Umbilical Doppler Studies Research Articles

English

BACKGROUND An important part of human placental development is the extensive modification of maternal vasculature by trophoblasts. Fetal growth retardation (FGR) and preeclampsia (PE) are associated with deficient trophoblastic invasion and modification of the uterine spiral arteries leading to small-caliber vessels of high resistance which impairs placental blood flow, creating a hypoxic environment and subsequent oxidative stress. FGR and pre-eclampsia are important causes of maternal and perinatal morbidity and mortality and it is important to identify such ‘at risk’ pregnancies during routine antenatal care. Ultrasonography (USG) and colour-Doppler are readily available tools that may be used for identifying such ‘at risk’ pregnancies. The purpose of this study was to evaluate the accuracy of 2-D sonographic placental volumetry, umbilical arterial doppler and uterine arterial doppler in predicting adverse fetomaternal outcomes and compare the accuracy of these three tests with each other in terms of sensitivity and specificity. METHODS A total of 100 women were randomly selected from the antenatal clinics, and were subject to serial ultrasounds at 12 - 16 weeks, 20 - 24 weeks, and 28 - 32 weeks. The 2-D sonographic placental volume, umbilical and uterine arterial resistivity index (RI), and pulsatility index (PI) were measured. The pregnancies were followed up till delivery and the measurements were plotted against the actual placental weight and development of FGR and/or pre-eclampsia. RESULTS In pregnancies with FGR or pre-eclampsia, the placental volumes were low, and correspondingly the uterine and umbilical arterial RI and PI were high (increased impedance) as compared to the normal pregnancies. For the prediction of adverse outcomes, a receiver operating curve (ROC) analysis showed that placental volume and umbilical artery RI and PI had high sensitivity in the 1st-trimester, and high specificity in the 2nd-trimester. CONCLUSIONS 2-D sonographic placental volumetry and umbilical arterial Doppler studies may be used as 1st-trimester screening tools to predict adverse fetomaternal outcomes. These patients may be subjected to more intensive follow-up to minimize maternal and perinatal morbidity and mortality. KEYWORDS Doppler Ultrasonography; Fetal Growth Retardation; Placenta; Pre-eclampsia; Umbilical Arteries; Uterine Artery

EP04.09: The value of fetal umbilical Doppler study in prediction of adverse fetal outcome in early‐versus late‐onset intrauterine growth restriction

EP04.09: The value of fetal umbilical Doppler study in prediction of adverse fetal outcome in early‐versus late‐onset intrauterine growth restriction

Angiogenic factors and uterine Doppler velocimetry in early‐ and late‐onset preeclampsia

To assess correlations between maternal serum levels of pro- and anti-angiogenic factors with uterine perfusion in women with early- compared with late-onset preeclampsia, and in healthy pregnant women. Case-control study. Antenatal care clinic located within a hospital (São Bernardo do Campo, Brazil). We enrolled 54 preeclamptic and 54 healthy control women who were coming for routine ultrasound at 28-36 weeks' gestation. All participants had uterine artery and umbilical Doppler studies and a blood sample to assess maternal serum levels of soluble fms-like tyrosine kinase-1, soluble endoglin, adiponectin and plasminogen activator inhibitor-1. All angiogenic factors were measured using enzyme-linked immunosorbent assay. Levels of pro- and anti-angiogenic factors in maternal serum, and uterine artery Doppler findings. Concentrations of soluble fms-like tyrosine kinase-1 and soluble endoglin were significantly higher in preeclamptic than control women (p < 0.0001 and p < 0.0001, respectively), especially in those with early-onset (<34 weeks) preeclampsia. These two anti-angiogenic mediators were significantly correlated with increased uterine artery Doppler in the preeclamptic women. Plasminogen activator inhibitor-1 levels were significantly higher in preeclampsia (p = 0.03) but unrelated to uterine artery resistance. Adiponectin levels were similar in cases and controls, independent of body mass index and unrelated to uterine artery resistance. Preeclamptic patients have increased soluble fms-like tyrosine kinase-1 and soluble endoglin serum levels and this increase is directly correlated with uterine artery resistance, especially in those with early-onset preeclampsia.

