Lecture on maternal obesity and neonatal outcomes 12 April 2017, held at the 17th Annual Saudi Neonatology Society Conference, in Riyadh, Saudi Arabia.

1. Maternal obesity and
neonatal outcomes
STEFAN JOHANSSON, MD PhD
Sachs Children’s Hospital
Karolinska institutet
Stockholm, Sweden

2. Grand Slam - Björn Borg

3. Grand Slam - Sven Cnattinguis

4. Gold Mines of Data
• All Swedes get a personal id number at birth
enabling linkage of data
• National registers:
– Medical Birth Register
– Patient Register
– Population Register
– Multi-generation Register

5. Mother
Infant

6. Mother
Infant
Father Sister
Sibling

7. Why are family relations important?
• Families share conditions related
to health and disease
– environment
– genes
• Reduce confounding due to (unmeasured)
factors shared by families

9. Global epidemic of obesity
• 2 billion adults are overweight (BMI≥25), of
which 600 million are obese (BMI ≥30)
• Associated diseases are major causes of death
• Obesity is preventable

10. Obesity and child-bearing
• Maternal obesity increases risks of
preeclampsia and diabetes
• Research unconclusive on neonatal outcomes
– preterm birth
– birth asphyxia
– infant mortality

12. Our approach
• National data on mothers and infants,
from 1992 and onwards:
– antenatal care
– obstetric care
– neonatal care
• Depending on study design, we used data from
150.000 – 1.800.000 women and their infants

13. Our papers
In Lancet, JAMA, BMJ, PLoS Med, Am J Epidemiology, Diabetologica:
• Preterm delivery. PMID 23757084
• Infant mortality. PMID 25467170
• Birth-asphyxia. PMID 24845218
• Inter-pregnancy weight change; infant mortality. PMID 26651225
• Inter-pregnancy weight change; birth asphyxia. PMID 27270217
• Sibling study; infant mortality. PMID 27358265
• Pre-eclampsia risk of diabetic women. PMID 27369871
• Cerebral palsy. PMID 28267854

14. • Preterm birth
• Infant mortality
• Birth asphyxia and CP

15. Maternal BMI and preterm birth
% extremely, very and moderately preterm births
among 1.8 million mothers in Sweden
BMI 22-27 wks 28-31 wks 32-36 wks
18.5 - 24.9 0.17 0.40 4.0
25.0 - 29.9 0.21 0.44 4.2
30.0 - 34.5 0.27 0.57 4.7
35.0 - 39.9 0.35 0.71 5.4
40.0 - 0.52 0.94 6.0

16. Maternal BMI and preterm birth
Maternal BMI ≥25 increased risks of
both extremely and very preterm birth
* Odds ratios were adjusted for maternal age, parity, smoking, education, maternal height, maternal country of
birth, and year of delivery.

17. Maternal BMI and preterm birth
• Obesity increased risks of
– medically induced deliveries
– spontaneous deliveries

18. • Preterm birth
• Infant mortality
• Birth asphyxia and CP

19. Maternal BMI and infant mortality
• Among 1.8 million, infant mortality rates
increased with maternal BMI:
– 2.4/1000 among normal weight (BMI 18.5–24.9)
– 5.8/1000 among obese grade 3 (BMI ≥40.0)

20. Maternal BMI and infant mortality
BMI <18.5 18.5-24 25-29 30-34 35-39 40-
* Odds ratios were adjusted for maternal age, parity, smoking, education, height,
country of birth, and year of delivery.

