Scholarly article on topic 'Prenatal, perinatal and postnatal factors associated with autism spectrum disorder'

Prenatal, perinatal and postnatal factors associated with autism spectrum disorder Academic research paper on "Clinical medicine"

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{"Autism spectrum disorder" / Child / "Risk factors" / Prenatal / Perinatal / Postnatal / "Transtorno do espectro do autismo" / Criança / "Fatores de risco" / Pré-natal / Perinatal / Pós-natal}

Abstract of research paper on Clinical medicine, author of scientific article — Imen Hadjkacem, Héla Ayadi, Mariem Turki, Sourour Yaich, Khaoula Khemekhem, et al.

Abstract Objective To identify prenatal, perinatal and postnatal risk factors in children with autism spectrum disorder (ASD) by comparing them to their siblings without autistic disorders. Method The present study is cross sectional and comparative. It was conducted over a period of three months (July–September 2014). It included 101 children: 50 ASD's children diagnosed according to DSM-5 criteria and 51 unaffected siblings. The severity of ASD was assessed by the CARS. Results Our study revealed a higher prevalence of prenatal, perinatal and postnatal factors in children with ASD in comparison with unaffected siblings. It showed also a significant association between perinatal and postnatal factors and ASD (respectively p =0.03 and p =0.042). In this group, perinatal factors were mainly as type of suffering acute fetal (26% of cases), long duration of delivery and prematurity (18% of cases for each factor), while postnatal factors were represented principally by respiratory infections (24%). As for parental factors, no correlation was found between advanced age of parents at the moment of the conception and ASD. Likewise, no correlation was observed between the severity of ASD and different factors. After logistic regression, the risk factors retained for autism in the final model were: male gender, prenatal urinary tract infection, acute fetal distress, difficult labor and respiratory infection. Conclusions The present survey confirms the high prevalence of prenatal, perinatal and postnatal factors in children with ASD and suggests the intervention of some of these factors (acute fetal distress and difficult labor, among others), as determinant variables for the genesis of ASD.

Academic research paper on topic "Prenatal, perinatal and postnatal factors associated with autism spectrum disorder"

J Pediatr (Rio J). 2016;xxx(xx):xxx-xxx

ORIGINAL ARTICLE

Prenatal, perinatal and postnatal factors associated with autism spectrum disorder*

Imen Hadjkacem *, Héla Ayadi, Mariem Turki, Sourour Yaich, Khaoula Khemekhem, Adel Walha, Leila Cherif, Yousr Moalla, Farhat Ghribi

University of Sfax, Hedi Chaker Hospital, Department of Child and Adolescent Psychiatry, Sfax, Tunisia Received 19 September 2015; accepted 25 January 2016

KEYWORDS

Autism spectrum

disorder;

Child;

Risk factors; Prenatal; Perinatal; Postnatal

Abstract

Objective: To identify prenatal, perinatal and postnatal risk factors in children with autism spectrum disorder (ASD) by comparing them to their siblings without autistic disorders. Method: The present study is cross sectional and comparative. It was conducted over a period of three months (July-September 2014). It included 101 children: 50 ASD's children diagnosed according to DSM-5 criteria and 51 unaffected siblings. The severity of ASD was assessed by the CARS.

Results: Our study revealed a higher prevalence of prenatal, perinatal and postnatal factors in children with ASD in comparison with unaffected siblings. It showed also a significant association between perinatal and postnatal factors and ASD (respectively p = 0.03 and p = 0.042). In this group, perinatal factors were mainly as type of suffering acute fetal (26% of cases), long duration of delivery and prematurity (18% of cases for each factor), while postnatal factors were represented principally by respiratory infections (24%). As for parental factors, no correlation was found between advanced age of parents at the moment of the conception and ASD. Likewise, no correlation was observed between the severity of ASD and different factors.

After logistic regression, the risk factors retained for autism in the final model were: male gender, prenatal urinary tract infection, acute fetal distress, difficult labor and respiratory infection.

Conclusions: The present survey confirms the high prevalence of prenatal, perinatal and postnatal factors in children with ASD and suggests the intervention of some of these factors (acute fetal distress and difficult labor, among others), as determinant variables for the genesis of ASD.

© 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

* Please cite this article as: Hadjkacem I, Ayadi H, Turki M, Yaich S, Khemekhem K, Walha A, et al. Prenatal, perinatal and postnatal factors associated with autism spectrum disorder. J Pediatr (Rio J). 2016. http://dx.doi.org/10.1016/j.jped.2016.01.012

* Corresponding author.

