Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study.

Objectives: To assess the accuracy of fetal RHD genotyping using cell-free fetal DNA in maternal plasma at different gestational ages.

Design: A prospective multicentre cohort study.

Setting: Seven maternity units in England.

The role of VEGF-A165b in trophoblast survival.

Background: Pre-eclampsia remains a dominant cause of maternal and fetal mortality in developed countries. In a previous prospective study we identified a fall in the VEGF-A isoform VEGF-A165b in the plasma of patients in the first trimester to be a predictor of later pre-eclampsia. VEGF-A165b has been shown to have potent cytoprotective properties in many cell types.

Routine administration of Anti-D: the ethical case for offering pregnant women fetal RHD genotyping and a review of policy and practice.

Background: Since its introduction in the 1960s Anti-D immunoglobulin (Anti-D Ig) has been highly successful in reducing the incidence of haemolytic disease of the fetus and newborn (HDFN) and achieving improvements to maternal and fetal health. It has protected women from other invasive interventions during pregnancy and prevented deaths and damage amongst newborns and is a technology which has been adopted worldwide. Currently about one third of pregnant women with the blood group Rhesus D (RhD) negative in the UK (approximately 40,000 women per year in England and Wales), receive antenatal Anti-D Ig in pregnancy when they do not require it because they are carrying a RhD negative fetus.

Neonatal outcomes of pregnancies affected by haemolytic disease of the foetus and newborn and managed with intrauterine transfusion: a service evaluation.

Background: This study, conducted in the tertiary Foetal Medicine Unit at St Michael's Hospital, Bristol, was designed to obtain information regarding neonatal outcomes of pregnancies affected by haemolytic disease of the foetus and newborn and managed by intrauterine transfusion, and to determine whether a change in intrauterine transfusion protocol in 2004 had improved safety. The new protocol included attendance of two Foetal Medicine Unit consultants, foetal sedation and use of the intrahepatic vein as an alternative route to placental cord insertion if deemed safer.

Materials And Methods: Data for pregnancies affected by haemolytic disease of the foetus and newborn as a result of haemolytic red cell alloimmunisation and managed with intrauterine transfusion at St Michael's Hospital between 1999 and 2009 were retrospectively collected using local databases, and medical note review.

First trimester prediction of early onset preeclampsia using demographic, clinical, and sonographic data: a cohort study.

Objective: The aim of this research was to evaluate the performance of a predictive model for early onset preeclampsia (PE) during early gestation.

Method: Prospective multicenter cohort study was performed in women attending 11-14 weeks ultrasound. Medical history and biometrical variables were recorded and uterine artery Doppler was performed.

Quantification of free fetal DNA in multiple pregnancies and relationship with chorionicity.

Objective: Free fetal DNA (ffDNA) in the maternal plasma appears to originate mainly from the trophoblast. We tested the hypothesis that ffDNA concentration is increased in multiple pregnancies where trophoblastic mass has been shown to be increased.

Methods: Quantitative real-time PCR was used to measure the plasma concentration of DYS14 in singleton and twin pregnancies with one or two male fetuses.

Antenatal interventions for fetomaternal alloimmune thrombocytopenia.

Background: Fetomaternal alloimmune thrombocytopenia results from the formation of antibodies by the mother which are directed against a fetal platelet alloantigen inherited from the father. The resulting fetal thrombocytopenia (reduced platelet numbers) may cause bleeding, particularly into the brain, before or shortly after birth. Antenatal treatment of fetomaternal alloimmune thrombocytopenia includes the administration of intravenous immunoglobulin (IVIG) and/or corticosteroids to the mother to prevent severe fetal thrombocytopenia.

Noninvasive approach for the management of hemolytic disease of the fetus.

Hemolytic disease of the fetus and newborn (HDFN) is due to maternal alloantibodies directed against paternally inherited antigens on fetal red cells, and it is still a problem in affected pregnancies despite the routine use of anti-D immunoglobulin during pregnancy and shortly after delivery. The current noninvasive management of HDFN starts with the determination of fetal RhD genotype by use of cell-free fetal DNA in maternal plasma. When the fetus is antigen positive, the follow-up is performed by Doppler ultrasonography for the detection of moderate or severe anemia on the basis of an increase peak velocity of systolic blood in the middle cerebral artery.

