Prenatal, perinatal and neonatal risk factors of Autism Spectrum Disorder: A comprehensive epidemiological assessment from India

https://doi.org/10.1016/j.ridd.2013.06.019Get rights and content

Highlights

  • Ours is the first epidemiological report from India on risk factors of Autism Spectrum Disorder.

  • We conducted a large population based case-cohort study across India.

  • Out of 25 factors evaluated, advanced maternal age, fetal distress, gestational respiratory infections, labor complications, pre-term birth, neonatal jaundice, delayed birth cry and birth asphyxia were significantly associated with the risk of ASD.

  • These conditions can independently and collectively exert their effect as risk factors, adding important country specific information to existing literature.

Abstract

Incidence of Autism Spectrum Disorder (ASD) is increasing across the globe and no data is available from India regarding the risk factors of ASD. In this regard a questionnaire based epidemiological assessment was carried out on prenatal, perinatal and neonatal risk factors of ASD across 8 cities in India. A retrospective cohort of 942 children was enrolled for the study. 471 children with ASD, under age of 10, were analyzed for pre-, peri-, and neonatal factors and were compared with the observations from equal number of controls. The quality control of the questionnaire and data collection was done thoroughly and the observations were computed statistically. A total of 25 factors were evaluated by unadjusted and adjusted analysis in this study. Among the prenatal factors considered, advanced maternal age, fetal distress and gestational respiratory infections were found to be associated with ASD and had an odds ratio of 1.8. Evaluation of perinatal and neonatal risk factors showed labor complications, pre-term birth, neonatal jaundice, delayed birth cry and birth asphyxia to be associated with ASD with an odds ratio greater than 1.5. This important study, first of its kind in Indian population gives a firsthand account of the relation of pre-, peri- and neonatal risk factors on ASD from an ethnically and socially diverse country like India, the impact of which was unknown earlier. This advocates additional focused investigations on physiological and genetic changes contributed by these risk factor inducing environments.

Introduction

Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, associated with restricted and repetitive behavior (Zhang et al., 2010). Autism is becoming a growing challenge in developing countries like India as well, and the earlier notion of it being uncommon is no longer justified. It poses a much greater and serious challenge in countries like India, because of the severity of the impact on the affected individuals and their families, along with the economic burden that it imposes coupled with lack on scientific know how about the disorder (Daley, 2004). Due to lack of awareness about the condition, often, misdiagnosis or inclusion of ASD under the general category of mental retardation and/or speech and language disorders is commonly noticed (Singhi & Malhi, 2001). Globally, a number of systematic population surveys and routine monitoring systems in various countries since 1990s have indicated a rise in prevalence from 0.7% to 1% (Chakrabarti and Fombonne, 2001, Fombone, 2002). According to Centers for Disease Control and Prevention (CDC) – recent study from 14 communities, 1 in 88 children in the United States have been identified as having an Autism Spectrum Disorder (ASD) (CDC, 2012), indicating a rise in the past two decades. But this may not be the true picture as the prevalence estimates from Asian countries like China (0.003–0.17%), Japan (0.011–0.21%) and South Korea (2.64%) vary widely across time and country (Kim et al., 2011, Sun and Allison, 2010). Based on the studies in Asian countries, nearly 1.7–2 million individuals are estimated to be affected (Karande, 2006, Krishnamurthy, 2008) with ASD in India. With such high estimated figures, it becomes a necessity to look into the probable risk factors of ASD in Indian population as well.

The extreme complexity in the behavioral, developmental and associated medical conditions across ASD indicates existence of multiple unknown causal factors. Studies based on concordance rates among monozygotic twins and families suggest a possible role of both genetic and environmental factors in the etiology of ASD (Bailey et al., 1995, Guinchat et al., 2012, Parner et al., 2008). Despite significant research in the field, the etiology of ASD is not well established. The neuropathology of ASD remains unclear and the reported brain abnormalities among children with ASD indicate a probable link with disturbances in the in utero period (Gardener et al., 2011, Minshew and Williams, 2007, Pardo and Eberhart, 2007). Hence, it is imperative to focus of prenatal, perinatal events as risk factors for ASD.