Clinical Prediction in Early Pregnancy of Infants Small for Gestational Age by Customised Birthweight Centiles: Findings from a Healthy Nulliparous Cohort

ObjectiveSmall for gestational age (SGA) infants comprise up to 50% of all stillbirths and a minority are detected before birth. We aimed to develop and validate early pregnancy predictive models for SGA infants.Methods5628 participants from SCOPE, a prospective study of nulliparous pregnant women, were interviewed at 15±1 weeks’ gestation. Fetal anthropometry, uterine and umbilical Doppler studies were performed at 20±1 weeks’. The cohort was divided into training (n = 3735) and validation datasets (n = 1871). All-SGA (birthweight <10th customised centile), Normotensive-SGA (SGA with normotensive mother) and Hypertensive-SGA (SGA with mother who developed hypertension) were the primary outcomes. Multivariable analysis was performed using stepwise logistic regression firstly using clinical variables and then with clinical and ultrasound variables. Receiver operator curves were constructed and areas under the curve (AUC) calculated.Results633 infants (11.3%) in the whole cohort were SGA; 465 (8.3%) Normotensive-SGA and 165 (3.0%) Hypertensive-SGA. In the training dataset risk factors for All-SGA at 15±1 weeks’ included: family history of coronary heart disease, maternal birthweight <3000 g and 3000 g to 3499 g compared with ≥3500 g, >12 months to conceive, university student, cigarette smoking, proteinuria, daily vigorous exercise and diastolic blood pressure ≥80. Recreational walking ≥4 times weekly, rhesus negative blood group and increasing random glucose were protective. AUC for clinical risk factors was 0.63. Fetal abdominal or head circumference z scores <10th centile and increasing uterine artery Doppler resistance at 20±1 weeks’ were associated with increased risk. Addition of these parameters increased the AUC to 0.69. Clinical predictors of Normotensive and Hypertensive-SGA were sub-groups of All-SGA predictors and were quite different. The combined clinical and ultrasound AUC for Normotensive and Hypertensive-SGA were 0.69 and 0.82 respectively.ConclusionPredictors for SGA of relevance to clinical practice were identified. The identity and predictive potential differed in normotensive women and those who developed hypertension.

Could adverse perinatal outcome be predicted from intrapartum umbilical vessels Doppler in women with abnormal cardiotocography?

Abstract Objectives To evaluate the value of umbilical artery and umbilical vein Doppler study in predicting adverse perinatal events in low risk women with abnormal cardiotocography during labor. Design Prospective cohort study. Setting Emergency unit of obstetrics & gynecology department, Royal Commission hospital, El Gubail Industrial City, Saudi Arabia. Population Sixty-six women with uncomplicated pregnancy were classified according to cardiotocography (CTG) findings during the active phase of labor into, 33 cases with normal CTG (group 1) and 33 cases with pathological CTG (group 2). Colour Doppler study of the umbilical artery (UA) and umbilical vein (UV) were performed for both groups and the results were correlated to perinatal outcome. Main outcome measures Meconium stained amniotic fluid, emergency Cesarean deliveries for suspected fetal distress. Apgar score at 1 and 5 min, UA and UV cord blood pH, and the need for neonatal intensive care unit (NICU) admission. Results In the pathological CTG group two (6.1%) cases had high UA Doppler indices with no adverse perinatal outcome, while 13 (39.4%) cases showed UV pulsations of them 12 (92.3%) cases underwent emergency cesarean section for fetal distress, 5 (38.4%) cases delivered babies with UV pH Normal UA Doppler indices and no UV pulsations were seen in all cases with normal CTG group with no adverse perinatal outcome. Conclusion UV Doppler study in combination with CTG monitoring as a part of the intra partum fetal surveillance in low risk pregnancy might give additional useful information about fetal condition and suspected intrapartum fetal hypoxia.

A prospective study of doppler velocimetry in pregnancy-induced hypertension in a rural population of a developing country

