Question:

Discuss the Birth order, and the reproductive stoppage in children suffering from ASD.

Answer to Question: PSKL441 Clinical Psychology

The purpose of this study was to analyze the relationship between ASD-related birth order and methods of birth (including the phenomenon known as reproductive stoppage) and siblings in case families (families with children with ASD). It also sought to establish if ASD’s incidence can be correlated with the method of birth.

Materials and Methods

There were 196 ASD patients and 54 children who weren’t autistic.

The mean age was 56.9 Months (SD 27.1 Months; median: 51), in ASD children, and 55.7 Months (SD13.8 months; median is 54) in control group children.

Demographics also were collected.

ASD cases were identified with the Autism Behaviour Checklists, Aberrant Behaviour Checklists and Childhood Autism Rating Scale (CARS).

The type of data used and the objective of the assessment influenced the use of Mann Whitney U Tests, Chi-square Tests, and Spearman Tests for statistical analysis.

A p value of 0.05 or less was considered statistically not significant.Result:

In the study group consisting of ASD-related children, the rate at which they were forced to labor was significantly higher than that in the control (p=0.001).

The statistical analysis did not show a statistically significant difference in the rates of reproductive stoppage for the families that were excluded from the study (p0.001).Conclusion:

ASD can be understood by considering the birth order, CS, and forced labor. These factors are important in understanding how environmental factors may contribute to phenotypic complexity.

Methodology

DSM-5 diagnoses Autism Spectrum Disorder, or ASD, is a developmental disorder characterised by impairments of social interactions and communication. This condition also has restricted interest and repetitive behaviours.

ASD’s prevalence ranges between 0.9-2.7%, and has increased in recent years (1;2).

Research from epidemiological and clinical studies has shown that autism is 4 to 5 times more common in boys (3).

ASD has a genetic basis. However, we still have much to learn about the processes and mechanisms that cause it.

ASD may also be caused by prenatal exposure to environmental stimuli ((5)).

These factors include maternal and paternal advanced age, parity, gender, birth order, and obstetric issues like bleeding and preeclampsia. In addition, drug use during pregnancy (like psychotropic medications), pre and/or post maturity, birthweight, low Apgar scores and birth defects have been frequently studied (5;6;7,8;9).

Although birth order studies of psychiatric conditions continue to be very popular, it is not clear if there is an association with autism.

The results of some studies that claim ASD develops in the first-born child are contradictory.

Some reports indicate a negative or positive correlation (11) between ASD (13;13;14) and birth order. Other reports report that ASD is not related to birth order ((5)).

If a parent has a child with severe diseases, it is known as “stoppage”. This refers to the phenomenon when they have fewer children later on or stop conceiving.

Studies have indicated that the presence of an autistic baby could affect future pregnancy decisions.

Many studies have reported that an autistic child may affect the next pregnancy decision. However, some studies show conflicting results.

Hoffmann and Wood (2015) reported that ASD was associated with reproductive stopping. Gronborg and colleagues (2017) had contradictory findings on the same topic (15-16-17).

This study was designed to provide additional knowledge in this area. The goal of the study was for siblings to be compared with those of non-autistic children.

ASD was also assessed for risk factors by evaluating the roles of parental education, birth type, delivery method and associated reproductive techniques. In addition to the assessment on the number and order of siblings, the study also looked at the role of these factors in ASD’s etiopathogenesis.

Additionally, we evaluated whether autistic children affect the decision making process for subsequent pregnancies.Methods:

A total number of 196 children with ASD were examined in our clinic. We used the DSM 5 criteria. It was conducted between January 2015 to January 2016.

Two psychiatrists with specializations in child and young adult psychiatry were involved in the diagnosis.

Using standard clinical forms, the primary caregiver obtained a history of the family and information about the children’s symptoms.

A Autism Behavior Checklist, (ABC), and an Aberrant Behavior Checklist were completed by primary caregivers to children with ASD (18-19;20-21).

Another scale, the Childhood Autism Rating Scale scores was (CARS), was administered to ASD children and adolescents by a qualified child-adolescent psychiatrist (22).

The study did not include autistics suffering from chronic diseases or cancers.

The control group comprised 54 children without ASD, who were seen at the pediatric outpatient clinic for vaccination. Their ages as well as genders were matched to the study group.

The primary caregiver used standardized clinical forms to obtain information about the children’s symptoms and their family history.

To be examined were their maternal and paternal years, as well as their educational levels, number and siblings of patients, birth orders, type of birth at delivery, assisted reproductive methods, and the effects of having ASD on the reproductive behaviour of case families.