21. Causes of infant deaths
• Increased risk of infant mortality was due to
– more prevalent preterm births
– increased risk of birth asphyxia
• 11% of all infant deaths were attributed to
maternal overweight/obesity
(PAF; population attributable fraction)

22. Case-control study of sisters
• Is association between BMI and infant mortality
explained (confounded) by familial factors?
• In a case-control study design, we included
primiparous women with singleton births who
also had a sister who also had given birth

23. Case-control study of sisters
Singleton Live Births Occurring at 22 Weeks’
Gestation or Later (n = 203,021)
Cases of Infant
Mortality (n = 558)
Population Controls
(n = 201,905)
Sister Controls
(n = 558)
• BMI-related infant mortality risks similar,
regardless if we used population or sister controls
• Confounding by shared familial factors unlikely

24. • Preterm birth
• Infant mortality
• Birth asphyxia and CP

25. Birth asphyxia-related disease
1
1.6
1.8
2.3
3.6
1
1.3
1.6
1.8
3.4
18.5-24 25-29 30-34 35-39 40-
Apgar 0-3 at 5' Apgar 0-3 at 10'
1
1.6
1.9
2.9 2.9
1
1.4
1.7
2.2
4.1
18.5-24 25-29 30-34 35-39 40-
Meconium aspiration Seizures
* Odds ratios were adjusted for maternal age, parity, smoking, education, maternal
height, maternal country of birth, and year of delivery.

26. Inter-pregnancy weight change
• Comparison of two consecutive pregnancies,
and risks related to BMI-change
outcome odds ratio per +1 BMI-unit
Apgar score 0-6 at 5' 1.07 (1.04-1.09)
neonatal seizures 1.05 (1.01-1.09)
meconium aspiration 1.11 (1.06-1.17)
* Odds ratios were adjusted for BMI at first pregnancy, maternal age at 2nd
delivery, smoking, education, mother´s country of birth, and year of 2nd delivery.

27. Maternal BMI and cerebral palsy
• Birth asphyxia increase risk of cerebral palsy
• But also… cerebral palsy is commonly
considered NOT due to by birth asphyxia
• Our hypothesis:
maternal obesity is associated with cerebral
palsy, and the risk is mediated by birth asphyxia

28. Maternal BMI and cerebral palsy
• 1.400.000 children, followed on average 8 years
• 3.000 were diagnosed with cerebral palsy
BMI mothers (%) CP (nb) rate (/10k) risk (adj HR)
18.5-24 62 1487 2.4 1.00 (ref)
25-29 25 728 2.9 1.22 (1.11-1.33)
30-34 8 239 3.2 1.28 (1.11-1.47)
35-39 3 88 4.0 1.54 (1.24-1.93)
≥40 1 38 5.2 2.02 (1.46-2.79)
* Hazard ratios were adjusted for maternal age, country of origin, education,
cohabitation with a partner, height, smoking, and year of delivery.

29. Maternal BMI and cerebral palsy
• Gestational length modified the association
between BMI and cerebral palsy.
• Stratified analyses showed a significant
association only among children born at term,
comprising 71% of all cases of cerebral palsy.
• Birth asphyxia-complications mediated 45% of
the risk

31. Findings suggest causation
• Maternal BMI ≥ 25 increased risks of adverse
pregnancy and neonatal outcomes
• Risks increased with increasing BMI
• Women with inter-pregnancy weight increase
faced higher risks

32. What could explain associations?
• socioeconomy
• monitoring during antenatal care
• inflammation
• preeclampsia and gestational diabetes
• fetal growth disorders (SGA / LGA)
• malformations
• preterm births
• more complicated term deliveries

33. What can we do about this?
• Guidelines for antenatal and obstetric care
• Think big, think public health
– politicians and authorities need to set the agenda
– we all can learn to live a more healthy life
– particular focus on children, the adults of the future

34. And not to forget…
• Ensure all women, regardless of BMI, that they
will probably have a healthy baby, as absolute
risks (rates) are low for adverse outcomes
• The public health context is different
from councelling of parents-to-be

35. Conclusions
• Maternal obesity increase risks of preterm
birth, birth asphyxia, and infant mortality
• Observational findings suggest causality
• Normalisation of BMI in the young could
improve health in their children
• We should try do something about the global
epidemic of obesity!