Evaluation of the Newborn with Single or Multiple Congenital Anomalies: Statement of Purpose

Major congenital malformations are common, are the leading cause of neonatal mortality, contribute substantially to chronic disease morbidity, have a high societal cost and profoundly affect families.

This Guideline describes critical components of the approach to the diagnosis and initial management of newborn infants with one or more congenital malformations for use by health care practitioners who care for neonates, irrespective of specialty orientation. It was developed in response to the perception that some newborns with malformations receive inadequate evaluation while others are inappropriately or excessively investigated. The orderly process described in the Guideline includes components which should be part of the evaluation of any newborn with one or more congenital anomalies, but does not specify an inflexible sequence, recognizing that evaluation involves repeated synthesis and modification of the process as information is gathered. Although many of the components of the Guideline reflect usual practice, some aspects require greater emphasis in this setting. For purposes of completeness, a comprehensive process is described. Adherence is intended to facilitate an accurate diagnosis and appropriate family counseling. Expected positive outcomes include a more consistent approach to assessment, improved determination of prognosis, better management of affected newborns, improved cost-benefit and provision of accurate information to families. If this cannot be accomplished by the primary care provider, referral should be made to a specialist in medical genetics. Even with the most comprehensive workup, 30-60% of infants with malformations will not be given a specific diagnosis.

These recommendations were developed by an interdisciplinary task force convened under the sponsorship of the New York State Department of Health and the American College of Medical Genetics Foundation. Participants included representatives from Family Medicine, Pediatrics, Obstetrics, Pediatric Surgery, Medical Genetics, Public Health and consumer groups (see Table 1 for participating organizations). The Guideline is based on a review of the available literature and a consensus of expert opinion, with recognition that evidence-based literature in this area is limited. Because of its length, the entire Guideline (see Table of Contents) has not been distributed to all providers. Only the Table of Contents, Purpose, Algorithm, and Executive Summary have been mailed to most. References and specific citations do not appear in this short version, but are provided in the expanded Guideline Justification segment. Those wishing a more detailed elaboration of the statements and recommendations in the Executive Summary - with supporting references - should request the complete document from the New York State Department of Health’s Genetic Services Program at (phone) 518-474-1222 or (fax) 518- 473-1733. The complete version of this document is also available from the New York State Department of Health site on the Internet: http://www.health.state.ny.us.

Components of Evaluation and Care

When a newborn with one or more malformations is identified, a detailed history and physical examination must be undertaken to ascertain whether additional malformations are present and to seek a specific etiologic diagnosis. Diagnostic studies should be selected based on the information elicited and a working diagnosis should be developed. The family should receive detailed counseling in a setting and with content that is appropriate to their needs. Medical records and reports should reflect available laboratory and clinical data, diagnostic considerations and a plan for ongoing care, evaluation and management.

Although reaching an etiologic diagnosis for the newborn with multiple malformations is a primary goal of the evaluation process, a specific diagnosis might not be apparent after detailed evaluation and diagnostic testing. For a variety of reasons, such as age-dependent phenotypic or behavioral manifestations or uniqueness of the pattern of malformations, diagnosis is not always apparent in the newborn period.

History

A comprehensive history is a critical component of the evaluation of a newborn with single or multiple malformations. The sequence described suggests an orderly passage from history to physical examination to diagnostic evaluation. However, in actual practice, the history and physical examination represent a dynamic and interactive process in which certain elements of history may be sought after the physical exam. Likewise, certain physical parameters may be assessed further and more carefully based on information derived from historical data. Additionally, results of initial diagnostic testing may suggest the need for further history or physical examination. The following elements should be included:

• Prenatal history
  • Maternal age, parity and health, including maternal illnesses and medications used
  • Onset and quality of fetal movements throughout pregnancy
  • Pregnancy complications
  • Viral and parasitic infections
  • Teratogenic exposures, such as alcohol, tobacco, drugs and medications
  • Periconceptional supplementation with folate
  • Prenatal testing (nature of testing and where performed)
• Perinatal history
  • Duration of pregnancy
  • Intrapartum course and duration
  • Intrapartum drug or medication exposure
  • Presentation and mode of delivery
  • Complications of delivery and infant’s condition at birth (Apgar score)
  • Description of placenta
  • Birth weight; appropriate for gestational age? (See Physical Examination section)
  • Neonatal course, including diet, medications and complications
• Family history
  • A three generation family history (see example pedigrees in sidebar - Available only as a PDF file) with health information about all relatives, including parents, siblings, grandparents, uncles, aunts and cousins and noting any instances of reproductive losses or infertility
  • Specific information should be elicited regarding:
    • any relative with mental retardation or known malformations
    • infants in immediate or extended family with malformations or birth defects
    • neonatal deaths, stillbirths or childhood deaths in immediate or extended family
    • familial disorders or physical features that “run in the family”
  • Consanguinity in parents
  • Ethnic background
  • Prior genetic testing or screening

Medical records and correspondence regarding parents, siblings or other relatives should be reviewed to corroborate any significant positive findings elicited through the history.

