Longitudinal Doppler Assessments in Late Preterm Fetal Growth Restriction.

PURPOSE: To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). MATERIALS AND METHODS: A prospective European multicenter observational study included women with a singleton pregnancy, 32+ 0-36+ 6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. RESULTS: 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. CONCLUSION: An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.

Fetal cerebral Doppler changes and outcome in late preterm fetal growth restriction: prospective cohort study.

OBJECTIVES: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. METHODS: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. RESULTS: The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n = 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33 weeks and 1.0 at 34-36 weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association. CONCLUSION: In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Cost effectiveness of nifedipine compared with atosiban in the treatment of threatened preterm birth (APOSTEL III trial).

OBJECTIVE: To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth. DESIGN: An economic analysis alongside a randomised clinical trial (the APOSTEL III study). SETTING: Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium. POPULATION: Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban. METHODS: We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses. MAIN OUTCOME MEASURES: Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes. RESULTS: Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: €34,897 versus €43,376, mean difference (MD) -€8479 [95% confidence interval (CI) -€14,327 to -€2016)]; multiple pregnancies: €90,248 versus €102,292, MD -€12,044 (95% CI -€21,607 to € -1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group. CONCLUSION: Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation. TWEETABLE ABSTRACT: In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban.

Assessment of venous hemodynamics and volume homeostasis during pregnancy: recommendations of the International Working Group on Maternal Hemodynamics.

Venous hemodynamics and volume homeostasis are important aspects of cardiovascular physiology. However, today their relevance is still very much underappreciated. Their most important role is maintenance and control of venous return and, as such, cardiac output. A high-flow/low-resistance circulation, remaining constant under physiological circumstances, is mandatory for an uncomplicated course of pregnancy. In this article, characteristics of normal and abnormal venous and volume regulating functions are discussed with respect to normal and pathologic outcomes of pregnancy, and current (non-invasive) methods to assess these functions are summarized. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Maternal venous Doppler characteristics are abnormal in pre-eclampsia but not in gestational hypertension.

OBJECTIVE: To compare functional characteristics of maternal thoraco-abdominal arteries and veins in proteinuric and non-proteinuric hypertension in pregnancy. METHODS: This retrospective study included women with singleton pregnancies during the third trimester, which were either uncomplicated or complicated with different clinical types of hypertension: non-proteinuric gestational hypertension (GH), early-onset pre-eclampsia (PE) diagnosed < 34 weeks or late-onset PE diagnosed ≥ 34 weeks. Demographic maternal and neonatal data were recorded, together with maternal serum and urine analytes. All women underwent standardized automated blood-pressure measurement, together with non-invasive impedance cardiography (ICG), for measurement of cardiac output (CO), aortic flow velocity index (VI) and aortic flow acceleration index (ACI). A standardized combined Doppler-electrocardiography assessment of maternal venous hemodynamics was performed to measure renal interlobar vein impedance index (RIVI), hepatic vein impedance index (HVI) and venous pulse transit time (VPTT) in liver and kidneys. Finally, resistance index (RI), pulsatility index (PI) and arterial pulse transit time (APTT) were measured in the uterine arcuate arteries. Mann-Whitney U-tests and Fisher's exact tests were used for intergroup comparisons, and linear dependence between variables was assessed using Pearson's correlation coefficient (r). RESULTS: A total of 150 pregnancies were evaluated: 22 with uncomplicated pregnancy, 41 GH, 31 early PE and 56 late PE. Aortic VI and ACI were lower in GH, early PE and late PE than in uncomplicated pregnancy. Both early PE and late PE differed from GH by having shorter APTT in the uterine arcuate arteries and higher RIVI. Hemodynamic abnormalities were most pronounced in early PE, during which uterine arcuate artery RI was higher and VPTT in kidneys was shorter than in late PE. There was a significant correlation between degree of proteinuria and RIVI for the left (r = 0.381) and right (r = 0.347) kidney in late PE, but this was not true for early PE. CONCLUSIONS: There is a gradient of worsening arterial and venous hemodynamic abnormalities from GH to late PE and then to early PE. Venous hemodynamic abnormalities are present only in PE, with a linear correlation between proteinuria and RIVI in late PE. The role of the maternal venous compartment in the pathophysiology and etiology of PE-related symptoms may be much more important than considered at present.

Effects of lifestyle intervention in obese pregnant women on gestational weight gain and mental health: a randomized controlled trial.

OBJECTIVE: Lifestyle intervention could help obese pregnant women to limit their weight gain during pregnancy and improve their psychological comfort, but has not yet been evaluated in randomized controlled trials. We evaluated whether a targeted antenatal lifestyle intervention programme for obese pregnant women influences gestational weight gain (GWG) and levels of anxiety or depressed mood. DESIGN AND SUBJECTS: This study used a longitudinal interventional design. Of the 235 eligible obese pregnant women, 205 (mean age (years): 29±4.5; body mass index (BMI, kg m(-)(2)): 34.7±4.6) were randomized to a control group, a brochure group receiving written information on healthy lifestyle and an experimental group receiving an additional four antenatal lifestyle intervention sessions by a midwife trained in motivational lifestyle intervention. Anxiety (State and Trait Anxiety Inventory) and feelings of depression (Edinburgh Depression Scale) were measured during the first, second and third trimesters of pregnancy. Socio-demographical, behavioural, psychological and medical variables were used for controlling and correcting outcome variables. RESULTS: We found a significant reduction of GWG in the brochure (9.5 kg) and lifestyle intervention (10.6 kg) group compared with normal care group (13.5 kg) (P=0.007). Furthermore, levels of anxiety significantly decreased in the lifestyle intervention group and increased in the normal care group during pregnancy (P=0.02); no differences were demonstrated in the brochure group. Pre-pregnancy BMI was positively related to levels of anxiety. Obese pregnant women who stopped smoking recently showed a significant higher GWG (ß=3.04; P=0.01); those with concurrent gestational diabetes mellitus (GDM) (ß=3.54; P=0.03) and those who consumed alcohol on a regular base (ß=3.69; P=0.04) showed significant higher levels of state anxiety. No differences in depressed mood or obstetrical/neonatal outcomes were observed between the three groups. CONCLUSIONS: A targeted lifestyle intervention programme based on the principles of motivational interviewing reduces GWG and levels of anxiety in obese pregnant women.

Time interval between maternal electrocardiogram and venous Doppler waves in normal pregnancy and preeclampsia: a pilot study.

PURPOSE: To evaluate the time interval between maternal electrocardiogram (ECG) and venous Doppler waves at different stages of uncomplicated pregnancy (UP) and in preeclampsia (PE). MATERIALS AND METHODS: Cross-sectional pilot study in 40 uncomplicated singleton pregnancies, categorized in four groups of ten according to gestational age: 10 - 14 weeks (UP1), 18 - 23 weeks (UP2), 28 - 33 weeks (UP3) and ≥ 37 weeks (UP4) of gestation. A fifth group of ten women with PE was also included. A Doppler flow examination at the level of renal interlobar veins (RIV) and hepatic veins (HV) was performed according to a standard protocol, in association with a maternal ECG. The time interval between the ECG P-wave and the corresponding A-deflection of the venous Doppler waves was measured (PA), and expressed relative to the duration of the cardiac cycle (RR), and labeled PA/RR. RESULTS: In hepatic veins, the PA/RR is longer in UP 4 than in UP 1 (0.48 ± 0.15 versus 0.29 ± 0.09, p ≤ 0.001). When all UP groups were compared, the PA/RR increased gradually with gestational age. In PE, the HV PA/RR is shorter than in UP 3 (0.25 ± 0.09 versus 0.42 ± 0.14, p < 0.01) and this difference persisted under anti-hypertensive treatment (0.28 ± 0.06 versus 0.42 ± 0.14, p ≤ 0.01, n = 6). Similar results were found in both kidneys. In UP 1 but not in UP 3 or UP 4, the HV PA/RR is shorter in the liver than in the left and right kidney (0.29 ± 0.09 versus 0.38 ± 0.12, p < 0.01, and versus 0.36 ± 0.09, p ≤ 0.01). CONCLUSION: The PA/RR is organ-specific and gestation-dependent, and is considered to relate to venous vascular tone and/or intravascular filling. Increased values at advanced gestational stages are consistent with known features of maternal cardiovascular adaptation. Shorter values in preeclampsia are consistent with maternal cardiovascular maladaptation mechanisms. Our pilot study invites more research of the relevance of the time interval between maternal ECG and venous Doppler waves as a new parameter for studying the gestational cardiovascular (patho)physiology of the maternal venous compartment by duplex sonography.

Impedance cardiography in uncomplicated pregnancy and pre-eclampsia: a reliability study.

It has been reported that cardiac contractility is altered in pre-eclampsia compared with normal pregnancy. Because of the non-invasive nature of impedance cardiography (ICG), this method is gaining popularity in the obstetric field. We assessed the reliability of ICG measurements in uncomplicated 3rd trimester pregnancies (UP) and pre-eclamptic pregnancies (PE). ICG measurements were recorded before and after three position changes, and this examination was done twice (session 1 and 2) per subject. For each of the 22 haemodynamic parameters, inter- and intrasession Pearson's correlation coefficients (PCC) were calculated for mean values of 30 measurements per position per subject. PCC was consistently ≥ 0.80 for contractility parameters 'acceleration-', 'velocity-' and 'heather-index' in both UP and PE. These data illustrate that correlation between repeated ICG measurements of cardiac contractility is high under standardised conditions, and that ICG may be useful to study changes of cardiac contractility in pregnancy.

Role of dysfunctional maternal venous hemodynamics in the pathophysiology of pre-eclampsia: a review.

The venous compartment has an important function in regulation and control of cardiac output. Abnormalities of cardiac output have been found in early gestational stages of both early- and late-onset pre-eclampsia. The venous compartment also maintains the balance between circulating and non-circulating blood volumes and regulates the amount of reserve blood stored in the splanchnic venous bed. It is well known that adaptive regulation of maternal blood volume is disturbed in pre-eclampsia. Abnormal venous hemodynamics and venous congestion are responsible for secondary dysfunction of several organs, such as the kidneys in cardiorenal syndrome and the liver in cardiac cirrhosis. Renal and liver dysfunctions are among the most relevant clinical features of pre-eclampsia. Doppler sonography studies have shown that the maternal venous compartment is subject to gestational adaptation, and that blood flow characteristics at the level of renal interlobar and hepatic veins are different in pre-eclampsia compared with uncomplicated pregnancy. In comparison to late-onset pre-eclampsia, in early-onset pre-eclampsia venous Doppler flow abnormalities are more prominent and present up to weeks before clinical symptoms. This paper reviews the growing evidence that dysfunction of maternal venous hemodynamics is part of the pathophysiology of pre-eclampsia and may perhaps be more important than is currently considered. Doppler sonography is a safe and easily performed method with which to study maternal venous hemodynamics. Therefore, exploring the role of maternal venous hemodynamics using Doppler sonography is an exciting new research topic for those who are interested in cardiovascular background mechanisms, as well as prediction and clinical work-up of pre-eclampsia.

Maternal renal interlobar vein impedance index is higher in early- than in late-onset pre-eclampsia.

OBJECTIVES: To test the hypothesis that Doppler characteristics of maternal renal interlobar veins (RIV) are different between pregnancies affected by early-onset pre-eclampsia (EP) and those affected by late-onset pre-eclampsia (LP). METHODS: A gestational age of 34 weeks was considered to differentiate EP from LP. All women had a renal duplex scan according to a standard protocol, with known intraobserver correlation coefficient (0.88). Maximum (Vmax) and minimum (Vmin) RIV velocities were measured on two occasions (between 28 and 32 and between 34 and 37 weeks) in 18 women with uncomplicated pregnancy (UP). In women with EP (n = 32) or LP (n = 41), these variables were measured once, within 3 days following hospital admission. Delta velocity (DeltaV) was calculated as Vmax - Vmin and the RIV impedance index (RIVI) was calculated as DeltaV/Vmax. Data on neonatal outcome and maternal renal function were obtained for UP and those with EP and LP, and group-specific means +/- SD were calculated and compared. RESULTS: Compared with UP, the RIVI of both left and right kidneys was higher in those with EP (0.49 +/- 0.13 vs. 0.36 +/- 0.04, P = 0.0001, and 0.46 +/- 0.15 vs. 0.33 +/- 0.04, P = 0.0008) and in those with LP (0.41 +/- 0.07 vs. 0.37 +/- 0.06, P = 0.04, and 0.38 +/- 0.12 vs. 0.30 +/- 0.05, P = 0.009). RIVI was higher in pregnancies with EP than in those with LP (P < or = 0.01), and this difference was associated with lower median birth-weight percentiles (22.5 (interquartile range (IQR), 15-35) vs. 40.0 (IQR, 12-55), P = 0.01), higher maternal serum uric acid concentrations (419 +/- 84 vs. 374 +/- 85 micromol/L, P = 0.03) and higher proteinuria (4131 +/- 3885 vs. 1190 +/- 1133 mg/24 h, P < 0.0001). CONCLUSION: Maternal vascular maladaption in pre-eclampsia is associated with abnormal Doppler findings in the venous compartment. RIVI is higher in EP than in LP pregnancies and this is associated with lower birth-weight percentiles and higher proteinuria.

Interlobar venous flow is different between left and right kidney in uncomplicated third trimester pregnancy.

AIM: To investigate Doppler flow patterns of renal interlobar veins (RIV) in left (L) and right (R) kidney in relation to gestational age and to intrarenal pyelocalyceal diameters (PCD). METHODS: Cross-sectional study involving 6 groups of women: (1) non-pregnant women, women pregnant between weeks (2) 11-14, (3) 18-23, (4) 28-33, (5) 37-40 and (6) women <5 days post delivery. During standardized renal duplex ultrasound scan, PCD (mm) was measured and venous impedance index (VI = [peak flow (PV) - presystolic flow]/PV) of RIV was defined. Comparison between L and R kidney was performed by repeated-measures analysis of variance for VI and by t tests for PCD. RESULTS: A total of 150 women were examined, 25 in each group. In the early third trimester of pregnancy, L VI was significantly higher than R VI (0.38 +/- 0.01 vs. 0.33 +/- 0.01, p < 0.0001) and L PCD was significantly lower than R PCD (3.90 +/- 3.68 vs. 6.25 +/- 4.03, p = 0.03). CONCLUSION: RIV Doppler flow is different between left and right kidney only in the third trimester of pregnancy. This difference is inversely related to PCD, which may be explained by pelvic compression from the gravid uterus.

Limitations of ST analysis in clinical practice: three cases of intrapartum metabolic acidosis.

OBJECTIVE: To examine detailed intrapartum events in cases of neonatal metabolic acidosis despite monitoring using STAN (cardiotocography [CTG] plus ST waveform analysis of fetal electrocardiogram [ECG]). DESIGN: Retrospective case review. SETTING: High-risk pregnancies monitored by STAN. METHODS: Case note review was performed in newborns with metabolic acidosis where no significant ST changes in the fetal ECG occurred prior to birth. MAIN OUTCOME MEASURES: Metabolic acidosis. RESULTS: Detailed review of three cases identified poor signal quality, difficulties in CTG interpretation, failure to comply with STAN clinical guidelines and deterioration of the CTG without ECG alert as the leading causes of these adverse outcomes. CONCLUSIONS: The cases illustrate some of the pitfalls associated with the clinical application of the STAN technology which prevent severe metabolic acidosis being eradicated completely. It may be useful to expand the STAN guidelines protocol towards the identification of exceptional clinical situations, such as in our cases, and towards appropriate additional interventions, as this may lead to a further reduction in adverse neonatal outcomes.

Do biphasic uterine contractions imply poor uterine function?

In a retrospective study of 362 cardiotocographic recordings of primigravidae in labour we found 8% biphasic or coupled uterine contractions. In augmented labour, biphasic contractions occurred almost twice as often as in spontaneous and induced labour. The duration of labour complicated with biphasic contractions was increased significantly in all types of labour. Therefore biphasic contractions may reflect uneffective uterine function. Contrary to other studies, the appearance of biphasic contractions showed no correlation with epidural analgesia and the incidence of instrumental deliveries or caesarean sections was not increased.

Identification of peripartum near-miss for perinatal audit.

INTRODUCTION: Today, perinatal audit focuses basically on cases of perinatal mortality. In most centres in Western Europe, perinatal mortality is low. Identification of metabolic acidosis at birth may increase index cases eligible for evaluation of perinatal care, and this might improve quality of perinatal audit. The aim of this study is to assess the incidence of metabolic acidosis at birth in order to estimate its impact on perinatal audit. PATIENTS AND METHODS: Cord blood was analysed for every neonate born between January 1, 2010 and December 31, 2012 in Ziekenhuis Oost-Limburg, Genk. Acidosis was defined as an umbilical arterial pH ≤ 7.05 with or without a venous pH ≤ 7.17. Respiratory acidosis (RA) was defined as acidosis with normal base excess, and metabolic acidosis (MA) was defined as acidosis with an arterial or venous base excess ≤ -10 mmol/L. In case of failed cord blood sampling, 5 minute Apgar score ≤ 6 was considered as the clinical equivalent of MA. Retrospective chart review of obstetric and paediatric files was performed for all cases of MA, together with review of paediatric follow-up charts from at least 6 months after birth. Perinatal asphyxia was defined as biochemical evidence for MA at birth, associated with early onset neonatal encephalopathy and long-term symptoms of cerebral palsy. RESULTS: In a total of 6614 babies, perinatal death up to 7 days of life occurred in 40 babies (6.0‰). Acidosis was present in 183 neonates (2.8%), of which 130 (2.0%) had RA and 53 (0.8%) had MA. Of the 173 neonates with unknown pH values, 6 had Apgar scores ≤ 6. Of 59 babies born with MA or its clinical equivalent, 52 (88.1%) showed no neurologic symptoms at birth. Two (3.4%) died in the early neonatal period, one after abruptio placentae and one due to chorioamnionitis and severe prematurity. Five (8.5%) MA babies had symptoms of early onset neonatal encephalopathy, which recovered in three (5.1%), and persisted long-term in two others (3.4%). The two babies with cerebral palsy (prevalence 1/3300) were both born after instrumental vaginal delivery for foetal distress. CONCLUSION: In our study cohort, the incidence of perinatal mortality is 6‰. The incidence of metabolic acidosis is 9‰. Addition of cases of metabolic acidosis to those of mortality doubles index cases eligible for perinatal audit. The incidence of babies surviving with cerebral palsy after metabolic acidosis at birth is very low (0.3‰). Our results suggest that instrumental delivery for foetal distress might be a risk factor for metabolic acidosis with persisting neurologic dysfunction. Our study illustrates that identification of peripartum near-miss is useful for perinatal audit.