Variation of the maximum velocity along the umbilical vein supports the Reynolds pulsometer model.

OBJECTIVE: To challenge, with a modern sonographic approach and a numerical model, the Reynolds's concept which suggests that the vascular structure of the umbilical cord could act as a pulsometer facilitating the venous return to the foetus. METHOD: Forty-five patients between 20 and 28 weeks of gestation were included in the study. The blood maximum velocity in the umbilical vein, measured at both foetal and placental ends, was assessed. Several sonographic parameters of the cord, including the diameter of the umbilical vein at both extremities, cord cross-sectional area and Wharton's jelly section surface were measured. We compare our data with those of a numerical model. RESULTS: A difference in maximum velocity between the two extremities of the umbilical vein (ΔUVVmax) was noted. The maximum velocity was significantly higher at the foetal umbilical end (14.12 +/-3.18 cm/s) than at the placental end (11.93 +/-2.55 cm/s; p < 0.0001). The mean difference is 2.2 +/- 2.3 cm/s. No difference in the umbilical vein diameter was measured at both cord ends (umbilical 4.85 +/-0.9 mm, placental 4.86 +/-0.87 mm, p < 0.0001). There is no significant relationship between ΔUVVmax and the cord cross-sectional area or Wharton's jelly index. CONCLUSION: Modifications of the spatial velocity profile together with the pulsometer model could explain the maximum velocity changes that is measured in the umbilical vein along the cord. This numerical model consolidates the sonographic observations.

[Clinical case of the month. Unfavourable outcome of a triplet gestation]. / Issue d favorable d'une grossesse triple.

Body stalk anomaly is rarely described in triplet gestation after medically assisted procreation. The relationship between congenital anomaly, multiple pregnancy, and medically assisted procreation is briefly discussed.

[X-linked hydrocephaly. A case report in fetal medicine]. / Le cas clinique du mois. Hydrocéphalie liée à i'X: à spropos d'un cas en médecine foetale.

X-linked hydrocephaly (Li Syndrome) is a rare cause of hydrocephaly. It is, however, the most common genetic form of congenital hydrocephaly and consists of the association of hydrocephaly, mental retardation, leg spasticity and adducted thumbs. The phenotype is variable. A mutation of the LICAM gene is known to be the aetiology of the syndrome. We present an antenatal case managed in our department.

Dysregulation of anti-angiogenic agents (sFlt-1, PLGF, and sEndoglin) in preeclampsia--a step forward but not the definitive answer.

Preeclampsia (PE) is a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, which resolves on placental delivery. It is thought to be the consequence of impaired placentation due to inadequate trophoblastic invasion of the maternal spiral arteries. In PE the maternal plasma concentration of free vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) is decreased whereas the concentration of soluble fms-like tyrosine kinase-1 (sFlt-1) and of soluble endoglin (sEng) is increased. These soluble receptors may bind VEGF, PLGF and TGFbeta1 and TGFbeta3 in the maternal circulation, causing endothelial dysfunction in many maternal tissues. Hence there is a view that the pathogenesis is more or less clarified. According to the vascular theory, poor placentation leads to poor uteroplacental perfusion and hypoxia, which stimulates sFlt-1 and sEng production causing the maternal syndrome. This assumption has been recently challenged. The role of hypoxia as the main stimulus for release of sFlt-1 has been questioned and the role of inflammatory mechanisms has been emphasized. According to this inflammatory theory, poor placentation may predispose more to placental oxidative stress than hypoxia and endothelial dysfunction may be part of a broader disorder of systemic inflammation. Finally, the recent demonstration of activating auto-antibodies to the angiotensin 1 receptor that experimentally play a major pathogenic role in PE further suggests a pleiotropism of aetiologies for this condition. The purpose of this review is to critically evaluate the recent hypotheses and their possible insights on early diagnosis, prevention and treatment.

Rh D foeto-maternal alloimmunization prophylaxis with anti-D immunoglobulins reviewed in the era of foetal RHD genotyping.

