Uterine artery Doppler and mid-trimester maternal plasma homocysteine in subsequent pre-eclampsia.

OBJECTIVE: To investigate whether mid-trimester maternal plasma homocysteine concentration is elevated in women who develop pre-eclampsia and in those women identified at high risk by abnormal uterine artery Doppler examination. METHODS: This was a multicenter study involving healthy women undergoing screening for pre-eclampsia by uterine artery Doppler velocimetry at 22-24 weeks' gestation. Abnormal uterine artery blood flow was defined as a mean pulsatility index (PI) above the 95th centile (1.6). Controls (mean PI < 1.6) were matched for gestational age and date of blood sample collection. Maternal plasma homocysteine concentration was measured retrospectively using a chemiluminescent immunoassay. RESULTS: In total, 683 women were recruited. Maternal plasma homocysteine concentration did not vary with gestation. Maternal plasma homocysteine concentration in women who subsequently developed pre-eclampsia (n = 80, 12%) was not significantly different from women with uncomplicated pregnancies (n = 536, 78%) (median 5.1, range 2.7-14.1 micromol/l vs. median 5.5, range 1.9-27.9 micromol/l, p = 0.44). There were no significant differences in the maternal plasma homocysteine concentration in women with abnormal uterine artery Doppler findings (n = 275) compared with controls (n = 408), (median 5.6, range 2.6-17.7 micromol/l vs. median 5.4, range 1.9-27.9 micromol/l, p = 0.13). CONCLUSION: Mid-trimester maternal plasma homocysteine concentration is not elevated in women who developed pre-eclampsia even in those at high risk defined by abnormal uterine artery Doppler velocimetry.     

Prediction of pregnancy complications by first-trimester maternal serum PAPP-A and free beta-hCG and with second-trimester uterine artery Doppler

BACKGROUND: Previous studies have shown an association between low first trimester maternal serum free beta-hCG and PAPP-A and subsequent development of pregnancy complications. Similarly, uterine artery Doppler in the late second trimester has shown that high impedance to flow is associated with increased risk for preeclampsia and fetal growth restriction. The objective of this study is to determine whether there is an association between the maternal serum concentration of PAPP-A and free beta-hCG at 11-13(+6) weeks with the uterine artery pulsatility index (PI) at 22-24 weeks, and secondly, to compare the screening characteristics of the two methods in the prediction of adverse pregnancy outcome. METHODS: Maternal serum PAPP-A and free beta-hCG at 11-13(+6) weeks and uterine artery PI at 22-24 weeks were measured in 4390 women with singleton pregnancies. Pregnancies with chromosomal defects or fetal anomalies were excluded. The biochemical and Doppler measurements were compared between those with normal outcome and those resulting in spontaneous preterm delivery, pre-eclampsia and fetal growth restriction (FGR). Detection rates using a combination of the biochemical and Doppler measurements were investigated. RESULTS: In the pregnancies resulting in pre-eclampsia (n = 64) and FGR (n = 172), the median PAPP-A was lower (0.844 and 0.813 MoM), the median uterine artery mean PI was higher (1.56 and 1.18) but the median free betahCG was not significantly different (0.923 and 0.933 MoM) than in the normal outcome group. In the preterm delivery group (n = 159), the median free beta-hCG (0.944 MoM) and uterine artery mean PI (1.06) were not significantly different from normal but the median PAPP-A (0.928 MoM) was significantly lower than normal. In screening for pre-eclampsia, the detection rate, for a 5% false-positive rate, was 14.1% for PAPP-A, 54.7% for uterine artery mean PI and 62.1% for a combination of PAPP-A and uterine artery mean PI. CONCLUSION: Maternal serum PAPP-A at 11-13(+6) of gestation is significantly lower in adverse pregnancy outcomes. The combination of first trimester serum PAPP-A and uterine artery mean PI at 22-24 weeks improves the screening efficacy for the prediction of pre-eclampsia.     

