BRS – Pediatrics: Neonatology
Source: BRS Pediatrics, 2018
I. Evaluation of the Newborn
Features of the newborn history and physical examination that differ from those of children and adolescents include the following:
A. Pregnancy and maternal history. Information from the maternal record informs the assessment and care for all newborn infants.
1. Maternal history: age, gravidity, parity, prenatal laboratory studies, maternal obstetric history, and maternal medical history, including medications taken during the pregnancy
2. Pregnancy history:
a. Estimation of gestational age and evaluation of fetal growth
b. Studies during pregnancy: genetic testing, fetal anomaly ultrasound or echocardiogram results
c. Complications of gestation: twin gestation, fetal growth restriction (FGR), preeclampsia or premature onset of labor
3. Labor history: spontaneous or induced labor, fetal monitoring during labor, need for and type of anesthesia, medications given during labor, risk of perinatally acquired infection, and need for instrumented or surgical delivery
B. General appearance and initial assessment
1. Careful observation is necessary to assess respiratory, cardiovascular, and neurologic status immediately after birth. Evaluation should include work of breathing, perfusion, color, passive muscle tone, spontaneous activity, and response to stimulation. Abnormal signs should be noted, including central cyanosis (i.e., trunk, lips, tongue), increased work of breathing, poor perfusion, meconium staining, and depressed level of activity.
2. The need for advanced resuscitation is indicated for the following:
a. Abnormal response to routine stabilization and resuscitation
b. Problems associated with preterm gestation
c. Issues that require additional intervention, including congenital malformations
3. When indicated, resuscitation should follow the Neonatal Resuscitation Program (NRP) guidelines.
4. Apgar scores (Table 4-1) are a simple, systematic means of assessing objective data that indicate intrapartum stress and neurologic depression in newborns.
a. Apgar scores are calculated at 1 and 5 minutes after birth, and additional scores are calculated every 5 minutes until a score ≥7 is obtained.
b. The 1-minute Apgar score correlates with the infant’s status at the beginning of the resuscitation, whereas the 5-minute Apgar score indicates the infant’s progress in response to the resuscitation.
c. The 1- and 5-minute Apgar scores do not predict long-term neurologic outcome.
C. Neurologic examination should include level of alertness, responsiveness to stimulation, spontaneous breathing, spontaneous movements, passive and active muscle tone, and primitive reflexes (see Chapter 2, Table 2-2).
D. Craniofacial examination should include head size, shape, and symmetry of facial features, while noting congenital malformations.
1. Head examination should note size, shape, fontanels, and evidence of trauma.
a. Head size
1. Microcephaly, defined as head circumference 2 standard deviations below the mean or below the third percentile for gestational age, may be familial or caused by structural brain malformations, genetic syndromes, congenital infections (e.g., cytomegalovirus, toxoplasmosis), or fetal exposure to illicit drugs, alcohol, or environmental toxins (see Chapter 1, section II.B.2.b).
2. Macrocephaly, defined as head circumference 2 standard deviations above the mean or above the 97th percentile for gestational age, may be caused by increases in any component of the cranium (brain, cerebrospinal fluid, or blood). Examples include increased intracranial pressure, increased brain tissue (megalencephaly, typically from metabolic or familiar causes), or an arteriovenous malformation.
b. Cranial trauma can occur during both spontaneous deliveries and instrumented deliveries.
1. Caput succedaneum (Figure 4-1) is a common finding and consists of a midline or diffuse soft tissue swelling of the scalp that “crosses the cranial sutures” (i.e., because the swelling is extrinsic to the bone, involvement can spread across a cranial suture line).
2. Cephalohematoma is a subperiosteal hemorrhage that is “limited by the cranial sutures” (i.e., because the hemorrhage is subperiosteal, and the periosteum is tacked down at the suture line, a cephalohematoma is well demarcated at the suture line and cannot spread beyond the cranial suture). Cephalohematomas usually involve the parietal or occipital bones (see Figure 4-1).
3. Subgaleal hemorrhage is rare, but can occur after vacuum delivery, and is caused by shearing of the emissary veins. Hemorrhage occurs into the space between the periosteum and scalp aponeuroses. It presents as a boggy swelling over the scalp with extension down the neck. Subgaleal hemorrhage may be life-threatening, as massive blood loss may occur.
c. Fontanels and sutures (see Chapter 1, section II.B.2, and Figure 1-3)
d. Craniosynostosis is premature fusion of the cranial sutures that may result in abnormal head shape and size, and can cause neurologic impairment if space for brain growth is inadequate (see Chapter 1, section II.B.2.d).
e. Craniotabes is thinning or softening of the skull with a “Ping-Pong ball” feel. It most commonly involves the parietal bone of premature infants, or term infants who have metabolic syndromes, although it can be observed in healthy term infants. Craniotabes typically self-resolves within weeks to months.
2. Ears should be examined for preauricular tags or sinuses, appropriate shape, rotation, and location, and to assess maturity. By term, the ears are firm and have assumed their characteristic shape.
3. Eyes should be examined for position, spacing, sloping, and evidence of trauma, with attention to the conjunctiva and sclera as well as the pupils, including response to light. An abnormal red reflex may be caused by cataracts, congenital glaucoma, retinoblastoma, or severe chorioretinitis.
4. Nose should be examined immediately for symmetry and evidence of patency, as infants are predominantly obligate nasal breathers. Evaluate for unilateral or bilateral choanal atresia by occluding the nares sequentially or by passing a nasogastric tube.
5. Mouth examination should include evaluation of symmetry, size, and shape.
a. Clefting of the lip and of the soft and hard palates is noted by inspection. A submucosal cleft, which is a cleft covered by a layer of mucous membrane, requires digital palpation to detect. Clefts may be isolated or associated with other dysmorphic features.
b. Micrognathia, a small jaw, may be isolated or associated with other findings. Consider Pierre Robin sequence when micrognathia is associated with cleft palate, glossoptosis (downward displacement or retraction of the tongue), and obstruction of the upper airway (see Chapter 5, section IV.I.7).
c. Macroglossia, enlargement of the tongue, may be caused by vascular abnormalities, Beckwith–Wiedemann syndrome (hemihypertrophy, visceromegaly, macroglossia), hypothyroidism, and mucopolysaccharidosis.
d. Neonatal teeth are rare and typically are lower incisors. Neonatal teeth may be removed, especially if hypermobile, due to risk of impairing oral feeding, trauma, and possible aspiration of the tooth (see Chapter 1, section VI.D.1).
e. Epstein pearls are small, white epidermoid–mucoid cysts found on the hard palate that usually disappear within a few weeks.
E. Neck and clavicle examination
1. Lateral neck cysts or sinuses include branchial cleft cysts and cystic hygromas.
2. Midline clefts or masses may be caused by cysts of the thyroglossal duct or by goiter secondary to maternal antithyroid medication or transplacental passage of long-acting thyroid-stimulating antibodies.
3. Neonatal torticollis, an asymmetric shortening of the sternocleidomastoid muscle (SCM), may result from malposition in utero or trauma to the SCM during delivery with subsequent intramuscular hematoma formation (see Chapter 17, section II.A.1.a).
4. Edema and webbing of the neck suggest Turner or Noonan syndrome.
5. Clavicles should be examined for fracture. Clavicle fractures typically occur during delivery, especially in large-for-gestational-age (LGA) infants.
F. Chest examination
1. Respiratory examination should include evaluating the pattern of breathing and listening to breath sounds, noting symmetry, adequacy of air movement, and additional sounds (e.g., crackles, wheezes, stridor, and coarse breath sounds).
a. Respiratory distress is diagnosed when tachypnea (respiratory
rate > 60 breaths/minute), increased work of breathing (deep respirations, expiratory grunting, suprasternal/intercostal/subcostal retractions, nasal flaring), or cyanosis is present.
b. Preterm infants breathe irregularly with short, apneic pauses lasting less than 5–
10 seconds (periodic breathing) owing to immature control of breathing.
2. Cardiac examination should include observation of perfusion, heart rate (normal heart rate is 95–180 beats/minute and varies during feeding, sleep, or crying), rhythm, evaluation of heart sounds, including murmurs, and peripheral pulses.
a. Diminished femoral pulses. Consider obstructive cardiac lesions, such as coarctation of the aorta, or depressed cardiac contractility.
b. Increased femoral pulses. Consider patent ductus arteriosus (PDA).
3. Accessory nipples, if present, they are along the anterior axillary or midclavicular lines, and may grow because of the presence of glandular tissue in these areas.
4. Congenital deformities, including pectus carinatum (prominent and bulging sternum) and pectus excavatum (depressed sternum), are generally benign. Chest asymmetry as a result of absent or abnormal rib formation, or agenesis of the pectoralis muscle, is more serious.
G. Abdominal examination. Focus on size, shape, and color of the abdomen, while noting presence and quality of bowel sounds, and response to palpation.