In Belgium, prevention of anti-D immunization is currently based on systematic postnatal prophylaxis associated with targeted antenatal injection in high-risk situations of foeto-maternal haemorrhage.The failures of prevention are mainly due to the non-respect of established guidelines for RhlG prophylaxis, and to spontaneous undetected foetal-maternal haemorrhages without any obvious cause during the third trimester of pregnancy. In order to reduce the rate of residual post-pregnancy anti-D immunization, several countries decided to associate the classical prophylaxis to a routine antenatal anti-D prophylaxis (RAADP) during the 28th or 29th week of gestation. Since a few years, the foetal RHD genotyping in maternal plasma enables us to limit the antenatal prophylaxis only to those D- women carrying a D+ foetus. This paper deals with: the advantages of an antenatal prevention in the light of non-invasive foetal RHD genotyping, the rules rendering prevention protocols efficient whatever the algorithm applied, and the recommended immuno-haematology follow-up of women who received RhlG.

[A rare case of placental chorioangioma associated with neonatal disseminated hemangiomatosis]. / Association rare d'un choriangiome et d'une hémangiomatose néonatale diffuse.

Placental chorioangioma is a benign vascular tumor. Lesions larger than 4 cm may cause fetal and maternal complications. Its association with disseminated neonatal hemangiomatosis is rarely described. We report a case of a large chorioangioma associated with an hydrops foetalis and disseminated neonatal hemangiomatosis. The relationship between placental chorioangioma and hemangioma is briefly discussed.

[How I explore...the benefit of 3D/4D ultrasound in obstetrics]. / Comment j'explore... Apport de l'échographie 3D/4D en obstétrique.

During recent years, 3D has become an important tool in ultrasound. In obstetrics, the classic 2D examination with Doppler is now often completed by 3D. In this article the strengths and weaknesses of this technique are discussed.

[New methods of prenatal screening for trisomy 21]. / Nouvelles méthodes d'évaluation du risque de trisomie 21 en consultation prénatale.

Down syndrome is the most commonly recognized genetic cause of mental retardation. The risk of trisomy 21 is directly related to maternal age which can be viewed as the first screening test in the 1970's. New strategies for Down syndrom, have emerged with higher sensitivity and lower false-positive rate. These strategies are based on sonographic and maternal serum markers. The most specific but complex strategy is based on the integrated test, i.e., the integration of the quadruple test performed in the second trimester to the first trimester combined screening: for a 85% detection rate, the false positive rate is estimated to 0.9%. This strategy deprives the patient of an early diagnosis. Alternatives strategies do exist which can perform similar detection rate but with increasing false positive rate. To date Down syndrom, screening has not been coordinated by a national body; it would be usefull to ensure the sonographist formation, perform quality audit and decrease variations in practice.

[Predictive value of antenatal ultrasound for the neonatal diagnostic of renal and ureteral anomaly]. / La valeur prédictive de néphro-uropathie des pyélectasies foetales.

Pyelectasis is a dilatation of the renal pelvis. It must be differentiated from hydronephrosis which is a dilation of the renal pelvis and of the renal calyces. In this retrospective study, we focused on the treatment and follow up of 31 newborns in whom a pyelectasis had been diagnosed in utero. At the end of the study, 20 babies showed no sign of an urologic disorder whereas 11 babies did. Our study suggests that it is crucial to search for an urologic disorder in the neonatal period when a fetal pyelectasis has been diagnosed.

[Prenatal care and postnatal outcome for fetuses with laparoschisis]. / Gestion anténatale et issue postnatale des foetus atteints de laparoschisis.

