Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Haemolytic Disease of the Fetus and Newborn

Key Points Fetal hydrops is defined as the accumulation of fluid in two fetal compartments (abdominal ascites, pleural effusion, pericardial effusion, skin or scalp oedema). It may also be associated with polyhydramnios and placental oedema. Immune hydrops is the result of alloimmunisation to red blood cell antigens. Rhesus (Rh) immunoglobulin has decreased the relative frequency of RhD disease. Kell alloimmunisation is associated with the least predictable…

Fetal Growth and Growth Restriction

Key Points Fetal growth restriction (FGR) is practically defined as a sonographic estimated fetal weight of less than the 10th percentile for gestational age. In actuality, a growth-restricted fetus is one that is unable to meet its inherent growth potential secondary to an underlying pathologic process. Distinguishing between a pathologically growth-restricted fetus and a constitutionally small one is imprecise, and using an estimated fetal weight cutoff…

Open Fetal Surgery

Key Points Most fetuses with a prenatal diagnosis of a congenital abnormality can be managed expectantly. For some conditions, in utero referral is mandatory for planned delivery and management after birth. Fetal surgery is only required for conditions that cannot await therapy after birth and when there is enough evidence that prenatal surgery partly reverses the natural course. Open fetal surgery (OFS) is one modality to…

Fetal Tumours

Key Points Fetal tumours are rare and should be managed by an experienced multidisciplinary team. Magnetic resonance imaging is an important imaging modality in the diagnosis and management of fetal tumours. Fetal neck masses may result in airway obstruction and the ex utero intrapartum treatment (EXIT) procedure may need to be planned for delivery. In utero treatment of sacrococcygeal teratomas can be performed in fetuses showing…

Fetal Hydrops

Key Points Hydrops fetalis is a pathological condition of excessive fluid accumulation in at least two extravascular compartments, including fetal soft tissues and body cavities. Hydrops fetalis is a clinical finding and not a final diagnosis. There are two main pathophysiologies for hydrops fetalis, immune and nonimmune. For nonimmune, the diagnostic categories are placental, cardiovascular, chromosomal, haematologic, lymphatic dysphasia, infection, thoracic malformations, genetic syndromes, inborn errors…

Diagnosis and Management of Abnormalities of the Face

Key Points The fetal face can be visualised by ultrasound from 9 weeks’ gestation onwards. After 9 weeks’ gestation, only proportional changes occur in the fetal face. Clefts and micrognathia are the most common facial anomalies. In many genetic disorders, the face has a deviant appearance. At the routine anomaly scan the profile, the lip and the eyes should be examined. A detailed ultrasound investigation in…

Diagnosis and Management of Fetal Skeletal Abnormalities

Key Points Diagnosis of skeletal anomalies is challenging and requires time and a team approach, including clinical geneticists, paediatricians and pathologists. This chapter deals with the prenatal diagnosis of skeletal anomalies. It gives aids to diagnosis and categorises conditions by sonographic findings to help sonographers narrow the differential diagnoses. Increasingly, with advances in genomic medicine, the definitive diagnosis can be achieved prenatally after targeted molecular genetic…

Kidney and Urinary Tract Disorders

Key Points When a fetal urinary tract anomaly is identified, careful ultrasound examination is required to exclude coexistent anomalies. In the presence of a coexistent anomaly, the risk for aneuploidy and single-gene disorders as an underlying aetiology should be considered and investigated. Sonographic features associated with long-term poor renal function include hyperechogenic kidneys, renal cyst formation, oligohydramnios and the inability of the bladder to refill after…

Abdomen

Key Points The embryologic processes involved in development of the abdominal wall and viscera are complex and most anomalies can be defined through their developmental origin. The abdominal viscera are our metabolic powerhouse but have little functional significance in a fetus. Some signs of abnormality develop late in pregnancy after the abdominal viscera become functional. Most major abdominal defects can be detected sonographically from early gestations…

Congenital Diaphragmatic Hernia

Key Points Congenital diaphragmatic hernia occurs in 1 to 4 in 10,000 births. The condition is isolated in more than 50% of the cases. The main causes of mortality and morbidity are respiratory insufficiency and persistent pulmonary hypertension of the newborn. Prenatal diagnosis should be made by screening ultrasound, after which patients are referred to specialised centres. In isolated cases, the size of the lungs and…

