The Essay Explores The Relation Between Birth Order, Delivery Method, And Autism Spectrum Disorder. (70 Characters)

Discuss about the Birth order and reproductive stoppage in children with ASD.

Methods

The objective of the study was to describe the relation between birth order of children with Autism Spectrum Disorder (ASD), and ways of delivery at birth, together with the phenomenon of reproductive stoppage and the number of siblings in the case families (families of children with ASD in the study), and to ascertain whether the incidence of ASD has any relation to the delivery method.

196 participants with ASD and 54 non autistic children were included into the study. The mean age were 56.9 months (SD 27.1 months; median: 51) for the ASD children, and 55.7 months (SD 13.8 months; median: 54) for the control group children.

Demographics were also collected. Autism Behaviour Checklist (ABC), Aberrant Behaviour Checklist (AbBC), and Childhood Autism Rating Scale (CARS) were used to identify ASD cases. Depending on the type of data and on the objective of the assessment, Mann Whitney U Test, Chi-square Test, and Spearman Tests were used for statistical analysis. A p value smaller than 0.05 was considered to be statistically non significant.

In this study group, consisting of children with ASD, the rate of being born of forced labor was determined to be significantly more frequent, compared to the control group (p=0.001). With the exclusion of one child families from the statistical analysis, the assessment of the rate of reproductive stoppage did not demonstrate a statistically significant difference for the families studied in the case (p<0.001).

Conclusion:

Birth order and the type of birth (normal, CS, forced labor) can be considered to be one of the several factors that will help in understanding ASD, in which environmental factors can be the cause of phenotypic complexity.

According to the DSM-5 diagnostic criteria, Autism Spectrum Disorder (ASD) is a developmental disorder characterized by impairment in social interactions and communication accompanied with restricted interest and repetitive behaviors. The estimated prevalence of ASD varies between 0.9-2.7% and has increased noticeably during the past 20 years (1;2). Both clinical and epidemiological studies have shown that autism is 4-5 times more common in boys (3).

ASD seems to have a genetic basis (4), however there is much to be discovered and understood about the processes and mechanisms involved with it. Prenatal exposures to certain environmental stimuli also have been implicated in having a role in the etiopathogenesis of ASD (5). Among these factors, advanced maternal and paternal age, parity, birth order, and obstetric related issues like bleeding, preeclampsia, induced or prolonged labor, type of delivery, intrauterine meconium exposure, fetal distress, drug use by the mother during pregnancy (like psychotropic drugs), pre and post maturity, birth weight, low Apgar scores, and birth defects,  have been the frequently studied parameters (5;6;7;8;9). Although birth order studies in psychiatric diseases maintain their popularity, there are no definite results identified, especially whether there is an association between autism and birth order (5;10;11).  Despite the presence of some studies claiming that ASD emerges in the first child, the results are considered to be contradictory. There are some reports pointing out a negative correlation (11) or a positive correlation (12;13;14) between birth order and ASD, as well as others reporting that there was no relation between birth order and ASD (5).  

Results

Stoppage is defined as a phenomenon in which parents of a child with a severe disease tend to have fewer subsequent children or halt reproduction. Having an autistic child has been evaluated by many studies as a potential factor to affect subsequent pregnancy decisions of case families. In literature, there are studies reporting that the presence of an autistic child in a family affects the next pregnancy decision; however, some other studies present conflicting results. Hoffmann et al., (2015) and Wood et al., (2016) reported that having a child with ASD is associated with reproductive stoppage, whereas Grønborg et al., (2017) reported contradictory results on the same issue (15;16;17).

In order to contribute to the knowledge base in this area of research, the aim of the study was to compare the birth orders and the number of siblings of the children with ASD, compared to those in the control group (of non autistic children). The risk factors were also investigated regarding the etiopathogenesis of ASD, by assessing the potential roles of parental age (in the chosen range in the study group), educational level, delivery type and associated reproductive techniques in addition to the assessment of the number of siblings and birth order. Furthermore, we assessed whether having an autistic child affects the decision making for subsequent pregnancies or if it leads to a reproductive stoppage.

