Spontaneous intrauterine umbilical artery thrombosis leading to severe fetal growth restriction

Intrauterine thrombosis of umbilical cord vessels is a rare event (2.5-4.5/10,000) and usually followed by poor fetal outcome. We present the rare case of spontaneous intrauterine thrombosis of an umbilical artery leading to severe intrauterine growth restriction (IUGR) and provide clinical and pathological findings. A 28-year-old nulliparous third gravida was referred to our institution because of IUGR at 32+4 weeks of gestation. Fetal growth had been appropriate until the 31st week of gestation and had stopped thereafter. There were no signs of abruption of the placenta and no structural abnormalities except an absent paravesical colour Doppler flow in the region of the right umbilical artery. Other Doppler measurements, karyotype and TORCH serology were normal. Intermittent non-reassuring fetal heart rate led to cesarean section at 34+3 weeks of gestation. A healthy girl with measurements on the 3rd centile was born (weight of 1,590 g, length of 41 cm and head circumference of 29 cm). Gross examination displayed an elongated, highly twisted umbilical cord with a length of 70 cm, central insertion and three umbilical vessels. Microscopic examination confirmed the diagnosis of umbilical artery thrombosis along the entire length of the umbilical cord. Calcification within the thrombus and microcalcification in occluded chorionic vessels were observed as well as hemorrhagic endovasculitis and endangiopathia obliterans in the stem villi arteries. This fetal thrombotic vasculopathy (FTV) comprised about 40% of the parenchyma. The coagulation parameters and blood counts of the mother and the infant were normal apart from transient neonatal thrombocytopenia. The reason for thrombosis remained unclear but could be attributed to the elongated and highly twisted umbilical cord. Intrauterine arterial thrombosis may cause severe IUGR. This condition might be detectable by ultrasound in the course of an IUGR workup, especially when no other reasons can be found.     

Antenatal sonographic detection of single umbilical artery.

The absence of one umbilical artery of single umbilical artery (SUA) is one of the most common congenital malformations in man. This vascular anomaly of the umbilical cord is frequently associated with other congenital malformations as well as some adverse perinatal events such as intrauterine growth retardation (IUGR), premature delivery, and increased perinatal mortality. Five cases of SUA detected prenatally by ultrasound are reported here in detail, including the first reported case in a twin gestation. None of the 5 affected infants had associated anomalies, but 2 cases of intrauterine growth retardation (IUGR) and 1 stillborn infant were noted in this series. An umbilical vein/umbilical artery ratio less than 2 was invariably found in all cases, making this observation another useful sonographic characteristic to use in the antenatal detection of SUA. Since the umbilical cord can be easily seen prenatally by ultrasound, and SUA is recognized as an important index for detecting congenital malformations, examination of the umbilical cord for the absence of one umbilical artery is an extremely valuable tool in prenatal diagnosis. The prenatal detection of SUA demands an extensive search for associated anomalies and a close surveillance of fetal well-being, since these fetuses have a high risk of fetal death or IUGR. Sonologists and sonographers should be aware of the possibility of SUA, especially in those cases associated with congenital malformations or IUGR.     

The clinical significance of hemorrhagic endovasculitis of the placenta

Hemorrhagic endovasculitis of the placenta has been reported to correlate with intrauterine growth retardation, perinatal morbidity and mortality, and long-term developmental delay. At a regional obstetric hospital we identified 13 cases of hemorrhagic endovasculitis among 1938 placentas from singleton pregnancies of greater than or equal to 20 weeks' gestation over a 3-month period, an incidence of 0.67% of unselected pregnancies. All cases were live-births without intrauterine growth retardation. Associated clinical features were pregnancy-induced hypertension, nuchal cord at delivery, and postterm gestation. One infant had severe perinatal asphyxia with long-term psychomotor retardation. In the placenta, hemorrhagic endovasculitis was associated with infarction, fetal vessel thrombosis, and villitis of unknown cause. Interference with umbilical blood flow or regional compromise of villous perfusion may be an initiating event in the development of this lesion.     

