|Year : 2021 | Volume
| Issue : 3 | Page : 158-165
Impact of familial and perinatal risk factors in children with attention deficit hyperactivity disorders: an Egyptian sample
Manal Omar1, Dina Y ElAlfy1, Michael Sobhi2
1 Department of Medical Studies for Children, Faculty of Postgraduate Childhood Studies, Ain Shams University, Cairo, Egypt
2 Psychological Studies for Children, Faculty of Postgraduate Childhood Studies, Ain Shams University, Cairo, Egypt
|Date of Submission||09-May-2021|
|Date of Decision||20-May-2021|
|Date of Acceptance||09-Jun-2021|
|Date of Web Publication||28-Sep-2021|
PhD Dina Y ElAlfy
Department of Medical Studies for Children, Faculty of Postgraduate Childhood Studies, Ain Shams University, Cairo, 11771
Source of Support: None, Conflict of Interest: None
Introduction Attention-deficit hyperactivity disorders (ADHD) are reported in children who have a higher risk of perinatal complications, reaching up to 35–50% of children born with low birth weight, or preterm, and other natal and neonatal complications.
Objective To study the patterns and extent of familial and perinatal risk factors in children with ADHD.
Patients and methods The sample was 456 ADHD cases out of 3152 children who were attending a Neurodevelopmental Child Psychiatry Clinic in Cairo, Egypt, from April 2010 to October 2018. The control group was 274 apparently normal children attending the Neurodevelopmental Child Psychiatry Clinic for parental consultations and counseling.
Results The most prominent significant risk factors were the existence of attacks of skin allergy and cerclage prenatally, while asphyxia and neonatal ICU admission were significant risk factors postnatally. There was a significant correlation between the cerclage and in-vitro fertilization with no significant correlation with previous abortion. There is a significant correlation with threatened abortion, using drug treatment for threatened abortion, infection, and inflammation during pregnancy, also the placenta was not nutritive, kidney, lung, cardiac problems postnatally, and cesarean section were significantly correlated with cerclage as a risk factor.
Conclusions There was a complex interaction of familial and other antenatal risk factors of ADHD, the role of an inadequate maternal and child healthcare delivery system was also evident.
Keywords: attention deficit, hyperactivity, perinatal risk factors
|How to cite this article:|
Omar M, ElAlfy DY, Sobhi M. Impact of familial and perinatal risk factors in children with attention deficit hyperactivity disorders: an Egyptian sample. Egypt J Psychiatr 2021;42:158-65
|How to cite this URL:|
Omar M, ElAlfy DY, Sobhi M. Impact of familial and perinatal risk factors in children with attention deficit hyperactivity disorders: an Egyptian sample. Egypt J Psychiatr [serial online] 2021 [cited 2021 Dec 6];42:158-65. Available from: http://new.ejpsy.eg.net/text.asp?2021/42/3/158/326850
| Introduction|| |
Attention-deficit hyperactivity disorder (ADHD) is a multifactorial disorder; both genetic and environmental factors have been implicated in its etiology. Factors affecting resilience during perinatal development remain unexpected (Rodriguez, 2008). Neonatal complications were quite common nearly (30%) among children diagnosed with ADHD (Mitra and Kunar Ray, 2013). Among the known ‘fetal environment,’ important questions remain to be answered concerning whether these neurobehavioral deficits mark teratogenic influences that will challenge the behavioral process throughout development (Charil et al., 2010). The most dramatic rapid period of brain development in the life span occurs prenatally (Rodriguez, 2008). There were risk factors such as maternal lifestyle, smoking, drinking (Ornoy et al., 2015), drug abuse, and maternal stress (Van den Bergh and Marcoen, 2004; Rodriguez, 2008; Motlagh et al., 2010).
Also, socioeconomic status or low level of parental education influences the kind of disorder that the child might develop as ADHD (Van den Bergh and Marcoen, 2004), or the psychosocial adversities may result in maternal stress during the postnatal period (Mitra and Kunar Ray, 2013). The role of an inadequate maternal and child healthcare delivery system is also evidenced by environmental risk factors related to ADHD (Anthony et al., 2009; Mitra and Kunar Ray, 2013; Doaa et al., 2018).
Timing of the stress may be the most important moderator for the effects on the fetus (Charil et al., 2010). The very low birth weight is the most important perinatal factor, which causes up to twofold increase in ADHD, while other complications such as asphyxia, jaundice, and sepsis, also are found to have relations with ADHD (Mitra and Kunar Ray, 2013; Smith et al., 2016).
