Gestational weight gain in a UK cohort: patterns, risk factors and

associations with later mother and offspring health

Debbie A Lawlor (d.a.lawlor@bristol.ac.uk)

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