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

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

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

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

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)

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

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

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)

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

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

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

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

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

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

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

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

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