J. Tay

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

BACKGROUND Preeclampsia and fetal growth restriction 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 preeclampsia considered to be phenotypically distinct. Recent studies have reported conflicting findings in relation to cardiovascular function, and in particular cardiac output, in preeclampsia and fetal growth restriction. OBJECTIVE We conducted this study to examine the possible relation between cardiac output and peripheral vascular resistance in preeclampsia and fetal growth restriction. STUDY DESIGN We investigated maternal cardiovascular function in relation to clinical subtype in 45 pathological pregnancies (14 preeclampsia only, 16 fetal growth restriction only, 15 preeclampsia and fetal growth restriction) and compared these with 107 healthy person observations. Cardiac output was the primary outcome measure and was assessed using an inert gas‐rebreathing method (Innocor), from which peripheral vascular resistance was derived; arterial function was assessed by Vicorder, a cuff‐based oscillometric device. Cardiovascular parameters were normalized for gestational age in relation to healthy pregnancies using Z scores, thus allowing for comparison across the gestational range of 24–40 weeks. RESULTS Compared with healthy control pregnancies, women with preeclampsia had higher cardiac output Z scores (1.87 ± 1.35; P = .0001) and lower peripheral vascular resistance Z scores (–0.76 ± 0.89; P = .025); those with fetal growth restriction had higher peripheral vascular resistance Z scores (0.57 ± 1.18; P = .04) and those with both preeclampsia and fetal growth restriction had lower cardiac output Z scores (–0.80 ± 1.3 P = .007) and higher peripheral vascular resistance Z scores (2.16 ± 1.96; P = .0001). These changes were not related to gestational age of onset. All those affected by preeclampsia and/or fetal growth restriction had abnormally raised augmentation index and pulse wave velocity. Furthermore, in preeclampsia, low cardiac output was associated with low birthweight and high cardiac output with high birthweight (r = 0.42, P = .03). CONCLUSION Preeclampsia is associated with high cardiac output, but if preeclampsia presents with fetal growth restriction, the opposite is true; both conditions are nevertheless defined by hypertension. Fetal growth restriction without preeclampsia is associated with high peripheral vascular resistance. Although early and late gestation preeclampsias are considered to be different diseases, we show that the hemodynamic characteristics of preeclampsia were unrelated to gestational age at onset but were strongly associated with the presence or absence of fetal growth restriction. Fetal growth restriction more commonly coexists with preeclampsia at early gestation, thus explaining the conflicting results of previous studies. Furthermore, antihypertensive agents act by reducing cardiac output or peripheral vascular resistance and are administered without reference to cardiovascular function in preeclampsia. The underlying pathology (preeclampsia, fetal growth restriction, preeclampsia and fetal growth restriction) defines cardiovascular phenotype, providing a rational basis for choice of therapy in which high or low cardiac output or peripheral vascular resistance is the predominant feature.

Use of magnesium sulfate in preterm deliveries for neuroprotection of the neonate

The prevalence of preterm birth is increasing and owing to advances in neonatal care, more infants are surviving. However, in parallel with this, the incidence of cerebral palsy (CP) is also rising. Magnesium sulfate (MgSO4) is currently recommended for use in women who are at risk of giving birth at less than 30–32 weeks of gestation for neuroprotection of their infants. The exact mechanism of action remains unclear. Meta‐analyses report encouraging results that are consistent with a modest but tangible benefit for the use of MgSO4, and suggest a number needed to treat (NNT) to prevent one in 46 cases of CP in infants born preterm before 30 weeks of gestation and one in 63 cases of CP in infants born preterm before 34 weeks of gestation.

OP19.09: Fetal middle cerebral artery Doppler impedance is not related to maternal hemodynamic function: Short oral presentation abstracts

L. Youssef1, J. Miranda2, C. Paules2, F. Crovetto2, F. Figueras2, E. Eixarch2, A. Nadal1, C. Rovira3, F. Crispi2, E. Gratacós2 1Pathology, Hospital Clinic-IDIBAPS, Barcelona, Spain; 2BC Natal, Barcelona, Centre for Maternal-Fetal and Neonatal Medicine (Hospital Clı́nic and Hospital Sant Joan de Deu) and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain; 3Pathology, Hospital Sant Joan de Deu, Barcelona, Spain

Uterine and fetal placental Doppler indices are associated with maternal cardiovascular function