Methods:

A total of 196 children, diagnosed with ASD in our clinic, using the DSM 5 criterions, between January 2015 and January 2016, in Turkey, were included in the study. The diagnosis was made by two psychiatrists specialized in child and adolescent psychiatry and psychiatric examination. A family history and information about children’s symptoms were obtained from the primary caregiver using standardized clinical forms. Autism Behavior Checklist (ABC) and Aberrant Behavior Checklist (AbBC) were administered to the primary caregivers of children with ASD (18;19;20;21). Another scale, the Childhood Autism Rating Scale scores (CARS) was administered by an experienced child and adolescent psychiatrist (22). Autistics with chronic diseases or malignancies were excluded from the study.  The control group consisted of 54 children without ASD who presented to the pediatric outpatient clinic for vaccination and their ages and genders matched with the study group. A family history and information about children’s symptoms were obtained from the primary caregiver using standardized clinical forms.

Maternal and paternal age and their educational levels, patient age, number of siblings, birth order, type of delivery at birth, assisted reproductive techniques and the impact of both being the first-born child and having ASD on reproductive behavior of case families were the parameters to be examined. Statistical analysis was performed via IBM SPSS Statistics for Windows, version 17.0. All continuous variables were defined as means and standard deviations (SD), whereas categorical ones were assessed by frequencies and percentages. Comparisons were performed by Student-T test or Mann Whitney U test and Pearson chi-square test as its non-parametric equivalents. A ‘p’ value of ‘0.05’ was considered to be statistically significant. To conduct the study, approval of the local ethics committee was obtained. Informed consent was obtained from all individual participants and their legal representatives.

Discussion

Reproductive stoppage was analyzed based on the incidence of a child birth, after a child with ASD was already done. However, due to limitations of the timeframe, the study could not observe whether the families analyzed to have reached a reproductive stoppage have had a child beyond the timeframe of the study conducted. An extension of the study can be done by future observations of these families to ascertain if they continue to be in reproductive cessation.

In total, 250 participants from Turkey, consisting of 54 control children without ASD and 196 children with ASD, diagnosed according to DSM-5 criteria, were included into the study.

Demographics:

The mean age of the children with ASD and the controls were 56.9 months (SD 27.1 months; median: 51), and 55.7 months (SD 13.8 months; median: 54), respectively. P Value (Claculated Probability) or Hypothesis Testing and Chi Square Test  showed that there was no significant difference between the two groups in terms of age (p>0.05). The maternal and paternal ages of children with ASD with ASD was higher than those of controls, though there was no statistical significance (p>0.05) (Table 1).

In the ASD group, 163 children with ASD (83.2%) were males and 33 children with ASD (16.8%) were females. In the healthy control group, 47 children (%85.1) were males and 7 children (%14.9) were females. There was no significant difference between the two groups in terms of gender (p>0.05).

The rates of spontaneous vaginal delivery and Caesarean section (C-section) were similar between the children with ASD and the controls (p>0.05). The rates of assisted reproductive techniques (including in vitro fertilization) were similar between the groups (p>0.05). Difficulties experienced during labor (prolonged labor, vacuum or forceps-assisted vaginal delivery) were significantly higher in the ASD group than the controls (21.4% versus 3.7%, respectively; p=0.002) (Table 1).

Birth Order:

In regards to birth order, 63.3% (n=124) of the children with ASD with autism were first-born, 26.0% (n=51) were the second, 7.7% (n=15) were the third, 2.6% (n=5) were the fourth, and 0.5% (n=1) were the fifth-born child in their families (_X²=15.729, p=0.003). Because there were no children in the control group born as the fourth or the fifth child in their families, those children were excluded from analysis. When data were re-analyzed by excluding children born on the fourth and fifth birth order ranks,  the result showed statistically significant for being the first-born child in ASD group compared to the control group (x²=13.792, p=0.001).

Conclusion

Upon exclusion of the one-child families from the statistical analysis (n=214), evaluation of being the first-born child in the ASD group as a parameter (n=170) resulted in a statistical significance compared to controls (n=44) with a rate of 57.6% (98/170) vs. 27.3% (12/44), respectively (Chi Square Test=18.727, p=0.000) (Table 3).