There has been a huge focus on pre- and perinatal events as risk factors in various studies across the globe, wherein disruptions and disorders of pregnancy, labor complications, fetal distress, low birth weight and premature birth have been studied and implicated in ASD (Bilder et al., 2009, Bolton et al., 1997, Bryson et al., 1988, Buchmayer et al., 2009, Burd et al., 1999, Burstyn et al., 2010, Cryan et al., 1996, Deb et al., 1997, Deykin and MacMahon, 1980, Dodds et al., 2011, Dubovický, 2010, El-Baz et al., 2011, Finegan and Quarrington, 1979, Gardener et al., 2011, Ghaziuddin et al., 1995, Gillberg and Gillberg, 1983, Glasson et al., 2004, Guinchat et al., 2012, Hultman et al., 2002, Johnson et al., 2010, Juul-Dam et al., 2001, Kinney et al., 2008, Kolevzon et al., 2007, Kröger et al., 2011, Kuban et al., 2009, Larsson et al., 2005, Lord et al., 1991, Losh et al., 2012, Maimburg and Vaeth, 2006, Mason-brothers et al., 1987, Nelson, 1991, Ornitz, 1985, Piven et al., 1993, Schendel and Bhasin, 2008, Stein et al., 2006, Wallace et al., 2008, Zambrino et al., 1995, Zwaigenbaum et al., 2002). Despite several studies being conducted worldwide to analyze the risk factors of ASD, the results are not conclusive.

Research reports on epidemiology of ASD from India are not available (Sharan, 2006). Analysis of such risk factors is pertinent in India, as the above mentioned risk conditions like fetal distress inducing conditions and labor complications are well documented to be prevalent with significant impact on survival and development of children in India (Kumar and Bhat, 1996, March of Dimes, 2012, NFHS-3, 2007, Singh et al., 2007). However, the exact impact of these conditions as risk factors for ASD needs to be established. Moreover, globalization, secondary to industrialization and the enhanced communication pathways, had led to significant cultural, political and economic changes, requiring an individual to adapt to these changing scenarios (Banerjee, 2009). This need for adaptation contributes to increased mental stress among individuals for gaining resources to cope (Banerjee, 2009). Mental stress, in turn, has reflected in stressful pregnancies due to associated psychosocial stress among Indian women (UNICEF, 2006). Hence, it is imperative to understand the implications of these on the pre-, peri events and disease etiology from India.

Thus, the aim of our study is to perform a population based cohort study to characterize the pre-, peri- and neonatal risk factors and assess their association with ASD in Indian population. The data generated in this study is the first epidemiological report from India and the results obtained strengthens similar observations from other studies reporting pre-, peri- and neonatal risk factors of ASD.

Section snippets

Methods

The study was conducted by following Code of human research ethics guidelines laid down by Indian Council of Medical Research [ICMR] (ICMR, 2006). An informed consent was taken from the participating parent after detailed explanation of the rationale behind the study and about the questions in the questionnaire. Care was taken to ensure confidentiality of the data collected. This study was approved by Institutional Human Ethics Committee (IHEC).

Results

A total of 942 participants (471 cases and 471 controls) were included in the study with age group ranging from 2 to 10 years. The average age at which the ASD was diagnosed was found to be 3 years in our study.

Discussion

This is the first study to analyze the prenatal, perinatal and neonatal risk factors of ASD in Indian population. We conducted a questionnaire-based case–control epidemiological study. The strength of the current study lies in its large country wide data collection with validated questionnaire, precise confirmation of the ASD diagnosis by physicians, active participation of parents and volunteers (teachers and therapists) from various schools and hospitals in filling up of the questionnaire,

Conclusion

Our study categorically implicates many pre, peri and neonatal conditions to be risk factors for ASD independently and collectively, adding important country specific information to existing literature. Out of all the factors analyzed, advanced maternal age, fetal distress and gestational respiratory infections were found to be associated with ASD and had an odds ratio of 1.8. Evaluation of perinatal and Neonatal risk factors showed labor complications, pre-term birth, neonatal jaundice,

Acknowledgements

This research was completely funded by University Grants Commission, India. We would also like to extend our acknowledgement to Department of Science and Technology, India for funding the research scholar. We would like to thank Dr. M. Gowri Devi, Professor and HOD Department of Psychiatry, Niloufer Hospital for permitting us for data collection. Our extended appreciation to Mr. V. Shankaran, Mr. C. N. Rahul, Ms. N. Geetanjali and Dr. S. Kalidasan for helping us in the collection of control

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