OBJECTIVES: To assess the relevance and the quality of gastroschisis's care in a mid level referral centre. METHOD: A retrospective analysis was performed for infants diagnosed or born with gastroschisis between 1992 and 2003 at the Citadelle hospital, Department of Obstetrics and Gynaecology, University of Liège. RESULTS: Twenty-four cases of gastroschisis were identified. For 22 of them (92%) antenatal sonographic diagnosis was performed at a mean gestational age of 23 weeks. Antenatal diagnosis did not allow to identify additional malformation or chromosomal anomaly. Postnatal diagnosis allows to identify 3 infants with minor cardiac anomalies without functional consequence and one X fragile syndrome. One pregnancy was electively terminated at 24 weeks and one late intrauterine death was reported at 35 weeks. Bowel atresia, stenosis or ischemia were present at birth for 8 cases (33%). Out of 24 cases 22 were live born. 10 infants out of 22 (45%) underwent uncomplicated primary surgical repair. Three infants out of 22 (14%) underwent delayed closure without complications. Nine infants out 22 (41%) underwent multiple surgery (2 to 6). In this group all had postnatal complications, some with multisystem complications, including 3 deaths, 6 with infectious complications, 5 with gastrointestinal complications and 2 with genitourinary or haematological complications. Hospital stay range from 19 to 378 days (median, 51 days). Length of stay and time to full enteral feeding were longer if oligohydramnios or sonographic signs of intestinal damage were found. Among infants born before 35 weeks, only those with intestinal damage at birth had length of stay or time to full enteral feeding longer. Out of 22 live born infants 19 survived (86%) after one year. Survival rate without handicap due to gastroschisis is 84%. CONCLUSION: Sonographic examination is a valid method for prenatal diagnosis and surveillance. Our survival rate agrees with recent data in the literature. It has to be noticed that hospital stay is lengthy and complications are frequent. The most important prognostic factor is the condition of the bowel at birth and there is no antenatal means to predict severe damage.

[New approaches to prenatal diagnosis of rhesus incompatibility]. / Nouvelles stratégies dans la prise en charge de l'allo-immunisation foeto-maternelle anti-RHD (Rhésus).

Despite generalisation of anti-D immunoprophylaxis, RhD allo-immunisation still remains the major cause of severe haemolytic disease of the fetus and of the newborn (HDFN). The routine follow up of pregnant women comprises: the ABO/D, Rh/Kell red cells typing and the search for irregular antibodies. In case of anti-D immunisation, the paternal Rh phenotype, when known, provides useful information regarding the probability for the fetus to have inherited the D antigen and thereby to be exposed to the risk of HDFN. The antibody titre, which is predictive of possible in vivo haemolysis, must be interpreted in the light of the previous obstetric history, and can lead to the decision of invasive amniocentesis. Then the measurement of the optical density (deltaOD450 nm) and the fetal RhD typing can be realised on amniotic fluid. New molecular techniques make it possible now to demonstrate the presence of fetal DNA in maternal plasma. These methods lying on non invasive procedures could advantageously be applied to the genotyping of fetal RHD during pregnancy. The present paper aims to discuss the predictive values of RHD fetal genotype in maternal plasma of RhD negative mothers. The ante-partum management of immunised pregnant women is reviewed in the light of this new molecular approach combined to Doppler ultrasonography of the fetal middle cerebral artery. This non invasive method for determining fetal RHD genotype could be systematically proposed to all RhD negative pregnant women for a better targeted prenatal follow-up and an increased efficacy of RhD prophylaxis.

[Fetal RHD in maternal plasma in prenatal follow-up]. / Le génotypage RHD foetal sur sang maternel dans le suivi prénatal des patientes Rh D négatif.

Since the beginning of RHD genotyping in maternal plasma, no Rh D positive baby was diagnosed RHD negative in our institution. Genotyping from circulating DNA in maternal plasma is as efficient as genotyping on amniocyts but without the associated risks. We propose a prophylactic injection based on fetal genotyping RHD in maternal blood with 300 microg anti-D immunoglobulin at 28 weeks of amenhorrea in all of Rh D negative pregnant women whitch fetuses positive RHD.

