Epidemiology Complications in Pregnancy

Question: Describe about the Epidemiology for Complications in Pregnancy. Answer: Evidence presented in the paper selected The research is on the Danish national based register study on the obstetric condition on risk of admission with schizophrenia. The research study by Byrne et al., (2007) proposed that complications in pregnancy are associated with increased risk of schizophrenia. This fact is also supported by Nordentoft et al., (2015) who showed that delay in sampling of blood for neonatal screening increased risk of schizophrenia. The researcher analyzes genetic and environmental exposure to schizophrenia to identify its risk with obstetric condition. The exposure or intervention in the study was presence of obstetric condition and the outcome was diagnosis of schizophrenia in patients. Byrne et al., (2007) conducted a nested case control study to evaluate range of obstetric events that lead to schizophrenia as obtained from the records of Danish register. The sample consisted of subset on control patients and those diagnosed with ICD-8 or ICD schizophrenia. The case population consisted of patients above 15 years who had first contacted Danish psychiatric facility after the diagnosis of ICD-8 schizophrenia and also had maternal identity. Among 1039 patients with schizophrenia, 97.5% were diagnosed according to ICD-10 and remaining as ICD-8. The control population comprised of randomly selected control who had same year of birth, same sex and those who had never been admitted to psychiatric clinic in Denmark. The exposure found in the study was related to lack of monitoring during antenatal appointments, gestation age of 37 weeks, maternal influenza, premature delivery. The patients were also exposed to risk of schizophrenia due to hemorrhage during delivery of baby or when delivery takes place by the manual extraction of the baby. The findings of the study showed the relation between exposure and outcome of schizophrenia. The researcher had stated that family psychiatric history, socioeconomic and demographic factors also play a role in risk of schizophrenia apart from other obstetric condition. The findings of the research showed that patients psychiatric history and obstetric factors do not interact with each other. However, modest association of outcome was also linked to exposures or presence of conditions like maternal infection, hypoxia, prematurity and behavior of maternal mother. Non-causal explanation for observed association between the exposure and the outcome There can be non-causal explanation too for the association between exposure and the outcome. The analysis of different literature in the study showed that the exposure and outcome is linked not only due to obstetric condition but also due to environmental mediators and genetic predisposition (Forsyth et al., 2013). The analysis of research by Byrne et al., (2007) mainly gives causal explanation of association between exposure and outcome. This was explained by obstetric variables like manual extraction, low birth weight, small gestation period and pattern of previous pregnancies. However, it is necessary to identify the non-causal explanation for the relation between exposure and outcome of epidemiological study. Firstly, there is chance that the result might be affected by selection or measurement bias as the research relied on record of Danish based register. The sample population was also selected on the basis of mixture of diagnoses of ICD-8 and ICD-10. Including both type of disease classification system may also contribute to limitations in the result. Hence due to error in selection criteria, it is possible that the results of the association between obstetric condition and schizophrenia may not be reliable results for all generalized population with schizophrenia. This kind of weakness in selection of sample in research might lead to misleading results. Low statistical precision might also be the reason for this association. Standardization of research with consideration of general population would help to enhance the credibility of the research findings (Ioannidis et al., 2014). The result is also affected by confounding factors. This is because the research by Byrne et al., (2007) mainly analyzed the data related to obstetric condition, psychiatric history and demographics details. However, considering gene-environment interaction is also important to understand the risk factors of schizophrenia. This kind of risk operates prenatally and perinatally and then proceeds to the progression of the disease. There are many evidence of risk to schizophrenia due to hypoxia, fetal retardation, drug abuse and migration (Kimberlie Dean, 2005). Byrne et al. had taken an epidemiologist perspective to carry out the research, however, it was necessary to combine the clued of genetics as well as epidemiology to optimize the research on schizophrenia. This identification of shared pathway is essential to get the true picture of association between outcome and exposure. Byrne et al., (2007) had conducted a nested case control study by getting access to national register to st udy the risk factors of obstetric condition. However, the research has not been strengthened by avoidance of selection bias and considering multiple confounders in the etiology of schizophrenia. The research could have considered genetic data such as heritability factor and the recurrence of certain disorder within the family (McGrath et al., 2013). The results of