1. Multilevel spline models for blood pressure changes in pregnancy
Corrie Macdonald-Wallis

2. Overview Background and aims
Linear spline models of blood pressure in pregnancy
Adding maternal characteristics as covariates
Modelling weight gain and blood pressure changes in pregnancy together
Summary

3. Blood pressure in pregnancy
Hypertensive disorders of pregnancy are associated with maternal and offspring adverse health outcomes
Aims:
To describe patterns of blood pressure change across pregnancy
To investigate determinants of blood pressure change
To relate gestational weight gain to blood pressure changes

4. ALSPAC
14,541 women living in Avon, UK with expected delivery dates between April 1991 and December 1992 recruited
Routine antenatal BP (median 14 per woman) and weight (median 12 per woman) measurements abstracted from obstetric records
11,789 women with singleton or twin pregnancies who had live term births and no previous diagnosis of hypertension or pre-eclampsia included in BP spline models

5. Linear spline models
Multilevel linear spline models represent trajectories of
change over time with linear slopes between knot points
Patterns of change can be estimated for each individual as each individual has a residual for the intercept and each of the slope parameters
These models have been used to describe childhood
growth trajectories (McCarthy et al, 2007; Howe et al, 2010)

6. Choice of knot points for BP models
Knot points (indicating a change in slope) were chosen by:
Fitting fractional polynomial curves to the data and using the best-fitting curve to estimate approximate locations of knot points
Comparing the fit of spline models to the fractional polynomial curve
Comparing the fit of the spline model predicted values to the actual blood pressure measurements across pregnancy

7. Choice of knot points: fractional polynomial curves
used to find approximate position of knot points in spline models
suggests knot points at around 22, 30 and 36 weeks gestation

8. Linear spline models for BP change
Mean at 8 weeks
(mm Hg)
Average change per week (mm Hg/week)
8-18 weeks
18-30 weeks
30-36 weeks
36+ weeks
SBP
112.2
(111.9, 112.4)
-0.131
(-0.16, -0.10)
0.153
(0.13, 0.17)
0.281
(0.24, 0.32)
1.131
(1.06, 1.20)
DBP
66.0
(65.8, 66.2)
-0.183
(-0.21, -0.16)
0.105
(0.09, 0.12)
0.459
(0.43, 0.49)
1.279
(1.23, 1.33)

9. Determinants of BP change
SBP by maternal BMI
SBP by pregnancy type
Established risk factors for pre-eclampsia: maternal BMI, age, parity, smoking status, education and twin pregnancy included in spline models, mutually-adusted for and a main effect and interaction with each of the splines included: gives an association with blood pressure at 8 weeks (baseline) and rate of change in blood pressure in each of the periods of gestation. Graphs show the predicted bp trajectories by maternal risk factor (in reference category for each of the other risk factors).
model adjusted for maternal pre-pregnancy BMI, age, parity, smoking status, highest educational qualification and pregnancy type

10. Determinants of BP change
SBP by parity
SBP by smoking status
model adjusted for maternal pre-pregnancy BMI, age, parity, smoking status, highest educational qualification and pregnancy type

11. Spline model for gestational weight gain
Fitted by Kate Tilling.
weeks
weeks
Weight gain has 2 knots at 18 and 28 weeks

12. Relationships between weight gain and blood pressure change
Is an increase in weight in one period of pregnancy related to a rise in blood pressure in the next?
Multivariate multilevel spline model with knots at 18, 29 and 36 weeks for SBP and DBP and knots at 18 and 29 weeks for weight
Relationships between rates of change in weight and BP in different periods of pregnancy derived from variance-covariance matrix of the random effects

13. SBP changes by baseline weight/ weight gain up to 18 weeks
Weight at 8 weeks
Weight gain up to 18 weeks

14. SBP changes by weight gain 18-29 weeks and 29+ weeks

15. Summary
Linear spline multilevel models describe patterns of non-linear change in an interpretable way
We were able to explore associations of maternal characteristics with blood pressure changes in different periods of pregnancy
We also modelled three response variables together: SBP, DBP and weight to investigate temporal relationships between changes in weight and blood pressure in pregnancy

16. Future work
Latent class growth models to group particular patterns of blood pressure change during pregnancy – compare these with definitions of gestational hypertension and pre-eclampsia
Relate patterns of change in BP to birth weight of offspring and cardiovascular risk factors measured during childhood in offspring

17. Acknowledgements PhD supervisors: Kate Tilling, University of Bristol
Debbie Lawlor, University of Bristol
Also:
Abigail Fraser, University of Bristol
Scott Nelson, University of Glasgow