IBM SPSS Statistics, version 17.0, was used to conduct statistical analysis.

All continuous variables were described as means and standard errors (SD), while categorical variables could be viewed by frequency or percentages.

As non-parametric counterparts, Student-T and Mann Whitney U tests, Pearson chi-square tests and Student-T were used for comparisons.

A statistically significant value was defined to be a p-value of 0.05.

In order to conduct the research, the local ethics commission had to be approved.

All participants, as well as their legal representatives, gave informed consent.

After the birth of an ASD-affected child, reproductive stoppage was determined based on the frequency of that child being born.

Because of limitations in the time frame, it was not possible to observe if families found to be at reproductive stoppage were pregnant after the study was completed.

Future observations can be made of these families in order to confirm if they are still in a state of reproductive cessation.

There were 250 participants from Turkey. The sample included 54 control kids without ASD and the 196 ASD children, as per DSM-5 criteria.Result:Demographics:

The mean ages of ASD patients and controls was 56.9 month (SD 27.1 mos; median 51), 55.7 months (13.8 m; median 54), respectively.

P Value (Claculated probability) or Hypothesis Test and Chi Square Test indicated that there was no difference in age between the two groups (p>0.05).

While the maternal and paternal age of ASD-afflicted children was higher than that of controls, statistical significance was not found (Table 1).

In the ASD study, 163 ASD patients (83.2%) were men and 33 ASD patients (16.8%), were women.

In the healthy control, 47 children (%85.1) had ASD and 7 (%14.9) had it.

There was no difference in gender between the two groups (p>0.05).

The rates for spontaneous vaginal delivery and Caesarean Section (C-section), were similar in the ASD children to those of the controls (p>0.05).

The rates for assisted reproductive techniques (including in-vitro fertilization), were similar among the two groups (p>0.05).

The ASD group was significantly more likely to experience labor-related difficulties (prolonged labor or vacuum delivery, forceps assisted vaginal delivery, and forceps-assisted vaginal deliveries; p=0.002) (Table 1).

Birth Order

Concerning birth order, 63.3%, (n=124), of the ASD/autism children were first-born. 26.0%, (n=51), were the second-born, 7.7%, (n=15), were the third-born, 2.6%, (n=5) were fourth-born and 0.5%, (X2=15.729. p=0.003).

Children who were the fourth or fifth children in their families were not included in the control group.

Data were reanalyzed, with the exception of children born on the fourth or fifth birth order rank. The result was statistically significant when compared to the ASD group (x2=13.792,p=0.001).

Excluding one-child families from statistical analysis (n=214), evaluations of being first-born in the ASD group as parameters (n=170), resulted in statistical significance relative to controls (n=44), at a rate 56.6% (98/170), vs 27.3% (12/44), respectively (Chi Square Test=18.727 and p=0.000, Table 3).

Birth Order Demographics

According to Chi Square Test=14.338, statistically, first-born ASD children were statistically more likely to be a girl than those born to a male (p=0.002).

A larger percentage of ASD babies were born in the C-section section group than those who were born to control children (Chi Square Test=8.035 and p=0.032).

The proportions of ASD-related first-born children who were born in prolonged labor or via vacuum-forceps application were significantly higher than those in the control group. (Chi Square Test=9.429. p=0.024. Table 4).

After excluding the one child families (n=36), it was clear that ASD can develop in any type of birth regardless of gender.

When controlling for one-child family, there was no association between SC and difficult labors. However, an important relation (p=.0.85) could be found in forced (vacuum prolong) labour. (Table 5).Stoppage:

All participants had 14.4% of the chance to have a single child (36/250).

13.3% of ASD families (26/196) had one child. However, 18.5% of control families (10/54) had one child. This indicates a statistically non-significant result for stoppage. (X2=0.948. p=0.330).

It was found that 86.7%, n=170, of the children in ASD group had at most one sibling. This compares to the rate of 81.5% and n=44 for their counterparts in control (Table 6).

Table 7 shows that the stoppage phenomenon was not evaluated for single-child families, (n=36), or families whose first child was diagnosed as having ASD.

The statistical analysis showed that 100.0% of ASD mothers (n=87), whose first-born child was diagnosed with ASD, gave birth (X2=15.250) to their second child.

100.0% of mothers with ASD who had their first child were able to have children.

14.3% (n=4) mother’s gave birth in ASD families that had second-born children.

A total of 100.0% (n=2) were mothers whose first-born child suffered from ASD. 22.2% (n=2) were mothers whose second-born child also had ASD.

Discussion

Many disease etiologies have recently investigated the birth or, which is the order of arrival among siblings.

