Oral presentation given at the jENS conference Nov 3, 2017, in Venice/Italy. The presentation is a short summary of a project on maternal overweight and obesity and how that relates to offspring risk of cerebral palsy. The study was published in in JAMA in 2017, where it is available as open access on https://jamanetwork.com/journals/jama/fullarticle/2608220

1. Association between maternal BMI and
incidence of cerebral palsy
Stefan Johansson, MD PhD
associate professor, Clinical Epidemiology Unit, Karolinska Institutet
consultant neonatologist, Sachs’ Children and Youth Hospital
Stockholm, Sweden
stefan.johansson@ki.se

2. Financial conflicts of interest
 None.
jENS, 3 November 2017Stefan Johansson

3. www.ebneo.org

4. www.99nicu.org

5. Association between maternal BMI in early
pregnancy and incidence of cerebral palsy
 Full-text online
 JAMA. 2017;317(9):925-936
 doi:10.1001/jama.2017.0945
 Project group:
 Eduardo Villamor (US)
 Kristina Tedroff (Swe)
 Mark Peterson (US)
 Stefan Johansson (Swe)
 Martin Neovius (Swe)
 Gunnar Petersson (Swe)
 Sven Cnattingius (Swe)
jENS, 3 November 2017Stefan Johansson

6. Maternal obesity linked to neonatal morbidities
 Maternal overweight and obesity is associated with
 preterm birth
 birth asphyxia in term births
 Although preterm birth and birth asphyxia increase the risk,
the cause of cerebral palsy is commonly unknown
 Link between maternal obesity and offspring cerebral palsy?
jENS, 3 November 2017Stefan Johansson

7. Nationwide cohort study
 Medical Birth Register:
live-born singleton births at ≥22 weeks, in Sweden 1997-2011
 National Patient Register:
recorded diagnosis of cerebral palsy (ICD10-code G80) 1997-2012
jENS, 3 November 2017Stefan Johansson

8. Study population and occurence of cerebral palsy
 1.4 million children, followed during 11.5 million person-years
 3029 children had cerebral palsy
 2.1 per 1000 children
 2.6 per 10.000 person-years
jENS, 3 November 2017Stefan Johansson

9. Apgar scores at 5 minutes
No. with
cerebral palsy
Rate / 10.000
person-years
7-10 2359 2
4-6 339 42
0-3 223 134
missing data 108 12
jENS, 3 November 2017Stefan Johansson

10. Hypoxic ischemic encephalopathy
No. with
cerebral palsy
Rate / 10.000
person-years
No 2623 2
Yes 406 253
jENS, 3 November 2017Stefan Johansson

11. Neonatal seizures
No. with
cerebral palsy
Rate / 10.000
person-years
No 2519 2
Yes 510 267
jENS, 3 November 2017Stefan Johansson

12. Gestational age at delivery
No. with
cerebral palsy
Rate / 10.000
person-years
Term (≥37w) 2082 2
Moderately preterm (32-36w) 376 8
Very preterm (28-31w) 287 62
Extremely preterm (22-27w) 197 115
missing data 87 16
jENS, 3 November 2017Stefan Johansson

13. jENS, 3 November 2017Stefan Johansson
Maternal BMI Cerebral palsy
Main exposure and primary outcome

14. jENS, 3 November 2017Stefan Johansson
Maternal BMI Cerebral palsy
confounders
Confounders
Maternal covariates:
• Age
• Country of origin
• Educational level
• Cohabitation
• Parity
• Height
• Smoking
• Year of delivery

15. jENS, 3 November 2017Stefan Johansson
Maternal BMI Cerebral palsy
confounders
Confounders and mediators
Maternal covariates:
• Age
• Country of origin
• Educational level
• Cohabitation
• Parity
• Height
• Smoking
• Year of delivery
mediators
Infant covariates:
• Instrumental delivery
• Macrosomia
• Apgar scores
• Asphyxia-related diagnoses
• Congenital malformations
• Neonatal infections

16. jENS, 3 November 2017Stefan Johansson
Beware of the
CAUSAL PATHWAY POLICE DEPARTMENT

17. jENS, 3 November 2017Stefan Johansson
But… it is possible to investigate
exposure-mediator relations
 What is happening where*
 total BMI effect
 direct BMI effect
 indirect BMI effect
through mediator
*Possible to explore with the Valeri and
VanderWeele’s formulas applied in Cox
regression analyses

18. Maternal BMI-class and risk of cerebral palsy
jENS, 3 November 2017Stefan Johansson
1.09
1.00
1.22 1.28
1.54
2.02
Numbers of children with cerebral palsy* and adjusted** hazard ratios (95% CI)
BMI <18.5
(n=64)
BMI 18.5-24.9
(n=1487)
BMI 25.0-29.9
(n=728)
BMI 30.0-34.9
(n=239)
BMI 35.0-39.9
(n=88)
BMI ≥40.0
(n=38)
*(n=x) denotes number of cerebral palsy cases per BMI-category
**adjusted for maternal age, country of origin, education level, cohabitation with a partner, parity, height, smoking during
pregnancy and year of delivery

19. Stratification by gestational age
 Association between maternal BMI and cerebral palsy
was significant only in children born at term
jENS, 3 November 2017Stefan Johansson

20. Mediation analyses (term births)
jENS, 3 November 2017Stefan Johansson
Potential mediator Total BMI effect BMI effect through
mediator
Percentage of BMI
effect mediated*
Asphyxia-related complications 1.39 (1.26 - 1.53) 1.15 (1.12 - 1.17) 45
Apgar <7 at 5 minutes 1.38 (1.25 - 1.51) 1.09 (1.08 - 1.10) 30
Instrumental delivery 1.41 (1.29 - 1.55) 1.05 (1.04 - 1.06) 17
CNS malformation 1.40 (1.28 - 1.54) 1.04 (1.02 - 1.06) 13
Any congenital malformation 1.40 (1.27 - 1.53) 1.02 (1.02 - 1.03) 7
Neonatal infection 1.41 (1.28 - 1.55) 1.02 (1.01 - 1.02) 6
Traumatic delivery 1.42 (1.29 - 1.55) 1.00 (1.00 - 1.01) 2
Macrosomia (LGA) 1.42 (1.29 - 1.56) 0.99 (0.98 - 1.00) 0
*Sum of percentages is not 100% because the effects of mediators are not mutually exclusive,
and mediators could interact with each other.

21. Summary
jENS, 3 November 2017Stefan Johansson
 Cerebral palsy was diagnosed in ~ 2 per 1000 children,
and ~ ¾ cases occured in children born at term
 The higher maternal BMI, the higher the risk of cerebral palsy
 The association was limited to children born at term and
partly mediated by asphyxia-related complications
 Given the high rate of obesity, a small effect has public health
relevance, especially considering that obesity is preventable