Although these factors are well studied in other populations, we could hardly find studies in the Egyptian population.
| Objective|| |
This study aimed to find out the extent of prenatal, natal, and postnatal risk factors, and patterns of sociodemographic factors in children with ADHD in Egypt.
| Patients and methods|| |
This retrospective study was conducted at Neurodevelopmental Child Psychiatry Clinic (NDCPC) in Cairo, Egypt. All children aged 3–14 years (mean, 7±2 years), attending the clinic from April 2010 to October 2018, diagnosed with ADHD, according to Diagnostic and Statistical Manual of Mental Disorders, 4th edi. (Wiggs et al., 2016), were selected. Their intelligence quotient (IQ) was assessed by Stanford Binet 4th ed. (APA, 1994), or draw a Person Test (Prewett, 1992) and it ranged from 71 to 144 (mean, 92±21). Parents of these diagnosed cases of ADHD were interviewed regarding perinatal (prenatal, natal, and postnatal) risk factors on a semistructured scale. The scale was prepared after overviewing numerous scales, offering an opportunity to identify risk factors during pregnancy, complications of labor, and infants with later complications. Ethical consideration and approval according to the instruction of the Research Ethics Committee in the Faculty of Postgraduate Childhood Studies (IPGCS, 2014) were taken following the code of ethics of the World Medical Association (Declaration of Helsinki, 1989) for experiments involving humans. Oral informed consent was obtained from the parents and children after explaining the aim of the study and its benefits for their children.
A cumulative risk factor based on the antepartum fetal risk scale (Goodwin et al., 1969; Harris, 1963), The Nesbitt and Aubry, the maternal–child healthcare index (1969) (Goodwin et al., 1969), and the maternal perinatal scale of Dean and Gray (1985) (Aubry and Nesbitt, 1969), and Trammell, the maternal perinatal scale as a predictor of developmental risk (2012) (Dean and Gray, 1985), our perinatal risk factor scale was created. Sociodemographic status was taken in detail. The ‘prenatal period’ included 30 risk factors such as eclampsia, skin allergy, sepsis, bleeding, etc., and 23 risk factors in the ‘natal period’ such as fetal distress, meconium aspiration, etc., and (20) risk factors such ‘postnatal’ prematurity, low birth weight, asphyxia, etc.
Our scale was applied through a personal interview by the same psychiatrist and the mothers to be more reliable by answering (yes, no, don’t know).
The raw scores of all the items were changed to T-standard scores, with a mean 50±10 to differentiate between the different groups.
The reliability of the scale was 0.848 using ‘Cronbach’s alpha reliability,’ which was considered a highly reliable quotient.
The validity of the scale was calculated through the relation between the total and subtotal scale scores by using Pearson correlation ([Table 1]).
|Table 1 The correlation between total scale score and subscale score validity|
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These results showed a significant positive correlation between the total scale scores and the subscale scores at 0.01 level denoting the cohesion of the items, all of them were in the same scope that was assessed by our perinatal risk factors’ scale (consisted of prenatal, natal, and postnatal risk factors). This proved the validity of the items of the scale.
Recorded data were analyzed using the Statistical Package for Social Sciences, version 20.0 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean±SD (t test). Qualitative data were expressed as frequency and percentage (χ2) and Spearman’s correlation.
| Results|| |
Three thousand one hundred and fifty-two children with age range 3–14 years (mean 7±2 years) were registered in the NDCPC over 8 years (2010–2018). After exclusion of other neurodevelopmental disorders (NDS) and diagnosis, the final sample was 456 ADHD children, 15% of the attendance of the clinic; 379 (83.1%) males and 77 (16.9%) females with a ratio 5 : 1 males to females. The control group was 274; 145 (52.9%) males and 129 (47.1%) females, with a ratio 1 : 0.88 of males to females.
The ADHD group IQ ranged 71–144 (mean, 92±21), while the control group ranged 95–108 (mean, 100.1±3.6).
These children predominantly belonged to middle socioeconomic status families of both the ADHD and control group.
Father’s and mother’s job of ADHD children and the control group, respectively, showed a statistically significant difference, except for business the difference was nonsignificant. As regards positive parental consanguinity, there was a significant difference between ADHD and the control group ([Table 2]).
There was no significant difference between the below-average and above-average IQ ADHD children concerning the perinatal risk factors ([Table 3]).
|Table 3 Comparison between attention-deficit hyperactivity disorder children as regards perinatal risk factors and intelligence quotient|
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Comparing the ADHD group and the control group, there was no significant difference as regards being twins, while there is a significant difference being the second order of birth among the ADHD group.