ADAM12s in maternal serum as a potential marker of pre-eclampsia

OBJECTIVE: To examine whether maternal serum ADAM12s, a potential first- and second-trimester marker of fetal aneuploidy and fetal growth, had altered concentrations in the first or second trimester of pregnancies subsequently developing pre-eclampsia. METHODS: ADAM12s was measured by a time-resolved fluoroimmunoassay developed by PerkinElmer Life Science. Maternal serum samples from women taking part in early first-trimester aneuploidy screening in whom the pregnancy resulted in pre-eclampsia (64) were identified from a cohort of 4,390 singleton pregnancies in which uterine artery Doppler mean Pulsatility Index (PI) had been measured at 22-24 weeks. From amongst those cases delivering a normal term infant with birth weight greater than the 10th centile for gestational age 240 cases were selected as gestational age-matched controls. A second study group consisting of maternal serum taken at 22-24 weeks at the time of uterine artery Doppler in a group of 12 women developing pre-eclampsia were compared with 86 matched controls from a previously studied cohort of 24 cases and 144 controls. Serum ADAM12s concentrations were converted to multiple of the median (MoM) to take account of gestational age variation. RESULTS: First-trimester maternal serum ADAM12s levels in women who developed pre-eclampsia were reduced with a median MoM of 0.71 which was further reduced in those delivering prior to 35 weeks (0.50). At the 5th centile of normal (0.48 MoM) ADAM12s identified 27% of cases with pre-eclampsia and 47% of those with early pre-eclampsia. Combining ADAM12s with PAPP-A from a previous study only resulted in a further 1% increase in detection of all women developing pre-eclampsia. However combining ADAM12s with mean PI increased the detection rate to 66%. In the second trimester at 22-24 weeks the maternal serum ADAM12s levels were increased in those women developing pre-eclampsia compared to controls (709 vs 486 ug/L, p = 0.045). CONCLUSION: ADAM12s in addition to being a potential marker of aneuploidy may also be a marker of pre-eclampsia. Further studies are required to see if this can improve on the clinical discrimination already provided by PAPP-A in the early first trimester.     

Low levels of maternal serum PAPP-A in the first trimester and the risk of pre-eclampsia

BACKGROUND: Low levels of pregnancy associated plasma protein-A (PAPP-A) have been previously shown to be associated with pregnancies that subsequently develop pre-eclampsia. The objective of this study was to establish the relative risk for pre-eclampsia at various PAPP-A levels as an aid to counselling and follow up of pregnancies. METHODS: Maternal serum PAPP-A and free ss-human chorionic gonadotropin (ss-hCG) levels at 11 to 13 weeks of gestation from 224 singleton pregnancies that subsequently developed pre-eclampsia were compared to those from 47,770 normal singleton pregnancies resulting in live births after 37 weeks with birth weight greater than or equal to the 10th centile of normal for gestation. In all cases, the measured PAPP-A and free ss-hCG levels were expressed as multiple of the median (MoM). The association between metabolite levels and the incidence of pre-eclampsia was assessed by comparing the relative incidence at a number of MoM cut-offs and at various centiles. At various marker levels, the likelihood ratio for pre-eclampsia was also calculated. RESULTS: In the pre-eclampsia group the median PAPP-A MoM was significantly reduced (0.772 MoM, p < 0.0001) whilst the median free beta-hCG MoM was not different from controls (0.981 MoM, p = 0.26). With decreasing levels of PAPP-A, the likelihood ratio for pre-eclampsia increased. At the 5th centile of normal (PAPP-A MoM 0.415) the odds ratio was increased 4-fold and at this cut-off 15% of cases of pre-eclampsia would be identified. CONCLUSIONS: The graphical presentation of a likelihood ratio curve for pre-eclampsia at any PAPP-A MoM level is likely to be useful in counselling women with low levels of PAPP-A and a normal karyotype. Use of low levels of PAPP-A for selecting women for further follow-up with uterine artery Doppler may further improve the clinical discrimination.     

Cell-free fetal DNA concentration in plasma of patients with abnormal uterine artery Doppler waveform and intrauterine growth restriction--a pilot study

