Means “small for gestational age.”  Three causes:

1. Fetal:  chromosomal disorders (trisomy 13, 18, 21, etc.), congenital anomalies, and congenital infections (CMV, rubella, syphilis, toxo).
2. Placental:  abruptio placenta, placenta previa, thrombosis, infarctions, infections, confined placental mosaicism.
3. Maternal (most common):  decreased blood flow to the placenta.  Toxemia of pregnancy, chronic hypertension, poor nutrition, narcotic abuse, EtOH, tobacco, Dilantin.

Born at 37-38 weeks or earlier.

Structural and functional immaturity of organ systems is a major cause of morbidity and mortality in preterm infants, esp. those who are small for gestational age.

q       Lungs:  Thick-walled alveolar septa, connective tissue separating alveoli from capillaries, proteinaceous precipitate in alveolar spaces.  Development of alveoli continues after birth up until about age 8.

q       Kidneys:  Deep glomeruli are well formed, but glomeruli in subcapsular zone are still primitive.  Function is usually adequate, even in a preemee.

q       Brain:  Smooth surface (lissencephalic), cell migration and myelination is incomplete, poor demarcation of white and gray matter structures, vital brain centers developed enough to sustain life, but hemostasis (temperature, respiration) is imperfect.

q       Liver:  Presence of extramedullary hematopoiesis.  Many enzymes are not well developed, including those responsible for biliary excretion, explaining jaundice in premature infants.

A measure of physiologic condition and responsiveness of the newborn.  It is calculated at 1 and 5 minutes of life based on heart rate, respiratory effort, muscle tone, response to moxious stimulus, and ksin color, each scored 0, 1, or 2.  The higher the score, the better the outlook.

Vary with gestational age, most commonly involving the head, skeletal system, liver, adrenal glands, and peripheral nerves.

q       Intracranial hemorrhage:  Prolonged labor, hypoxia, hemorrhagic disorders, vascular anomalies.  Can cause herniation of medulla into foramen magnum, depressing the function of vital centers.

q       Caput succedaneum:  Accumulation of interstitial fluid in soft tissue of the scalp.  If associated with blood, it is called a cephalohematoma.  Clinically unimportant unless associated with an underlying skull fracture.

Amniotic bands, denoting rupture of the amnion resulting in the formation of “bands” that may compress, attach to, or encircle parts of the developing fetus, are the classic example of a disruption. 

Decreased amniotic fluid, resulting from renal agenesis or an amniotic leak, result in the compression of the fetus and a classic phenotype in the newborn infant, including flattened facies and positional abnormalities of the hands and feet.  This is a sequence, a series of multiple congenital anomalies arising from a single localized aberration in organogenesis.

1. Genetic causes:
   1. Karyotypic abnormalities:  present in 10-15% of live-born infants with congenital malformations (trisomy 21, Klinefelter, 47, XXY, Turner syndrome 45, XO, and trisomy 13).  Defect in gametogenesis, so these are not familial.
   2. Single gene mutations:  uncommon but follow Mendelian patterns of inheritance.
   3. Multifactorial.
2. Environmental causes:
   1. CMV: affects CNS, resulting in mental retardation, microcephaly and deafness.
   2. Rubella:  Before 16 weeks’ gestation, causes cataracts, heart defects, and deafness.
   3. Herpes simplex
   4. Drugs and chemicals:  Less than 1% of malformations.  Thalidomide, folate antagonists, androgenic hormones, alcohol, anticonvulsants, Accutane (13-cis retinoic acid).
   5. Radiation:  Microcephaly, blindness, skull defects, spina bidida.

1. Transcervical (ascending) infections:
   1. Fetus acquires infection by “inhaling” infected amniotic fluid.
   2. Herpes simplex
   3. Most bacterial infections of female reproductive tract
   4. Chorioamniotitis = inflammation of placental membrane.
2. Transplacental (hematologic) infections:
   1. Most parasitic infections
   2. Most viral infections
   3. A few bacterial infections (Listeria, treponema)
   4. Parvovirus B19 causes fifth disease in mother and hydrops fetalis and spontaneous abortion in the fetus.
   5. TORCH:  toxo, rubella, CMV, herpes virus, other bacteria

                                                               i.      Evoke similar clinical manifestations

                                                              ii.      Growth and mental retardation

                                                            iii.      Cataracts

                                                            iv.      Congenital cardiac anomalies

                                                             v.      Bone defects

6. “Early” (e.g., E. coli”) sepsis versus “late” (e.g., Listeria, Candida) infections.

1. Aspiration of blood, amniotic fluid during birth
2. Brain injury with failure of respiratory centers
3. Asphyxiating coils of umbilical cord around neck
4. Excessive maternal sedation
5. Idiopathic = hyaline membrane disease

Lungs are solid, airless, and reddish purple. 

