Association Of Prenatal SSRI Use With Autism Spectrum Disorders: Case-control Study

Solution 1

The main research question is to examine the association of prenatal use of selective serotonin reuptake inhibitors and the risk of Acquiring Spectrum Disorders.

Case control study designs are crucial in establishing cause and effect associations between treatments and causality effect. The design is essential in ensuring that it compares patients who have the disease and those who do not have as controls. Hence this gives high level of evidence through comparative analysis for cause effect of treatment allocations.

The source of this population study is the families who are enrolled child hood autism risks and genetic environment. The choice of the study population is relevant in that these are the patients who are already identified and enrolled in the program for facilitating help, thus they have been selectively been chosen as the study is primary to them being study participants.

The cases and controls were recruited in the study through careful approaches. Children with Autism Spectrum Disorder and delay development from the general population were identified, with an eligibility criterion of those aged between 2-5 years. Children who are the cases identified through those receiving services from state department. Cases were identified through state files and were frequently matched with other parameters such as age, gender and regional centre.

Selection bias in case control studies results when subjects are selected into the study when they are not a representative of the entire population, this might lead to differential loss in follow up and the likelihood of the participants being lost. In this study selection biases has occurred in that only children seeking treatment in state department of health, California could be selectively selected, thus not having a representative sample of the entire population. this has impact on the overall research, is that the findings could be generalised as the selection of the sample is not a representative of the general population suffering from Autism Spectrum Disorder and delay development. 

	Unadjusted	Adjusted	Number per group
Exposure present	29	11	40
Exposure absent	21	10	31
Number per group	50	21	71

The difference signified in the study shows the difference on how selection bias could influence the study findings. The unadjusted factors shows high values compared to the adjusted values in the research. Hence the impact of selection biases if not not controlled carefully can have significant impact on the study results.

SSIR was defined as the usage of the serotonin inhibitor uptake and was measured using self reporting schedule through self reporting from the mothers prior to the pregnancy or conception phase.

Solution 2

ASD was defined as the autism spectrum disorder and delayed development was assessed in the studies. ASD referred to children diagnosed with autism disorder and delayed development children defined those with DD. ASD and DD were identified through those receiving treatment and qualified for care services at California State of health department. ASD patients were assed using Autism Diagnostic Interview Revised while DD utilised adaptive behaviour scales of early learning.

SSRI use was based on the self reporting where it is prone to recall biasness. This can be be occasioned with under reporting or over reporting , further the data source which is the prenatal record may not capture the SSRI prescriptions, thus indicating recall biases.

On the ASD and DD, the participants were identified using those quantifying health services from the state department, those that may not having qualifying for the services could have been included in the study. The recall bias in these case was limited since the participants were selectively identified and were assessed using the appropriate assessment tools. 

There will be an increased in exposure levels of the treatment effect on the participants.

	Unadjusted	Adjusted	Number per group
Exposure present	31	12	42
Exposure absent	21	10	31
Number per group	52	22	73

Calculated odd ratio

ad/bc

31*10/21*12

Calculated odds ratio is 1.23

This could be attributed to misclassification biases as the pregnant women were not supposed to be categorised and are grouped wrongfully in the study. Hence calling wrong treatment allocation approaches. The women were wrongfully classified to SSRI exposure relative to the truth.

Precision refers to the resolution of the representation of the study participants. In the study the level of precision shows that ASD children showed similar birth weight with TD children. Further with p value of 0.001, delayed development children were more likely to be female population. The main items of determination included the level of socio economic aspects towards access to health services in determining growth aspects of the children. I assessed the precision using the calculated p-values and the standards deviation mean shown from the study findings.

In statistical terms confounder are the variables which influence both the dependant and independent variables in any study causing a spurious association. In this study breast feeding was a identified as confounding factor, however it was not associated with prenatal SSRI exposure thus could be include as a confounding factor to study results. Possible exposure misclassification was assessed in this study so as to identify the confounder.

There is higher risk observed among the ASD compared to TD in the study. The adjustment of confounders shows that there are increased risks of autism occurrence among the adjusted group. While in the DD category there was a relatively high risk of delayed development when compared with TD among boys when the confounding factors were assessed.

