Methodological challenges in using human umbilical artery as a model for in vitro studies.

NEW FINDINGS: What is the central question of this study? What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries? What is the main finding and its importance? The protocols presented in this study indicate some potential outcomes important for interpretation of the vascular responsivities of human umbilical arteries and could be useful for planning future in vitro studies with human umbilical arteries. ABSTRACT: Human umbilical artery (HUA) preparations are of particular importance for in vitro studies on isolated blood vessels because their sampling is not risky for the patient, and they can provide the closest possible impression of changes related to the uteroplacental circulation during pre-eclampsia. Using organ bath techniques, useful experimental protocols are provided for measuring some pathophysiological phenomena in the vascular responses of HUAs. Several vasoconstrictors (serotonin, prostaglandin F and phenylephrine) and vasodilators (acetylcholine and minoxidil) were seleted for determination of their vasoactivity in HUAs. The role of L-type voltage-operated calcium channels and different types of potassium channels (KATP , BKCa and KV ) were assessed, as was the impact of homocysteine. Serotonin was confirmed to be the most potent vasoconstrictor, while acetylcholine and phenylephrine caused variability in the relaxation and contraction response of HUA, respectively. The observed increase in serotonin-induced contraction and a decrease in minoxidil-induced relaxation in the presence of homocysteine suggested its procontractile effect on HUA preparations. Using selective blockers, it was determined that KATP and KV channels participate in the minoxidil-induced relaxation, while L-type voltage-dependent Ca2+  channels play an important role in the serotonin-induced contraction. The presented protocols reveal some of the methodological challenges related to HUA preparations and indicate potential outcomes in interpreting the vascular effects of the investigated substances, both in physiological conditions and in the homocysteine-induced pre-eclampsia model.

Hemodynamic changes in late advanced pregnant Zaraibi goats during the peripartum period.

The objective of the present study was to demonstrate the blood flow velocities, blood flow rate (BFR; bpm) with the accurate ratio of both systolic and diastolic velocities points (S/D) in addition to Doppler indices (resistive and pulsatility index [RI and PI]) in both fetal [fetal heart (FH), fetal abdominal aorta (Ab. A), and umbilical artery (UM.A)] and maternal [Middle uterine artery (MU.A)] sides during the last month of gestation. Ten Zaraibi (Egyptian Nubian) goats weighing 40-50kg and aged from 5-7 years were examined twice per month till reached the last month of pregnancy. Then all females were examined every 5 days starting from day -35 till day -1 before kidding.The pregnant goats were examined by ultrasonic and Doppler indices were recorded with Doppler scanning (7.5 -12 MHz, with colored and spectral graph to form the perfect wave to assess Doppler measurements). The obtained data were analyzed using analysis of variance. Results indicated that on the fetal side; the maximum point of velocity (MSV; cm/sec) in the FH and BFRwere elevated from day -35 till day -10 with a slight decline at days -5 and -1 at the peripartum period (P < 0.05), while FH.PI and S/D ratio declined till day -1(P < 0.05). In addition, the fetal Ab. A, and UM.A PI, RI, and S/D ratio declined from day -35 till day -1 at the peripartum period with a significant increase in the peak systolic velocity (PSV) and BFR(P < 0.05). However, non-significant changes in the end diastolic velocity (EDV) were detected. On the maternal side, the MU.A PI and S/D declined from day -35 till day -1 with an elevation of both PSV and BFRat the same time points (P < 0.05). In conclusion, the Doppler evaluation of fetal and maternal blood flow vessels is important to give complete information that directly affects the health status of the mother and fetus.

Disrupting effects of the emerging contaminant octylmethoxycinnamate (OMC) on human umbilical artery relaxation.

Cardiovascular diseases (CVD) represent the number one cause of death worldwide. The vascular endothelium may play a role in the pathophysiology of CVD diseases. Octylmethoxycinnamate (OMC) is a UV-B filter (CAS number: 5466-77-3) widely used worldwide in numerous personal care products, including sunscreens, daily creams, and makeup. This UV-B filter is considered an endocrine disruptor. Therefore, this investigation aimed to evaluate the direct effects of OMC in human umbilical arteries (HUAs) with endothelium and the possible mechanisms involved in the response. The results demonstrated that OMC exerts a rapid (non-genomic) and endothelium-dependent arterial relaxant effect on HUAs previously contracted with serotonin (5-HT) and Histamine (His). On the other hand, when HUAs were contracted with potassium chloride (KCl), the relaxing effect was only observed in HUAs without endothelium, and it appeared to be inhibited in HUAs with endothelium. Thus, the vasorelaxant effect of OMC depends on the endothelium and depends on the contractile agent used, suggesting that OMC may act through different signaling pathways. Furthermore, computational modulation studies, corroborated the binding of OMC to all the proteins under investigation (eNOS, COX-2, ET-1, and TxA2), with higher affinity for COX-2. In summary, the vascular effect of OMC may involve activating different pathways, i.e., acting through the NO pathway, COX pathway, or activating the endothelin-1 pathway.

Fetal pulmonary artery Doppler blood flow velocity measures and early infant lung function. A prospective cohort study.

BACKGROUND: Reduced lung function at birth has evident antenatal origins and is associated with an increased risk of wheezing and asthma later in life. Little is known about whether blood flow in the fetal pulmonary artery, may impact postnatal lung function. OBJECTIVE: Our primary aim was to investigate the potential associations between fetal Doppler blood flow velocity measures in the fetal branch pulmonary artery, and infant lung function by tidal flow-volume (TFV) loops at three months of age in a low-risk population. Our secondary aim was to explore the association between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries, and the same lung function measures. METHODS: In 256 non-selected pregnancies from the birth cohort study Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL) we performed fetal ultrasound examination with Doppler blood flow velocity measurements at 30 gestational weeks (GW). We recorded the pulsatility index, peak systolic velocity, time-averaged maximum velocity, acceleration time/ejection time ratio, and time velocity integral primarily in the proximal pulmonary artery close to the pulmonary bifurcation. The pulsatility index was measured in the umbilical and middle cerebral arteries and the peak systolic velocity in the middle cerebral artery. The cerebro-placental ratio (ratio between pulsatility index in the middle cerebral and umbilical arteries) was calculated. Infant lung function was assessed using TFV loops in awake, calmly breathing three months old infants. The outcome was the time to peak tidal expiratory flow to expiratory time ratio (tPTEF/tE), tPTEF/tE <25th percentile, and tidal volume per kg body weight (VT/kg). Potential associations between fetal Doppler blood flow velocity measures and infant lung function were assessed using linear and logistic regressions. RESULTS: The infants were born at median (min - max) 40.3 (35.6 - 42.4) GW, with a mean (SD) birth weight of 3.52 (0.46) kg, and 49.4% were females. The mean (SD) tPTEF/tE was 0.39 (0.1) and the 25th percentile was 0.33. Neither univariable nor multivariable regression models revealed any associations between fetal pulmonary blood flow velocity measures and tPTEF/tE, tPTEF/tE <25th percentile, or VT/kg at three months of age. Similarly, we did not observe associations between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries and infant lung function measures. CONCLUSION: In a cohort of 256 infants from the general population, fetal third-trimester Doppler blood flow velocity measures in the branch pulmonary, umbilical, and middle cerebral arteries were not associated with infant lung function measures at three months of age.

The preeclampsia condition alters external potassium-evoked contraction of human umbilical vessels.

INTRODUCTION: Pre-eclampsia (PE) is a disease of high incidence in parturients, that adversely affects both mother and fetus. Although PE prevalence is high, there are few studies on literature describing its etiology or its mechanism of action. Thus, the aim of this study was to elucidate PE-induced alterations of contractile reactivity in umbilical vessels. METHOD: Segments of human umbilical artery (HUA) and human umbilical vein (HUV) from neonates of normotensive or PE parturients were obtained and contractile responses measured with a myograph. The segments were allowed to stabilize (2 h) under 1.0, 2.0 and 3.0 g force (gf) at pre-stimulation and, then, were stimulated with high isotonic K+ concentrations ([K+]o; 10-120 mM). RESULTS: All preparations responded to increases in isotonic K+ concentrations. In HUA and HUV of neonates of normotensive parturients, and in HUV of neonates of PE parturients, the contraction saturated at nearly 50 mM [K+]o, while in HUA of neonates of PE parturients, saturation occurred at 30 mM [K+]o. Additionally, several differences between contractile responses of HUA and HUV from neonates of normotensive parturients and those from neonates of parturients with PE were observed. PE alters the contractile response of the HUA and HUV to increased [K+]o, and its contractile modulation by the pre-stimulus basal tension. Moreover, in HUA of PE, reactivity is decreased for 2.0 and 3.0 gf basal tensions and increased for 1.0 gf; in the HUV of PE condition, it is increased for all basal tensions. DISCUSSION: In conclusion, PE promotes several alterations in HUA and HUV contractile reactivity, vessels in which important circulatory alterations are known to occur.

Diastolic deceleration area in the fetal MCA: a new Doppler parameter.

Objective: Doppler velocimetry has been widely used throughout the years as a valuable tool in the follow-up and prognosis of various pregnancy complications. Numerous Doppler indices have been introduced to qualitatively describe fetal blood flow. Currently, the Pulsatility index (PI) is the most widely used index for this purpose. In current clinical practice, middle cerebral artery (MCA) PI measurement is commonly used to assess fetal well-being, especially in late-onset fetal growth restriction (FGR). However, existing evidence suggests that MCA PI alone is inferior to the ratio between MCA and umbilical artery (UA) pulsatility indices in predicting adverse perinatal and neonatal outcomes. When comparing normal and abnormal MCA Doppler waveforms, it is evident that most changes appear in the diastolic part of the heart cycle. Therefore, the PI, which contains elements from both systole (peak systolic velocity-PSV) and diastole (end-diastolic velocity), may not be the most effective tool for quantifying fetal brain sparing (BS).Methods: We hypothesize that another measurement modality that focuses predominantly on the diastole could be more efficient for evaluating the amount of vasodilatation. In ultrasound velocimetry of larger blood vessels, there is a well-known phenomenon called "dicrotic notch" (DN), which appears on the declining part of each Doppler waveform and can be used to precisely pinpoint the end of systole and the start of diastole. We hypothesized that the extent of cerebral vasodilation can be more accurately assessed by measuring the area between the dicrotic notch (DN) and the end-diastolic velocity (which we refer to as the "diastolic deceleration area-DDA"). In this study, we introduced a new Doppler parameter along with a rationale for DDA measurement in the fetal MCA. We also defined third-trimester nomograms and provided a preliminary assessment of the correlation between DDA and fetal oxygen deficiency.Results: Our findings suggest that the DDA may serve as an independent instrument for identifying hypoxia during late pregnancy, either on its own or in conjunction with other Doppler and cardiotocography modalities.Conclusion: However, before incorporating DDA into clinical practice, it is crucial to conduct further research and validation studies with larger sample sizes and more diverse populations. This would help assess the generalizability of the results and establish optimal cutoff points for DDA in various clinical settings. It is also important to prospectively study the role of DDA in early- and late-onset fetal growth restriction (FGR), Rh-isoimmunization/anemia, preeclampsia, gestational diabetes, and other pregnancy complications. In fact, we believe that the concept of measuring specific areas in arterial Doppler velocimetry indices could have significant implications not only in fetal medicine and obstetrics, but also in other areas of human and veterinary medicine.

Influence of fetal hiccups on Doppler blood flow waveform of fetal arteries: Difference among arteries.

BACKGROUND: A few studies have been reported on the influence of fetal hiccups on umbilical artery. The aim of this study is to clarify the influence of fetal hiccups on Doppler blood flow waveform (DBFW) of some fetal arteries, and to show the difference in these influences among fetal arteries. OBJECTIVE: DBFW of umbilical artery, descending aorta, and middle cerebral artery were recorded at hiccups in normal fetuses between 34th and 40th gestational weeks. The changes on DBFW were classified into three shapes by the direction and the size of the changes. Shape 1: sharp decrease but not to the baseline, Shape 2: sharp decrease to the baseline (absence), and Shape 3: reverse flow. RESULTS: At all hiccups, the changes on DBFW of these arteries were observed. These changes were classified into three shapes. Changes of umbilical artery were widely distributed in three shapes depending on when hiccup occurred during cardiac cycle. On the other hand, most changes of the descending aorta and middle cerebral artery were Shape 3 whenever the hiccup occurred during cardiac cycle. CONCLUSION: The changes on DBFW of fetal arteries were observed at all hiccups. Changes of umbilical artery were widely distributed in three shapes depending on when hiccup occurred during cardiac cycle. On the other hand, most changes of descending aorta and middle cerebral artery were Shape 3. This is the first study clarified the influence of fetal hiccups on DBFW of some fetal arteries, and showed the difference in these influences among fetal arteries.

Fetal and maternal Doppler adaptation to maternal exercise during pregnancy: a randomized controlled trial.

BACKGROUND: Regular and supervised exercise during pregnancy is worldwide recommended due to its proven benefits, but, during exercise, maternal blood flow is redirected from the viscera to the muscles and how fetal wellbeing may be affected by this redistribution is still not well known. OBJECTIVE: To analyze the longitudinal effect of a supervised moderate physical exercise program during pregnancy on uteroplacental and fetal Doppler parameters. METHODS: This is a planned secondary analysis of an randomized controlled trial (RCT), performed at Hospital Universitario de Torrejón, Madrid, Spain, including 124 women randomized from 12+0 to 15+6 weeks of gestation to exercise vs. control group. Fetal umbilical artery (UA), middle cerebral artery, and uterine artery pulsatility index (PI), were longitudinally collected by Doppler ultrasound assessment throughout gestation, and derived cerebroplacental ratio (normalized by z-score), and maternal mean PI in the uterine arteries (normalized by multiplies of the median). Obstetric appointments were scheduled at 12 (baseline, 12+0 to 13+5), 20 (19+0 to 24+2), 28 (26+3 to 31+3) and 35 weeks (32+6 to 38+6) of gestation. Generalized estimating equations were adjusted to assess longitudinal changes in the Doppler measurements according to the randomization group. RESULTS: No significant differences in the fetal or maternal Doppler measurements were found at any of the different checkup time points studied. The only variable that consistently affected the Doppler standardized values was gestational age at the time of assessment. The evolution of the UA PI z-score during the pregnancy was different in the two study groups, with a higher z-score in the exercise group at 20 weeks and a subsequent decrease until delivery while in the control group it remained stable at around zero. CONCLUSIONS: A regular supervised moderate exercise program during pregnancy does not deteriorate fetal or maternal ultrasound Doppler parameters along the pregnancy, suggesting that the fetal well-being is not compromised by the exercise intervention. Fetal UA PI z-score decreases during pregnancy to lower levels in the exercise group compared with the control group.

Effects of maternal anxiety on fetal and maternal circulation.

OBJECTIVE: The aim of this study was to evaluate the association between maternal anxiety in the third trimester and changes in fetal and maternal circulation assessed by Doppler velocimetry. METHODS: This is a prospective, cross-sectional study. The inclusion criteria were good health, a singleton pregnancy, maternal age between 18 and 40 years, and gestational age between 34 and 40 weeks. Doppler measurements included mean uterine artery pulsatility index, fetal middle cerebral artery pulsatility index, peak of systolic velocity, umbilical artery, and umbilical vein. The Beck Anxiety Inventory questionnaire, validated for the Brazilian population, with 21 self-reported items, was applied. RESULTS: The study included 34 pregnant women, and 6 (17.7%) presented a total Beck Anxiety Inventory score showing moderate or severe maternal anxiety. The mean maternal age was 28.1 years (SD 5.7 years); the mean gestational age at interview was 36.5 weeks (SD 1.8 weeks), and the mean Beck Anxiety Inventory total score was 12.3 (SD 9.8). The group with moderate or severe anxiety, compared to the group with minimal or mild anxiety, presented an association with lower maternal age (median 21.5 vs. 29.5 years, p=0.019), lower fetal umbilical vein blood flow (median 189.4 vs. 249.5 mL/min, p=0.047), and lower umbilical vein-corrected blood flow (median 68.5 vs. 84.9 mL/kg/min, p=0.038). CONCLUSION: Maternal anxiety may affect fetal circulation patterns in late pregnancy and is associated with reduced blood flow in the fetal umbilical vein. The underlying physiopathology needs further investigation.

Reduced fetal growth velocity and weight loss are associated with adverse perinatal outcome in fetuses at risk of growth restriction.

BACKGROUND: Although fetal size is associated with adverse perinatal outcome, the relationship between fetal growth velocity and adverse perinatal outcome is unclear. OBJECTIVE: This study aimed to evaluate the relationship between fetal growth velocity and signs of cerebral blood flow redistribution, and their association with birthweight and adverse perinatal outcome. STUDY DESIGN: This study was a secondary analysis of the TRUFFLE-2 multicenter observational prospective feasibility study of fetuses at risk of fetal growth restriction between 32+0 and 36+6 weeks of gestation (n=856), evaluated by ultrasound biometry and umbilical and middle cerebral artery Doppler. Individual fetal growth velocity was calculated from the difference of birthweight and estimated fetal weight at 3, 2, and 1 week before delivery, and by linear regression of all available estimated fetal weight measurements. Fetal estimated weight and birthweight were expressed as absolute value and as multiple of the median for statistical calculation. The coefficients of the individual linear regression of estimated fetal weight measurements (growth velocity; g/wk) were plotted against the last umbilical-cerebral ratio with subclassification for perinatal outcome. The association of these measurements with adverse perinatal outcome was assessed. The adverse perinatal outcome was a composite of abnormal condition at birth or major neonatal morbidity. RESULTS: Adverse perinatal outcome was more frequent among fetuses whose antenatal growth was <100 g/wk, irrespective of signs of cerebral blood flow redistribution. Infants with birthweight <0.65 multiple of the median were enrolled earlier, had the lowest fetal growth velocity, higher umbilical-cerebral ratio, and were more likely to have adverse perinatal outcome. A decreasing fetal growth velocity was observed in 163 (19%) women in whom the estimated fetal weight multiple of the median regression coefficient was <-0.025, and who had higher umbilical-cerebral ratio values and more frequent adverse perinatal outcome; 67 (41%; 8% of total group) of these women had negative growth velocity. Estimated fetal weight and umbilical-cerebral ratio at admission and fetal growth velocity combined by logistic regression had a higher association with adverse perinatal outcome than any of those parameters separately (relative risk, 3.3; 95% confidence interval, 2.3-4.8). CONCLUSION: In fetuses at risk of late preterm fetal growth restriction, reduced growth velocity is associated with an increased risk of adverse perinatal outcome, irrespective of signs of cerebral blood flow redistribution. Some fetuses showed negative growth velocity, suggesting catabolic metabolism.

The effects of aging and gestational month on uteroplacental vascular perfusion, and umbilical artery hemodynamics in pregnant jennies.

