A comparison of risk factors for breech presentation in preterm and term labor : a nationwide, population-based case-control study

Purpose To determine if the common risks for breech presentation at term labor are also eligible in preterm labor. Methods A Finnish cross-sectional study included 737,788 singleton births (24-42 gestational weeks) during 2004-2014. A multivariable logistic regression analysis was used to calculate the risks of breech presentation. Results The incidence of breech presentation at delivery decreased from 23.5% in pregnancy weeks 24-27 to 2.5% in term pregnancies. In gestational weeks 24-27, preterm premature rupture of membranes was associated with breech presentation. In 28-31 gestational weeks, breech presentation was associated with maternal pre-eclampsia/hypertension, preterm premature rupture of membranes, and fetal birth weight below the tenth percentile. In gestational weeks 32-36, the risks were advanced maternal age, nulliparity, previous cesarean section, preterm premature rupture of membranes, oligohydramnios, birth weight below the tenth percentile, female sex, and congenital anomaly. In term pregnancies, breech presentation was associated with advanced maternal age, nulliparity, maternal hypothyroidism, pre-gestational diabetes, placenta praevia, premature rupture of membranes, oligohydramnios, congenital anomaly, female sex, and birth weight below the tenth percentile. Conclusion Breech presentation in preterm labor is associated with obstetric risk factors compared to cephalic presentation. These risks decrease linearly with the gestational age. In moderate to late preterm delivery, breech presentation is a high-risk state and some obstetric risk factors are yet visible in early preterm delivery. Breech presentation in extremely preterm deliveries has, with the exception of preterm premature rupture of membranes, similar clinical risk profiles as in cephalic presentation.Peer reviewe

An International Contrast of Rates of Placental Abruption : An Age-Period-Cohort Analysis

Background Although rare, placental abruption is implicated in disproportionately high rates of perinatal morbidity and mortality. Understanding geographic and temporal variations may provide in-sights into possible amenable factors of abruption. We examined abruption frequencies by maternal age, delivery year, and maternal birth cohorts over three decades across seven countries. Methods Women that delivered in the US (n = 863,879; 1979-10), Canada (4 provinces, n = 5,407,463; 1982-11), Sweden (n = 3,266,742; 1978-10), Denmark (n = 1,773,895; 197808), Norway (n = 1,780,271, 1978-09), Finland (n = 1,411,867; 1987-10), and Spain (n = 6,151,508; 1999-12) were analyzed. Abruption diagnosis was based on ICD coding. Rates were modeled using Poisson regression within the framework of an age-period-cohort analysis, and multi-level models to examine the contribution of smoking in four countries. Results Abruption rates varied across the seven countries (3-10 per 1000), Maternal age showed a consistent J-shaped pattern with increased rates at the extremes of the age distribution. In comparison to births in 2000, births after 2000 in European countries had lower abruption rates; in the US there was an increase in rate up to 2000 and a plateau thereafter. No birth cohort effects were evident. Changes in smoking prevalence partially explained the period effect in the US (P = 0.01) and Sweden (P <0.01). Conclusions There is a strong maternal age effect on abruption. While the abruption rate has plateaued since 2000 in the US, all other countries show declining rates. These findings suggest considerable variation in abruption frequencies across countries; differences in the distribution of risk factors, especially smoking, may help guide policy to reduce abruption rates.Peer reviewe

Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids

BACKGROUND: Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure. METHODS: The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records. RESULTS AND DISCUSSION: The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS

Consortium for the Study of Pregnancy Treatments (Co-OPT) : An international birth cohort to study the effects of antenatal corticosteroids

