Umbilical vein blood flow: State-of-the-art.

Placental blood supply to the fetus can be measured by evaluating the umbilical vein blood flow. Despite its potential application in healthcare, the umbilical vein blood flow volume is still used only in research setting. One of the reasons is a concern regarding its reproducibility, partly due to technology issues. Nowadays, technology improvements make this evaluation accurate and reproducible. The aim of this review is to refresh basic elements of the physiology of umbilical vein blood flow and its analysis. Its evaluation in normal and abnormal fetal growth is also discussed.

Quantification of blood flow in the fetus with cardiovascular magnetic resonance imaging using Doppler ultrasound gating: validation against metric optimized gating.

INTRODUCTION: Fetal cardiovascular magnetic resonance (CMR) imaging is used clinically and for research, but has been previously limited due to lack of direct gating methods. A CMR-compatible Doppler ultrasound (DUS) gating device has resolved this. However, the DUS-gating method is not validated against the current reference method for fetal phase-contrast blood flow measurements, metric optimized gating (MOG). Further, we investigated how different methods for vessel delineation affect flow volumes and observer variability in fetal flow acquisitions. AIMS: To 1) validate DUS gating versus MOG for quantifying fetal blood flow; 2) assess repeatability of DUS gating; 3) assess impact of region of interest (ROI) size on flow volume; and 4) compare time-resolved and static delineations for flow volume and observer variability. METHODS: Phase-contrast CMR was acquired in the fetal descending aorta (DAo) and umbilical vein by DUS gating and MOG in 22 women with singleton pregnancy in gestational week 360 (265-400) with repeated scans in six fetuses. Impact of ROI size on measured flow was assessed for ROI:s 50-150% of the vessel diameter. Four observers from two centers provided time-resolved and static delineations. Bland-Altman analysis was used to determine agreement between both observers and methods. RESULTS: DAo flow was 726 (348-1130) ml/min and umbilical vein flow 366 (150-782) ml/min by DUS gating. Bias±SD for DUS-gating versus MOG were - 45 ± 122 ml/min (-6 ± 15%) for DAo and 19 ± 136 ml/min (2 ± 24%) for umbilical vein flow. Repeated flow measurements in the same fetus showed similar volumes (median CoV = 11% (DAo) and 23% (umbilical vein)). Region of interest 50-150% of vessel diameter yielded flow 35-120%. Bias±SD for time-resolved versus static DUS-gated flow was 33 ± 39 ml/min (4 ± 6%) for DAo and 11 ± 84 ml/min (2 ± 15%) for umbilical vein flow. CONCLUSIONS: Quantification of blood flow in the fetal DAo and umbilical vein using DUS-gated phase-contrast CMR is feasible and agrees with the current reference method. Repeatability was generally high for CMR fetal blood flow assessment. An ROI similar to the vessel area or slightly larger is recommended. A static ROI is sufficient for fetal flow quantification using currently available CMR sequences.

Pathophysiological Mechanism of Extravasation via Umbilical Venous Catheters.

A rare complication of umbilical venous catheter (UVC) insertion is the extravasation of the infusate into the peritoneal cavity. We report 3 cases of abdominal extravasation of parenteral nutrition (PN) fluid via UVCs. Two of these cases presented as "acute abdomen" which were assumed to be necrotizing enterocolitis clinically; however, during postmortem, PN ascites and liver necrosis were found. A further case is described in an infant with congenital diaphragmatic hernia. While we were unable to ascertain direct vessel perforation by the catheter in any of these cases, based on pathological and histological examination, the proposed mechanism of PN fluid extravasation is leakage through microinjuries of liver vessel walls and necrotic parenchyma. PN extravasation should be considered as a differential diagnosis of acute abdomen when PN is infused via an UVC presumably as PN may have a direct irritant effect on the peritoneum.

Uterine artery and umbilical vein blood flow are unaffected by moderate habitual physical activity during pregnancy.

