The importance of the accurate recording and monitoring of the occurrence of disease is well recognized. There is a long history of the establishment of disease registers and this is also the case for congenital anomaly registers. This chapter provides an overview of 2 congenital anomaly register networks, focusing on factors that lead to the successful operating of a register and the main uses of their data.

Twin-twin transfusion syndrome (TTTS) complicates 10–15% of monochorionic twin pregnancies. In the majority of cases, and for still unexplained reasons, the condition usually presents between 16 and 26 weeks’ gestation. When left untreated, mid-trimester TTTS carries a very high mortality rate, either due to preterm birth as a result of the ever-present polyhydramnios [1], or due to fetal death as a result of cardiac failure [2,3].

In humans the immune system develops early during fetal life, most immune cells being detectable by mid-gestation. This early developmental process prepares the fetus for the challenge of controlling a large diversity of infectious pathogens at birth while establishing regulated interactions with non-pathogenic commensals. Following congenital infections with viruses, bacteria, or protozoa, the fetal immune system is challenged to generate antimicrobial effector functions. The immune system of the fetus has long been considered as non-reactive or prone to tolerance to foreign antigens. Recent clinical studies have demonstrated that immune effector functions can develop during fetal life. This chapter first provides an overview of the immune system and describes current knowledge of its development during fetal life. The capacity of the fetal immune system to respond to infectious pathogens is then summarized, focusing on the most studied congenital infections.

Unlike other fetal therapies, cardiac interventions have not been tested by randomized controlled trials (RCT), such as the one to determine the optimal management of twin-to-twin transfusion syndrome (TTTS) [1]. Most reports of fetal cardiac interventions have no appropriate control subjects and have resulted in level three evidence at best, so their clinical value and generalizability to the fetal population with obstructive cardiac lesions remain uncertain.

Stillbirth remains a global health challenge, with more than 2.6 million stillbirths per year [1]. Although only 2% of the global burden of stillbirths is in high-income countries (HICs), with virtually no improvement in rates for over two decades, action in HICs is urgently needed [2]. There is a six-fold difference between the highest and lowest rates (Ukraine 8.8 stillbirths per 1,000 births after 28 weeks vs. Iceland 1.3 stillbirths per 1,000 births). As well as variation between countries it is well established that there is variation within countries, with women from indigenous or minority ethnic groups, migrant populations or socioeconomically deprived groups as well as women at extremes of maternal age being at increased risk of stillbirth [2]. The disparity between and within countries suggests that more could be done in HICs to reduce stillbirth rates: this includes reducing the frequency of substandard care recurrently described in Confidential Enquiries into Stillbirth and implementing strategies to mitigate the increased risk of stillbirth in specific groups of women [3, 4].

Human pregnancies contain large amounts of water in several compartments, including the fetal body, the placenta and membranes, and the amniotic fluid (AF). This water circulates within the conceptus and also between fetus and mother. Normal acquisition and circulation of water is critical to fetal health and development, and abnormal amounts of water, evidenced as insufficient (oligohydramnios) or excessive (polyhydramnios) amounts of AF, are associated with impaired fetal outcome, even in the absence of structural fetal abnormalities. This chapter will review the current understanding of water flow to the fetus and into and out of the amniotic cavity, and the evidence suggesting that the fetus may regulate AF volume.

Fetal surgery has evolved over the last three decades from an innovative and ambitious concept into an accepted reality. The metamorphosis from curiosity to sought-after therapy has been driven by the refinement of techniques used in open hysterotomy surgeries, advances in the available technology and instrumentation, expansion of the repertoire of minimally invasive image-guided percutaneous interventions, and the development of safe and effective fetoscopic surgical procedures. Serious complications associated with the early era fetal surgery procedures such as intraoperative fetal death, abruptio placentae and pulmonary edema have been largely eliminated, and extreme preterm delivery (<28 weeks) has been significantly reduced. Specialized anesthesia protocols and intraoperative management algorithms have led to improved fetal tolerance of these procedures, and advancements in neonatal intensive care have dramatically improved neonatal outcomes.

