Jane E Norman Director of Tommy’s Centre for Maternal and Fetal Health Vice Principal, Equality and Diversity University of Edinburgh jane.norman@ed.ac.uk

Excesses of modern societies

Declarations

•  I have funding from government and charities for research on preterm birth, stillbirth and obesity in pregnancy

•  I am on a DSMB for GSK –  fee goes to University of Edinburgh

•  I am Chair of the NICE (National Institute of Clinical Excellence) guideline development committee on Preterm Labour and Birth (pub. Date Nov 2015)

Preterm birth - trends and strategies for reduction

Chang  HH  Lancet  2013    381:  223  -­‐  234  

Systematic review of strategies to prevent preterm birth with analysis of

effects on a population basis

•  Smoking cessation •  Avoidance of non medically indicated elective delivery •  Single embryo transfer at ART •  Cervical cerclage •  Progesterone prophylaxis

Chang  HH  Lancet  2013    381:  223  -­‐  234  

Systematic review of strategies to prevent preterm birth with analysis of

effects on a population basis

•  Smoking cessation 0.01 % •  Avoidance of non medically indicated elective delivery 0.29% •  Single embryo transfer at ART 0.06% •  Cervical cerclage 0.15% •  Progesterone prophylaxis 0.01%

•  Implementing all of these, rates would fall from 9.59% to 9.07% of livebirths

Chang  HH  Lancet  2013    381:  223  -­‐  234  

Smoking and PTB

Evidence on smoking cessation

Smoking cessation rates •  Health education: RR 1.51 (0.64 to 3.59) •  Counselling: RR 1.44 (1.19 to 1.75) •  Pharmacotherapy: RR 1.80 (1.32–2.44)

Incentive based interventions vs others •  typical RR 3.64 (1.84 to 7.23) Reduction in preterm birth rates: •  14 studies; average RR 0.82 (0.70 to 0.96)

Myung  SK  et  al  2012  BJOG  119:1029  Chamberlain  C  et  al  Cochrane  Database  Syst  Rev.  2013:CD001055.  

Evidence on smoking cessation

Smoking cessation rates •  Health education: RR 1.51 (0.64 to 3.59) •  Counselling: RR 1.44 (1.19 to 1.75) •  Pharmacotherapy: RR 1.80 (1.32–2.44)

Incentive based interventions vs others •  typical RR 3.64 (1.84 to 7.23) Reduction in preterm birth rates: •  14 studies; average RR 0.82 (0.70 to 0.96)

Myung  SK  et  al  2012  BJOG  119:1029  Chamberlain  C  et  al  Cochrane  Database  Syst  Rev.  2013:CD001055.  

Evidence on smoking cessation

Smoking cessation rates •  Health education: RR 1.51 (0.64 to 3.59) •  Counselling: RR 1.44 (1.19 to 1.75) •  Pharmacotherapy: RR 1.80 (1.32–2.44)

Incentive based interventions vs others •  Typical RR 3.64 (1.84 to 7.23) Reduction in preterm birth rates: •  14 studies; average RR 0.82 (0.70 to 0.96)

Myung  SK  et  al  2012  BJOG  119:1029  Chamberlain  C  et  al  Cochrane  Database  Syst  Rev.  2013:CD001055.  

Paid incentives for smoking cessation

•  Relative risk of not smoking at the end of pregnancy

was 2.63 (95% confidence interval 1.73 to 4.01) P<0.001

•  The absolute risk difference was 14.0% (95% confidence interval 8.2% to 19.7%).

•  The number needed to treat) was 7.2 (95% confidence interval 5.1 to 12.2).

Tappin D et al 2015 BMJ ;350:h134

Evidence on smoking cessation

Smoking cessation rates •  Health education: RR 1.51 (0.64 to 3.59) •  Counselling: RR 1.44 (1.19 to 1.75) •  Pharmacotherapy: RR 1.80 (1.32–2.44)

Incentive based interventions vs others •  Typical RR 3.64 (1.84 to 7.23) Reduction in preterm birth rates: •  14 studies; average RR 0.82 (0.70 to 0.96)

Myung  SK  et  al  2012  BJOG  119:1029  Chamberlain  C  et  al  Cochrane  Database  Syst  Rev.  2013:CD001055.  