BACKGROUND: The mechanism underlying fetal‐placental Doppler index changes in preeclampsia and/or fetal growth restriction are unknown, although both are associated with maternal cardiovascular dysfunction. OBJECTIVE: We sought to investigate whether there was a relationship between maternal cardiac output and vascular resistance and fetoplacental Doppler findings in healthy and complicated pregnancy. STUDY DESIGN: Women with healthy pregnancies (n=62), preeclamptic pregnancies (n=13), preeclamptic pregnancies with fetal growth restriction (n=15), or fetal growth restricted pregnancies (n=17) from 24–40 weeks gestation were included. All of them underwent measurement of cardiac output with the use of an inert gas rebreathing technique and derivation of peripheral vascular resistance. Uterine and fetal Doppler indices were recorded; the latter were z scored to account for gestation. Associations were determined by polynomial regression analyses. RESULTS: Mean uterine artery pulsatility index was higher in fetal growth restriction (1.37; P=.026) and preeclampsia+fetal growth restriction (1.63; P=.001) but not preeclampsia (0.92; P=1) compared with control subjects (0.8). There was a negative relationship between uterine pulsatility index and cardiac output (r2=0.101; P=.025) and umbilical pulsatility index z score and cardiac output (r2=0.078; P=.0015), and there were positive associations between uterine pulsatility index and peripheral vascular resistance (r2=0.150; P=.003) and umbilical pulsatility index z score and peripheral vascular resistance (r2= 0.145; P=.001). There was no significant relationship between cardiac output and peripheral vascular resistance with cerebral Doppler indices. CONCLUSION: Uterine artery Doppler change is abnormally elevated in fetal growth restriction with and without preeclampsia, but not in preeclampsia, which may explain the limited sensitivity of uterine artery Doppler changes for all these complications when considered in aggregate. Furthermore, impedance within fetoplacental arterial vessels is at least, in part, associated with maternal cardiovascular function. This relationship may have important implications for fetal surveillance and would inform therapeutic options in those pathologic pregnancy conditions currently, and perhaps erroneously, attributed purely to placental maldevelopment. Uterine and fetal placental Doppler indices are associated significantly with maternal cardiovascular function. The classic description of uterine and fetal Doppler changes being initiated by placental maldevelopment is a less plausible explanation for the pathogenesis of the conditions than that relating to maternal cardiovascular changes.

OP05.04: Cross‐sectional comparison of two techniques for the non‐invasive measurement of cardiac output in and outside pregnancy

imaging) to obtain the fetal uterus in frontal view after rotation of the different axis. Results: During the study period, a total of 29 patients were included after identification of the female fetal external genitals. In 29 fetuses. the volume was acquired by a sagittal posterior view. The volume was assessed for 27 fetuses (93%). For every fetus, the fetal uterus was visualised through a 3D rendered coronal view the Multiplanar-triplan mode and VCI. Conclusions: This study demonstrated the ability to visualised fetal uterus through a 3D rendered coronal view. Based upon the reproducibility of the procedure, we should need to investigate prospectively the intra and inter operator reliability. Due to the potential functional issues associated with such anomalies of the uterus (infertility, hydrometrocolpos) and its association with renal anomalies, there is a clinical value in looking at the fetal pelvis, and thus, to establish a standardised view of the fetal pelvis floor.

EP14.21: Longitudinal comparison of two techniques for non-invasive measurement of cardiac output from pre-conception to postpartum

Objectives: To determine if fetal liver length measured at 14 to 40 weeks gestational age is significantly greater in diabetic Filipino mothers compared to non-diabetic Filipino mothers. Methods: A total of 160 pregnant women with a live singleton pregnancy between 14 to 28 weeks gestational age, seen at the Obstetrics Out-patient Department Unit-Clinical Division of the University of Santo Tomas Hospital, were included in the study. Subjects were classified into non-diabetic (122 subjects) and diabetic (38 subjects). Diabetic subjects (84% were diet-controlled) were further classified into having gestational diabetes (32 subjects) and overt diabetes (6 subjects). All subjects underwent two sonographic measurements of the fetal liver length by a single sonographer, who was blinded as to the glycemic status of the subject. Measurements were analysed using t-test to compare liver lengths between non-diabetic and diabetic subjects. Results: Analysis showed that liver lengths for diabetic subjects were larger compared to non-diabetic subjects, but was only significantly in the overt diabetic group. Conclusions: The fetal liver lengths of overt diabetic Filipino mothers at 14 to 40 weeks gestational age were significantly larger compared to non-diabetics. There was no statistical difference in fetal liver lengths in those with gestational diabetes and those who were non-diabetic.