While no significant difference as regards the age of the mother between the ADHD and control groups.
Risk factors during the prenatal period showed a significant difference between the ADHD and control group, as regards the incidence of maternal skin allergy, obstetrical intervention with a cervical cerclage, and in-vitro fertilization (IVF) as a way of conception. While there was no significant difference concerning any risk factor among the ADHD group during the natal/delivery period. Nevertheless, postnatally, asphyxia/cyanosis and Rh incompatibility were the two risk factors, which showed significant differences among the ADHD group when compared with the control group ([Table 4]).
|Table 4 Comparison between attention-deficit hyperactivity disorder and control group as regards perinatal risk factors|
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As regards the correlation between skin allergy and perinatal risk factors, there was no significant correlation with any prenatal risk factors, and as regards postnatal risk factors, there were no significant correlations, except for kidney, lung, and cardiac problems where there was a positive significant correlation. As regards the correlation between cerclage and perinatal risk factors, as regards prenatal risk factors, there was a high positive significant correlation with IVF, infection and inflammation, and nonnutritive placenta as prenatal risk factors and there was no significant correlation with skin allergy. While as regards postnatal risk, there was a high positive significant correlation with kidney and positive significant correlation with cesarean section, lung problems, and neonatal intensive care unit (NICU) admission, and there was no significant correlation with Rh incompatibility, cardiac problems, or asphyxia. As regards the correlation between asphyxia and perinatal risk factors, as regards prenatal risk factors, there was a positive significant correlation with IVF, threatened abortion, infection and inflammation, and nonnutritive placenta, and there was no significant correlation with skin allergy or cerclage. While as regards postnatal risk, there was a positive significant correlation with kidney, lung, cardiac problems and NICU admission, and Rh incompatibility ([Table 5]).
|Table 5 Correlation between skin allergy, cerclage, asphyxia, and perinatal risk factors|
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| Discussion|| |
The etiology of ADHD is complex, involving both genetic variants, as well as multiple environmental risk factors (Trammell, 2012). Neonatal complications are more frequent in ADHD children, compared with their nonaffected sibs (Dunn et al., 2019).
In fact, 30–40% of neonates and infants with brain injury die, while 20–40% of survivors develop significant neurological impairments (Ben Amor et al., 2005). The central nervous system begins to develop just (Ben Amor et al., 2005) days post conception, with the induction of the neural plate (Van den Bergh and Marcoen, 2004; Ben Amor et al., 2005; Sauber-Schatz, 2009).
Any alteration in the developmental process will lack both normal circuit and adequate autoregulation of the brain areas to recover (Ben Amor et al., 2005; Motlagh et al., 2010; Ornoy et al., 2015). The severity of the perinatal complications and their prolonged character, suggests the fact that these factors may play a role in the etiology of ADHD (Anthony et al., 2009; Dunn et al., 2019).
In our study, 456 (15%) children were diagnosed with ADHD out of 3152 children who attended the NDCPC; the ratio of male children to females was 5 : 1. Most of them were from the middle social class. As regards positive parental consanguinity, there was a significant difference (P=0.05) between ADHD and control groups, and the highest order of birth were being the second sibs (66.7%) in the ADHD group with a significant difference when compared with the control group (33.2%) (P=0.05).
In another study in ElQalyubia Governorate, 21.8 and 16.2% of 921 study group were diagnosed as ADHD based on teachers and parents scale, respectively, in primary school children, less likely in urban than high socioeconomic level, assuming that the region and social and school demands were the main factor that elevates the concern and diagnosis, more than any other social factors (Brites, 2012).
In Menoufia Governorate in Egypt and Qatar, (6.9 and 11.1%), respectively, of the preschool children in their studies were diagnosed with ADHD (Farahat et al., 2014; El Gendy, 2017).
Previous studies showed high significant ADHD symptoms and consanguineous parents might reach seven times higher in ADHD than the control group (Brites, 2012; Farahat et al., 2014; El Gendy, 2017), while in developed countries, consanguineous parents were almost nil, it is forbidden among some orthodox religion families and culturally not accepted.
Consanguinity in developing countries must be taken into good consideration for further studies and counseling.
As per the ADHD order of birth, also researches in the developing countries mostly showed contradicting results from being significant in the first and second sibs, as there were more pregnancy and delivery complications in primigravida than multigravida (Bener et al., 2008; Brites, 2012; Marín et al., 2014), which came in agreement with our results, while other studies showed that sixth one of the family, where 47.1% of ADHD were born in families more than four children (Evrensel et al., 2014). Studies in developed countries, natality is decreasing, most of the families had one or two children, where the order of birth as a factor cannot be studied properly (Bener et al., 2008).