OBJECTIVE: To evaluate if an increased amount of fetal DNA concentration can be found in women screened positive for intrauterine growth restriction because of abnormal uterine artery Doppler waveforms. METHODS: We enrolled eight pregnant women (each bearing a male fetus), with the evidence of abnormal uterine artery Doppler waveforms, and 16 control patients for a case-control study matched for gestational age (1 : 2). Uterine artery Doppler was carried out at 20 to 35 weeks' gestation (median 29). The mean uterine artery resistance index (RI) was subsequently calculated, and a value >0.6 was considered positive for the clinical features of pre-eclampsia. The SRY locus was used to determine the amount of male fetal DNA in the maternal plasma at the time of Doppler analysis. RESULTS: Two controls (normal Doppler) were excluded from the final analysis because they had a pre-term delivery. One case (abnormal Doppler) had evidence of intrauterine growth restriction at the time of enrolment. In four out of eight cases (abnormal Doppler), intrauterine growth restriction was subsequently observed. Multiples of median (MoM) conversion of the fetal DNA values showed an increase of 1.81 times in the cases when compared to the controls. An increase of 2.16 times was instead observed for the cases with a growth-restricted fetus (5 cases out of 8) in comparison with the controls (14 cases). CONCLUSIONS: In subjects positive to uterine artery Doppler velocimetry analysis (Doppler analysis for pre-eclampsia screening), the fetal DNA concentration is higher than expected, in the absence of any other clinical feature. Since the increase in fetal DNA seems to be related to the presence or to the future development of intrauterine growth restriction, this paper suggests a possible integration between ultrasound and molecular markers for predicting the disease in some cases.     

Plasma endothelin, atrial natriuretic peptide (ANP) and uterine and umbilical artery flow velocity waveforms in hypertensive pregnancies.

OBJECTIVE: To investigate the relation between concentrations of endothelin and atrial natriuretic peptide (ANP) in maternal plasma and vasospasm in the uterine and umbilical arteries as detected by duplex pulsed colour Doppler ultrasonography in hypertensive pregnancies. DESIGN: An observational study. SUBJECTS: 32 women admitted consecutively to hospital with pregnancy induced hypertension (seven without proteinuria and 25 with proteinuria) and 78 healthy pregnant women examined at 28-40 weeks gestation. MAIN OUTCOME MEASURES: Systolic/diastolic (S/D) ratio in flow velocity waveforms (FVWs) and plasma concentrations of endothelin and ANP in the 32 women with pregnancy induced hypertension; plasma concentrations of endothelin and ANP in 78 healthy pregnant women (controls). RESULTS: Pathological FVWs suggesting vasospasm in the uterine or umbilical artery, or both arteries, were found in 12 women with hypertension. Plasma ANP was significantly higher (P = 0.03) in the women with hypertension and pathological FVWs (median 23.0, range 10.1-52.8 pmol/l) than in those with hypertension and normal FVWs, (median 13.8, range 5.3-42.3 pmol/l) but corresponding plasma endothelin levels did not show any significant difference (median 1.63, range 0.51-3.33 pmol/l and median 1.38, range 0.51-3.51 pmol/l, respectively). CONCLUSION: Local release of endothelin from the vascular endothelium is thought to cause vasospasm in pregnancy induced hypertension but this does not seem to increase the concentration of endothelin in the maternal peripheral plasma, probably because of its rapid disappearance from the blood circulation. As ANP dilates the blood vessels, the increase of its release in hypertensive pregnancies may be a compensatory mechanism against vasospasm.     

Levels of C-reactive protein in pregnant women who subsequently develop pre-eclampsia

Objective To investigate whether a maternal inflammatory response precedes the development of pre-eclampsia.
Design Cross-sectional study.
Setting Antenatal clinic in an inner city teaching hospital.
Population Two groups of women were examined at 23–25 weeks of gestation. The first group (45 women) had normal uterine artery Doppler waveforms and subsequently had a normal pregnancy outcome. The second group (45 women) had Doppler evidence of impaired placental perfusion and 21 (47%) of them had normal outcome, 14 (31%) developed intrauterine growth restriction and 10 (22%) developed pre-eclampsia, with or without intrauterine growth restriction.
Methods C-reactive protein, an acute-phase reactant, was measured in maternal serum using a highly sensitive method with a detection limit of 0.05mg/L.
Main Outcome Measures Development of pre-eclampsia, as defined by the International Society for the Study of Hypertension in Pregnancy. Intrauterine growth restriction was defined as birthweight <5th centile for gestation and sex of the neonate.
Results The serum C-reactive protein concentration in women who subsequently developed pre-eclampsia (median 1.56, range 0.55–3.12mg/L) or delivered a baby with birthweight <5th centile (median 0.74, range 0.64–1.58mg/L) was not significantly different from that in women with uncomplicated pregnancies (median 1.28, range 0.75–2.08mg/L;   P = 0.95  and   P = 0.62  , respectively).
Conclusion These findings suggest that the onset of clinical signs of pre-eclampsia may not be preceded by a maternal inflammatory response, as assessed by measurement of C-reactive protein.     