Acknowledgments We are grateful to the Co-OPT collaborators from Finland, Iceland, Israel, Nova Scotia, and Scotland, who have provided high-quality patient data, without which the Co-OPT ACS cohort would not have been possible. We acknowledge Public Health Scotland for providing us with a secure data analytical platform in which to undertake this research and are particularly grateful to Anna Schneider who has been the data controller for this project. Co-OPT collaborators: Karel Allegaert (Belgium), Jasper Been (Netherlands), David Burgner (Australia), Sohinee Bhattacharya (UK), Kate Duhig (UK), Kristjana Einarsdóttir (Iceland), John Fahey (Canada), Lani Florian (UK), Abigail Fraser (UK), Mika Gissler (Finland), Cynthia Gyamfi-Bannerman (USA), Bo Jacobsson (Sweden), Eyal Krispin (Israel), Stefan Kuhle (Canada), Marius Lahti-Pulkkinen (Finland), Jessica Miller (Australia), Ben Mol (Australia), Sarah Murray (UK), Jane Norman (UK), Lars Henning Pedersen (Denmark), Richard Riley (UK), Devender Roberts (UK), Ewoud Schuit (Netherlands), Aziz Sheikh (UK), Ting Shi (UK), Joshua Vogel (Australia), Rachael Wood (UK), John Wright (UK), Helga Zoega (Australia). Funding Information: The Co-OPT ACS study is funded through a Wellcome Trust Clinical Career Development Fellowship grant (Funding Reference number 209560/Z/17) awarded to Sarah J Stock. The funders had no role in study design, data collection, data analysis, decision to publish, or preparation of the manuscript. The Sponsor of the study is the University of Edinburgh (www.ed.ac. uk), Sponsor reference AC19119. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.Peer reviewedPublisher PD

Socioeconomic inequalities in stillbirth rates in Europe: measuring the gap using routine data from the Euro-Peristat Project

Background Previous studies have shown that socioeconomic position is inversely associated with stillbirth risk, but the impact on national rates in Europe is not known. We aimed to assess the magnitude of social inequalities in stillbirth rates in European countries using indicators generated from routine monitoring systems. Methods Aggregated data on the number of stillbirths and live births for the year 2010 were collected for three socioeconomic indicators (mothers’ educational level, mothers’ and fathers’ occupational group) from 29 European countries participating in the Euro-Peristat project. Educational categories were coded using the International Standard Classification of Education (ISCED) and analysed as: primary/lower secondary, upper secondary and postsecondary. Parents’ occupations were grouped using International Standard Classification of Occupations (ISCO-08) major groups and then coded into 4 categories: No occupation or student, Skilled/ unskilled workers, Technicians/clerical/service occupations and Managers/professionals. We calculated risk ratios (RR) for stillbirth by each occupational group as well as the percentage population attributable risks using the most advantaged category as the reference (post-secondary education and professional/managerial occupations). Results Data on stillbirth rates by mothers’ education were available in 19 countries and by mothers’ and fathers’ occupations in 13 countries. In countries with these data, the median RR of stillbirth for women with primary and lower secondary education compared to women with postsecondary education was 1.9 (interquartile range (IQR): 1.5 to 2.4) and 1.4 (IQR: 1.2 to 1.6), respectively. For mothers’ occupations, the median RR comparing outcomes among manual workers with managers and professionals was 1.6 (IQR: 1.0–2.1) whereas for fathers’ occupations, the median RR was 1.4 (IQR: 1.2–1.8). When applied to the entire set of countries with data about mothers’ education, 1606 out of 6337 stillbirths (25 %) would not have occurred if stillbirth rates for all women were the same as for women with post-secondary education in their country. Conclusions Data on stillbirths and socioeconomic status from routine systems showed widespread and consistent socioeconomic inequalities in stillbirth rates in Europe. Further research is needed to better understand differences between countries in the magnitude of the socioeconomic gradient

