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Gestational weight gain in a UK cohort: patterns, risk factors and
associations with later mother and offspring health
Debbie A Lawlor ([email protected])
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)
Background
To examine the associations of pre-pregnancy weight and GWG with long term outcomes in mothers and offspring
1. Determinants of GWG
2. Cardiovascular risk factors in offspring at age 9
3. Asthma in offspring at age 7.5
4. BMI, WC and BP in mothers 16 years post-pregnancy
5. Future plans
Aims and Objectives
• 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.
Participants
Statistical methods1. Categorise women according to IOM
categories; using pre-pregnancy BMI and highest gestational weight
2. 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)
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)
12.5-18 0.51 12.9 (-2.0, 30.5)
0.54 (0.14)
Normal weight (18.5-24.9kg/m2)
11.5-16 0.42 12.8 (-2.2, 37.8)
0.53 (0.14)
Overweight (25-29.9kg/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)
---- 18
w
ee
ks
----- 28
w
ee
ks
IOM categories
Less than adequate: 35%Adequate: 38%More than adequate: 27%
6065
7075
80w
eig
ht (
kg)
0 10 20 30 40age
fractional polynomial weight spline weight
Results: Descriptive
DETERMINANTS OF GWG
Maternal Education
60
65
70
75
80
Wei
ght
(kg
)
0 10 20 30 40Gestational age (weeks)
CSE baseline'A' Level Degree
Maternal age
60
65
70
75
80
Wei
ght
(kg
)
0 10 20 30 40Gestational age (weeks)
<20 20-25baseline 30-35>35
Number of previous pregnancies
60
65
70
75
80
Wei
ght
(kg
)
0 10 20 30 40Gestational age (weeks)
baseline 12 >2
Maternal smoking
Genetic variants and GWG
• Variants known to be robustly associated with greater adiposity
• Both maternal and fetal variants• FTO• MC4R• TMEM18• GNPDA2
Mean difference per additional maternal risk allele adjusted for offspring risk score
BMI (kg/m2)
Pre-pregnancy weight (kg)
GWG in 1st period (kg/wk)
GWG in 2nd period (kg/wk)
GWG in 3rd period (kg/wk)
Post natal weight retention (kg)
ID
Study
0.21 (0.12, 0.30)
0.67 (0.38, 0.97)
-0.01 (-0.02, 0.00)
-0.00 (-0.01, 0.00)
0.00 (-0.00, 0.01)
0.05 (-0.07, 0.18)
ES (95% CI)
0.21 (0.12, 0.30)
0.67 (0.38, 0.97)
-0.01 (-0.02, 0.00)
-0.00 (-0.01, 0.00)
0.00 (-0.00, 0.01)
0.05 (-0.07, 0.18)
ES (95% CI)
0-.967 0 .967
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)
• 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
Association of GWG with offspring CVD risk factors
• Using IOM categories:
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 - 1.004 (1.00, 1.01)
No strong assoc. of GWG in 1st and 2nd period with childhood asthma
In late pregnancy - 1.20 (1.10, 1.30)
With offspring Asthma
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 = 1000-1500)
BMI (kg/m2) - low GWG
BMI (kg/m2) - high GWG
WC (cm) - low
WC (cm) - high
SBP (mmHg) - low
SBP (mmHg) - high
DBP (mmHg) - low
DBP (mmHg) - high
ID
Study
-1.52 (-2.07, -0.96)
3.26 (2.63, 3.89)
-2.98 (-4.45, -1.51)
3.11 (1.52, 4.69)
-1.07 (-2.49, 0.34)
3.11 (1.52, 4.69)
-0.48 (-1.36, 0.39)
1.08 (0.10, 2.06)
ES (95% CI)
-1.52 (-2.07, -0.96)
3.26 (2.63, 3.89)
-2.98 (-4.45, -1.51)
3.11 (1.52, 4.69)
-1.07 (-2.49, 0.34)
3.11 (1.52, 4.69)
-0.48 (-1.36, 0.39)
1.08 (0.10, 2.06)
ES (95% CI)
0-4.69 0 4.69
IOM categories
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.
Pre-pregnancy
0-18 weeks
18-28 weeks 29+ weeks
Pre-preg BMI
<25kg/m2
Pre-preg BMI
≥25kg/m2
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)
0.16(-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)
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
Associations of GWG with:• Cognition in offspring at age 4 and educational
achievements at age 15-16 – 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).
Future plans
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;121:2557-2564
• 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
Acknowledgements
• Kate Tilling
• Abigail Fraser
• Corrie MacDonald-Wallis
• US NIH
• Wellcome Trust
• MRC
• British Heart Foundation