Management of red cell alloimmunisation in pregnancy: the non-invasive monitoring of the disease.

Haemolytic disease of the fetus and newborn (HDFN) due to red cell alloimmunization was a significant cause of fetal and neonatal morbidity and mortality until the introduction of anti-D immunoglobulin, which has dramatically changed the incidence of the disease. However, it is still a major problem in affected pregnancies. The emphasis of current clinical management has shifted from an invasive approach to non-invasive monitoring of the disease.

Prognosis of spina bifida in the era of prenatal diagnosis and termination of pregnancy.

Objective: To evaluate the current outcome of a selected prenatally diagnosed spina bifida group.

Materials And Methods: We analyzed and followed up 74 cases of prenatally diagnosed spina bifida.

Results: Termination of pregnancy was chosen in 72% of the cases and 28% were live-born.

The SAFE project: towards non-invasive prenatal diagnosis.

After the revolutionary detection of ffDNA (free fetal DNA) in maternal circulation by real-time PCR in 1997 and advances in molecular techniques, NIPD (non-invasive prenatal diagnosis) is now a clinical reality. Non-invasive diagnosis using ffDNA has been implemented, allowing the detection of paternally inherited alleles, sex-linked conditions and some single-gene disorders and is a viable indicator of predisposition to certain obstetric complications [e.g.

Cell-free fetal DNA in the maternal serum and plasma: current and evolving applications.

Purpose Of Review: Free fetal nucleic acids, found in the plasma of every pregnant woman, have made a substantial impact on prenatal diagnosis. The past decade has seen the introduction of routine noninvasive prenatal diagnosis (NIPD) using DNA extracted from maternal plasma for a number of clinical complications of pregnancy, notably feto-maternal blood group incompatibility, fetal sexing and exclusion/detection of single-gene disorders. It appears that mass-scale analysis of all RhD-negative pregnant women will be adopted to conserve stocks of prophylactic anti-D and avoid the administration of a blood product unnecessarily.

Quantification of cell free fetal DNA in maternal plasma in normal pregnancies and in pregnancies with placental dysfunction.

Objective: To assess the normal levels of free fetal DNA in maternal plasma through pregnancy compared with those in pregnancies complicated with placental dysfunction manifested by preeclampsia and/or fetal growth restriction.

Study Design: Maternal blood samples from 138 singleton male pregnancies were divided into 3 groups; normal pregnancies (77), preeclampsia (49), and fetal growth restriction (12). Royston and Wright's methods were used to calculate gestational age-related reference limits of free fetal DNA in the 3 groups.

Failure to up-regulate VEGF165b in maternal plasma is a first trimester predictive marker for pre-eclampsia.

Pre-eclampsia is a pregnancy-related condition characterized by hypertension, proteinuria and endothelial dysfunction. VEGF(165)b, formed by alternative splicing of VEGF (vascular endothelial growth factor) pre-mRNA, inhibits VEGF(165)-mediated vasodilation and angiogenesis, but has not been quantified in pregnancy. ELISAs were used to measure means+/-S.

Ultrastructural localization of glycoprotein IIIa (GPIIIa, beta 3 integrin) on placental syncytiotrophoblast microvilli: implications for platelet alloimmunization during pregnancy.

Background: Fetal and neonatal alloimmune thrombocytopenia due to anti-human platelet antigen (HPA)-1a more commonly occurs in first pregnancies, unlike hemolytic disease of the newborn. Anti-D is produced after D+ fetomaternal hemorrhage; this usually occurs at parturition. Anti-HPA-1a could develop during pregnancy if maternal immunization is stimulated by HPA-1a expressed not only on platelets but also on other fetal cells.

Post-genomics studies and their application to non-invasive prenatal diagnosis.

Non-invasive prenatal diagnosis (NIPD) offers the opportunity to eliminate completely the risky procedures of amniocentesis and chorionic villus sampling. The development of NIPD tests has largely centred around the isolation and analysis of fetal cells in the maternal circulation and the analysis of free fetal DNA in maternal plasma. Both of these techniques offer difficult technical challenges, and at the current moment in time the use of free fetal DNA is the simplest and most effective method of defining paternally inherited fetal genes for diagnosis.

PLUTO trial protocol: percutaneous shunting for lower urinary tract obstruction randomised controlled trial.

