Route of Delivery and the Incidence of Asthma

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Introduction
Problem Statement: The incidence of asthma has increased dramatically in developed countries in the last few decades. Asthma is a chronic immunological disease, characterized by airway inflammation, bronchoconstriction, mucus production and airway hyperreactivity. One of the hypothesis mentioned for this increased trend in asthma rates is the hygiene hypothesis, which basically states that individuals growing in clean cities and households are more likely to have asthma compared to those living in downtown areas, the likely explanation being that individuals in polluted areas are constantly challenged by allergens in the environment and hence develop immunity against the allergens. According to recent estimates, over 20 million Americans are affected by asthma. Asthma itself can be classified into different types such as allergic asthma, stress induced asthma and cold induced asthma.

Research Question: The last few years have seen an increase in research studies that investigate the role of the maternal immune system on the risk of developing asthma in the pediatric age group as well as their follow-up into adulthood. However, few studies have investigated the role of the route of delivery and its subsequent relationship with the risk of developing asthma. The materno-fetal interface is a complex physiological and immunological system that confers protection to the growing fetus. The fetus is primarily a foreign body, why the maternal immune system does not reject it, has been intensively researched. Of interest for this study is the fact that as asthma rates have been rising, so has the trend in Caesarean sections. The question that we are going to ask in this proposal is, whether the mode of delivery has a role in influencing asthma development?

Purpose of the Study: The purpose of the study is to determine the incidence of asthma development in children born via Caesarean Section (CS) to those born via normal vaginal delivery. It is hypothesized that the risk of asthma is higher in children born via CS than those born after a normal vaginal delivery. The study will also determine the incidence of CS in hospital-based deliveries in the last 5 years and the follow up on those children for hospital based admissions for asthma in those years compared to control vaginal deliveries.

Literature Review

A few studies have looked into the role of the route of delivery and asthma predisposition, Jarvelin et al. (2001), have looked into this association, in their findings the authors report their observations based on a cohort group of over 12,00 births from the middle 1960’s in Northern Finland. Their study design is flawed in the sense that they invite the individuals in the study group; they are well over 30 yrs now and based on their recall of asthma and allergy attacks, tabulate their results. No considerations are made on hospital-based admissions for the same, or looking into their medical records over the last 30 years. The authors make the conclusion that the hypothesis of CS delivery and its association with asthma does not have much validity.

In another study conducted by Kero et al. (2002), the authors use a more exhaustive method to come to their conclusions. From a cohort group of over a 1000 hospital based records in the early 1990’s, they track down 167 mothers who underwent CS and hand them a questionnaire to report on allergy and bronchial asthma attacks of their children. They further verify these by hospital recorded medical visits for the same. The authors come to the conclusion that the incidence of asthma and allergies in these children born via CS was increased, compared to those who were delivered by the normal vaginal route. These studies suggest that CS delivered children have alterations in their immune system, either the materno-fetal interface is disrupted when a CS is performed or the initial exposure to microbes in the vaginal tract plays a crucial role in the infants immune system development.

Bager et al. (2003) in their study, report an increased incidence of asthma in CS sections delivered children but their finding are suggestive of the fact that the normal immune mechanisms are altered more so because that most CS deliveries are associated with high risk pregnancies, pre-term babies, the development of hypertension or diabetes in mothers, as such the infants immune system is already compromised, and the resulting asthma risk relates to it. In our current studies we aim to replicate these studies in our hospital-based setup, and validate this association of asthma risk and CS route of delivery.

Research Design and Methods

Design & Participants: Our hospital’s record of asthma reported admissions in children below the age of 10 years, over the last 10 years would be acquired. Questionnaires to the mother’s of these children will be mailed on their mode of delivery. The questionnaire in addition to the age of the mother, history of allergies and asthma in the family and route of delivery would ask for subsequent pregnancies and any observed allergy or asthma attacks in the respective children. It is common for CS delivering mothers to undergo the same procedure with subsequent pregnancies and it will be interesting to observe if the same is true for all the children in the family.

In addition, we will acquire records of mothers undergoing CS deliveries at our hospital setup and determine the risk of asthma and allergic related incidences in their children, these finding will be compared to a control cohort of mothers who delivered via the normal route. The incidence of maternal asthma and its subsequent influence on their children will also be assessed in these patients.

Procedure: As mentioned above, the main mode of acquiring data would be to design a questionnaire. The questionnaire would be mailed to all mothers of asthmatic children reporting to our hospital in the last 10 years. They would be queried for a) a family history of asthma, b) a family history of cesarean section and complicated pregnancies, c) number of average visits to the hospital with their children, d) incidence of asthma in all siblings in the family and e) complication involved during delivery that led to the CS We would also collect the same data from all registered CS in the last ten years at our hospital; subsequently the same questionnaires would be mailed to the mothers delivering via CS. The same would be mailed to another group of 200 women delivering via the vaginal route in the same years at our hospital.

Data Collection and Analysis: The answered questionnaires would be evaluated, the answers entered manually into two groups, those delivering via vaginal route or those with CS. The data would then be statistically analyzed for average incidence of asthma or allergy attacks in women delivering via CS to those delivering normally through the vaginal route. Means and standard deviation would be accounted, and an ANOVA test would be done to compare the statistical significance. (p value).

Potential Risk: the potential risks of doing such a study is, basing the data on the answers entered by the subjects. Some subjects are likely to forget key events in the last few years of their child’s medical history that could lead to deviations in the significance of women delivering via CS to those delivering via the normal route.

Most asthma-reporting patients are actively managed by a regimen of inhaled corticosteroids, it will be important to consider the subsequent admissions, active management of disease can result in false negatives.

Risk Management: Consent forms will be mailed along with the questionnaires to avoid any medico–legal issues; only those agreeing to the terms of the questionnaire, would be included in the results. Also, recent studies have indicated that mothers developing allergies during their term period render the offspring tolerant to the allergen.  This additional fact would be considered and we will not include any mothers who delivered via CS, but had reported for allergies or an asthma attack during the course of their pregnancy.

Potential Benefits: The potential benefits arising from the study would provide authentication to previous reports associating mode of delivery to the development of asthma in children. If CS section deliveries were associated with an increased incidence of asthma, then our studies would validate the same. These studies would also set base for a more thorough education of mothers delivering via CS and increase their awareness to their children being prone to asthma and allergy. Biomedical research could possibly start looking at alterations at the maternal-fetus interface that enhance the risk of asthma in CS deliveries.

References:

1)      Xu, B., Pekkanen, A. J., Hartikainen, A. L., Jarvelin, M. R. (2001). Caesarean section and risk of asthma and allergy in childhood. Journal of Allergy and Clinical Immunology. 107,723-3

2)      Kero, J., Gisller, M., Gronlund, M. M., Kero, P., Koskinen, P., Hemminki, E., Isolauri, E. (2002). Mode of delivery and asthma- is there a connection? Pediatric Research. 52, 6-11

3)      Bager, P., Melbye, M., Rostgaard, K., Benn, C. S., Westergaard, T. (2003). Mode of delivery and risk of allergic rhinitis and asthma. Journal of Allergy and Clinical Immunology. 111, 51-6

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