Birth order demographics:

In regards to the association between gender and birth order, the rate of being a female in the first-born children in ASD group was found to be statistically higher than that of the control group (Chi Square Test=14.338, p=0.002). In the C-section group, a larger proportion of the ASD children were first-born, compared to the control children (Chi Square Test=8.035, p=0.032). The proportions of the first-born children delivered after a prolonged labor or by vacuum-forceps applications in ASD group were significantly higher compared to the control group (Chi Square Test=9.429, p=0.024, Table 4).

The analysis of data, after excluding the one-child families (n=36), demonstrated that development of ASD in the first child was independent of gender or type of delivery at birth. In addition, upon controlling for the one-child families, there was no relation between difficult labors and SC and being the first-born children with ASD (p<0.05), however a significant relation (p=.0.85) was found in case of forced (vacuum prolonged) labour.  (Table 5).

Stoppage:

The proportion of having a single child was 14.4% for all participants (36/250). While 13.3% of the families (26/196) in ASD group had one child, 18.5% of families (10/54) in the control group had one child, revealing a statistically not significant result for stoppage (_X²=0.948, p=0.330). It was found that 86.7% (n=170) of the children in the ASD group had at least one sibling compared to the rate of 81.5% (n=44) for their counterparts in the control group (Table 6).

To evaluate the stoppage phenomenon, the single-child families (n=36) and families whose last child was diagnosed with ASD were excluded from the analysis (Table 7). The statistical analysis revealed that in the ASD group, A 100.0% (n=87) of the mothers whose first-born child had ASD, gave birth to their second child (_X²=15.250, p=0.000). In three-children families, 100.0% (n=9) of the mothers, whose first-born child was diagnosed with ASD gave birth to other children. When the families having the second children diagnosed with ASD were examined, 14.3% (n=4) of the mothers gave birth to the other children in the family. For families with four children, 100.0% (n=2) of the mothers, whose first-born child had ASD, and 22.2% (n=2) of the mothers whose second children had ASD, gave birth to other children in their families.

Limitations

The birth order, which is defined as the order of arrival among the siblings of the individual, has been investigated in many disease etiologies in recent years (23). There are different results and interpretations in the literature with respect to the relation between birth order and ASD. Our study compared ASD group to controls in terms of birth order, demonstrating a significant difference for being the first-born child in the ASD group.  Reviewing the research carried out in this area, a study in which pregnancy complications were not controlled, reported that there was no association between ASD and maternal age or birth order (11). However other studies demonstrated a higher risk for ASD in the children born by forced labor compared to the control participants (12;13;14). Our results confirm the reports of the latter studies.

It has been reported that during the first labor, the child is exposed to the birth canal stress, congenital complications, and asphyxia at a greater extent and more frequently in forced labor, and that each of these factors might lead to minimal brain damage (24;25). In our study, the rate of difficulties during labor was determined to be higher in the ASD group than that of the control group.  Evaluation of these findings, that is the higher rates of being the first-born children and the higher rates of difficult labors in the ASD group, suggests that the children born by forced labor may be more exposed to perinatal stress, resulting in minimal brain damage, which may have a role in ASD etiopathogenesis.

There are contradictory results on the potential role of maternal or paternal age in ASD.  A cohort of ASD cases reported that the probability of developing autism in their third children, whose mothers’ ages were between 20 and 34,  and fathers’ ages were below 40, was 3-times higher than that of first-born children of older parents  (10). In another study, the order of birth and maternal age in 113 families having children with ASD were compared with the general population. No correlation was reported for birth order in the ASD group. Especially risky pregnancies (including first, fourth or later births) demonstrated more autistic children compared to the population sample (26;27).

Examining the designs of the studies, in general, reveals some limitations such as inadequate selection of the control group, insufficient diagnostic tools, and lack of identification of delivery types at birth. In our study, the maternal and paternal ages were higher in the ASD group; however, this difference was not statistically significant. This result supports the findings of other studies reporting that parental age does not seem to be the primary risk factors for having autistic children. However, it must also be noted that the only risk factor of parental age on ASD is that older parents of autistic children might stop at one child, owing to their ages. Therefore, the correlation of advanced age of parents as risk factor for ASD still needs to be understood clearly. Similarly, race might also have an association to the access to ASD diagnosis and reproductive patterns, as might poor pregnancy outcomes like preeclampsia and preterm birth.

