Measures of association in epidemiological studies : smoking mothers and low birth weight children in the city of Campina Grande – PB

The aim of this study was to present and describe the essential aspects, and to discuss the use of measures of association, relative risk and odds ratio, including formulas for calculating confidence intervals of obtained data from a cohort study of underweight live births of mothers who smoked during pregnancy, whose deliveries were performed in hospitals and maternity wards located in Campina Grande, state Pernambuco. Smoking during pregnancy was analyzed as a potential risk factor for low birth weight among 3612 newborns. In assessing the association of outcome, there were no large numeric differences between the estimates of the relative risk, odds ratios and confidence intervals obtained. It is an acceptable approximation to the relative risk and the odds ratio. It is up to the researcher to choose the most appropriate technique to its subject matter and should be determined according to the surveyed data.


Introduction
Smoking is considered a serious public health problem and a leading cause of morbidity and mortality worldwide.The incidence of smoking in women of childbearing age population has increased over the years.The use of cigarettes by this class becomes even more worrisome because studies show that smoking in pregnancy is not harmful only to the mother but also to the fetus.
When a woman smokes during pregnancy, exposes her fetus not only to cigarette smoke components that cross the placenta, but also to changes in oxygenation and placental metabolism, and changes in its own metabolism secondary related to smoking.Smoking in pregnancy is responsible for 20% of fetuses with low birth weight, 8% of premature births and 5% of all perinatal deaths (Paranhos, Figueiredo Filho, Rocha, & Silva Júnior, 2013).
Moreover, international research conducted in the mid and late 1990s, both in Canada and in the United States, showed that among pregnant women, 20% smoked during pregnancy.Since about 4 to 5 million live births occur annually in North America, it is huge the number of children who will be born exposed to constituents of cigarette smoke due to maternal smoking -not to mention passive exposure to cigarette smoke, even if the mother is non-smoker -and it has large, comprehensive repercussions for them.. Meta-analysis of 23 studies shows that children of mothers who smoke during pregnancy are around two times more likely to have low birth weight (< 2.500 g) at birth [relative risk (RR) = 1.82;IC95% (confidence interval of 95%): 1.67; 1.97] (Difranza & Lew, 1995).A work by (Pagano & Gauvreau, 2013). in Rio Grande do Sul confirms that, apart from the effects on weight, there is the negative impact of smoking in length and head circumference of newborns, indicating that maternal smoking during pregnancy inversely affected all three anthropometric measurements evaluated at birth that reflect the intrauterine growth.
The low birth weight occurs due both to premature birth, most common in developing countries, as the constraint of intrauterine growth, most frequently in developing countries, or as a combination of both.Factors associated with low birth weight are: maternal low height and weight, multiple births, low calorie intake, hypertension during pregnancy, maternal smoking, genetic syndromes, physical labor during pregnancy, maternal exposure to toxic substances and inappropriate prenatal.Low birth weight rates differ in various regions of the world, being higher in less developed countries, since they are associated with unfavorable socioeconomic conditions.Underweight rates at birth are estimated at 15% in developing countries and 7% in developed countries.In Brazil, in 2010, the rate was 9.1% (Veloso et al., 2014).
Maternal cigarette smoking in the third trimester of pregnancy is a strong predictor of low percentile of birth weight.Thus, the reduction or complete cessation of smoking for the mother during pregnancy will result in a higher birth weight, regardless of prenatal consumption levels.For each additional cigarette a day that the participant smoked in the third quarter, there was a 27 g reduction in the estimated birth weight.This low birth weight observed in newborns of smoking mothers may have consequences in the long run, since the evidence points to a significant pediatric and adult morbidity (Bernstein et al., 2005).
Considering all the harmful effects of tobacco, both for human health and for the environment, it is imperative to reduce smoking in all population groups.Given the almost universal antenatal care in urban areas of Brazil, pregnancy should be seen as the ideal time to encourage smoking cessation, since at this period there is an intensification of contacts with health professionals, thus providing an opportunity so there is this incentive.In this sense, it is important to all professionals who are part of maternal and child care to guide the pregnant smoking women, highlighting the great harm on your health and especially about his son, both during intrauterine life, as after birth.
In epidemiological studies, it is common to wonder if certain characteristics of human life, as habits or aspects of the environment where the individual lives, are associated with certain disease, with manifestations of a disease or other events of interest to the researcher.Often the questioning is done to relate the attributes of a person with risk of developing certain event (Arango, 2009).For example, an investigator (physician) may want to assess whether infants born to mothers who smoked during pregnancy had characteristics resulting from contact with chemicals from the cigarette, as low weight and reduced head circumference.
To study a situation as exemplified above, we should be familiar with some basic terms used in epidemiological research, such as 'outcome' and 'risk factor'.Outcome is the name used to designate the event of interest in a search.The outcome may be the emergence of a disease, in a particular symptom, death or any other event that happens in the health-disease process.In the example above, the outcome is 'low weight and reduced head circumference'.But the risk factor (also known as 'factor under study') is the name used in Epidemiology to designate a variable that is supposed to be associated with the outcome.Often, people who have the supposed risk factor are designated as 'exposed'.In that instance, the risk factor is 'born to mothers who smoked during pregnancy'.Finally, we can, in a simplified manner, considering risk as the probability of an individual presenting the outcome (probability of developing low weight and reduced head circumference) at any given time.The risk is usually assessed in epidemiological studies by cumulative incidence.
There are some measures of association that have been developed to evaluate the relationship between the risk factor and the outcome (Margotto, 2015).Among these measures, it can be highlighted the relative risk (RR) and odds ratio (OR).Although they have a common goal (to assess the association between variables 'risk factor' and 'outcome' in epidemiological studies), these measures of association have their own characteristics and should be used in accordance with the employee research design.There are several designs ratings research proposed in the literature, which can be consulted, for details (Zychar, Borda, Moreira, Pereira, & Mário, 2016).This study will be focused on the calculation of unadjusted estimates (i.e., who do not consider potential confounding factors) for RR and OR with their confidence intervals, indicating what kind of design each of these measures is more widely used.

