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Chromosomal Microarray Analysis

Introduction For more than half a century, classical cytogenetics was the standard of care in the diagnosis of developmental disabilities and congenital anomalies. More recently, the introduction of microarray technology into clinical medicine has allowed the identification of subchromosomal abnormalities leading to the diagnosis of an increasing number of genetic conditions in both the fetus and the child. A chromosomal microarray analysis (CMA) is a high-resolution…

Genetic Evaluation of Fetal Sonographic Abnormalities

Introduction Structural malformations, many of which can be diagnosed antenatally, are present in approximately 2%–3% of live births. Fetuses with structural malformations are at increased risk for an underlying genetic disorder, even in the setting of a normal karyotype. The clinical prognosis is highly variable depending on the presence of a genetic syndrome, the specific type of anomaly that is present, as well as whether the…

Ultrasound Markers for Aneuploidy in the Second Trimester

Introduction Soft ultrasound markers were initially described as a screening method for trisomy 21 to improve the detection rate over that based on age-related risk alone. Soft markers are not structural abnormalities; rather, they are minor ultrasound findings identified in the midtrimester that may be a variant of normal but are noteworthy because they have been associated with an increased risk of fetal aneuploidy. Commonly identified…

Cell-Free DNA Screening

Overview Cell-free DNA (cfDNA) screening has been rapidly introduced into prenatal care since it became clinically available in 2011. cfDNA screening can detect more than 99% of cases of trisomy 21 and also has high sensitivity and specificity for the detection of trisomy 13 and 18 and the common sex chromosome aneuploidies. cfDNA screens for aneuploidy by sequencing cfDNA from the maternal serum, which includes fetal…

Serum and Ultrasound Based Screening Tests for Aneuploidy

What Is the History of Serum Screening? Prenatal screening for aneuploidy has evolved dramatically over a short period of time. The purpose of prenatal screening for aneuploidy is to identify women who are at an increased risk for the most common aneuploidies. Down syndrome is the most common aneuploidy seen in live births. Chromosomal abnormalities occur in approximately 1 in 150 live births with Down syndrome…

Carrier Screening for Genetic Conditions

Introduction Prenatal genetic carrier screening has evolved over a period of about 25 years. Advances in technology and health policy have ushered this evolution. With these changes, new terminology has appeared, whereas old terms and their definitions have evolved. It is helpful for the reader to understand the current core terminology around the topic of carrier screening. Definitions Condition : There has been a general trend…

Molecular Genetics

Introduction In 2003, the sequencing of the human genome propelled the field of genetics in two important directions. Firstly, the concept of “genomics” emerged, which includes both the DNA sequence itself (the blueprint letters that direct genetic contributions to health, variation, and disease) and the response of the DNA to modifiers that alter gene expression (such as the environment or other genes). Additionally, genomics encompasses the…

Cytogenetics: Part 2, Structural Chromosome Rearrangements and Reproductive Impact

What Are Structural Chromosome Rearrangements and How Frequently Are They Seen in the General Population? As part of cytogenetic testing, the structure of each chromosome is assessed for (1) evidence of losses or gains of material; (2) internal rearrangements within the chromosomes; (3) exchange of material between members of the same chromosome pair; or (4) exchange of material between chromosomes of different pairs. Rearrangements are described…

Cytogenetics: Part 1, General Concepts and Aneuploid Conditions

What Is Cytogenetics? Cytogenetics is the study of chromosomes and the clinical application of chromosome analysis for diagnostic purposes. This chapter will deal with traditional cytogenetics, which involves examination of metaphase chromosomes. The normal euploid or diploid chromosome constitution in human cells is 46. These are present in the nucleus of the cell as 23 pairs. Germ cells in the gonads with the normal diploid chromosome…

Principles of Genetic Counseling

Overview Genetic counseling is a process of evaluating family history and medical information to advise patients of the risk of a genetic condition. This can have both a diagnostic and supportive element. The National Society of Genetic Counselors officially defines genetic counseling as, “the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease. This process integrates…

Non-Mendelian Genetics

Introduction Mendel wrote in 1865 that when crossing plants, “numerous experiments have demonstrated that the common characters are transmitted unchanged to the hybrids and their progeny.” Mendel described that “common characters,” or genes, are passed unchanged from the parent to the offspring, and therefore Mendelian patterns of inheritance are very predictable. Classically, these include single-gene disorders that follow autosomal dominant, autosomal recessive, and X-linked inheritance patterns.…

