L. Foo

Hypertension in Pregnancy: Natural History and Treatment Options

Hypertensive disorders of pregnancy affect approximately 5–10xa0% of all maternities and are major contributors of maternal and neonatal morbidity and mortality worldwide. This group of disorders encompasses chronic hypertension, as well as conditions that arise de novo in pregnancy: gestational hypertension and pre-eclampsia. The latter group is thought to be part of the same continuum but with arbitrary division. Research into the aetiology of hypertension in pregnancy have largely been focused on pre-eclampsia, with a majority of studies exploring either pregnancy-associated factors such as placental-derived or immunologic responses to pregnancy tissue, or maternal constitutional factors such as cardiovascular health and endothelial dysfunction. The evidence base for the pathophysiology and progression of hypertensive disorders in pregnancy, particularly pre-eclampsia, is reviewed. Clinical algorithms and pharmacological agents for the management of hypertension in pregnancy are summarised, with a brief focus on post-partum considerations and long-term health implications. Novel therapeutic options for the management of pre-eclampsia are also explored.

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.

OC07.01: Pre‐conception maternal hemodynamics is associated with subsequent development of pre‐eclampsia (PE) or intrauterine growth restriction (IUGR)

Objectives: Enlargement and abnormal sulcation of the temporal lobes have been described as a hallmark of thanatophoric dysplasia, while less severe abnormalities of the temporal lobes can be seen in achondroplasia or hypochondroplasia. Compared to fetal neurosonography, fetal MRI offers various advantages in the assessment of brain malformations, and may be of value in the prenatal diagnosis of CNS abnormalities in various skeletal dysplasias. The aim of this study was to describe the spectrum of temporal lobe abnormalities in skeletal dysplasias in a perinatal setting, using fetal MRI as well as postnatal in vivo and postmortem brain MRI. Methods: We included 6 cases of thanatophoric dysplasia in which 1,5T or 3T fetal MRI had been performed between GW17 and 23. In 2 of those cases postmortem MRI at 3T and in 3 cases histological analysis with H&E-staining was available and enabled us to correlate postmortem findings with in utero fetal MRI results. In addition we included 1 fetal MRI and 3 postnatal MRI of fetuses with achondroplasia/hypochondroplasia. Results: Enlargement of the temporal lobes with abnormal sulcation was seen in all 6 subjects of thanatophoric dysplasia in fetal MRI and was confirmed in 2 cases with postmortem MRI and in 3 cases at autopsy. Abnormalities in the 4 subjects with achondroplasia/hypochondroplasia included bilateral or unilateral sagittalisation of the parahippocampal sulcus, seen both in fetal MRI as well as in postnatal MRI. Conclusions: Temporal lobe abnormalities of different severities can be an independent marker of the presence of a skeletal dysplasia, as seen both in thanatophoric dysplasia as well as achondroplasia/hypochondroplasia.

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.

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.

OP21.01: Pre-pregnancy exercise stress testing is related to normal physiological adaptation from pre-pregnancy to mid-pregnancy

Objectives: Uterine sarcoma is a rare disease with a poor prognosis, and its preoperative diagnosis is difficult. The author previously presented the finding that a tumour with high tumour-to-subcutaneous fat signal intensity ratio on MRI T2 weighted imaging (TFSIR) and low ADC is highly suspected of sarcoma. However, its sensitivity and specificity are not high enough to diagnose sarcoma. The purpose of this study is to improve the preoperative diagnostic reliability through further investigation of previous and additional cases. Methods: MRI was performed in 6 cases (7 tumours) of uterine sarcoma in the last 3 years (sarcoma group), and in 31 cases of leiomyoma in 2015 (myoma group) at the author’s hospital. TFSIR and ADC were calculated and compared between 2 groups. The cut-off values of these parameters to predict sarcoma were also calculated. Finally, a preoperative prediction method using both of these parameters was considered through the application to the 40 tumours which were examined in 2016. Results: The sarcoma group had significantly higher TFSIR than the leiomyoma group (p<0.01). The minimum cut-off value of TFSIR to diagnose sarcoma was 0.515 (sensitivity: 100%, specificity: 94%). The sarcoma group had significantly lower ADC values than the leiomyoma group (p<0.01). The maximum cut-off value of ADC to diagnose sarcoma was 1.280 (sensitivity: 86%, specificity: 87%). All tumours with both positive TFSIR and ADC were sarcoma (High Suspicion group). All tumours with negative TFSIR were leiomyoma (Low Suspicion group). Tumours with positive TFSIR and negative ADC included both sarcomas and leiomyomas (Intermediate Suspicion group). Among 40 uterine tumours in 2016, two (5.0%) belonged to the High Suspicion group (all sarcoma), three (7.5%) belonged to the Intermediate Suspicion group (all leiomyoma), and the other 35 tumours (87.5%) belonged to the Low Suspicion group (all leiomyoma). Conclusions: Preoperative prediction of uterine sarcoma is possible using both TFSIR and ADC scores on MRI.

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.

P05.08: Differences in pre-pregnancy stress response between healthy and PE/FGR pregnancies

Methods: Serum s-Flt-1 and PlGF and their ratio pre-eclamptic index (PEI) were measured in a case-control study of patients that developed PE before or after 34 weeks and unaffected controls. Pre-eclampsia was defined by blood pressure > 140/90mmHg and proteinuria > 300mg/24h. We analysed s-Flt-1 and PlGF (Brahms Kryptor). PEI was calculated for patients before and after 34 weeks of pregnancy. We observed gestational age at delivery (GA), incidence of PE, HELLP syndrome, FGR, SGA, IUFD and perinatal outcomes. Statistical analysis was performed using IBM SPSS Statistics 24. Results: Our study included 339 patients. Average maternal age was 32.9 years, average BMI 24.9, 43% was primigravids and 56% was nulliparous. Patients with subsequent adverse outcomes (n=87) had significantly higher sFlt-1, lower PlGF and higher PEI than women without adverse outcomes (n=252), p<0.001. PEI ratio correlated with prematurity. GA was significantly lower in the PE group: 34.7 vs 39.5 weeks, p<0.001. We calculated a cut-off for PEI ratio (>300) with good sensitivity and specificity for prediction of early PE. This cut-off shows good prediction value (AUC 0.86) for measurements by Brahms Kryptor. Conclusions: Our study shows that previously published PEI cut-off levels did not improve pre-eclampsia detection when measuring sFlt-1/PlGF ratio with Brahms Kryptor in our setting. We propose cut-off (PEI > 300) that shows high diagnostic accuracy for early PE. Further analysis is needed.

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 (ACu2009<u200910th 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 4.99u2009l/min and 5.65u2009l/min in healthy pregnancies (pu2009=u20090.08). Mean TPR (dyn.s.cm−5) was 0.95 in FGR and 0.83 in healthy pregnancies (pu2009=u20090.05). 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 (biasu2009±u20091.96 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 erroru2009<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 –0.12u2009l/min. 95% limits of agreement were betweenu2009+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.