Background: Pregnancy-induced hypertension (PIH) remains a great challenge to obstetricians. Doppler velocimetry can detect fetal compromise much before other antepartum tests. Aim: The aim of this study is to detect the changes of uterine artery, umbilical artery and middle cerebral artery in PIH by Doppler velocimetry. Subjects and Methods: This prospective study was conducted on hundred subjects with PIH. Doppler studies were carried, and parameters recorded in uterine, umbilical and middle cerebral artery (MCA) were Systolic/Diastolic ratio, Resistance Index, Cerebro-Placental Index (CPI). Fetal outcomes were monitored. Statistical analysis was performed using Epi Info TM software (Version 3.5.1, CDC, Atlanta). Test for significance was done with student's t -test and Chi-square where applicable. A P- value of Results: Among the 100 subjects, 76 (76%) of fetuses had abnormal and 24% normal umbilical artery Doppler velocimetry; 62% had abnormal and 38% normal MCA Doppler velocimetry; 64% fetuses had abnormal and 36% normal CPI. In 95% of subjects having abnormal umbilical Doppler studies, caesarean section had to be done for acute fetal distress. Incidence of caesarean section was 61% in abnormal MCA group and 63% in abnormal CPI group. Among 14 patients who had abnormal uterine artery Doppler, four developed pre-eclampsia, 2 IUGR. In patients with notches in uterine artery Doppler, 38% developed pre-eclampsia, 38% had IUGR, 13% babies were still born and 25% of newborns required NICU admission. In umbilical artery Doppler, when S/D ratio was abnormal, 60% developed pre-eclampsia, 40% had IUGR and 40% of newborns had to be admitted in NICU. Conclusion: Doppler study for fetal surveillance in pregnancy-induced hypertension is a very useful device and abnormal umbilical artery and uterine artery velocimetry seems to have worse pregnancy outcomes in the present study. Notch as a single parameter is the best indicator with highest sensitivity and positive predicative values. However, combination of parameters is the best indicator.

Prenatal Diagnosis of Spontaneous Septostomy in Dichorionic Diamniotic Twins and Review of the Literature

We present 2 cases of spontaneous septostomy in dichorionic diamniotic twins and review the literature regarding the incidence, etiology, and complications of this condition. The following key words were used in the literature search: "rupture dividing membrane twin," "disruption dividing membrane twin," "pseudomonoamniotic twin," "spontaneous septostomy twin," "interfetal membrane disruption," "intertwin membrane rupture," and "intertwin membrane disruption." We present 2 cases in which an intertwin membrane defect was found prenatally in dichorionic diamniotic twins. In both cases, a portion of one twin's body was found traversing the spontaneous septostomy and in the sac of its cotwin. Umbilical cord Doppler studies showed no abnormalities in either case as the cord crossed the membrane disruption. In both cases, the fetuses had no notable sequelae from the ruptured intertwin membrane. The literature review revealed no cases of spontaneous septostomy in dichorionic diamniotic twins but 15 cases in monochorionic diamniotic twins. Possible etiologies include chorioamnionitis, trauma or physical rupture by the fetuses, developmental disturbances represented by amniotic plica, and polyhydramnios. In cases of monozygotic twins, a vascular etiology could explain this rare defect with formation of anastomoses of the outer embryonic vasculature. Complications of the spontaneous septostomy cases identified in the literature included cord entanglement (8 cases), preterm delivery (9 cases), and death (8 cases), although our 2 cases had minimal complications. Spontaneous septostomy in dichorionic diamniotic twins has not previously been reported.

621: How should the growth restricted (FGR) fetus be monitored before delivery? Results of a national survey

DELIVERY? RESULTS OF A NATIONAL SURVEY AHMET BASCHAT, CHRISTOPHER HARMAN, JULIAN ROBINSON, HENRY L. GALAN, University of Maryland at Baltimore, Baltimore, Maryland, Harvard Medical School, Boston, Massachusetts, University of Colorado Health Sciences Center, Denver, Colorado OBJECTIVE: To determine diagnostic criteria and typical surveillance management of pregnancies complicated by FGR by perinatologists practicing in the US. STUDY DESIGN: An internet questionnaire investigating practice patterns pertaining to the management of FGR was sent to 1123 Society for Maternal Fetal Medicine (MFM) members. RESULTS: 368/443 respondents were MFM Board certified (83%) and 52% (231) in fulltime academic practice. 62% (273) had highest level NICU available. 44% managed between 10-20 FGR 32 weeks annually. (226, 51%) based FGR diagnosis on an estimated fetal weight (SFW) 10th %, by Hadlock formula (343. 77%). Other FGR criteria were any growth abnormality in combination with abnormal umbilical artery Doppler (24%) or an abdominal circumference 5th %ile. Growth was assessed at 2 3 week intervals by 92% (362). Karyotyping by amniocentesis (73%), TORCH titer (63%) and thrombophilia studies (56%) were the most common added tests. The most common surveillance combination was weekly umbilical artery Doppler and twice weekly NST/AFI (74% of responses) When NST or NST/AFI are used as primary surveillance tools these are performed twice weekly (77%) whereas umbilical artery Doppler, BPP and other Doppler studies are performed weekly. Umbilical artery Doppler status (88%), amniotic fluid volume (77%) and maternal disease (73%) were the primary factors modifying testing frequency. There were no differences in any of these responses between academic and private practice. CONCLUSION: For FGR fetuses primary surveillance is based on biophysical parameters while cardiovascular fetal factors and maternal disease impact the frequency of testing. The testing schemes chosen appear surprisingly uniform. This suggests that perinatologists may not take advantage of more sophisticated testing protocols to individualize management of FGR.