E-mail: hadjkacemimen@yahoo.fr (I. Hadjkacem).

http://dx.doi.org/10.1016/jjped.2016.01.012

0021-7557/© 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Hadjkacem I et al.

Fatores pré-natais, perinatais e pós-natais associados ao transtorno do espectro do autismo

Resumo

Objetivo: Identificar fatores de risco pré-natal, perinatal e pós-natal em criancas com transtorno do espectro do autismo (TEA) ao compará-las a irmaos sem transtornos de autismo. Método: Este estudo é transversal e comparativo. Ele foi conduzido em um período de tres meses (julho a setembro de 2014). Incluiu 101 criancas: 50 criancas com TEAs diagnosticadas de acordo com os critérios do DSM-5 e 51 irmaos nao afetados. A gravidade do TEA foi avaliada pela Escala de Avaliacao do Autismo na Infancia (CARS).

Resultados: Nosso estudo revelou uma prevalencia maior de fatores pré-natais, perinatais e pós-natais em criancas com TEA em comparacao a irmaos nao afetados. Também mostrou uma associacao significativa entre fatores perinatais e pós-natais e TEA (respectivamente p = 0,03 e p = 0,042). Nesse grupo, os fatores perinatais foram principalmente do tipo sofrimento fetal agudo (26% dos casos), longa duracao do parto e prematuridade (18% dos casos em cada fator), ao passo que fatores pós-natais foram representados principalmente por infeccoes respiratórias (24%). No que diz respeito a fatores dos pais, nenhuma correlacao foi encontrada entre a idade avancada dos pais no momento da concepcao e o TEA. Da mesma forma, nenhuma correlacao foi estabelecida entre a gravidade do TEA e fatores diferentes.

Após regressao logística, os fatores de risco de autismo encontrados no modelo final foram: sexo masculino, infeccao pré-natal do trato urinário, sofrimento fetal agudo, parto difícil e infeccao respiratória.

Conclusoes: Esta pesquisa confirma a alta prevalencia de fatores pré-natais, perinatais e pós-natais em criancas com TEA e sugere a intervencao de alguns desses fatores (sofrimento fetal agudo, parto difícil...) como variáveis determinantes para a genese do TEA. © 2016 Sociedade Brasileira de Pediatria. Publicado por Elsevier Editora Ltda. Este e um artigo Open Access sob uma licenca CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

PALAVRAS-CHAVE

Transtorno do espectro do autismo; Crianca;

Fatores de risco; Pré-natal; Perinatal; Pós-natal

Introduction

Autism spectrum disorder (ASD) is a complex neurodevel-opmental condition. Based on the 5th edition of Diagnostic Statistical Manual of Mental Disorders (DSM-5), specific diagnostic criteria for childhood autism include social skills and communication deficit associated with restrictive and repetitive behaviors, interests, or activities.1 ASD is currently one of the most common childhood morbidities, presenting in various degrees of severity. The most recent global prevalence of autism was estimated at 0.62%.2

This disorder has grown into a constant challenge for many countries such as Tunisia, as it has a severe impact on both the affected individuals and their families. The financial burden, which has become more acute since the Tunisian revolution, along with the lack of scientific knowledge about the epidemiology, etiology, and natural course of this condition, have rendered the situation more complex.3"5

The spectrum of symptoms and the extreme complexity in the developmental and associated medical conditions within ASD do not necessarily mean a single etiology. Several hypotheses concerning the pathogenesis have been proposed, including the interaction of environmental factors and various genetic predispositions.5,6 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.7

A recent study suggests that genetic factors account for only 35-40% of the contributing elements.8,9 The remaining 60-65% are likely due to other factors, such as prenatal, perinatal, and postnatal environmental factors. Since ASDs are neurodevelopmental disorders, neonatally-observed complications that are markers of events or processes that emerge early during the perinatal period may be particularly important to consider.8

To the best of our knowledge, in Tunisia, there are no studies that have considered the relationship between prenatal, perinatal, and postnatal risk factors and ASD.

Thus, the aim of the present study was to identify the pre-, peri-, and postnatal factors associated to ASD by comparing children with ASD to their siblings who do not present any autistic disorders.

Methods Study

This was a cross sectional and comparative study. It was conducted over a period of three months from July to September 2014.