Incidence of aplasia of the umbilical artery in fetuses with intrauterine retardation]

The author analysed the occurrence of the aplasia of the umbilical artery in 320 umbilical cords of fetuses with intrauterine retardation and in 225 umbilical cords of normal fetuses and a normal course of pregnancy used as controls. Aplasia of the umbilical artery in umbilical cords of fetuses with intrauterine retardation was found in 5.93% and in the control group in 0.44% of cases (P less than 0.05). Fetuses with intrauterine retardation and aplasia of the umbilical artery showed a velamentous insertion of the umbilical cord in 31.57% of cases, an approximate duration of pregnancy of 36 weeks and 5 days, and the mean birth weight of 2250 +/- 2 S.D. 420 g. Out of 19 fetuses with intrauterine retardation and aplasia of the umbilical artery, 6 had congenital anomalies which in 50% of cases could not be detected by external examination. Perinatal mortality of fetuses with intrauterine retardation and aplasia of the umbilical artery proved to amount to 368.43% and of fetuses in the control group to 8.88% (P less than 0.05).     

The association of single umbilical artery with cytogenetically abnormal pregnancies

The clinical significance of the absence of one of the two umbilical arteries (single umbilical artery) lies in its association with congenital malformations. Whether this association includes cytogenetic abnormalities is less clear. A retrospective review of all detected chromosomally abnormal pregnancies at the University of Maryland was carried out. Of 109 cytogenetically abnormal pregnancies, the number of umbilical cord vessels could be documented in 53 cases. Six (11.3%) had a single umbilical artery. A single umbilical artery was noted in two of nine fetuses (22.2%) with trisomy 18 and in two of six fetuses (33.3%) with trisomy 13. Two other unusual chromosomal constitutions were noted in cases of a single umbilical artery. None of the 11 fetuses with sex chromosome abnormalities (including eight with monosomy X) had a single umbilical artery. Of 18 fetuses with trisomy 21, none had a single umbilical artery. This study suggests that a single umbilical artery is preferentially associated with certain karyotypic abnormalities and that trisomy 21 does not appear to be associated with a single umbilical artery.     

Single umbilical artery: prenatal findings

In 450 patients with pregnancy at high risk for fetal malformation and/or intrauterine growth retardation, the umbilical cord was investigated sonographically for the presence of a single umbilical artery. A single umbilical artery was diagnosed in four fetuses between 23 and 33 weeks of gestation and suspected in two. Three cases were overlooked at sonography. All seven surviving fetuses had growth retardation at delivery and four also showed severe malformations. Whenever a single umbilical artery is found at sonography, further work-up is required to rule out associated anomalies, intrauterine growth retardation, or chromosomal abnormality.     

Single umbilical artery: review of 12 cases

The umbilical cord normally consists of three vessels, two arteries and one vein. The absence of one umbilical artery or single umbilical artery (SUA) has been associated with some adverse perinatal events, such as low birth weight, prematurity, congenital malformations and perinatal mortality. The authors present 12 cases of SUA confirmed by histologic examination and the principal maternal and perinatal features of these cases are analyzed. In our study there were a prematurity rate of 58%, a low birth weight rate of 66% and a perinatal mortality rate of 580/1000. Among our patients, 42% of the infants with SUA had major congenital malformations. An accurate examination of the umbilical cord at delivery is suggested, mainly because SUA is an important index to detect associated congenital malformations.     

Factors associated with umbilical artery acidemia in term infants with low Apgar scores at 5 min

Objective

To evaluate predictors of umbilical artery acidemia in term neonates with low Apgar score.

Study design

From a cohort of term singleton deliveries over a 13-year period, we selected neonates with 5-min Apgar score <7. Acidemia was defined as umbilical artery pH < 7.00 or base excess (BE) ≤−12 mmol/L. Three pathogenic processes of neonatal acidemia were evaluated: (1) intrauterine vascular disease, defined as preeclampsia, clinical diagnosis of placental abruption, birth weight <10th centile, or histologic evidence of placental infarction or severe vascular pathology, (2) intrauterine infection, defined as clinical chorioamnionitis, histologic chorioamnionitis, or early neonatal sepsis, and (3) acute intrapartum events, which included cases of cord prolapse, amniotic fluid embolism, uterine rupture, sudden and sustained fetal bradycardia or absence of FHR variability with a previously normal pattern, shoulder dystocia or complicated breech extraction. The associations of such processes with umbilical artery evidence of acidemia were tested using χ², Fisher's exact test, Student's t-test, and logistic regression, with P < 0.05 or odds ratio (OR) with 95% confidence interval (CI) not inclusive of the unity considered significant.

Results

Among the 27,395 neonates in the cohort, an Apgar score at 5 min <7 was recorded in 94 (0.32%) and it was associated with umbilical artery acidemia in 33 cases. Logistic regression analysis showed that intrauterine vascular disease was independently associated with umbilical cord acidemia (P = 0.035, OR = 3.2, 95% CI = 1.1–9.7) whereas intrauterine infection (OR = 1.1, 95% CI 0.4–3.4) and acute intrapartum events (OR = 2.1 95% CI 0.6–7.0) were not.

