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      Geographical differences in preterm delivery rates in Sweden: A population‐based cohort study

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          Abstract

          Introduction

          Preterm delivery is a major global public health challenge. The objective of this study was to determine how preterm delivery rates differ in a country with a very high human development index and to explore rural vs urban environmental and socioeconomic factors that may be responsible for this variation.

          Material and methods

          A population‐based study was performed using data from the Swedish Medical Birth Register from 1998 to 2013. Sweden was chosen as a model because of its validated, routinely collected data and availability of individual social data. The total population comprised 1 335 802 singleton births. A multiple linear regression was used to adjust gestational age for known risk factors (maternal smoking, ethnicity, maternal education, maternal age, height, fetal sex, maternal diabetes, maternal hypertension, and parity). A second and a third model were subsequently fitted allowing separate intercepts for each municipality (as fixed or random effects). Adjusted gestational ages were converted to preterm delivery rates and mapped onto maternal residential municipalities. Additionally, the effects of six rural vs urban environmental and socioeconomic factors on gestational age were tested using a simple weighted linear regression.

          Results

          The study population preterm delivery rate was 4.12%. Marked differences from the overall preterm delivery rate were observed (rate estimates ranged from 1.73% to 6.31%). The statistical significance of this heterogeneity across municipalities was confirmed by a chi‐squared test ( P < 0.001). Around 20% of the gestational age variance explained by the full model (after adjustment for known variables described above) could be attributed to municipality‐level effects. In addition, gestational age was found to be longer in areas with a higher fraction of built‐upon land and other urban features.

          Conclusions

          After adjusting for known risk factors, large geographical differences in rates of preterm delivery remain. Additional analyses to look at the effect of environmental and socioeconomic factors on gestational age found an increased gestational age in urban areas. Future research strategies could focus on investigating the urbanity effect to try to explain preterm delivery variation across countries with a very high human development index.

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          Most cited references16

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          A quality study of a medical birth registry.

          A quality control study was made of the Swedish Medical Birth Registry. This registry used one mode of data collection during 1973-1981 and another from 1982 onwards. The number of errors in the register was checked by comparing register information with a sample of the original medical records, and the variability in the use of diagnoses between hospitals was studied. Different types of errors were identified and quantified and the efficiency of the two methods of data collection evaluated.
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            Association between ambient fine particulate matter and preterm birth or term low birth weight: An updated systematic review and meta-analysis.

            An increasing number of studies have been conducted to determine a possible linkage between maternal exposure to ambient fine particulate matter and effects on the developing human fetus that can lead to adverse birth outcomes, but, the present results are not consistent. A total of 23 studies published before July 2016 were collected and analyzed and the mean value of reported exposure to fine particulate matter (PM2.5) ranged from 1.82 to 22.11 We found a significantly increased risk of preterm birth with interquartile range increase in PM2.5 exposure throughout pregnancy (odds ratio (OR) = 1.03; 95% conditional independence (CI): 1.01-1.05). The pooled OR for the association between PM2.5 exposure, per interquartile range increment, and term low birth weight throughout pregnancy was 1.03 (95% CI: 1.02-1.03). The pooled ORs for the association between PM2.5 exposure per 10 increment, and term low birth weight and preterm birth were 1.05 (95% CI: 0.98-1.12) and 1.02 (95% CI: 0.93-1.12), respectively throughout pregnancy. There is a significant heterogeneity in most meta-analyses, except for pooled OR per interquartile range increase for term low birth weight throughout pregnancy. We here show that maternal exposure to fine particulate air pollution increases the risk of preterm birth and term low birth weight. However, the effect of exposure time needs to be further explored. In the future, prospective cohort studies and personal exposure measurements needs to be more widely utilized to better characterize the relationship between ambient fine particulate exposure and adverse birth outcomes.
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              Cross-Country Individual Participant Analysis of 4.1 Million Singleton Births in 5 Countries with Very High Human Development Index Confirms Known Associations but Provides No Biologic Explanation for 2/3 of All Preterm Births

