–5]. Sub-Saharan Africa and parts of Asia, for example, continue to report high rates of NTDs [6]. In Ethiopia, the prevalence of NTDs is significantly higher than in Western countries seven times greater, in fact with marked regional variation. In Addis Ababa, the rate is 126 per 10,000 births, while Tigray reports a considerably higher rate ranging from 131 to 215 per 10,000 births [7–9].

The prevalence and risk factors for NTDs differ across regions, and these factors are particularly exacerbated in populations affected by war and siege. Armed conflict is a major disruptor of public health systems, with maternal and reproductive health being particularly vulnerable [10]. War zones present numerous barriers to healthcare, directly and indirectly affecting maternal and birth outcomes. Limited access to healthcare services, particularly prenatal care, is a well-established risk factor for NTDs [2, 7, 11]. In the case of Tigray, the war and prolonged siege have severely impacted healthcare infrastructure, leading to the closure of health facilities, displacement of healthcare workers, and obstructing pregnant women’s access to essential care [12–15]. The destruction of health infrastructure has also disrupted access to folic acid supplementation, which is crucial for the prevention of NTDs.

Given these circumstances, it is essential to examine how sociodemographic, obstetric, and conflict-related factors intersect to influence the prevalence of NTDs. Understanding the clinical and epidemiological implications of these factors can guide future interventions and health strategies, particularly for women in war-affected areas. In Tigray, the war and prolonged siege have been intensified instability, limiting access to vital health services and family planning, which in turn jeopardizes maternal and child health [12–15]. Our recent retrospective study conducted during the war in Tigray showed a significant increase in the prevalence of NTDs, with a rate of 262.5 per 10,000 births [16], compared to pre-war rates in Tigray of 215 and 131 per 10,000 births [8, 9]. This increase is likely a direct consequence of the war and siege, which have disrupted essential health services like antenatal care and contributed to shortages of food and basic necessities [12–15]. These factors have likely compounded the situation, leading to the observed rise in NTDs. Therefore, this study aims to identify the key risk factors for NTDs in this context, improving our understanding of the role the war and prolonged siege have played in their increased prevalence. The study also seeks to inform more effective prevention and treatment strategies for Tigray’s healthcare system moving forward.

Methodology

Study area and setting

This study was conducted across 11 public hospitals and their respective catchment areas within the Tigray Region, situated in the northernmost part of Ethiopia. These hospitals encompass both urban and rural settings, providing a representative overview of the healthcare landscape in the region. The Tigray Region is inhabited predominantly by the Tigrayan (Tegaru), Irob, and Kunama ethnic groups. Mekelle, the regional capital and largest city, serves as a major administrative and economic hub. Tigray is Ethiopia’s fifth-largest region by area, fourth in population size, and fifth in population density among the country’s 11 regional states. As of 2019, the estimated population was approximately 9.4 million, with a total fertility rate of 4.6 children per woman [16]. Agriculture is the primary livelihood, with approximately 80% of the population engaged in farming, contributing 46% to the regional gross domestic product.

In November 2020, an armed conflict erupted between the Tigray regional government, led by the Tigray People’s Liberation Front (TPLF), and the Ethiopian federal government, supported by Eritrean and Amhara regional forces. This conflict rapidly escalated into a regional war, leading to widespread humanitarian and infrastructural devastation, including the reported deaths of over 600,000 individuals [17–21] The healthcare system was severely affected, with an estimated 89% of health facilities looted and destroyed during the conflict.

Selection of study hospitals

The study targeted 11 public hospitals within the Tigray Region that remained relatively functional during the conflict and subsequent blockade. Hospitals were selected using a simple random sampling technique from the available pool of operational public hospitals. This approach was employed to minimize selection bias and ensure equal probability of inclusion for all eligible facilities, despite the challenges posed by the conflict and limited accessibility. Although the number of functioning hospitals was relatively small, random sampling was considered methodologically sound to ensure a representative sample.

The selected hospitals included: Yechila Hospital, Wukro Maray Hospital, Adwa Hospital, Shul Shire Hospital, Selekleka Hospital, Samre Hospital, Hagereselam Hospital, Lemlem Karl Hospital, Adishu Hospital, Fresemaetat Hospital, and Ayder Comprehensive Specialized Hospital. These facilities provide a broad spectrum of healthcare services, including pediatric care, gynecology and obstetrics, midwifery, and general nursing services.

Study design and period

A case-control study design was used to identify and analyze the risk factors associated with neural tube defects (NTDs) among mothers who gave birth in health care facilities in the Tigray Regional State of Ethiopia. The study was conducted in selected hospitals that provide maternal and child health services within the region, which has been affected by the recent war and prolonged siege. The collection of data was from participants at a single point in time, providing insights into the risk factors for NTDs in this context. Data collection took place from December 2023 to January 2024.

Study population and sample size

The study population consisted of cases of mothers who gave births affected with neural tube defects (NTDs), including both live-born and stillborn cases. The conditions under investigation included spina bifida, anencephaly, encephalocele, and other forms of NTDs. The control group was composed of mothers of infants without any congenital anomalies, who gave birth in the same hospitals concurrently. The sample size for this unmatched case-control study was determined using OpenEpi, Version 3, an open-source calculator. The following assumptions were used in the calculation:

• Two-sided confidence level (1-alpha): 95%.