1. Umbilicus. The umbilical cord should be inspected to confirm the presence of two arteries and one vein and the absence of a urachus [see section I.G.5]. The presence of a single umbilical artery may suggest additional congenital malformations, including heart and renal anomalies.
2. Diastasis recti is the separation of the left and right rectus abdominis muscles at the abdominal midline and is common, especially in premature and African American infants. Treatment is not necessary because the condition resolves as the infant develops increased truncal tone and the rectus abdominis muscles grow.
3. An umbilical hernia occurs due to incomplete closure of the umbilical ring. The hernia is noticed as a soft swelling beneath the skin around the umbilicus, which often protrudes during crying or straining. Umbilical hernias occur more frequently in African American children and typically resolve spontaneously. Those that persist beyond 4–5 years of age or cause symptoms may require surgical treatment.
4. Omphalocele and gastroschisis [see sections XII.C.1 and XII.C.2]
5. Persistent urachus is due to failure of the urachal duct to close, resulting in a fistula between the bladder and the umbilicus. It typically presents with urine draining from the umbilicus.
6. Abdominal masses in the neonate may be caused by multiple abnormalities, including hydronephrosis (most common), multicystic kidneys, ovarian cysts, or other lesions. The liver edge is normally palpable 1–3 cm below the right costal margin in healthy term infants. If the liver is palpated on the left side, situs inversus or asplenia syndrome may be present.
7. The anus should be examined for position and patency. In some cases, an imperforate anus may not be visible. Anal patency can be confirmed with careful introduction of either a soft rubber catheter or a rectal thermometer.
H. Genitalia examination. The appearance of the genitalia changes with gestational age. Examination should include descriptions of the normal anatomic features while noting any anomalies.
1. Female genitalia abnormal findings
a. A hypertrophied clitoris may result from virilization and androgen excess associated with virilizing adrenal hyperplasia (see Chapter 6, section III.E). Clitoral hypertrophy is also seen in premature infants.
b. Hydrometrocolpos is caused by an imperforate hymen with retention of vaginal secretions. It presents as a small cyst between the labia at the time of birth, or as a lower midline abdominal mass during childhood.
2. Male genitalia abnormal findings
a. Hypospadias is ventral displacement of the urethral meatus from its normal position at the tip of the penis to abnormal position at various locations along the ventral shaft. Isolated hypospadias is not associated with increased incidence of other urinary malformations; however, hypospadias with cryptorchidism (undescended testes) is associated with disorders of sexual differentiation (see Chapter 6, section III) and warrants further evaluation of the endocrine and genitourinary systems.
b. Epispadias is a rare condition with displacement of the urethral meatus to the dorsal surface of the penis and is often associated with bladder extrophy (bladder protrusion from the abdominal wall with exposure of its mucosa).
c. Hydrocele is a scrotal swelling caused by fluid accumulation in the tunica vaginalis adjacent to the testis. Although isolated hydroceles are typically asymptomatic and resolve spontaneously within a few weeks or months, some hydroceles are associated with inguinal hernias (see Chapter 3, section IX.C.3).
d. Cryptorchidism, or undescended testes, may be associated with inguinal hernia, genitourinary malformations, hypospadias, and genetic syndromes. The testes typically descend spontaneously by 3–4 months and, in most cases, by 6 months. Testes that remain undescended are at risk of testicular torsion, impaired fertility, and testicular cancer.
I. Spine examination. The spine should be examined for evidence of spina bifida, including the presence of hair tufts, hemangioma, lipoma, or dimples in the lumbosacral area. If a sacrococcygeal pilonidal dimple is present, a careful attempt to identify the base should be made to rule out a neurocutaneous sinus tract. A myelomeningocele (hernial protrusion of the cord and its meninges through a defect in the vertebral canal) may be present anywhere along the spine and is usually obvious at birth.
J. Extremity examination. The extremities should be examined to detect anatomic and functional abnormalities. The lack of spontaneous movements in the upper extremities may suggest fractures, infection, or brachial plexus injury.
1. Brachial plexus injuries: Erb palsy and Klumpke palsy (see Chapter 17, sections I.A.1 and I.A.2)
2. Absence or hypoplasia of the radius may be associated with TAR syndrome
(thrombocytopenia absent radii), Fanconi anemia, and Holt–Oram syndrome.
3. Syndactyly (fusion of the digits) or polydactyly (extra digits) may occur as isolated anomalies or as part of a genetic syndrome.
4. Edema of the feet with hypoplastic nails is characteristic of Turner and Noonan
syndromes.
5. Rocker bottom feet is frequently seen in trisomy 18.
6. The hips should be examined for developmental dysplasia of the hips (see Chapter 17, section III.A).
K. Skin examination findings vary with gestational age. As an example, skin texture is softer and thinner in premature infants.
1. Lanugo is the thin hair that covers the skin of preterm infants and is minimally present in term infants.
2. Vernix caseosa is a thick, white, creamy material that covers large areas of the skin in late preterm infants. It gradually decreases with increasing gestational age and is typically absent in postterm infants.
3. The skin color is pink a few hours after birth, but acrocyanosis (cyanosis of the hands and feet) is frequently seen during the first 48–72 hours. In some infants, acrocyanosis can last throughout the first month of life, particularly when the infant is cold. Acrocyanosis and cutis marmorata (mottling of the skin with venous prominence) are common intermittent signs of the vasomotor instability characteristic of newborn infants.
4. Pallor may be a sign of neonatal asphyxia, shock, sepsis, or anemia.
5. Jaundice is always abnormal if detected within the first 24 hours of birth. Subsequently, it is frequently seen during the first few days after birth and, in most cases, is not associated with significant underlying disease, although it may require intervention [see section X].
6. Milia are very small cysts formed around the pilosebaceous follicles that appear as tiny whitish papules seen over the nose, cheeks, forehead, and chin. They usually disappear within a few weeks and do not require treatment.
7. Slate gray patches (hyperpigmented macules) are dark blue hyperpigmented macules over the lumbosacral area and buttocks of no pathologic significance. These areas of pigmentation are most frequently seen in Hispanic, Asian, and African American infants.
8. Pustular melanosis is a benign transient rash characterized by small, dry superficial pustules or vesicles over a dark macular base. This rash is more frequently seen in African American infants. Lesions are filled with neutrophils and no treatment is required. Pustular melanosis must be differentiated from pathologic conditions that cause vesicular lesions, including viral infections (e.g., herpes simplex) and pustular bacterial infections.
9. Erythema toxicum neonatorum is a benign rash seen most frequently in the first 72 hours after birth and characterized by erythematous macules, papules, and pustules (resembling “flea bites”) on the trunk and extremities but not on the palms and soles. The rash occurs in about 50% of full-term infants and is less common in preterm infants.
Lesions are filled with eosinophils and no treatment is required.
10. Nevus simplex (or “salmon patch” or telangiectatic nevus) is the most common vascular lesion of infancy. It is composed of capillary proliferations and occurs in 30–40% of newborns as a pink macular lesion on the nape of the neck (“stork bite”), upper eyelids, glabella, or nasolabial region (“angel kiss”). It is often transient.
11. Nevus flammeus, or “port wine stain,” is a congenital vascular malformation composed of dilated capillary-like vessels (a form of capillary hemangioma), which may be located over the face or trunk and becomes darker with increasing age. Those located in the area of the ophthalmic branch of the trigeminal nerve (cranial nerve V-1) may be associated with intracranial or spinal vascular malformations, seizures, and intracranial calcifications (Sturge–Weber syndrome).
12. Hemangiomas are benign proliferative vascular tumors occurring in approximately 10% of infants. Often first noticed a few days after birth, they increase in size after birth for the next several months and subsequently resolve slowly within 18–24 months. Some hemangiomas can take years to fully resolve. Hemangiomas that compromise the airway or functional structures (e.g., affecting vision, urination, swallowing) require intervention.
13. Neonatal acne occurs in approximately 20% of newborns. It appears after 1–2 weeks of life and is virtually never present at birth. Typically, the lesions are comedones, but inflammatory pustules and papules may be present. Treatment is not necessary.
Table 4-1
Apgar Scoring System*
Score 0 1 2
Heart rate Absent <100 per minute >100 per minute
Respirations Absent Slow, irregular Good, crying
Muscle tone Limp Some flexion Active motion
Reflex irritability (response to catheter in
nose) No response Grimace Cough, sneeze, cry
Color Blue, pale Body pink, blue extremities Completely pink
*Five variables are evaluated at 1 and 5 minutes after birth, and each one is scored from 0 to 2. The final score is the sum of the five individual scores, with 10 representing the optimal score.
FIGURE 4.1 A. Caput succedaneum. From pressure of the birth canal, an edematous area is present beneath the scalp. Note how it crosses the midline of the skull. B. Cephalohematoma. A small capillary beneath the periosteum of the skull bone has ruptured, and blood has collected under the periosteum of the bone. Note how the swelling now stops at the midline.
Reprinted with permission from Pillitteri A. Maternal and Child Health Nursing. 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2013.
II. Abnormalities of Maturity
A. Preterm delivery
1. Definition. A preterm delivery is any delivery that occurs less than 37 completed weeks from the first day of the last menstrual period.
2. Incidence. Preterm delivery occurs in approximately 11% of all births; however, this figure varies widely across the United States and throughout the world. Multiple factors have been linked to increased risk of preterm birth, including young (<20 years) and advanced (>35 years) maternal age, lower socioeconomic status, lack of prenatal care, multiple gestation, and the use of assisted reproductive technology.
3. Complications. Premature infants may have multiple complications that affect every organ system and range from acute issues to chronic conditions that are lifelong in nature (Table 4-2).
B. Postterm delivery
1. Definition. A postterm delivery occurs >42 weeks from the first day of the last menstrual period. Up to 10% of deliveries occur beyond 42 weeks of gestation.
2. Complications include increased incidence of fetal and neonatal morbidity and death due to placental insufficiency and related severe intrauterine asphyxia, meconium aspiration syndrome (MAS), and polycythemia.
Table 4-2
Frequent Problems of Preterm Infants
Disrupted mother–father–infant interaction
Perinatal asphyxia
Hypothermia
Hypoglycemia
Hypocalcemia
Respiratory distress syndrome (hyaline membrane disease; surfactant deficiency syndrome)
Fluid and electrolyte abnormalities
Indirect hyperbilirubinemia
Patent ductus arteriosus
Intracranial hemorrhage
Necrotizing enterocolitis
Infections
Retinopathy of prematurity
Bronchopulmonary dysplasia
Anemia
Neurodevelopmental impairment
III. Growth Abnormalities
A. Small-for-gestational-age (SGA) infants and FGR
1. Definition
a. SGA: Infants with a birth weight below the 10th percentile for their gestational age are SGA. SGA is a diagnosis based exclusively on the birth weight.
b. FGR: Fetuses who develop at less than their expected growth potential, with an estimated fetal weight below the 10th percentile for gestational age, have FGR. FGR is a diagnosis made during gestation and is classified based on the pattern of intrauterine growth parameters. Symmetric FGR affects all growth parameters equally (head circumference, length, and weight), whereas asymmetric FGR affects birth weight but preserves length and head circumference.
2. Etiology. Causes of FGR are listed in Table 4-3.
3. Clinical features. Clinical problems of SGA infants are listed in Table 4-4.
B. LGA infants
1. Definition. Newborns are considered LGA if their birth weight is above the 90th percentile for gestational age. These infants should be distinguished from those with high birth weight (>4000 g). A newborn may be LGA with a birth weight above the 90th percentile for gestational age but not have an absolute birth weight above 4000 g.
2. Etiology. Commonly due to maternal diabetes. Additional causes include Beckwith– Wiedemann syndrome, Prader–Willi syndrome (see Chapter 5, section IV.E.2), and congenital hyperinsulinism (nesidioblastosis, with diffuse proliferation and dysfunction of pancreatic islet cells).
3. Complications. LGA infants have increased risk of birth trauma (such as shoulder dystocia, brachial plexus injury, and clavicular fracture), hypoglycemia, polycythemia, and perinatal asphyxia. LGA infants also have an increased association with congenital malformations and increased risk of neonatal mortality compared with age-matched appropriate-for-gestational age (AGA) infants.
Table 4-3
Causes of Fetal Growth Restriction
Type I: Early interference with fetal growth from conception to 24 weeks’ gestation
Chromosomal anomalies (including trisomies 21, 13–15, and 18) Fetal infections (TORCH)
Maternal drug use (chronic alcoholism, heroin, and cocaine) Maternal chronic illness (hypertension, severe diabetes mellitus)
Type II: Intrauterine malnutrition from 24 to 32 weeks’ gestation
Inadequate intrauterine space (multiple pregnancies, uterine tumors, uterine anomalies)
Placental insufficiency from maternal vascular disease (renal failure, chronic essential hypertension, collagen vascular diseases, pregnancy-induced hypertension)
Small placenta with abnormal cellularity
Type III: Late intrauterine malnutrition after 32 weeks’ gestation
Placental infarct or fibrosis Maternal malnutrition Pregnancy-induced hypertension
Maternal hypoxemia (lung disease, smoking)
TORCH = toxoplasmosis, other (syphilis), rubella, cytomegalovirus, herpes simplex virus.
Table 4-4
Clinical Problems of Small-for-Gestational-Age Infants
Perinatal asphyxia
Hypothermia
Hypoglycemia
Polycythemia
Thrombocytopenia
Hypocalcemia
Meconium aspiration syndrome
Intrauterine fetal death
Hypermagnesemia (if the mother is treated with magnesium for hypertension or preterm labor)
IV. Cyanosis
A. Definition. Cyanosis is the bluish discoloration of the skin and mucous membranes that is directly related to the absolute concentration of deoxygenated hemoglobin (more than 3 g/dL of deoxygenated, reduced Hgb in the capillary blood).
B. Clinical significance. After birth, the oxygen saturation in healthy term infants gradually increases over the first 10 minutes of life and parallels the resolution of central cyanosis. Persistent central cyanosis (trunk, lips, tongue) is an emergency and requires immediate diagnosis and treatment. This is in contrast to acrocyanosis (fingers, toes) that is typical in healthy infants, is transient, and does not require further evaluation.
C. Etiology. The causes of central cyanosis are broad and include impairments in ventilation (e.g., central nervous system and airway abnormalities), lung pathology (e.g., imbalance of ventilation and perfusion, diffusion abnormalities), right-to-left cardiac shunts (e.g., the “5 T’s” of cyanotic congenital heart disease: tetralogy of Fallot, transposition of the great vessels, truncus arteriosus, tricuspid atresia, and total anomalous pulmonary venous
connection—see also Chapter 8, section IV), hematologic disorders (e.g., polycythemia), and metabolic abnormalities (e.g., hypoglycemia, hypocalcemia, hypothyroidism, and hypothermia). Infection/sepsis is also a common cause of cyanosis due to respiratory depression and lung pathology.
D. Evaluation
1. Initial steps include a detailed history and physical examination, serum electrolytes and glucose, arterial blood gas (ABG; ±100% oxygen test—see below), complete blood count (CBC), and chest radiograph (CXR). Additional tests may be warranted, including preductal (measured at the right wrist or hand) and postductal (measured in either lower extremity) oxygen saturation measurements, electrocardiogram, echocardiogram, and blood culture.
2. The 100% oxygen test (hyperoxia test): ABG is performed before and after administration of 100% oxygen. The hyperoxia test helps to distinguish between respiratory and cardiac causes of cyanosis.
a. Hyperoxia test in infants with lung disease. The PaO2 usually increases considerably when 100% oxygen is given, often reaching levels greater than 150 mm Hg. Cyanosis due to lung disease is typically due to ventilation– perfusion mismatch that is improved by giving 100% oxygen.
b. Hyperoxia test in infants with heart disease. Cyanosis associated with congenital heart disease is due to right-to-left shunting of deoxygenated blood. Giving 100% oxygen does not significantly improve the PaO2 because deoxygenated blood bypasses the pulmonary circulation. In infants with cyanotic congenital heart disease, the PaO2 usually increases minimally (less than 10–15 mm Hg) and will almost never exceed 150 mm Hg.
E. Management. Immediate treatment of cyanosis may be necessary and often includes empiric administration of oxygen and correction of abnormalities of temperature, hematocrit, glucose, and calcium levels. In severely cyanotic infants, intubation and mechanical ventilation may be necessary until a diagnosis is made and definitive treatment is initiated. Infants with congenital heart disease may require treatment with prostaglandin (PGE1) to maintain patency of the ductus arteriosus until surgical repair can be performed.
V. Respiratory Distress
A. General concepts. Respiratory problems are among the most common and significant causes of morbidity and mortality during the neonatal period. Some of the more common pulmonary causes of respiratory distress in the neonate include respiratory distress syndrome (RDS; also termed hyaline membrane disease and surfactant deficiency syndrome) in preterm infants, transient tachypnea of the newborn (TTN) from delayed clearance of fetal lung fluid in term infants during the first day of life, and MAS with persistent pulmonary hypertension of the newborn (PPHN) in full-term infants.
B. Clinical features. Manifestations include cyanosis, respiratory distress (which may be characterized by tachypnea, retractions, expiratory grunting, nasal flaring, and stridor), and decreased air entry or gas exchange. Many of these signs are nonspecific responses of the newborn to serious illness.
C. Etiology. Causes are extensive and involve multiple organ systems, because many conditions that produce neonatal respiratory distress are not primary diseases of the lungs (Figure 4-2).