Impact of smoking ban in Scotland on preterm birth rates

11.7 % reduction in rates of preterm birth - amongst current and never smokers

MacKay D et a 2012 PLOS Med 9:e1001175

Obesity

Maternal obesity - what are the problems (annual UK impact)

•  Deaths of 9 women •  Stillbirth of 2,520 babies

•  Macrosomia (birthweight > 4kg) of 11,200 babies •  25,200 extra Caesarean sections

•  Impaired later life health for offspring

•  Increased costs to the health service –  £550 to £1035 per woman (Denison et al, 2014, BJOG)

Effects of obesity on preterm birth and low birthweight

•  Overweight and obese women have increased risks of preterm birth and induced preterm birth and…appeared to have increased risks of preterm birth overall.

McDonald  SD  et  al  2010  BMJ;341:c3428  

Odds ratio of of PTB in relation to maternal BMI

Cnattingius S 2013 JAMA 309: 2365

Adjusted for maternal age, parity, smoking, education, maternal height, maternal country of birth, and year of delivery

Maternal obesity increases risk of infant mortality

Johanssen S et al 2014 BMJ 349:g6572

Maternal  BMI  

Risk of specific adverse outcomes

Johanssen S et al 2014 BMJ 349:g6572

Adjusted odds ratios (95% CI) Analysis by cause of death

BMI 18.5–24.9 Referent

BMI 25.0–29.9 Overweight

BMI 30.0–34.9 Obese

Congenital anomalies

1 1.16 (0.98 to 1.36) 1.13 (0.87 to 1.47)

Birth asphyxia

1 2.19 (1.59 to 3.02) 2.79 (1.76 to 4.43)

Other neonatal morbidity

1 1.57 (1.13 to 2.17) 2.47 (1.60 to 3.82)

SIDS

1 1.31 (1.03 to 1.66) 1.06 (0.71 to 1.58)

Infection

1 1.56 (1.10 to 2.22) 1.01 (0.52 to 1.97)

Contribution of lifestyle factors to infant mortality

Population attributable fractions: Obesity - 11% Smoking - 6.9%

This is in a country and over a period where 24% were overweight and 9% were obese in early pregnancy….and rates of smoking were 11.6%

Johanssen S et al 2014 BMJ 349:g6572

Reynolds  R  et  al  2013  BMJ;347:f4539  doi:  10.1136/bmj.f4539  

Maternal obesity increases all cause death in ofspring after adjustment

0.60

0.70

0.80

0.90

1.00

10 20 30 40 50 60Offspring time to Death (in Years)

Underweight Normal

Overweight Obese

K-M Curve for Maternal BMI categories (WHO)

Maternal obesity increases all cause death in offspring after adjustment

Reynolds  R  et  al  2013  BMJ;347:f4539  doi:  10.1136/bmj.f4539  

0.60

0.70

0.80

0.90

1.00

10 20 30 40 50 60Offspring time to Death (in Years)

Underweight Normal

Overweight Obese

K-M Curve for Maternal BMI categories (WHO)

Maternal obesity increases all cause death in offspring after adjustment

Hazard ratio of death by age 50:

1.42 (1.19 – 1.69)

Reynolds  R  et  al  2013  BMJ;347:f4539  doi:  10.1136/bmj.f4539  

Studies of interventions to prevent the adverse outcomes associated with

maternal obesity

•  Diet and exercise (LIMIT, UPBEAT) •  Drug to treating inflammation and / or

glucose tolerance (EMPOWaR)

Effect of lifestyle interventions in obese pregnant women

•  Overall –  1.42 kg reduction (95% CI 0.95 to 1.89 kg) in

gestational weight gain –  Reduction in pre-eclampsia (RR 0.74, 0.60 to 0.92) –  Reduction in shoulder dystocia (RR 0.39, 0.22 to

0.70) –  No significant differences in birth weight, incidence of

large for gestational age, incidence of small for gestational age

S Thangaratinam S et al 2012 BMJ 344:e2088

Effect of lifestyle interventions in obese pregnant women Preterm birth outcome

S Thangaratinam S et al 2012 BMJ 344:e2088

OR 0.78 (0.60 – 1.02)

Obese pregnant women

EMPOWaR: Metformin in non-diabetic pregnant women

Johansson K et al 2015 N Engl J Med: 372:814-24.