Conclusions

Umbilical artery evidence of acidemia is present in 38% of term babies with low Apgar score and it is predominantly associated with chronic antepartum vascular disease. Neither intrauterine infection nor acute intrapartum events are significantly associated with umbilical artery acidemia.     

Clinical significance of the umbilical cord twist

OBJECTIVE: The objective of this study was to determine the clinical significance of the umbilical cord twist direction. STUDY DESIGN: Two hundred singleton third-trimester placentas with a right umbilical cord twist and 200 placentas with a left umbilical cord twist, which was determined by pathologic examination, were included. Maternal and neonatal outcomes were compared with the use of Fisher's exact and Mann Whitney U tests; a probability value of <.05 considered statistically significant. RESULTS: Placenta previa was more common in patients with a right umbilical cord twist compared with a left umbilical cord twist (6.0% vs 1.5%; P<.05). There was a trend towards an increased incidence of single umbilical artery in patients with a right umbilical cord twist (2.5% vs 0%; P=.06). The incidence of fetal demise, intrauterine growth restriction, chromosomal abnormalities, congenital anomalies, preterm delivery, infant gender, birth weight, maternal age, and parity were similar between the 2 groups. CONCLUSION: Placenta previa is associated with a right umbilical cord twist.     

Placental pathology in early intrauterine growth restriction associated with maternal hypertension

Introduction

To identify key pathological characteristics of placentas from pregnancies complicated by early intrauterine growth restriction, and to examine their relations with maternal hypertensive disease and umbilical artery Doppler waveform abnormalities.

Methods

Single-center retrospective cohort study of singleton pregnancies with abnormal umbilical artery Doppler flow patterns resulting in a live birth <34 weeks of a baby with a weight <10th percentile for gestational age. Umbilical artery end diastolic flow was classified as being either present or absent/reversed (AREDF). Data were stratified into intrauterine growth restriction with or without hypertensive disease and pathological characteristics were compared between these various conditions according to predefined scoring criteria.

Results

Among 164 placentas studied, we found high rates of characteristic histopathological features that were associated with intrauterine growth restriction, including infarction (>5% in 42%), chronic villitis (21%), chronic chorioamnionitis (36%), membrane necrosis (20%), elevated nucleated red blood cells (89%), increased syncytial knotting (93%), increased villous maturation (98%), fetal thrombosis (32%) and distal villous hypoplasia (35%). Chronic inflammation of fetal membranes and syncytial knotting were more common in women with concomitant hypertensive disease as compared to women with normotensive IUGR (p < 0.05). Placentas from women with umbilical artery AREDF were more likely to show increased numbers of nucleated red blood cells and distal villous hypoplasia (p < 0.05).

Discussion

Placentas of women with early IUGR show high rates of several histological aberrations. Further, concomitant maternal hypertension is associated with characteristic inflammatory changes and umbilical artery AREDF with signs of chronic hypoxia.     

Gross Abnormalities of the Umbilical Cord: Related Placental Histology and Clinical Significance

ObjectiveTo evaluate umbilical cord abnormalities predisposing to mechanical cord compression and determine their relationship to adverse clinical outcomes and stasis-associated histologic changes in the placenta.MethodsPlacental slides of 224 singleton pregnancies with gross cord abnormality (true knots, long cords, nuchal/body cords, abnormal cord insertion, hypercoiled cords, narrow cords with diminished Wharton's jelly), delivered on or after 28 weeks gestational age, and 317 gestational age-matched controls, were reviewed and specifically evaluated for the following histologic changes: (1) fetal vascular ectasia, (2) fetal vascular thrombosis, (3) and fetal thrombotic vasculopathy/avascular villi. These changes were analyzed in relation to both clinical information and findings at gross pathologic examination.ResultsGross cord abnormalities were associated with stillbirth, intrauterine growth restriction, non-reassuring fetal tracing, meconium-stained amniotic fluid, and increased rate of emergency Cesarean section. At microscopic evaluation, cases with gross cord abnormalities showed a statistically significant association with both ectasia and thrombosis in the fetal vasculature, as well as changes of fetal thrombotic vasculopathy in the terminal villi. When considering individual gross cord abnormalities, long cord and nuchal cord had the highest rates of thrombosis-related histopathology. Finally, cases with both abnormal cords and histologic thrombosis had significantly higher rates of adverse outcomes, including IUGR and stillbirth.ConclusionGross cord abnormalities predispose the fetus to stasis-induced vascular ectasia and thrombosis, thus leading to vascular obstruction and adverse neonatal outcome, including IUGR and stillbirth. We recommend a thorough histopathologic evaluation of all placentas with gross cord abnormalities predisposing to cord compression.     