Principles of Genetics and Genomics

Introduction Few areas in medicine have seen such rapid and dramatic advances in knowledge and technology as the field of genetics has over the past two decades. Breakthroughs such as the mapping of the human genome and technological advancements enabling rapid gene sequencing have not only greatly enhanced our understanding of common and uncommon disorders but also changed the way the medical profession approaches the diagnosis,…

Neurodevelopmental outcomes following very preterm birth: What clinicians need to know

Introduction The vast majority of children born very preterm (<32 weeks’ gestation) now survive, with survival rates increasing significantly over the past three decades due to advances in obstetric and neonatal care. While important, survival is only one outcome, and it is possible that reductions in mortality are associated with increases in short- and long-term morbidity. Long-term outcome studies of children born very preterm are essential…

Congenital heart disease: An important cause of brain injury and dysmaturation

Key points Although there have been significant improvements in the survival of infants with congenital heart disease (CHD), they remain at high risk for neurodevelopmental impairments. Brain dysmaturation and brain injury are key brain changes contributing to adverse neurodevelopmental outcomes in CHD. Fetal neuroimaging studies have found that brain dysmaturation begins in utero and may be linked to altered cerebral blood flow and oxygenation in fetuses…

Magnetic resonance imaging—newer techniques and overall value in diagnosis and predicting long-term outcome

Introduction Despite marked improvements in antenatal and perinatal care, perinatal brain injury remains one of the most important medical complications in the newborn resulting in significant handicap later in life. Experimental advances have helped to understand many of the cellular and vascular mechanisms of perinatal brain damage, showing a correlation between the nature of the injury and the maturation of the brain, but effects on long-term…

Amplitude-integrated EEG and its potential role in improving neonatal care within the NICU

Case description ( Fig. 14.1 ) The patient was born at 40 weeks’ gestation and weighed 3150 g at birth. An emergency cesarean section was performed for suspected fetal compromise with bradycardia on the cardiotocogram because of a nuchal cord. Apgar scores were 1, 0, 0 at 1, 5, and 10 minutes, respectively. The infant was resuscitated for 15 minutes with intravenous adrenalin given once. The…

Neonatal hypotonia and neuromuscular disorders

Gaps in knowledge 1. The severe hypotonia and hyporeflexia in Prader-Willi syndrome (PWS) may lead to unnecessary invasive tests such as electromyography, muscle biopsy, and/or genetic testing for spinal muscular atrophy (SMA). Genetic testing for PWS is not well understood by most clinicians and, if ordered incorrectly, may lead to false normal results. 2. It is important for clinicians to know that normal creatine phosphokinase (CPK)…

Neonatal herpes simplex virus, congenital cytomegalovirus, congenital Zika, and congenital and neonatal SARS-CoV-2 virus infections

Key points After reading this chapter, readers will be familiar with the epidemiology of congenital infections such as CMV, HSV, Zika, and SARS-CoV-2 virus. Risk factors for acquiring these infections are discussed. Clinical manifestations, diagnosis, treatment, and clinical outcomes are also discussed in detail. Among the numerous viral pathogens that cause central nervous system (CNS) infections in the neonatal period, herpes simplex virus (HSV) and cytomegalovirus…

Neonatal meningitis: Current treatment options—an update

Summary As many as 40% of infants with meningitis do not have a positive blood culture at the time of their diagnosis. Infants with uncomplicated meningitis due to group B streptococcus should receive a 14-day course of antimicrobial therapy. A minimum of a 4-week treatment course is recommended for infants with complicated courses (e.g., abscess). The treatment of gram-negative meningitis initially includes the addition of a…

Glucose and perinatal brain injury: Questions and controversies

Introduction Neonatal hypoglycemia is the most common biochemical abnormality of the newborn, affecting 5%–15% of all infants and 50% of those with risk factors. Although severe hypoglycemia has been incontrovertibly linked with brain injury and impairment, the glucose thresholds below which injury occurs have not been clearly established, and in fact, may differ based on various host factors. In the absence of clear evidence of a…