Stillbirth

Variation in rates of stillbirth in high income countries

Flenady  V  et  al  Lancet  2011;  377:  1703–17  

Declining infant death rates in England and Wales

Declining infant death rates in England and Wales

Stillbirth rate: 4.7 per 1000 in

2013

Effect  of  risk  factors  in  high  income  countries    

Increase  in  SB   PAR  %  

Illicit  drug  use   1.9  x     2.1  

Low  educa]on   1.7  x   4.9  

Low  socioeconomic  status   1.2  x   9.0  

No  antenatal  care   3.3  x   0.7  

Assisted  reproduc]on   2.7  x   3.1  

High  blood  pressure   1.3  to  2.2  x   5.1  

Small  baby  <  10th  cen]le   3.9  x   23.3  

Post  term  pregnancy  >  42  weeks   1.3  x   0.3  

Previous  s]llbirth   2.6  x   0.8  

Flenady V et al 2011 Lancet; 377: 1331–40

Conclusion

•  The excesses of modern societies: obesity, tobacco, other drugs contribute to stillbirth, preterm birth, and neonatal mortality

•  (Semi) effective smoking cessation therapies exist

•  Obesity is a major public health problem, and deserves urgent attention in pregnancy

Trends in obstetric causes of preterm birth in Scotland, 1980 to 2004

•  40.5 % increase in medically indicated preterm birth rates (p < 0.01)

•  10.7 % rise in rates of spontaneous preterm birth per 1000 singleton births (p< 0.01)

Spontaneous PTBpPROMInduced elective

Norman et al (2009) PLoS Med 6(9): e1000153

Bit more about drugs

Obesity – induced PTB

McDonald  SD  et  al  2010  BMJ;341:c3428  

Put  in  some  data  about  overall  PTB  rates  

Taylor et al Lead and preterm delivery

Declining infant death rates in England and Wales

Stillbirth in Scotland – 1974 - 2010

Scocsh  Perinatal  and  Infant  Mortality  and  Morbidity  Report  2010  -­‐  www.isdscotland.org        

Effect  of  risk  factors  in  high  income  countries    

Increase  in  SB   PAR  %  

Illicit  drug  use   1.9  x     2.1  

Low  educa]on   1.7  x   4.9  

Low  socioeconomic  status   1.2  x   9.0  

No  antenatal  care   3.3  x   0.7  

Assisted  reproduc]on   2.7  x   3.1  

High  blood  pressure   1.3  to  2.2  x   5.1  

Small  baby  <  10th  cen]le   3.9  x   23.3  

Post  term  pregnancy  >  42  weeks   1.3  x   0.3  

Previous  s]llbirth   2.6  x   0.8  

Flenady V et al 2011 Lancet; 377: 1331–40

Effect  of  risk  factors  in  high  income  countries    

Increase  in  SB   PAR  %  

Illicit  drug  use   1.9  x     2.1  

Low  educa]on   1.7  x   4.9  

Low  socioeconomic  status   1.2  x   9.0  

No  antenatal  care   3.3  x   0.7  

Assisted  reproduc]on   2.7  x   3.1  

High  blood  pressure   1.3  to  2.2  x   5.1  

Small  baby  <  10th  cen]le   3.9  x   23.3  

Post  term  pregnancy  >  42  weeks   1.3  x   0.3  

Previous  s]llbirth   2.6  x   0.8  

Flenady V et al 2011 Lancet; 377: 1331–40

Effect  of  risk  factors  in  high  income  countries    

Increase  in  SB   PAR  %  

Illicit  drug  use   1.9  x     2.1  

Low  educa]on   1.7  x   4.9  

Low  socioeconomic  status   1.2  x   9.0  

No  antenatal  care   3.3  x   0.7  

Assisted  reproduc]on   2.7  x   3.1  

High  blood  pressure   1.3  to  2.2  x   5.1  

Small  baby  <  10th  cen]le   3.9  x   23.3  

Post  term  pregnancy  >  42  weeks   1.3  x   0.3  

Previous  s]llbirth   2.6  x   0.8  

Flenady V et al 2011 Lancet; 377: 1331–40

Effect  of  risk  factors  in  high  income  countries    

Increase  in  SB   PAR  %  

Illicit  drug  use   1.9  x     2.1  

Low  educa]on   1.7  x   4.9  

Low  socioeconomic  status   1.2  x   9.0  

No  antenatal  care   3.3  x   0.7  

Assisted  reproduc]on   2.7  x   3.1  

High  blood  pressure   1.3  to  2.2  x   5.1  

Small  baby  <  10th  cen]le   3.9  x   23.3  

Post  term  pregnancy  >  42  weeks   1.3  x   0.3  

Previous  s]llbirth   2.6  x   0.8  

Flenady V et al 2011 Lancet; 377: 1331–40

OPERA - Aims

•  1) to determine how to assess risk for preterm birth and other adverse pregnancy outcomes simply, inexpensively and as early as possible in pregnancy,

•  2) to identify the women in the highest (20%) at-risk group (with 80% precision), and

•  3) to share this information with other studies, care-providers and interested parties.