              Background Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countries with high rates. We thus sought to assess the contributions of known risk factors for both spontaneous and provider-initiated preterm birth in selected high income countries, estimating also the potential impact of successful interventions due to advances in research, policy and public health, or clinical practice. Methods We analyzed individual patient-level data on 4.1 million singleton pregnancies from four countries with very high human development index (Czech Republic, New Zealand, Slovenia, Sweden) and one comparator U.S. state (California) to determine the specific contribution (adjusting for confounding effects) of 21 factors. Both individual and population-attributable preterm birth risks were determined, as were contributors to cross-country differences. We also assessed the ability to predict preterm birth given various sets of known risk factors. Findings Previous preterm birth and preeclampsia were the strongest individual risk factors of preterm birth in all datasets, with odds ratios of 4.6–6.0 and 2.8–5.7, respectively, for individual women having those characteristics. In contrast, on a population basis, nulliparity and male sex were the two risk factors with the highest impact on preterm birth rates, accounting for 25–50% and 11–16% of excess population attributable risk, respectively (p<0.001). The importance of nulliparity and male sex on population attributable risk was driven by high prevalence despite low odds ratios for individual women. More than 65% of the total aggregated risk of preterm birth within each country lacks a plausible biologic explanation, and 63% of difference between countries cannot be explained with known factors; thus, research is necessary to elucidate the underlying mechanisms of preterm birth and, hence, therapeutic intervention. Surprisingly, variation in prevalence of known risk factors accounted for less than 35% of the difference in preterm birth rates between countries. Known risk factors had an area under the curve of less than 0.7 in ROC analysis of preterm birth prediction within countries. These data suggest that other influences, as yet unidentified, are involved in preterm birth. Further research into biological mechanisms is warranted. Conclusions We have quantified the causes of variation in preterm birth rates among countries with very high human development index. The paucity of explicit and currently identified factors amenable to intervention illustrates the limited impact of changes possible through current clinical practice and policy interventions. Our research highlights the urgent need for research into underlying biological causes of preterm birth, which alone are likely to lead to innovative and efficacious interventions.
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                Author and article information

                Contributors
                sarah.murray@doctors.org.uk
                Journal
                Acta Obstet Gynecol Scand
                Acta Obstet Gynecol Scand
                10.1111/(ISSN)1600-0412
                AOGS
                Acta Obstetricia et Gynecologica Scandinavica
                John Wiley and Sons Inc. (Hoboken )
                0001-6349
                1600-0412
                08 October 2018
                January 2019
                : 98
                : 1 ( doiID: 10.1111/aogs.2019.98.issue-1 )
                : 106-116
                Affiliations
                [ 1 ] MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh Edinburgh UK
                [ 2 ] Department of Obstetrics and Gynecology, Institute of Clinical Sciences Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden
                [ 3 ] Karolinska University Hospital Stockholm Sweden
                [ 4 ] Department of Genetics and Bioinformatics, Area of Health Data and Digitalization Norwegian Institute of Public Health Oslo Norway
                Author notes
                [*] [* ] Correspondence

                Sarah R. Murray, MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK.

                Email: sarah.murray@ 123456doctors.org.uk

                Author information
                http://orcid.org/0000-0002-2344-6852
                http://orcid.org/0000-0001-5079-2374
                Article
                AOGS13455
                10.1111/aogs.13455
                6492021
                30169899
                4e3cc80b-a776-458a-a45b-e8a3e6607355
                © 2018 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 March 2018
                : 20 August 2018
                : 22 August 2018
                Page count
                Figures: 5, Tables: 2, Pages: 11, Words: 10590
                Funding
                Funded by: National Institute of Health Research
                Funded by: Agreement concerning the Research and Education of Doctors
                Award ID: ALFGBG‐426411
                Funded by: Sahlgrenska University Hospital, March of Dimes
                Award ID: 21‐FY16‐121
                Funded by: Swedish Research Council
                Award ID: 2015‐02559
                Funded by: Research Council of Norway
                Award ID: FRIMEDBIO ES547711
                Funded by: Jane and Dan Olsson Research Foundation, Gothenburg
                Funded by: Wellcome Trust
                Award ID: 104490/Z/14/Z
                Categories
                Original Research Article
                Pregnancy
                Custom metadata
                2.0
                aogs13455
                January 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.2.1 mode:remove_FC converted:01.05.2019

                Obstetrics & Gynecology
                epidemiology,premature,premature obstetric labor,preterm birth,preterm infant

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