• Power (probability of detecting the effect): 80%.

• Ratio of Controls to Cases: 2:1.

• Hypothetical proportion of controls with exposure: 40%.

• Hypothetical proportion of cases with exposure: 57.57%.

• Least extreme Odds Ratio to be detected: 2.04.

Based on these assumptions, the calculated sample sizes were as follows:

• Sample Size for Cases: 103.

• Sample Size for Controls: 205.

• Total Sample Size: 308.

Based on these parameters, the required sample size was calculated to be 103 cases and 205 controls, resulting in a total of 308 participants. All cases were compared with a randomly selected group of controls drawn from the same facilities, using an unmatched concurrent case-control approach.

Sampling technique and procedure

To ensure proportional representation across participating health facilities, the calculated sample size was allocated according to the annual number of deliveries at each site. Facility-specific delivery volumes over the preceding year were obtained from Health Management Information System (HMIS) reports. This proportional allocation was intended to enhance the representativeness of the sample and reduce potential selection bias.

Eligibility criteria

Inclusion criteria

Cases

All mothers who gave birth affected with any form of neural tube defects (live and stillbirths) and who consented to provide adequate information were included.

Control

Mothers of infants without any congenital anomalies during the same period were included.

Exclusion criteria

Mothers who were seriously ill and unable to provide information. Live births, stillbirths, and elective terminations involving non-permanent -resident women of the study districts (mothers residing outside the study districts for < 6 months prior to delivery).

Study variables

Dependent variable

The dependent variable in this study is the presence or absence of neural tube defects (NTDs), which includes conditions such as anencephaly, spina bifida, and encephalocele (as defined by International Classification of Diseases, Tenth Revision (ICD-10) [22]. This variable also accounts for medically terminated NTDs that are incompatible with life, across infants of any gestational age.

Independent variables

Sociodemographic and Obstetric Factors: Maternal age, marital status, residence, religion, education, occupation, parity, history of pregnancy outcomes, sex of baby in last pregnancy, family history of birth defects, history of children with birth defects, practice of periconceptional folic acid supplementation, and history of X-ray imaging.

Data collection tool and technique

The NTDs survey tool was adapted from the WHO birth defect surveillance tool [23]. Data were gathered electronically using the ODK/KOBO Collect software. The data collection tool/checklist contained variables representing maternal and fetal characteristics, including socio-demographic and clinical data, obstetric history, and conflict-related factors. If a study case had more than one birth defect, it was counted only once. Cases were included when they met the case definition for the specific condition being studied. The study employed prospective data collection, with interviews and questionnaires administered to mothers of both NTD cases and controls to collect information on potential risk factors (sociodemographic, obstetric, and conflict-related).

Daily data collection was carried out by midwives who had received structured training in the pathophysiology of neural tube defects (NTDs) and standardized newborn assessment protocols. Throughout the study period, these trained midwives systematically screened all deliveries for potential NTD cases. Data were recorded during the postpartum or post-abortal period, prior to maternal discharge from the health facility. For the purposes of this study, NTDs were defined as cases of anencephaly or spina bifida in infants of any gestational age. Suspected cases were verified through physical examination by senior physicians, including pediatricians, obstetricians, gynecologists, or general practitioners, based on the availability of medical personnel at the participating hospitals.

Quality assurance

Eleven well-trained BSc midwives were involved in data collection. Both data collectors and supervisors underwent five days of training on the data collection procedure and the use of the ODK data collection software before the actual data collection. Supervisors checked all filled questionnaires daily for completeness using the ODK data collection server. Both supervised and unsupervised visits to study sites were regularly conducted by the core study team to ensure data quality.

Data analysis

Data were analyzed using SPSS version 27. Descriptive statistics were used to summarize the demographic and clinical characteristics of the study population. Binary logistic regression analysis was conducted to determine the strength of association between various risk factors and the occurrence of NTDs. Variables with p < 0.25 were considered for further multivariate analysis. Multivariate logistic regression analysis was used to identify independent risk factors for NTDs, adjusting for potential confounders. A significance level of p < 0.05 was used to determine statistically significant associations. Results were interpreted in the context of existing literature and public health implications, and risk factors identified were compared with findings from other studies to validate results and understand their relevance to the local context.

Ethical considerations

This study was part of a PhD program within Mekelle University’s large-scale research initiative focused on using periconceptional folic acid supplementation to prevent neural tube defects in Tigray, Northern Ethiopia. Ethical approval was obtained from the Mekelle University Institutional Review Board (MU-IRB) under protocol number MU-IRB 1800/2020, with a subsequent renewal (ref No. MU-IRB 2101/2023). Orally informed consent was obtained from all participants before data collection. All personal and medical information was kept confidential and used only for research purposes. All study procedures adhered to the Declaration of Helsinki [24], which outlines ethical principles for medical research involving human subjects. This includes ensuring the study was conducted with respect for the rights, dignity, and well-being of participants.

Result

A total of 308 participants were recruited (103 NTD cases and 205 controls) in the selected study hospitals with two-month period.