Anomalies of the neural tube are a group of severe birth defects involving the central nervous system, with a global prevalence rate of approximately 1 in 1000 births [1]. The birth prevalence varies substantially between geographical locations, socioeconomic status and ethnic groups because of genetic and environmental differences, including maternal conditions, medication, toxins, nutrition, and lifestyle. Worldwide, each year approximately 130 000 newborns are born with a neural tube defect (NTD). The clinical spectrum of neural tube defects includes spina bifida, anencephaly, encephalocele, and although rare, craniorachischisis and iniencephaly. Spina bifida accounts for 57% of all NTDs, anencephaly 33%, and encephalocele 10%.

This chapter focuses upon pathogenic organisms that may be responsible for fetal infection during pregnancy and have significant effects on outcome. Many infections have associated serious consequences, including fetal/perinatal mortality and significant morbidity. Each of the pathogenic organisms will be discussed in turn and specific risks and morbidity outlined.

We first published on the subject of pregnancy management via fetal reduction (FR) 30 years ago [1]. Dramatic changes have occurred in medical technology, outcomes, and patient choices – large demographic and cultural shifts that have driven the pace and direction of progress and research [2, 3].

Monochorionic twin placentation occurs in 20% of spontaneous twin pregnancies and almost 5% of those are obtained by medically assisted reproduction [1]. Monochorionic twin fetuses have the unique characteristic of living upon one single placenta and therefore share some cotyledons through vascular anastomoses running on the chorionic plate. This situation can lead to specific complications, including twin-to-twin transfusion syndrome (TTTS) [2, 3], twin-anemia-polycythemia sequence (TAPS) [4, 5], and selective intrauterine growth restriction (sIUGR) [6]. These complications are likely to explain most of the 6- to 12-fold increase in perinatal mortality in monochorionic compared with dichorionic twins [7–10].

Advances in obstetrical ultrasound technology, combined with newer magnetic resonance imaging (MRI) methods, cell-free fetal DNA testing in maternal blood, and comprehensive molecular testing of the fetus, have greatly improved prenatal diagnostic capabilities in the context of fetal growth restriction (FGR) as shown in Chapter 24. Increased understanding and use of these resources means the likelihood of recognizing a fetal basis for FGR before birth, and managing it accordingly, will increase. The presumption of a placental basis for FGR dominates everyday clinical practice, yet paradoxically at present the application of current knowledge of what constitutes true ‘placental insufficiency’ has not translated into improved maternal care and perinatal outcomes. As an example, 33% of 650 women recruited to the landmark DIGITAT (Disproportionate Intrauterine Growth Intervention Trial at Term) trial had no postnatal evidence of FGR (defined as birth weight <10th percentile) [1]. Since obstetricians manage suspected FGR prior to delivery, they fear a risk of antepartum stillbirth and deploy frequent short-term tests of fetal well-being (biophysical profile, Doppler ultrasound, and non-stress tests), even via hospital admission, in the absence of any objective placental diagnosis. Fortunately, recent advances in the understanding of the placental basis of FGR have led to much-improved precision in both screening for the disease [2, 3] and in the prenatal diagnosis of the placental basis of FGR [4]. This chapter is designed to equip obstetricians, midwives and maternal–fetal medicine sub-specialists with key concepts in placental development and pathology that directly contribute to the care of women with suspected FGR pregnancies.

Selective fetal growth restriction (sFGR) affects about 10–15% of monochorionic (MC) twin pregnancies. When presenting during the second trimester, sFGR is a severe complication, with potentially significant risks of intrauterine demise or neurological adverse outcome for both the growth-restricted and the normally grown [1–9] fetuses. Unequal placental sharing (Figure 37.1), often associated with velamentous cord insertion, is the main cause of the development of sFGR in MC twins [10–14]. The natural history of sFGR in MC twins depends both on the discordance in placental territories and on the pattern of placental anastomoses. The blood flow interchange through vascular anastomoses interferes with the natural evolution of placental insufficiency, because the small fetus receives extra oxygen and nutrients from its normally grown co-twin. The pattern of vascular anastomoses, which may differ substantially among MC pregnancies, explains the remarkable differences in clinical course and outcomes that can be observed in pregnancies with similar degrees of fetal weight discordance [1, 12, 15, 16]. Consequently, a large interfetal blood flow interchange will result in a milder clinical course and better outcomes, while placentas with small/few anastomoses and little blood flow interchange will usually be associated with a more severe clinical course. Aside from these, large artery-to-artery (AA) anastomoses connecting the two cords may be present, and also have a strong influence on the clinical evolution.