References

In our study, it was found that there were no statistically significant differences between birth order and sibling numbers and CARS, ABC, AbBC scores in the autistic group.   A study with a small sample size including sixteen families, reported that non-verbal IQ scores decreased as the number of births increased (28). A different study with one hundred and sixty-one families showed a significant increase in speech difficulties and repetitive behaviors in the first and second children, diagnosed with ASD, in these case families (29). In the same study, it was observed that there was a negative correlation between birth order and intelligence level in children affected by autism. Another similar study suggested that difficulties in verbal and non-verbal communication were more common in autistic children born as the first and second children, and that autism-related symptoms were more severe in those participants (30). These studies demonstrate similar patterns and limitations, such as the inadequacy of the control groups, and the selection of study children with ASD among the participants, who present to the clinic. Although our results are not parallel to those reported in the literature, the differences are interpreted to be due to cultural variability.

86.7% (n=170) of the children in the autism group and 81.5% (n=44) of children in the control group had at least one sibling. It was determined that 92 (46.9%) mothers having autistic children did not give birth to others. However, it was observed that 53.1% (104/196) of the mothers continued to give birth even though they had autistic children. There are conflicting results in the literature whether having autistic children affects the decision for the next pregnancy (15;16;17). These studies published by Hoffmann et al., (2014) in the US, and by Wood et al., (2015) in England, demonstrated that mothers with autistic children did not give birth to other children (15;16). However, another study published by Gronborg et al., (2015) reported that Danish mothers with autistic children continued to give birth (17). Psychosocial implications of having children with ASD may cause fewer children in families by influencing the decision for the next pregnancy. In our study, it was observed that having a child with autism in the Turkish sample did not affect the decision for the next pregnancy.

We also investigated the relationship between gender, type of delivery (C-section or vaginal), and assisted reproductive techniques used for conception in the study groups. No study results on the sex of the first-born child with autism exist in the literature. As regards to the method of deliveries, contradictory findings have been reported. It was emphasized in some studies that Cesarean sections increased the risk of ASD; however, it was reported to be lower in some other studies (31;32;33;34). In a retrospective cohort study, birth history records were analyzed, concluding that there was no significant difference between the type of delivery and ASD (34). In another study, assisted reproductive techniques were demonstrated to be one of the risk factors for developing autism, but another study reported no significant difference (35;36).

In our study, by the statistical analysis including single-child families as well, the first-born autistic children were demonstrated at significantly higher rates among girls, Cesarean section cases, and forced deliveries. However, when single-child families were excluded, these factors were found to be independent risk factors. Our research findings provide supportive evidence that these factors are not the indicated associated risk factors for ASD when single-child families are excluded (6;37).

There are some limitations of our study that it is not a community-based study as the study sample consists of children with ASD applying to the clinic. The other limitation is the smaller size of the control group compared to the patient group. However, the results of community-based studies may demonstrate variability. Since our study included a control group, despite the small sample size compared to the patient group, the comparative analysis of the parameters including the type of deliveries at birth and one-child families to the control group are our study’s strong aspects.

Although a large number of studies have reported that there is a significant relationship between birth order and autism, this relationship is not consistent and often not linear. There is a fundamental difficulty in enlightening this relationship between the birth order and autism, because of the fact that the mother with autistic children does not prefer to give birth to another child. Thus, evaluating birth order in autism, is naturally handicapped with the mothers had twin children with both autism, or all children had autism. Despite the fact that studies conducted in this area shed light on the link between autism and the birth order, the small sample sizes and lack of systematic evaluations limit the generalization of the results. The order and type of birth can be considered to be some of the many environmental factors, which will help in understanding ASD. However, as it is well known, ASD has a complex and multifactorial etiology. Environmental interactions apart from the birth order and genetics can also be the cause of phenotypic complexity in the ASD.

The local ethics committee approval was obtained for the study. Local Ethics Committee approval for this study is registered as 2015-30.

Consent was obtained from all individual participants and their legal representatives included in the study.

All authors declare that they do not have any type of conflict of interest.

Research involving human participants and/or animals:

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Local Ethics Committee approval for this study is registered as 2015-30

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