FIGURE 4.2 Differential diagnosis of respiratory distress in neonates. CNS = central nervous system; RDS = respiratory distress syndrome; MAS = meconium aspiration syndrome; PPHN = persistent pulmonary hypertension of the newborn; TTN = transient tachypnea of the newborn; IDM = infant of diabetic mother.
VI. Respiratory Distress Syndrome (RDS)
A. Definition. RDS is respiratory distress caused by a lack of surfactant, most frequently in preterm infants.
B. Pathophysiology
1. Pulmonary surfactant is the surface-active material that decreases alveolar surface tension and prevents atelectasis. Although surfactant is first noted in the lungs at approximately 23–24 weeks’ gestation, a sufficient quantity of effective surfactant is produced only after 30–32 weeks’ gestation.
2. Assessment of fetal lung maturity can be made by determining the presence of surfactant in amniotic fluid obtained by amniocentesis. A lecithin-to-sphingomyelin (L:S) ratio greater than 2:1 and the presence of phosphatidylglycerol (a minor phospholipid in surfactant) are indicators of fetal lung maturity.
C. Epidemiology
1. Incidence. RDS affects approximately 0.5% of all neonates and is the most frequent cause of respiratory distress in preterm infants. The incidence is inversely related to gestational age with greater than 90% of infants <28 weeks being affected, whereas only 10% of infants are diagnosed with RDS if born between 34 and 35 weeks. RDS is also more frequent and more severe in white male infants.
2. Risk factors. The risk of RDS increases with a low L:S ratio, prematurity, a mother with a previous preterm infant with RDS, maternal diabetes mellitus, neonatal hypothermia, and neonatal asphyxia.
D. Clinical features. Infants show progressive respiratory distress during the first 24–48 hours of life with tachypnea, retractions, expiratory grunting, and cyanosis. Symptoms are more severe and prolonged in preterm infants less than 31 weeks’ gestation.
E. Evaluation. A CXR is diagnostic and shows diffuse atelectasis with a resulting pattern of low lung volumes, diffuse homogeneous opacity of both lungs with a fine, granular, ground glass appearance, and air bronchograms (darker open airways being highlighted by the surrounding brighter collapsed distal air sacs).
F. Management
1. Supplemental oxygen is often necessary.
2. Continuous positive airway pressure (CPAP) is used to maintain end-expiratory airway pressure, decrease atelectasis, and improve air exchange.
3. Mechanical ventilation via an endotracheal tube may be indicated if hypercarbia and respiratory acidosis develop.
4. Exogenous surfactant administered into the trachea is often curative.
G. Complications
1. Acute complications include air leaks (e.g., pneumothorax and pulmonary interstitial emphysema), intraventricular hemorrhage, and right-to-left shunting across a PDA.
2. Chronic complications
a. Bronchopulmonary dysplasia (BPD). This term is often used to describe chronic lung disease (CLD) that can develop in preterm infants. BPD is defined as progressive pathologic changes in the immature lung that affect both the parenchyma and airways and alter normal lung growth, specifically with impairment of alveolar development. The criteria used to diagnose BPD continue to evolve and currently include the need for supplemental oxygen or positive pressure ventilation beyond 28 days of age. The severity of BPD is further subcategorized based on the amount of respiratory support required beyond
28 days; however, this subcategorization does not clearly predict pulmonary outcome in later life.
b. Retinopathy of prematurity (see Chapter 18, section VII)
H. Prognosis. With aggressive treatment in an intensive care nursery, more than 90% of infants with RDS survive.
VII. Meconium Aspiration Syndrome (MAS)
A. Definition
1. Meconium (first stools) is a material in the fetal gut consisting of water, mucopolysaccharides, desquamated skin and gastrointestinal mucosal epithelial cells, vernix, bile salts, and amniotic fluid.
2. MAS describes an acute respiratory disorder caused by aspiration of meconium into the lungs of the fetus or neonate.
B. Pathophysiology. Meconium is often passed as a consequence of fetal distress (e.g., hypoxemia) in a near-term fetus and becomes more frequent after 42 weeks’ gestation. The consistency of meconium-stained amniotic fluid (MSAF) varies from thin and slightly green to thick and dark green. MSAF can reach the distal airways and alveoli in utero if the fetus becomes hypoxic and develops gasping respirations, or this condition may occur at the time of birth with the first inspirations. In some infants with MSAF, aspirated meconium causes respiratory distress due to mechanical obstruction with both atelectasis and air trapping and chemical pneumonitis with diffuse inflammation. This combination results in MAS.
C. Clinical features. Patients with MAS typically present with mild or moderate respiratory distress within the first hours after birth. In severe cases, respiratory failure with profound hypoxemia and cyanosis occurs immediately after birth.
D. Evaluation. MAS is suggested by history of meconium noted at or before delivery and presence of respiratory distress. CXR reveals increased lung volume with diffuse patchy areas of atelectasis and parenchymal infiltrates alternating with hyperinflation. Pneumothorax or pneumomediastinum may occur.
E. Management. Prevention is key and requires obstetric and pediatric collaboration, including prevention of fetal hypoxemia and delivery after 41 weeks. Intrapartum suctioning of the airway has not proven to reduce the incidence of MAS; however, endotracheal suctioning of the infant to remove meconium from the airway is recommended if the infant is not vigorous at birth. Oxygen is usually required if MAS is present, and if MAS is severe, mechanical ventilation and treatment with inhaled nitric oxide (iNO) or extracorporeal membrane oxygenation (ECMO) may be necessary. Complications include persistent pulmonary hypertension of the newborn (PPHN), bacterial pneumonia, and long-term increased risk of reactive airway disease or asthma.
VIII. Persistent Pulmonary Hypertension of the Newborn (PPHN)
A. Definition and pathophysiology. PPHN is any condition other than congenital heart disease associated with abnormally elevated pulmonary vascular resistance and decreased blood flow to the lungs after birth. As a result, deoxygenated blood shunts away from the pulmonary circulation into the systemic circulation via the PDA and patent foramen ovale (PFO), a sequence that mimics the fetal circulation and causes cyanosis with systemic hypoxemia. It occurs most frequently in near-term, full-term, or postterm infants.
B. Etiology. Causes are extensive, but perinatal asphyxia and MAS are most common. The perinatal history is often remarkable for evidence of fetal distress.
C. Clinical features. Severity can range from cyanosis to multisystem organ failure due to inadequate oxygen delivery. PaO2 is often significantly decreased and improves only minimally with increased supplemental oxygen. Pre- and postductal oxygen saturation and PaO2 may be significantly different if there is large right-to-left shunt through the ductus arteriosus.
D. Evaluation
1. CXR findings are variable because of the many causes of this syndrome. Pulmonary vascular markings are usually decreased in infants with idiopathic PPHN not caused by MAS or perinatal asphyxia.
2. Echocardiogram is important to rule out congenital heart disease and to assess the degree of pulmonary hypertension, right-to-left shunting, and right ventricular function.
E. Management
1. Prevention of hypoxemia is the cornerstone of therapy because hypoxemia is a potent pulmonary vasoconstrictor, whereas oxygen is a potent pulmonary vasodilator.
2. Mechanical ventilation must be started early if oxygen alone is insufficient.
3. iNO improves ventilation and perfusion matching while decreasing intrapulmonary shunting by inducing pulmonary vasodilation in well-ventilated regions of the lung.
4. In severe cases, and for infants who do not respond to standard measures, high- frequency oscillatory ventilation (HFOV) and ECMO are necessary.
IX. Apnea of Prematurity
A. Definition. Apnea of prematurity is a respiratory pause with no airflow lasting more than
20 seconds, or a respiratory pause of any duration if accompanied by bradycardia and cyanosis or oxygen desaturation in a preterm infant. It occurs most commonly in infants less than 34 weeks’ gestation.
B. Categories of apnea. Preterm infants can have apneic events for several reasons that are classified based on the respiratory activity observed during the event.
1. Central apnea describes an episode with complete cessation of chest wall movement and no airflow. These episodes imply a lack of normal central respiratory drive.
2. Obstructive apnea describes an episode with normal or increased chest wall movements and respiratory effort but without airflow. These episodes imply a normal respiratory drive that is impaired by obstruction of the airways.
3. Mixed apnea is a combination of central and obstructive apnea and constitutes the most frequent type encountered in preterm infants.
C. Etiology. Causes of apnea in preterm infants include infection/sepsis, lung disease, hypothermia, hyperthermia, hypoglycemia, seizures, exposure to maternal medication or drugs of abuse, drug withdrawal, anemia, and gastroesophageal reflux, in addition to idiopathic apnea of prematurity.
D. Idiopathic apnea of prematurity
1. Incidence. Frequency increases with decreasing gestational age, affecting 85% of infants
<28 weeks’ gestation and 25% of infants 33–34 weeks’ gestation.
2. Clinical features. Idiopathic apnea of prematurity occurs in the absence of any identifiable cause, usually appearing 24 hours after birth or during the first week of life, and resolving by 38–44 weeks’ gestational age.
3. Management. Idiopathic apnea of prematurity is a diagnosis of exclusion and therefore requires a search for other potential causes. Management principles include the following:
a. Maintenance of a neutral thermal environment, treatment of hypoxia, and tactile stimulation (including rubbing the back or repositioning the infant, as needed).
b. Acute respiratory support for severe episodes (including bag and mask ventilation) and chronic respiratory support to maintain adequate lung inflation (nasal CPAP or invasive mechanical ventilation) may be needed.
c. Respiratory stimulant medications (caffeine or theophylline) may be used to limit the frequency and severity of apnea events.
X. Neonatal Jaundice
A. Definition. Jaundice is the yellow discoloration of mucous membranes and skin due to increased bilirubin levels. It usually occurs during the first week of life and is most frequently caused by indirect (unconjugated) hyperbilirubinemia that is physiologic in nature. Visible jaundice occurs in the neonate when the serum bilirubin level exceeds 5 mg/dL.
B. Classification of jaundice
1. Physiologic jaundice. This term describes the benign and self-limited indirect hyperbilirubinemia that typically resolves by the end of the first week of life and requires no treatment.
a. Causes of physiologic jaundice
1. Increased bilirubin load on hepatocytes due to breakdown of red blood cells after birth
2. Delayed activity of the hepatic enzyme glucuronyl transferase
b. Clinical features include jaundice in well-appearing infants with elevated indirect bilirubin levels. Peak serum concentrations in normal full-term infants reach 5–
16 mg/dL by 3–4 days of life and begin decreasing before the end of the first week of life. In preterm infants, bilirubin levels continue to rise later than in term infants (reaching peak levels after 5–7 days) and have a more delayed and gradual decline (requiring 10–20 days before decreasing without treatment).
2. Nonphysiologic jaundice. This term describes jaundice that is secondary to pathophysiologic causes and may be further classified as follows:
a. Indirect hyperbilirubinemia is an elevated bilirubin in which the conjugated or direct component is <15% of the total bilirubin level.
b. Direct hyperbilirubinemia is a conjugated or direct bilirubin level that is >15% of the total bilirubin level. This is always pathologic in neonates.
C. Differential diagnosis of indirect hyperbilirubinemia. Possible causes include physiologic jaundice, excessive bilirubin production, impaired bilirubin clearance, and defective conjugation of bilirubin by the liver (Figure 4-3). Breastfeeding is associated with higher peak bilirubin levels compared with formula feeding, and the resulting indirect hyperbilirubinemia is of two types:
1. “Breastfeeding jaundice” typically occurs during the first week of life with increased bilirubin levels related to suboptimal milk intake. Poor intake leads to weight loss, dehydration, and decreased passage of stool. This sequence results in impaired bilirubin clearance and increased enterohepatic circulation of bilirubin.
2. “Breast milk jaundice” typically occurs after the first week of life and is likely related to breast milk’s high levels of β-glucuronidase and high lipase content. In this case, the bilirubin is often highest in the second and third weeks of life; however, moderately elevated levels of bilirubin may persist until 10 weeks of life.
D. Differential diagnosis of direct hyperbilirubinemia. Possible diagnoses include obstruction of the hepatobiliary tree, neonatal infection, and metabolic disorders (Figure 4-4).
E. Evaluation of hyperbilirubinemia (see also Chapter 10, section XI.C)
1. Bilirubin is now routinely checked in all infants at 24 hours of life owing to the inability of visual inspection to accurately diagnose hyperbilirubinemia.
2. Jaundice should always be evaluated under the following circumstances:
a. Jaundice appears at <24 hours of age.
b. Bilirubin rises >5–8 mg/dL in a 24-hour period.
c. The rate of rise between two sequential bilirubin measurements exceeds 0.5 mg/dL per hour (suggestive of hemolysis).
3. To evaluate indirect hyperbilirubinemia, infant and maternal blood types, Coombs test, CBC, reticulocyte count, and peripheral blood smear (for hemolysis) are necessary. Evaluation for sepsis may be considered.
4. To evaluate direct hyperbilirubinemia, hepatic and biliary ultrasound (to evaluate for biliary atresia and choledochal cyst), serologies for viral hepatitis, evaluation for metabolic disease, evaluation for α-1-antitrypsin disease, and liver biopsy may be warranted.
F. Management
1. Serial bilirubin assessments, observation, and reassurance are appropriate for
physiologic jaundice.
2. Phototherapy creates water-soluble photoisomers of indirect bilirubin that are more readily excreted. Phototherapy may be indicated depending on the infant’s gestational age at birth, postnatal age, bilirubin levels, and risk factors for significant jaundice and impairment of the blood–brain barrier (e.g., blood group incompatibility with hemolysis, suspected sepsis, or severe acidosis).
3. Exchange transfusion is performed for rapidly rising bilirubin levels and dangerously elevated bilirubin levels to prevent complications.
G. Complications include acute bilirubin encephalopathy and kernicterus.
1. Unconjugated bilirubin that is not bound by albumin can pass through the blood–brain barrier and produce irreversible damage and neuronal cell death. This typically does not happen unless the indirect bilirubin level is >25 mg/dL.
2. Bilirubin injury occurs most frequently within the basal ganglia and brainstem nuclei
involved in vision, hearing, movement, language, and cognitive function.
3. Clinical features of acute bilirubin encephalopathy range from lethargy, hypotonia, and high-pitched cry to coma, apnea, seizures, and death. Rapid early treatment may prevent progression, irreversible brain injury, and kernicterus. Features of kernicterus include choreoathetoid cerebral palsy, hearing loss, and oculomotor paralysis.
FIGURE 4.3 Differential diagnosis of indirect hyperbilirubinemia. RBC = red blood cell;
GI = gastrointestinal.
FIGURE 4.4 Differential diagnosis of direct hyperbilirubinemia. EBV = Epstein–Barr virus;
TORCH = toxoplasmosis, other (syphilis), rubella, cytomegalovirus, herpes simplex virus.
XI. Fetal Exposure to Drugs of Abuse
A. Epidemiology
1. Incidence. Fetal exposure to drugs of abuse is common: tobacco in nearly 20%, alcohol in 10%, and illicit drugs in 5% of all pregnancies.
2. Drugs used. Most women who use illicit drugs take multiple drugs. Use of alcohol, cocaine, amphetamines, phencyclidine (PCP), and narcotics may compound the fetal risk in women already using tobacco, caffeine, or prescribed drugs.
3. Risk factors and clinical complications vary with the substance used.
a. Mothers who use illicit drugs may also have poor nutritional status, inadequate prenatal care, anemia, endocarditis, hepatitis, tuberculosis, HIV, sexually transmitted diseases, low self-esteem, and depression.
b. Obstetric complications include placental abruption, precipitous delivery, and preterm labor and delivery.
B. Clinical features vary with the individual agent and include both acute intoxication and chronic withdrawal symptoms, as well as a combination of these problems. The most common signs are jitteriness and hyperreflexia, together with irritability, tremulousness, feeding intolerance, and excessive wakefulness. Presence of these symptoms in a neonate should alert the clinician to the possibility of drug exposure that may be identified by toxicology screens of urine, meconium, or umbilical cord tissue.
C. Management of infants born to women using drugs includes early identification in the neonatal period and observation for signs of withdrawal. Infants with fetal exposure to opiates (heroin, methadone, and related compounds) frequently require narcotic replacement therapy to minimize withdrawal symptoms, support feeding and weight gain, and minimize risk of seizures. Consultation with child protective services may be required.
D. Infant mortality rates range from 3 to 10%, and fetal demise can occur in utero from withdrawal. Causes of mortality include perinatal asphyxia, congenital anomalies, child abuse, and sudden infant death syndrome.
XII. Surgical Conditions of the Newborn
A. Esophageal atresia with tracheoesophageal fistula (EA/TEF)
1. Epidemiology. This condition occurs in 1:3500 infants. The most common type of esophageal atresia (>90% of cases) involves proximal esophageal atresia with a distal tracheoesophageal fistula (see Figure 4-5).
2. Clinical features
a. Polyhydramnios in utero in two-thirds of cases, due to inability of the fetus to swallow amniotic fluid
b. After birth, copious oropharyngeal secretions with feeding difficulty, with increased risk of choking and aspiration
c. Associated malformations are found in 50% of patients with esophageal atresia, including vertebral, anorectal, cardiac, renal, and limb anomalies (VACTERL association) (see Chapter 5, section IV.I.2).
3. Evaluation and diagnosis. An oral gastric tube is inserted until it meets resistance. Radiographs show the tube in the upper part of the thorax. In Esophageal atresia with distal tracheoesophageal fistula (Figure 4-5A), air that has crossed through the distal fistula from the trachea is seen in the stomach and intestine.
4. Management. Surgical repair consists of ligation of the fistula and anastomosis of the two esophageal segments.
B. Congenital diaphragmatic hernia (CDH)
1. Overview. The diaphragm develops between the fifth and eighth weeks of gestation. Abnormalities in the development of the diaphragm can allow herniation of the abdominal contents into the thorax, which in turn impairs appropriate growth and maturation of the lungs. Most cases involve the left diaphragm in the posterior and lateral area.
2. Epidemiology. The incidence is 1:3500 live births.
3. Clinical features. Newborns present with severe respiratory distress and scaphoid abdomen due to displacement of the abdominal contents into the thorax. Severe respiratory insufficiency from pulmonary hypoplasia and pulmonary hypertension is common in patients with CDH, due to mechanical compression of the lung and defective pulmonary vascular development. Breath sounds are decreased, and bowel sounds may be heard in the chest. The condition has a wide spectrum of severity.
4. Evaluation. The diagnosis is often made by prenatal fetal ultrasound, noting the abnormal position of the stomach in the thorax and rightward deviation of the heart (in cases of left CDH). After birth, chest radiographs reveal little or no gas in the abdomen, absence of the diaphragmatic dome, mediastinal shift to the contralateral side (usually to the right), and bowel loops in the thorax (usually on the left side).
5. Management. Bag-and-mask ventilation should not be used because this may distend the bowel and increase compression of the lung. Intubation and mechanical ventilation with 100% oxygen should be initiated immediately. Correction of acidosis, hypoxemia, and hypercarbia are paramount. Once the infant is stabilized, management includes surgical reduction of the hernia and closure of the diaphragmatic defect.
6. Complications and associations. PPHN, pneumothorax, gastroesophageal reflux, intestinal obstruction, recurrent herniation, and progressive sensorineural hearing impairment may occur.
7. Prognosis is worse with larger defects, presence of liver herniation into the thorax, more severe lung hypoplasia, and pulmonary hypertension. Fetal and neonatal mortality remains high (50% or greater) in infants in whom the condition is diagnosed before
25 weeks’ gestation.
C. Abdominal wall defects. By the 10th week of gestation, the midgut enters the abdomen. If this process is disturbed, the result is an abdominal wall defect associated with a decrease in intra- abdominal volume. Omphalocele and gastroschisis are the most common defects, and both require surgical treatment.
1. Omphalocele occurs in approximately 1:6000–8000 live births. The defect is a centrally localized herniation of abdominal organs through the umbilical ring with a true hernia sac (abdominal organs are covered with a peritoneal sac). Omphalocele is frequently associated with other congenital anomalies, including congenital heart defects (most commonly tetralogy of Fallot and atrial septal defects), Beckwith–Wiedemann syndrome, and chromosomal disorders (trisomy 13 or, less frequently, trisomy 18; see also Chapter 5, section IV.E.5).
2. Gastroschisis is a congenital fissure of the anterior abdominal wall, usually located to the right of the umbilical cord stump (in the right paraumbilical area). There is no true hernia sac (no peritoneal sac covering), and the bowel is usually the only viscera that herniates. There is no increased association with other extraintestinal anomalies; however, there is an increased incidence of other bowel abnormalities, including malrotation and volvulus, and stenosis and atresia that are attributed to inadequate intestinal blood flow. The intestine of patients with gastroschisis may be affected by abnormalities in intestinal vascular supply or by inflammation due to exposure to the amniotic fluid. As a result, the intestine of gastroschisis patients may develop narrowed or atretic segments and cause bowel obstruction.
D. Intestinal obstruction may be functional or mechanical, and if mechanical, this condition may be acquired or congenital (see Figure 4-6 for a complete differential diagnosis).
1. Meconium is passed within 24 hours after birth in 90% of term infants and within
48 hours in 99% of term infants. Meconium plug is delayed passage of meconium (>24– 48 hours after birth) due to obstruction of the left colon and rectum by dense dehydrated meconium. Meconium plug may occur not only in infants with cystic fibrosis or Hirschsprung disease but also in normal infants.
2. Intestinal atresia is the most common cause of obstruction in the neonatal period. It can occur in the small or large bowel. Intestinal atresias are discussed in Chapter 10, section IV.C.
3. Meconium ileus is obstruction of the distal ileum caused by inspissated (thickened and dried) meconium, secondary to deficiency of pancreatic enzymes. Meconium ileus is a common neonatal manifestation of cystic fibrosis.
a. Clinical features include abdominal distension, lack of meconium passage, vomiting, and bowel perforation.
b. Diagnosis is by abdominal radiographs that reveal intestinal distension with minimal air–fluid levels. Air remains trapped in the meconium; thus, there is no definite air–fluid interface. Fine gas bubbles may be seen mixed within meconium, producing a characteristic soap-bubble appearance.
c. Management often includes an enema that may relieve the obstruction, and surgery for persistent obstruction and resection of injured bowel in cases with perforation. Early diagnosis and treatment are ixmportant to avoid intestinal perforation, meconium peritonitis, and volvulus.
4. Intestinal malrotation may result in volvulus (loops of intestine twist if attached to a narrow band of mesentery) with restricted circulation to the rotated segment, leading to intestinal gangrene. Malrotation and volvulus are discussed in Chapter 10, section IV.B.
5. Hirschsprung disease, or congenital aganglionic bowel disease, is caused by a lack of caudal migration of the ganglion cells from the neural crest. It results in persistent
contraction of a distal segment of colon, causing obstruction with proximal dilatation.
a. Incidence is approximately 1:5000 live births. Hirschsprung disease is five times more frequent in male infants, and in 80% of cases there is a family history.
b. Clinical features include constipation, vomiting, and abdominal distension.
c. Diagnosis is by rectal biopsy revealing absence or paucity of ganglion cells.
d. Management includes resection of the aganglionic segment.
E. Necrotizing enterocolitis (NEC)
1. Epidemiology. NEC is one of the most common surgical conditions in preterm neonates with an incidence as high as 8–10% in infants <30 weeks’ gestation.
2. Clinical features. Manifestations include abdominal distension, abdominal tenderness, bilious emesis, bloody stools, and abdominal wall erythema. Cardiovascular compromise can result in metabolic acidosis and oliguria. In severe cases, NEC may progress rapidly and lead to thrombocytopenia, disseminated intravascular coagulation, and death.
3. Diagnosis. Classic radiographic findings include intestinal distension, thickened bowel wall, pneumatosis intestinalis (air in the bowel wall), and portal venous gas. Intestinal perforation results in pneumoperitoneum.
4. Management
a. Medical treatment includes bowel rest with no oral feedings and gastric decompression, antibiotics, and parenteral fluids/nutrition. Supporting tissue perfusion with fluids and vasoactive medications may be required. Transfusion with platelets and fresh frozen plasma may also be required.
b. Surgical management with exploratory laparotomy may be indicated, including for infants who develop pneumoperitoneum or necrotic bowel.
5. Late complications may include intestinal obstruction (e.g., adhesions, stenosis), and nutritional deficiencies (e.g., malabsorption, short gut syndrome), and cholestasis.
6. Prevention. The incidence of NEC is lower in preterm infants who receive enteral feedings with breast milk.
FIGURE 4.5 Types of tracheoesophageal anomalies.
From Lippincott’s Nursing Advisor 2012. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins.
FIGURE 4.6 Differential diagnosis of intestinal obstruction in neonates.
XIII. Hypoglycemia
A. Definition. Hypoglycemia is defined as serum glucose concentration below 40 mg/dL.
B. Etiology. Causes are extensive and include the following:
1. Conditions that result in insulin excess. Infants of diabetic mothers (IDMs) commonly have transient hypoglycemia. Persistent hypoglycemia may result from insulin- producing tumors or islet cell hyperplasia.
2. Conditions that result in diminished glucose production or substrate supply include FGR and preterm infants, both having limited hepatic glycogen stores and immature gluconeogenesis; stressed infants who have been asphyxiated or have sepsis; infants with inborn errors of metabolism, such as galactosemia, hereditary fructose intolerance, and aminoacidopathies; and infants with endocrinopathies, such as growth hormone deficiency and panhypopituitarism.
C. Clinical features. The neonate may be asymptomatic or may present with diaphoresis,
jitteriness, feeding problems, tachycardia, hypothermia, hypotonia, or seizures.
D. Management. Depending on the degree of hypoglycemia and associated symptoms or illness, interventions include either oral feeding or intravenous glucose.
XIV. Infants of Diabetic Mothers (IDMs)
A. Pathophysiology. Maternal hyperglycemia results in fetal hyperglycemia with subsequent fetal hyperinsulinemia. This causes increased hepatic glucose uptake and glycogen synthesis, accelerated lipogenesis, augmented protein synthesis, and macrosomia.