SMALL FOR GESTATIONAL AGE FETUS

Objective: To evaluate the role of Colour Doppler Ultrasound in the management of small forgestational age fetus. SGA or IUGR. Design: Descriptive study. Place &amp; duration of study: Study performed in theDeptt. of Radiology &amp; Deptt. of Gynae. &amp; Obstetrics in Allied Hospital, Faisalabad from August 2005 to July 2006.Material &amp; Methods: This study was carried out on 45 patients admitted through antenatal clinic having suspicion ofcarrying small for gestational age fetus. A brief clinical record including age, parity, nutritional status, intercurrent illness,per-vaginum bleeding, history of drug intake, smoking, past obstetrical history was recorded. Methods involved inscreening SGA fetuses were measurement of Symphyseal Fundal Height chart &amp; Ultrasound biometry, Biophysicalprofile (BPP), Cardiotocography (CTG), Middle cerebral and Umbilical Arteries Doppler studies were performed afteradmission in the management of SGA fetuses. All these information were recorded in a specially designed Performa.Results: Out of 45 SGA fetuses 15(33.3%) were constitutionally small, 20(44.4%) had history of pre-eclampsia,2(4.4%) had cardiac disease, 3(6.6%) had placental abnormalities, 5(11.1%) had multiple gestations. Gestation ofpatients ranged between 30-36 weeks. Umbilical Artery Doppler was used as the primary surveillance tool. Smallfetuses with normal Doppler and anomaly scan were managed on out-patient basis with fortnightly Doppler ultrasound.15 patients (33.3%) with normal end-diastolic flow were delivered at 37 weeks. 20 patients (44.47%) with absent orreversed end-diastolic flow were delivered at 34-35 weeks. 10 patients (22.2%) at 30 weeks gestation with abnormalDoppler study were managed on CTG (Cardiotocography) &amp; biophysical profile over a period ranging between 1-14days. Perinatal mortality was 8.8% (4 cases) mostly due to extreme prematurity. Conclusion: Doppler ultrasound isa very helpful tool in the management of small for gestational age fetuses &amp; it reduces perinatal morbidity &amp; Mortality.

Egr‐1 transcription activation exists in placental endothelium when vascular disease is present

To seek evidence of early vascular injury in the placental villous microcirculation in placental insufficiency identified by a high-resistance umbilical Doppler study by examining for expression of fibroblast growth factor receptor-1 (FGFR-1), its transcription factor, early growth response factor-1 (Egr-1) and plasma fibroblast growth factor-2 (FGF-2). Case-control study. University teaching hospital. Placentas and umbilical vein blood were collected at delivery from 12 women with normal pregnancy delivered at term and 14 with placental vascular disease defined by an abnormal umbilical artery Doppler study. Microvascular endothelial cells were isolated from fresh human placentas using collagenase digestion and Dynabeads coated with monoclonal antibody against CD31. RNA was extracted from the isolated endothelial cells. The messenger RNA (mRNA) expression of FGFR-1 and Egr-1 production were assessed by reverse transcription polymerase chain reaction and factored relative to 18S ribosomal RNA. To confirm that FGF-2 was playing a significant role in this microvascular endothelial cell injury in the placenta, we also measured the soluble fraction of FGF-2 in fetal plasma from same groups of pregnancies using an enzyme-linked immunosorbent assay. Microvascular endothelial cells expression of Egr-1mRNA, FGFR-1 mRNA and presence of soluble FGF-2 in fetal plasma. The soluble level of FGF-2 in the fetal placental circulation from pregnancy with placental vascular disease was increased when compared with normal pregnancy (median 10.15 pg/ml and interquartile range 5.34-21.83 pg/ml versus 4.46 pg/ml and 3.69-5.66 pg/ml; P < 0.05). Microvascular endothelial cells from the placental villi with placental vascular disease showed upregulation of both FGFR-1 mRNA expression (median 0.72 and interquartile range 0.40-1.64 versus 0.34 and 0.19-0.71; P<0.05) and Egr-1 expression (median 0.79 and interquartile range 0.27-1.86 versus 0.23 and 0.17-0.67; P<0.05) in comparison with normal pregnancy. Endothelial cells from the placental villi are upregulated for expression of Egr-1 transcription factor gene in placental vascular disease. The FGFR-1 activation and increase in FGF-2 in the fetal circulation are known to be very early features of the response of endothelium to injury. Egr-1 is a promoter of many key pathophysiologically relevant target genes, which influence the development of subsequent vascular lesions. This change may occur before the pathological features recognised on microscopy.