[Prenatal determination of fetal RHD in maternal plasma: two-years experience of routine clinical use]. / Utilisation en routine clinique du génotypage foetal RHD sur plasma maternel: bilan de deux ans d'activité

OBJECTIVES: To evaluate the predictive value of RHD fetal genotype in maternal plasma of Rh D negative mothers after 10 weeks of gestation in a clinical use. MATERIAL AND METHOD: Prospective, comparative study between fetal RHD genotyping in maternal plasma, with amplification of exons 4,5,10 of the RHD gene, by real-time multiplex PCR, and Rh D serology at birth, in 218 pregnancy and their 223 babies, between November 2002 and 2004. RESULTS: Combining the amplification of three exons, the concordance rate of fetal Rh D genotyping in maternal plasma and baby phenotyping at delivery was 100%. Four women whose the babies were Rh D negative were positive for RHD exon 10 during pregnancy. This positivity was, in three cases, correlated with the presence of RHDpsi pseudogene and in last case, with a haplotype Cdes (r's). RHD genotyping was performed for five twin pregnancies. CONCLUSION: Multiplex PCR using maternal plasma provides perfect prenatal prediction of fetal RHD gene. These results confirm that this non invasive procedure is the preferred method for assessing Rh D fetal status in Rh negative mothers. Using this method for two years in routine practice has led us to modify our management scheme for sensitized Rh D-negative pregnant women.

Delayed delivery of second twin: a multicentre study of 35 cases.

OBJECTIVE: The aim of this study was to conduct a statistical analysis to determine the outcome of conservative treatment after delivery of a first fetus in multiple pregnancy and thus define new prognostic factors. STUDY DESIGN: Multicentre retrospective study involving 12 centers over a 10-year period. RESULTS: Twenty-eight twin pregnancies and seven triplet pregnancies which were managed conservatively. In twin pregnancies, 79% of the delayed-delivery fetuses survived; only 7% of the first delivered fetuses survived. The mean interval between deliveries was 47 days. No statistical difference was found concerning cerclage, antibiotic therapy, tocolysis and hospitalization. Earlier delivery of the first twin and premature rupture of membranes for the second twin were significantly related to a longer interval between deliveries. CONCLUSION: Delayed delivery in multifetal pregnancies can be successful if there are no contraindications and these pregnancies are managed in a tertiary perinatal center. Publications limited to successful cases have undoubtedly introduced some bias in assessment.

[Uteroplacental vascularization]. / La vascularisation utéroplacentaire.

The intervillous space is considered as receiving the most important part of the uterine flow input (> 90%), reaching the placenta through the modified spiral arteries network. The low vascular resistance detected on the uterine arteries is thought to be due to the presence of the placental shunt. Using a 3D Colour Doppler technology (ATL 5000), a complex anastomotic and intra-myometrial network has been detected. This vascular network is always detected during the first 48 hours of after delivery. During this time, the placenta has been removed, the uterine muscle is contracted, a low resistance of the uterine flow is systematically detected. A extraplacental vascular component must be considered as taking a functional part in the foeto-maternal exchanges.

Fetal renal hyperechogenicity in intrauterine growth retardation: importance and outcome.

The object of the study was to investigate the outcome in growth-retarded newborns who were diagnosed with fetal renal hyperechogenicity without anatomical abnormality during any stage of pregnancy. Depending on the fetal renal ultrasonography result, the cases were divided into two study groups. There was an intrauterine growth-retarded group with fetal renal medullary hyperechogenicity and another group without fetal renal medullary hyperechogenicity. The renal parenchyma was observed after birth, within the first 5 days of life, and several times until the 14th postpartum day in positive cases. Hyperechogenic renal medullae were detected in 25 of 90 cases with intrauterine growth retardation during the 8-month study period. This may be an in utero cause of subsequent intrauterine and neonatal complications, such as cesarean section because of fetal distress (36%), perinatal infection (24%), treatment in a neonatal intensive care unit (52%), or increased perinatal mortality (8%). The results demonstrate that fetuses with hyperechoic medullae had 1.5 times the risk of an abnormal outcome compared with fetuses with normal echoic kidneys and intrauterine growth retardation. Detailed ultrasound examinations of renal parenchyma appear to be useful for the prenatal diagnosis of intrauterine hypoxia, allowing the detection of possible pathological fetal conditions in utero.