Screening for pre-eclampsia by using maternal serum inhibin A, activin A, human chorionic gonadotropin, unconjugated estriol, and alpha-fetoprotein levels and uterine artery Doppler in the second trimester of pregnancy

AIMS: To analyse the predictive power of maternal serum inhibin A, activin A, human chorionic gonadotropin (hCG), unconjugated estriol (uE(3)), alpha-fetoprotein (AFP) levels and uterine artery Doppler in the second trimester of pregnancy in screening for pre-eclampsia. METHODS: Maternal serum inhibin A, activin A, hCG, uE(3), and AFP levels and uterine artery Doppler were determined in 178 healthy, pregnant women in the second trimester of pregnancy. Serum samples were collected between the 16th and 18th weeks of gestation, and Doppler investigation was performed between the 24th and 26th weeks of gestation. Receiver operating characteristic curves were created to analyse the predictive powers of the above parameters in screening for pre-eclampsia. Different combinations also were analysed. RESULTS: The rate of pre-eclampsia was 7.9% (14/178). Maternal serum inhibin A, activin A, hCG, AFP levels, the rate of presence of the prediastolic notch and uterine artery resistance index (RI) values in pre-eclamptic pregnancies were significantly higher than those in healthy pregnancies. Presence of the prediastolic notch, uterine artery RI, maternal serum activin A and inhibin A levels had high predictive efficacy, and each had a sensitivity between 70 and 93% and a specificity between 87% and 98%. The addition of inhibin A or activin A measurement to the Doppler velocimetry improved the specificity to 99-100%. CONCLUSIONS: Maternal serum inhibin A and activin A levels and uterine artery Doppler appear to be useful screening tests during the second trimester for pre-eclampsia. However, addition of these hormonal markers to Doppler velocimetry only slightly improves the predictive efficacy, which appears clinically insignificant.     

Evidence of in vivo generation of thrombin in patients with small-for-gestational-age fetuses and pre-eclampsia

Objective: Thrombotic lesions in the maternal or fetal compartments are frequently observed in the placentas of patients with small-for-gestational-age (SGA) fetuses and in pre-eclampsia. The objective of this study was to determine whether there was evidence of in vivo generation of thrombin, the ratelimiting enzyme responsible for the formation of fibrin. The plasma concentrations of thrombin-antithrombin (TAT) complexes were used as an index of thrombin generation. Methods: TAT complexes were measured in the plasma from 68 women from the following groups: normal pregnancy (n = 29); pre-eclampsia (n = 26); and SGA (defined as estimated fetal weight below the 10th centile for gestational age, which was confirmed by neonatal birth weight) (n = 13). TAT complex plasma concentrations were determined with a specific and sensitive immunoassay. Statistical analysis was performed with non-parametric statistics. Results: The median plasma TAT complex concentrations were significantly higher in patients who delivered SGA neonates than in normal pregnant women (SGA, median 24.2 μg/l; range 11.9-788.7 vs. normal pregnancy, median: 14.4 μg/l; range 6.8-26.9; p = 0.001). Patients with pre-eclampsia had a higher median plasma TAT complex concentration than normal pregnant women (pre-eclampsia, median 18.1 μg/l; range 10.0-75.2 vs. normal pregnancy, median 14.4 μg/l; range 6.8-26.9; p = 0.02). Conclusion: In vivo generation of thrombin, determined by the plasma concentrations of TAT complexes, is higher in patients with SGA fetuses and patients with pre-eclampsia than in normal pregnancy.     