F3. Cardiac output and total peripheral resistance in pregnancies with fetal growth restriction

Abstract Introduction: This pilot study aims to compare cardiac output (CO) and total peripheral resistance (TPR) in pregnancies with fetal growth restriction (FGR) with healthy normal third trimester of pregnancies. Most studies previously done on cardiac parameters in pregnancy focused mainly on pre-eclampsia (PE) and FGR with PE, but not in normotensive FGR women. Methods: Eight pregnancies with FGR (AC < 10th percentile with raised umbilical PI) in the third trimester (27–35 weeks gestation) compared with 42 uncomplicated ongoing pregnancies within similar gestation bands. CO was measured non-invasively using INNOCOR inert gas re-breathing technique, with the participant standing upright. TPR was measured by the Vicorder device with women in the left lateral position. Unpaired t-test is used to calculate the p values among these groups. Results: Mean CO in pregnancies with FGR was 4.99 l/min and 5.65 l/min in healthy pregnancies (p = 0.08). Mean TPR (dyn.s.cm−5) was 0.95 in FGR and 0.83 in healthy pregnancies (p = 0.05). See Charts. Conclusions: There is no significant difference in CO between the two groups but TPR is higher in fetal growth restriction. This would support the theory of a hypodynamic circulation affecting these pregnancies, suggesting maternal cardiovascular maladaptation. It is worth noting that the numbers of patients in this early work are still small; however, the general trend does reflect that of the finding of Valensise et al. [1]. We plan to determine CO and TPR in relation to both gestation of onset and clinical deterioration prompting delivery. By characterizing these cardiovascular changes and their timing might allow for future intervention to modify cardiovascular function and plan optimal time of delivery.

B2. Measurement of cardiac output in a healthy pregnancy cohort: comparison of vicorder and inert gas re-breathing technique (Innocor).

Abstract Introduction: There are multiple modalities used to measure cardiac output in pregnancy. The accepted gold standard is cardiac catheterisation, then measurement via direct Fick method or thermo-dilution. These methods are invasive and not feasible for assessment of healthy pregnant women. There are several non-invasive devices widely used to measure cardiac output including Innocor, an inert gas re-breathing technique which has been validated against thermodilution [1–3] and direct Fick methods [4,5] for measurement of pulmonary blood flow and thus, cardiac output. Measurements of cardiac output by non-invasive cuff-based device (Vicorder) has been validated against Innocor [6], however, this was in a health non-pregnant cohort, and validation between these two devices has not been previously reported in a pregnancy cohort. Methods: Healthy women who were recruited as part of a preconception cohort undergoing comprehensive cardiovascular measurements were seen at 6, 10, 22 and 34 weeks of pregnancy once they had conceived. In total, there were 40 women seen at each gestation band, giving a total of 160 measurements. For each, cardiac output was measured in the left lateral lying position using the Vicorder and Innocor device. All the measurements were performed by one assessor. All statistical analyses were carried out using SPSS and MedCalc. Agreement between both methods of cardiac output estimation was assessed using Bland Altman plots and statistics (Mean cardiac output, bias (mean difference), limits of agreement (bias ± 1.96 SD of bias) and percentage error ((1.96 SD of bias/mean CO) X 100%) and intra-class correlation (ICC). A low bias indicating accuracy, narrow limits of agreement with percentage error <30% reflecting precision and ICC 40.7 are considered to reflect good agreement between two methods of CO determination. Results: Bias between the two methods was –0.12 l/min. 95% limits of agreement were between +2.5184 and –2.7716. Percentage error was 41%. ICC between both methods of assessment was 0.597. Conclusions: While bias is low, percentage error and ICC indicate only moderate agreement between Innocor and Vicorder for CO measurements.

D5. Is maternal arterial function impaired in pregnancies with fetal growth restriction

Abstract Introduction: Studies in pre-eclampsia have demonstrated that central haemodynamic changes give more insight than peripheral measures into maternal cardiac and vascular physiology. This study aims to investigate augmentation index (AIX) and pulse wave velocity (PWV) in pregnancies affected by fetal growth restriction (FGR) and compare them to healthy women in the third trimester of pregnancy. Augmentation index (AIx) is a measure of systemic arterial stiffness derived from the ascending aortic pressure waveform. PWV is widely used as measure of arterial stiffness and predictor of future cardiovascular risk outside pregnancy. Methods: Eight pregnancies with fetal growth restriction (AC < 10th percentile and raised umbilical PI) in the third trimester (27–35 weeks gestation) were compared with 42 healthy pregnancies in similar gestation band. AIX and PWV were measured by the Vicorder device with women in the left lateral position. Unpaired t-test was used to calculate the p values amongst these groups. Results: The mean AIX in pregnancies with FGR was 22.63 compared to 10.10 in healthy pregnancies (p = 0.0005). PWV was 8.15 in the FGR group compared to 7.08 in healthy controls (p = 0.004). See charts. Conclusions: These results show that pregnancies affected by third trimester FGR in the absence of pre-eclampsia show impairment of maternal arterial function with high arterial stiffness. To date, many studies have shown impaired maternal arterial function in preeclampsia but little has been done to characterize maternal arterial function in fetal growth restriction alone. Considering both these conditions are thought to have common underlying etiology, these results suggest that arterial function is impaired in fetal growth restriction independent of hypertension or pre-eclampsia. Characterization of arterial profile could play an important role in the understanding of the etiology of this condition which has hitherto been ascribed purely to placental dysfunction.