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Epidemiology of preterm birth
Stefan Johansson
Department of Neonatology, Karolinska university hospital
Department of Medical Epidemiology and Biostatistics, Karolinska institutet
Stockholm, Sweden
25 October 2006Stefan Johansson 2
Preterm birth
preterm≤ 36 weeks
term37-41 weeks
postterm≥ 42 weeks
extremelypreterm≤ 27 weeks
very preterm28-31 weeks
moderatelypreterm32-36 weeks
25 October 2006Stefan Johansson 3
Preterm birth - not uncommon• extremely preterm 500 per year• very preterm 1500• moderately preterm 4500
25 October 2006Stefan Johansson 4
Preterm birth - part of being human?
Preterm birth more common in humanscompared 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
25 October 2006Stefan Johansson 5
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
25 October 2006Stefan Johansson 6
Rates of preterm birth varies in the world
Sweden 6 % US 10 % Malawi 22 %
Why do ratesvary?
25 October 2006Stefan Johansson 7
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
25 October 2006Stefan Johansson 8
Preterm birth and mortality - world-wide
One million infants born preterm die during the first four weeks (26% of neonatal mortality).
Asphyxia
Preterm birth Sepsis
Congenital
Tetanus
DiarrheaOther
Lawn et al, Lancet 2005;365:891-900
25 October 2006Stefan Johansson 9
Gestational age and mortality - Sweden
0
10
20
30
40
50
60
-27 wks 28-30 31-33 34-36 37-39 40-42 43-45
Perinatal mortality (%) in Sweden 2003,by gestational age.
25 October 2006Stefan Johansson 10
Very preterm birth and mortality - Sweden
0
10
20
30
40
50
60
24 25 26 27 28 29 30 31
Infant mortality (%) in Sweden1992-98, by gestational week
0
10
20
30
40
50
60
-27 wks 28-30 31-33 34-36 37-39 40-42 43-45
25 October 2006Stefan Johansson 11
Methodological problems - gestational length
How is gestational length defined? last menstrual period early ultrasound (measuring bones, head and abdomen)
25 October 2006Stefan Johansson 12
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
25 October 2006Stefan Johansson 13
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.
25 October 2006Stefan Johansson 14
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?
25 October 2006Stefan Johansson 15
Methodological aspects of mortality
Consistent definition of outcome…
Consensus on definitions: Perinatal mortality stillbirths + death during the first week Neonatal mortality during the first four weeks Infant mortality during the first year
25 October 2006Stefan Johansson 16
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
25 October 2006Stefan Johansson 17
25 October 2006Stefan Johansson 18
Why preterm deliveries?
induced
spontaneous
25 October 2006Stefan Johansson 19
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
25 October 2006Stefan Johansson 20
Spontaneous preterm delivery
Infections (malaria)
Preterm rupture of membranes (PROM)
Preterm contractions
Placental bleeding
25 October 2006Stefan Johansson 21
Risks of recurrent preterm delivery
Preterm birth,
first pregnancy
Risk of preterm birth,
second pregnancy
< 37 weeks 2.9 [2.8-3.0]
< 35 weeks 3.6 [3.4-3.9]
< 32 weeks 4.9 [4.2-5.7]
Ananth. AJOG 2006;195:643
25 October 2006Stefan Johansson 22
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
25 October 2006Stefan Johansson 23
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
25 October 2006Stefan Johansson 24
Preterm birth…genes or environment?
25 October 2006Stefan Johansson 25
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;107:375Nilsson. BJOG 2004;111:200
25 October 2006Stefan Johansson 26
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
25 October 2006Stefan Johansson 27
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;108:721Cleary-Goldman, Obstet Gynecol 2005;105:983
25 October 2006Stefan Johansson 28
Risk factors of preterm birth - education
Thompson. Paediatr Perinat Epidemiol. 2006;20:182
25 October 2006Stefan Johansson 29
Risk factors of preterm birth - smoking
Kyrklund-Blomberg. AJOG 1998;179:1051
25 October 2006Stefan Johansson 30
Risk factors of preterm birth - others
Periodontal infections. Interpregnancy weight loss. Previous induced abortion. Air pollutants and ozone.
25 October 2006Stefan Johansson 31
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 aboutmodifiable risk factors.
25 October 2006Stefan Johansson 32
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.