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      Methodological challenges when estimating the effects of season and seasonal exposures on birth outcomes

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      1 , 1 , , 1
      BMC Medical Research Methodology
      BioMed Central

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          Abstract

          Background

          Many previous studies have found seasonal patterns in birth outcomes, but with little agreement about which season poses the highest risk. Some of the heterogeneity between studies may be explained by a previously unknown bias. The bias occurs in retrospective cohorts which include all births occurring within a fixed start and end date, which means shorter pregnancies are missed at the start of the study, and longer pregnancies are missed at the end. Our objective was to show the potential size of this bias and how to avoid it.

          Methods

          To demonstrate the bias we simulated a retrospective birth cohort with no seasonal pattern in gestation and used a range of cohort end dates. As a real example, we used a cohort of 114,063 singleton births in Brisbane between 1 July 2005 and 30 June 2009 and examined the bias when estimating changes in gestation length associated with season (using month of conception) and a seasonal exposure (temperature). We used survival analyses with temperature as a time-dependent variable.

          Results

          We found strong artificial seasonal patterns in gestation length by month of conception, which depended on the end date of the study. The bias was avoided when the day and month of the start date was just before the day and month of the end date (regardless of year), so that the longer gestations at the start of the study were balanced by the shorter gestations at the end. After removing the fixed cohort bias there was a noticeable change in the effect of temperature on gestation length. The adjusted hazard ratios were flatter at the extremes of temperature but steeper between 15 and 25°C.

          Conclusions

          Studies using retrospective birth cohorts should account for the fixed cohort bias by removing selected births to get unbiased estimates of seasonal health effects.

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          Most cited references26

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          Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis.

          The cognitive and behavioral outcomes of school-aged children who were born preterm have been reported extensively. Many of these studies have methodological flaws that preclude an accurate estimate of the long-term outcomes of prematurity. To estimate the effect of preterm birth on cognition and behavior in school-aged children. MEDLINE search (1980 to November 2001) for English-language articles, supplemented by a manual search of personal files maintained by 2 of the authors. We included case-control studies reporting cognitive and/or behavioral data of children who were born preterm and who were evaluated after their fifth birthday if the attrition rate was less than 30%. From the 227 reviewed studies, cognitive data from 15 studies and behavioral data from 16 studies were selected. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were extracted from each study, entered in a customized database, and reviewed twice to minimize error. Differences between the mean cognitive scores of cases and controls were pooled. Homogeneity across studies was formally tested using a general variance-based method and graphically using Galbraith plots. Linear meta-analysis regression models were fitted to explore the impact of birth weight and gestational age on cognitive outcomes. Study-specific relative risks (RRs) were calculated for the incidence of attention-deficit/hyperactivity disorder (ADHD) and pooled. Quality assessment of the studies was performed based on a 10-point scale. Publication bias was examined using Begg modified funnel plots and formally tested using the Egger weighted-linear regression method. Among 1556 cases and 1720 controls, controls had significantly higher cognitive scores compared with children who were born preterm (weighted mean difference, 10.9; 95% confidence interval [CI], 9.2-12.5). The mean cognitive scores of preterm-born cases and term-born controls were directly proportional to their birth weight (R(2) = 0.51; P<.001) and gestational age (R(2) = 0.49; P<.001). Age at evaluation had no significant correlation with mean difference in cognitive scores (R(2) = 0.12; P =.20). Preterm-born children showed increases in externalizing and internalizing behaviors in 81% of studies and had more than twice the RR for developing ADHD (pooled RR, 2.64; 95% CI, 1.85-3.78). No differences were noted in cognition and behaviors based on the quality of the study. Children who were born preterm are at risk for reduced cognitive test scores and their immaturity at birth is directly proportional to the mean cognitive scores at school age. Preterm-born children also show an increased incidence of ADHD and other behaviors.
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            Maternal age and fetal loss: population based register linkage study

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              The influence of season and ambient temperature on birth outcomes: a review of the epidemiological literature.

              Seasonal patterns of birth outcomes, such as low birth weight, preterm birth and stillbirth, have been found around the world. As a result, there has been an increasing interest in evaluating short-term exposure to ambient temperature as a determinant of adverse birth outcomes. This paper reviews the epidemiological evidence on seasonality of birth outcomes and the impact of prenatal exposure to ambient temperature on birth outcomes. We identified 20 studies that investigated seasonality of birth outcomes, and reported statistically significant seasonal patterns. Most of the studies found peaks of preterm birth, stillbirth and low birth weight in winter, summer or both, which indicates the extremes of temperature may be an important determinant of poor birth outcomes. We identified 13 studies that investigated the influence of exposure to ambient temperature on birth weight and preterm birth (none examined stillbirth). The evidence for an adverse effect of high temperatures was stronger for birth weight than for preterm birth. More research is needed to clarify whether high temperatures have a causal effect on fetal health. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                BMC Med Res Methodol
                BMC Medical Research Methodology
                BioMed Central
                1471-2288
                2011
                18 April 2011
                : 11
                : 49
                Affiliations
                [1 ]School of Public Health and Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia
                Article
                1471-2288-11-49
                10.1186/1471-2288-11-49
                3102035
                21501523
                12dc97f3-0157-426d-a4d3-f73de7875a68
                Copyright ©2011 Strand et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 January 2011
                : 18 April 2011
                Categories
                Research Article

                Medicine
                Medicine

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