Fetal renal artery flow and renal echogenicity in the chronically hypoxic state.

The object of this study was to investigate the fetal renal arterial blood flow in normal and hyperechogenic kidneys during the third trimester of gestation. The pregnancies screened were all chronically hypoxic. Depending on the etiology of the intrauterine chronic hypoxia, the cases were divided into two study groups. Group I comprised 120 pregnant women with pregnancy-associated hypertension and/or proteinuria. Group II consisted of 87 pregnancies with intrauterine growth retardation. Both study groups included pregnant women from the third trimester. Hyperechogenic renal medullae were detected in 15 out of 120 cases with pregnancy-associated hypertension and/or proteinuria, and in 22 fetuses of the 87 pregnancies involving intrauterine growth retardation. Fetal renal hyperechogenicity appears to be an indicator of fetal arterial circulatory depression, correlated with pathological changes in the resistance index for the fetal renal arteries. The fetal renal arterial blood flow resistance index was significantly lower in hyperechogenic cases. This may also be an in utero indication of subsequent intrauterine and neonatal complications, such as cesarean section because of fetal distress (43%), treatment in a neonatal intensive care unit (51%) or increased perinatal mortality (5.4%, as compared with 0.8-1.0% in the normal population). Detailed ultrasound and Doppler examinations of renal parenchyma and arteries appear to be useful methods in the prenatal diagnosis of reduced renal perfusion and of intrauterine hypoxia to detect possible pathological fetal conditions in utero.

Embryonic and early fetal development of the human neocortex.

Early corticogenesis was studied in human embryos and early fetuses from Carnegie stages 16 to 22 (5-8 gestational weeks) by using immunohistochemistry for Reelin (Reln), calretinin (CR), and glutamic acid decarboxylase (GAD). A first population of Reln-positive cells appears in the neocortical anlage at stage 16 and increases in number at stages 17-18. At stages 19-20, a monolayer of horizontal CR- and GAD-positive, Reln-negative neurons forms in the preplate, whereas Reln-positive cells shift into a subpial position. Another cell class, the pioneer projection neuron, is CR-positive but GAD- and Reln-negative; pioneer cells contribute early corticofugal axons. Pioneer cells first appear below the monolayer at stage 20 and form a pioneer plate at stage 21. The cortical plate (CP) proper emerges at stage 21 and inserts itself within the pioneer plate, which is thus split into a minor superficial component and a larger deep component that presumably corresponds to the subplate. Initial CP neurons are radially organized and mostly CR-negative. Reln-positive cells remain consistently segregated from the pioneer cells and are thus not directly involved in preplate partition. Our data indicate that the neuronal composition of the human neocortical preplate is more complex than generally described and that various neurons participate in a sequence of events that precede the emergence of the CP.

[Successful PMA. Review of the activities of the Center for Medically Assisted Procreation of University of Liege, 1985-1997]. / La PMA qui réussit Bilan d'activité du Centre de Procréation Médicalement assistée de l'ULg, 1985-1997.

Assisted reproductive treatments (ART) hold an increasing place in the field of female infertility but also of male infertility with the development of new micromanipulative technologies. From January 1985 to December 1997, more than 3,000 ovarian punctures were achieved at the CPMA of the University of Liege and more than 40,000 oocytes were recovered. Global results show a take home baby rate of 23% per ovum pick-up and 27% per embryo transfer. Embryo cryopreservation offers an efficient solution to the problem of supernumerary embryos and opens the way for IVF-derived procedures such as oocyte or embryo donation, surrogate mother. The transfer of frozen-thawed embryos increases the total ongoing pregnancy rate per cycle of 31%. One of the aims of our Centre in the near future is the development of new technologies such as control of chromosomal abnormalities or genetic defect in preimplantation embryos and clinical applications of oocyte or ovarian tissue freezing.