Fetal medicine: screening, diagnosis and therapy

Abstract

As a trainee, the fascination of being able to observe early human development played a big part in my decision to go into the field of Maternal–Fetal Medicine. My enthusiasm to enter the subspeciality was helped by clinicians and researchers with immense charisma and talent, who still lead the way in diagnosis and even treatment of babies before birth, in how to best prepare for postnatal management and in how to communicate difficult issues to parents. Fetal medicine has always been closely linked to technological advances, and in my experience most specialists in the field are early adopters of new technologies. Of course these include improvements in fetal imaging and ultrasound, but also rapid developments in genomics and in the kind of surgical equipment (and know-how) required for delicate intrauterine procedures. Some of the greatest advances, however, revolve around the ability to use these techniques to improve our understanding of pregnancy-related conditions: imaging and other biomarkers have proven powerful tools to understand the physiology, aetiopathogenesis and natural history not only of congenital fetal abnormalities, but also of conditions that may put a healthy pregnancy outcome at risk, such as pre-eclampsia, poor placental function, impaired glucose tolerance, preterm birth and stillbirth. Over 150 articles were submitted to this BJOG themed issue (and the acceptance rate was about 20%, a little higher than usual for BJOG). The wide variety of the articles demonstrate how the field has advanced in many areas, and is of relevance to the entire care pathway that a pregnant woman follows. Screening at 11–13 weeks In many settings, screening for chromosomal abnormalities using a combination of maternal age, fetal nuchal translucency, maternal serum human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPPA) remains the standard of care. It is known that screening using cell-free DNA in the maternal circulation allows very accurate prenatal screening for fetal trisomies, and Guy et al. show that secondary screening using this technology forms the basis of an effective strategy in a public health setting (pages 440–447). There is little doubt that we will move to primary screening for chromosomal abnormalities based on cell-free DNA in the not too distant future, once the rapidly declining price crosses a cost-effectiveness threshold, and the accompanying mini-commentary by Howard Cuckle explains these different screening models. In addition, there is the prospect of such technology also being used to screen for genetic disorders such as b-thalassaemia (pages 448–457) or even in the prediction of fetal growth restriction (pages 458– 466). ‘Genomics’ are of course also relevant after invasive prenatal diagnosis. The articles by Mardy et al., on variants of uncertain significance in prenatal microarrays, and the review by Prof. Kilby, on the role of next-generation sequencing, provide excellent insights into the advances made in this field. Predicting pre-eclampsia is another important aspect of early pregnancy screening. Randomised trial evidence shows that low-dose aspirin in women at high risk results in a lower incidence of preterm pre-eclampsia than placebo (Rolnik et al. N Engl J Med 2017;377:613–22); an important study of implementation has shown that this translates into clinically effective reductions of pre-eclampsia in a London hospital (pages 149–156). Nevertheless, despite early screening and treatment, pre-eclampsia will continue to occur, and the clinical value of angiogenic factors in established disease is assessed in the study by Peguero et al. The debate on pages 158–165 will give you a good overview of the current thinking on the relative contributions of the placenta versus the maternal cardiovascular response to pregnancy as a cause of pre-eclampsia.