1. Gestational weight gain in a UK cohort: patterns, risk factors and associations with later mother and offspring health
Debbie A Lawlor

2. Background Importance
Inform policy on the ideal GWG for supporting both short and long-term optimal health in offspring and mother
2009 IOM guidelines; NICE guidelines
Should weight be measured in pregnancy?
Science
Scant evidence of associations of GWG with long term outcomes in both mothers and offspring.
Even with short-term outcomes often based on just two measures (with one or both retrospectively reported)
Will screening identify women at risk and provide an opportunity to intervene

3. Aims and Objectives
To examine the associations of pre-pregnancy weight and GWG with long term outcomes in mothers and offspring
Determinants of GWG
Cardiovascular risk factors in offspring at age 9
Asthma in offspring at age 7.5
BMI, WC and BP in mothers 16 years post-pregnancy
Future plans

4. Participants
Mothers and offspring enrolled in the Avon Longitudinal Study of Parents and Children, a population-based birth cohort study that recruited 14,541 pregnant women resident in Avon, UK with expected dates of delivery 1st April 1991 to 31st December 1992
Gestational weight available for 12,484 mothers; of which 12,449 had a term pregnancy and offspring who survived 1 year.

5. Statistical methods
Categorise women according to IOM categories; using pre-pregnancy BMI and highest gestational weight
Use all of the available repeat ANC weight measurements
Median (IQR): 10 (8, 11)
MLwiN - linear spline random effects model with two knots (fractional polynomials to identify position of knots)

6. Mean rate of weight gain in 2nd and 3rd trimesters in kg/week
IOM recommendations
ALSPAC
Pre-pregnancy BMI
Absolute
weight gain in kg
Mean rate of weight gain in 2nd and 3rd trimesters in kg/week
Mean (range) absolute weight gain in kg*
Mean rate (SD) of weight gain in 2nd and 3rd trimesters in kg/week
Underweight (<18.5kg/m2)
0.51
12.9
(-2.0, 30.5)
0.54 (0.14)
Normal weight ( kg/m2)
0.42
12.8
(-2.2, 37.8)
0.53 (0.14)
Overweight
( kg/m2)
7-11.5
0.28
11.9
(-3.0, 33.5)
0.49 (0.17)
Obese (>=30kg/m2)
5-9
0.22
9.5
(-6.9, 30.9)
0.41 (0.20)
Overweight and obese gain too much

7. Results: Descriptive IOM categories Less than adequate: 35%
More than adequate: 27%
weeks
weeks

8. Determinants of gwg

9. Maternal Education

10. Maternal age

11. Number of previous pregnancies

12. Maternal smoking Never Stopped during pg Smoked throughout Pre-pg wt
-0.77 (0.53)
-0.66 (0.36)
GWG 0-18 wks
0.08 (0.01)
0.00 (0.01)
GWG wks
0.03 (0.01)
-0.03 (0.01)
GWG 28+ wks
0.02 (0.01)
-0.05 (0.01)

13. Genetic variants and GWG
Variants known to be robustly associated with greater adiposity
Both maternal and fetal variants
FTO
MC4R
TMEM18
GNPDA2

14. FTO MC4R TMEM18 and
Mean difference per additional maternal risk allele adjusted for offspring risk score

15. Association of GWG with offspring CVD risk factors
Previous studies showing +ve associations with offspring BMI / fat mass
Varied results with BP
All used two measurements of weight only (one or both retrospectively reported)
None looked at risk factors beyond adiposity & BP
Our findings published (Circulation 2010)

16. Association of GWG with offspring CVD risk factors
Offspring of women with higher than IOM recommended GWG were more adipose and had more adverse CVD risk factor levels; those with lower than IOM recommended GWG were less adipose but had similar CVD risk factor levels to those with recommended IOM GWG.
Offspring of women with greater GWG up to 28 weeks were more adipose and had more adverse CVD risk factor levels
The associations of greater GWG with more adverse offspring CVD risk factor levels were largely mediate by associations with offspring adiposity
Non-linear associations of GWG with outcomes

17. With offspring Asthma Using IOM categories: Using spline estimates:
OR of childhood asthma (vs. =recommended GWG):
< recommended GWG – 1.10 (95%CI: 0.99, 1.26)
> Recommended GWG – 1.05 (95%CI: 0.91, 1.22)
When adjusting for potential confounders
Using spline estimates:
Pre-pregnancy (1.00, 1.01)
No strong assoc. of GWG in 1st and 2nd period with childhood asthma
In late pregnancy (1.10, 1.30)