Customized Birthweight Centiles Predict SGA Pregnancies With Perinatal Morbidity

Birth weight traditionally is classified using population-based, sex-adjusted centiles. An infant weighing less than the 10th percentile at birth is considered to be small for gestational age (SGA). Some of these infants, however, are constitutionally small but not growth-restricted. This study was an attempt to reclassify infants using and percentiles, and to compare perinatal morbidity rates in those classified as and those appropriate for gestational age. The cohort study included 374 pregnancies from a general obstetric of 12,879. Pregnancy outcomes were compared for SGA infants who were below the 10th percentile by both and percentiles; SGA only; and SGA only. All pregnancies were evaluated by an ultrasound at less than 20 weeks gestation and by umbilical Doppler study within 2 weeks of delivery. The National Women's Hospital database of births in the years 1993-2000 was used to study the use of percentiles in a general obstetric population. Customized was the birth weight below 10th percentile using the New Zealand percentile calculator. Population was sex-adjusted birth weight less than 10th percentile and was birth weight of 10th percentile or more by both and parameters. At delivery, 80% of infants were by percentiles and 81% were by percentiles. The proportion of infants who were by both these percentiles was 72%. In addition, 7% of infants were customized only, 9% were population only, and 12% were non-SGA both. Mothers of infants who were reclassified as population only had lower body mass indices than those who were SGA both, and they also were likelier to be nulliparous. Women in the customized only group tended to have higher body mass indices. Rates of preeclampsia, abnormal Doppler findings, and cesarean section for fetal distress all were greater in the SGA and customized only groups than in the non-SGA group. These forms of morbidity were similarly frequent in the SGA and customized only groups. Indices of newborn morbidity, including a long hospital stay and composite morbidity, were increased to similar degrees in the SGA and customized only groups. Morbidity was comparatively low in the population only and non-SGA groups. All seven perinatal deaths were in the SGA group. Morbidity risk in babies who were customized only-and who would not have been detected using percentiles-had high morbidity rates comparable to those of infants in the SGA group. Compared with the non-SGA group, relative risk figures for perinatal death were high in the SGA and customized only groups. It appears that the use of birth weight percentiles is able to identify small infants who are at increased risk of perinatal morbidity and mortality.

Customised birthweight centiles predict SGA pregnancies with perinatal morbidity

To determine the following: (1) the proportion of babies reclassified as small or appropriately grown using customized and population centiles; and (2) the relative risks of perinatal morbidity, including abnormal umbilical Doppler studies, in babies classified as small for gestational age (SGA) and appropriate for gestational age (non-SGA) using the two centile calculations. Cohort study in SGA and general hospital populations. National Women's Hospital, Auckland, NZ. A cohort of SGA pregnancies (n= 374) and a general obstetric population (n= 12,879). Pregnancy outcomes were compared between 'non-SGA both' (> or =10th% by population and customized centiles) and those who were 'SGA both' (<10th% by population and customized centiles), 'SGA customized only' (SGA by customized but non-SGA by population centiles) and 'SGA population only' (SGA by population but non-SGA by customized centiles). Maternal and newborn morbidity and perinatal death. In the SGA cohort 271 (72%) babies were 'SGA both', 27 (7%) were 'SGA customized only', 32 (9%) were 'population SGA only' and 44 (12%) were 'non-SGA both'. In the general obstetric population 863 (6.7%) babies were 'SGA both', 445 (3.5%) were 'customized SGA only', 285 (2.2%) were 'population SGA only' and 11,286 (88%) were 'non-SGA both'. Perinatal death and newborn morbidity including nursery admission and long hospital stay were increased and comparable between 'SGA both' and 'customized SGA only' in both study populations. Newborn morbidity was low and comparable between 'population SGA only' and 'non-SGA both'. No perinatal deaths occurred in 'population SGA only' babies. Abnormal Doppler studies were more common in 'SGA both' or 'customized SGA only' but not in 'population SGA only' groups compared with 'non-SGA both'. Customized birthweight centiles identified small babies at risk of morbidity and mortality. Use of customized centiles is likely to detect more babies at risk of perinatal morbidity and mortality than would be detected by population centiles.

Use of umbilical artery Doppler velocimetry in the monitoring of pregnancy in women with pre-existing diabetes.

The usefulness of umbilical artery Doppler velocimetry for the monitoring of diabetic pregnancies is controversial. The aim of the present study was to assess whether umbilical artery Doppler velocity waveform analysis can predict adverse perinatal outcomes for pregnancies complicated by pre-existing diabetes mellitus. All diabetic pregnancies (type 1 and 2) delivered at Mater Mothers' Hospital, Queensland, between 1 January 1995 and 31 December 1999 were included. All pregnant diabetic women were monitored with umbilical artery Doppler velocimetry at 28, 32, 36, and 38 weeks' gestation. Adverse perinatal outcome was defined as pregnancies with one or more of the following: small-for-gestational age, Caesarean section for non-reassuring cardiotocography, fetal acidaemia at delivery, 1-min Apgar of 3 or less, 5-min Apgar of less than 7, hypoxic ischaemic encephalopathy or perinatal death. Abnormal umbilical artery Doppler velocimetry was defined as a pulsatility index of 95th centile or higher for gestation. One hundred and four pregnancies in women with pre-existing diabetes had umbilical arterial Doppler studies carried out during the study period. Twenty-three pregnancies (22.1%) had an elevated pulsatility index. If the scans were carried out within 2 weeks of delivery, 71% of pregnancies with abnormal umbilical Doppler had adverse outcomes (P < 0.01; likelihood ratio, 4.2). However, the sensitivity was 35%; specificity was 94%; positive predictive value was 80%; and negative predictive value was 68%. Only 30% of women with adverse perinatal outcomes had abnormal umbilical arterial Doppler flow. Umbilical artery Doppler velocimetry is not a good predictor of adverse perinatal outcomes in diabetic pregnancies.

Transmitted Arterio-arterial Anastomosis Waveforms Causing Cyclically Intermittent Absent/Reversed End-diastolic Umbilical Artery Flow in Monochorionic Twins

Objectives: To characterize the phenomenon of retrograde transmission of arterio-arterial anastomosis (AAA) interference patterns on umbilical artery (UA) waveform by (a) documenting the periodicity, (b) correlation with in vivo and in vitro demonstration of AAAs and (c) reproducing these patterns by computer modelling. Methods: Monochorionic twins (MC) twins underwent placental and umbilical Doppler studies. AAAs were sought by pulse wave Doppler of their bi-directional interference pattern and confirmed by postnatal injection studies. The periodicity of transmitted patterns in the UA was determined. Determinants of the transmitted patterns were ascertained by computer modelling of physiological and fetal variables. Results: Among 83 prospectively studied MC twin pregnancies; a transmitted pattern was observed in 6 (7 per cent) patients for 15–114 days. This was found in 20 per cent (6/30) of smaller MC twins discordant for growth restriction but in no appropriately grown twins. It was only observed in association with AAAs validated both in vivo and in ex vivo. Computer modelling demonstrated that this pattern could be reproduced by summating end diastolic flow with a high pulsatility index in the UA in the presence of a large AAA. Consistent with this, MC twins with a transmitted pattern had larger AAAs (median diameter 4.3 mm interquartile range 4.1–5.2) compared to MC twins discordant for intrauterine growth restriction (2.1 mm interquartile range 1.5 to 2.8) ( P<0.05) without a transmitted pattern. Perinatal mortality was similar in the fetuses with and without transmitted patterns (0/12 vs. 2/48 P=0.7).

Inherited thrombophilias are not increased in “idiopathic” small-for-gestational-age pregnancies

Objective: The purpose of this study was to determine (1) whether the inherited thrombophilias (the factor V Leiden and prothrombin gene mutations and the methylenetetrahydrofolate reductase [C677T] polymorphism) are increased in women with “idiopathic” (normotensive) small-for-gestational-age pregnancies and/or in their babies and (2) whether fetal carriage of a thrombophilia is associated with abnormal umbilical Doppler studies. Study Design: This was a case-controlled study of normotensive women who were delivered of a singleton small-for-gestational-age baby (birth weight, <10th percentile adjusted for sex) with no clinical evidence of chromosomal or congenital abnormality. Control subjects were healthy women who were delivered of appropriate-for-gestational-age babies. Results: One hundred forty-five women with small-for-gestational-age pregnancies and 290 control subjects were recruited. Small-for-gestational-age babies were born at an earlier gestational age (38 ± 3.0 weeks) and with a lower birth weight (2373 ± 521 g) than control babies (39.7 ± 1.3 weeks and 3606 ± 423 g, P <.01). There were no differences in the rates of factor V Leiden (2.8% vs 3.8%; relative risk, 0.79; 95% CI, 0.34-1.85), prothrombin gene mutation (2.8% vs 3.1%; relative risk, 0.92; 95% CI, 0.40-2.09), and methylenetetrahydrofolate reductase C677T polymorphism (13% vs 9%; relative risk, 1.27; 95% CI, 0.87-1.84) between mothers with small-for-gestational-age babies and control subjects, respectively. Inherited thrombophilias were not increased in small-for-gestational-age babies compared with control babies. Of small-for-gestational-age babies with abnormal umbilical artery Doppler studies (n = 25), 21% had a thrombophilia compared with 11% with normal umbilical artery Doppler studies (n = 68; relative risk, 1.75; 95% CI, 0.81-3.81). Conclusion: The rates of these inherited thrombophilias are not increased in normotensive women with small-for-gestational-age pregnancies. Further studies are required to determine whether thrombophilias are increased in small-for-gestational-age babies with abnormal umbilical Doppler study results.

Gene expression of nitric oxide synthase by human umbilical vein endothelial cells: the effect of fetal plasma from pregnancy with umbilical placental vascular disease

Objective To determine whether endothelial cell injury would be produced by factor(s) released into the fetal circulation, manifested by altered messenger RNA expression of nitric oxide synthase. Design Case–control study. Setting University teaching hospital. Samples Fetal plasma was collected from 34 normal pregnancies, 44 pregnancies with umbilical placental vascular disease identified by an abnormal umbilical Doppler and 11 pregnancies with maternal pre-eclampsia but with normal umbilical Doppler studies. Methods Aliquots from a common culture of human umbilical vein endothelial cells (HUVECs) were incubated with fetal plasma from the members of the three patient groups. The total RNA was extracted from the endothelial cells and mRNA for nitric oxide synthase was measured by reverse transcription and semi-quantitative polymerase chain reaction (RT-PCR). This was standardised by comparison of the amplified inducible nitric oxide synthase (iNOS) or endothelial constitutive nitric oxide synthase (ecNOS) to glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Main outcome measure Endothelial cell gene expression of iNOS and ecNOS. Results The mRNA expression of iNOS and ecNOS were significantly higher ( P < 0.05) in HUVECs stimulated by fetal plasma from pregnancies with umbilical placental vascular disease [iNOS 1.12 (0.16); ecNOS 1.78 (0.18)] when compared with normal pregnancies [iNOS 0.56 (0.06); ecNOS 1.06 (0.10)]. In the maternal pre-eclampsia group, the NOS expression [iNOS 0.76 (0.11); ecNOS 1.39 (0.26)] did not differ from normal pregnancy. In the vascular disease group, there was no difference in NOS expression between the subgroups with and without maternal pre-eclampsia. Conclusions Our study demonstrates that umbilical placental vascular disease is associated with a factor(s) in fetal plasma that produces an increase in the expression of iNOS and ecNOS mRNA by endothelial cells. Our findings raise the possibility that the release of factors causing an up-regulation of iNOS and ecNOS in the endothelium in the fetal placenta may occur as part of an inflammatory response of the vascular endothelium to injury.

