OBJECTIVE: Infants from multiple pregnancies have higher rates of preterm birth, stillbirth and neonatal death and differences in multiple birth rates (MBR) exist between countries. We aimed to describe differences in MBR in Europe and to investigate the impact of these differences on adverse perinatal outcomes at a population level. METHODS: We used national aggregate birth data on multiple pregnancies, maternal age, gestational age (GA), stillbirth and neonatal death collected in the Euro-Peristat project (29 countries in 2010, N = 5 074 643 births). We also used European Society of Human Reproduction and Embryology (ESHRE) data on assisted conception and single embryo transfer (SET). The impact of MBR on outcomes was studied using meta-analysis techniques with random-effects models to derive pooled risk ratios (pRR) overall and for four groups of country defined by their MBR. We computed population attributable risks (PAR) for these groups. RESULTS: In 2010, the average MBR was 16.8 per 1000 women giving birth, ranging from 9.1 (Romania) to 26.5 (Cyprus). Compared to singletons, multiples had a nine-fold increased risk (pRR 9.4, 95% Cl 9.1-9.8) of preterm birth (<37 weeks GA), an almost 12-fold increased risk (pRR 11.7, 95% CI 11.0-12.4) of very preterm birth (<32 weeks GA). Pooled RR were 2.4 (95% Cl 1.5-3.6) for fetal mortality at or after 28 weeks GA and 7.0 (95% Cl 6.1-8.0) for neonatal mortality. PAR of neonatal death and very preterm birth were higher in countries with high MBR compared to low MBR (17.1% (95% CI 13.8-20.2) versus 9.8% (95% Cl 9.6-11.0) for neonatal death and 29.6% (96% CI 28.5-30.6) versus 17.5% (95% CI 15.7-18.3) for very preterm births, respectively). CONCLUSIONS: Wide variations in MBR and their impact on population outcomes imply that efforts by countries to reduce MBR could improve perinatal outcomes, enabling better long-term child health.

Centre for Maternal and Child Health Research School of Health Sciences City University London London Great Britain

Department of Epidemiology National Research Institute of Mother and Child Warsaw Poland

Department of Global Public Health and Primary Care University of Bergen and Medical Birth Registry of Norway Norwegian Institute of Public Health 5018 Bergen Norway

Department of Obstetrics and Gynaecology Landspitali University Hospital Reykjavik Iceland

INSERM Obstetrical Perinatal and Paediatric Epidemiology Research Team Centre for Epidemiology and Biostatistics Paris Descartes University Paris France

Institute for the Care of Mother and Child Prague Czech Republic

Ljubljana University Medical Center Ljubljana Slovenia

THL National Institute for Health and Welfare Helsinki Finland

TNO Netherlands Organisation for Applied Scientific Research Department Child Health Leiden The Netherlands Anton de Kom University of Suriname Faculty of Medical Sciences Department Public Health Paramaribo Suriname

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