Case series

Characteristic of the observed the neural tube defects (NTDs) cases, n = 103

The study examined 103 cases of mothers who gave birth affected with any form of neural tube defects, including anencephaly, spina bifida, and encephalocele (Table 1). Among these, anencephaly was the most common (54 cases, 52.4%), followed by spina bifida (43 cases,41.75%) and encephalocele (6 cases, 5.8%). Stillbirths occurred in 82 cases (79.7%), with anencephaly accounting for 54cases (52.4%), spina bifida for 22 cases (21.35%), and encephalocele for 6 cases (5.8%). Live births were reported in 21 cases of spina bifida, representing 20.4% of the total.

Table 1.

Characteristics of the mothers who gave birth affected with the neural tube defects (NTDs), n = 103 cases

Characteristics			Type of neural tube defects (n = 103 cases)
			Anencephaly	Spina bifida	Encephalocele	Total N (%)
			N (%)	N (%)	N (%)
Baby status	Live birth			21(20.4)		21(20.4)
	Stillbirth		54(52.42)	22(21.35)	6(5.83)	82(79.7)
	Total		54(52.42)	43(41.75)	6(5.83)	103(100)
Sex	Male		10(9.7)	13(12.6)	1	24(23.3)
	Female		7(6.8)	9(8.7)	3(2.9)	19(18.4)
	Unidentified		37(36)	21(20.4)	2(1.9)	60(58.3)
	Total		54(52.42)	43(41.75)	6(5.83)	103(100)
Associated congenital malformations	Hydrocephalous			3(2.9)		3(2.9)
	Club foot			1		1
	Omphalocele			2(1.9)		2(1.9)
	Cleft palate			2(1.9)		2(1.9)
Recurrence risk associated with neural tube defect
Blood relative with birth defects (BD)	No
	Yes	Grandmother (club foot)	1			1
		Cousin (clubfoot)	1			1
		Aunt (Congenital heart defect)	1	1		2(1.9)
		Grandfather (polydactyl)	1			1
Previous child with birth defects (BD)	No
	Yes	Spinal bifda	1	1		2(1.9)
		Club foot	3(2.9)			3(2.9)
		Anencephaly		1		1
		Abdominal defect		1		1
		Ventromegally		1		1

Regarding sex distribution, 24 cases (23.3%) were male, which included 10 cases of anencephaly (9.7%), 13 cases of spina bifida (12.6%), and 1 case of encephalocele (1%). Female cases totaled 19 (18.4%), including 7 cases of anencephaly (6.8%), 9 cases of spina bifida (8.7%), and 3 cases of encephalocele (2.9%). Additionally, 60 cases (58.3%) were unidentified sex, which consisted of 37 cases of anencephaly (36%), 21 cases of spina bifida (20.4%), and 2 cases of encephalocele (1.9%). Associated congenital malformations were observed in several affected pregnancies, including hydrocephalus (3 cases, 2.9%), clubfoot (1 case, 1%), omphalocele (2 cases, 1.9%), and cleft palate (2 cases, 1.9%). The study also assessed the recurrence risk of NTDs, focusing on both blood relatives with a history of birth defects (BD) and prior births affected. Five cases reported a family history of birth defects, including a grandmother with clubfoot, a cousin with clubfoot, an aunt with congenital heart defects, and a grandfather with polydactyly. Additionally, eight cases had a history of birth defects, including two with spina bifida, three with clubfoot, one with anencephaly, one with an abdominal defect, and one with ventriculomegaly, all recurring in the current pregnancy.

Case control analysis

Sociodemographic and Obstetric Characteristics of Study Participants (n = 308: 103 NTDs cases and 205 controls)

The findings offer valuable insights into how various factors, including maternal age, marital status, education, occupation, obstetric history, and family history, contribute to the risk of giving birth affected with the neural tube defects (NTDs) (Table 2).

Table 2.

Sociodemographic and obstetric characteristics of study participants, n = 308 (103 cases, 205 controls

