Effect of a nitric oxide donor on maternal hemodynamics in fetal growth restriction.

OBJECTIVE: To evaluate the effect on maternal cardiovascular parameters of treatment with a nitric oxide (NO) donor and plasma volume expansion in pregnancies complicated by fetal growth restriction (FGR). METHODS: Twenty-six pregnant women with a diagnosis of FGR were treated with transdermal patches of a NO donor and plasma volume expansion by co-administration of oral fluids. We compared the treated group to a historical control group of untreated FGR patients. Hemodynamic indices were obtained using the UltraSonic Cardiac Output Monitor system. RESULTS: At diagnosis, the two groups were similar in terms of maternal and hemodynamic characteristics. In the treated group, we found a significant increase in maternal cardiac output and stroke volume and a decrease in systemic vascular resistance after 2 weeks of therapy. No significant differences were found 2 weeks after diagnosis in the untreated group. The treated group delivered infants with higher birth-weight centile than did the untreated control group. CONCLUSIONS: The combined therapeutic approach of NO donor administration and plasma volume expansion in FGR apparently improves significantly maternal hemodynamic indices. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Maternal hemodynamics early in labor: a possible link with obstetric risk?

OBJECTIVE: To determine if hemodynamic assessment in 'low-risk' pregnant women at term with an appropriate-for-gestational age (AGA) fetus can improve the identification of patients who will suffer maternal or fetal/neonatal complications during labor. METHODS: This was a prospective observational study of 77 women with low-risk term pregnancy and AGA fetus, in the early stages of labor. Hemodynamic indices were obtained using the UltraSonic Cardiac Output Monitor (USCOM® ) system. Patients were followed until the end of labor to identify fetal/neonatal and maternal outcomes, and those which developed complications of labor were compared with those delivering without complications. RESULTS: Eleven (14.3%) patients had a complication during labor: in seven there was fetal distress and in four there were maternal complications (postpartum hemorrhage and/or uterine atony). Patients who developed complications during labor had lower cardiac output (5.6 ± 1.0 vs 6.7 ± 1.3 L/min, P = 0.01) and cardiac index (3.1 ± 0.6 vs 3.5 ± 0.7 L/min/m2 , P = 0.04), and higher total vascular resistance (1195.3 ± 205.3 vs 1017.8 ± 225.6 dynes × s/cm5 , P = 0.017) early in labor, compared with those who did not develop complications. Receiver-operating characteristics curve analysis to determine cut-offs showed cardiac output ≤ 5.8 L/min (sensitivity, 81.8%; specificity, 69.7%), cardiac index ≤ 2.9 L/min/m2 (sensitivity, 63.6%; specificity, 76.9%) and total vascular resistance > 1069 dynes × s/cm5 (sensitivity, 81.8%; specificity, 63.6%) to best predict maternal or fetal/neonatal complications. CONCLUSIONS: The study of maternal cardiovascular adaptation at the end of pregnancy could help to identify low-risk patients who may develop complications during labor. In particular, low cardiac output and high total vascular resistance are apparently associated with higher risk of fetal distress or maternal complications. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Restricted physical activity in pregnancy reduces maternal vascular resistance and improves fetal growth.

OBJECTIVES: To test the efficacy of maternal activity restriction for reducing peripheral vascular resistance in normotensive pregnant women with raised total vascular resistance (TVR) and to evaluate its effect on fetal growth. METHODS: This was a prospective case-control study of 30 women enrolled between 27 and 29 weeks' gestation. All patients met the following criteria: normal blood pressure before and during pregnancy, TVR between 1300 and 1400 dynes × s/cm5 at enrolment, normal fetal Doppler parameters at enrolment and abdominal circumference between the 10th and 25th centiles. Patients were assigned to activity restriction (activity-restriction group; n = 15) or no treatment (control group; n = 15) and were assessed after 4 weeks for TVR and fetal growth. RESULTS: TVR at enrolment and estimated fetal weight centile were similar in the activity-restriction group vs controls (1358 ± 26 vs 1353 ± 30 dynes × s/cm5 ; 18th ± 4 vs 19th ± 4 centile; P = NS). After 4 weeks, the activity-restriction group compared with controls showed significantly lower TVR (1165 ± 159 vs 1314 ± 190 dynes × s/cm5 ; P < 0.05), which was associated with higher estimated fetal weight centile (25th ± 5 vs 20th ± 5 centile; P < 0.05). TVR was lower and estimated fetal weight centile higher for the activity-restriction group after 4 weeks compared with at enrolment. CONCLUSIONS: In normotensive pregnant women with raised TVR, maternal activity restriction appears to be effective in reducing TVR and therefore enhancing fetal growth. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Correlation between maternal body composition and haemodynamic changes in pregnancy: different profiles for different hypertensive disorders.

OBJECTIVES: To assess and correlate changes in body composition and haemodynamic function during pregnancy. To identify different haemodynamic profiles based on the onset of hypertensive diseases such as gestational hypertension and preeclampsia. METHODS: We enrolled 265 healthy, normotensive pregnant women throughout pregnancy (from 6+0 to 36+0weeks). They were subjected to assessment of body composition and haemodynamic function using non-invasive methods. We divided our population in three groups: group A with physiological pregnancy, group B with gestational hypertension and group C with preeclamptic patients. RESULTS: In patients who developed gestational hypertension we found lower total body water (TBW) percentage, higher Fat Mass (FM), associated with lower Cardiac Output (CO) and higher Total Vascular Resistance (TVR) during the second trimester. In the third trimester we didn't find haemodynamic differences, but a significative increase in extracellular water (ECW) percentage. In patients who developed preeclampsia we found since the first trimester significative higher TVR and hypodynamic circulation, associated with lower FM percentage. CONCLUSIONS: Assessment of body composition and maternal cardiac function may help to identify earlier in pregnancy, patients with different (mal) adaptations to pregnancy. Women with high TVR, hypodynamic circulation and low fat mass during the first trimester, might be at higher risk to develop preeclampsia. Patients with higher BMI and FM percentage, and increased TVR in the second trimester, might be at risk of gestational hypertension and excessive fluid retention at the end of pregnancy.

Screening for pre-eclampsia in the first trimester: role of maternal hemodynamics and bioimpedance in non-obese patients.

OBJECTIVE: To test if maternal hemodynamics and bioimpedance, assessed at the time of combined screening for PE, are able to identify in the first trimester of gestation normotensive non-obese patients at risk for pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR). METHODS: One hundred and fifty healthy nulliparous non-obese women (body mass index < 30 kg/m2 ) in the first trimester of pregnancy underwent assessment by UltraSonic Cardiac Output Monitor (USCOM) to detect hemodynamic parameters, bioimpedance analysis to characterize body composition, and combined screening for PE (assessment of maternal history, biophysical and maternal biochemical markers). Patients were followed until term, noting the appearance of PE and/or IUGR. RESULTS: One hundred and thirty-eight patients had an uneventful pregnancy (controls), while 12 (8%) developed complications (cases). USCOM showed, in cases compared with controls, lower cardiac output (5.6 ± 0.3 vs 6.7 ± 1.1 L/min, P < 0.001), lower inotropy index (1.54 ± 0.38 vs 1.91 ± 0.32 W/m2 , P < 0.001) and higher total vascular resistance (1279.8 ± 166.4 vs 1061.4 ± 179.5 dynes × s/cm5 , P < 0.001). Bioimpedance analysis showed, in cases compared with controls, lower total body water (53.7 ± 3.3% vs 57.2 ± 5.6%, P = 0.037). Combined screening was positive for PE in 8% of the controls and in 50% of the cases (P < 0.001). After identification of cut-off values for USCOM and bioimpedance parameters, forward multivariate logistic regression analysis identified as independent predictors of complications in pregnancy the inotropy index (derived by USCOM), fat mass (derived from bioimpedance analysis) and combined screening. CONCLUSIONS: Combined screening for PE and assessment of bioimpedance and maternal hemodynamics can be used to identify early markers of impaired cardiovascular adaptation and body composition that may lead to complications in the third trimester of pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Preterm delivery and elevated maternal total vascular resistance: signs of suboptimal cardiovascular adaptation to pregnancy?

OBJECTIVE: To evaluate the maternal hemodynamic profile in women with a diagnosis of threatened preterm delivery (TPD) in order to understand the possible pathophysiologic mechanism leading to an increased lifetime risk for future cardiovascular disease. METHODS: Patients with a diagnosis of TPD were enrolled and assessed using a non-invasive method (USCOM® ) for the determination of hemodynamic parameters. Vaginal and rectal swabs were taken, cervical length, blood inflammatory indices, fetal blood-vessel Doppler velocimetry were measured and gestational age at the time of delivery and neonatal outcomes were noted. RESULTS: A total of 68 patients were enrolled and included in the analysis. The population was divided into two groups according to total vascular resistance (TVR): Group A with a TVR of ≤ 1000 dynes × s/cm5 (n = 48) and Group B with a TVR of > 1000 dynes × s/cm5 (n = 20). C-reactive protein (CRP) was higher in Group B than in Group A, suggesting a systemic inflammation status. Group B delivered earlier (32 + 4 weeks vs 38 + 2 weeks; P < 0.01) and neonatal outcome was worse than in Group A. Significantly lower values of cardiac output, stroke volume, peak velocity of flow, velocity time integral, minute distance, stroke volume index, cardiac index, stroke work, cardiac power, inotropy index and potential-to-kinetic energy ratio were observed in Group B than in Group A. CONCLUSIONS: Women with a diagnosis of TPD showing TVR values of > 1000 dynes × s/cm5 and elevated levels of CRP are at high risk of preterm delivery. An impaired maternal cardiovascular adaptation during pregnancy in these patients might suggest a possible higher risk for subsequent future cardiovascular disease. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Assessment of total vascular resistance and total body water in normotensive women during the first trimester of pregnancy. A key for the prevention of preeclampsia.

INTRODUCTION: Maternal cardiovascular system adapts to pregnancy, thanks to complex physiological mechanisms that involve cardiac output, total vascular resistance and water body distribution. Abnormalities of these adaptive mechanisms are connected with hypertensive disorders. OBJECTIVE: To identify patients at a high risk of developing hypertensive complications of pregnancy during the first trimester of pregnancy, through the use of non-invasive methods such as USCOM (Ultrasonic Cardiac Output Monitor) and Bioimpedance. MATERIALS AND METHODS: We enrolled 120 healthy normotensive women during the first trimester of pregnancy obtaining all measurements with the USCOM system and Bioimpedance. RESULTS: 20 patients were excluded for a bad USCOM signal. The remaining patients (n = 100) were retrospectively divided into two groups: Group A (n = 75) TVR<1200 dynes s cm(-5), Group B (n = 25) TVR>1200 dynes s cm(-5). No statistically significant difference was identified in terms of water distribution, Fat Free Mass, Systolic/Diastolic Blood Pressure, Heart Rate, Hematocrit, Flow Time Corrected and Water Balance Index between the two groups. In contrast, higher values of the Cardiac Output, Stroke Volume, Fat Mass and Inotropy Index have been highlighted in the Group A. Moreover, in the Group A we found a better maternal-neonatal outcome and a lower incidence of hypertensive complications. CONCLUSIONS: High TVR during the first weeks of gestation may be an early marker of cardiovascular maladaptation more than the evaluation of water distribution and, in particular, with respect to the single blood pressure assessment. Moreover lower values of Inotropy Index could be an indicative of the worst cardiac performance.

Left ventricular midwall mechanics at 24 weeks' gestation in high-risk normotensive pregnant women: relationship to placenta-related complications of pregnancy.

OBJECTIVES: Most studies during pregnancy have assessed maternal left ventricular (LV) function by load-dependent indices, assessing only chamber function. The aim of this study was to assess afterload-adjusted LV myocardial and chamber systolic function at 24 weeks' gestation and 6 months postpartum in high-risk normotensive pregnant women. METHODS: A group of 118 high-risk women with bilateral notching of the uterine arteries underwent an echocardiographic examination to evaluate midwall mechanics (midwall shortening (mFS%) and stress-corrected midwall shortening (SCmFS%)) of the LV at 24 weeks' gestation and 6 months postpartum. Patients were followed until delivery and pregnancies were classified retrospectively as uneventful (uncomplicated outcome) or complicated. A control group of 54 low-risk women with uneventful pregnancies without bilateral notching was also enrolled. RESULTS: The pregnancy was uneventful in 74 (62.7%) women, whereas 44 (37.3%) developed complications. At 24 weeks' gestation, mFS% and SCmFS% were greater in the uncomplicated-outcome compared with the complicated-outcome group (25.9 ± 4.8 vs 18.8 ± 5.0%, P < 0.001 and 107.9 ± 18.4 vs 77.9 ± 20.7%, P < 0.001, respectively). At 6 months postpartum, SCmFS% remained greater in the uncomplicated-outcome compared with the complicated-outcome group (100.4 ± 21.6 vs 87.8 ± 19.1, P < 0.05). In the uncomplicated-outcome group, SCmFS% was higher during pregnancy than it was postpartum, whereas in the complicated-outcome group, it was lower during pregnancy than it was postpartum (P < 0.05). CONCLUSIONS: Maternal cardiac midwall mechanics appear to be enhanced (SCmFS% increased compared with controls) during pregnancy compared with postpartum in high-risk patients with uncomplicated pregnancy, whereas midwall mechanics are depressed both during pregnancy and postpartum in patients with pregnancy complications.

Medical treatment of early-onset mild gestational hypertension reduces total peripheral vascular resistance and influences maternal and fetal complications.

OBJECTIVE: Complications in early-onset mild gestational hypertension (GH) are better predicted by total peripheral vascular resistance (TPVR) > 1350 dyne than by blood pressure. We therefore aimed to assess the possible reduction of severe complications by lowering TPVR with nitric oxide (NO) donors, oral fluids and standard antihypertensive therapy in women with early-onset mild GH. METHODS: A group of 400 patients with early-onset (20-27 weeks' gestation) mild GH (systolic and diastolic blood pressure < 170/110 mmHg) and TPVR > 1350 dyne were enrolled in a prospective non-randomized trial with sequential allocation: 100 patients were treated with nifedipine (Group A); 100 with nifedipine and NO donors (Group B); 100 with nifedipine and oral fluids (Group C); and 100 with nifedipine, NO donors and oral fluids (Group D). TPVR was checked 1 month after initiation of therapy, and the number of patients with severe maternal and fetal complications was recorded in each group. The relationship between reduction in TPVR and the frequency of severe complications was assessed. RESULTS: Severe complications developed in 51% of patients in Group A, 48% in Group B, 53% in Group C and 35% in Group D, the frequency in Group D being significantly lower than that in the other treatment groups (P < 0.05). A reduction in TPVR of < 15% predicted the occurrence of severe complications with sensitivity 95.2% and specificity 88.3%. In Group D a reduction in TPVR of ≥ 15% was more probable (odds ratio (OR) = 2.03; 95% CI, 1.15-3.60; P < 0.015) and severe complications were less probable (OR = 0.52; 95% CI, 0.29-0.91; P < 0.023). CONCLUSION: In women with early-onset mild GH, combined treatment with NO donors, oral fluids and nifedipine optimally reduces TPVR and seems to reduce maternal and fetal complications.

The maternal cardiovascular effect of carbetocin compared to oxytocin in women undergoing caesarean section.

OBJECTIVE: To compare haemodynamic changes, measured noninvasively using the USCOM monitor, after combined spino-epidural anaesthesia and after administration of two different uterotonic drugs, oxytocin and carbetocin, in a population of pregnant women during elective caesarean delivery. METHODS: Haemodynamic measurements were obtained with the USCOM system, by positioning a probe at maternal suprasternal notch (SSN) until the aortic valve flow's profile was optimally identified. Evaluations of the haemodynamic profile were obtained in seven different moments: before anaesthesia; during skin incision; 60, 180 and 300s after administration of uterotonic drug, at closure of the uterus, at closure of the skin. Doses of uterotonic drugs were: Oxytocin 5UI in 500cc NaCl eV, Carbetocin 100mcg in bolus eV. Main measured parameters were: heart rate, mean blood pressure, stroke volume, cardiac output and total vascular resistance. RESULTS: We enrolled 32 pregnant women. Patients were randomized in two groups: oxytocin and carbetocin. A reduction in mean blood pressure, a reduction of total vascular resistance and an increase of cardiac output and of stroke volume were seen, while heart rate values remained stable in both treatment groups. No statistically significant differences were found. DISCUSSION: Administration of carbetocin is associated with a substantial global haemodynamic stability in patients undergoing elective caesarean section without any difference with oxytocin. This observation allows us to consider carbetocin comparable to oxytocin, with minimum haemodynamic impact on the maternal circulation. This minimal effect on global haemodynamic stability might extend the use of this uterotonic drug in patients at high haemorrhagic risk with preeclampsia.