ART in Europe, 2016 : results generated from European registries by ESHRE

STUDY QUESTION: What are the reported data on cycles in ART, IUI and fertility preservation (FP) interventions in 2016 as compared to previous years, as well as the main trends over the years? SUMMARY ANSWER: The 20th ESHRE report on ART and IUI shows a progressive increase in reported treatment cycle numbers in Europe, with a decrease in the number of transfers with more than one embryo causing a reduction of multiple delivery rates (DR), as well as higher pregnancy rates and DR after frozen embryo replacement (FER) compared to fresh IVF and ICSI cycles, while the outcomes for IUI cycles remained stable. WHAT IS KNOWN ALREADY: Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been collected, analysed by the European IVF-monitoring Consortium (EIM) and reported in 19 manuscripts published in Human Reproduction and Human Reproduction Open. STUDY DESIGN, SIZE, DURATION: Yearly collection of European medically assisted reproduction (MAR) data by EIM for ESHRE. The data on treatments performed between 1 January and 31 December 2016 in 40 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organizations. PARTICIPANTS/MATERIALS, SETTING, METHODS: In all, 1347 clinics offering ART services in 40 countries reported a total of 918 159 treatment cycles, involving 156 002 with IVF, 407 222 with ICSI, 248 407 with FER, 27 069 with preimplantation genetic testing, 73 927 with egg donation (ED), 654 with IVM of oocytes and 4878 cycles with frozen oocyte replacement (FOR). European data on IUI using husband/partner’s semen (IUI-H) and donor semen (IUI-D) were reported from 1197 institutions offering IUI in 29 and 24 countries, respectively. A total of 162 948 treatments with IUI-H and 50 467 treatments with IUI-D were included. A total of 13 689 FP interventions from 11 countries including oocyte, ovarian tissue, semen and testicular tissue banking in pre-and postpubertal patients were reported. MAIN RESULTS AND THE ROLE OF CHANCE: In 20 countries (18 in 2015) with a total population of approximately 325 million inhabitants, in which all ART clinics reported to the registry, a total of 461 401 treatment cycles were performed, corresponding to a mean of 1410 cycles per million inhabitants (range 82–3088 per million inhabitants). In the 40 reporting countries, after IVF the clinical pregnancy rates (PR) per aspiration and per transfer in 2016 were similar to those observed in 2015 (28.0% and 34.8% vs 28.5% and 34.6%, respectively). After ICSI, the corresponding rates were also similar to those achieved in 2015 (25% and 33.2% vs 26.2% and 33.2%). After FER with own embryos, the PR per thawing is still on the rise, from 29.2% in 2015 to 30.9% in 2016. After ED, the PR per fresh embryo transfer was 49.4% (49.6% in 2015) and per FOR 43.6% (43.4% in 2015). In IVF and ICSI together, the trend towards the transfer of fewer embryos continues with the transfer of 1, 2, 3 and 4 embryos in 41.5%, 51.9%, 6.2% and 0.4% of all treatments, respectively (corresponding to 37.7%, 53.9%, 7.9% and 0.5% in 2015). This resulted in a proportion of singleton, twin and triplet DRs of 84.8%, 14.9% and 0.3%, respectively (compared to 83.1%, 16.5% and 0.4%, respectively in 2015). Treatments with FER in 2016 resulted in twin and triplet DR of 11.9% and 0.2%, respectively (vs 12.3% and 0.3% in 2015). After IUI, the DRs remained similar at 8.9% after IUI-H (7.8% in 2015) and at 12.4% after IUI-D (12.0% in 2015). Twin and triplet DRs after IUI-H were 8.8% and 0.3%, respectively (in 2015: 8.9% and 0.5%) and 7.7% and 0.4% after IUI-D (in 2015: 7.3% and 0.6%). The majority of FP interventions included the cryopreservation of ejaculated sperm (n¼7877 from 11 countries) and of oocytes (n¼4907 from eight countries). LIMITATIONS, REASONS FOR CAUTION: As the methods of data collection and levels of completeness of reported data vary among European countries, the results should be interpreted with caution. A number of countries failed to provide adequate data about the number of initiated cycles and deliveries. WIDER IMPLICATIONS OF THE FINDINGS: The 20th ESHRE report on ART and IUI shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Being already the largest data collection on MAR in Europe, continuous efforts to stimulate data collection and reporting strive for future quality control of the data, transparency and vigilance in the field of reproductive medicine.The study has no external funding and all costs were covered by ESHRE.peer-reviewe