Physical Examination

A complete physical examination must be performed, with particular attention to major and minor malformations and to physical variations. The same areas should be examined in other family members, when appropriate. Medical photography is invaluable, particularly to enable documentation of changes over time and for the purpose of referral. Essential components of the newborn physical examination include:

• Growth parameters
  • Assessment of gestational age by physical parameters (see Appendix 2A - Available only as a PDF file.)
  • Length, weight and head circumference, with percentiles (see Appendix 2B - Available only as a PDF file.)
  • Assessment of proportionality and symmetry
  • Specific measurements where indicated by observation, such as inner-canthal distance or upper to lower segment ratio (see Appendices 2C-J - Available only as a PDF file)
• General appearance
  • Tone, posture, positioning, alertness, vigor, color, respiratory effort and other observations
• Detailed examination
  • Skin - pigmentation pattern (areas of increased or decreased pigmentation), dimples, vascular or other lesions, or excessive peeling
  • Head - shape, symmetry, fontanelles
  • Scalp - hair patterning and location of hair whorls
  • Facial features
    • Eyes - pupils, orbits (hyper or hypotelorism) including palpebral fissure inclination and length
    • Ears - location, rotation, configuration and size, patency
    • Nose - appearance and patency of nares
    • appearance of nasal bridge and columella
    • Mouth - appearance of upper lip, philtrum and vermilion border
    • intra-oral examination of palate, alveolar ridges and tongue
    • Mandible - shape and symmetry
  • Neck - posterior hairline, presence of sinus tracts, torticollis, redundant skin or webbing
  • Chest - shape, symmetry, circumference, location of nipples, accessory nipples
  • Cardiovascular - heart murmurs, pulses, blood pressure
  • Lungs - symmetry of breath sounds
  • Abdomen - appearance of umbilicus, muscle tone, integrity of wall, enlarged organs or masses
  • Genitalia - size, appearance, palpation of testes (in males), presence of ambiguity
  • Anus - location and patency
  • Back - symmetry, spine, presence of sinuses or hair tufts in inter-gluteal cleft
  • Extremities - proportions, appearance, range of motion (including hips), pulses, presence of reduction or duplication of segments
  • Hands and feet - nails; creases (palmar, phalangeal and flexion); joints
  • Neurological - tone, response, alertness, reflexes

Initial Impression and Differential Diagnosis

The history and physical findings should lead to an initial impression and differential diag-nosis. These will guide selection of preliminary tests, the content of initial counseling of the family and development of an immediate plan for management, which can be modified as new information is developed and synthesized. Initial impression should fit into one of three categories:

• Single (isolated) malformation
• Multiple malformations, recognizable pattern (syndrome identification)
• Multiple malformations, pattern not recognized

Diagnostic Evaluation

Diagnostic tests should be selected to clarify or establish a clinical diagnosis when possible. Such tests may be of particular value when a syndrome pattern is not recognized or to facili-tate risk assessment for genetic counseling. Single (isolated) malformations or syndromes which are recognized on a clinical basis may not require additional diagnostic tests. It is important to discuss with the family the possible ramifications of genetic testing, including the implications for relatives.

• Select tests in a prioritized order, rather than using a “shotgun” approach; initial results can guide selection of more specific subsequent tests
• Consultations with specialists in pertinent fields may clarify diagnostic possibilities
• Request medical genetics consultation when a clear working diagnosis is not evident, to confirm a questionable diagnosis, to seek further information about an established diagnosis, or to provide detailed genetic counseling, particularly in complex situations.
  (See Appendix 4 for Genetic Service Providers in New York State and Appendix 5 for State Genetics Coordinators. - Available only as a PDF files)

Diagnostic tests which should be considered include:

• Diagnostic Imaging
  • Radiographs, computed tomography (CT), magnetic resonance imaging (MRI) or ultrasonography (US) should not be considered routine, but should be employed as indicated by the differential diagnosis.
• Chromosomal analysis
  Banded chromosomal analysis should be obtained in the following situations:
  • Infants with two or more major malformations
  • Infants with a single major malformation or multiple minor malformations who are also small-for-dates
  • Infants with a single major malformation who also have multiple minor anomalies
  • In selected cases - usually in consultation with a medical geneticist - high resolution chromosome banding or fluorescence in situ hybridization (FISH) may be indicated to detect sub-microscopic structural chromosome changes or microdeletions (as in DiGeorge or Williams Syndrome).