OBJECTIVE: This study aims to noninvasively quantify blood flow in the uterine arteries (UTAs) and umbilical vein (UV) using phase-contrast magnetic resonance imaging (PC-MRI) and test whether these correlate with maternal fitness parameters. METHOD: Resting UTA and UV flows were measured in 23 healthy 30 ± 3-year-old women who engaged in moderate-intensity physical activity during pregnancy. Participant fitness was characterized in the second and third trimesters using the submaximal oxygen uptake (VO2 ) test measuring heart rate (HR), VO2 , ventilation (ventilatory equivalent [VE]/VO2 ), and the Borg rating of perceived exertion (respiratory quotient [RQ]). Linear regression models were used to determine the associations between blood flow and maternal fitness measures. RESULTS: Blood flows in the UTA (957 ± 241 mL/min) and UV (132 ± 38 mL/min/kg) were successfully measured in 20 (87%) participants. Neither was associated with any physical fitness parameters (HR, VO2 , VE/VO2 , and RQ) nor with any second-to-third trimester change in these parameters. CONCLUSION: PC-MRI can be used to noninvasively measure blood flow in the UTA and UV. Neither resting UTA nor UV flow is associated with maternal fitness parameters. This is the first MRI-based study to provide novel hemodynamic data suggesting decoupling between maternal moderate fitness level and the maternal-placental-fetal hemodynamic system in healthy, normal body mass index (BMI) pregnancies.

Umbilical cannulation optimizes circuit flows in premature lambs supported by the EXTra-uterine Environment for Neonatal Development (EXTEND).

KEY POINTS: Bronchopulmonary dysplasia is a disease of extreme prematurity that occurs when the immature lung is exposed to gas ventilation. We designed a novel 'artificial womb' system for supporting extreme premature lambs (called EXTEND) that obviates gas ventilation by providing oxygen via a pumpless arteriovenous circuit with the lamb submerged in sterile artificial amniotic fluid. In the present study, we compare different arteriovenous cannulation strategies on EXTEND, including carotid artery/jugular vein (CA/JV), carotid artery/umbilical vein (CA/UV) and umbilical artery/umbilical vein (UA/UV). Compared to CA/JV and CA/UV cannulation, UA/UV cannulation provided significantly higher, physiological blood flows to the oxygenator, minimized flow interruptions and supported significantly longer circuit runs (up to 4 weeks). Physiological circuit blood flow in UA/UV lambs made possible normal levels of oxygen delivery, which is a critical step toward the clinical application of artificial womb technology. ABSTRACT: EXTEND (EXTra-uterine Environment for Neonatal Development) is a novel system that promotes physiological development by maintaining the premature lamb in a sterile fluid environment and providing gas exchange via a pumpless arteriovenous oxygenator circuit. During the development of EXTEND, different cannulation strategies evolved with the aim of improving circuit flow. The present study examines how different cannulation strategies affect EXTEND circuit haemodynamics in extreme premature lambs. Seventeen premature lambs were cannulated at gestational ages 105-117 days (term 145-150 days) and supported on EXTEND for up to 4 weeks. Experimental groups were distinguished by cannulation strategy: carotid artery outflow and jugular vein inflow (CA/JV; n = 4), carotid artery outflow and umbilical vein inflow (CA/UV; n = 5) and double umbilical artery outflow and umbilical vein inflow (UA/UV; n = 8). Circuit flows and pressures were measured continuously. As we transitioned from CA/JV to CA/UV to UA/UV cannulation, mean duration of circuit run and weight-adjusted circuit flows increased (P < 0.001) and the frequency of flow interruptions declined (P < 0.05). Umbilical vessels generally accommodated larger-bore cannulas, and cannula calibre was directly correlated with circuit pressures and indirectly correlated with flow:pressure ratio (a measure of post-membrane resistance). We conclude that UA/UV cannulation in fetal lambs on EXTEND optimizes circuit flow dynamics and flow stability and also supports circuit flows that closely approximate normal placental flow.

The long non-coding RNA MALAT1 activates Nrf2 signaling to protect human umbilical vein endothelial cells from hydrogen peroxide.

The potential effect of the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) against hydrogen peroxide (H2O2)-induced oxidative injury in endothelial cells was tested. We show that forced-expression of MALAT1 using a lentiviral vector ("LV-MALAT1") significantly attenuated H2O2-induced death and apoptosis of human umbilical vein endothelial cells (HUVECs). Conversely, knocking down of MALAT1 by targeted siRNA exacerbated H2O2-induced HUVEC injury. For the mechanism study, we show that LV-MALAT1 induced Keap1 downregulation, leading to nuclear-factor-E2-related factor 2 (Nrf2) stabilization and activation. Critically, Nrf2 shRNA almost completely abolished LV-MALAT1-mediated HUVEC protection against H2O2. Significantly, H2O2-induced oxidative stress, lipid peroxidation and DNA damages in HUVECs were attenuated by LV-MALAT1, but were intensified with MALAT1 siRNA. In summary, we identified a novel signaling axis involving MALAT1, Keap1 and Nrf2, which in turn protects HUVECs from oxidative injury.

Interleukin-33 induces growth-regulated oncogene-α expression and secretion in human umbilical vein endothelial cells.

Although interleukin-33 (IL-33), a member of the IL-1 cytokine family, plays proinflammatory roles in immune cells as an "alarmin," little is known regarding the biological actions of IL-33 on vascular endothelial cells. To investigate the effects of IL-33 on vascular endothelial cells, we first screened the IL-33-regulated proteins in human umbilical vein endothelial cells (HUVECs) using a dot blot array and observed that IL-33 markedly increased growth-regulated oncogene-α (GRO-α), a chemokine that is also known as chemokine (C-X-C motif) ligand 1 (CXCL1). Real-time reverse transcription PCR and ELISA demonstrated that IL-33 induced GRO-α expression and secretion in HUVECs in a dose- and a time-dependent manner. Western immunoblot assay revealed that IL-33 activated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK). In addition, translocation of nuclear factor-κB (NF-κB) p65 to the nucleus of HUVECs was observed by IL-33 stimulation. Furthermore, treatment with pharmacological inhibitors against ERK1/2 (PD98059), JNK (SP600125), or NF-κB (BAY11-7085) significantly suppressed IL-33-induced GRO-α gene expression and secretion from HUVECs. Moreover, immunohistochemical staining demonstrated that IL-33 and GRO-α coexpressed in the endothelium of human carotid atherosclerotic plaque. Taken together, the present study indicates that IL-33 localized in the human atherosclerotic plaque increases GRO-α mRNA expression and protein secretion via activation of ERK1/2, JNK, and NF-κB in HUVECs, suggesting that IL-33 plays an important role in the pathophysiology and development of atherosclerosis.

Identification of Antiangiogenic Potential and Cellular Mechanisms of Napyradiomycin A1 Isolated from the Marine-Derived Streptomyces sp. YP127.

Angiogenesis is the process of new blood vessel formation. Excessive angiogenesis is a critical factor in the progression of cancer, macular degeneration, and other chronic inflammatory diseases. When investigating the effects of crude extracts of cultured marine microorganisms, an extract of the cultured Streptomyces sp. YP127 strain was found to inhibit human umbilical vein endothelial cell (HUVEC) tube formation. Bioassay-guided fractionation and spectroscopic data analyses led to the identification of napyradiomycin A1 (1) as an antiangiogenic component of the extract. Compound 1 inhibited HUVEC tube formation in a concentration-dependent manner. It inhibited endothelial cell proliferation but did not affect human dermal fibroblast proliferation. Compound 1 also suppressed migration and invasion of vascular endothelial cells. In addition, compound 1 suppressed vascular endothelial cadherin expression and increased the permeability of the endothelial cell membrane. These results suggested that compound 1 modulates cell permeability and inhibits the angiogenesis of endothelial cells.

Sexual Dimorphism in Umbilical Vein Blood Flow During the Second Half of Pregnancy: A Longitudinal Study.

OBJECTIVES: To investigate gestational age-specific serial changes in umbilical vein (UV) volume blood flow during the second half of normal pregnancy and establish sex-specific reference ranges. METHODS: This work was a prospective longitudinal study of singleton low-risk pregnancies. The UV diameter and maximum blood flow velocity were serially measured by sonography at the intra-abdominal portion of the UV over 19 to 41 weeks. Umbilical vein volume blood flow was calculated and normalized for estimated fetal weight. RESULTS: One hundred seventy-nine women and their fetuses (87 male and 92 female) were included in the final analysis, and a total of 746 observations were used to construct sex-specific reference intervals. We found no statistically significant sex-specific differences in the UV parameters examined. However, the temporal development patterns of normalized UV volume blood flow appeared to differ between male and female fetuses during the second half of pregnancy, with crossovers at 24 and 32 weeks' gestation. CONCLUSIONS: Umbilical vein volume blood flow is similar among male and female fetuses in quantitative terms, but the pattern of gestational age-dependent temporal changes may be different, which may have important physiologic implications with regard to in utero development and maturation of the fetoplacental unit.

Transient fetal blood redistribution associated with maternal supine position.