ART in Europe, 2017: results generated from European registries by ESHRE

© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Study question: What are the data on ART and IUI cycles, and fertility preservation (FP) interventions reported in 2017 as compared to previous years, as well as the main trends over the years? Summary answer: The 21st ESHRE report on ART and IUI shows the continual increase in reported treatment cycle numbers in Europe, with a decrease in the proportion of transfers with more than one embryo causing an additional slight reduction of multiple delivery rates (DR) as well as higher pregnancy rates (PR) and DR after frozen embryo replacement (FER) compared to fresh IVF and ICSI cycles, while the number of IUI cycles increased and their outcomes remained stable. What is known already: Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been gathered and analyzed by the European IVF-monitoring Consortium (EIM) and communicated in a total of 20 manuscripts published in Human Reproduction and Human Reproduction Open. Study design size duration: Data on European medically assisted reproduction (MAR) are collected by EIM for ESHRE on a yearly basis. The data on treatments performed between 1 January and 31 December 2017 in 39 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organizations. Participants/materials setting methods: Overall, 1382 clinics offering ART services in 39 countries reported a total of 940 503 treatment cycles, including 165 379 with IVF, 391 379 with ICSI, 271 476 with FER, 37 303 with preimplantation genetic testing (PGT), 69 378 with egg donation (ED), 378 with IVM of oocytes, and 5210 cycles with frozen oocyte replacement (FOR). A total of 1273 institutions reported data on 207 196 IUI cycles using either husband/partner's semen (IUI-H; n = 155 794) or donor semen (IUI-D; n = 51 402) in 30 countries and 25 countries, respectively. Thirteen countries reported 18 888 interventions for FP, including oocyte, ovarian tissue, semen and testicular tissue banking in pre- and postpubertal patients. Main results and the role of chance: In 21 countries (20 in 2016) in which all ART clinics reported to the registry, 473 733 treatment cycles were registered for a total population of approximately 330 million inhabitants, allowing a best-estimate of a mean of 1435 cycles performed per million inhabitants (range: 723-3286).Amongst the 39 reporting countries, the clinical PR per aspiration and per transfer in 2017 were similar to those observed in 2016 (26.8% and 34.6% vs 28.0% and 34.8%, respectively). After ICSI the corresponding rates were also similar to those achieved in 2016 (24% and 33.5% vs 25% and 33.2% in 2016). When freeze all cycles were removed, the clinical PRs per aspiration were 30.8% and 27.5% for IVF and ICSI, respectively.After FER with embryos originating from own eggs the PR per thawing was 30.2%, which is comparable to 30.9% in 2016, and with embryos originating from donated eggs it was 41.1% (41% in 2016). After ED the PR per fresh embryo transfer was 49.2% (49.4% in 2016) and per FOR 43.3% (43.6% in 2016).In IVF and ICSI together, the trend towards the transfer of fewer embryos continues with the transfer of 1, 2, 3 and ≥4 embryos in 46.0%, 49.2%, 4.5% and in 0.3% of all treatments, respectively (corresponding to 41.5%, 51.9%. 6.2% and 0.4% in 2016). This resulted in a reduced proportion of twin DRs of 14.2% (14.9% in 2016) and stable triplet DR of 0.3%. Treatments with FER in 2017 resulted in a twin and triplet DR of 11.2% and 0.2%, respectively (vs 11.9% and 0.2% in 2016).After IUI, the DRs remained similar at 8.7% after IUI-H (8.9% in 2016) and at 12.4% after IUI-D (12.4.0% in 2016). Twin and triplet DRs after IUI-H were 8.1% and 0.3%, respectively (in 2016: 8.8% and 0.3%) and 6.9% and 0.2% after IUI-D (in 2016: 7.7% and 0.4%). Amongst 18 888 FP interventions in 13 countries, cryopreservation of ejaculated sperm (n = 11 112 vs 7877 from 11 countries in 2016) and of oocytes (n = 6588 vs 4907 from eight countries in 2016) were the most frequently reported. Limitations reasons for caution: As the methods of data collection and levels of reporting vary amongst European countries, interpretation of results should remain cautious. Some countries were unable to deliver data about the number of initiated cycles and deliveries. Wider implications of the findings: The 21st ESHRE report on ART, IUI and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Being already the largest data collection on MAR in Europe, efforts should continue to optimize data collection and reporting with the perspective of improved quality control, transparency and vigilance in the field of reproductive medicine. Study funding/competing interests: The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.info:eu-repo/semantics/publishedVersio