Screening for pre-eclampsia and small for gestational age fetuses at the 11-14 weeks scan by uterine artery Dopplers

OBJECTIVE: To assess the role of uterine artery Doppler studies at 11-14 weeks in screening for pre-eclampsia (PET), small for gestational age (SGA) fetuses, and placental abruption. METHODS: Prospective study on 1,123 women presenting for routine ultrasound examination at 11-14 weeks for nuchal translucency measurement. Uterine artery blood flow was studied by transvaginal colour Doppler, the mean pulsatility index (PI) was calculated, and the presence of a diastolic notch was recorded. RESULTS: The mean, median and 95th centile of uterine artery PI were 1.71, 1.64 and 2.54, respectively. Bilateral notches were observed in 63.4%, and a unilateral notch in 18.4% of cases. The sensitivity of mean uterine artery PI>or=95th centile for PET, early onset severe PET necessitating delivery before 34 weeks, SGA相似文献   

Uteroplacental blood flow and placental vascular endothelial growth factor in normotensive and pre-eclamptic pregnancy

Objective To determine whether placental vascular endothelial growth factor (VEGF) is increased in pre-eclampsia.
Design Prospective cohort study.
Setting Royal Prince Alfred Hospital, Sydney, Australia.
Sample Eleven normotensive women and eight women with pre-eclampsia matched for age and gestation.
Methods Uterine artery Doppler ultrasound flow velocity profiles were recorded in the third trimester and resistance index calculated as (V_s-V_d)/V_s (V_s= peak systolic flow velocity, V_d= end diastolic flow velocity). Placental tissue at delivery was examined for VEGF distribution with avidin-biotin-peroxidase immunohistochemistry.
Results Uterine resistance index [median (range)] was significantly increased in pre-eclamptic women (normotensive: 0.42 (0.36–0.51); pre-eclampsia: 0.59 (0.40–0.75);   P = 0.005  ). Notching of the uterine artery waveform, consistent with a high resistance circulation, was evident in early diastole in five women with pre-eclampsia but only one normotensive woman (   P = 0.013  ). Placental VEGF was increased in women with pre-eclampsia in the decidual trophoblast (normotensive: 34% (4–59) cells stained for VEGF; pre-eclampsia: 58% (15–95);   P = 0.033  ) and in the villous syncytiotrophoblast (normotensive: VEGF count 1.4 arbitrary units (1.1–2.1); pre-eclampsia: 1.8 arbitrary units (1.4–2.2);   P = 0.041  ). Analysis indicated that uterine artery resistance index was directly correlated with placental VEGF staining, mean arterial pressure and birthweight.
Conclusions Abnormal uterine artery Doppler ultrasound flow velocity profiles in pre-eclampsia indicate increased uteroplacental resistance. The associated increase in placental VEGF may represent a compensatory mechanism attempting to restore blood flow towards normal.     

Umbilical cord plasma homocysteine concentrations at delivery in pregnancies complicated by pre-eclampsia

Aim: To determine whether homocysteine concentrations in umbilical cord plasma of neonates born to mothers with pre-eclampsia are elevated compared to concentrations in neonates born to normotensive women.
Method: Maternal blood from eight women with pre-eclampsia and ten women without pre-eclampsia was collected on admission for labour. Cord blood was collected from these same pregnancies at delivery. Plasma was extracted and stored at −70°C. Samples were batch-analysed for homocysteine.
Result: Maternal plasma homocysteine levels were observed to be significantly higher in the pregnancies complicated by pre-eclampsia compared to the control pregnancies ( P  = 0.043) with median levels of 5.4 µmol/L (interquartile range (IQR) 4.6–7.9; range 3.6–16.7) versus 4.1 µmol/L (IQR 3.4–5.1, range 3.1–6.7). Homocysteine concentrations in umbilical cord plasma in pregnancies complicated by pre-eclampsia were also significantly higher compared to those in normotensive pregnancies ( P  = 0.016) with median concentration levels of 5.3 µmol/L (IQR 4.8–7.2, range 2.5–16.6) versus 3.8 µmol/L (IQR 2.8–4.4, range 0.8–1.6).
Conclusion: Both maternal and umbilical cord plasma homocysteine concentrations were elevated in pregnancies complicated by pre-eclampsia compared to normotensive controls.     

Tissue factor and its natural inhibitor in pre-eclampsia and SGA

Objective. Tissue factor (TF), the major activator of the extrinsic pathway of coagulation, is abundant in the placenta and decidua. The aim of this study was to determine the maternal plasma concentrations of TF and its primary inhibitor, tissue factor pathway inhibitor (TFPI), in women who delivered small for gestational age (SGA) neonates, and in pre-eclampsia.

