Peter Soothill

Prediction of fetal D status from maternal plasma: introduction of a new noninvasive fetal RHD genotyping service.

BACKGROUND : Invasive procedures to obtain fetal DNA for prenatal blood grouping present a risk to the fetus. During pregnancy, cell‐free fetal DNA is present in maternal blood. The detection of RHD sequences in maternal plasma has been used to predict fetal D status, based on the assumption that RHD is absent in D– genomes.

Management of fetal growth restriction.

Fetal growth restriction (FGR) is challenging because of the difficulties in reaching a definitive diagnosis of the cause and planning management. FGR is associated not only with a marked increased risk in perinatal mortality and morbidity but also with long-term outcome risks. Combinations of fetal biometry, amniotic fluid volume, heart rate patterns, arterial and venous Doppler, and biophysical variables allow a comprehensive fetal evaluation of FGR. However, no evidence supports that the use of cardiotocography or the biophysical profile improves perinatal outcome. Therefore, obstetricians aim to identify fetuses with early FGR so delivery can be planned according to gestational age and severity of the condition. The balance of risks and the need for the availability of services mean that the involvement of neonatologists in FGR management is vital. In this review, the focus is on the pathophysiology and management of FGR caused by placental diseases.

Prediction of chorionicity in twin pregnancies at 10–14 weeks of gestation

Objective To examine the accuracy of sonographic determination of chorionicity in twin pregnancies at 10–14 weeks of gestation.

Mucinases and sialidases: their role in the pathogenesis of sexually transmitted infections in the female genital tract

Background: Mucinases and sialidases contribute to the process of invasion and colonisation in many conditions and infections of the female reproductive tract by degrading the protective cervical mucus. The role of hydrolytic enzymes in the pathogenesis of sexually transmitted diseases and their effect on cervical mucus are discussed in this review. Methods: Articles were searched for using the keywords “sialidase,” “mucinase,” “protease,” and “sexually transmitted infections.” As well as review and other articles held by our group, searches were conducted using PubMed, Grateful Med, and the University of Bath search engine, BIDS. Results: Numerous publications were found describing the production of hydrolytic enzymes in sexually transmitted diseases. Because the number of publications exceeded the restrictions imposed on the size of the review, the authors selected and discussed those which they considered of the most relevance to sexually transmitted infections.

Fetal blood group genotyping from DNA from maternal plasma: an important advance in the management and prevention of haemolytic disease of the fetus and newborn

The cloning of blood group genes and subsequent identification of the molecular bases of blood group polymorphisms has made it possible to predict blood group phenotypes from DNA with a reasonable degree of accuracy. The major application of this technology, which has now become the standard of care, is the determination of a fetal RHD genotype in women with anti‐D, to assess whether the fetus is at risk of haemolytic disease of the fetus and newborn (HDFN). Initially, the procurement of fetal DNA required the invasive procedures of amniocentesis or chorionic villus sampling. Since the discovery of fetal DNA in maternal plasma in 1997, the technology of detecting an RHD gene in this very small quantity of fetal DNA has developed rapidly, so that non‐invasive fetal D typing can now be provided as a diagnostic service for D‐negative pregnant women with anti‐D. Within a few years, it is probable that fetuses of all D‐negative pregnant women will be tested for RHD, to establish whether the mother requires antenatal anti‐D immunoglobulin prophylaxis.

Increase in incidence of gastroschisis in the South West of England in 1995

Objective To describe the incidence of gastroschisis and to identify possible aetiological factors.

Fetal and maternal plasma insulin-like growth factors and binding proteins in pregnancies with appropriate or retarded fetal growth

A prospective observational study of 104 women was performed to study whether the insulin-like growth factor (IGF) system in pregnancy before labour is associated with reduced fetal growth. Fetal blood was obtained by cordocentesis for prenatal diagnosis or at elective caesarean delivery and a maternal sample was also obtained, IGF-1 and IGF-2 and their binding proteins -1 and -3 were measured by RIA. The 35 case were smaller than -2S.D.s by ultrasound abdominal circumference and birthweight and were subdivided into fetal growth retardation (FGR, n = 20) and small for gestational age (SGA, n = 15) by Doppler velocimetry and neonatal outcome. Controls (n = 69) were normally grown. Control maternal IGF-1 (r = 0.65, P < 0.0001) and IGFBP-3 (r = 0.46, P = 0.001) increased with advancing gestational age. In FGR cases, maternal IGF-1 was low (P = 0.0001) and IGFBP-1 was high (P = 0.03) and maternal IGF-2 was low in SGA (P = 0.005). In the SGA fetus, IGF-2 was low (P = 0.0009) and IGFBP-3 (P = 0.02) was high. In FGR, IGFBP-1 (P < 0.0001) and IGFBP-3 (P = 0.002) were both elevated. These data do not support the hypothesis that fetal IGF-1 deficiency is a common cause of FGR. Elevated binding proteins may lead to a relative deficiency of free IGF but changes in binding proteins may be secondary to metabolic changes. In FGR, maternal IGF-1 was low with high binding proteins, so this system may be important in controlling placental transfer.

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 Wrights methods were used to calculate gestational age-related reference limits of free fetal DNA in the 3 groups. The DYS14 gene of the Y chromosome was quantified and compared in maternal plasma by using real-time quantitative polymerase chain reaction. RESULTS Free fetal DNA in normal pregnancies increased with gestational age. Results were significantly higher in preeclampsia and fetal growth restriction groups than in normal pregnancy and were higher in severe preeclampsia than in milder disease. CONCLUSION Free fetal DNA is a potential marker for placental dysfunction in pregnancy. Large prospective studies are now needed to investigate its role in the prediction of pregnancy complications and severity and or timing of delivery.

Pregenesys pre-eclampsia markers consensus meeting: What do we require from markers, risk assessment and model systems to tailor preventive strategies?

The Pregenesys Consensus Meeting held in Cambridge on 13 July 2009 was organized by the Pregenesys Consortium to review and critically discuss current knowledge regarding early markers of preeclampsia, to identify priorities and opportunities for future research, to consider issues that may need to be addressed in future recommendations and to highlight key issues in cost effectiveness and national policies concerning prediction and early screening for the risk of developing preeclampsia. This report summarizes the outcome of the Consensus Meeting and draws attention to issues for further investigation with specific regard to single versus multiple markers, early versus late risk identification, and the long-term effects on both maternal and perinatal health and the need to include these in any future cost-benefit assessment.

Prenatal diagnosis of echogenic lung: evolution and outcome

Despite the feasibility of detecting lung lesions by antenatal ultrasound, there are problems in correlating the prenatal diagnosis with the final histology and in predicting the outcome. In order to better describe these factors, we reviewed the outcome of fetuses that had been diagnosed with echogenic lung in a referral fetal medicine unit.