Characteristics		Neural tube defects (NTDs)
		Yes	No	Total
		N (%)	N %	N %
Sociodemographic history
Maternal age	<=25	46(14.9)	99(32.1)	145(47.1)
	26–35	4614.9)	94(30.5)	140(45.5)
	> 35	11(3.6)	12(3.9)	23(7.5)
Marital status	Not married	16(5.2)	31(10.1)	47(15.3)
	Divorced	2(0.6)	4(1.3)	6(1.9)
	Married	85(27.6)	170(55.2)	255(82.8)
Residence	Rural	57(18.5)	110(35.7)	167(54.2)
	Urban	46(14.9)	95(30.8)	141(45.8)
Religion	Orthodox	98(31.8)	201(65.3)	299(97.1)
	Muslim	5(1.6)	4(1.3)	9(2.9)
Education	No formal education	20(6.5)	47(15.3)	67(21.8)
	Elementary school	36(11.7)	70(22.7)	106(34.4)
	High school	33(10.7)	60(19.5)	93(30.2)
	College diploma and above	14(4.5)	28(9.1)	42(13.6)
Occupation	House wife	41(13.3)	65(21.1)	106(34.4)
	Farmer	23(7.5)	60(19.5)	83(26.9)
	Labor	39(12.7)	27(8.8)	66(21.4)
	Merchant		25(8.1)	25(8.1)
	Collage educated professional		28(9.1)	28(9.1)
Obstetric history
Parity	Prime	35(11.4)	60(19.5)	95(30.8)
	parity 1–3	48(15.6)	99(32.1)	147(47.7)
	parity > 3	20(6.5)	46(14.9)	66(21.4)
History of Pregnancy outcome	No prior pregnancy	35(11.4)	60(19.5)	95(30.8)
	Abortion/stillbirth	9(2.9)	40(13.0)	49(15.9)
	Full-term live baby	59(19.2)	105(34.1)	164(53.2)
Sex of baby of last pregnancy	No prior pregnancy	35(11.4)	60(19.5)	95(30.8)
	Unidentified	5(1.6)	15(4.9)	20(6.5)
	Female	36(11.7)	65(21.1)	101(32.8)
	Male	27(8.8)	65(21.1)	92(29.9)
Family history of birth defects	Yes	5(1.6)	7(2.3)	12(3.9)9
	No	98(31.8)	198(64.3)	296(96.1)
If yes relationship with you relative and Type of birth defect.	Club foot, uncle	2(0.6)	7(2.3)	9(2.9)
	Congenital heart defect, aunt	1(0.3)		1(0.3)
	Congenital heart defect, aunt	1(0.3)		1(0.3)
	Maternal cousin, club foot and hydrocephalous	1(0.3)	1(0.3)	2(0.6)
	maternal, club foot		1(0.3)	1(0.3)
Previous child with birth defects	Yes	8(2.6)	4(1.3)	12(3.9)
	No	95(30.8)	201(65.3)	296(96.1)
If yes, type of the birth defects	Anencephaly	2(0.6)		2(0.6)
	Club foot	3(1)	2(0.6)	5(1.6)
	Hydrocephalous		1(0.3)	1(0.3)
	Spina bifida	2(0.6)	2(0.6)	4(1.3)
History of X-ray imaging	No	101(32.8)	202(65.6)	303(98.4)
	Yes	2(0.6)	3(1)	5(1.6)
Consumption of Periconceptional folic acid supplementation	Yes
	No	103(33.4)	205(66.6)	308(100)

In the NTDs cases, 14.9% of mothers were 25 years or younger, 14.9% were between 26 and 35 years, and 3.6% were older than 35. In the control group, 32.1% were 25 or younger, 30.5% were between 26 and 35, and 3.9% were older than 35. Most mothers in both cases and controls were married, comprising 27.6% of NTD cases and 55.2% of controls. Unmarried individuals accounted for 5.2% of NTD cases and 10.1% of controls, while divorced individuals made up 0.6% and 1.3%, of the cases and controls respectively. Regarding residence, a larger percentage of NTD cases (18.5%) lived in rural areas, while 14.9% of cases resided in urban areas. In comparison, 35.7% of the control group lived in rural areas, and 30.8% lived in urban areas. Religious affiliation was predominantly Orthodox in both cases and controls, with 31.8% of NTD cases and 65.3% of controls identifying as Orthodox Christians.

Educational attainment varied between the cases and controls. Among NTD cases, 6.5% had no formal education, 11.7% had completed elementary school, 10.7% had finished high school, and 4.5% had attained a college diploma or higher. In the control group, 15.3% had no formal education, 22.7% had completed elementary school, 19.5% had finished high school, and 9.1% had a college degree or higher. Occupational patterns also differed between the groups. Among NTD cases, 13.3% were housewives, 12.7% were laborers, 8.1% were merchants, and 7.5% were farmers. In the control group, the most common occupation was housewife (21.1%), followed by farmer (19.5%) and laborer (8.8%).

Regarding obstetric history, 15.6% of NTD cases had 1–3 children, 6.5% had more than 3 children, and 11.4% were primiparous. Among controls, 32.1% had 1–3 children, and 19.5% were primiparous. regarding the history of the pregnancy outcomes, 19.2% of NTD cases had previously given birth to full-term live babies, while 2.9% had experienced an abortion or stillbirth. Among controls, 34.1% had full-term live births, and 13.0% had experienced an abortion or stillbirth. The sex distribution of the last pregnancy revealed that 11.7% of NTD cases had a female child, 8.8% had a male child, and 1.6% had an unidentified sex. In the control group, 21.1% had a female child, and 21.1% had a male child.

Concerning family history of birth defects, 1.6% of NTD cases and 2.3% of controls reported a family history of conditions such as clubfoot and congenital heart defects. Notably, 2.6% of NTD cases had a previous child with birth defects, compared to 1.3% of controls, with conditions including anencephaly, clubfoot, hydrocephalus, and spina bifida. Exposure to X-ray imaging during pregnancy was reported by 0.6% of NTD cases and 1.0% of controls. Lastly, the study revealed that none of the cases and controls, had consumed periconceptional folic acid supplementation.

Effects of adverse conditions on Pre-pregnancy safe motherhood practices and neural tube defects in war and siege-affected Tigray (n = 308: 103 NTDs cases and 205 controls).

This study highlights the multifaceted challenges faced by both study groups due to the war and siege, including exposure to various form of attack, limited access to healthcare, unintended pregnancies, and food insecurity (Table 3). These conditions have had a significant impact on maternal health and are likely contributors to the increased prevalence of neural tube defects (NTDs) in the region. The findings provide critical insights into the complex factors affecting the health of pregnant women in Tigray.

Table 3.