18. Associations with maternal outcomes
Expectation for positive association with adiposity, but few studies examined this beyond early postnatal period
Other CVD outcomes not studied
Used ‘opportunistic data’ from mothers attending 15+ clinic with their offspring
SBP, DBP (N ~ 2000)
BMI, WC (N = )

19. IOM categories

20. Is pre-pregnancy weight driving associations. i. e
Is pre-pregnancy weight driving associations? i.e. heavier women more likely to exceed recommended weight gain (which is lower for them), and therefore account for the observed association.
In order to examine this we used the splines and stratified by pre-pregnancy overweight

21. Pre-pregnancy 0-18 weeks 18-28 weeks 29+ weeks BMI (kg/m2) 0.34
Pre-preg BMI <25kg/m2
Pre-preg BMI ≥25kg/m2
BMI (kg/m2)
0.34
(0.32, 0.36)
1.43
(0.97, 1.89)
1.58
(1.07, 2.09)
0.16
(-1.46, 1.78)
(-0.10, 0.41)
1.33
(0.47, 2.19)
WC (cm)
0.73
(0.68, 0.78)
3.55
(2.20, 4.90)
4.05
(2.55, 5.56)
1.49
(-3.19, 6.19)
-0.005
(-0.74, 0.73)
2.66
(0.40, 4.91
SBP (mmHg)
0.36
(0.31, 0.42)
0.27
(-1.21, 1.75)
2.29
(0.46, 4.11)
-1.99
(-6.19, 2.21)
0.44
(-0.41, 1.28)
DBP
(mmHg)
0.17
(0.14, 0.20)
-0.08
(-1.00, 0.85)
1.38
(0.22, 2.53)
-2.39
(-4.82, -0.04)
0.05
(-0.48, 0.57)
In mid preg it is the normal weight women in which we see associations.
positive associations of pre-pregnancy weight with all outcomes.
WG in early pregnancy (0-18 weeks) positively associated with BMI and WC.
Mid pregnancy GWG (19-28 weeks) positively associated with BMI, WC in normal weight prior to pregnancy.
LAte pregnancy GWG (29+ weeks) positively associated with BMI, WC in overweight prior to pregnancy.

22. Conclusions
Using repeat measurements of weight suggests a much more complex picture than when IOM categories used
Maternal education, age, parity and smoking related to patterns of GWG, but neither maternal nor fetal ‘fat-related’ genetic variants are.
Greater pre-pregnancy BMI and GWG associated with greater offspring and maternal adiposity in later life and via this with adverse lipids, inflammatory markers and blood pressure in offspring
May be a U-shaped association with offspring asthma

23. Future plans Associations of GWG with:
Cognition in offspring at age 4 and educational achievements at age – Suzi Gage, PhD student.
Cardiovascular risk factors in offspring at age 15, including fasting insulin and glucose – Sumaiya Patel, Post-doc.
Maternal cIMT, DXA determined fat mass, fasting insulin, glucose, and lipids in mothers 17 years post pregnancy – Abi Fraser MRC research fellow
Joint modelling of trajectories of BP and GWG during pregnancy – Corrie MacDonald-Wallis, PhD student.
GWAS to identify genetic variants associated with GWG that could be used to improve causal inference (through MR).

24. Papers
Fraser A, Tilling K, Macdonald-wallis C, Sattar N, Brion M-J, Benfield L, Ness A, Deanfield J, Hingorani A, Nelson SM, Davey Smith G, Lawlor DA. Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood. Circulation 2010;121:
Fraser A, Tilling K, Macdonald-Wallis C, Sattar N, Nelson SM, Lawlor DA. Associations of pre-pregnancy weight and gestational weight gain with mothers’ BMI, waist circumference and blood pressure measured 16 years post-pregnancy: the Avon Longitudinal Study of Parents and Children. Submitted to American Journal of Clinical Nutrition 2011 in press
Lawlor DA, Fraser A, MacDonald-Wallis, Palmer T, Davey Smith G, Tilling K. Maternal and offspring adiposity related genetic variants and gestational weight gain. American Journal of Clinical Nutrition 2011 in press
Fraser A, Tilling K, Henderson J, Grannell R, MacDonald-Wallis C, Lawlor DA. The association of gestational weight gain and offspring asthma. Thorax Submitted February 2011 (under review)
Gage S, Lawlor DA, Tilling K, MacDonald-Wallis C, Fraser A. Gestational weight gain and offspring intelligence: findings from the Avon Longitudinal Study of Parents and Children. Pediatrics Submitted April 2011

25. Acknowledgements Kate Tilling Abigail Fraser Corrie MacDonald-Wallis
US NIH
Wellcome Trust
MRC
British Heart Foundation