Study design. A cross-sectional study included the following groups: 1) women with normal pregnancies (n = 86); 2) patients who delivered SGA neonates (n = 61) and 3) women with pre-eclampsia (n = 133). Maternal plasma concentrations of TF and TFPI were measured by a sensitive immunoassay. Non-parametric statistics were used for analysis.

Results. 1) Women with pre-eclampsia had a significantly higher median plasma concentration of TF than patients with a normal pregnancy (median: 1187 pg/mL; range: 69–11675 vs. median: 291.5 pg/mL; range: 6.3–2662.2; p < 0.0001, respectively); 2) Similarly, TFPI concentrations were higher in pre-eclampsia than in normal pregnancy (median: 87.5ng/mL; range 25.4–165.1 vs. median: 66.1 ng/mL; range: 14.3–86.5; p < 0.0001, respectively); 3) Surprisingly, mothers with SGA neonates had a lower median maternal plasma concentration of TF (median: 112.2 pg/mL; range: 25.6–1225.3) than women with a normal pregnancy (p < 0.0001).

Conclusion. 1) Maternal plasma concentrations of TF in patients with pre-eclampsia, but not in those who delivered an SGA neonate, were higher than in women with normal pregnancies; 2) Although the role of immunoreactive plasma TF in coagulation remains controversial, our observations suggest that changes are present in the context of complications of pregnancy.     

First trimester uterine Doppler and three-dimensional ultrasound placental volume calculation in predicting pre-eclampsia

OBJECTIVE: To compare the efficacy of uterine artery Doppler velocimetry and three-dimensional ultrasound placental volume calculation alone or in combination in predicting at 11-14 weeks of gestation those pregnancies who will develop pre-eclampsia. STUDY DESIGN: This was a prospective study of 348 nulliparous women scheduled for a routine prenatal ultrasound examination at 11-14 weeks. Color and pulsed wave Doppler was used to obtain uterine artery flow velocity waveforms transabdominally and the mean pulsatility index (PI) of the uterine arteries was calculated. The placental volume was measured by three-dimensional ultrasound using the virtual organ computer-aided analysis. Outcome variables considered were pre-eclampsia and pre-eclampsia requiring delivery <32 weeks. RESULTS: Pre-eclampsia developed in 4.1% of the patients studied and in 1.7% a delivery before 32 weeks was required. Placental volume resulted significantly lower in pregnancies who will develop pre-eclampsia (t=4.636, p<0.003) and this was particularly evident in those pregnancies delivering <32 weeks (t=9.704, p<0.0002). No relationship was found between placental volume and mean uterine artery PI (r=-0.08, p=0.327). Uterine artery PI and placental volume showed similar sensitivities in predicting pre-eclampsia (50% vs. 56%) and pre-eclampsia with delivery <32 weeks (66.7% vs. 66.7%). The combination of uterine artery PI and placental volume gave better results when compared to the single use of one of these parameters (pre-eclampsia sensitivity 68.7%, pre-eclampsia requiring delivery <32 weeks 83.3%). CONCLUSIONS: The combination of abnormal uterine artery Doppler and low placental volume at 11-14 weeks achieves better results than does either test alone in the prediction of pre-eclampsia.     

Circulating Angiogenic Factors and Abnormal Uterine Artery Doppler Velocimetry in the Second Trimester

Objective: Circulating angiogenic growth factors (such as vascular endothelial growth factor [VEGF] and placental growth factor [PlGF]) and their interaction may be associated with vascular remodeling of spiral arteries in normal pregnancy. Soluble Flt-1, an antagonist of both VEGF and PlGF, has been shown to be increased, while PlGF is decreased in women prior to the onset of preeclampsia. The purpose of this study was to compare maternal soluble Flt-1 and PlGF levels in the second trimester with a marker of abnormal placentation, abnormal uterine artery Doppler (UAD). Method: A prospective cohort of women, 16 to 24 weeks estimated gestational age (EGA), with singleton pregnancies, underwent UAD and phlebotomy. Maternal soluble Flt-1 and free PlGF were measured by ELISA in samples from women with abnormal UAD with a group, controlled for EGA, with normal UAD. Mann-Whitney Rank-Sum test was used to compare maternal serum levels of both soluble Flt-1 and PlGF between women with abnormal uterine artery Doppler versus women with normal uterine artery Doppler. Results: Of the 222 study subjects enrolled, 34 (15%) had abnormal UAD. The mean EGA at enrollment of subjects in each group was 18 weeks. There was no difference in PlGF between subjects with abnormal UAD (median, 191 pg/mL; range, 187 to 337 pg/mL) versus controls (median, 171 pg/mL; range, 169 to 289 pg/mL) (p = 0.59) or soluble Flt-1 (median, 780 pg/mL; range, 280 to 3200 pg/mL) or between subjects with abnormal UAD versus controls (median, 720 pg/mL; range, 220 to 1980 pg/mL) (p = 0.36). Conclusion: Concentrations of maternal soluble Flt-1 and free PlGF in the second trimester do not appear to be altered in women with abnormal UAD. This suggests that these biochemical markers are independent of the increased placental resistance seen with abnormal uterine artery Doppler.     

Circulating angiogenic factors and abnormal uterine artery Doppler velocimetry in the second trimester.

OBJECTIVE: Circulating angiogenic growth factors (such as vascular endothelial growth factor [VEGF] and placental growth factor [PlGF]) and their interaction may be associated with vascular remodeling of spiral arteries in normal pregnancy. Soluble Flt-1, an antagonist of both VEGF and PlGF, has been shown to be increased, while PlGF is decreased in women prior to the onset of preeclampsia. The purpose of this study was to compare maternal soluble Flt-1 and PlGF levels in the second trimester with a marker of abnormal placentation, abnormal uterine artery Doppler (UAD). METHOD: A prospective cohort of women, 16 to 24 weeks estimated gestational age (EGA), with singleton pregnancies, underwent UAD and phlebotomy. Maternal soluble Flt-1 and free PlGF were measured by ELISA in samples from women with abnormal UAD with a group, controlled for EGA, with normal UAD. Mann-Whitney Rank-Sum test was used to compare maternal serum levels of both soluble Flt-1 and PlGF between women with abnormal uterine artery Doppler versus women with normal uterine artery Doppler. RESULTS: Of the 222 study subjects enrolled, 34 (15%) had abnormal UAD. The mean EGA at enrollment of subjects in each group was 18 weeks. There was no difference in PlGF between subjects with abnormal UAD (median, 191 pg/mL; range, 187 to 337 pg/mL) versus controls (median, 171 pg/mL; range, 169 to 289 pg/mL) (p = 0.59) or soluble Flt-1 (median, 780 pg/mL; range, 280 to 3200 pg/mL) or between subjects with abnormal UAD versus controls (median, 720 pg/mL; range, 220 to 1980 pg/mL) (p = 0.36). CONCLUSION: Concentrations of maternal soluble Flt-1 and free PlGF in the second trimester do not appear to be altered in women with abnormal UAD. This suggests that these biochemical markers are independent of the increased placental resistance seen with abnormal uterine artery Doppler.     

First trimester sex hormone-binding globulin and subsequent development of preeclampsia or other adverse pregnancy outcomes.

OBJECTIVE: To investigate whether first trimester maternal serum sex hormone-binding globulin (SHBG) concentrations are altered in women who subsequently develop preeclampsia or other pregnancy complications. POPULATION: Women undergoing first trimester combined ultrasound and biochemical screening for chromosomal anomalies. We searched the database and identified 32 pregnancies resulting in miscarriage, 64 pregnancies with preexisting or gestational diabetes mellitus, 107 with fetal growth restriction, 103 with preeclampsia, 64 with pregnancy-induced hypertension, and 26 with spontaneous preterm delivery. We also selected 400 controls from among the population of pregnancies that had a delivery of a normal baby with no pregnancy complications. METHODS: Maternal serum SHBG concentrations were measured retrospectively using a competitive chemiluminescent immunoassay. The levels between those with normal outcome and those resulting in adverse outcome were compared. RESULTS: The median maternal serum SHBG concentration was not significantly different from controls, in those that subsequently developed preeclampsia (median MoM 1.05), non-proteinuric hypertension (median MoM 0.94) or preterm delivery (median MoM 1.15). The levels were significantly lower in those with diabetes (median MoM, 0.81 p=0.0005) and those pregnancies resulting in miscarriage (median MoM 0.80, p=0.008). CONCLUSION: First trimester maternal serum SHBG concentrations are no different from controls in women who subsequently develop preeclampsia, pregnancy-induced hypertension, fetal growth restriction, or preterm delivery. Levels are reduced in those who subsequently miscarry or in those presenting with diabetes.     

Uterine artery Doppler in the prediction of adverse pregnancy outcome

PURPOSE OF REVIEW: To review publications, published during the past year, that have examined uterine artery Doppler findings in women with adverse pregnancy outcome. RECENT FINDINGS: Almost two-thirds of stillbirths that occur in the early preterm period (up to 32 weeks) can be predicted by uterine artery Doppler at 23 weeks. First trimester screening studies have shown that an abnormal result increases the risk of subsequent fetal growth restriction, and such women are at particularly high risk when indices remain abnormal in the second trimester. Studies combining uterine artery Doppler with maternal serum markers have demonstrated that measurement of first-trimester maternal serum pregnancy-associated plasma protein A and free beta human chorionic gonadotrophin improve sensitivities of second-trimester Doppler. As these are frequently measured in Down syndrome screening and they lend themselves in screening for pre-eclampsia. Women with abnormal first and second-trimester serum markers constitute a high-risk group. Maternal serum placental protein 13 remains a promising method for early screening, although a recent study suggests lower sensitivities than initially reported. SUMMARY: Uterine artery Doppler screening identifies women at high risk for developing adverse pregnancy outcomes. Detection rates may be increased and false positive rates reduced by combination with maternal characteristics or serum markers.     

Metastin levels in pregnancies complicated by pre-eclampsia and their relation with disease severity

Aims: To evaluate the role of metastin levels in the pathophysiology of pre-eclampsia and to determine whether there is a relationship between the severity of the disease and Doppler velocimetry measurements. Methods: This cross-sectional study included 89 pregnant women (50 healthy normotensive pregnant women, 15 patients with mild pre-eclampsia, and 24 patients with severe pre-eclampsia) at the third trimester of pregnancy. The maternal levels of plasma metastin were determined by enzyme-linked immunosorbent assay. The umbilical artery and uterine artery blood flow velocities were measured by transabdominal color and pulsed Doppler ultrasound. Results: Plasma metastin levels were lower in patients with pre-eclampsia than those in the normotensive pregnant women. Four patients with mild pre-eclampsia and seven patients with severe pre-eclampsia had abnormal Doppler velocimetry findings. Metastin levels of pre-eclamptic patients with abnormal Doppler velocimetry findings were significantly lower than those in patients with normal Doppler velocimetry findings. Plasma metastin levels negatively correlated with proteinuria in 24 hours and with mean arterial pressure in the cases of pre-eclampsia. Conclusions: The findings suggest that decreased maternal concentrations of plasma metastin may be involved in the pathogenesis of pre-eclampsia. Plasma metastin levels may be useful in the assessment of the severity of pre-eclampsia. However, further trials are needed to clarify the role of metastin in pre-eclampsia.     

Relationship of maternal plasma leptin and risk of pre-eclampsia: a prospective study.

OBJECTIVE: We measured maternal plasma leptin concentrations in 55 women with pre-eclampsia and 487 normotensive women to determine whether elevated leptin concentrations were associated with the occurrence of pre-eclampsia. METHODS: Maternal blood samples were collected at 13 weeks' gestation, on average. Plasma leptin concentrations were determined using immunoassay. Logistic regression procedures were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Leptin concentrations were 78% higher in cases than control subjects (median 34.6 vs. 19.5 ng/ml; p < 0.001). Relative to women with leptin concentrations of < 27.4 ng/ml, those with elevated leptin concentrations (> or = 27.4 ng/ml) experienced a 2.3-fold increased risk of pre-eclampsia (OR 2.3; 95% CI 1.1-4.6). We observed evidence of a strong linear component of trend in risk of pre-eclampsia with increasing maternal plasma leptin concentration. Each 10-ng/ml increase in leptin concentration was associated with a 30% increase in pre-eclampsia risk (OR 1.3; 95% CI 1.1-1.5). Overweight women with elevated leptin concentrations experienced the highest risk of pre-eclampsia (OR 6.4; 95% CI 3.1-13.2) as compared with lean women with no leptin elevations. CONCLUSION: Elevated plasma leptin concentration and maternal overweight status appear to be independently associated with an increased risk of pre-eclampsia.