Pre-pregnancy safe motherhood among study participants amidst challenging conditions in War-Torn Tigray

Characteristics		Neural tube defects (NTDs)
		Yes	No	Total
		N (%)	N (%)	N (%)
Type of conflict event?	Act of war	35(11.4)	52(16.9)	87(28.3)
	Attack on populations	46(14.9)	110(35.6)	156(50.6)
	Damage to property	22(7.1)	43(14)	65(21.1)
Use health service	No	94(30.5)	189(61.4)	292(91.9)
	Yes	9(2.9)	16(5.2)	25(8.1)
Pregnancy intended/wanted	No	79(25.7)	119(38.6)	222(64.3)
	Yes	24(7.8)	86(27.9)	110(35.7)
If No, Reason for unwanted/intended pregnancy	Health facility damaged	4(1.3)	20(6.5)	24(7.8)
	lack of family planning	51(16.6)	74(24)	125(40.6)
	Not supported by family	48(15.6)	18(5.8)	66(21.4)
	pregnancy from unknown person/rape		7(2.3)	7(2.3)
Family food Source	Cultivation/production	36(11.7)	76(24.7)	112(36.4)
	Food aid	25(8.1)	51(16.6)	76(24.7)
	Purchasing	29(9.4)	64(20.8)	93(30.2)
	support from relative	13(4.2)	14(4.5)	27(8.8)
Meal frequency	<=2 times per day	84(27.3)	96(31.2)	180(58.4)
	>=3 times per day	19(6.2)	109(35.4)	128(41.6)

A substantial proportion of the study participants experienced various war-related events, with attacks on populations being the most common (50.6%). Other reported events included acts of war (28.3%) and property damage (21.1%), all of which disrupted access to essential services and resources, exacerbating maternal health challenges. Healthcare access was particularly affected, with 91.9% of women not receiving any health services during their pregnancy. Only 8.1% of participants were able to access medical care, underscoring the significant barriers created by the destruction of healthcare facilities and war. The absence of prenatal care emerged as a critical factor contributing to the elevated risk of NTDs in the region.

The study also revealed a high prevalence of unintended pregnancies, accounting for 64.3% of all pregnancies. This lack of control over reproductive health was attributed to several factors: 7.8% of women cited the destruction of health facilities as a barrier to accessing family planning services, 40.6% reported the unavailability of family planning options, and 21.4% indicated a lack of support from their families. Additionally, 2.3% of pregnancies resulted from rape or unknown circumstances.

Food insecurity emerged as another significant challenge in Tigray, with 24.7% of families relying on food aid and 30.2% purchasing food, while only 36.4% depended on their own cultivation. Nutritional inadequacy was widespread, as 58.4% of women reported consuming two or fewer meals per day. This food insecurity likely contributed to poor maternal nutrition, which is a well-established risk factor for NTDs.

Association Between Sociodemographic Factors and Neural Tube Defects in Tigray: A Binary Logistic Regression Study

The findings highlight several significant associations suggesting that maternal characteristics play a critical role in the occurrence of neural tube defects (NTDs) (Table 4).

Table 4.

Association of sociodemographic and obstetric factors with the occurrence of neural tube defects (NTDs) in Tigray

Characteristics		95% C.I. for EXP(B)			P value
		COR		AOR
Sociodemographic and obstetric history
Maternal age	<=25	1.973(0.810–4.803)	6.585 (1.799–24.101)		0.004
	26–35	1.873(0.769–4.566)	3.530 (1.123–11.091)		0.031
	> 35
Marital status	Not married	0.969(0.502–1.869)	1.917 (0.713-5.151)		0.197
	Divorced	1(0.180–5.569)	1.32(0.136-12.822)		0.811
	Married
Residence	Rural	1.070(0.665-1.722)	0.808(0.390-1.673)		0.566
	Urban
Education	No formal education	1.175(0.513–2.689)	20.846(2.265-191.856)		0.007
	Elementary school	0.972(0.456–2.073)	14.365(1.703-121.177)		0.014
	High school	0.909(0.421–1.962)	13.801(1.672-113.911)		0.015
	College diploma and above
Parity	Prime	0.745(0.381–1.457)	0.677(0.220-2.084)		0.497
	parity 1–3	0.897(0.479–1.680)	0.714(0.293-1.742)		0.459
	parity > 3
History of Pregnancy outcome	No prior pregnancy	0.963(0.570–1.628)
	Abortion/stillbirth	2.497(1.133–5.504)	2.516 (0.990–6.397)		0.053
	Full-term baby

Women aged ≤ 25 years were significantly more likely to have a child with NTDs, with an adjusted odds ratio (AOR) of 6.585 (95% CI: 1.799–24.101, p = 0.004), compared to older age groups. Similarly, women aged 26–35 years also exhibited an increased risk, with an AOR of 3.530 (95% CI: 1.123–11.091, p = 0.031), compared to those over 35 years.

Maternal education level was strongly associated with NTD occurrence. Women with no formal education had significantly higher odds of having a child with NTDs (AOR = 20.846, 95% CI: 2.265–191.856, p = 0.007). Likewise, those with elementary school education (AOR = 14.365, 95% CI: 1.703–121.177, p = 0.014) and high school education (AOR = 13.801, 95% CI: 1.672–113.911, p = 0.015) were also at significantly increased risk compared to women with a college diploma or higher.

Additionally, a history of abortion or stillbirth was associated with an elevated risk of NTDs, with an AOR of 2.516 (95% CI: 0.990–6.397, p = 0.053). Although this association was borderline significant, it indicates that women with a history of adverse pregnancy outcomes might face a heightened risk of having children with NTDs.

Discussion

Characteristics of pregnancy outcomes affected by neural tube defects (NTDs)

Our findings provide important insights into the characteristics of pregnancy outcomes affected by neural tube defects (NTDs), focusing on types of NTDs, the associated outcomes, and additional factors like sex, associated congenital malformations, and recurrence risks.

This study reveals that anencephaly is the most common type of neural tube defect (NTD), followed by spina bifida and encephalocele, respectively. A significant trend observed is the high rate of stillbirths among pregnancies affected by NTDs. The majority of pregnancies with anencephaly and spina bifida ended in stillbirths. This highlights the severe prognosis typically associated with these NTDs, particularly anencephaly, where the absence of a major portion of the brain and skull contributes to in utero death. These findings align with those of other studies, which similarly report a poor prognosis for pregnancies affected by NTDs, especially anencephaly, which is often fatal either in utero or shortly after birth [25, 26]. Spina bifida, although often survivable with surgical intervention, still has a high rate of fetal loss, especially in settings with limited access to prenatal care or surgical treatments [27].

In this study, the majority of cases had an unidentified sex, which is unusually higher than in most studies, where NTDs, particularly spina bifida, show a slight male predominance [28]. Research generally indicates that males are more commonly affected by NTDs, particularly spina bifida [29–31]. The observed high proportion of unidentifiable sex in our finding could primarily due to the nature of the cases: most were stillbirths, often severely macerated or with major cranial or spinal malformations (particularly anencephaly), which made external genital examination inconclusive or impossible. In some cases, medical records lacked documentation of sex due to the advanced stage of tissue degradation or the absence of diagnostic imaging or autopsy confirmation. And also lack of ANC reported in this study may also attribute for this. This also underscores the challenges of documenting sex in stillbirth cases, which are often less systematically recorded than live births.

This study highlights the incidence of associated congenital malformations, such as hydrocephalus, club foot, and cleft palate, which aligns with findings from other studies reporting that NTDs, particularly spina bifida, often occur alongside other anomalies [31, 32]. For instance, a study by Blount JP et al. [33] found that hydrocephalus is frequently observed in spina bifida cases due to the obstruction of cerebrospinal fluid flow, which increases the risk of developmental delays and other neurological issues. However, the incidence of other malformations, such as club foot and omphalocele, is somewhat lower than expected when compared to other large cohort studies. For example, club foot is commonly reported in association with spina bifida and other NTDs [34, 35]. This discrepancy may be attributed to the relatively small sample size in the current study or differences in the diagnostic criteria used to identify co-occurring defects.

This study found that some cases had a family history of birth defects, including congenital heart defects and clubfoot, with a recurrence of NTDs such as spina bifida and anencephaly. These findings are consistent with established research suggesting an increased risk of recurrence for NTDs among individuals with a family history of birth defects [36]. Studies have shown that having a sibling with an NTD or a family history of congenital anomalies can increase the risk of recurrence in subsequent pregnancies [28, 36, 37]. Specifically, the recurrence risk of spina bifida in siblings can range from 2–5%, depending on the severity and nature of the family history [38, 39].

The recurrence of neural tube defects (NTDs) is a crucial topic for understanding the genetic and environmental factors that influence these conditions. Numerous studies have examined the familial patterns associated with NTDs, highlighting the importance of family history in assessing the risk of recurrence [37, 38, 40]. The presence of NTDs in a family can led to increased awareness and concern about the potential for recurrence in future offspring. Specific studies suggest that the recurrence rate of NTDs can be significantly higher in families with a history of these defects [37, 38, 40]. The genetics of NTDs plays a key role in their development [37, 38, 40]. These defects are believed to result from a combination of genetic and environmental factors [36–38]. Genetic studies indicate that certain hereditary factors may predispose individuals to NTDs, suggesting that families with a history of these defects may share common genetic susceptibilities [41]. These hereditary factors can vary, and identifying specific genetic markers could help predict the recurrence risk for affected families. This emphasizes the importance of genetic counseling and monitoring for women with a history of NTDs, particularly in settings with limited access to healthcare. However, the small number of affected families in this study limits the strength of the conclusions that can be drawn regarding genetic predispositions. Despite this, the findings reinforce the need for genetic counseling and careful monitoring for women with a history of NTDs, especially in environments with severely restricted healthcare access.

Key determinants and risk factors

Sociodemographic and obstetric disparities

This study highlights significant associations between maternal age, educational level, and prior pregnancy outcomes with the occurrence of NTDs.

The analysis reveals a significant association between maternal age and the occurrence of NTDs. Maternal age was identified as a key risk factor, with women aged ≤ 25 years and 26–35 years showing a notably higher likelihood of having children with these defects. This finding is consistent with previous studies, which have consistently linked younger maternal age to an increased risk of NTDs, often due to inadequate prenatal care, nutritional deficiencies, and limited access to health services during pregnancy [11, 42]. The increased risk can be attributed to various socio-economic factors, including limited access to prenatal care and a higher prevalence of adverse pregnancy outcomes, such as low birth weight and preterm delivery, among young mothers [43]. In conflict zones, these challenges are further exacerbated by limited resources and ongoing instability, which hinder young mothers from accessing essential healthcare services.

This study also found a strong association between lower maternal education and an increased risk of NTDs. Multiple studies have consistently shown that mothers with lower maternal education attainment are more likely to have children with NTDs [5, 44–46]. For example, women with less than a high school education face a 1.7-fold higher risk of delivering infants with NTDs compared to those with at least a high school diploma. This elevated risk persists even when accounting for other socioeconomic factors [5, 44–46].

Mothers from lower socioeconomic status (SES) often encounter barriers such as limited healthcare access, inadequate nutrition, and lower health literacy, all of which contribute to poor pregnancy outcomes. Education plays a crucial role in promoting awareness of health-related behaviors, including preconception care and folic acid supplementation, which are essential for preventing NTDs [10, 14, 44]. These findings underscore the importance of targeted health education initiatives to improve maternal health and encourage folic acid use, particularly among women with lower levels of education.

A history of abortion or stillbirth showed a borderline association with the occurrence of NTDs (AOR = 2.516, 95% CI: 0.990–6.397, p = 0.053). While not statistically significant, this finding suggests that women with previous adverse pregnancy outcomes may have an increased risk of NTD-affected pregnancies. Research indicates that such outcomes can be predictive of future birth defects [7, 37, 47]. Family history is a crucial factor, as maternal genetics and a prior occurrence of birth defects, such as spina bifida, can elevate the risk of NTD recurrence in future pregnancies [2, 7, 37]. The association identified in this study underscores the need for further research with a larger sample size to better assess its strength and significance. Moreover, women with a history of pregnancy complications may have underlying health conditions or environmental exposures that could contribute to the recurrence of birth defects, highlighting the importance of targeted prenatal care and risk assessment.

A striking finding in this study is that neither woman in the NTD group nor those in the control group reported consuming peri-conceptional folic acid supplements, despite its well-established role in preventing NTDs [2, 3, 48]. This lack of supplementation in Tigray may stem from limited access to preconception care within the healthcare system. The war and siege have further worsened these challenges [12–15, 49], emphasizing the urgent need to improve access to folic acid supplements and strengthen maternal health education to help reduce the prevalence of NTDs in the region.

Conflict-Related Factors

This study highlights the severe impact of war on maternal health in Tigray, where many women with pregnancies affected by neural tube defects faced significant barriers such as exposure to violence, unintended pregnancies, limited access to health services, inadequate family planning, and food insecurity. These factors emphasize the public health challenges in conflict zones, where the collapse of healthcare services worsens pregnancy outcomes, increasing vulnerability to neural tube defects and other birth defects [50]. Armed conflicts often destroy healthcare facilities and displace medical personnel, significantly limiting women’s access to maternal health services [12–15]. This disruption increases the risk of adverse pregnancy outcomes, including neural tube defects and maternal mortality, as essential care becomes inaccessible [49, 51]. These gaps in maternal healthcare contribute to congenital malformations, such as neural tube defects. Mlambo C et al. [50]. also highlight that living in conflict zones increases women’s vulnerability to sexual violence, poor reproductive health, unintended pregnancies, and negative maternal outcomes.

Armed conflict disrupts vital infrastructure such as food, water, and sanitation systems, further limiting healthcare access and worsening maternal health risks. Our study found that 50.6% of participants faced attacks on civilians, 28.3% experienced acts of war, and 21.1% suffered property damage, underscoring the severe impact of the war in Tigray on maternal well-being [12–15, 49]. Research shows that violence, displacement, and trauma in conflict zones significantly increase the risk of adverse maternal outcomes, including birth defects [50, 52, 53]. The high rates of violence in this study indicate that conflict impedes access to prenatal care and safe delivery services, crucial for reducing the risk of neural tube defects. Additionally, psychosocial stress from such instability is linked to poor pregnancy outcomes like preterm births and low birth weights [54–56].

Only 8.1% of women in Tigray, both with and without NTD-affected pregnancies, reported accessing health services, while 91.9% were unable to seek care due to the war and siege. This highlights the collapse of the region’s healthcare system, with attacks on medical facilities, shortages of healthcare professionals, and resource depletion severely limiting access to essential prenatal care [12–15, 49]. Prenatal care, especially folic acid supplementation, is crucial for preventing NTDs [2, 3, 49]. The lack of these services emphasizes the urgent need for humanitarian intervention and healthcare reconstruction to improve maternal health and reduce the high prevalence of NTDs and other birth defects in the region.

Limited healthcare access during armed conflict is a well-documented issue, with many women unable to receive basic maternal care due to the destruction of medical infrastructure, displacement of healthcare workers, and insecurity [50, 57, 58]. This study’s findings align with other conflict settings, where disruptions in healthcare contribute to adverse pregnancy outcomes, increased birth defects, and higher maternal and infant mortality [59, 60]. This study also shows many women with NTD-affected pregnancies reported unintended pregnancies, often due to limited family planning services and lack of family support, which is linked to delayed prenatal care, higher stress, poor nutrition, and increased NTD risks [50, 55, 56, 58]. Additionally, many women faced gender-based violence, such as rape, which further worsened their health and the risk of adverse pregnancy outcomes [50, 55, 56, 58].