Perinatality and autism spectrum disorder

110 111 112

120 121 122

Population Participants

The sample included 101 children divided into two groups:

1. The first group was composed of 50 autistic children previously identified and followed regularly in the child and adolescent psychiatry department of the Hedi CHAKER Hospital of Sfax (Tunisia). These patients came from different regions of Tunisia, as there are only three child psychiatry departments in the entire country. Subject ages ranged between 3 and 7 years.

2. The second group was composed of 51 non-autistic children, aged between 3 and 12 years.

Inclusion and exclusion criteria

Inclusion criteria.

- For the first group, the study included children who both met the DSM-5 criteria for ASD and whose score at the Child Autistic Rating Scale (CARS) was >30.

- For the second group, the unaffected siblings were included as controls.

In both groups, the children were aged at least 3 years. This criterion for age selection is based on the fact that ASD is identified with a high degree of certainty at the age of 3. Exclusion criteria. Exclusion criteria: known neurogenetic conditions (e.g., tuberous sclerosis, neurofibromatosis, fragile X syndrome, Down syndrome).

The control group shared the same exclusion criteria.

DSM-5 diagnostic criteria for ASD. In DSM-5, ASD encompasses the previous DSM-IV autistic disorder (autism), Asperger's disorder, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified.1

CARS assesses the intensity of ASD symptomatology

It evaluates the severity of autistic behaviors in 14 functional areas by assigning a score from 1 to 4. An overall score is calculated by adding all the grades, to stratify patients into three levels: ''severely autistic'' (score between 37 and 60), ''mildly to moderately autistic'' (score between 30 and 36.5), and ''absence of ASD'' (score less than 30).10 The time for administering this questionnaire is around 20-30 min.

Procedures

All study procedures were approved by the local Research Ethics Committee.

Informal consent from parents or legal guardians of participants was obtained after the nature of the procedures had been fully explained.

The interviews were conducted with mothers in 78% of the cases, with fathers in 4% of the cases, and with both parents in 18% of the cases, by a properly trained child psychiatrist.

Parents completed a medical history questionnaire with a combination of closed and open-ended questions regarding

pregnancy, labor, and complications during and after birth. 157

Additionally, data were collected with reference to medical 158

record and medical birth book. 159

The studied variables were designed according to the 1®

probable risk factors of ASD from existing literature. The 161

following variables, which were considered for both groups, 162

were classified as parental factors, pre-, peri-, and post- 163

natal characteristics and were codified as binary variables 164

(yes/no). 165

Parental factors: Advanced maternal and paternal age at 166

the time of childbirth (>35 years), consanguinity. 167

Prenatal factors: These consisted of conditions that arose 168

during pregnancy, such as gestational diabetes, which usu- 169

ally develops in the second half of pregnancy; high and 170

low blood pressure; gestational infections; and fetal distress 171

inducing threatened abortion conditions, such as amni- 172

otic fluid loss, bleeding during gestation, and suboptimal 173

intrauterine conditions. Perinatal factors: delivery charac- 174

teristics, such as term birth (premature or post-term birth); 175

delivery types, including forceps or cesarean section; acute 176

fetal distress; and birth weight (low birth weight [<2500 g] 177

and macrosomia [>4000 g]) 178

Postnatal factors: All conditions occurring in the first six 179

weeks after birth, such as respiratory and urinary infections; 180

auditory deficit (a loss of 30dB); and blood disorders such 181

as anemia and thrombopenia. 182

The diagnosis of respiratory and urinary infections was 183

achieved during hospitalizations in pediatric services. 184

Statistical analysis 185

Statistical analysis was done using SPSS software for Win- 186

dows, release 20.0 (IBM Corp. Released 2011. IBM SPSS 187

Statistics for Windows, version 20.0, USA). The analysis 188

included a descriptive study, observing the frequencies for 189

the quantitative variables and means and standard devia- 190

tions for the qualitative variables, as well as an analytical 191

study, using Pearson's correlation coefficient to establish 192

correlations between the two groups. The level of statistical 193

significance was set at p < 0.05 (alpha level of 5%). 194

In the multivariable analysis, logistic regression was 195

performed to identify risk factors for autism, taking into 196

account confounding factors and using the down method of 197

Wald. 198

Initially, all the variables significantly associated with 199

autism were included in the univariable analysis, as well as 200

those found as risk factors in the literature. The significance 201

level was set at 20%. The final model accuracy was verified 202

and calculated according to the Hosmer and Lemeshow test. 203

The results were expressed by the adjusted odds ratio (ORa) 204

with their confidence intervals, 95% CI (ORa). 205

Results 206

Clinical profile of children with ASD 207

This study included 50 children. A male predominance 208

(37 boys and 13 girls) was observed, as well as a moderate 209

socioeconomic level in 90% of cases, and a predominance of 210

+Model ARTICLE IN PRESS

Hadjkacem I et al.