B. Clinical features
1. IDMs are large because of increased body fat and visceromegaly, primarily of the liver, adrenal glands, and heart.
2. The skeletal length is increased in proportion to weight, but the head and face appear disproportionately small. The umbilical cord and placenta are also enlarged.
3. IDMs appear plethoric with round facies.
4. Although IDMs are usually LGA, they may be SGA secondary to placental insufficiency in women with severe diabetic-induced vascular complications.
C. Complications
1. IDMs are at considerable risk for the perinatal difficulties summarized in Table 4-5.
2. Congenital anomalies, such as congenital heart disease, are two to four times more frequent in IDMs than in normal infants.
3. Small left colon syndrome is a condition occurring most frequently in IDMs, in which infants present with abdominal distension and failure to pass meconium secondary to the decreased caliber of their left colon.
Table 4-5
Clinical Problems of Infants of Diabetic Mothers
Increased risk before and at delivery
Sudden intrauterine death Large for gestational age Increased rate of birth trauma
Increased rate of cesarean section Increased risk of asphyxia
Increased risk of common neonatal problems
Hypoglycemia Polycythemia Hypocalcemia
Hypertrophic cardiomyopathy
Persistent pulmonary hypertension of the newborn Respiratory distress syndrome
Renal vein thrombosis
Increased risk of developing congenital malformations
Structural heart disease Central nervous system Musculoskeletal
Small left colon syndrome
Caudal regression syndrome (hypoplasia of the sacrum and lower extremities)
XV. Polycythemia
A. Definition. Polycythemia is defined as a central venous hematocrit greater than 65%.
B. Epidemiology. Polycythemia occurs in 2–4% of infants born at sea level.
C. Etiology. Causes include increased erythropoietin secretion secondary to placental insufficiency, increased red blood cell production by the fetus in response to hypoxemia, or increased placental transfusion from delayed cord clamping.
D. Clinical features. Manifestations include plethora, poor perfusion, cyanosis, poor feeding, respiratory distress, lethargy, jitteriness, seizures, renal vein thrombosis, and metabolic acidosis. There is an increased risk of NEC.
E. Management. Treatment includes partial exchange transfusion, in which blood is removed and replaced by the same volume of plasma substitute (normal saline).
Review Test
1. Soon after birth, a term newborn infant presents with increased oral secretions and mild respiratory distress. Which of the following is the most likely diagnosis?
A. Persistent pulmonary hypertension of the newborn
B. Pneumonia
C. Esophageal atresia
D. Respiratory distress syndrome (surfactant deficiency syndrome)
E. Diaphragmatic hernia
2. An abdominal mass is detected on examination of a 2-day-old infant in the newborn nursery. Which of the following is the most likely cause of this abdominal mass?
A. Ovarian cyst
B. Hydronephrosis
C. Wilms tumor
D. Multicystic kidney
E. Hydrometrocolpos
3. The parents of a 5-day-old term infant notice that he is jaundiced. Your physical examination is remarkable only for scleral icterus and jaundice. The infant’s total bilirubin level is
15 mg/dL, with a direct component of 0.4 mg/dL. Which of the following is the most likely diagnosis?
A. Breastfeeding jaundice
B. Choledochal cyst
C. Biliary atresia
D. Neonatal hepatitis
E. Breast milk jaundice
4. You are called to the delivery room to evaluate a newborn infant born at 37 weeks’ gestation who has an abdominal wall defect noted on delivery. Based on your initial physical examination, you diagnose an omphalocele. Which of the following statements is consistent with this clinical diagnosis?
A. To rule out gastroschisis definitively, an abdominal computed tomographic scan is necessary.
B. Compared with gastroschisis, omphalocele is more frequently associated with other congenital malformations.
C. This abdominal wall defect is just lateral to the umbilicus.
D. The incidence of bowel obstruction is higher in this infant than in one with gastroschisis.
E. Omphaloceles may be associated with trisomy 21.
5. You are evaluating a 3-day-old infant with significant respiratory distress. He was delivered by emergency cesarean section at 42 weeks’ gestation because of fetal distress. You note that he has an oxygen saturation of 76% in room air that increases to 95% with administration of 100% oxygen. Which of the following statements most accurately supports your suspected diagnosis of persistent pulmonary hypertension of the newborn (PPHN)?
A. This patient is likely to have an associated cyanotic congenital cardiac defect.
B. PPHN occurs most frequently in premature infants but may occur in postterm infants.
C. PPHN usually resolves spontaneously.
D. This infant is likely to have significant left-to-right shunting.
E. Adequate oxygenation is the best preventive measurement and treatment.
6. A male infant was born at 32 weeks’ gestation via cesarean section because of bleeding from placenta previa. Soon after birth, he developed respiratory distress requiring supplemental oxygen and mechanical ventilation. Chest radiograph shows decreased lung volumes and a
diffuse ground glass pattern with air bronchograms. Which of the following is the most likely cause of this condition?
A. Persistent pulmonary hypertension of the newborn (PPHN)
B. Deficient surfactant
C. Fluid retention in the lungs
D. Bronchopulmonary dysplasia
E. Congenital heart disease
7. The parents of a term infant diagnosed with physiologic jaundice are very concerned that their child is at risk for brain damage. Which of the following statements regarding the infant’s hyperbilirubinemia is most accurate?
A. Breastfeeding, compared with formula feeding, is associated with higher peak serum bilirubin levels.
B. Serum conjugated bilirubin concentration is the best predictor of bilirubin encephalopathy.
C. Bilirubin encephalopathy does not occur in healthy term infants.
D. Increased conjugated (direct) bilirubin levels cause neuronal damage, including choreoathetoid cerebral palsy, hearing loss, and opisthotonus.
E. This infant’s jaundice is expected to peak at 10–14 days of life.
8. A 2-day-old term male infant is being evaluated before discharge from the nursery. The parents are concerned about a skin rash on his face. As you perform the physical examination, you contemplate skin disorders that are benign compared with those that may indicate underlying pathology. Which of the following skin findings is most likely to be associated with underlying pathology?
A. Pustular melanosis
B. Nevus simplex
C. Milia
D. Nevus flammeus
E. Erythema toxicum neonatorum (ETN)
9. At a routine health maintenance visit, a 2-week-old infant appears jaundiced. Laboratory evaluation reveals a total bilirubin level of 12.6 mg/dL with a direct bilirubin level of
6.9 mg/dL. Which of the following is the most likely diagnosis?
A. Breastfeeding jaundice
B. Breast milk jaundice
C. Crigler–Najjar syndrome
D. ABO incompatibility
E. Choledochal cyst
10. A female infant born at 30 weeks’ gestation develops abdominal distension, abdominal tenderness, and bloody stools on the third day of life. Which of the following statements regarding the most likely diagnosis is correct?
A. The diagnosis is supported by a double-bubble sign on abdominal radiographs.
B. The diagnosis is supported by pneumatosis intestinalis on abdominal radiographs.
C. The diagnosis is supported by a soap-bubble appearance on abdominal radiographs.
D. The infant will ultimately require pancreatic enzyme supplementation.
E. The diagnosis has an increased association with Down syndrome.
Questions 11 and 12: The response options for statements 11 and 12 are the same. You will be required to select one answer for each statement in the set.
A. 2
B. 3
C. 4
D. 5
E. 6
F. 7
G. 8
In each case, select the infant’s 1-minute Apgar score.
1. At 1 minute of life, a newborn’s respiratory rate is slow and irregular with a heart rate of 120 beats/minute. There is some flexion of her upper and lower extremities; she grimaces
when a catheter is placed into her nose; and she appears to be pink and well perfused, except for some cyanosis of the distal extremities.
2. At 1 minute of life, a newborn’s respiratory rate is slow and irregular with a heart rate of
80 beats/minute. There is some flexion of his upper and lower extremities; he does not respond when a catheter is placed into his nose; and he is blue and pale.
You’re called to the Nursery to evaluate a cyanotic infant with significant respiratory distress. After 100% oxygen is administered to the infant, there is almost no improvement in the PaO2 (only 10 mm Hg). Which of the following is the patient’s most likely diagnosis?
A. Tetralogy of Fallot
B. Pneumonia
C. Respiratory Distress Syndrome (RDS)
D. Meconium aspiration syndrome
E. Transient tachypnea of the newborn
Answers and Explanations
1. The answer is C [XII.A.3]. Esophageal atresia in a newborn is characterized by increased oral secretions as a result of the accumulation of saliva in the proximal esophageal pouch. Respiratory distress may occur if the infant aspirates this saliva. The presence of a distal tracheoesophageal fistula may also result in the passage of gastric contents to the trachea and lung, exacerbating the respiratory problem. Half of children with esophageal atresia have other congenital malformations, such as congenital heart disease. Both pneumonia and persistent pulmonary hypertension of the newborn also present with respiratory distress, but without increased oral secretions. Respiratory distress syndrome occurs less commonly in term infants, and increased oral secretions are not expected. Congenital diaphragmatic hernia usually presents with acute respiratory distress soon after birth in a newborn with a scaphoid abdomen. Bowel sounds can be heard on auscultation of the chest.