Material and methods
The sample was composed of live births in hospitals and maternity hospitals in Campina Grande in 2012.Smoking during pregnancy has been studied as a potential risk factor for low birth weight between 3612 newborns.Obtaining measures of association for the epidemiological data are usually presented in tables 2 X 2 or contingency tables as shown in Table 1.To study a presumed association between risk factors (smoking during pregnancy) and outcome (low birth weight), a cohort study was conducted.It is longitudinal, retrospective or prospective observational study, in which a defined group of people (cohort) is followed over a period of time.The outcomes are compared from exposure or not an intervention or other factor of interest.Is the study design most appropriate to describe the incidence and natural history of a condition (Glantz, 2013) In a cohort study, we can assess the risk by measuring the cumulative incidence of an outcome by the number of cases (new) occurred during the study period, divided by the population size (or sample) studied.

Relative risk and odds ratio
The relative risk or odds ratio are strength of association measures (effect measures), i.e., measure the association between outcome variable with the exposure variable: as the occurrence probability due to the dependent variable and its relationship with independent variable.The terms association and effect refers to the fact that a variable would have a relationship or exert an effect on another variable.The results are due to a reason, the null value for these is 1 (one).A relative risk or an odds ratio of 1.0 indicates that the probability of disease in the exposed and non-exposed groups are identical; consequently, there is no association between exposure and disease.A RR or OR higher than 1.0 implies that there is increased risk of disease in individuals exposed, while a value less than 1.0 suggests that there is a reduced risk that the exposed individuals develop the disease (Margotto, 2015).

Relative risk
The relative risk is a measure of strength of association between exposure to the risk factor and the event (outcome), indicating how often the occurrence of the outcome in exposed is higher than that among non-exposed.The RR is defined as the ratio between the incidence of outcome in exposed and the incidence of outcome we unexposed.It is defined as the cohort, a group of individuals/ units of analysis who experienced the same event.Cohort studies, in turn, are observational studies in which individuals are classified/ selected according to the exposure status to a particular event.This type of study is fairly frequent in epidemiology to 'evaluate the incidence of the disease in a given period of time'.Cohort studies can also be used to assess the risks and benefits of the use of certain medication (Oliveira & Parente, 2010).
When one want to compare, in a cohort study, the incidence of an outcome between exposed mothers (smokers) with that obtained from unexposed mothers (non-smokers), usually calculate the relative risk.The RR can be used both to compare cumulative effects as compare incidence densities (Pagano & Gauvreau, 2013).In this study, cumulative incidences were considered, and the RR is calculated as Equation 1: In order to demonstrate the calculation of a 95% confidence interval for the RR (the confidence interval shows the limit within which there is the certainty of the true treatment effect, estimates the magnitude of the association and informs the variability of the estimate through the lower and upper limits), it can be used the method described by the logarithmic transformation (Glantz, 2013).This method assumes that the sampling distribution of RR values has an asymmetrical shape of the lognormal type.Thus, by means of a logarithmic transformation, we obtain a curve with nearly normal way.Using formulas similar to those used The odds compare the o the relative ris the odds ratio of the event i smoke 21 ciga the last two y cancer on the would be calcu We are 95% confident that the chance that pregnant smokers may give birth to infants with low birth weight is 1.46 to 2.35 times higher than the chance of a newborn do not born with low weight.

Conclusion
Smoking is considered a serious public health problem and a leading cause of morbidity and mortality worldwide.The incidence of smoking in women of childbearing age population has been increasing over the years.The use of cigarettes by this class becomes even more worrisome because studies show that smoking in pregnancy is not harmful only to the mother but also to the fetus.Maternal cigarette smoking in the third trimester of pregnancy is a strong predictor of low percentile of birth weight.Thus, the reduction or complete cessation of smoking during pregnancy will result in a higher birth weight, regardless of prenatal consumption levels.
Measures of association based on risk factors and odds ratios provide information about the strength of association between the study factor and the outcome, allowing it to make an analysis on a comparison of possibilities.Evaluating the outcome of association, there were no numerical differences between the estimates of the relative risk, odds ratios and confidence intervals obtained.It is an acceptable approximation to the relative risk and the odds ratio.It is up to the researcher to choose the most appropriate technique to his object of study and should be determined according to the surveyed data.

Table 1 .
Incidence of low birth weight in newborns in hospitals and maternity wards located in Campina Grande, Permanbuco State, according to smoking during pregnancy, in 2012.
If any of the contingency table entries is equal to 0, the standard error will be undefined.In this case, add 0.5 to each of the values a, b, c and d corrects the situation and also provides a reasonable estimate; thus, the standard error of the modified estimator is Equations 12 and 13: