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Alder og perinatalt utfall Ulla Waldenström Jordmor Professor Emerita Perinataldag Oslo 28 mars 2019

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Page 1: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Alder og perinatalt utfall

Ulla Waldenström Jordmor

Professor Emerita

Perinataldag Oslo 28 mars 2019

Page 2: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during
Page 3: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Syfte

Att undersöka om risken för - fosterdöd - för tidig födsel

- värkrubbningar - perinealbristning ökar med kvinnans ålder, oberoende av paritet

Page 4: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Metodik i alla 4 studier

Page 5: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Data

Medicinska födelseregistret

- 98% av alla förlossningar

- Årlig validering i relation till befolkningsregistret

Page 6: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Analyser

Ett dataset för varje paritetsgrupp Logistisk regressionsanalys med 3 modeller för varje dataset • Model 1: justerad för förlossningsår • Model 2: justerad för störande faktorer (confounding

factors)

• Model 3: justerad för störande och medierande faktorer

Page 7: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during
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Bakgrund

• Hög ålder (advanced maternal age) och förstföderska (nulliparity) är var för sig en oberoende riskfaktor för fosterdöd.

• Hög ålder har samband med åldersförändringar I blodkärlen och minskad funktion i placenta.

• Paritet kan möjligen påverka risken för fosterdöd på olika sätt

• Så vilken är den kombinrade effekten av hög ålder och paritet?

Page 9: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Causes of stillbirth in 617 cases* - Placental pathology 29%

- Infection 12%

- Cord complication 9%

- Maternal medical disorders 7%

- Congenital anomalies 6%

- Intrapartum events 3%

- No explanation found 30%

* Flenady et al 2011.

Page 10: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Alla 1 804 442 graviditeter i Medicinska födelseregistret 1990-2011 som

uppfyllde följande kriterier:

- Enkel börd

- Gestation 28 veckor eller senare

- Kvinnans ålder 25 år och äldre

- 1:a , 2:a och 3:e barnet

Population

Page 11: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Ålderskategorier

25-29 år : Referens = 1

30-34 år

35-39 år

≥ 40 år

Page 12: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Störande faktorer • Förlossningsår

• Familjesituation (bor med barnafaderna eller ej)

• Födelseland (Sverige/ Ej Sverige)

• Utbildning

• Rökare i tidig graviditet

• Moderns längd

• BMI

• Anamnes på fosterdöd i tidigare graviditet

• Intervall (år) från föregående graviditet

Page 13: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Medierande faktorer

Pregestational diabetes

Gestational diabetes

Pregestational hypertension

Preeclampsia

Intrauterine growth restriction

Page 14: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Resultat

Page 15: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Rates (%) of stillbirth by maternal age

0,3

0,4

0,6

0,7

0,2 0,3

0,4

0,7

25-29 30-34 35-39 ≥ 40 25-29 30-34 35-39 ≥ 40

Maternal age

1st births 2nd births 3rd births

Women with low or medium level of education

Women with high level of education

Page 16: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Age-related risk of stillbirth*

(Reference 1: 25-29 years)

1 1.23

1.86

2.72

0

0,5

1

1,5

2

2,5

3

3,5

4

25-29

30-34

35-39

≥40 25-29

30-34

35-39

≥40 25-29

30-34

35-39

≥40

Ad

just

ed

OR

( 9

5%

CI)

Maternal age

1st births (n=349 801)

2nd births (n=309 914)

3rd births (n=108 125)

*Analyses based on high educatad women

Page 17: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Risk of stillbirth by maternal age in a low-risk group

of non-smokers of normal weight

1

1.33

1.96

1.27 1.42

1.61

0

0,5

1

1,5

2

2,5

3

3,5

4

25-29 30-34 ≥35 25-29 30-34 ≥35 25-29 30-34 ≥35

Ad

just

ed

Od

ds

Rat

io w

ith

95

% C

I

Maternal age

1st births (n=341 759)

2nd births (n=323 744)

3rd births or more (n=153 355)

Page 18: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Slutsats

Advanced maternal age is an independent risk factor for stillbirth in nulliparous women.

This age-related risk is reduced or eliminated in parous women, possibly as a result of physiological adaptation during the first pregnancy.

Page 19: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Fysiologiska mekanismer Utero-placental underperfusion caused by sclerotic lesions in the myometrial arteries?

Autopsy of 62 non-pregnant women after accidental death: increase of sclerotic lesions in the myometrical arteries increased from 11% at age 17-19 years to 83% after age 39 (Naeye R,1983).

There is some evidence suggesting that the haemodynamic adaptation occurring during the first pregnancy may permanently modify uterine arteries, contributing to decreased vascular resistance and facilitated uteroplacental blood flow in the next pregnancy.

Hormonal changes?

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Bakgrund

För tidig födsel har ännu inte kunna förebyggas, främst för att dess specifika orsaker är komplexa och svåra att identifiera hos enskilda patienter.

Spontan för tidig födsel betraktas som ett syndrom initierat av av multipla meknismer, såsom infektion och inflammation, uteroplacentär ischemi och blödning, uterin uttänjning, cervixinsufficiens, hormonella störningar, stress, eller immunologiska processer.

Page 23: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Alla 2 009 068 graviditeter i Medicinska födelseregistret 1990-2011 som uppfyllde följande kriterier:

- Levande barn

- Enkel börd

- Kvinnan 20 år och äldre

- 1:a , 2:a och 3:e barnet

Population

Page 24: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Ålderskategorier

20-24 år 25-29 år: Reference = 1 30-34 år 35-39 år ≥ 40 år

Page 25: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Störande faktorer preterm birth

• Förlossningsår

• Utbildning

• Födelseland

• Rökare i tidig graviditet

• BMI

• Anamnes på för tidig födsel

Page 26: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Medierande faktorer preterm birth

Pregestational diabetes

Gestational diabetes

Hypertension

Preeclampsia

SGA

Page 27: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Result

Page 28: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Rates (%) of very and moderately preterm birth by maternal age

0.7 0.7 0.9 1.3

1.8

5.1 5.1 5.2

5.9 6.2

0

1

2

3

4

5

6

7

20-24 25-29 30-34 35-39 ≥40 20-24 25-29 30-34 35-39 ≥40

Pe

rce

nt

Maternal age

1st births 2nd births 3rd births

Very PTB (22-31 weeks)

Moderately PTB (32-36 weeks)

Page 29: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Rates (%) of very preterm birth by maternal age

0,7 0,7 0,9

1,3

1,8

0,5

0,4 0,5

0,7

0,9 0,8

0,5 0,5

0,6

1,1

20-24 25-29 30-34 35-39 ≥ 40

Maternal age

1st births 2nd births 3rd births

Page 30: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Age-related risk of very preterm birth (Reference 1: 25-29 years)

0.84 1

1.28

1.70

2.37

1 1.18

1.68

1.97

1.34

1 1.20

1.59

2.40

0

0,5

1

1,5

2

2,5

3

3,5

4

20-24

25-29

30-34

35-39

≥ 40 20-24

25-29

30-34

35-39

≥ 40 20-24

25-29

30-34

35-39

≥ 40

Ad

just

ed

OR

(9

5%

CI)

Maternal age

1st births (n=841 046)

2nd births (n=655 008)

3rd births (n=248 928)

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Risk of very preterm spontaneous births by maternal age and parity

0

0,5

1

1,5

2

2,5

3

3,5

4

4,5

20-2425-2930-3435-39 ≥ 40 20-2425-2930-3435-39 ≥ 40 20-2425-2930-3435-39 ≥ 40

Ad

just

ed

OR

(9

5%

CI)

Maternal age

1st births (n=474516)

2nd birth (n=393803)

3rd birth (n=144 090)

Page 32: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Risk of very preterm indicated* births by maternal age and parity

0

0,5

1

1,5

2

2,5

3

3,5

4

4,5

5

20-24 25-29 30-34 35-39 ≥ 40 20-24 25-29 30-34 35-39 ≥ 40 20-24 25-29 30-34 35-39 ≥ 40

Ad

just

ed

OR

(9

5%

CI)

Maternal age

1st births (n=474 116)

2nd births (n=393 591)

3rd births (n=144 043)

* Starting with induction or caesarean section before the onset of labour

Page 33: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Slutsats

Advanced maternal age is associated with an increased risk of preterm birth, irrespective of parity, especially very preterm birth. Women aged 35 years and older should be regarded as a risk group for very preterm birth.

Page 34: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Fysiologiska meknismer

• Blood circulation?

• Lower levels of progesterone?

• Stress?

Page 35: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during
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Bakgrund

Hög ålder (advanced maternal age) har samband med värkrubbningar (labour dystocia) hos förstföderskor.

Otillräckligt med kunskap om effekten hos omföderskor.

Page 38: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Tidigare kunskap

11,5 14,5

17,8

22,9

30

<25 25-29 30-34 35-39 ≥40

Caesarean section (%)

Swedish Medical Birth Register 1999-2011 (n=1 301 128 pregnancies)

Maternal age

Page 39: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Definition

Labour dystocia was defined by one or more of the following ICD codes (International Classification of Diseases

10):

O620 Primary inadequate contractions

O621 Secondary uterine inertia

O622 Other uterine inertia

O629 Abnormality of forces of labour, unspecified

O630 Prolonged first stage of labour

O631 Prolonged second stage of labour

O639 Long labour, unspecified

Page 40: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Alla 998 675 graviditeter i Medicinska födelseregistret 1999-2011 som uppfyllde följande kriterier:

- Fullgången graviditet (≥ 37 veckor)

- Levande barn

- Enkel börd

- Huvudbjudning

- Vaginal förlossning eller akut kejsarsnitt

- 1:a, 2:a and 3:e barnet

Population

Page 41: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Ålderskategorier

< 25 år: Reference = 1 25-29 år 30-34 år 35-39 år ≥40 år

Page 42: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Störande faktorer labour dystocia

• Förlossningsår

• Utbilding

• Födelseland

• Rökare i tidig graviditet

• Moderns längd

• BMI

• Gestation (vecka)

• Bjudning

• Barnets födelsevikt

Page 43: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Medierande faktorer labour dystocia

Induktion

Epidural

Page 44: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Resultat

Page 45: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Rates (%) of labour dystocia by maternal age

0

5

10

15

20

25

30

35

Pe

rce

nt

Maternal age Alla births (except elective Cesarean sections)

1st births 2nd births 3rd births

Page 46: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Age-related risk of labour dystocia (Reference 1: <25 years)

1

1.36

1.76

2.13 2.29

1 1.20

1.59

2.05

2.51

1

1.44

1.82

2.59

0

0,5

1

1,5

2

2,5

3

3,5

4

Ad

just

ed

OR

, 95

% C

I

Maternal age

1st births (n=401 234)

2nd births (n=332 451)

3rd births (n=119 644)

Page 47: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Slutsats

Maternal age is an independent risk factor for labour dystocia in first, second and third births.

Although age-related risks by parity are relatively similar, more nulliparous women will be exposed to labour dystocia due to their higher baseline rate.

Page 48: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Fysiologiska meknismer

• Ageing processes in the myometrium?

• Blood circulation?

• Hormones?

Page 49: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during
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Definition av OASI (Obstetric Anal Sphincter Injury)

Perinealbristning som omfattar den externa

och/eller den interna analsfinktern

Page 52: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Bakgrund

Page 53: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Ökad uppmärksamhet på grund av…

• Allvarliga konsekvenser i form av anal inkontinens

• Ökad förekomst i många länder

• Stor variation i rapporterad förekomst, från mindre än 2% till 27% hos förstföderskor och 8,5% hos omföderskor vid bedömning med endoanalt ultraljud

Page 54: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Obstetric anal sphincter injury in the Nordic countries 1997-2012 %

Page 55: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Obstetric anal sphincter injury in primiparas in Swedish counties 2014

Page 56: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Varför sådana skillnader?

• Diagnostisering?

• Dokumentation?

• Handläggning?

• Population? (etnicitet, moderns ålder, barnets födelsevikt…?

• Obstetriska interventioner? (tång, sugklocka…)

Page 57: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Rapporterade riskfaktorer • Barnet Hög födelsevikt Stort huvudomfång Vidöppen bjudning Skulderdystoci Långt utdrivningsskede

• Handläggning av förlossningen Instrumentell förlossning Medial episiotomi Förlossningsställning Sätt att skydda perineum (Motstridiga resultat om effekten av epidural)

• Modern Förstföderska Hög ålder Tidigare kejsarsnitt Anamnes på OASI Födelseland i Asien eller Africa Åldersrelaterad morbiditet: diabetes och gestationsdiabetes

Page 58: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Alla 959 559 graviditeter i Medicinska födelseregistret 1999-2011 som uppfyllde följande kriterier:

- Fullgången graviditet (≥ 37 veckor)

- Levande barn

- Enkel börd

- Vaginal förlossning

- 1:a, 2:a och 3:e barnet

Population

Page 59: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Ålderskategorier

< 25 år: Reference =1

25-29 år

30-34 år

> 35 år

Page 60: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Störande faktorer

• Förlossningsår

• Utbildning

• Födelseland

• Rökare i tidig graviditet

• BMI

• Bjudning

• Födelsevikt

• Anamnes på OASI

• Anamnes på kejsarsnitt

Page 61: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Medierande faktorer

Epidural

Episiotomi

Sugklocka

Åldersrelaterad morbiditet: diabetes, gestatiosdiabetes, högt blodtryck och preeklampsi

Page 62: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Resultat

Page 63: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Rates (%) of OASI by maternal age

4,1

6,9

8 7,8

1

2 2,7 3

0,4 0,6 0,8 1,1

<25 25-29 30-34 ≥ 35

1st births 2nd births 3rd births

Maternal age

Page 64: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Age-related risk of OASI (Reference 1: <25 years

0

0,5

1

1,5

2

2,5

3

3,5

4

<25 25-29

30-34

≥35 <25 25-29

30-34

≥35 <25 25-29

30-34

≥35

Ad

just

ed

OR

( 9

5%

CI)

Maternal age

3rd births (n=128 668)

1st births (n=412 442)

2nd births (n=350 987)

Page 65: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Slutsats

Maternal age is an independent risk factor for OASI in first, second and third births.

Although age-related risks by parity are relatively similar, more nulliparous women will be exposed to OASI due to their higher baseline rate.

Page 66: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Fysiologiska meknismer

• Ageing processes in muscles and connective tissues?

• Blood circulation caused by more sclerotic lesions?

Page 67: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Summering

Page 68: Alder og perinatalt utfall - Oslo universitetssykehus · *Analyses based on high educatad women. ... There is some evidence suggesting that the haemodynamic adaptation occurring during

Risk of adverse outcomes in nulliparas by maternal age, OR (95% CI)

Maternal age (years)

Outcome <25 25-29 30-34 35-39 ≥ 40 Stillbirth

1 (Reference)

1.23 (1.07-1.43)

1.86 (1.55-2.22)

2.72 (2.01-3.69)

Very preterm birth (22-31 weeks)

1

(Reference)

1.28 (1.20-1.36)

1.70 (1.56-1.84)

2.37 (2.04-2.77)

Labour dystocia

1 (Reference)

1.36 (1.33-1.39)

1.76 (1.72-1.81)

2.13 (2.06-2.20)

2.28 (2.14-2.43)

OASI

1 (Reference)

1.66 (1.59-1.72)

1.94

(1.86-2.02)

1.95

(1.85-2.05)

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Hela kroppen åldras!

Prevention?

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Tack för er uppmärksamhet!

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Medelålder vid barnafödande 1750-2000

1:a barnet: 29 år (2015) 1: barnet:

27-28 år (andra halvan av 1800-talet)

SCB

1:a barnet 24 år (början av 70-talet)