Epidemiology of preterm birthStefan JohanssonDepartment of Neonatology, Karolinska university hospitalDepartment of Medical Epidemiology and Biostatistics, Karolinska institutetStockholm, Sweden

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Preterm birth

preterm≤ 36 weeks

term37-41 weeks

postterm≥ 42 weeks

extremelypreterm≤ 27 weeks

very preterm28-31 weeks

moderatelypreterm32-36 weeks

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Preterm birth - not uncommon• extremely preterm 500 per year• very preterm 1500• moderately preterm 4500

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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

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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

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Rates of preterm birth varies in the world

Sweden 6 % US 10 % Malawi 22 %

Why do ratesvary?

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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

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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

TetanusDiarrhea

Other

Lawn et al, Lancet 2005;365:891-900

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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.

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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

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Methodological problems - gestational length

How is gestational length defined? last menstrual period early ultrasound (measuring bones, head and abdomen)

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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

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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.

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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?

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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

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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

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Why preterm deliveries?

induced

spontaneous

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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

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Spontaneous preterm delivery

Infections (malaria)

Preterm rupture of membranes (PROM)

Preterm contractions

Placental bleeding

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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

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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

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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

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Preterm birth…genes or environment?

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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

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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

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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

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Risk factors of preterm birth - education

Thompson. Paediatr Perinat Epidemiol. 2006;20:182

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Risk factors of preterm birth - smoking

Kyrklund-Blomberg. AJOG 1998;179:1051

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Risk factors of preterm birth - others

Periodontal infections. Interpregnancy weight loss. Previous induced abortion. Air pollutants and ozone.

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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.

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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.