  A list of cytogenetics laboratories approved by the New York State Department of Health is included in Appendix 6 (Available only as a PDF files). Updates are available on the web at www.wadsworth.org/labcert/clep/clep.html. Consideration should be given to compliance with federal and state regulatory requirements and professional accreditation, such as that provided by the American College of Medical Genetics or College of American Pathologists, when selecting a diagnostic cytogenet-ics laboratory.

  • Other genetic tests
    • Testing for the Fragile X syndrome is not generally useful in the evaluation of the newborn with single or multiple malformations, because congenital malformations are not a typical sign of the condition.
    • Biochemical, metabolic or molecular genetic tests may be indicated in specific circumstances (see Tables 2 and 3). A list of genetic testing laboratories approved by the New York State Department of Health is included in Appendix 7 (Available only as a PDF files). Updates are available on the web at www.wadsworth.org/labcert/clep/clep.html.

  Table 2. Situations Suggesting the Need for Metabolic Testing in the Newborn with Malformations:
  	Selected clinical findings	Selected laboratory findings	Selected radiologic findings
  	Ambiguous genitalia Enlarged fontanelle Seizures Severe hypotonia Cataracts Coarse facies Hepatosplenomegaly Lethargy or coma Persistent vomiting Unusual odor	Metabolic acidosis Abnormal liver function tests Persistent hyperbilirubinemia Hyperammonemia Hypocholesterolemia Hypoglycemia	Punctate calcifications Severe osteopenia

  Working Diagnosis

  The working diagnosis is established by data obtained from the history, physical examina-tion and preliminary diagnostic results and forms the basis for counseling and longitudinal care. Positive findings in the family history should be confirmed by a review of medical records and/or family photographs when possible. Corroboration by collection and review of records may be required and is often invaluable in clarifying an otherwise confusing history.

  Counseling the Family

  The approach taken in counseling the family of a newborn with congenital anomalies sets the stage for future interactions. Counseling is an ongoing process; its staging and depth should be matched to each family. The items below should eventually be covered, but the depth of coverage in the initial session may vary according to family circumstances.

   
  Table 3. A Sampling of Congenital Malformation Syndromes for which Specific Molecular Tests may be Available:

  SYNDROME	MOLECULAR TEST
  MICRODELETION SYNDROMES
  Williams	ELN (elastin)
  Velocardiofacial/DiGeorge	Microdeletion within 22q11
  Miller-Dieker	Microdeletion within 17p13.3
  CRANIOSYNOSTOSIS SYNDROMES
  Apert and Crouzon	FGFR2
  Pfeiffer	FGFR1
  Saethre-Chotzen*	Twist or FGFR3
  MALFORMATION SYNDROMES
  Treacher Collins	Treacle
  Waardenburg*	PAX3 or HOX10
  Alagille	Jagged
  BONE DYSPLASIAS
  Achondroplasia or thanatophoric dysplasia	FGFR3
  Osteogenesis imperfecta*	COL1A1 or COL1A2
  Spondyloepiphyseal dysplasia congenita	COL2A1
  * Linkage to two different genes has been found in different families

  • Counseling Principles

    • Supportive, family-centered, non-judgmental attitude

    • Respect for family privacy, confidentiality and autonomy

    • Sensitivity to ethno-cultural and language differences

    • Acknowledgment and facilitation of the grieving process

  • Supportive Setting

    • Quiet, private location

    • Inclusion of additional family members, clergy, etc, as desired by family

  • Content

    • Medical facts

    • Diagnostic considerations

    • Mechanisms and cause

    • Realistic prognosis and optimism when appropriate

    • Treatment plan and priorities

    • Acknowledgment of uncertainties

    • Early intervention and support resources

    • Recurrence risks and reproductive options

    • Assistance with family adjustment to information

    • Referral to psycho-social services as needed

  Patient Record

  In addition to information on the history and physical examination, the following should be included in the patient’s file:

  • Diagnostic considerations

  • Documentation of positive and negative findings

  • Management plan for further evaluation and treatment

  • Issues discussed in counseling, including recurrence risk and availability of prenatal diagnosis including serial ultrasound monitoring of subsequent pregnancies.

  Privacy and confidentiality of the medical record must be assured.