Solution 3

The impact of confounder adjustment was assessed using multivariate analysis of the result and further assessing the RR of the disease in maternal health among the participants.

Effect modifiers that were established in this study include child gender. The gender effect is relevant in the ways mothers respond to SSRI. Hence modifier effect could be felt in the study, thus in order to counter act this, stratification was utilised in the study.

Another modifier effect assessed was the preterm low birth weight. However this was not included in the study due to the effects it would on the SSRI adjustments.  The two effects were present in the study having observed carefully the results analysis and how these effect modifiers could have changed the results obtained.

The effect size for girls would reveal a small effect in the sense that when they are both combined the estimated risks are relatively low, while when boys alone are assessed their estimated risks are higher, thus girls alone effect would reveal a smaller effect, since it seems the effect being observed from girls neutralizes that observed in boys only category. Hence few girls’ exposure would have a significant lower effect on the general analysis of the given information provided.

Internal validity refers how the experiment is done and how it negates the effects of confounding factors. Hence less the chance of confounding in the study, the higher the internal validity of the result. Internal validity entails how the causal conclusions are reached in the study. Thus internal validity ensures that aspects of confounding factors and biases are controlled in the study.

In the study potential recall biases could have been encountered with regard to SSRI use among mothers and further the presence of residual confounding factors. Further another potential biases shown is the preterm and low birth weight children however for effects aspects this was not included in the study so as not to affect the true nature of results to be obtained. Further reporting biases were assessed in the study with an aim of assessing whether the information obtained was true. The prenatal medical record information was compared with self reporting SSRI so as to mitigate any reporting biases. Further selection biases and relevant confounder were assessed in the study, thus improving the internal validity of the results.

Thus with careful consideration of these aspects in the study, the mitigation of the relevant effect modifiers, confounding factors and biases consideration, this study has the adequate threshold for internal validity.

Solution 4

The study results cannot be generalised to the general population since there are other aspects which need to be considered as the general predisposing to the effect like the genetic factors linked to SSRI, results generalibility could be influenced by other factors.  There are other factors which could be confounding and needs assessment in order to scientifically demonstrate the causality effect of the treatments.

the paper establish dose effect relationship in the participants. The association of the SSRI use was analysed and compared among the participants. In the study, SSRI use by CHARGE participants reveals significant association with ASD among boys than girls. Hence there was a positive effect on the dose effect on the male gender. Another case example in the study is that mother who had used SSRI during pregnancy were associated with the risk of ASD and DD were boys. Thus this showed how the dosage of SSRI affected the male gender thus establishing a relationship effect.

The study findings are similar with other research done by other researchers. A study by Tohru et al,  (2016), shows that SSRI use in pregnancy is associated with increased risks of ASD in the offspring. Further other research conducted shows that there is significant associations of SSRI exposure and ASD in children, however confounding factors seems to be a significant association factor in these assessments, (Yusus, et al 2016). Meta analyis studies done have shown that there is a link between SSRI uptake and development of exposure to ASD, (Kaplan et al 2017), thus strengthened the significance of these study in relation to other studies as illustrated in research work.

Bradford Hill criteria of temporality, is crucial in establishing causality in research work and established causal relationships between cases and observed effects. With reference to temporality, the effect has to occur after the cause. In the study temporality is significant in that the effect is felt after the work dose treatment has been subjected. The usage of SSRI injects a substantive effect on the occurrence of ASD among the children in the study, with result showing higher temporal effect among boys than girls. 

References

Kaplan, Y. C., Keskin?Arslan, E., Acar, S., & Sozmen, K. (2017). Maternal SSRI discontinuation, use, psychiatric disorder and the risk of autism in children: A meta?analysis of cohort studies. British Journal of Clinical Pharmacology.

Kaplan, Y. C., Keskin-Arslan, E., Acar, S., & Sozmen, K. (2016). Prenatal selective serotonin reuptake inhibitor use and the risk of autism spectrum disorder in children: A systematic review and meta-analysis. Reproductive Toxicology, 66, 31-43.

Kobayashi, T., Matsuyama, T., Takeuchi, M., & Ito, S. (2016). Autism spectrum disorder and prenatal exposure to selective serotonin reuptake inhibitors: a systematic review and meta-analysis. Reproductive Toxicology, 65, 170-178.