This study aimed to correlate the pulsed wave spectral indices of the middle uterine artery at both sides with placental development in jenny within mid-late pregnancies, and establish umbilical Doppler values for different ages and different gestational months. Twenty Equus Asinus pregnant jennies 260-450 kg (average, 320 ± 10 kg) were examined from 5 to 9 months of pregnancy with different ages (4-14 years). Monthly B-mode ultrasound examination was performed on both the combined thickness of the uterus and placenta (CTUP; mm) and umbilical artery cross-sectional diameter, and Doppler mode examination was performed on both the middle uterine (MUA at right [R] and left [L] sides) and umbilical arteries to measure both Doppler indices that expressed by resistance (RI) and pulsatility indices (PI), and blood flow rate. CTUP was elevated within pregnancy time at different ages (P < 0.05). L. PI was significantly declined throughout different ages (P < 0.05), but this declining trend was not observed in L. RI. The L. blood flow rate (R; bpm) was elevated among different ages and different months (P < 0.05). Both RI and PI were significantly decreased from 5 to 9 month of gestation period in jennies (P < 0.05).. The umbilical arteries cross-sectional diameter (Umb A; mm), was elevated among different ages and different months, while both Doppler indices were declined. A positive correlation was found (between both Doppler indices of both umbilical and uterine arteries P < 0.001). There was elevated vascular perfusion in uterine and umbilical arteries associated with reduced both Doppler indices along the course of pregnancy at different ages.

Effect of a standardized maternal meal on fetal middle cerebral artery Doppler indices: A single-blinded crossover study.

OBJECTIVE: Measures of Doppler blood flow velocity profiles are an integral part of monitoring fetal well-being during pregnancy. These examinations are performed at different times of the day and at different maternal meal states. In uncomplicated pregnancies, we assessed the effect of a standardized maternal meal on middle cerebral artery (MCA) and umbilical artery (UA) Doppler blood flow velocity pulsatility indices (PIs) and MCA peak systolic velocity (PSV). METHODS: In this prospective single-blinded crossover study 25 healthy women were examined at 36 weeks of pregnancy. The first examination was performed in the morning following overnight fast, and repeated after extended fast (state A), and after a standard breakfast meal (state B). RESULTS: Irrespective of maternal prandial status, the MCA-PI values were lower in the 2nd compared to the 1st examination (-0.187; p = 0.071, and -0.113; p = 0.099, state A and B, respectively). Compared to the values in the 1st examination, the UA-PI values, were higher after extended fast (0.014; p = 0.436), and lower post-prandially (-0.036; p = 0.070). The difference (state B minus state A) between the meal states were not significant (0.074; p = 0.487 and -0.050; p = 0.058, for MCA-PI and UA-PI, respectively). Adjusting for the possible influence of fetal heart rate on MCA-PI and UA-PI, the differences between meal states remained non-significant (p = 0.179, p = 0.064, respectively). The MCA-PSV values increased after the meal (6.812; p = 0.035), whereas no increase was observed following extended fast (0.140; p = 0.951). The difference in MCA-PSV values between the two meal states was not significant (6.672; p = 0.055). CONCLUSION: Our results demonstrate possible diurnal variations in MCA-PI and UA-PI, with and without adjustment for fetal heart rate, that seem to be unaffected by maternal meal intake in healthy pregnancies.

Ultrasound parameters of early pregnancy and Doppler indices of blood vessels in the placenta and umbilical cord throughout the pregnancy period in sheep.

BACKGROUND: Ultrasonography is one of the most important techniques that enable the detection and monitoring of pregnancy. One such study using this technique is the assessment of the hemodynamics of fetal and umbilical blood vessels. However, there is little data on blood flow in the placentomes, which is the basic structural unit of the sheep's placenta. Therefore, the aim of this study was to determine the Doppler parameters in the arterial vessels of the caruncles, cotyledons and the umbilical cord as well as measuring venous flow rates during the entire gestation period of the sheep. Additionally, the usefulness of various other ultrasound parameters in the early diagnosis of pregnancy in sheep was analyzed. RESULTS: Most of the Doppler parameters in umbilical, cotyledonary and caruncular arteries were significantly correlated with the day of pregnancy (p < 0.01). In the early stages of pregnancy, the peak systolic velocity (PSV), regardless of the location of the artery, was significantly lower than that in the later stages of pregnancy (p < 0.01). PSV was also found to be significantly higher in the umbilical artery than in the cotyledonary and caruncular arteries (p < 0.01). Until the 50th day of pregnancy, the end diastolic velocity (EDV) was not found in the umbilical and cotyledonary arteries. EDV was significantly higher in the caruncular arteries than in the cotyledonary and umbilical arteries (p < 0.01). The resistance index (RI) and pulsatility index (PI) in the early stages of pregnancy were found to be significantly higher than that in the later stages of pregnancy (p < 0.01). The RI and PI were significantly lower in the caruncular arteries than in the arteries of the cotyledons and umbilical cord (p < 0.01). In the umbilical vein, all Doppler parameters were observed to be significantly higher than those in the placentomal veins (p < 0.01 or p < 0.05). Using transrectal ultrasound, pregnancy was detected between 20 and 28 days after mating. The ovaries were observed to have corpora lutea, the diameter of which was fairly consistent from the 17th to the 56th day of pregnancy. CONCLUSIONS: It has been demonstrated that both the location of the arterial vessel in the placental-umbilical circulation and the gestational age have a significant impact on hemodynamic parameters. The results also provide new insights about the blood flow in caruncular and cotyledonary arteries, which could contribute to a more holistic understanding of hemodynamic changes in the placentas of sheep. Analyzing haemodynamic parameters in the umbilical and placental veins are preliminary studies in sheep, but it could inspire further research in this field. Furthermore, the research conducted confirms the practicality and convenience of transrectal ultrasonography in the early diagnosis of pregnancy in sheep and also indicates that the identification and imaging of the corpus luteum using B-mode ultrasonography can be a very early and simple method of confirming effective mating in sheep.

Longitudinal changes in fetal head biometry and fetoplacental circulation in fetuses with congenital heart defects.

INTRODUCTION: Objectives were to analyze changes in fetal cephalic biometry and fetoplacental circulation throughout pregnancy in fetuses with congenital heart defects. MATERIAL AND METHODS: Prospective study conducted on three university tertiary referral hospitals. Fetuses with the diagnosis of isolated congenital heart defects attending between 2014 and 2018 were included. Congenital heart defects were divided into two groups according to the oxygen supply to the central nervous system: group I (expected low placental blood content and low oxygen delivery to the brain) and group II (expected intermediate and high placental blood content). Fetal biometry and Doppler parameters were collected between 25-30 weeks of gestation and 34-40 weeks of gestation and transformed into Z scores. The results were compared with healthy controls. Finally, general linear modeling was performed to analyze repeated measurements. RESULTS: In all, 71 fetuses met the inclusion criteria. Fetuses with congenital heart defects had significantly smaller head (biparietal diameter [p < 0.001], head circumference [p = 0.001]) and abdominal circumference (p < 0.001), and lower estimated fetal weight (p < 0.001) than controls. When analyzing according to congenital heart defects type, head size was significantly smaller in group I compared with group II (p = 0.04). Regarding Doppler parameters, fetuses with congenital heart defects showed higher umbilical artery pulsatility index (p < 0.001) and lower cerebroplacental ratio (p = 0.044) than controls. In group I, umbilical artery pulsatility index was above the 95th centile in 15.4% of fetuses compared with 6.7% in group II and 1.9% in controls (p < 0.001); moreover, middle cerebral artery pulsatility index was below the 5th centile in 5.4% of group I fetuses compared with 0% in group II and 1.2% in controls (p = 0.011). General linear model for two measurements showed significant longitudinal changes in biometric parameters. Growth rate of fetal head through pregnancy (head circumference Z score) was lower in fetuses with congenital heart defects compared with controls (p = 0.043). In group I, the head circumference Z score longitudinal decrease was significantly higher than in group II (p < 0.001). CONCLUSIONS: Fetuses with congenital heart defects are at risk of smaller head size and Doppler changes. Growth rate of fetal head throughout pregnancy is also affected. These findings are mainly associated with cardiac defects with expected low oxygen supply to the central nervous system.

Ultrasonographic study of umbilical cord twist direction during second trimester.

OBJECTIVE: To explore/study/evaluate the relationships among umbilical twist direction, the degree of umbilical twist and differences of umbilical arterial diameters (UAD). METHODS: All obstetric patients presenting for prenatal care of singleton fetuses between 18 and 25 weeks gestation to a single provider (MN) from 2015 to 2018 had detailed umbilical cord Doppler measurements. Data including the cord twist direction, degree of twist and number of twists per cord segment length, and the diameters of each UA (UAD) and the umbilical vein (UVD) were extracted from the records. UAs were described as right or left depending on their position at the fetal cord insertion. Three groups were identified: Group A: right UAD > left UAD and Group B: left UAD > right UAD Group C: equal UAD. The coiling index was calculated as the inverse of the length of cord required for one complete 360 degrees wrap of the UA around the cord. According to the difference of UADs, the variables of right and left UADs, the coiling index, and frequencies of umbilical twist direction were analyzed using non-parametric methods. RESULTS: 485 singleton fetuses and umbilical cords were examined. The value of the antenatal coiling index in cases with left UAD greater than right was 0.43 ± 0.16, which was significantly higher than 0.38 ± 0.16 with right UAD greater than left (p = .001). There were significant differences between the two groups in the values of right and left UAD, value of right minus left UAD, absolute value between right and left UAD, antenatal coiling index, antenatal coiling index due to umbilical twist direction and frequencies of cord twist direction. CONCLUSION: The direction of umbilical twist may be in part dependent on differences in diameters of the umbilical arteries, in addition to other fetal characteristics such as fetal movement, or handedness of fetus or mother, fetal hemodynamic forces and structure of muscles of umbilical vessels.

Acute fetal response to high-intensity interval training in the second and third trimesters of pregnancy.

The majority of women do not meet the recommended levels of exercise during their pregnancies, frequently due to a lack of time. High-intensity interval training offers a potential solution, providing an effective, time-efficient exercise modality. This exercise modality has not been studied in pregnancy therefore, the objective of this study was to evaluate fetal response to a high-intensity interval training resistance circuit in the late second and early third trimesters of pregnancy. Fourteen active, healthy women with uncomplicated, singleton pregnancies participated in a high-intensity interval training resistance circuit between 28 + 0/7 and 32 + 0/7 weeks. A Borg rating of perceived exertion of 15-17/20 and an estimated heart rate of 80%-90% of maternal heart-rate maximum was targeted. Fetal well-being was evaluated continuously with fetal heart-rate tracings and umbilical artery Doppler velocimetry conducted pre-and post-exercise. Fetal heart rate tracings were normal throughout the exercise circuit. Post-exercise, umbilical artery end-diastolic flow was normal and significant decreases were observed in the mean systolic/diastolic ratios, pulsatility indexes and resistance indexes. Therefore, in a small cohort of active pregnant women, a high-intensity interval training resistance circuit in the late second and early third trimesters of pregnancy appears to be a safe exercise modality with no acute, adverse fetal effects but further study is required. Novelty: High-intensity interval training, at an intensity in excess of current recommendations, does not appear to be associated with any adverse fetal effects in previously active pregnant women. High-intensity interval training is an enjoyable and effective exercise modality in previously active pregnant women.

Dexamethasone on absent end-diastolic flow in umbilical artery, in growth restricted fetuses from early-onset preeclamptic pregnancies and the perinatal outcome.

BACKGROUND: Absent end-diastolic flow (AEDF) in the umbilical artery (UA) worsens the already poor prognosis of growth-restricted fetuses (GRFs) in pregnancies complicated by early-onset preeclampsia with severe features (ESP). METHOD: We assessed the correlation between the effect of maternal dexamethasone (Dex) on AEDF in the UA and perinatal outcomes, in 59 GRFs from EPS-complicated pregnancies. The maternal outcome was also evaluated. RESULTS: The mean maternal age at inclusion was 22.4 ± 5.9 years. Dex transiently restored EDF in the UA in 38 (64.4%) cases (trAEDF group), but in 21 (35.6%) patients, the flow was persistently absent (prAEDF group). The effect lasted up to the 4th day.The gestational age at diagnosis, number of days from admission until delivery, and fetal weight were significantly lower in the prAEDF group than in the trAEDF group (p < .05). The same group had a significantly increased rate of fetal proximal deterioration, low APGAR scores, neonatal hypoxia, assisted ventilation, mild intraventricular haemorrhage (I/II), and respiratory distress syndrome, as well as maternal deterioration, especially in cases of resistant hypertension (p < .05). Although the rates of fetal acidemia and perinatal mortality in the prAEDF group were respectively three times and two times higher, the differences were not significant (p > .05). CONCLUSIONS: The Dex no-effect on UA Doppler in GRFs with AEDF in the UA, in EPS-complicated pregnancies, can be a useful marker for a higher risk of proximal fetal deterioration, poor state at delivery, neonatal hypoxic complications, and worsening maternal condition, but not for perinatal mortality. The findings also highlight the alarmingly younger age of patients with EPS. Finally, all these pregnancies should be monitored in a complex multidisciplinary manner in tertiary referral units.Key messageThe effect of dexamethasone on absent end-diastolic flow in the umbilical artery in growth-restricted fetuses from pregnancies complicated by early-onset preeclampsia with severe features can be a useful prognostic factor for perinatal outcomes.

Predicting Adverse Outcomes in Monochorionic-Diamniotic Twins: The Role of Intertwin Discrepancy in Middle Cerebral Artery Doppler Measurements and the Cerebroplacental Ratio.