Single umbilical artery and umbilical cord torsion leading to fetal death. A case report

BACKGROUND: Intrauterine fetal death is a complication that cannot often be predicted by standard obstetric management. Cord accident may be responsible for about 5% of cases. Umbilical cord torsion is an extremely rare cause of intrauterine fetal death. CASE: An 18-year-old, nulliparous woman presented with a complaint of decreased fetal movement at 38 weeks' gestation. Intrauterine fetal death was diagnosed on ultrasound. The pathologic examination revealed umbilical cord torsion and confirmed a single umbilical artery that was diagnosed on ultrasound. CONCLUSION: Umbilical cord torsion that leads to intrauterine fetal death is extremely rare. A pregnancy with a single umbilical artery may need fetal monitoring during the third trimester.     

Sonographic atypical vascular coiling of the umbilical cord

OBJECTIVE: To investigate whether an atypical umbilical coiling pattern at prenatal sonography is associated with adverse pregnancy outcome. METHODS: A targeted sonographic evaluation of the umbilical cord (UC) was performed in 758 women with singleton gestation, and gestational age above 20 weeks. Atypical coiling was defined as the presence of a spring-shape UC (supercoiling) or an unusual, aperiodic coiling pattern (uncoordinated coiling). Umbilical artery Doppler assessment was conducted in cases with atypical coiling. Pregnancy and neonatal outcomes were investigated. RESULTS: Of the study population, 7 and 16 fetuses had an umbilical cord with uncoordinated coiling and supercoiling respectively. Three umbilical cords had a single umbilical artery. Eight patients delivered before 34 weeks of gestation. Eight fetuses were growth restricted. In seven cases, abnormal sonographic findings were detected (three meconium peritonitis, two severe hydronephrosis and two cardiac anomalies). One fetus affected by trisomy 18 presented multiple anomalies. Perinatal death occurred in three cases. Of the surviving newborns, eight were admitted to NICU. Umbilical artery Doppler waveforms presented a systolic notch in seven (30.4%) cases. CONCLUSIONS: The presence of an atypical umbilical cord vascular coiling is associated with an increased risk of unfavourable pregnancy outcome. The identification of an umbilical artery notch at Doppler investigation is frequently associated with an atypical UC coiling pattern.     

Histomorphology of the placenta and the placental bed of growth restricted foetuses and correlation with the Doppler velocimetries of the uterine and umbilical arteries

The aim of the present study was to evaluate the histomorphology of the placenta and the placental bed and to correlate this with the Doppler study of the uterine and umbilical arteries of intrauterine growth restricted pregnancies. The study group consisted of 47 women with intrauterine growth restricted foetuses. Twenty-five uneventful pregnancies with appropriate for gestational age foetuses were selected as controls. Doppler studies of umbilical and uterine arteries were performed within the last week before delivery. Placental bed biopsies were obtained at Caesarean section with direct visualization of the placental site. The incidence of pathologic bed biopsies in control, IUGR with normal uterine artery Doppler velocimetry and IUGR with abnormal uterine artery Doppler velocimetry was 0 per cent, 16.6 per cent and 79.3 per cent respectively (P< 0.001). Placentae from IUGR cases with abnormal umbilical artery Doppler velocimetries had a significantly increased number of villous infarcts, cytotrophoblast proliferation and thickening of the villous trophoblastic basal membrane (P=0.001, P=0.038 and P=0.02 respectively). Abnormal placental bed biopsy pathology was significantly associated with abnormal uterine artery velocimetry (OR 33.7, 6.5-173.6; P< 0.001). Abnormal placental pathology was significantly associated with abnormal umbilical artery Doppler velocimetry (OR 21.04, 3.8-115.9;P< 0.001). Women with both abnormal uterine and umbilical artery Doppler velocimetries were delivered earlier and their babies had lower mean birth and placental weight (P< 0.001). In conclusion, placental bed biopsy and placental pathologies are best reflected by abnormal uterine and umbilical artery velocity waveforms, respectively. The most severe clinical outcomes and perinatal mortality are present when both uterine and umbilical districts are altered.     