Oocyte and ovarian tissue cryopreservation in European countries : statutory background, practice, storage and use

STUDY QUESTION: What is known in Europe about the practice of oocyte cryopreservation (OoC), in terms of current statutory background, funding conditions, indications (medical and ‘non-medical’) and specific number of cycles? SUMMARY ANSWER: Laws and conditions for OoC vary in Europe, with just over half the responding countries providing this for medical reasons with state funding, and none providing funding for ‘non-medical’ OoC. WHAT IS ALREADY KNOWN: The practice of OoC is a well-established and increasing practice in some European countries, but data gathering on storage is not homogeneous, and still sparse for use. Ovarian tissue cryopreservation (OtC) is only practiced and registered in a few countries. STUDY DESIGN, SIZE, AND DURATION: A transversal collaborative survey on OoC and OtC, was designed, based on a country questionnaire containing information on statutory or professional background and practice, as well as available data on ovarian cell and tissue collection, storage and use. It was performed between January and September 2015. PARTICIPANTS/MATERIALS, SETTING AND METHODS: All ESHRE European IVF Monitoring (EIM) consortium national coordinators were contacted, as well as members of the ESHRE committee of national representatives, and sent a questionnaire. The form included national policy and practice details, whether through current existing law or code of practice, criteria for freezing (age, health status), availability of funding and the presence of a specific register. The questionnaire also included data on both the number of OoC cycles and cryopreserved oocytes per year between 2010 and 2014, specifically for egg donation, fertility preservation for medical disease, ‘other medical’ reasons as part of an ART cycle, as well as for ‘non-medical reasons’ or age-related fertility decline. Another question concerning data on freezing and use of ovarian tissue over 5 years was added and sent after receiving the initial questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: Out of 34 EIM members, we received answers regarding OoC regulations and funding conditions from 27, whilst 17 countries had recorded data for OoC, and 12 for OtC. The specific statutory framework for OoC and OtC varies from absent to a strict frame. A total of 34 705 OoC cycles were reported during the 5-year-period, with a continuous increase. However, the accurate description of numbers was concentrated on the year 2013 because it was the most complete. In 2013, a total of 9126 aspirations involving OoC were reported from 16 countries. Among the 8885 oocyte aspirations with fully available data, the majority or 5323 cycles (59.9%) was performed for egg donation, resulting in the highest yield per cycle, with an average of 10.4 oocytes frozen per cycle. OoC indication was ‘serious disease’ such as cancer in 10.9% of cycles, other medical indications as ‘part of an ART cycle’ in 16.1%, and a non-medical reason in 13.1%. With regard to the use of OoC, the number of specifically recorded frozen oocyte replacement (FOR) cycles performed in 2013 for all medical reasons was 14 times higher than the FOR for non-medical reasons, using, respectively, 8.0 and 8.4 oocytes per cycle. Finally, 12 countries recorded storage following OtC and only 7 recorded the number of grafted frozen/thawed tissues. LIMITATIONS, REASONS FOR CAUTION: Not all countries have data regarding OoC collection, and some data came from voluntary collaborating centres, rather than a national authority or register. Furthermore, the data related to use of OoC were not included for two major players in the field, Italy and Spain, where numbers were conflated for medical and non-medical reasons. Finally, the number of cycles started with no retrieval is not available. Data are even sparser for OtC. WIDER IMPLICATIONS OF THE FINDINGS: There is a need for ART authorities and professional bodies to record precise data for practice and use of OoC (and OtC), according to indications and usage, in order to reliably inform all stakeholders including women about the efficiency of both methods. Furthermore, professional societies should establish professional standards for access to and use of OoC and OtC, and give appropriate guidance to all involved. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by ESHRE. There are no conflicts of interest.peer-reviewe

