1. Abnormally invasive placenta Prevalence, risk factors and antenatal suspicion: Results from a large population-based pregnancy cohort study in the Nordic Countries Thurn L, Lindqvist PG, Jakobsson M, Colmorn LB, Klungsoyr K, Bjarnadóttir RI, Tapper AM, Børdahl PE, Gottvall K, Petersen KB, Krebs L, Gissler L, Langhoff-Roos J, Källen K. The Nordic Obstetric Surveillance Study (NOSS)

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3. Scenario A 32-year-old woman presents with small amount of vaginal bleeding at 26 weeks of her pregnancy. She has no other symptoms and is stable. She had two previous caesarean sections; for breech presentation in her first pregnancy and a subsequent elective caesarean section. Ultrasound assessment confirms the fetus is viable with normal growth. However, placenta is anterior and low-lying (placenta praevia). How would you manage this woman?

4. Background Abnormally invasive placenta (AIP) features abnormal invasion of chorionic villi into the myometrium AIP can invade adjacent organs and cause major haemorrhage, which leads to complicated surgeries and hysterectomies Incidence of AIP has increased over the past 30 years: now reported to occur in 2-90 per 10 000 births Known risk factors of AIP: placenta praevia (low-lying placenta), previous caesarean section, increasing maternal age and high parity If suspected before birth, planned operative delivery for AIP was associated with fewer complications and blood transfusions.

5. Background How do you define and diagnose abnormally invasive placenta (AIP)? How common is AIP in your practice? What is the Nordic Obstetric Surveillance Study (NOSS)?

6. The Clinical Question What are the relative and absolute risks of AIP in different groups of pregnant women? Can we identify AIP before birth? Does identification of AIP before birth improve clinical outcomes?

7. Structured question (PICOD) ParticipantsWomen giving birth in the Nordic Countries between 2009-2012 InterventionWomen with abnormally invasive placenta (AIP), with or without antenatal suspicion of AIP ComparisonThe respective background population of each country (women without AIP) OutcomesPrevalence, risk factors, antenatal suspicion, birth complications and risk estimations using aggregated national data. Study DesignPopulation-based Cohort Study, the Nordic Obstetric Surveillance Study (NOSS)

8. Women giving birth in the Nordic Countries between 2009-2012 n=666 698 Women identified with AIP n=205 Women with antenatal suspicion of AIP n=60 Women gave birth in centers that did not participate n=61 336 Women without antenatal suspicion of AIP n=145

9. Methods What are the benefits of prospective registration of rare complications of pregnancy? – compared to existing retrospective registration systems based on ICD-10 codes What are the strengths and pitfalls of amalgamating data from multiple countries?

10. Prevalence of AIP (per 10,000 deliveries)

11. Prevalence & Antenatal suspicion The prevalence of AIP in the Nordic Countries was 3.4 per 10 000 deliveries In women with previous CS, it increased to 13.9 per 10,000 deliveries AIP was suspected before birth in 29% of confirmed cases

13. Risks of AIP (see previous slide) Pregnancies with placenta praevia (absolute risk: 2- 10%): 170x to 640x increased relative risks Previous CS (13.9 per 10,000 deliveries): dose- dependent relationship – 7x increased relative risk after one previous CS – 56x increased after >3 previous CS Postpartum haemorrhage in previous births (21 per 10,000 deliveries): 6x increased relative risk

14. Results What are the major risk factors of AIP identified in this study? How much more likely are women with these risk factors to have AIP? Is antenatal suspicion of AIP associated with improved maternal and neonatal outcomes?

15. Strategies to minimise the number of caesarean sections can reduce the incidence of AIP Targeted screening of 0.8% by ultrasound assessment for placenta praevia or placenta overlying a prior CS scar could improve the rate of antenatal detection of AIP by two folds Authors’ Conclusion

16. Discussion Can you briefly summarise the results of this study in one sentence? How would the results of this study influence your daily practice? How can we develop an internationally agreed definition of AIP?

17. Suggested reading Linked mini-commentary Fitzpatrick KE, Sellers S, Spark P, Kurinczuk JJ, Brocklehurst P, Knight M. The management and outcomes of placenta accreta, increta, and percreta in the UK: a population-based descriptive study. BJOG. 2014 Jan;121(1):62- 70; discussion 70-1. Calì G, Giambanco L, Puccio G, Forlani F. Morbidly adherent placenta: evaluation of ultrasound diagnostic criteria and differentiation of placenta accreta from percreta. Ultrasound Obstet Gynecol. 2013 Apr;41(4):406-12. Rustamov O, Alfirevic Z, Arora R, Siddiqui I, Mitchell AL. Imaging techniques for antenatal detection of morbidly adherent placenta (Protocol). Cochrane Database of Systematic Reviews 2011, Issue 2. Art. No.: CD008985.

19. Authors’ Affiliations L Thurn a, PG Lindqvist b, M Jakobsson c, LB Colmorn d, K Klungsoyr e, RI Bjarnadóttir f, AM Tapper g, PE Børdahl h, K Gottvall i,j, Kathrine B. Petersen k, L Krebs l, M Gissler m,n, J Langhoff-Roos d, K Källen i,o a Department of Obstetrics and Gynaecology, Blekinge Hospital, Karlskrona, Sweden. b Department of Obstetrics and Gynaecology, Clinitec, Karolinska University Hospital, Stockholm, Sweden, c Department of Obstetrics and Gynaecology, University Hospital, Helsinki, Finland, d Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark, e Department of Global Public Health and Primary Care, University of Bergen, and Medical Birth Registry of Norway, Norwegian Institute of Public Health, Bergen, Norway, f Department of Obstetrics and Gynaecology, Landspitali University Hospital, Reykjavik, Iceland, g Department of Gynaecology and Paediatrics, University Hospital, Helsinki, Finland, h Department of Obstetrics and Gynaecology, Haukeland University Hospital, and University of Bergen, Norway, i Department of Evaluation and Analysis, Epidemiology and Methodological support unit, National Board of Health and Welfare, Stockholm, Sweden, j Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden, k Fertility Clinic, Copenhagen University Hospital, Rigshospitalet, Denmark, l Department of Obstetrics and Gynaecology, Holbæk Hospital and University of Copenhagen, Denmark, m THL National Institute for Health and Welfare, Helsinki, Finland, n Nordic School of Public Health, Gothenburg, Sweden, o Department of Reproduction Epidemiology, Tornblad Institute, Institution of Clinical Sciences, Lund University, Lund, Sweden There were no conflicts of interest. Corresponding author: Pelle.lindqvist@ki.se.