Isolated acute funisitis in the absence of acute chorioamnionitis: What does it mean?

ObjectiveAcute funisitis (AF) is most commonly associated with acute chorioamnionitis (AC) and ascending infection. The significance of cases of AF without associated AC or isolated funisitis (IF) is unknown. Our objective was to evaluate clinical and pathologic features of IF and to determine its significance.Study designThis was a retrospective review of placentas of patients delivering at our institution from 1997 to 2017. Placentas with the diagnosis of IF comprised the study population and placentas without either AF or AC served as controls.ResultsThere were 156 cases and 181 controls identified. Maternal age, gestational age, birthweight and mode of delivery were similar in both groups. 132 (84.6%) of cases of IF had meconium, with 62 (47.0%) having meconium only in the membranes, 36 (27.3%) in the membranes and cord and 34 (25.6%) in the membranes and cord with associated myonecrosis. 72 (38.7%) of controls had microscopically identified meconium, with only one (1.4%) showing meconium in the cord. None had myonecrosis (p < .001). There was also a significantly higher rate of intrauterine fetal demise (IUFD) in the IF group (p = .027). but the rate of suspected Intrauterine growth restriction (IUGR) was significantly greater in the controls (p = .014).ConclusionIF is highly associated with the presence of meconium discharge and meconium-associated myonecrosis of umbilical vessels. The inflammation in IF may be the result of damage to the muscle fibers of the cord due to meconium but additional studies are necessary to understand the significance of these findings.     

Intrapartum Fever at term: diagnostic markers to individualize the risk of fetal infection: a review

Intrauterine infection is a serious complication during labor at term and is associated with adverse neonatal outcome. Early and accurate diagnosis is of great concern for both obstetrician and pediatrician with the use of current diagnostics. Clinical symptoms are often regarded as the main sign of intrauterine infection but this approach is highly unreliable and leads to both under- and overtreatment. Currently, no distinct fetal heart rate (FHR) patterns have been found that reliably identify neonates with intrauterine infection. Using a systematic literature search, this article reviews possible markers for the early detection of intrauterine or neonatal infection in maternal serum, amniotic fluid, and umbilical cord blood during labor at term. Maternal serum markers, with the possible exception of interleukin (IL)-8, are unreliable for the detection of intrauterine infection. In contrast, amniotic fluid levels of especially IL-6 and IL-8 are significantly associated with intrauterine infection. Umbilical cord blood IL-6 has been extensively investigated and is usually elevated in case of intrauterine or neonatal infection but shows only modest positive and negative predictive values (NPVs) for clinical use. Umbilical cord IL-8 concentration could be a valuable addition in the diagnostic process, as it has shown to have an NPV of 84% to 92% in the detection of neonatal infection and histological chorioamnionitis. Future research is essential and should focus on the combination of different markers and on the development of a prediction model, to improve the positive and NPVs of our arsenal to detect intrauterine and neonatal infections. Amniotic fluid and umbilical cord values of IL-6 and IL-8 levels are likely candidates for such a prediction model. Target Audience: Obstetricians & Gynecologists and Family Physicians Learning Objectives: After the completing the CME activity, physicians should be better able to evaluate the use of clinical chorioamnionitis with regard to histological evidence and as a diagnostic tool in early diagnosis of intra-amniotic infection. Asses the use of amniotic fluid IL-6 and IL-8 as diagnostic tools to detect early intra-amniotic infection and assess umbilical cord blood IL-8 in case of intrauterine- or neonatal infection using positive (PPV) and negative predictive values (NPV).     

Antenatal detection of a single umbilical artery: does it matter?

The presence of a single umbilical artery is recognised as a soft marker for congenital anomalies, aneuploidy, earlier delivery and low birthweight. Most of the available data are derived from case series or highly selected populations and are therefore likely to be unrepresentative. In this retrospective case-comparison study, we firstly aimed to determine the incidence of a single umbilical artery in an unselected population and secondly to examine the clinical significance of this soft marker. Over a 40-month period, 107 cases were identified from a cohort of 35 066 births giving an incidence of 3.1 per 1000 total births and late pregnancy losses. The antenatal detection rate was only 30%. Compared to fetuses with normal cord vasculature, fetuses with a single umbilical artery were more likely to be delivered at an earlier gestation and to weigh less, were 1.7 times more likely to be delivered by a Caesarean section and 19% of the cases had a congenital anomaly. The perinatal mortality was 49.0 per 1000 total births, which was 6 times higher than the background hospital rate. The presence of a single umbilical artery is associated with a poorer perinatal outcome compared to that in fetuses with three vessels in the cord. Unfortunately, the antenatal detection rate is poor. Recognising the importance of this soft marker in counselling and management of pregnancies should provide the stimulus to improve detection rates.     