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries

Funding Information: M.B.A. holds a Tier 2 Canada Research Chair in the Developmental Origins of Chronic Disease at the University of Manitoba and is a Fellow in the Canadian Institutes for Advanced Research (CIFAR) Humans and the Microbiome Program. Her effort on this project was partly supported by HDR UK and ICODA. K.K.C.M. declares support from The Innovation and Technology Commission of the Hong Kong Special Administrative Region Government, and Hong Kong Research Grants Council Collaborative Research Fund Coronavirus Disease (COVID-19) and Novel Infectious Disease Research Exercise (Ref: C7154-20G) and grants from C W Maplethorpe Fellowship, National Institute of Health Research UK, European Commission Framework Horizon 2020 and has consulted for IQVIA Ltd. A.S. is supported by ICODA and HDR UK, and has received a research grant from HDR UK to the BREATHE Hub. He participates on the Scottish and UK Government COVID-19 Advisory Committees, unremunerated. S.J.S. is supported by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z) and HDR UK, and has received personal fees from Hologic and Natera outside the submitted work. D.B. is supported by a National Health and Medical Research Council (Australia) Investigator Grant (GTN1175744). I.C.K.W. declares support from The Innovation and Technology Commission of the Hong Kong Special Administrative Region Government, and Hong Kong Research Grants Council Collaborative Research Fund Coronavirus Disease (COVID-19) and Novel Infectious Disease Research Exercise (Ref: C7154-20G), and grants from Hong Kong Research Grant Council, National Institute of Health Research UK, and European Commission Framework Horizon 2020. H.Z. is supported by a UNSW Scientia Program Award and reports grants from European Commission Framework Horizon 2020, Icelandic Centre for Research, and Australia’s National Health and Medical Research Council. H.Z. was an employee of the UNSW Centre for Big Data Research in Health, which received funding from AbbVie Australia to conduct research, unrelated to the current study. I.I.A.A., C.D.A., K.A., A.I.A., L.C., S.S., G.E.-G., O.W.G., L. Huicho, S.H., A.K., K.L., V.N., I.P., N.R.R., T.R., T.A.H.R., V.L.S., E.M.S., L.T., R.W. and H.Z. received funding from HDRUK (grant #2020.106) to support data collection for the iPOP study. K.H., R.B., S.O.E., A.R.-P. and J.H. receive salary from ICODA. M.B. received trainee funding from HDRUK (grant #2020.106). J.E.M. received trainee funding from HDRUK (grant #2020.109). Other relevant funding awarded to authors to conduct research for iPOP include: M.G. received funding from THL, Finnish Institute for Health and Welfare to support data collection. K.D. received funding from EDCTP RIA2019 and HDRUK (grant #2020.106) to support data collection. R.B. received funding from Alzheimer’s Disease Data Initiative and ICODA for the development of federated analysis. A.D.M. received funding from HDR UK who receives its funding from the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation (BHF) and the Wellcome Trust; and Administrative Data Research UK, which is funded by the Economic and Social Research Council (grant ES/S007393/1). N.A. received funding from the National Institutes of Health (R35GM138353). O.S received funding from NordForsk (grant #105545). The remaining authors declare no competing interests. Funding Information: Funding and in-kind support: This work was supported by the International COVID-19 Data Alliance (ICODA), an initiative funded by the Bill and Melinda Gates Foundation and Minderoo as part of the COVID-19 Therapeutics Accelerator and convened by Health Data Research (HDR) UK, in addition to support from the HDR UK BREATHE Hub. Several ICODA partners contributed to the study, including: Cytel (statistical support), the Odd Group (data visualization) and Aridhia Informatics (development of federated analysis using a standardized protocol ([Common API] https://github.com/federated-data-sharing/ ) to be used in future work). Additional contributors: We acknowledge the important contributions from the following individuals: A. C. Hennemann and D. Suguitani (patient partners from Prematuridade: Brazilian Parents of Preemies’ Association, Porto Alegre, Brazil); N. Postlethwaite (implementation of processes supporting the