Fetal Lung Lesions

Key Points A limited number of congenital malformations of the respiratory tract can be identified directly by prenatal sonography. These malformations should be described systematically because definitive diagnosis requires histologic examination. The identification of subtle lesions that have no detrimental effect on a fetus or postnatal respiratory function is increasingly common. A lack of evidence surrounding the natural history of asymptomatic cystic lung lesions has resulted…

The Heart

Key Points Current evidence suggests that prenatal diagnosis of congenital heart disease (CHD) reduces morbidity and mortality, gives expectant parents time to prepare and allows planning for delivery in a tertiary care centre. About 85% of babies born with CHD are born to mothers that are ‘low risk’, suggesting that screening of the entire pregnant population is essential to optimise detection. A comprehensive fetal heart examination…

Sonography of the Fetal Central Nervous System

Key Points Prenatal ultrasound of the fetal brain in the second and third trimester is described, from basics to advanced neurosonography. Classification of central nervous system anomalies is discussed. The neurodevelopment stage determines some of the pathological conditions; others are related to external factors interfering with normal brain development. The diagnosis of neural tube defects deserves attention in the light of potential fetal surgery. Analysis of…

Prenatal Screening for Thalassemias

Key Points Homozygous α 0 -thalassemia and β-thalassemia major are global autosomal disorders. Different α- and β-thalassemia genotypes may be associated with variable phenotypes. Universal screening is preferred for high-prevalence areas and countries with migrants from high-prevalence areas. Screening by mean corpuscular volume or mean corpuscular haemoglobin with or without haemoglobin (Hb) pattern is feasible. Workup for screen-positive couples includes Hb and molecular studies. Molecular diagnosis…

Expanded Carrier Screening

Key Points This chapter describes the novel concept of expanded carrier screening (ECS), whereby individuals are simultaneously screened for up to 200 genetic conditions. Different laboratory techniques are used in ECS and include targeted genotyping and next-generation sequencing approaches. The choice of conditions to be included in ECS varies among laboratories, and no consensus presently exists. Various screening strategies exist, including premarital carrier screening, cascade screening,…

Advances in Molecular Genetics Including Fetal Sequencing

Key Points Fetal malformations can be caused by chromosomal defects detectable by fetal karyotype and chromosomal microarray analysis, by sequence variants (mutations) in single genes or can be multifactorial in origin. Single-gene disorders can be inherited from parents (autosomal recessive, autosomal dominant or X-linked) with substantial recurrence risk or can be caused by de novo mutations in the fetus with an extremely low recurrence risk. When…

Prenatal Diagnosis of Chromosome Abnormalities

Key Points Chorionic villi, amniotic fluid and fetal blood are the specimen types currently used for prenatal diagnostic testing for chromosome abnormalities. The spectrum of chromosomal alterations seen during prenatal testing include autosomal or sex chromosome aneuploidy, balanced or unbalanced structural rearrangements, triploidy, supernumerary marker chromosomes, submicroscopic deletions and duplications, mosaicism and uniparental disomy. Methods for detecting chromosomal abnormalities in prenatal specimens include karyotype of G-banded…

Invasive Diagnostic Procedures

Key Points Amniocentesis is used from 15 weeks of gestation onwards for prenatal diagnosis of chromosomal abnormalities, single-gene disorders, fetal lung maturity, fetal infections and inflammation. Chorionic villus sampling (CVS) is used from 10 weeks of gestation onwards for prenatal diagnosis of single-gene defects and chromosomal abnormalities. Early amniocentesis (<15 weeks) and early CVS (<10 weeks) have been proscribed because of increased risk for fetal loss…

Noninvasive Prenatal Diagnosis for Single-Gene Disorders

Key Points Noninvasive prenatal diagnosis (NIPD) based on analysis of cell-free DNA in maternal plasma for fetal sex determination is now an established clinical service in many countries. NIPD for a small number of single-gene disorders, including achondroplasia, thanatophoric dysplasia, Apert and Crouzon syndromes, congenital adrenal hyperplasia and cystic fibrosis, is now offered in accredited clinical practice in the United Kingdom. NIPD for monogenic disorders offers…

Noninvasive Screening for Cytogenetic Disorders (Fetal Aneuploidy Including Microdeletions)

Key Points The origins of intact fetal circulating trophoblast cells and nucleated red blood cells in maternal plasma are reviewed, and their pitfalls and promises for noninvasive prenatal testing are discussed. The discovery of cell-free fetal DNA (cffDNA) in maternal circulation and how it has allowed the development of an excellent noninvasive screening test for common aneuploidies and sex chromosomal abnormalities in both the high-risk and…