Table 1 Parental age at the time of conception in both groups.

Group 1 Group 2 p-Value

N % N %

Fathers

<35 years 17 34 25 50.9 0.12

>35 years 33 66 26 49.01

Mothers

<35 years 38 72 41 80.4 0.59

>35 years 12 24 10 19.6

the mild to moderate form of ASD at the CARS (62% vs. 38% for the severe form).

213 Parental factors

214 Table 1 shows the distribution of parental age at the

215 moment of conception in both groups. It indicates that

216 the rate of advanced age (>35 years) among parents

217 at the moment of conception was higher in children with

218 ASD than in their siblings (66% vs. 49.01% for fathers and 24%

219 vs. 19.6% for mothers), but the difference was statistically

220 non-significant.

221 In the present study, the rate of consanguinity was 28%

222 (first degree in 31% of cases, second degree in 26% of cases,

223 and third degree in 43% of cases).

Prenatal, perinatal, and postnatal factors (Table 2) 224

Table 2 displays a comparison of prenatal, perinatal, and 225

postnatal factors between both groups. Despite the fact 226

that no statistically significant differences were observed 227

between prenatal factors in the groups (p = 0.13), the preva- 228

lence was higher in the first group (50% vs. 35.3%). Table 2 229

shows that perinatal factors were more frequent in the first 230

group, with a rate of 60% vs. 11.8% in the second group, a sta- 231

tistically significant difference (p = 0.03). The most frequent 232

perinatal factors found in the ASD group were acute fetal 233

distress (26%), prematurity, and difficult labor observed in 234

18% in each case. 235

As for postnatal factors, they were associated with 236

ASD (40% in the first group vs. 9.8% in the second group, 237

p = 0.042); these postnatal factors were primarily a type of 238

respiratory infection (24% of the cases in the first group). 239

Table 2 Correlation between pre-, peri-, and postnatal factors in both groups.

Group 1 (n = 50) Group 2 (n = 51) p-Value

N % N %

Prenatal factors 25 50 18 35.3 0.13

Exposure to cigarette smoking 11 22 6 11.8 0.16

Urinary infection 6 12 2 3.9 0.16

Hypertension in pregnancy 5 10 3 5.9 0.48

Threatened abortion 5 10 3 5.9 0.48

Gestational diabetes 4 8 1 2 0.2

Hypotension 1 2 0 0 0.49

Perinatal factors 30 60 6 11.8 <0.01

Acute fetal distress 13 26 3 5.9 0.006

Prematurity 9 18 0 0 0.001

Exceeding the term 1 2 1 2 1

Difficult labor 9 18 3 5.9 0.06

Low birth weight3 6 12 1 2 0.06

Macrosomiab 3 6 1 2 0.36

Postnatal factors 20 40 5 9.8 <0.01

Respiratory infection 12 24 1 2 0.001

Urinary infection 3 6 1 2 0.36

Auditory deficit0 2 4 0 0 0.24

Blood diseased 1 2 2 3.9 1

a Low birth weight <2500 g. b Macrosomia >4000 g. c Auditory deficit (a loss of 30dB).

d Blood disease includes, in the G1, one case of anemia, and in the G2, one case of anemia and one case of thrombopenia.

Perinatality and autism spectrum disorder

Table 3 Adjusted analysis of risk factors of ASD.

Covariates Univariable analysis Multivariable analysis

OR p-Value ORa 95% CI (ORa) p-Value

Gender 2.15 0.07 2.5 [0.9-6.9] 0.07

Exposure to cigarette smoking 2.11 0.16 - - -

Urinary infection 3.34 0.16 5.7 [0.8-38.2] 0.07

Gestational diabetes 4.34 0.2 - - -

Acute fetal distress 5.6 0.006 5.2 [1.2-21.6] 0.02

Prematurity 0.001 - - -

Difficult labor 3.51 0.06 3.6 [0.8-16] 0.09

Low birth weight 6.8 0.06 - - -

Respiratory infection 15.7 0.001 22.2 [2.5-191.03] 0.005

■ Light to moderate autism ■ severe autism

p=.16 P=.5

64% „67^ 65%

Prenatal factors Perinatal factors Postnatal factors

Figure 1 Distribution of prenatal, perinatal, and postnatal factors according to the severity of ASD (a total of 50 cases).