With respect to ASD, there are many interpretations and results in the literature.

ASD group and controls were compared in terms of birth orders. We found a significant distinction for being the first born child in the ASD-group.

A review of research done in this area showed that ASD did not correlate with maternal birth order or maternal age.

Others have shown a higher chance of ASD for children born in forced labor than the control group (12;13;14).

Our results confirm those of the previous studies.

There have been reports that the first birth can be stressful for the child due to congenital and birth complications as well as as to asphyxia. These factors may lead to mild brain damage (24-25).

The ASD group experienced more difficulties during labor than the control. This was confirmed by our study.

These results, which included higher rates of being first-born children as well as higher rates of difficult labors in ASD, suggest that ASD may be influenced by perinatal stress.

ASD can be caused by both maternal and paternal age. However, there are conflicting results.

A cohort of ASD patients reported that their probability of developing autism in their third child, whose mothers were between 20-34 years old, and their fathers were below 40 years old, was three times greater than the probability for their first-born children from older parents (10).

A different study examined the relationships between maternal age and order of birth in ASD-afflicted families.

The ASD group did not show any correlation in birth order.

Particularly risky pregnancies (including first and fourth births) had more autistic kids than the population sample (26,27).

In general, there are limitations in the study designs, including insufficient selection of the control, inadequate diagnostic tools, and the inability to identify the delivery type at birth.

Although the difference in statistical significance was not significant, we found that ASD had higher maternal and father ages.

This support the results of other studies showing that parental age is not a primary risk factor for having autistic kids.

However, the only risk factor for ASD is that parents who have had autistic kids before their adulthood might not continue to be involved with them.

The risk of ASD being linked to parents of an advanced age must be clearly understood.

ASD diagnosis might be linked to race, reproductive patterns, and poor outcomes in pregnancy, such preeclampsia or preterm delivery.

Our study revealed that there were no statistically significant differences among siblings and birth order. There was also no difference in CARS scores, ABC scores, AbBC scores.

An analysis of sixteen families with a small sample size found that nonverbal IQ scores decrease as there are more births (28).

A different study, involving one hundred and sixty-one families, found that repetitive behaviors and speech difficulties were significantly higher in the first and second children diagnosed with ASD.

A negative correlation was found between autism and children’s intelligence levels.

Similar findings were made in another study that found difficulties in non-verbal and verbal communication were more common among autistic children whose first and second children were autistic, and that autism-related symptoms were greater in these children (30).

These studies reveal similar patterns and limitations such as inadequacy for the control groups and the choice of ASD patients among the participants who present at the clinic.

Although our results don’t match the literature, we interpret the cultural differences as being due to cultural variability.

In the autism group, 86.7% (n=170), and 81.5% (44) of the children of the control had at the least one sibling.

It was found that 92 (46.9%), of the autistic mothers had not given birth to any other children.

It was discovered that 53.1% (104.9/196) of these mothers gave birth to autistic kids, and that only 53.1% (104/196) did not.

It is not clear whether having autistic kids affects your decision about the next pregnancy.

Hoffmann (2014) in America and Wood (2015) in England published studies that showed autistic mothers were not able to give birth to other children (15-16).

Gronborg, et al. (2015), reported that Danish mothers with autistic kids continued to give birth (17).

Psychosocial implications of having ASD children could lead to fewer children in the family and influence the decision for next pregnancy.

It was found that the Turkish sample didn’t have any children with autism.

We also studied the relationship between gender and type of delivery (C section or vaginal), as well as assisted reproductive techniques used for conception.

In the literature, there are no studies that have examined the sex characteristics of the first child born with autism.

There are contradictory reports regarding the method used to deliver children with autism.

Some studies highlighted the fact that Cesareans increase the risk of ASD. But, in other studies it was found to be lower (31,32,33;34).

A retrospective cohort study looked at birth records. It concluded that there wasn’t a significant difference between type of delivery and ASD (34).

One study demonstrated that assisted reproductive technologies were one risk factor for autism. Another study however, 35;36, did not show any significant difference.

We found that the rates of first-born autistic kids were significantly higher among girls than in the Cesarean section cases and forced births.

These factors, however, were identified as independent risk factors when single-child households were excluded.

These factors, according to our research, are not associated risk factor for ASD in single-child families (6;37).Limitations:

Our study has some limitations. It is not a community-based research because the study sample includes children with ASD who have been admitted to the clinic.

A second limitation is the smaller size control group than patient group.

However, community-based studies might show more variability.