Our results showed a significant difference among the ADHD group concerning cervical cerclage during pregnancy 24%, while in the control group was 6% (P=0.05).
In the Royal College of Obstetricians and Gynecologists, the Green Top Guide Lines (Berger and Felsenthal-Berger, 2009) mentioned that cerclage should be offered to women with three or more previous preterm births, or second-trimester loss (Royal College of Obstetricians and Gynaecologists, 2011). In our study, there is no significant difference between the ADHD group and their control group concerning previous abortion.
Also, there was no significant correlation between the cerclage and previous abortions among the ADHD group itself. This means that obstetricians in Egypt may recommend cervical cerclage more-than-needed situation. The correlation in the ADHD mother’s group between cerclage and other factors shows a positive significant correlation with other risk factors as IVF (P=0.0001), significant correlation with threatened abortion (P=0.047), nonnutritive placenta (P=0.0001), infections and inflammations during pregnancy (P=0.003), cesarean section as a way of delivery (P=0.02), and kidney and lung problems postnatally (in both P=0.05), while there was no significant correlation with cardiac problems. It might be the IVF way of conception, and the consideration that the fetus is a precious baby, leads to intervention with cerclage, after trial of drug treatment of threatened abortion, which shows a high correlation with the cerclage as a risk factor among the ADHD group.
Since 1978, where the first IVF pregnancy was achieved, the procedure performed has dramatically increased. To reduce the chance of multiple pregnancies, a good-quality embryo (Brown et al., 2013; Epelboin et al., 2014) is chosen (Lu et al., 2013). In our study, although the IVF was a significant risk factor in the ADHD group, it is still not significantly correlated with twin pregnancy (P=0.129). Few studies have assessed the clinical and embryological factors affecting pregnancy outcome (Lu et al., 2013; Mohammed et al., 2016). Around 3% of children conceived by IVF are associated with a high risk of prematurity and neonatal complications (Brown et al., 2013), perinatal birth defects, epigenetic disorders (Epelboin et al., 2014), and congenital disease as the cardiovascular, urogenital, and musculoskeletal system (Brown et al., 2013). Our study results showed a significant difference as regards IVF as a risk factor in the ADHD group in comparison to the control group (P=0.05).
Nevertheless, in the ADHD group, those conceived via IVF, having a risk of threatened abortion (which was not responding to drug treatment), the intervention with cerclage, not following the guidelines, put the embryo in stressful conditions, showing its outcome and significantly correlated with kidney and lung problems postnatally.
Other studies showed an increased risk of autism-spectrum disorders (ASD), and cerebral palsy with IVF conception (Mohammed et al., 2016), but almost no studies found an association of high risk of IVF and ADHD.
Although injury during pregnancy has not been adequately studied as a risk factor for central nervous system birth defects, injury during pregnancy could alter developmental processes, and the reproductive organ injury results from mechanical forces inflict soft tissue, where cerclage is one type of it, considered as another potential mechanism for birth defects. Injuries that occur at different gestational ages have various severities that might have different effects (Ben Amor et al., 2005; Hediger et al., 2013; Ornoy et al., 2015).
In our study, the correlation between the cerclage and nonnutritive placenta showed a highly significant correlation, the poor nutritive placenta would be considered as another factor of risk in the ADHD group. The placental–fetal unit initiates a cascade of responses to preferentially allocate oxygen and nutrients to promote survival (Motlagh et al., 2010; Smith et al., 2016; Doaa et al., 2018).
Many studies assumed that obstetric complications as prenatal ischemic hypoxia lead to placental–fetal hypoxia response that partially determined the association between low birth weight and ADHD (Brake et al., 2000; Dunn et al., 2019).
In our results, nonnutritive placenta leading to placental hypoxia was significantly presented as a predictor of ADHD presentation. Exposure to ischemic-hypoxia status leads to changes in metabolic demand, angiogenesis inflammation, immune response, changes in the neuroprotective–neurotoxic systems, changes in the oxidative stress, and blood flow distribution (Low et al., 1993; Lu et al., 2013).
The placental–fetal unit may alter the structure and function of developmental systems, including the brain, increasing ADHD risk factor (Berger et al., 2000; Trammell, 2012; Lu et al., 2013) as shown in our study with the significant correlation of kidney, lung, and heart problems.
Studies showed that in response to prenatal ischemic hypoxia, the immune system responds by increasing the circulating proinflammatory cytokines with further compromises with fetal brain developmental deficit, including ADHD (Rodriguez, 2008; Lu et al., 2013; Smith et al., 2016); in response to fetal hypoxia, the brain shows an association with decreased vascular plasticity in the postnatal period and increased risk for ADHD. Our study results showed agreement with previous results, where there was a significant correlation between postnatal significant cyanosis and nonnutritive placenta (P=0.01) and NICU admission (P=0.01), suggesting that insults in the prenatal period might be the cause of more complications in the natal or postnatal periods (Low et al., 1993; Hediger et al., 2013; Dunn et al., 2019).
Studies suggested that chronic exposure to hypoxia is more likely to be associated with neuropsychological impact, specifically ADHD (Brake et al., 2000; Hediger et al., 2013; Dunn et al., 2019; Roigé-Castellví et al., 2020) rather than acute insults.
The cumulative factors, prenatally in our study results concerning ADHD groups and the significant presence of maternal infection and inflammation correlated to cervical cerclage, also correlated to drug treatment of threatened abortion. Moreover, there was a significant difference between the ADHD group and control group as regards the occurrence of maternal skin allergy during pregnancy (P=0.05), denoting that the inflammatory process plays an important role in association with ADHD (Brake et al., 2000; Trammell, 2012; Lu et al., 2013; Roigé-Castellví et al., 2020).
Studies showed a significant association between maternal chemical intolerance and diagnosis of ADHD, reporting two to three times more likely to report adverse allergic reaction (Ben Amor et al., 2005; Rodriguez, 2008; Charil et al., 2010; Mitra and Kunar Ray, 2013; Doaa et al., 2018).
From all the previous results and studies, risk factors that show a highly significant positive correlation with ADHD, show that hypoxia is the most clear associated factor with ADHD (Low et al., 1993; Berger et al., 2000; Brake et al., 2000; Dunn et al., 2019).
Either in the form of placental ischemia or postnatal cyanosis/hypoxia via the angiogenic system, or through inflammatory processing via allergy or infection and inflammation that the mothers suffer from or via neurotrophic process, via cerclage and soft-tissue injury, or teratogenic via drugs for threatened abortion, all processes adapt to ischemic–hypoxic environment altering the developmental system, or increasing ADHD risk factor.
In our study, there were no significant correlations between skin allergy as a significant risk factor in the prenatal period and other perinatal factors, while there was a significant correlation between asphyxia/cyanosis postnatally and the Rh incompatibility between the fetus and the mother.
The correlation showed a comprehensible relation with the fact that the highest percent in the ADHD group was being the second sib in order of birth, who is more susceptible to Rh incompatibility. Although the Rho immunoglobulin preparations were injected, it was hypothesized that the Rho immunoglobulin preparation exposure was a risk factor for NDS (Wei et al., 2015). Thimerosal ingredient used was considered to poison at a minute level with a plethora of deleterious consequences on fetal and infant neurodevelopmental deficits such as ASD, ADHD, and Tic disorders (Geier et al., 2008).
Nevertheless, studies compare children born before and after 2002 when thimerosal (49.5% mercury by weight) (TCR) was removed from the manufactured preparations, accused the TCR as a risk factor for NDS (Wei et al., 2015). In agreement with our results, other studies showed that Rh incompatibility between the fetus and his mother is considered a risk factor parse in ASD and ADHD children (Geier et al., 2015; Heron and Golding, 2004). While no other research correlates between the Rho incompatibility and the potentiality of the neonate to develop asphyxia/cyanosis after delivery. In Egypt, we use the thimerosal-free ingredient in the immunoglobulin preparation, so the relation of NDS in ADHD is not pointing to the preparation, as it is pointing to the Rho incompatibility as a risk factor parse, considered as a toxic environment, suggesting that it might aggravate the effect of other risk factors, hence that it is more likely to be involved in the chain of events leading to ADHD (Dunn et al., 2019).
| Conclusions|| |
The prevalence of ADHD in the NDCPC was 15%. Though similar to other studies, the pattern of risk factors was different. There was a complex interaction of familial and other antenatal risk factors. The role of an inadequate maternal and child healthcare delivery system was also evident. This indicates the importance of the implementation of a follow-up program for maternal and child health care by the health authorities all over Egypt.
The authors acknowledge and thank all participants and their families in the current study for their valuable time.
Authors’ contributions. M.O.: contributed to the study concept and design, analysis and interpretation of data and results, and writing of the paper, recruited and studied the patients, and gathered all the data. D.Y.E.: contributed to analysis and interpretation of data and results and critical revision and editing of the paper. M.S.: contributed to study the statistical analysis of the data and results.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]