Food insecurity emerged as a significant challenge in this study, with many women relying primarily on food aid or subsistence agriculture as their main sources of nutrition. A substantial proportion of participants reported consuming fewer than two meals per day, underscoring widespread nutritional deficiencies an established risk factor for neural tube defects (NTDs). These findings are consistent with those of Haileslasie et al. [61], who reported widespread starvation-related mortality in Tigray, Ethiopia, following the Pretoria peace agreement. Starvation was identified as the primary cause of death among both internally displaced persons and the general population, with many households experiencing prolonged periods without food. Only 43.1% had access to two meals daily, and just 18.6% consumed three meals. These outcomes underscore a severe breach of global nutrition targets outlined in the 2030 Agenda for Sustainable Development and violate internationally recognized rights to adequate food and living standards [62]. Research has consistently shown that inadequate maternal nutrition, particularly deficiencies in folic acid and other essential nutrients, plays a key role in the development of neural tube defects [2, 3, 49]. The combination of food scarcity and limited access to nutritional supplements, such as folic acid, may contribute to the heightened risk of NTDs in this population. This finding aligns with research by Carmichael et al. [63], which associates food insecurity with an increased risk of congenital anomalies, including cleft palate, tetralogy of Fallot, spina bifida, and anencephaly.

Conclusion

This study highlights the impact of neural tube defects (NTDs) on pregnancy outcomes, with anencephaly as the most common type, leading to a high rate of stillbirths. The high prevalence of unidentified sex and fewer associated congenital anomalies reflect diagnostic challenges and the complexity of NTDs. Limited prenatal care worsens prognosis, while maternal age and education were key risk factors. The war in Tigray has further intensified maternal health risks, with violence, healthcare disruptions, unintended pregnancies, and food insecurity collectively increasing NTD prevalence. These findings underscore the urgent need for improved maternal healthcare, particularly in conflict-affected regions. This study highlights the urgent need to strengthen maternal healthcare and public health infrastructure in Tigray. Targeted prevention strategies are essential to address key NTD risk factors. However, the small sample size and data limitations, including unidentified sex, underscore the need for further research on genetic and environmental determinants.

Recommendations

Enhance Prenatal Care Access: Prioritize the restoration and expansion of prenatal healthcare services in war-affected areas, particularly in Tigray, to prevent NTDs and improve pregnancy outcomes for women with limited healthcare access.

Expand Folic Acid Supplementation: Strengthen folic acid distribution programs in conflict-affected regions and launch public health campaigns emphasizing its critical role in preventing NTDs, especially in areas facing food insecurity.

Strengthen Maternal Health Education: Develop targeted health education initiatives to improve maternal health literacy, focusing on NTD risks, prenatal care, and the importance of proper nutrition, including folic acid intake.

Support Women in Conflict Zones: Provide access to family planning, reproductive health services, and psychosocial support for women affected by war. Addressing gender-based violence and unintended pregnancies is vital for improving maternal health.

Implement Genetic Counseling & Family Planning: Offer genetic counseling to families with a history of congenital anomalies to inform reproductive decisions. Expanding family planning services can help reduce unintended pregnancies and promote maternal health planning.

Conduct Further Research: Larger studies are needed to validate findings on environmental pollution or genetic factors, detailed study on the long-term outcomes of surviving infants with NTDs, NTDs recurrence, sex distribution, and associated anomalies. Future research should also examine the specific effects of conflict on maternal health and NTD outcomes.

Limitation of the study

The study provides important insights into the risk factors associated with neural tube defects (NTDs) in Tigray, Ethiopia, a region affected by devastating war and siege. However, several limitations must be considered when interpreting the findings and directing future research. First, as a cross-sectional study, it cannot establish causal relationships. Longitudinal research would provide a better understanding of the temporal effects of war on maternal and fetal health. Second, the sample was limited to 11 hospitals, which may not accurately represent the broader population, especially women from remote areas or those with severe complications. Third, the war and siege may have compromised data accuracy, and recall bias could have affected self-reported risk factors. The small sample size (308 participants) limits statistical power, particularly for rare risk factors. Additionally, unmeasured confounders, such as environmental pollution or genetic factors, were not explored and could have influenced the relationship between the studied variables and NTDs. The study also lacked detailed data on the long-term outcomes of surviving infants with NTDs, which limits understanding of the broader impacts on affected families. Finally, while the findings are valuable for the Tigray context, their applicability to other war-affected regions in Ethiopia or sub-Saharan Africa may be limited due to differences in healthcare access, and the nature of war and siege. Further studies in similar settings are needed to confirm and expand upon these results.

Abbreviations

NTDs

Neural Tube Defects

ICD-10

International Classification of Diseases

WHO

World Health Organization

ODK

Open Data Kit

ANC

Antenatal Care

Author contributions

Birhane Alem Berihu (BAB) wrote the research protocol and collected and analyzed the data under the supervision of HKM, AM, TM, PY, and TG. All authors reviewed and approved the final manuscript.

Funding

This study was funded by Mekelle University. The funding body was not involved in the study’s design, data collection, data analysis, interpretation, or writing of the manuscript.

Data availability

Data sharing is available upon request. Please contact the corresponding author for data and materials.

Declarations

Ethics approval and consent to participate

Ethical approval for this study was granted by the Mekelle University College of Health Sciences IRB (Protocol No. MU-IRB 1800/2020, renewal No. MU-IRB 2101/2023), and informed oral consent was obtained from all participants. The study adhered to the ethical principles of the Declaration of Helsinki, ensuring participants’ rights, dignity, and confidentiality.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.