The association of umbilical cord complications and variable decelerations with acid-base findings.

Variable decelerations during the last 2 hours of labor were associated with an abnormally positioned umbilical cord at delivery in 52% of cases. In cases where an abnormally positioned umbilical cord was seen at delivery, 89% had been preceded by variable decelerations. Cord compression resulted in an A-V difference in pH that was significantly increased when compared to a control group. This was mainly due to a decrease in the pH of the umbilical artery. The pathophysiology of cord compression is discussed.     

Profile of trace element concentrations in the feto-placental unit in relation to fetal growth

BACKGROUND: During pregnancy, trace elements are indispensable for life maintenance not only for the mother but also for the fetus. The purpose of this study was to examine whether fetal growth is associated with altered levels of trace elements in maternal blood, fetal blood, and placenta tissue. METHODS: Twenty-one pairs of healthy mothers and their newborns with intrauterine growth restriction delivered after 34 weeks of gestation were recruited for the study. In addition, 30 pairs of healthy mothers and their appropriate for gestational age newborns were included as controls. Maternal venous blood, umbilical cord venous and arterial blood, and placenta tissue were collected immediately after delivery. Six essential elements, magnesium, manganese, iron, copper, zinc, and selenium, and four other elements, rubidium, strontium, cadmium, and cesium, in those samples were determined by inductively coupled plasma mass spectrometry or inductively coupled plasma atomic emission spectrometry. RESULTS: Compared with appropriate for gestational age cases, intrauterine growth restriction cases showed higher magnesium, copper, and selenium concentrations in umbilical cord arterial sera, and higher magnesium and selenium concentrations in placenta tissue, but no significant differences appeared for the elements measured in maternal and umbilical cord venous sera. The umbilical cord venous vs. maternal sera concentration ratio was elevated for copper, and the umbilical cord arterial vs. umbilical cord venous sera concentration ratios were elevated for copper and zinc, but there were no differences in placenta tissue vs. maternal sera concentration ratios in intrauterine growth restriction cases. CONCLUSIONS: Among the trace elements evaluated, magnesium, copper, zinc, and selenium showed elevated concentrations in umbilical cord arterial blood, or elevated umbilical cord arterial vs. umbilical cord venous blood concentration ratios in intrauterine growth restriction cases. Reduced consumption efficiency of these four essential trace elements may be closely associated with retarded fetal development.     

Comparison of perinatal outcome in fetuses with reverse or absent enddiastolic flow in the umbilical artery and/or fetal descending aorta

OBJECTIVES: To examine the differences of perinatal outcome in fetuses with absent and reversed enddiastolic flow velocity waveforms of the umbilical artery or fetal descending aorta. DESIGN: In a retrospective study, 30 pregnant women with reversed enddiastolic flow in the umbilical artery or fetal aorta (group I) were compared with 30 cases of absent enddiastolic flow (group II). Patients were included in the groups according to the last Doppler finding before delivery. Perinatal and neonatal outcome was correlated with antenatal Doppler flow findings. RESULTS: The mean gestational age at birth was 31 weeks in both groups. Fetuses with reverse flow showed higher perinatal (27% and 7% respectively) and overall mortality (53.3% and 10% respectively) compared to the absent enddiastolic flow group (p < 0.05). All the intrauterine fetal deaths occurred in the reversed flow group (n = 12). The rates of intrauterine growth retardation, oligohydramnios and hypocalcemia were different between the groups (p < 0.05). The cesarean section rate, perinatal and neonatal complications including the incidence of acidosis, the number of cases admitted to neonatal intensive care unit and mean treatment time were not different between the groups. A tendency to higher incidence of neonatal cerebral hemorrhage in reversed flow cases (28%) compared to absent enddiastolic flow cases (17%) was observed, but this was not statistically significant. CONCLUSIONS: The present study suggests that reversed flow should be seen as a particular clinical entity with higher incidences of perinatal and overall mortality, and severe intrauterine growth retardation (< 5. perc) compared to the absent enddiastolic flow group. The optimal timing of delivery in pregnancies complicated by highly pathological Doppler flow findings is only to be resolved in well-designed randomized, multicenter clinical trials.