the study investigating the association between exposure and outcome of schizophrenia in the study might also be affected by chance variation. Sampling is one of the most critical phase of research by which an appropriate population relevant to the study is selected. Non-representative sample might reduce the credibility of the research. There might be uncontrolled factors that might have affected the response of population (Gallo et al., 2012). Instead of analyzing the risk factors according to national register, it would have been feasible to carry out investigation into current patients in a clinical setting. In the current literature by Byrne et al., (2007), some of the information on obstetric condition was not found for all patients. However, the researcher took steps to avoid chance variation in some of the national register data. For example, variables which hardly contributed to the research were eliminated and this was determined statistically by log likeliho od ratio test of the eliminated variables. By this approach, negligible variables were removed from the models. Evidence of causal association between the exposure and the outcome On analysis of result of the research by Byrne et al., (2007), univariate estimation highlighted the association of exposures such as prematurity, low birth weight and small gestation period with outcome (increased risk of schizophrenia). For some variables, temporal relationship between exposure and outcome was found, while in some case strong relation between exposure and outcome was found. For examples exposures like birth weight and small gestation age was not found to be associated with outcome. On the other hand, consideration of background factors showed that manual extraction and gestation age of less than 37 weeks had a strong association with outcome of schizophrenia risk. However the result was not clear for association between 40 weeks of pregnancy and risk of schizophrenia. The results of association between small gestation age and risk of schizophrenia are consistent as this is also seen in the study by (Takayanagi et al., 2014). They calculated hazard ratio of small fo r gestation age (SGA) for schizophrenia disorder and they also adjusted the possibility of confounding variables in the topic. In a case controlled study of patients with no schizophrenia spectrum disorder and those with past history of the disorder, it was found that there is strong relation between exposure and outcome and the association between SGA and risk of schizophrenia remained significant. Hence, there may be common and specific causative pathways for diagnosis of schizophrenia spectrum disorder (Takayanagi et al., 2014). The above association between exposure and outcome was for the period between 1973-1983. The consistency across the year for gestation was determined by the gestation age of greater than 40 weeks. For the period of 1978-1983, greater association between manual extraction and risk of schizophrenia was found. Other remaining variables (like provoked abortion, pregnancy complication such pregnancy influenza and neo and post-natal factors) were analyzed by adjusting the multivariate model. The retained variable in the model included risk factors like past antenatal visits, maternal influenza, maternal anemia, hemorrhage during pregnancy and threatened. These exposures were associated high incidence ratio of schizophrenia (outcome) (Byrne et al., 2007). The interaction between obstetric condition, sex and psychiatric history has also been analyzed by the researcher. No significant interaction was found between interactions of sex with the psychotic disorder. As the research was conducted with large sets of data from national register, Byrne et al., (2007) stratified the results considering family psychiatric history. According to socioeconomic and demographic factors, the only link with the risk of schizophrenia was related to one or more previous case of pregnancy, forceps delivery and vacuum extraction. Hence the results finding was consistent with similar studies in the area which reported about association between pregnancy complication and risk factors of schizophrenia. The consistency of finding was maintained by stating about all those factors which do not lead to risk of disease such as parental age, place of birth, citizenship and parent socioeconomic factors. This became possible by means of interpreting sample with odd ra tio estimates and incidence rate ratio (IRR) between control sample and case sample. The Danish national based register had a range of obstetric factors variables, however those variable were selected which were statistically significant and which has incidence rate ratio of greater than 2. As the data size was very large, the complexity in analysis was minimized by breaking the data and dividing it into data calculated for different stages. Consistence of findings with other evidence The findings were found to be consistent with other studies. Comparison with similar studies helped in understanding the reliability of the result. A similar national based cohort study similar to Byrne et al., (2007) was conducted by Eide et al., (2013) who investigated the association of fetal growth restriction with risk of schizophrenia. The researcher conducted this study as there was no direct research on the topic in previous literature. The focus was mainly on evaluating the degree of growth restriction and other complications such as pre-eclampsia and placental dysfunction. It was also conducted in the same period as in the evaluation literature from the data contained in Medical Birth Registry of Norway. Growth restriction is assessed using statistical tools like standard deviation for variables like birth weight for gestation age and length of birth. They used strictly defined criteria to adjust confounders and evaluate cased of maternal pre-eclampsia. The data analysis wa s also similar to the literature by Byrne et al., (2007). It was found that risk of schizophrenia increased with decrease in gestation age and birth length. Hence significant association between schizophrenia and degree of growth restriction was similar to the association between age of gestation and risk of schizophrenia. Hence, the research gives future implications etiology of schizophrenia (Eide et al., 2013). Byrne et al., (2007) gave insight into the association of risk of schizophrenia with three or previous case of emergencies pregnancy apart from other obstetric complications. Similarly, the study (Srensen et al., 2015) investigated two different case definitions of schizophrenia in a similar register based research. It compared two kinds of exposures to analyze the outcome of schizophrenia-one was the influence of one time contact with the disease and other was the two or more time contact with schizophrenia. Higher risk estimates were found for two or more contacts and gave the implication that selecting two or more case definition will lead to accurate estimation of risk factors. However, this would depend on selection of genetic study based research. One limitation of the Danish register based study of risk factor of schizophrenia was that the result just only linked the disease with obstetric risk factors and socioeconomic risk factors; however the result did not give indication of biological mechanism in epidemiological studies. This factor was present in the study by Rapoport et al., (2012) where the researcher showed the neurodevelopmental mechanism of schizophrenia. The neurodevelopmental model states that schizophrenia is the final stage of abnormal neurodevelopmental mechanism and the onset of the neuropsychiatric disorder occurs much earlier than the diagnosis of illness. It suggested that prenatal risk to schizophrenia can be determined placental pathology. Current studies revealed genetic variants related to schizophrenia. Apart from obstetric condition, the studies also linked the risk of the disorder with autism and other intellectual deficiencies. Brain imaging studies and gene expression studies is also giving new a dvancements in the etiology of schizophrenia and the research is going on the phenotypic characterization behind the development of schizophrenia. External validity of findings To understand the credibility of a research finding, it is necessary that the elements of research can be generalized for all kinds of population instead of just case population in the research. In the analysis of the results of the Danish register based study, it was seen that presence of risk factor was identified through hospital discharge diagnosis data in national register. There is limitation in this approach to investigating the risk factor of schizophrenia. This is because this may represent limited number of actual population which might give conflicting results. Besides the data were analyzed in the period between 1978-1983, therefore the etiology of this disease might have changes with change in environmental factors after many transformations from the past till now. The research was based clinical diagnoses in clinical setting instead of analyzing the risk in general population or in epidemic area. This is understood by the explanation by the researcher that exposure to i nfluenza is associated with outcome of disease. However, in other studies exposure to influenza was determined after assessment in generalized population. This study highlighted that prenatal exposure to influenza are associated with risk of schizophrenia after the result was obtained from biomarker assays in birth cohort studies. This research study gave the recommendation that if public health intervention is targeted at reducing exposure to neonatal infection, then cases of schizophrenia can be prevented (Brown, 2012). Due to the above mentioned limitation, the conclusion from the research cannot be applied to other relevant population. This is because the research study gave detail only on the infection present in hospital setting or during complications in pregnancy. However, it cannot be denied that risk factors are present across the entire lifespan of an individual due to several other biological and environmental mechanisms. Epidemiology studies first initiate with the prevalence of the disease within a specific population and then move to focused studies on determinants of disease (Fletcher et al., 2012). This literature review article was mainly a focused study to determine the association between risk and exposure. This research gave idea on the incidence rate of disease after analysis of data obtained from Danish national register. Hence for the application of the research to a generalized population, it is necessary that incidence rate is calculated for new case of disorder in a defined population instead of just relying on population of clinical setting. Hence despite some in study, the researcher was successful in proving the association of obstetric condition with risk of schizophrenia. 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