1. Epidemiology of preterm birth Stefan Johansson Department of Neonatology, Karolinska university hospital Department of Medical Epidemiology and Biostatistics, Karolinska institutet Stockholm, Sweden

2. 25 October 2006Stefan Johansson2 Preterm birth preterm ≤ 36 weeks term 37-41 weeks postterm ≥ 42 weeks extremely preterm ≤ 27 weeks very preterm 28-31 weeks moderately preterm 32-36 weeks

3. 25 October 2006Stefan Johansson3 Preterm birth - not uncommon extremely preterm500 per year very preterm1500 moderately preterm4500

4. 25 October 2006Stefan Johansson4 Preterm birth - part of being human?  Preterm birth more common in humans compared to other mammalian species.  Evolutionary trend towards earlier birth? narrow pelvis related to bipedal gait large brain / head and risk of obstructed labour Steer. BJOG 2005;112, S1:1

5. 25 October 2006Stefan Johansson5 Preterm birth ≠ prematurity  Preterm birth refers to the timing of birth.  Prematurity refers to immature organ systems at birth.  Most infants born in week 35-36 are ”mature” and cared for in regular maternity units.  infants born at term (37 weeks and onwards) can suffer from some degree of immaturity

6. 25 October 2006Stefan Johansson6 Rates of preterm birth varies in the world  Sweden 6 %  US 10 %  Malawi 22 %  Why do rates vary?

7. 25 October 2006Stefan Johansson7 Increasing rates of preterm birth  Due to factors such as  in vitro fertilization  higher maternal age  Induced delivery before term  ultrasound dating of pregnancy length  However, among Danish ”low risk” women the rate of preterm delivery has increased by 51% from 1995 to 2004, from 3.8 to 5.7%  why?? Langhoff-Roos. BMJ 2006;332:937

8. 25 October 2006Stefan Johansson8 Preterm birth and mortality - world-wide  One million infants born preterm die during the first four weeks (26% of neonatal mortality). Lawn et al, Lancet 2005;365:891-900

9. 25 October 2006Stefan Johansson9 Gestational age and mortality - Sweden Perinatal mortality (%) in Sweden 2003, by gestational age.

10. 25 October 2006Stefan Johansson10 Very preterm birth and mortality - Sweden Infant mortality (%) in Sweden 1992-98, by gestational week

11. 25 October 2006Stefan Johansson11 Methodological problems - gestational length  How is gestational length defined?  last menstrual period  early ultrasound (measuring bones, head and abdomen)

12. 25 October 2006Stefan Johansson12 Methodological problems - gestational length  Gestational length, based on last menstrual period (LMP)  true gestational length is shorter  the rate of preterm birth is underestimated  Gestational length, based on ultrasound  more exact  unavailable in most countries

13. 25 October 2006Stefan Johansson13 Methodological problems - preterm birth  What is the method of assessing gestational length?  Which preterm born infants are classified as alive / dead?  ”live-born infants”?  ”still-births”?  Border of viability and neonatal care policies?  Live-born infants>23-24 wks can be admitted to neonatal care.  The policy regarding which infants to treat vary between countries.

14. 25 October 2006Stefan Johansson14 Methodological problems - preterm birth  Rates of preterm birth and maternal and obstetric care  is expected day of delivery (i.e. 40 completed weeks) calculated?  are birth date recorded and gestational length calculated?  are those data registrered?

15. 25 October 2006Stefan Johansson15 Methodological aspects of mortality  Consistent definition of outcome…  Consensus on definitions:  Perinatal mortalitystillbirths + death during the first week  Neonatal mortalityduring the first four weeks  Infant mortalityduring the first year

16. 25 October 2006Stefan Johansson16 Methodological aspects of mortality  How is ”alive” determined at birth?  How are deaths recorded?  Mortality rates of live-born preterm infans underestimate the survival rate related to preterm birth  still-births are generally not included

17. 25 October 2006Stefan Johansson17

18. 25 October 2006Stefan Johansson18 Why preterm deliveries? induced spontaneous

19. 25 October 2006Stefan Johansson19 Induced preterm delivery  Preeclampsia (hypertension and urinary protein leakege)  delivery on ”maternal indication”  delivery on ”neonatal indication”  Other indications  maternal diseases (diabetes, cancer, trauma etc, etc)  fetal growth retardation  multiple pregnancies  malformations

20. 25 October 2006Stefan Johansson20 Spontaneous preterm delivery  Infections (malaria)  Preterm rupture of membranes (PROM)  Preterm contractions  Placental bleeding

21. 25 October 2006Stefan Johansson21 Risks of recurrent preterm delivery Preterm birth, first pregnancy Risk of preterm birth, second pregnancy < 37 weeks2.9 [2.8-3.0] < 35 weeks3.6 [3.4-3.9] < 32 weeks4.9 [4.2-5.7] Ananth. AJOG 2006;195:643

22. 25 October 2006Stefan Johansson22 Risks of recurrent preterm delivery, 34-36 wks 2nd preterm delivery, spontaneous 2nd preterm delivery, induced 1st preterm delivery spontaneous 3.0 [2.8-3.2]1.0 [0.8-1.2] 1st preterm delivery induced 0.8 [0.6-1.0]5.8 [5.0-6.7] Ananth. AJOG 2006;195:643

23. 25 October 2006Stefan Johansson23 Risks of recurrent preterm delivery, < 28 wks 2nd preterm delivery, spontaneous 2nd preterm delivery, induced 1st preterm delivery spontaneous 13.2 [8.8-19.8]12.6 [7.0-22.7] 1st preterm delivery induced 10.4 [5.0-21.4]22.7 [11.3-46.0] Ananth. AJOG 2006;195:643

24. 25 October 2006Stefan Johansson24 Preterm birth… genes or environment?

25. 25 October 2006Stefan Johansson25 Risk factors of preterm birth - genes  Genetic influence on gestational length.  genetic factors accounted for 36% of preterm births  Genetic component of pre-eclampsia  heritability for preeclampsia was 31%  If the mother/sister had preeclampsia, the risk of preeclampsia for the daughter/sister is tripled, compared to unrelated women. Clausson. BJOG 2000;107:375 Nilsson. BJOG 2004;111:200

26. 25 October 2006Stefan Johansson26 Risk factors of preterm birth - infections  Reproductive tract infections* have increased risk  20% of women with infections delivered preterm compared 9.5% of women without infection.  More than 40% of preterm deliveries attributed to infections.  Treatment of infections reduced the risk of preterm delivery  Relative risk 0.16 [0.04-0.66] *bacterial vaginosis, Chlamydia, Trichomonas, Mycoplasma, gr B strepto, Gonorrhoeae French. AJOG 2006;194:1717

27. 25 October 2006Stefan Johansson27 Risk factors of preterm birth - maternal age  Young maternal age  Teenage women have a doubled risk of preterm birth, compared to women aged 20-24  High maternal age  Women aged ≥40 are also at increased risk of preterm birth Olausson. BJOG 2001;108:721 Cleary-Goldman, Obstet Gynecol 2005;105:983

28. 25 October 2006Stefan Johansson28 Risk factors of preterm birth - education Thompson. Paediatr Perinat Epidemiol. 2006;20:182

29. 25 October 2006Stefan Johansson29 Risk factors of preterm birth - smoking Kyrklund-Blomberg. AJOG 1998;179:1051

30. 25 October 2006Stefan Johansson30 Risk factors of preterm birth - others  Periodontal infections.  Interpregnancy weight loss.  Previous induced abortion.  Air pollutants and ozone.

31. 25 October 2006Stefan Johansson31 Increasing rate of preterm birth - what to do?  Reduce the prevalance of smoking?  Screen for bacterial vaginos, chlamydia and other infections?  Sharpen indications for induced preterm deliveries?  More knowledge is needed about modifiable risk factors.

32. 25 October 2006Stefan Johansson32 Conclusions  Preterm birth is common and rates are increasing.  Substantial mortality.  Methodoligical issues.  Many risk factors identified:  genes  Infections  maternal age  Socioeconomic status  smoking  No succesful strategies to prevent preterm birth.