240 Table 3 shows that after logistic regression, the risk fac-

241 tors for autism that remained in the final model were: male

242 gender, prenatal urinary tract infection, acute fetal distress,

243 difficult labor, and respiratory infection.

244 Fig. 1 shows the distribution of prenatal, perinatal, and

245 postnatal factors according to the severity of autism.

246 No association was observed between the severity of

247 autism and the prenatal, perinatal, and postnatal factors.

248 Discussion

249 The present study discusses prenatal, perinatal, and postna-

250 tal complications, as well as some parental characteristics,

251 that could be considered as risk factors for ASD.

252 Parental factors

19.6% for maternal age and two-thirds vs. almost 50% for 262

paternal age). 263

Theories advocating the association between parental 264

age and increased risk for ASDs include the potential for 265

more genetic mutations in the gametes of older fathers and 266

mothers, as well as a less favorable in utero environment in 267

older mothers, with more obstetrical complications such as 268

low birth weight, prematurity, and cerebral hypoxia.11 269

Moreover, according to some studies, high prevalence of 270

chronic diseases among older women could contribute to 271

expand the risk of adverse birth outcomes.12,14 Data from 272

the literature trying to explain the increased risk for ASD' s 273

among older mothers have incriminated the high risk of 274

obstetric complications observed in these mothers.11,12,14 275

Furthermore, congenital anomalies are also more com- 276

mon in the fetuses and infants of older mothers, and these 277

conditions contribute in increasing the risk of ASD. 278

In the present study, a rate of 28% of consanguinity was 279

observed. In the literature, it is stated that consanguinity 280

increases the chances of inheriting a bad DNA fit, which 281

will definitely result in a birth defect. Inbred disorders may 282

cause other abnormalities, and ASD can also be brought on 283

by other conditions.15 Since the control group, in the present 284

study, was represented by the siblings conceived and born 285

from the same biological parents, consanguinity could not 286

be evaluated as a risk factor for ASD. 287

Prenatal, perinatal and postnatal factors 288

In the present survey, no correlation was observed between 289

the severity of ASD and prenatal, perinatal, and postnatal 290

factors. The present results are in agreement with some 291

recent studies.16,17 Conversely, some hypothesis have been 292

raised, indicating that the light form of autism would show 293

weaker or no association with obstetric risk factors. 294

Previous studies have linked advanced maternal and paternal age to increased risk for ASDs.11,12

In the present study, the chose 35 years as the age cut-off for both parents. This choice was based the recommendations of many authors.11"13 Despite the fact that a correlation between advanced age at the moment of the conception of both parents and ASD was not observed, the frequency of parents aged over 35 years was higher in children with ASD than their siblings (respectively 24% vs.

Prenatal factors 295

In the present study, the occurrence of maternal infection 296

was higher among cases when compared to controls (12% for 297

the first group vs. 3.9% for controls). 298

According to many studies, adverse intrauterine environ- 299

ment resulting from maternal bacterial and viral infections 300

during pregnancy is a significant risk factor for several 301

neuropsychiatric disorders including ASD.15 The association 302

between intrauterine inflammation, infection, and ASD is based on both epidemiological studies and case reports. This association is apparently related to maternal inflammatory process; hence, maternal immune activation may play a role in neuro-developmental perturbation.

In large population studies, researchers have not identified a specific infection, but rather an increased rate of ASD, especially when the maternal infection is rather severe and requires hospitalization.15,18

Among the prenatal factors identified in this study, exposure to cigarette tobacco (passive smoking) was noted in 22% of cases. Retrospective epidemiological studies have observed, among mothers of children with ASD, a significantly increased percentage of women who were exposed to tobacco during the conception of the child. Therefore, maternal smoking was considered as a potential maternal confounding factor, as well as other toxic chemicals.6

Some authors have demonstrated that maternal cigarette smoking during pregnancy may have a commutative impact on the lineage of her reproductive cells; it is also associated with an increased rate of spontaneous abortions, preterm delivery, reduced birth weight, among others.19 The findings regarding its relation with ASD are still controversial.20"22

The present study showed that the frequency of gesta-tional diabetes was higher in the first group (8% vs. 2% in the second group).

