10
Newborns, Infants, and Children
Ann H. Maradiegue
Genomic risk assessment of the pediatric population includes the recognition of genetic disorders including physical and dysmorphology features that may be present in some disorders that are indicative of disease. Equally important is the monitoring of growth, development, and milestones of infants and children in order to identify disease. This requires not only a basic knowledge and understanding of genetics/genomics and patterns of inheritance, but also recognition of the normal physical and psychosocial patterns of growth and behavior that occur in the developing child. Additionally, ethical issues related to genetic testing can provide unique challenges in this age group.
Objectives
1. Discuss the skills required to conduct a genetic/genomic risk assessment for the pediatrics patient
2. Explain newborn screening (NBS)
3. Outline the genomic RISK assessment process for the pediatric patient
4. Discuss ethical, legal, and social issues related to genomic testing in the pediatric population
124
Newborn Screening
Preconception counseling is important in preparing individuals and couples for pregnancy and provides a means to begin assessment for potential maternal–fetal risk that may occur during pregnancy. Preconception counseling enables interventions to be employed to reduce risk (e.g., folic acid; smoking cessation) and carrier genetic testing to be offered based upon personal and family history to identify potential risk for genetic disease to the infant. During pregnancy, early and continuous prenatal care enables health care providers, including advanced practice registered nurses (APRNs), to continue the maternal/fetal risk assessment process through obtainment of a comprehensive personal and family history, physical examination, and implementation of ancillary tests (e.g., ultrasound; prenatal blood tests—maternal serum alpha-fetoprotein [MSAFP]). Chapter 9 provides information on the genetic/genomic risk assessment process during the preconception and prenatal period.
After delivery, assessment for genetic/genomic disorders continues through NBS. NBS “identifies conditions that can affect a child’s long-term health or survival through early detection and diagnosis for the purpose 125of implementing interventions to prevent death or disability enabling children to reach their full potential” (Centers for Disease Control and Prevention [CDC], 2016b, para. 1). NBS was introduced to the United States in 1963 with the phenylalanine hydroxylase deficiency test, traditionally knows as phenylketonuria or PKU. Today, all 50 states screen newborns for PKU, galactosemia, and congenital hypothyroidism with additional routine newborn assessment for developmental, genetic, and metabolic disorders performed, with the type and number of tests varying by state. NBS also includes optoacoustic emissions (OAE) testing for hearing loss, allowing early identification and intervention for deafness and hearing impairment (National Human Genome Research Institute [NHGRI], 2016). Like other screening programs, NBS may generate false positive results. Babies who screen positive are referred to specialists for diagnostic testing and intervention if needed. More information about screening in different states is provided in Table 10.1.
Although the NBS tests provide a means to identify and diagnose a wide range of conditions in the newborn, it is not all inclusive and many other genetic or chromosomal disorders may exist warranting the need for risk assessment. The acronym RISK can be used in the risk assessment process regarding newborn assessment for genetic/genomic conditions.
Review of History
The maternal, paternal, and family history play a major role in assessment of genetic/genomic risk for numerous issues including single-gene disorders; chromosomal or polygenetic disorders; microdeletion syndromes; environmental issues (e.g., radiation exposures, teratogens); infectious diseases (e.g., Zika, toxoplasmosis, other agents, rubella, cytomegalovirus, herpes simplex [TORCH]); or occupational exposures (e.g., organic solvents). Of importance is the maternal history during the prenatal period: What was the age of the mother at the time of delivery? Did the patient receive prenatal care? When was prenatal care initiated during the pregnancy? Was any prenatal screening or testing conducted? If prenatal tests were conducted, when were they conducted, what was performed, and what were the findings? Were there any abnormal prenatal tests? In addition, a review of the mother’s medical history (e.g., diabetes; hypertension), obstetric (OB) history (e.g., multiple miscarriages), and behavioral history to include smoking, prescription medication, over-the-counter (OTC) medications, and drug and alcohol use should be assessed as these factors can have an impact on the infant at the time of delivery and later in life. Specific information regarding the pregnancy (e.g., intrauterine growth retardation, placental morphology) and delivery history (e.g., bleeding, fetal distress), birth weight, and Apgar scores, as well as other pertinent data, should also be evaluated. Scores using the new Ballard system can provide an assessment of a newborn’s gestational age (Phillips et al., 2013). Additional screening for hypoglycemia should be performed on newborns who are large or small for gestational age, or whose mothers were treated for gestational diabetes. Another important area that should always be explored with the family includes psychosocial situation (e.g., teenage or single mother, financial distress), as this has the potential to have long-term impacts on the newborn well into childhood.