2. The answer is B [I.G.6 and I.H.1.b]. The most likely cause of an abdominal mass detected during the newborn period is of renal origin, with hydronephrosis being the most common cause. In female infants, an ovarian cyst, which is usually a benign tumor, is not as common as hydronephrosis. Wilms tumor and multicystic kidneys may present as abdominal masses but are also less common causes. Hydrometrocolpos, a retention of vaginal secretions, most commonly presents just after birth as a small cyst located between the labia, although during childhood, it may present as a lower midline abdominal mass.
3. The answer is A [X.C.1]. Breastfeeding jaundice is typically associated with indirect, or unconjugated, hyperbilirubinemia and is caused by suboptimal milk intake during the first week of life, which causes weight loss, poor hydration, and decreased stool output. The treatment of breastfeeding jaundice is hydration, which typically includes increasing the frequency of breastfeeding, along with observation and serial bilirubin assessments. Breast milk jaundice, which occurs later, after the first week of life, is thought to be associated with high levels of lipase and β-glucuronidase within breast milk. Choledochal cysts, biliary atresia, and neonatal hepatitis are more typical causes of direct, or conjugated, hyperbilirubinemia.
4. The answer is B [XII.C]. Omphalocele is more frequently associated with congenital malformations, such as congenital heart defects, and with genetic conditions, such as trisomy 13, and less commonly with trisomy 18, but not with trisomy 21. Omphalocele and gastroschisis are easily distinguished and diagnosed by inspection. An omphalocele occurs centrally through the umbilical ring, whereas gastroschisis is a lateral abdominal wall defect in which the abdominal contents herniate into the amniotic cavity and are directly exposed to amniotic fluid. Because of this difference in clinical presentation, both omphalocele and gastroschisis are diagnosed clinically without the need for radiographic confirmation. In gastroschisis, exposure to the amniotic fluid may cause inflammation of the bowel with subsequent bowel damage and risk of bowel obstruction.
5. The answer is E [VIII.A, VIII.C, and VIII.E]. One of the most common causes of persistent pulmonary hypertension of the newborn (PPHN) is perinatal asphyxia, resulting in increased pulmonary vascular resistance and significant right-to-left shunting through the foramen ovale or the ductus arteriosus. Oxygen is the most potent vasodilator of pulmonary vessels, and in most cases, increases of both alveolar and arterial partial pressures of O2 produce a decrease in pulmonary vascular resistance and reversal of low blood flow to the lungs. By definition, PPHN excludes the presence of congenital heart disease. If left untreated, the hypoxemia caused by PPHN worsens the increased pulmonary vascular resistance, resulting in many cases in irreversible disease and death. In addition, PPHN occurs most commonly in near-term and full-term infants, as well as in postterm infants.
6. The answer is B [VI.A–H]. Respiratory distress syndrome (RDS), which is most common in
premature male infants, is caused by a lack or deficiency of surfactant, with alveolar atelectasis and hypoventilation. Chest radiographic findings usually include a diffuse ground glass pattern with air bronchograms. Pneumonia and sepsis should always be included in the differential diagnosis of RDS because their clinical presentations may be quite similar.
Persistent pulmonary hypertension of the newborn (PPHN) is more common in term infants than in premature infants and results most frequently from perinatal asphyxia and meconium aspiration syndrome (MAS). Fluid retention in the lungs may cause respiratory distress, but it is usually mild. The chest radiograph usually shows normal or increased lung volume with increased vascular markings. Bronchopulmonary dysplasia (BPD) is a chronic complication of RDS. Some causes of cyanotic congenital heart disease may cause hypoxemia and respiratory distress after birth; however, the chest radiograph does not show a ground glass appearance, nor air bronchograms.
7. The answer is A [X.A–G]. Newborn infants who breastfeed have higher peak serum bilirubin values. However, hyperbilirubinemia alone is not a reason to discontinue breastfeeding. Bilirubin encephalopathy is caused only by unconjugated (indirect) bilirubin because of the ability of unconjugated bilirubin to cross the blood–brain barrier. Encephalopathy caused by indirect hyperbilirubinemia does occur in healthy term newborns, and for this reason, high bilirubin levels in this group of infants should not be ignored. Benign physiologic indirect hyperbilirubinemia is expected to peak in term infants at 3–4 days of life and in preterm infants at 5–7 days of life.
8. The answer is D [I.K.11]. Nevus flammeus or “port wine stain” located over the V-1 branch of the trigeminal nerve may herald Sturge–Weber syndrome, with its associated, and potentially very significant, underlying intracranial vascular malformations and calcifications. Pustular melanosis is a benign rash, characterized by small, dry vesicles over a dark macular base, more frequently seen in African American infants. Nevus simplex is the most common vascular lesion of infancy and is also completely benign and often transient, appearing as a “salmon patch” or “stork bite” on the nape of the neck. Milia are benign very small cysts formed around the pilosebaceous follicles that appear as tiny whitish papules over the nose, cheeks, forehead, and chin. Erythema toxicum neonatorum (ETN) is a benign rash usually present in the first 72 hours of life and seen in approximately 50% of all infants. ETN is characterized by erythematous macules, papules, or pustules on the trunk and extremities.
9. The answer is E [Figures 4-3 and 4-4]. This infant’s presentation with hyperbilirubinemia and a markedly elevated direct bilirubin level is consistent with a choledochal cyst, a disorder that causes obstruction of the biliary tree. Both breastfeeding and breast milk jaundice are characterized by indirect, not direct, hyperbilirubinemia. Crigler–Najjar syndrome, or hereditary deficiency of glucuronyl transferase, would also be expected to result in an indirect, or unconjugated, hyperbilirubinemia. ABO incompatibility would lead to hemolysis, leading to an elevation of indirect bilirubin.
10. The answer is B [XII.E]. Necrotizing enterocolitis (NEC) is one of the most common surgical conditions in neonates, occurring most commonly in premature infants. Clinical features include abdominal distension, abdominal tenderness, residual gastric contents, bilious vomiting or bilious nasogastric aspirate, bloody stools, and, at times, abdominal wall erythema. Classic radiographic findings include abdominal distension, air–fluid levels, thickened bowel walls, and pneumatosis intestinalis (air within the bowel wall). In contrast, the double-bubble sign on abdominal radiographs is pathognomonic of duodenal atresia, which classically presents with nonbilious emesis and abdominal distension, but not with bloody stools. The presence of a soap-bubble appearance on abdominal radiographs is characteristic of meconium ileus, a presentation of cystic fibrosis during the neonatal period. Infants with meconium ileus would not be expected to pass bloody stools on the third day of life, but may require pancreatic enzyme supplementation if they are ultimately diagnosed
with fat malabsorption and cystic fibrosis. There is no known association between Down syndrome and NEC, although there is an association between Down syndrome and duodenal atresia.
11. The answers are E and B, respectively [Table 4.1]. The Apgar scoring system provides a simple, systematic, and objective assessment of intrapartum stress and neurologic depression. The female newborn earns 2 points for a heart rate >100 beats/minute, 1 point for slow and irregular respirations, 1 point for having some flexion of the extremities, 1 point for reflex irritability or grimace when a catheter is placed in her nose, and 1 point for her peripheral cyanosis or acrocyanosis, for a total Apgar score of 6 points. The male newborn earns 1 point for a heart rate <100 beats/minute, 1 point for slow and irregular respirations, 1 point for having some flexion of the extremities, 0 points for the absence of reflex irritability when a catheter is placed into his nose, and 0 points for his cyanosis, for a total Apgar score of 3 points.
12. The answer is A [IV.D.2 and V.A] The 100% oxygen test helps distinguish whether cyanosis is caused by cardiac or respiratory disease. When administered 100% oxygen, infants with primary lung pathology, such as neonatal pneumonia, meconium aspiration syndrome, transient tachypnea of the newborn or respiratory distress syndrome, have a very significant increase in PaO2 levels. In contrast, patients with cyanotic congenital heart disease would not be expected to have such a significant rise in their PaO2 level. For example, patients with Tetralogy of Fallot, a cyanotic congenital heart disease associated with reduced pulmonary blood flow, would not be expected to respond with any increase of significance in the PaO2 level when given 100% oxygen. Note that other cyanotic congenital heart diseases with normal or increased pulmonary blood flow, like truncus arteriosus, may have some increase in the PaO2 level, but nowhere near as much of an increase as that seen in infants with primary pulmonary disease.