Cardiac output in pre eclampsia is associated with the presence of fetal growth restriction, not gestation at onset: a prospective cohort study

BACKGROUND AND OBJECTIVES: Pre-eclampsia (PE) and fetal growth restriction (FGR) are considered to be placentally-mediated disorders. The clinical manifestations are widely held to relate to gestation age at onset with early- and late-onset PE considered to be phenotypically distinct. Recent studies have reported conflicting findings in relation to cardiovascular function, and in particular cardiac output, in PE and FGR. STUDY DESIGN: We investigated maternal cardiovascular function in relation to clinical subtype in 45 pathological pregnancies (14 'PE only', 16 'FGR only', 15 'PE and FGR') and compared these with 107 healthy person observations. Cardiac output (CO) was the primary outcome measure, and was assessed using an inert gas rebreathing method (Innocor®), from which peripheral vascular resistance was derived (PVR); arterial function was assessed by Vicorder ®, a cuff-based oscillometric device. Cardiovascular parameters were normalised for gestational age in relation to healthy pregnancies using Z scores, thus allowing for comparison across the gestational range 24-40 weeks. RESULTS: Compared with healthy control pregnancies, women with PE had higher CO Z scores (1.87 ± 1.35; p=0.0001) and lower PVR Z scores (-0.76± 0.89; p=0.025); those with FGR had higher PVR Z scores (0.57± 1.18; p=0.04) and those with both PE and FGR had lower CO Z scores (-0.80 ± 1.3; p= 0.007) and higher PVR Z scores (2.16 ± 1.96; p=0.0001). These changes were not related to gestational age of onset. All those affected by PE and/or FGR had abnormally raised augmentation index (AIx) and pulse wave velocity (PWV). Furthermore, in PE, low CO was associated with low birthweight and high CO with high birthweight. (r=0.42, p=0.03). CONCLUSIONS: PE is associated with high CO, but if PE presents with FGR, the opposite is true; both conditions are, nevertheless, defined by hypertension. FGR without PE is associated with high PVR. Though 'early' and 'late' gestation PE are considered to be different diseases, we show that the haemodynamic characteristics of PE were unrelated to gestation age at onset, but strongly associated with the presence or absence of FGR. FGR more commonly co-exists with PE at early gestation, thus explaining the conflicting results of previous studies. Furthermore, anti-hypertensive agents act by reducing CO or PVR and are administered without reference to cardiovascular function in PE. The underlying pathology (PE, FGR, PE and FGR) defines cardiovascular phenotype, providing a rational basis for choice of therapy where high or low CO or PVR are the predominant features