Burden of neurodevelopmental disorder in Lakki Marwat population of Khyber Pakhtunkhwa, Pakistan

Abstract

Background

Pakistan is a multi-cultural country with different ethnic groups living in both rural and urban communities. There is a significant occurrence of congenital and hereditary neurodevelopmental disorder (NDD) contributing to mortality and morbidity rates.

Objectives

This study aims to explore the prevalence, patterns, and phenotypic spectrum of NDD in district Lakki Marwat population of Khyber Pakhtunkhwa, Pakistan.

Methodology

From 2022 to 2023, a cross-sectional study was conducted and subjects or families with NDD were recruited from district hospitals, rural and urban areas. Door to door survey was also carried out to collect appropriate data. The study gathered phenotypic and descriptive data, clinical information including age, gender, family history, consanguinity and bio-demographic features were recorded.

Results

A total of 276 independent cases/families with NDD were ascertained. The malformations were grouped into major and minor categories. Most of the case/families (58.69%) were sporadic, and 38.04% of the population was classified as having a low-income status. The most frequent family type was a single spouse with children (27.89%), while extended families made up 21.37% of all cases. Demographic variables such as parental consanguinity, syndromic/non-syndromic, familial/sporadic nature, economics status, age of disease onset and pedigree structures showed conspicuous heterogeneity among the major and minor categories of NDD.

Conclusion

The high incidence of NDD indicates that nongenetic factors may play a vital role in their etiology which could be diminished by improving the healthcare system.

Introduction

Neurodevelopmental disorders (NDDs) are a heterogeneous group of complex brain disorder including attention deficit hyperactivity disorder (ADHD), intellectual disability (ID), autism spectrum disorder (ASD), global developmental delay (GDD), and developmental and epileptic encephalopathies [1, 2]. These disorders often develop in early infancy or childhood and tend to persist throughout a person's lifespan. NDD is clinically distinguished in syndromic and non-syndromic forms and both environmental and genetic factors have been associated with the disorder. Environmental factors such as infections (e.g., rubella, cytomegalovirus), iodine-deficient diet, ototoxic drug treatment, poor nutrition, prenatal/perinatal brain ischemia, advanced maternal age, prenatal/postnatal infections (meningitis, encephalitis), hypoglycemia, prenatal exposure to toxins (e.g., alcohol, drugs), inadequate medical services, and stress during pregnancy can affect fetal brain development have been described [3, 4]. The genetic causes of NDD are diverse and include chromosomal aberrations and single or multiple gene defects [3, 4]. NDD are individually rare but collectively they make a significant impact on the populations. The prevalence of NDD varies throughout the worldwide population.

Pakistan, a multicultural country with different ethnic groups living in both rural and urban communities, bears a high burden/rate of congenital anomalies [5,6,7,8,9,10]. Several surveys and studies conducted in different regions and hospitals in Pakistan demonstrated that consanguineous marriage, high-risk pregnancies, poor nutrition, lack of education and awareness and antenatal care are the major factors for congenital anomalies [5,6,7,8,9,10]. Towards this end, a population-based study was carried out in order to elucidate the burden and prevalence of NDD in district Lakki Marwat population of Pakistan.

Materials and methods

This epidemiological study was conducted in district Lakki Marwat of KPK province of Pakistan between January 2022 and 2023. This study was approved by the Ethical Review Committee of University of Lakki Marwat. After a comprehensive investigation of the literature, a particular kind of questionnaire was designed. A door-to-door survey of different areas of Lakki Marwat was carried out to collect NDD individuals or families. The collected data was enlisted in Microsoft Excel and categorized in 9 different tables on basis of their origin, gender, ethnicity, age range, family type, parental consanguinity, marital status, and economic status. The statistical analysis was carried out by GraphPad Prism (5.00) software.

Results

A total of 276 independent participating individuals or families having NDD were recruited. The index males were 168 (60.86%) and108 (39.13%) were female. Most of the cases/families were sporadic (162, 58.69%) and few were familial (114, 41.30%). Out of 276 case/families, 146 (52.89%) cases were syndromic and 130 (47.1%) were non-syndromic/isolated respectively (Table 1). Most of the cases/families belonged to rural areas (176; 63.76%), lived in nuclear or extended families (n = 102; 36.95%) (Table 1). Among the age distribution, most people (64, or 23.18%) were between the ages of 10 and 19. According to the study's analysis of economic position, most people (105, or 38.04%) fell into the poor category, followed by the intermediate category (76, or 27.53%), middle class category (61, or 22.1%), and the high-class category (34, or 12.31%). Out of 276 cases/families, 74.63% or 206 had congenital NDD, while the rest of them 25.72% or 71 with late onset (Mostly after age 10). According to the NDD severity, the cases were divided into three groups. Mild cases were most frequently observed with a percentage of 38.4% (106 cases) but the moderate and severe ID cases were equal in number (85) with a percentage of 30.79% (Table 1). When phenotypic features of the patients were taken into consideration, majority of the individuals (174 or 63.04%) were normal looking, 52 (18.84%) patients were having microcephaly while the rest of 50 or 18.11% were having epilepsy/seizure (Table 1). Depending on the nature of the parent's marriage, the cases were divided into 4 categories viz first cousin, second cousins, related and non-related groups (Table 1).

Table 1 Distribution of NDD with respect to Origin, Age, economic status, family type, Gender, phenotypic features, severity, onset and parental consanguinity

Discussion

District Lakki Marwat is situated in the southern part of Khyber Pakhtunkhwa (KPK) province of Pakistan. It touches district Mianwali of Punjab province to the east and Frontier Region (FR) Bhattani to the west. According to the 2017 Census of Pakistan, the population of district Lakki Marwat was about 817,256. Most of the peoples in district Lakki Marwat are reside in rural areas. Most peoples of Lakki Marwat speaks Pashto (99%), however Hindko is also spoken in Lakki city. Marwat, Battani, Kattak, Kundi, and Wazir are tribes reside in Lakki Marwat. Due to poor education system, low socioeconomic status, inadequate healthcare infrastructure and consanguineous marriages contributing to the high incidence of congenital anomalies including NDDs in Lakki Marwat population. The most common form of NDD among the 276 cases/families were mild type (38.4%), followed by a moderate and severe type that were almost equally distributed with percentage of 30.79%. Males’ cases/families were impacted more frequently than females among the index subjects. Numerous studies have shown that males predominate among infants with congenital malformations [11,12,13]. The current study indicated that, compared to the urban sample, sporadic cases predominated in rural areas, which might be understood by a lack of knowledge regarding healthcare, genetic counseling, and prenatal care. In our research it is prominent that consanguinity is highly prevalent that can be a vital cause of NDD. Consanguinity has a significant effect on the occurrence of NDD and ID, claims a 2010 study by Sharkia et al. [14]. As per Chapman et al. (2002), mothers who are in their twenties and those who are at the older end of their age range are more likely to give birth to children who are mentally retarded [15].

The study above has several shortcomings. For example, the study reported prevalence or incidence is based on a survey; it does not involve chromosomal or mutation analysis to provide a molecular diagnosis. Furthermore, several physiological and metabolic problems may exist but remain undiscovered. Moreover, the risk of prenatal and postnatal death, the mother's health and pregnancy circumstances, and etiological variables need to be investigated. The community should provide prenatal screening, genetic counseling, and molecular basis to lower disease risk.