Maternal obesity, and weight gain during or after pregnancy, are associated with adverse perinatal outcomes, as well as long-term cardiometabolic disease in the mother and offspring. Previous studies have demonstrated an association between maternal obesity and cardiovascular maladaptation to pregnancy. In turn, poor adaptation to pregnancy has been hypothesised to play an aetiological role in fetal growth restriction and the development of preeclampsia. This thesis aims to investigate the association between maternal weight dynamics and both cardiovascular adaptation to pregnancy and related perinatal outcomes.

First, a meta-analysis was conducted summarising the existing literature on the relationship between interpregnancy weight change and the risk of perinatal complications in a subsequent pregnancy. Interpregnancy weight gain was associated with a higher risk of gestational diabetes, preeclampsia, pregnancy induced hypertension and delivering a largefor- gestational age neonate. In contrast, interpregnancy weight loss was associated with a lower risk of delivering a large-for-gestational age neonate. Body mass index at the start of the first pregnancy modified this association; women with BMI <25kg/m2 had a larger relative increase in risk than women with a BMI ≥25kg/m2.

To further assess the relationship between maternal weight dynamics and the risk of preeclampsia and fetal growth restriction, the Pregnancy Outcome Prediction Study dataset was utilised. This dataset comprised 4212 nulliparous women who attended the Rosie Hospital in Cambridge, UK. Women underwent serial research ultrasound scans at 20-, 28- and 36-weeks gestation, with the clinician and the patient blinded to the outcome. Additionally, pregnancy outcomes including birth weight and perinatal complications were recorded.

In the first study, maternal cardiovascular adaptation to pregnancy was assessed through the physiological drop in uterine and umbilical artery resistance throughout gestation. Obese women had a significantly smaller drop in uterine artery resistance between 20- and 36-weeks’ gestation, compared to normal weight women (change -21.3% [95% confidence interval -18.3, -24.3] versus change -25.7% [-24.3, -27.0], respectively. In contrast, maternal obesity did not affect the drop in physiological resistance in the feto-placental circulation.

The second study aimed to clarify the effect of the timing of gestational weight gain on the risk of perinatal complications. Weight gain during late gestation (28-36 weeks) was associated with a higher risk of developing preeclampsia, whereas weight gain during early gestation (12-28 weeks) was associated with a lower risk of delivering a small for gestational age neonate. Maternal prepregnancy BMI did not modify these associations.

While it is known that maternal obesity is associated with a lower risk of delivering a small for gestational age neonate, the final study tested the hypothesis that maternal obesity is associated with a higher risk of delivering a growth-restricted neonate as opposed to a constitutionally small neonate. Consistent with previous studies, maternal prepregnancy weight was associated with a lower risk of delivering a small for gestational age neonate. However, this association was irrespective of the presence of ultrasonic markers of fetal growth restriction.

In conclusion, maternal obesity is associated with impaired cardiovascular adaptation to pregnancy, although prepregnancy weight was not associated with reduced growth potential in the fetus. The timing of gestational weight gain was key, with late weight gain associated with higher preeclampsia risk and early weight gain with a lower risk of delivering a small for gestational age neonate.