According to some authors, gestational diabetes is mainly associated with disturbed fetal growth and increased rate of a variety of pregnancy complications.23 It also affects fine and gross motor development and increases the rate of learning difficulties and of attention deficit hyperactiv-ity disorder, a common comorbid neurobehavioral problem in ASD. The negative effects of maternal diabetes on the brain may result from intrauterine increased fetal oxidative stress and epigenetic changes in the expression of several genes. The increased risk observed might be related to other pregnancy complications that are common in diabetes, or to effects on fetal growth rather than to complications of hyperglycemia. It is also unknown whether optimal control of diabetes will further decrease this association.23

Because of its rising incidence, maternal diabetes has been considered, by several studies, as an obvious candidate to be associated with ASD, whereas others have failed to demonstrate such associations.15,20,23

In the current survey, hypertension, hypotension, and threatened abortion were more frequent in the first group (respectively 10% vs. 5.9%, 2% vs. 0%, and 10% vs. 5.9% in the second group). These conditions are generally related to fetal loss and adverse infant outcomes, such as prematurity, intrauterine growth retardation, still birth, and neonatal death indicating fetal distress. Likewise, fetal hypoxia is one of the manifestations of fetal distress and has been reported to induce conditions such as placental abruption, threatened premature delivery, emergency cesarean section, forceps delivery, spontaneous abortion, and varying degrees of cerebral damage.4,5 Accordingly, ASD was linked to fetal distress: oxygen deprivation could damage vulnerable regions in the brain, such as the basal ganglia, hippocampus, and lateral ventricles. Some neuroimaging studies have demonstrated abnormalities in these regions among patients with ASD compared with controls.5,14

Hadjkacem I et al.

Perinatal factors

In the present series, perinatal factors were very significantly associated with ASD (p = 0.03). This result is consistent with the literature.4,24 In fact, complications occurring during labor affect the neurodevelopment of the fetus and infant in later stages, and can contribute toward the risk of ASD.

The current research also suggests that obstetric factors occur more frequently in ASD children than in their unaffected siblings. The present results corroborate other studies reporting an association between perinatal factors and ASD.

Perinatal factors were represented by a long duration of delivery and prematurity in 18% of the cases each one and suffering acute fetal in 26% of the cases. Therefore, it is admitted that these conditions may lead to fetal distress and asphyxia, resulting in brain damage. Fetal oxygen deprivation has been proposed to increase the risk for ASD. Recently, research has highlighted the occurrence of ASDs in very preterm infants, in addition to already identified developmental disorders.4,14,24

Postnatal factors

The present findings are in agreement with previous studies suggesting that postnatal events may increase the risk for ASDs in some children.4 In fact, a significant association between postnatal factors and ASD (p = 0.042) has been observed.

In the present study, an association was observed between both urinary and respiratory infections and ASD. These findings could be explained by the release of cytokines as immune responses of the baby to these infections, which can affect neural cell proliferation and differentiation. These impairments are known to be associated with ASD.5,25

Hearing deficits were more common in the first group (4% vs. 0% in the second group). The present results corroborate those of Fombonne,26 who reported, in a meta-analysis, that the prevalence of sensory deficits in autism vary from 0.9% to 5.9%.

Rosenhall et al.,27 in a study conducted on 199 children and adolescents with ASD, estimated that the prevalence of hearing impairment in autism is ten times higher than in general population (11%). They also observed that 7.9% of the patients had an moderate hearing loss, 3.5% were profoundly deaf, and 18% had hyperacusis in the audiogram, even after controlling for the age factor. More recently, Kielinen et al.28 observed, in a population of children with autism, that 8.6% had a mild hearing loss, 7% a moderate deficit, and 1.6% severe deficiency (hearing loss in more than 60dB at audiometry).

The strength of the present study lies in its precise confirmation of the ASD, the active participation of parents, and resorting to unaffected siblings as controls. This last feature may help to identify risk factors and to control for hereditary background, family environment, and maternal predisposition to complications in pregnancy or birth. Nonetheless, there are some limitations, namely the limited number of samples. Therefore, the present results should be completed by epidemiological studies with a larger scale and

Perinatality and autism spectrum disorder

in larger populations. To face the issue of ASD and consanguinity, a larger population with and without consanguinity should be evaluated.

In the present study, no individual factor in the prenatal period was consistently significant as a risk factor for ASD. In the literature, some of these factors were associated with autism; therefore, they should be considered as potential risk factors, as well as perinatal and postnatal events.

Prenatal, perinatal, and postnatal factors for ASD should be considered in the broadest sense: these events of the fetal, newborn, and infant environment could interact or contribute in combination with other co-factors (environmental and genetic, among others) to characterize ASD. Scores indicate that rather than focusing on a single factor, future studies should investigate the combination of several factors.

Conflicts of interest

The authors declare no conflicts of interest.

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