Objectives: The primary objective is to determine whether intrauterine vesicoamniotic shunting for fetal bladder outflow obstruction, compared with conservative, noninterventional care, improves prenatal and perinatal mortality and renal function. The secondary objectives are to determine if shunting for fetal bladder outflow obstruction improves perinatal morbidity, to determine if improvement in outcomes is related to prognostic assessment at diagnosis and, if possible, derive a prognostic risk index and to determine the safety and long-term efficacy of shunting.

Design: A multicentre randomised controlled trial (RCT).

Allometric growth ratios are independent of Igf2 gene dosage during development.

In the mouse, allelic dosage of the paternally expressed gene coding for insulin-like growth factor II (Igf2), from null to bi-allelic, results in dose-dependent growth, an effect which appears to be fully established during a discrete period of embryogenesis that then persists throughout life. Here, we specifically quantify the influence of Igf2 allelic dosage on the proportionality of regional embryonic growth rather than overall growth. Remarkably, preservation of allometric growth ratios between head and body regions were observed throughout development, irrespective of the range of overall growth phenotype (60-130% of wild type).

Maternal serum transformed alpha-fetoprotein levels in women with intrauterine growth retardation.

Objective: To evaluate maternal serum transformed alpha-fetoprotein (t-AFP) levels in women with intrauterine growth retardation (IUGR).

Methods: 60 pregnant women in two groups were studied: 30 with IUGR and 30 healthy pregnant women as a control group. t-AFP concentrations were determined by ELISA assay.

The obstetrician's view: ethical and societal implications of non-invasive prenatal diagnosis.

We believe non-invasive prenatal diagnosis is about to have a massive impact on the way fetal medicine is practised. There will be many great advantages and improvements, but the technology also has the potential to be used for non-medical reasons such as sex selection and paternity testing. We discuss some of the issues that may face obstetricians in the future as a result of this emerging technology.

Maternal serum alpha-fetoprotein, fetal middle cerebral artery blood flow velocity and fetal haemoglobin in pregnancies at risk of fetal anaemia.

Objectives: To evaluate the relationships between maternal serum alpha-fetoprotein (MSAFP) levels and both middle cerebral artery (MCA) peak systolic velocity and fetal haemoglobin in women at risk of fetal anaemia.

Methods: Forty-one measurements of MSAFP were carried out in 22 women at risk of fetal anaemia (16 alloimmunised patients and 6 cases of parvovirus infection) who were monitored by using MCA Doppler measurements. The relationships between MSAFP (MoM) and both MCA peak systolic velocity (z-scores) and fetal haemoglobin (MoM) were studied.

The endogenous anti-angiogenic family of splice variants of VEGF, VEGFxxxb, are down-regulated in pre-eclamptic placentae at term.

PET (pre-eclamptic toxaemia) has recently been linked with alterations in production of a VEGFR1 [VEGF (vascular endothelial growth factor) receptor 1] splice variant that acts as a circulating inhibitor. We have recently described a family of naturally occurring splice variants of VEGF, termed VEGFxxxb, that also appear to act as inhibitors of conventional VEGFxxx-mediated angiogenesis. To determine whether alteration in splicing of VEGF-VEGFR family members extended beyond VEGFR1, we investigated the effect of pre-eclampsia on placental VEGFxxxb mRNA and protein expression.

Optimal interval between middle cerebral artery velocity measurements when monitoring pregnancies complicated by red cell alloimmunization.

Objective: To evaluate the optimal interval between middle cerebral artery (MCA) Doppler measurements when monitoring pregnancies complicated by red cell alloimmunization.

Methods: Thirty-nine fetal blood samplings (FBS) performed on 24 pregnant women with red blood cell alloimmunization followed up using both MCA peak systolic velocity and time-averaged mean velocity measurements on weekly basis.

Results: In total, 65.

Is zygosity or chorionicity the main determinant of fetal outcome in twin pregnancies?

Objective: The purpose of this study was to examine whether fetal outcome in twin pregnancies is dependent on zygosity or chorionicity.

Study Design: This was a prospective observational study comprised of women with twin pregnancies who attended the fetal medicine unit at St Michael's Hospital, Bristol, Ireland, during the years 1998 to 2000 and who were delivered in hospitals in south west England. After delivery, zygosity was determined with umbilical cord blood with the use of microsatellite markers that were amplified by polymerase chain reaction.