trustworthy collection, governance and analysis of data from ICODA, HDR UK, London, UK); A. S. Babatunde (led data acquisition from University of Uyo Teaching Hospital, Uyo, Nigeria); N. Silva (data quality, revision and visualization assessment from Methods, Analytics and Technology for Health (M.A.T.H) Consortium, Belo Horizonte, Brazil); J. Söderling (data management from the Karolinska Institutet, Stockholm, Sweden). We also acknowledge the following individuals who assisted with data collection efforts: R. Goemaes (Study Centre for Perinatal Epidemiology (SPE), Brussels, Belgium); C. Leroy (Le Centre d'Épidémiologie Périnatale (CEpiP), Brussels, Belgium); J. Gamba and K. Ronald (St. Francis Nsambya Hospital, Kampala, Uganda); M. Heidarzadeh (Tabriz Medical University, Tabriz, Iran); M. J. Ojeda (Pontificia Universidad Católica de Chile, Santiago, Chile); S. Nangia (Lady Hardinge Medical College, New Delhi, India); C. Nelson, S. Metcalfe and W. Luo (Maternal Infant Health Section of the Public Health Agency of Canada, Ottawa, Canada); K. Sitcov (Foundation for Health Care Quality, Seattle, United States); A. Valek (Semmelweis University, Budapest, Hungary); M. R. Yanlin Liu (Mater Data and Analytics, Brisbane, Australia). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Funding Information: Funding and in-kind support: This work was supported by the International COVID-19 Data Alliance (ICODA), an initiative funded by the Bill and Melinda Gates Foundation and Minderoo as part of the COVID-19 Therapeutics Accelerator and convened by Health Data Research (HDR) UK, in addition to support from the HDR UK BREATHE Hub. Several ICODA partners contributed to the study, including: Cytel (statistical support), the Odd Group (data visualization) and Aridhia Informatics (development of federated analysis using a standardized protocol ([Common API] https://github.com/federated-data-sharing/) to be used in future work). Additional contributors: We acknowledge the important contributions from the following individuals: A. C. Hennemann and D. Suguitani (patient partners from Prematuridade: Brazilian Parents of Preemies’ Association, Porto Alegre, Brazil); N. Postlethwaite (implementation of processes supporting the trustworthy collection, governance and analysis of data from ICODA, HDR UK, London, UK); A. S. Babatunde (led data acquisition from University of Uyo Teaching Hospital, Uyo, Nigeria); N. Silva (data quality, revision and visualization assessment from Methods, Analytics and Technology for Health (M.A.T.H) Consortium, Belo Horizonte, Brazil); J. Söderling (data management from the Karolinska Institutet, Stockholm, Sweden). We also acknowledge the following individuals who assisted with data collection efforts: R. Goemaes (Study Centre for Perinatal Epidemiology (SPE), Brussels, Belgium); C. Leroy (Le Centre d'Épidémiologie Périnatale (CEpiP), Brussels, Belgium); J. Gamba and K. Ronald (St. Francis Nsambya Hospital, Kampala, Uganda); M. Heidarzadeh (Tabriz Medical University, Tabriz, Iran); M. J. Ojeda (Pontificia Universidad Católica de Chile, Santiago, Chile); S. Nangia (Lady Hardinge Medical College, New Delhi, India); C. Nelson, S. Metcalfe and W. Luo (Maternal Infant Health Section of the Public Health Agency of Canada, Ottawa, Canada); K. Sitcov (Foundation for Health Care Quality, Seattle, United States); A. Valek (Semmelweis University, Budapest, Hungary); M. R. Yanlin Liu (Mater Data and Analytics, Brisbane, Australia). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Publisher Copyright: © 2023, The Author(s).Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from −90% to +30%, were reported in many countries following early COVID-19 pandemic response measures (‘lockdowns’). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95–0.98, P value <0.0001), second (0.96, 0.92–0.99, 0.03) and third (0.97, 0.94–1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96–1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88–1.14, 0.98), third (0.99, 0.88–1.12, 0.89) and fourth (1.01, 0.87–1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02–1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03–1.15, 0.002), third (1.10, 1.03–1.17, 0.003) and fourth (1.12, 1.05–1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.Peer reviewe

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways