A. T. Papageorghiou

Absence of nasal bone in fetuses with trisomy 21 at 11-14 weeks of gestation: an observational study.

BACKGROUNDnPrenatal diagnosis of trisomy 21 requires an invasive test in women regarded as being at high risk after screening. At present there are four screening tests, and for a 5% false-positive rate, the sensitivities are about 30% for maternal age alone, 60-70% for maternal age and second-trimester maternal serum biochemical testing, 75% for maternal age and first-trimester fetal nuchal translucency scanning, and 85% for maternal age with fetal nuchal translucency and maternal serum biochemistry at 11-14 weeks. In this study, we examined the possible improvement in screening for trisomy 21 by examining the fetal nasal bone with ultrasound at 11-14 weeks of gestation.nnnMETHODSnWe did an ultrasound examination of the fetal profile in 701 fetuses at 11-14 weeks gestation immediately before karyotyping for a possible chromosomal abnormality detected by maternal age and fetal nuchal translucency screening. The presence or absence of a nasal bone was noted.nnnFINDINGSnThe fetal profile was successfully examined in all cases. The nasal bone was absent in 43 of 59 (73%) trisomy 21 fetuses and in three of 603 (0.5%) chromosomally normal fetuses. The likelihood ratio for trisomy 21 was 146 (95% CI 50-434) for absent nasal bone and 0.27 (0.18-0.40) for present nasal bone. In screening for trisomy 21, by a combination of maternal age and fetal nuchal translucency, we estimated that inclusion of examination of the fetal profile for the presence or absence of nasal bone could increase the sensitivity to 85% and decrease the false-positive rate to about 1%.nnnINTERPRETATIONnIn screening for trisomy 21, examination of the fetal nasal bone could result in major reduction in the need for invasive testing and a substantial increase in sensitivity.

Second-trimester uterine artery Doppler screening in unselected populations: a review

Objective: Doppler ultrasound provides a non-invasive method for the study of the uteroplacental circulation. In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation, which may be the consequence of trophoblastic invasion of the spiral arteries and their conversion into low-resistance vessels. Pre-eclampsia and fetal growth restriction are associated with failure of trophoblastic invasion of spiral arteries, and Doppler studies, in these conditions, have shown that impedance to flow in the uterine arteries is increased. A series of screening studies involving assessment of impedance to flow in the uterine arteries have examined the potential value of Doppler in identifying pregnancies at risk of the complications of impaired placentation. This review examines the findings of Doppler studies in unselected populations. Methods: Searches of a computerized medical database were performed to identify relevant studies. Only those studies that provided sufficient data to allow calculation of the performance of the test were included in the analysis. Likelihood ratios were calculated for each study and are reported for pre-eclampsia, fetal growth restriction and perinatal death as well as for more severe forms of pre-eclampsia and fetal growth restriction. Results: The literature search identified 19 relevant studies, four of which were excluded from the further analysis. The main characteristics and results of the 15 remaining studies provided discrepant results, which may be the consequence of differences in Doppler technique for sampling, the definition of abnormal flow velocity waveform, differences in the populations examined, the gestational age at which women were studied and different criteria for the diagnosis of pre-eclampsia and fetal growth restriction. Nevertheless, the studies provided evidence that increased impedance to flow in the uterine arteries is associated with increased risk for subsequent development of pre-eclampsia, fetal growth restriction and perinatal death. In addition, women with normal impedance to flow in the uterine arteries constituted a group that have a low risk of developing obstetric complications related to uteroplacental insufficiency. Conclusions: The review suggests that increased impedance to flow in the uterine arteries in pregnancies attending for routine antenatal care identifies about 40% of those who subsequently develop pre-eclampsia and about 20% of those who develop fetal growth restriction. Following a positive test, the likelihood of these complications is increased by about 6 and 3.5 times, respectively.

Prediction of pre-eclampsia by uterine artery Doppler ultrasonography and maternal serum pregnancy-associated plasma protein-A, free β-human chorionic gonadotropin, activin A and inhibin A at 22 + 0 to 24 + 6 weeks' gestation

To investigate the potential value of combining uterine artery Doppler ultrasonography with the measurement of maternal serum pregnancy‐associated plasma protein‐A (PAPP‐A), free β‐human chorionic gonadotropin (β‐hCG), activin A and inhibin A at 22 + 0 to 24 + 6 weeks gestation, in the prediction of pregnancies that subsequently develop pre‐eclampsia.

Assessment of risk for the development of pre-eclampsia by maternal characteristics and uterine artery Doppler.

Objectiveu2003 To develop a method for the estimation of patient‐specific risk for the development of pre‐eclampsia by combining maternal history and uterine artery Doppler.

Temporal regulation of the expression of syncytin (HERV-W), maternally imprinted PEG10, and SGCE in human placenta.

Abstract Maternally imprinted PEG10 and SGCE, separated by ∼2.15 Mb from Syncytin (HERV-W) gene at 7q21.3, are implicated in choriocarcinoma and Silver-Russell syndrome. Here we have analyzed the temporal regulation of mRNA expression of these genes in placenta and demonstrate that Syncytin gene activation is highest in term placenta, PEG10, downregulated at early hypoxic phase, and highly activated at 11–12 wk of gestation. In contrast, transcription from SGCE remained unchanged throughout pregnancy, suggesting two neighboring imprinted genes are differentially regulated at very early pregnancy. Additionally, accumulation of two major species of mRNA (8 kb and 3.1 kb) encoded by HERV-W in placenta is regulated: 3.1 kb mRNA level remained unchanged throughout pregnancy, whereas the production of 8 kb species was highest in term placenta. Western blot and immunohistochemical staining of placental tissues with monoclonal antibodies revealed a marked reduction of syncytin glycoprotein synthesis in late pregnancy. Therefore, the relative levels of 3.1 kb and 8 kb mRNAs in trophoblasts could regulate syncytin protein synthesis, possibly by competition of the two mRNA species for translational apparatus.

Maternal uterine artery Doppler flow velocimetry and the risk of stillbirth.

OBJECTIVE: We sought to relate the risk of antepartum stillbirth to uterine artery Doppler flow velocimetry at 22–24 weeks. METHODS: Data were available from 30,519 unselected women from seven units in the UK who had uterine artery Doppler performed between 22 and 24 weeks of gestation. The risk of stillbirth (n=109) was assessed using time to event and logistic regression analysis. Stillbirths were subdivided into placental (due to abruption, preeclampsia, or growth restriction) or unexplained. RESULTS: The risk of placental stillbirth was increased among women with a mean pulsatility index in the top decile (adjusted hazard ratio [HR] 5.5, 95% confidence interval [CI] 2.8–10.6) and those with a bilateral notch (adjusted HR 3.9, 95% CI 2.0–7.8). The relationship between a mean pulsatility index in the top decile and the risk of unexplained stillbirth was weaker (adjusted HR 2.5, 95% CI 1.1–5.6) and there was no association with a bilateral notch. Placental stillbirths occurred at earlier gestations than unexplained stillbirths (median [interquartile range] 30 [26–36] compared with 38 [36–40], P<.001). Consequently, being in the top 5% of predicted risk of stillbirth on the basis of the combination of mean pulsatility index and notching was a good predictor (sensitivity, specificity, and positive likelihood ratio) of all cause stillbirth up to 32 weeks (58%, 95%, and 12.1, respectively) but a poor predictor of stillbirth at later gestations (7%, 95%, and 1.3, respectively). CONCLUSION: Abnormal uterine artery Doppler was a better predictor of the risk of stillbirth due to placental causes than unexplained stillbirth. Consequently, abnormal uterine artery Doppler was a good predictor of stillbirth at extreme preterm gestations but a poor predictor of stillbirth at term. LEVEL OF EVIDENCE: II

Trichorionic triplet pregnancies at 10- 14 weeks: outcome after embryo reduction compared to expectant management

Objective: To compare the outcome of trichorionic triplet pregnancies managed expectantly with those reduced to twins or singletons. Methods: This was a retrospective study of trichorionic triplet pregnancies with three live fetuses at 10-14 (median 12) weeks gestation referred to our unit for consideration of embryo reduction. Women were counselled as to the available options of either expectant management or embryo reduction. In those choosing reduction, a needle was inserted into the uterus transabdominally and potassium chloride was injected into the fetal heart. Using data derived from this study and from a review of studies reporting on survival and handicap by gestational age in singletons, the effects of embryo reduction on survival and handicap rates were estimated. Main outcome measures were miscarriage before 24 weeks of gestation, preterm delivery before 32 weeks, perinatal death and handicap rates. Results: In total, there were 280 trichorionic triplet pregnancies and 125 of these were managed expectantly, 133 were reduced to two fetuses and 22 were reduced to one fetus. The rates of miscarriage were 3.2% for those managed expectantly, 8.3% for those reduced to twins and 13.6% for those reduced to singletons. The rates of early preterm delivery in those pregnancies that did not miscarry were 23.1%, 9.8% and 5.3%, respectively. The percentages for pregnancies with at least one survivor were 95.2%, 91.0% and 81.8%, respectively, and the median gestation at delivery was 34 weeks for the non-reduced, 36 weeks for those reduced to twins and 38 weeks for those reduced to singletons. From the published series on early preterm delivery, it was estimated that survival increases from about 27% at 24 weeks to about 98% at 32 weeks, and handicap decreases from 28% at 24 weeks to less than 5% at 32 weeks. From these estimates and the data on triplet pregnancies, it was calculated that, in triplets reduced to twins, compared to those managed expectantly, the chance of survival is similar (90.3% compared to 93.3%), but the risk of handicap may be lower (0.6% compared to 1.5% per fetus). Conclusions: In trichorionic triplet pregnancies, embryo reduction to twins does not improve the chance of survival but may reduce the rate of handicap. Reduction from triplets to singletons may reduce both the survival rate and the handicap rate among survivors.

Intrauterine growth in multiple pregnancies in relation to fetal number, chorionicity and gestational age

To examine birth weight in dichorionic and monochorionic twins and trichorionic triplets, and to estimate the relative independent importance on growth of fetal number, chorionicity and gestational age.

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

OBJECTIVEnTo 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.nnnMETHODSnThis 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.nnnRESULTSnIn 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).nnnCONCLUSIONnMid-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.

Relationship between second-trimester uterine artery Doppler and spontaneous early preterm delivery

To evaluate the relationship between impedance to flow in the uterine arteries at 22–24 weeks and subsequent spontaneous delivery before 33 weeks.