OBJECTIVE: To investigate whether fetal blood circulation is influenced by the maternal supine position. METHODS: The inclusion criteria were good health, a singleton pregnancy, maternal age between 18 and 40 years, gestational age between 36 and 40 weeks, and an agreement to participate in the study. Each participant (n=20) was initially asked to adopt the left lateral position for 5 min, while fetal Doppler measurements were taken of the fetal middle cerebral artery (MCA), umbilical artery (UA), and umbilical vein (UV). Subsequently, they were asked to change to the supine position for Doppler measurements at 5 and at 10 min. RESULTS: When a woman remained in the supine position for 5 min, there was a significant reduction in fetal MCA-pulsatility index (PI) (median 1.70 vs. 1.42, P=0.003). This reduction did not persist after 10 min (median 1.70 vs. 1.65 P=1.0). There was no significant difference between the left lateral and the supine position at 5 and at 10 min in terms of UA-PI (0.853 vs. 0.870 vs. 0.858, P=0.850), UV flow (217 vs. 242 vs. 236 mL/min, P=0.263), and normalized UV flow (72.2 vs. 80.8 vs. 78.8 mL/min/kg, P=0.271). CONCLUSIONS: Changing maternal position from the left lateral to the supine position caused a reduction in resistance in fetal MCA and no changes in UA or UV indices. However, despite the changes in cerebral circulation which occurred at 5 min by shifting position, they did not remain for 10 min. The changes may be related to reduction in maternal oxygen saturation as there was no decrease in UV blood flow.

Umbilical vein vasomotion detected in vivo by serial three-dimensional pixelwise spatially angle-corrected volume flow measurements.

OBJECTIVE: To explore changes in volume flow in the umbilical vein in healthy second-trimester fetuses. METHODS: This was a prospective observational pilot study performed at Stavanger University Hospital, Norway, between May and October 2013. Serial three-dimensional ultrasound recordings from the umbilical vein were acquired every 30 s in a 5-min period in 43 fetuses at 17-20 weeks' gestation. The recordings were analyzed with pixelwise spatially angle-corrected volume flow measurements. RESULTS: We observed variation in the umbilical vein volume flow in all fetuses, ranging from a mean minimum of 1.01 mL/s to a mean maximum of 2.60 mL/s. The minimum of all measurements was 57% compared with the mean value and the maximum was 148% of the mean value. The individual flow volume measurements ranged between 0.11 and 4.14 mL/s (mean, 1.76 mL/s). Within this range, an undulating course of all perfusion parameters was observed, with a full period of 4-5 min duration. CONCLUSION: Healthy second-trimester fetuses show cyclical variation in blood flow in the umbilical vein. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Hemodynamic aspects of normal human feto-placental (umbilical) circulation.

Understanding the changes in normal circulatory dynamics that occur during the course of pregnancy is essential for improving our knowledge of pathophysiological mechanisms associated with feto-placental diseases. The umbilical circulation is the lifeline of the fetus, and it is accessible for noninvasive assessment. However, not all hemodynamic parameters can be reliably measured in utero using currently available technology. Experimental animal studies have been crucial in validating major concepts related to feto-placental circulatory physiology, but caution is required in directly translating the findings of such studies into humans due to species differences. Furthermore, it is important to establish normal reference ranges and take into account gestational age associated changes while interpreting the results of clinical investigation. Therefore, it is necessary to critically evaluate, synthesize and summarize the knowledge available from the studies performed on human pregnancies to be able to appropriately apply them in clinical practice. This narrative review is an attempt to present contemporary concepts on hemodynamics of feto-placental circulation based on human studies.

Muscarinic-mediated vasoconstriction in human, rat and sheep umbilical cords and related vasoconstriction mechanisms.

