Prenatal Determination of Fetal Rhd in Maternal Plasma: Two-Years Experience of Routine Clinical Use

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

Routine Fetal Rhd Genotyping with Maternal Plasma: A Four-Year Experience in Belgium

peer reviewedBACKGROUND: The objective was to evaluate the diagnostic value of RHD fetal genotyping from the plasma of D- mothers as soon as 10 weeks' gestation in a routine clinical practice in Belgium. STUDY DESIGN AND METHODS: A prospective study was conducted between November 2002 and December 2006. DNA extraction was performed in an automated closed tube system. Fetal RHD/SRY genotypes were detected in the plasma of 563 pregnant mothers by real-time polymerase chain reaction (PCR) targeting multiple exons 4, 5, and 10 of the RHD gene and targeting an SRY gene sequence. These were compared to the D phenotypes determined in the 581 babies they delivered. RESULTS: By combining amplification of three exons, the concordance rate of fetal RHD genotypes in maternal plasma and newborn D phenotypes at delivery was 100 percent (99.8% including one unusual false-positive). The presence of nonfunctional RHD genes and the absence of a universal fetal marker, irrespective of fetal sex, did not influence the accuracy of fetal RhD status prediction. The RHD genotyping from 18 twin pregnancies was also assessed. Five weak D women were excluded from the RHD fetal genotyping prediction. Three discrepant results (0.5%) between predicted fetal genotype and cord blood phenotype were not confirmed by the baby phenotypes from venipuncture blood. CONCLUSION: Prenatal prediction of fetal RHD by targeting multiple exons from the maternal plasma with real-time PCR is highly sensitive and accurate. Over 4 years, this experience has highly modified our management of D- pregnant women

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

peer reviewedThe 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

Prenatal Care and Postnatal Outcome for Fetuses with 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 Liege. 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

Utero-Placental Circulation

peer reviewe

The Human Placenta Becomes Haemochorial at the 13th Week of Pregnancy

Histological specimens of recent implantation sites are the basis of our current concept on human embryo implantation and placental development. In the Carnegie Collection maternal red blood cells were detected early in the primitive intervillous space (10th-12th day after conception). These cells were localized to the trophoblastic lacunae and originated from distended peripheral maternal sinusoids (Kaufmann, 1981). The classical theory states that progressively more and more maternal vessels are tapped. A true maternal blood flow is established around the 29th day. Dynamic investigations of human placental development in vivo are scarce and hampered by ethical considerations and the absolute requirement to refrain from using non aggressive and potentially harmful techniques. Despite these limitations such studies provide new insights that surprisingly contradict our previously and seemingly definitely established knowledge of the early phases of placental vascularization, and lead us to conclude that there is an absence of maternal blood circulation in the intervillous placental space (IVS) during the 12 first weeks of human pregnancy

La valeur prédictive de néphro-uropathie des pyélectasies foetales

peer reviewedPyelectasis 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

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 TGFβ1 and TGFβ3 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

Individual decisions in placenta increta and percreta: a case series.

Abstract Objective: Placenta increta or percreta is an uncommon pathology, sometimes associated with high maternal morbidity. Its prevalence increases proportionally to the number of cesarean sections. This study analyzed the changes of our management strategy to devise treatment guidelines for this uncommon disorder. Materials and methodology: Between 2005 and 2011, 10 cases of placenta increta or percreta were managed at our university hospital maternity department. Results: Among the 10 cases, seven were diagnosed prenatally. Two patients were diagnosed early, at 14 and 17 weeks of gestational age, and their pregnancies were terminated. Five had hysterectomies during the intrapartum period, and despite attempted conservative treatment for the two others, hysterectomy proved necessary 2 months postpartum because of intrauterine infections. Seven of the 10 women had hysterectomies. Conclusion: Prenatal diagnosis of placenta increta or percreta is essential to plan the delivery in a competent tertiary care center. The decision to perform a cesarean hysterectomy or leave the placenta in situ for spontaneous delivery is based on the extent of infiltration, the patient's hemodynamic status, and her desire to remain fertile. The high-risk of infection and severe hemorrhage must not be overlooked should conservative treatment be chosen. This situation requires prolonged close monitoring

Unfavourable outcome of a triplet gestation

peer reviewedBody 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