OBJECTIVE: This study was aimed to evaluate the role of intertwin discrepancy in middle cerebral artery peak systolic velocity (MCA-PSV) and cerebroplacental ratio (CPR) for the prediction of adverse outcomes in monochorionic-diamniotic (MCDA) twin pregnancies. STUDY DESIGN: A retrospective cohort study of MCDA pregnancies that underwent ultrasound surveillance at a perinatal referral center from 2007 to 2017. Intertwin MCA-PSV discrepancy (MCA-ΔPSV-MoM) was defined as the absolute difference of MCA-PSV multiple of the median (MoM) for gestational age between twins. Intertwin CPR discrepancy (CPR-Δ) was defined as the absolute difference of CPR between twins. The maximum MCA-ΔPSV-MoM and CPR-Δ before and after 26 weeks of gestation were assessed as predictors of pregnancy and neonatal outcomes through simple logistic regression models and Pearson's correlation coefficients. Receiver operating characteristic (ROC) curves were generated to determine the predictive value of maximum MCA-ΔPSV-MoM and CPR-Δ. RESULTS: A total of 143 MCDA pregnancies met inclusion criteria. There was a significant association between MCA-ΔPSV-MoM at <26 weeks and the development of twin anemia-polycythemia sequence (TAPS; p = 0.007), intrauterine fetal demise (IUFD; p = 0.009), and neonatal intensive care unit (NICU) admission (p < 0.05). MCA-ΔPSV-MoM at ≥26 weeks was associated with the development of TAPS (p < 0.001). CPR-Δ at <26 weeks was associated with the development of twin-twin transfusion syndrome (TTTS; p = 0.03) and NICU admission (p = 0.02). MCA-ΔPSV-MoM at ≥26 weeks was highly predictive of TAPS (area under curve [AUC] = 0.92). A cut-off of 0.44 would identify TAPS with 100% sensitivity and 73% specificity. CONCLUSION: In MCDA pregnancies, intertwin MCA and CPR discrepancies are associated with adverse pregnancy and neonatal outcomes, including TAPS, TTTS, IUFD, and NICU admission. Evaluation of intertwin MCA and CPR differences demonstrated the potential for clinical predictive utility in the surveillance of MCDA twin pregnancies. KEY POINTS: · Intertwin discrepancy of MCA-PSV and CPR is associated with adverse pregnancy outcomes.. · Intertwin differences in Doppler ultrasound may occur prior to meeting diagnostic criteria for TTTS or TAPS.. · There is potential clinical predictive utility in MCA and CPR surveillance of MCDA twin pregnancies..

Placental characteristics in different types of selective fetal growth restriction in monochorionic diamniotic twins.

INTRODUCTION: This study aimed to explore the differences in placental characteristics among three types of selective fetal growth restriction (sFGR) in monochorionic diamniotic twin pregnancies. MATERIAL AND METHODS: A total of 123 placentas with sFGR between April 2013 and October 2019 were retrospectively analyzed after dye injection. Placental characteristics were compared among the three types. RESULTS: The gestational age at diagnosis and delivery was less in sFGR II and III than in sFGR I (22.9 [21.7-33.6], 23.3 [20.0-26.1] and 25.7 [19.0-35.0] weeks, p < 0.001; 32.3 [31.6-35.1], 34.1 [29.9-34.7] and 35.5 [34.0-37.0] weeks, p < 0.001). The birthweight discordance ratio was less in sFGR I than in sFGR II (0.28 [0.14-0.43] and 0.30 [0.23-0.37], p < 0.001). The prevalence of a thick artery-artery anastomosis was higher in sFGR III than in sFGR I or II (81.8%, 44.9% and 48.6%, p = 0.010). The placental territory discordance ratio was higher in sFGR II and III than in sFGR I (0.60 [0.17-0.88], 0.60 [0.01-0.80] and 0.50 [0.01-0.71], p = 0.001). CONCLUSIONS: Compared with sFGR I, the earlier onset time of sFGR II and III might be due to their higher placental territory discordance. The prevalence of thick artery-artery anastomoses was expected to be higher in sFGR III than in sFGR I or II.

Wave reflections in the umbilical artery measured by Doppler ultrasound as a novel predictor of placental pathology.

BACKGROUND: The umbilical artery (UA) Doppler pulsatility index is used clinically to detect elevated feto-placental vascular resistance. However, this metric is confounded by variation in fetal cardiac function and is only moderately predictive of placental pathology. Our group developed a novel ultrasound methodology that measures wave reflections in the UA, thereby isolating a component of the Doppler signal that is specific to the placenta. The present study examined whether wave reflections in the UA are predictive of placental vascular pathology. METHODS: Standard clinical Doppler ultrasound of the UAs was performed in 241 pregnant women. Of these, 40 women met narrowly defined preset criteria for the control group, 36 had maternal vascular malperfusion (MVM) and 16 had fetal vascular malperfusion (FVM). Using a computational procedure, the Doppler waveforms were decomposed into a pair of forward and backward propagating waves. FINDINGS: Compared to controls, wave reflections were significantly elevated in women with either MVM (p<0.0001) or FVM pathology (p = 0.02). In contrast, the umbilical and uterine artery pulsatility indices were only elevated in the MVM group (p<0.0001) and there were no differences between women with FVM and the controls. INTERPRETATION: The measurement of wave reflections in the UA, combined with standard clinical ultrasound parameters, has the potential to improve the diagnostic performance of UA Doppler to detect placental vascular pathology. Identifying women with FVM pathology is particularly challenging prenatally and future investigations will determine if women at risk of this specific placental disease could benefit from this novel diagnostic technique.