OBJECTIVE: The umbilical cord provides nutrition and oxygen to the fetus. The aim of this study was to determine the effects of acetylcholine (ACh) on umbilical cords from humans and other mammals, and the mechanisms of ACh-mediated vasoconstriction in the human umbilical cord. DESIGN: Human and animal umbilical cords used in vascular and cellular experiments. SETTING: Institute for Fetology, First Hospital of Soochow University, Suzhou, China. POPULATION: A total of 85 pregnant women, 16 Sprague Dawley rats and seven pregnant sheep. METHODS: Umbilical cord veins and arteries from humans, rats and sheep, aortas and mesenteric arteries from rats, and mesenteric, carotid and femoral arteries from ovine fetuses were used to compare vascular functions in response to ACh and to determine the mechanisms of ACh-mediated umbilical vasoconstriction. Vascular tension and ion channel currents were measured on isolated vessels and smooth muscle cells from human umbilical cords. MAIN OUTCOME MEASURES: Provision of new evidence to conclude that ACh-stimulated vasoconstriction is common to all umbilical cords, and cellular mechanisms are linked to potassium channels. RESULTS: ACh caused reliable vasoconstriction in umbilical veins/arteries in humans, rats and sheep, but not in any other vessels, including fetal vessels. Atropine inhibited the effects of ACh. The mRNA of ACh-muscarinic receptor subtypes M1 -M5 was expressed in human umbilical vessels. The protein kinase C antagonist GF109203X and the calcium inhibitor nifedipine decreased ACh-induced vasoconstriction in human umbilical vessels. ACh also caused a reduction in whole-cell potassium channel currents and the single-channel current of large-conductance calcium-activated potassium (BKca) channels. CONCLUSION: Umbilical vessels are significantly different from other vessels in their response to ACh. BKca channels in smooth muscle cells may play important roles in ACh-mediated vasoconstriction in human umbilical cords. This information may be important for fetal medicine and practice with regard to the effect on fetal development of umbilical vascular functions.

Influence of parity on fetal hemodynamics and amniotic fluid volume at term.

OBJECTIVES: Pregnancy complications, particularly those associated with placental dysfunction, occur more frequently in nulliparous than in parous women. This difference may be a consequence of improved trophoblastic invasion and, as a result, improved placental function following previous pregnancy. Placental dysfunction in cases of fetal growth restriction may be identified by ultrasound assessment of fetoplacental hemodynamics and amniotic fluid volume. In this prospective observational study, we investigated whether differences in these measures of placental function exist between nulliparous and parous women, prior to active labor. METHODS: Over a 2-year period, 456 nulliparous and 152 parous women with uncomplicated singleton pregnancies were recruited to this prospective observational study. Each participant underwent an ultrasound assessment prior to active labor, during which fetal biometry, umbilical artery, middle cerebral artery and umbilical venous Dopplers, as well as amniotic fluid volume, were assessed. All cases were followed up within 48 h of delivery. Ultrasound parameters and intrapartum outcomes were then compared between the nulliparous and parous groups. RESULTS: Compared with nulliparous women, parous women had significantly higher fetal middle cerebral artery pulsatility index, cerebroplacental ratio and amniotic fluid volume. In nulliparous women, middle cerebral artery flow rate was also significantly higher and represented a greater percentage of umbilical venous flow than was observed in parous women. CONCLUSION: Prior to the active phase of labor, ultrasound parameters indicative of placental function differ significantly between nulliparous and parous pregnancy, even amongst an uncomplicated, low-risk cohort.

Human fetoplacental and fetal liver blood flow after maternal glucose loading: a cross-sectional observational study.

OBJECTIVE: To study umbilical vein and fetal liver blood flow related to fetal anthropometric measures following maternal oral glucose loading. DESIGN: Experimental design in a cross-sectional observational study. SETTING: University hospital. POPULATION: A total of 113 low-risk pregnancies (30-32 weeks of gestation). METHODS: Ultrasound Doppler measurements of umbilical vein and ductus venosus blood flow (ml/min) before and 2 h after completed 75-g oral glucose tolerance test (OGTT). Liver blood flow was defined as the umbilical vein blood flow minus ductus venosus blood flow. MAIN OUTCOME MEASURES: Changes in umbilical vein and fetal liver blood flow following OGTT related to fetal biometric measurements. RESULTS: In the fasting state, fetal abdominal circumference z-scores did not correlate with any of the flow parameters; 120 min after glucose loading, the z-scores correlated positively with the changes in umbilical vein (r = 0.25, p = 0.010) and fetal liver blood flow (r = 0.25, p = 0.009), but not with those in ductus venosus (p = 0.84). In simultaneous multiple linear regression analyses, the effects of the changes in umbilical vein or fetal liver blood flow after OGTT on the fetal abdominal circumference z-scores were almost equal to or greater than other parameters related to fetal size (body mass index, fasting plasma glucose, parity, and sex). Fetal heart rate increased after OGTT, but did not influence the association between the blood flow parameters and fetal abdominal circumference z-scores. CONCLUSIONS: Changes in umbilical vein and fetal liver blood flow after glucose loading were positively related to fetal abdominal size.

Reference ranges for ductus venosus velocity ratios in pregnancies with normal outcomes.

OBJECTIVES: The purpose of this study was to establish reference ranges for ductus venosus velocity ratios. METHODS: Singleton pregnancies from 11 to 38 weeks with exactly established gestational ages (GAs) were recruited for the study. Pregnancies with fetal anomalies, growth abnormalities, maternal medical complications, stillbirth, birth weight below the 10th or above the 90th percentile, and neonatal anomalies were excluded. The ductus venosus pulsatility index for veins (PIV) and velocity ratios (S/v, S/D, v/D, S/a, v/a, and D/a, where S indicates ventricular systole [s-wave], v, ventricular end-systolic relaxation [v-descent], D, passive diastolic ventricular filling [D-wave], and a, active ventricular filling during atrial systole [a-wave]) were calculated. Separate regression models were fitted to estimate the mean and standard deviation at each GA for each ratio. RESULTS: A total of 902 velocity wave ratios and ductus venosus PIVs were used for reference ranges. The S/v, S/D, and v/D ratios were not changed with GA (P > .05 for all). The PIV and S/a, v/a, and D/a ratios were reduced with GA (P < .0001 for all). Significant reductions in the means and standard deviations of the PIV and S/a, v/a, and D/a ratios were observed between 17 and 18 weeks' gestation. Therefore, nomograms were separately created between 11 and 17 weeks and 18 and 38 weeks. CONCLUSIONS: We created reference ranges for ductus venosus velocity ratios between 11 and 38 weeks' gestation in normal pregnancies. These reference ranges may prove beneficial for evaluation of fetal conditions that are associated with cardiovascular abnormalities.

A reference for ductus venosus blood flow at 11-13+6 weeks of gestation.

OBJECTIVE: To establish reference ranges for ductus venosus (DV) blood flow assessment obtained transabdominally at 11-13(+6) weeks of gestation. METHODS: A cross-sectional study was conducted on singleton pregnancies with a crown-rump length (CRL) ranging from 45 to 84 mm, normal fetus, and subsequent newborn birth weight appropriate for gestational age. Measurements of DV Doppler variables were performed by experienced sonographers: peak velocity during ventricular systole (S-wave) and diastole (D-wave), nadir during atrial contraction (A-wave), time-averaged maximum velocity (TAmax), pulsatility index for veins (PIV), and peak velocity index for veins (PVIV). RESULTS: A total of 304 fetuses were included. The mean CRL was 60.7 ± 7.2 mm (range: 45.9-75.5). The mean nuchal translucency measurement was 1.4 ± 0.4 mm. The S-wave, D-wave, A-wave, and TAmax values varied significantly with gestational age (p < 0.05) and regression models were constructed for each variable. The remaining variables, systolic/atrial wave ratio, preload index, PVIV, and PIV, did not vary significantly with gestational age within this CRL range. CONCLUSION: Reference ranges for DV Doppler assessment were established in normal fetuses. These ranges may be a useful tool for evaluation of anueploidy and fetal cardiac function.

Are 1st-trimester ß-human chorionic gonadotrophin and pregnancy-associated plasma protein A levels predictive of intrapartum fetal compromise in a selected normal population?

BACKGROUND: The incidence of cerebral palsy in term infants has not changed over the last 30 years. Current intrapartum monitoring techniques are limited by their inherent poor specificity. Changes in fetal haemodynamics in the term fetus, similar to those seen in fetal growth restriction, have been associated with an increased risk of subsequent intrapartum fetal compromise. Alterations in first-trimester ß-hCG and PAPP-A levels are predictive of fetal growth restriction. AIMS: In this study, we aimed to establish whether first-trimester ß-hCG and PAPP-A levels were predictive of fetal compromise in labour and whether these first-trimester markers could be correlated with fetal haemodynamics at term in a low-risk population. MATERIALS AND METHODS: Over a two-year period, 427 women with low risk, uncomplicated pregnancies were recruited to this study. All participants underwent a prelabour ultrasound examination during which fetal biometry and haemodynamics were assessed. First-trimester ß-hCG and PAPP-A levels were recorded from the case notes. All cases were followed up within 48 hours of delivery, and first-trimester ß-hCG and PAPP-A levels correlated with intrapartum outcomes and fetal haemodynamics. RESULTS: No significant relationship between first-trimester ß-hCG and PAPP-A levels and subsequent intrapartum fetal compromise was observed. Weak but significant correlations were observed between ß-hCG levels and umbilical venous flow rate, as well as PAPP-A levels and uterine artery pulsatility index. CONCLUSIONS: ß-hCG and PAPP-A levels measured during the first trimester are not predictive of subsequent intrapartum fetal compromise within a low-risk population.