Despite the small sample size of our study, we were able to perform a comparative analysis on the parameters. This included the type of delivery at birth, one-child families, and other strengths.

Numerous studies have confirmed that autism is strongly linked to birth order. But, this relationship isn’t always linear and is often inconsistent.

Because autistic mothers do not prefer to have another child, it is difficult to determine the relationship between birth order and autism.

If the mothers had twins with autism or all three, then evaluating birth order is naturally difficult.

Although studies in this field have shed light on the relationship between autism, birth order and autism, there is limited data and no systematic evaluations to allow for generalization.

ASD can be explained through the influence of environmental factors such as birth order and type.

ASD’s multifactorial etiology is complex as we all know.

ASD can also result from environmental interactions other than genetics or birth order.

Compliance with Ethical Standards

Study was approved by the local ethics board.

Local Ethics Committee approval has been registered for this study as 2015-30.Informed Consent:

Each individual participant, along with their legal representatives, consented.

Disclosure of potential conflicts

All authors declare no conflicts of interest.

Human Participants in Research and/or Animals

All procedures that were used in human studies were compliant with the ethical standards for the institution or national research committee, the 1964 Helsinki declaration and its amendments, as well as comparable ethical standards.

Local Ethics Committee approval was received for this study in 2015-30References:Russell, G.,Steer, C., Golding, J. (2011).

Social and demographic factors can have an impact on the diagnosis of autistic disorders.

Social Psychiatry and Psychiatric Epidemiology. 46/12:1283-1293.Hansen, S.N.,Schendel, D.E., Parner, E.T. (2015).

Explaining the rise of autism spectrum disorders: changes in reporting practices.

JAMA Pediatrics. 169(1). 56-62.Rice, C. (2009).

Prevalences of autism spectrum disorders and developmental disabilities monitoring system, United States. 2006Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., et al. (1995).

A British twin study demonstrates that autism is strongly genetic.

Psychological Medicine. 25(1):63-77.Glasson, E.,Bower, C., Petterson, B., de Klerk, N., Chaney, G., Hallmayer, J.F. (2004).

Study of the population to determine the impact of perinatal factors on autism development.

Archives of General Psychiatry 61(6), 618-627.Guinchat, V.,Thorsen, P., Laurent, C., Cans, C., Bodeau, N., Cohen, D. (2012).

The pre?, peri. and neonatal risk of autism. Acta Obstetricia et Gynecologica Scandinavica, 91(3):287-300.Grether, J.K.,Anderson, M.C., Croen, L.A., Smith, D., Windham, G.C. (2009).

An increase in the maternal and paternal life expectancy and risk of autism in large populations north America.

American Journal of Epidemiology. 170 (9): 1118-1126.Sandin, S.,Hultman, C.M., Kolevzon, A., Gross, R., MacCabe, J.H., Reichenberg, A. (2012).

Review and meta-analysis: An increase in maternal age is associated to an increased risk of autism.

Journal of American Academy of Child and Adolescent Psychiatry. 51(5). 477-486.Liu, L.,Zhang, D., Rodzinka-Pasko, J.K., Li, Y.M. (2016).

Environmental risk factors for autism spectrum disorders. Der Nervenarzt, 87(2):55-61.Durkin, M.,Maenner, M., Newschaffer, C., et al. (2008).

Risk of autism spectrum disorder in those with advanced parental years

American Journal of Epidemiology. 168(11). 1268-76.Croen, L., Najjar, D.V., Fireman, B., Greather, J.K. (2007).

Risk of autism spectrum disorders and the paternal, maternal and paternal ages.

Archives of Pediatrics &Adolescent Medicine. 161(4). 334-340.Turner, T.,Pihur, V., Chakravarti, A. (2011).

(1). PLoSOne, 6:e26418.Deykin, E.Y.,& MacMahon, B. (1980).

Pregnancy, delivery, neonatal complications, and autistic children.

American Journal of Diseases of Children. 134:860-864.Tsai, L.Y.,& Stewart, M.A. (1983).

Etiological implications in infantile Autism of maternal gender and birth order.

Journal of Autism and Developmental Disorders. 13(1), 57-65.Hoffmann, T.J., Windham, G.C., Anderson, M., Croen, L.A., Grether, J.K., Risch, N. (2014).

Evidence of reproductive failure in families with autistic spectrum disorder: A large, population-based cohort research. JAMA Psychiatry, 71(8):943-51.Wood, C.L., Warnell, F., Johnson, M., Hames, A., Pearce, M.S., McConachie, H., et al.

(2015). Evidence of ASD recurrences and reproductive endangerment from large UK ASD family research databases.