The use of umbilical artery Doppler velocimetry in the monitoring of pregestational diabetic pregnancy

Purpose: To assess whether umbilical artery Doppler velocity waveform analysis can predict adverse perinatal outcomes for pregnancies complicated with pre‐existing diabetes mellitus (types 1 and 2 diabetes mellitus).Methods: All diabetic pregnancies (types 1 and 2) delivered at Mater Mothers' Hospital, Australia, between 1st January 1995 and 31st December 1999, were included. All pregnant diabetic women were monitored with umbilical artery Doppler velocimetry at 28, 32, 36, and 38 weeks gestation. Umbilical artery Doppler study was repeated on weekly basis for pregnancies complicated by macrosomia, polyhydramnios, or fetal growth restriction. Adverse perinatal outcome was defined as pregnancies with one or more of the following: small‐for‐gestational age (birth weight &lt;10th centile), cesarean section for non‐reassuring cardiotocography, fetal acidemia at delivery (cord blood arterial pH &lt; 7.2), 1‐min Apgar of ≤3, 5‐min Apgar of &lt;7, hypoxic ischaemic encephalopathy, stillbirth and perinatal deaths. Abnormal umbilical artery Doppler index was defined as systolic/diastolic ratio of 95th centile or higher for gestation (including absent or reversed end‐diastolic flow). The incidence of adverse perinatal outcomes was compared between those with normal umbilical artery Doppler and those with elevated systolic/diastolic (S/D) ratio.Results: One hundred and four pregnancies had umbilical arterial Doppler studies performed during the study period. Twenty‐three pregnancies (22.1%) had elevated S/D ratio of the umbilical artery Doppler velocimetry. If the scans were performed within 2 weeks of delivery, 71% of pregnancy with abnormal umbilical Doppler study have adverse outcome. For umbilical artery Doppler studies performed within 1 week of delivery, the sensitivity was 35%; specificity was 94%; positive predictive value was 80%; and negative predictive value was 68%. However, only 30% of women with adverse perinatal outcomes had abnormal umbilical Doppler flow.Conclusion: Elevated umbilical arterial Doppler S/D ratio is associated with adverse perinatal outcomes. However, the majority of diabetic pregnancies with adverse perinatal outcomes have normal umbilical artery Doppler velocimetry. Thus, this could be a useful test for monitoring, but is not a good predictor of adverse perinatal outcomes.

P107The study of the ductus venosus for predicting umbilical artery pH at birth below 7.10 in pregnancies with absent or reversed end‐diastolic velocity flow (ARED) in the umbilical arteries Doppler studies

BackgroundA study of the relation between methods for assessment of fetal well‐being and umbilical artery pH at birth below 7.10.MethodsA prospective study was conducted to assess the fetal well‐being in 61 singleton pregnancies with ARED. The results of these methods were compared with the occurrence of umbilical artery pH at birth &lt; 7.10. All data were analyzed and compared using logistic regression.ConclusionThe probability of umbilical artery pH below 7.10 in ARED fetuses could be predicted by means of the ductus venosus Doppler studies and the BPS. Knowledge of this probability can help to choose the best moment for delivery in these cases.

Administration of low-dose aspirin to mothers with small for gestational age fetuses and abnormal umbilical Doppler studies to increase birthweight: a randomised double-blind controlled trial

Administration of low-dose aspirin to mothers with small for gestational age fetuses and abnormal umbilical Doppler studies to increase birthweight: a randomised double-blind controlled trial

Umbilical Venous Doppler Waveform without Fetal Breathing: Its Significance

Umbilical venous waveforms by Doppler ultrasound are seen normally during fetal breathing movements. Each waveform extends two to four fetal cardiac cycles. During Doppler study of gross intrauterine growth retardation (IUGR) and twin to twin transfusion cases, single or double peaked umbilical venous waveforms were detected with each fetal cardiac cycle. Umbilical arterial Doppler study detected minimal, absent, or reverse diastolic flow. In these fetuses, the ratio of right and left ventricular diameters at the atrioventricular valve level was increased, and pulse-wave and color Doppler study showed tricuspid regurgitation. This tricuspid regurgitation caused reverse flow in the umbilical vein from the right atrium and inferior vena cava and produced characteristic venous waveforms. These umbilical waveforms were associated with gross IUGR or cardiac failure of the fetuses with perinatal morbidity and mortality.