126TABLE 10.1 Selected Online Resources for Newborn Screening
Online Resource | Description | Weblink |
Centers for Disease Control and Prevention | Public health initiative to provide information and resources on newborn screening, resources, and tools | |
Baby’s First Test | Offers a series of guidelines, testing information by state, and resources for health professionals | www.babysfirsttest.org/newborn-screening/health-professionals |
March of Dimes | Information for parents about newborn screening and health tips | www.marchofdimes.org/baby/newborn-screening-tests-for-your-baby.aspx |
National Newborn Screening and Global Resource Center | Newborn screening information with additional facts about genetic disorders, testing, and fact sheets | |
American College of Medical Genetics (ACMG) | Mission of ACMG is to develop and sustain genetic and genomic initiatives in clinical and laboratory practice, education, and advocacy | |
U.S. Department of Health and Human Services | Advisory Committee on Heritable Disorders in Newborns and Children recommended uniform screening panel | www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/recommendedpanel |
American Academy of Pediatrics | Newborn screening website | 127 |
Save Babies Through Screening Foundation | State-by-state view of newborn screening |
The family history is also an important part of the genetic/genomic risk assessment. Any significant history on both the maternal and paternal lineages should be assessed regarding its significance to the health of the newborn. Ancestry of origin history may play an important role in identifying potential genetic disorders that are found at higher rates among certain racial/ethnic populations (e.g., Eastern Europeans, Ashkenazi Jews) and a history of consanguinity may increase the risk for autosomal recessive (AR) disorders. A review of the family history, including evaluation of the children’s medical history (e.g., family history of birth defects, 128learning/mental disabilities, or genetic conditions), may also reveal conditions that may have a familial or inherited predisposition.
The physical examination of the newborn is central to the risk assessment process during the newborn period and continues to be an essential component of the assessment throughout pediatric development. The history data described previously in conjunction with the physical examination may reveal red flags that suggest a genetic or chromosomal disorder. Assessment of the newborn for features or characteristics that denote dysmorphology, “defined as the study of abnormal physical development” (Jorde, Carey, & Bamshad, 2016, p. 301), is an essential component of the physical exam. The newborn should have a thorough, systematic physical examination that includes weight, length, head circumference, and assessment of the skin, head and neck, heart and lungs, abdomen, genitalia, and nervous system, as well as reflexes to evaluate for abnormal development that may denote a genetic or medical condition. Similar examinations should occur throughout infancy and childhood. Of significance is the appearance of any abnormal characteristics or features that may be suggestive of a genetic/genomic condition warranting further evaluation or genetic testing. Infants who are born prematurely, with medical conditions, or have other problems may warrant additional assessment or tests. See Table 10.2 for components of a physical examination of the newborn, including examples of abnormalities that may be found based on the system.
Identification of Risk
Identification of risk is based on information obtained from the risk assessment process or screening tests. NBS tests are done within the first week of life to identify disorders before symptoms appear so that lifesaving interventions can be initiated. These screening tests help to identify potentially treatable or manageable congenital disorders within days of birth. Life-threatening health problems, mental disabilities, and serious lifelong disabilities can be avoided or minimized if a condition is quickly identified and treated. The tests are organized into broad categories: metabolic disorders (e.g., PKU, galactosemia); endocrine disorders (e.g., congenital hypothyroidism; congenital adrenal hyperplasia); hemoglobin disorders (e.g., sickle cell anemia); and other disorders (e.g., cystic fibrosis; American Association for Clinical Chemistry, n.d.; March of Dimes, 2016).
129TABLE 10.2 Selected Components of a Newborn Physical Examination With Examples of Abnormalities
System | Examination | Examples of Abnormalities |
Is there observable malformation/anomaly (e.g., cleft lip/palate; meningocele; absence of digits)? Is the malformation or anomaly associated with a genetic/chromosomal syndrome? | ||
Vital signs (normal levels) | • Heart rate 120–160 beats/min • Respiratory rate 40–60 breaths/min • Systolic blood pressure 60–90 mmHg • Temperature 97.7°F–99.5°F • Weight approximately 6–9 lb • Length 19–21 in. • Pulse oximetry ≥ 95% | Anything outside of the normal range (e.g., birth weight above the 90th percentile or greater than 9 lb) |
Head | • Head circumference (normal range 13–15 in.) • Head shape • Fontanelles (anterior 3–6 cm, posterior 1–1.5 cm) | • Microcephaly (indicates central nervous system malformation; Zika virus) |
Eyes | • Eye color • Palpebral fissures (slanting) • Inner canthal distance • Pupil size • Appearance (of conjunctiva, sclera, and eyelid) • Red reflex • Assess corneal opacities | Genetic syndromes often cause unusual eye shapes, hyper/hypotelorism (Down syndrome, fetal alcohol syndrome, and colobomas) |
Ears | • Size, shape, and position of ears • Hearing evaluation (otoacoustic emissions test) to take place before 1 month of age • There is a known association between ear and renal abnormalities | 130 Low set ears are often a sign of a genetic condition (e.g., Down, Turner, or trisomy 18) Isolated ear anomalies: Preauricular pits or cup ears associated with dysmorphic features, teratogenic exposures, family history of deafness, or maternal history of gestational diabetes. (Any newborn with isolated auricular anomaly should have ultrasonography of kidneys.) |
Nose | • Assess patency of both nostrils, asymmetry of nasal septum | Choanal atresia; encephalocele |
Mouth | • Assess mouth, maxilla, mandible for fit and opening at equal angles, frenulum, and natal teeth | Cleft lip/palate most common anomalies of the head/ neck; short, long, or flat philtrum |
Neck | • Inspect range of motion, webbing, clefts, pits, or fractures | Webbing can occur with Turner syndrome |
Heart | • Assess pulses, murmurs (benign murmurs common in the first hours of life), cyanosis | Tricuspid atresia, transposition of the great arteries |
Lungs | • Assess for respiratory distress (e.g., tachypnea, nasal flaring, grunting, retractions, cyanosis) | 131 Cystic fibrosis, primary ciliary dyskinesia |
Skin | • Color and integrity of skin and hair; birthmarks, erythema, milia, or pustules | Little or no pigmentation of skin and hair albinism |
Chest | • Observe for symmetric movement, nipple placement, and any deformities (e.g., pectus carniatum and excavatum generally inconsequential) | Asymmetry suggests pneumothorax, wide nipple placement seen in Turner syndrome, prominent precordium may be seen in heart defect |
Abdomen | • Observation for hernias or distension, omphalocele, bowel sounds, and organomegaly • Umbilical cord for signs of infection, number of arteries (two) and veins (one) | About one-half of the masses are renal in origin (e.g., Wilms tumor) |
Genitourinary | • Inspect for any abnormalities, and problems with urination | Ambiguous genitalia warrants evaluation by geneticist before gender assignment; hypospadias |
Anus/rectum | • Examine for normal placement and patency, problems with defecation, dimples, hairy patches | Imperforate anus |
Extremities | • Inspect for abnormalities of hands, finger, feet, and toes • Evaluate for brachial plexus injury, hip dysplasia, talipes equinovarus, and pedal edema | 132 Syndactyly, polydactyly; single palmar crease may be seen in trisomy 21 (Figure 10.1); pedal edema in the newborn may indicate Turner syndrome |
Neuromuscular | Examination to elicit primitive instincts and muscle tone | Congenital myopathies |
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