Autism Research 8(1):73-81.Gronborg, T.K., Hansen, S.N., Nielsen, S.V., Skythhe, A., Parner, E.T. (2015).

Stoppage in Autism spectrum disorders.

Journal of Autism and Developmental Disorders. 45 (11):3509-19.Davenport, T. L. (2011).

Autism Behavior Checklist.

Encyclopedia of Child Behavior and Development (pp. 182-183). Springer US.Cassidy, A. (2013).

Autism Behavior Checklist.

Encyclopedia of Autism Spectrum Disorders. 342-343.Aman, M. G., Singh, N. N., Stewart, A. W., & Field, C. J. (1985).

Psychometric characteristics and aberrant behavior checklist.

American journal for mental deficiency.Farmer, C., & Aman, M. G. (2017). Aberrant Behavior Checklist.

Encyclopedia of Autism Spectrum Disorders.Nah, Y. H., Young, R. L., & Brewer, N. (2014).

Predicting long-term outcomes in autism spectrum children using the Autism Detection early childhood (ADEC) & Childhood Autism Rating Scales(CARS).

Journal of developmental and autism disorders, 44(9). 2302–2310.Farbstein, I., Mansbach-Kleinfeld, I., Levinson, D., Lee, L.C., Cunniff, C.E., Daniels, J.L, et al. (2010).

Results of a national mental-health survey in Israel on the prevalence and correlations between mental disorders in Israeli teenagers.

Journal of Child Psychology and Psychiatry. 51(5). 630-639.Biederman, J. (2005). Attention-deficit/hyperactivity disorder: a selective overview.

Biological Psychiatry. 57.1215-1220.Biederman, J., &Faraone, S.V. (2005).Attention-deficit hyperactivity disorder. Lancet, 366(9481): 237-248.Bolton, P.F., Murphy, M., MacDonald, H., Whitlock, M., Pickles, A., Rutter, M. (1997).

What are the causes or consequences of obstetric complications in autism?

Journal of American Academy of Child and Adolescent Psychiatry. 36, 272-281.Zwaigenbaum, L.,Szatmari, P., Jones, M.B., Bryson, S.E., MacLean, J.E., Mahoney, W.J., et al. (2002).

Pregnancy complications and birth complications in autism. Liability to the larger autism phenotype.

Journal of American Academy of Child and Adolescent Psychiatry. 41, 572-9.

Lord C. (1992).

Birth order has an impact on the nonverbal intelligence of families with autism and pervasive developmental disorders.

Journal of Autism and Developmental Disorders. 22, 663-666.Reichenberg, A., Smith, C., Schmeidler, J., Silverman, J.M. (2007).

Birth orderr effects of autism symptom areas. PsychiatryResearch, 150:199-204.Martin, L.A.,&Horriat, N.L. (2012).

Effects of birth sequence and interval on the expression of autism spectrum disorders phenotypically. PloSOne, 7(11):e51049.Bilder, D.,Pinborough-Zimmerman, J., Miller, J., et al. (2009).

The prenatal, perinatal, as well as neonatal aspects of autism spectrum disorders. Pediatrics; 123:1293-300.Dodds, L.,Fell, D.B., Shea, S., Armson, B.A., Allen, A.C., Bryson, S. (2011).

The role prenatal, obstetrical and neonatal factors have in the development of autism.

Journal of Autism and Developmental Disorders. 41.891-902.Zhang, X.,Lv, C.C., Tian, J., Miao, R.J., Xi, W., et al. (2010).

China.

Journal of Autism and Developmental Disorders.Burstyn, I.,Sithole, F., Zwaigenbaum, L. (2010).

Alberta singletons are more likely to have autism spectrum disorders than their mothers and to experience obstetric complications.

Chronic Diseases in Canada, 30, 125-34.Knoester, M., Helmerhorst, F.M., van der Westerlaken, L.A., Walther, F.J., Veen, S., Leiden Artificial Reproductive Techniques Project. (2007).

Study of 5 8 year-old ICSI singletons. Matched follow up study: child behaviour, parenting stress, quality of child’s life (health-related).

Human Reproduction (Oxford England), 22:3098-107.Lehti, V., Brown, A.S., Gissler, M., Rihko, M., Suominen, A., Sourander, A. (2013).

An IVF study in Finland on autism spectrum disorders among children.

Human Reproduction (Oxford England), 28(3). 812-818.Conti, E., Mazzotti, S., Calderoni, S., Saviozzi, I., Guzzetta, A. (2013).

(2013).

Systematic review.

Human Reproduction (Oxford England), 28(12).