Infant is almost always preterm.  There is a strong association with diabetes in the mother and delivery by Cesarean section.  The fundamental defect is a deficiency in pulmonary surfactant, consisting of dipalmotoyl phosphatidylcholine.  It is synthesized by type II alveolar cells most abundantly after the 35^th week of gestation.  Microscopy reveals alternating atelectasis and dilatation of alveoli, and many airspaces are filled with fluid and lined by thick hyaline membranes.

Fibrosing condition brought about by sustained mechanical ventilation.  BPD is characterized by persistence of respiratory distress for up to 3 to 6 months.  Pathollgically, the larger airways  show epithelial hyperplasia and squamous metaplasia.  If oxygen toxicity can be avoided and the infant can be kept alive for 3 to 4 days, recovery can be anticipated without permanent sequelae.

AKA, erythroblastosis fetalis.  This occurs as a consequence of blood group incompatibility between mother and fetus (inherited D antigen of the Rh group from the father).  The first exposure elicits production of IgM antibodies and the mother is now sensitized.  If she carries another Rh+ fetus, maternal IgG antibodies will cross the placenta and cause fetal blood cell lysis.  Kernicterus can cause damage to the brain as a result of unconjugated bilirubin molecules attaching to lipids the brain.  Anemia and generalized edema (hydrops fetalis) can also result.

Homozygotes for one of several mutations for phenylalanine hydroxylase cannot break phenylalanine down, resulting in increased levels of it in the blood. Infants appear normal at birth, but mental retardation can result if the PKU is not diagnosed.

Phenylalanine and metabolites are teratogenic, causing normal infants born to mothers with PKU to have offspring that are microcephalic and mentally retarded (maternal PKU).

Dietary lactose is split into galactose and glucose in the intestinal mucosa by the enzyme lactase.  Galactose is then converted to glucose by three additional enzymes.  A deficiency is one of those enzymes can result in buildup of a galactose metabolite in the blood.  The most common enzyme deficiency is galactose-1 phosphate uridyl transferase (GALT) and the product that accumulates is galactose-1-phosphate.

Infants fail to thrive at birth and develop vomiting and diarrhea within a few days of milk ingestion.  Liver, eyes, and brain are most severly affected.  Hepatomegaly and fatty change in the liver can also result.  Avoidance of galactose in the first two years of life can protect these organ systems.  Adults with galactosemia often have a speech disorder and gonadal failure.

1 in 2000 live births. 

q       Etiology:  cystic fibrosis gene on chromosome 7 encodes CFTR, a chloride channel,  important in epithelial chloride transport.

o        Sweat gland ducts cannot reabsorb chloride, resulting in a higher-than-normal chloride concentration in sweat.

q       Morphology: 

o        Pancreas:  Atrophy of exocrine glands and ducts, leaving only the islets and a fibrofatty stroma.

o        Intestine:  Thick, viscous plugs (meconium ileus).

o        Liver:  Plugging of bile canaliculi leading to cirrhosis.

o        Salivary glands:  squamous metaplasia of ductal epithelia.

o        Lungs:  Hyperplasia of mucus-secreting cells, infections.

o        Epididymis and vas deferens:   thick secretions.

q       Clinical course: 

o        Malabsorption:  foul-smelling stools, abdominal distension, deficiencies in fat-soluble vitamins.

o        Persistent pulmonary infections

o        Median life expectancy is 26 years.

o        Gene therapy in the future

Defined as “sudden death of an infant under 1 year of age which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and a review of the clinical history.” 

Most SIDS deaths occur between months 2 and 4 of life.  Usually evidence of a minor upper respiratory tract infection.  Potential risk factors include sleeping in a prone position, prematurity, low birth weight, young or unmarried mother, low socioeconomic status.

The hypothalamic centers for breathing may not be mature.  Autopsy findings can include astrogliosis of the brain stem, thymic and epicardial petichiae, and evidence of a mild respiratory tract infection.

Most common tumor of infancy, rarely become malignant.  They  usually appear on the face and scalp, commonly spontaneously regress.  May represent one facet of a hereditary disorder, Hippel-Lindau disease.

Malignant tumors that arise in adrenal medulla or various ganglia in children under 5 years of age.  Made up of sheets of small, round blue cells within a neurofibrillary background and the presence of pseudorosettes.  A worse prognosis is associated with a near-diploid or near-tetraploid overall DNA content, deletions of the distal short arm of chromosome 1, and amplification of the n-myc oncogene.  A better prognosis is associated with expression of Trk A.

A malignant tumor of the kidney, but survival rate is at 90%.  Can be associated with malformation syndromes:

1. WAGR:  Wilms’ tumor, aniridia, genital anomalies, and mental retardation. 
2. Denys-Drash syndrome:  Gonadal dysgenesis and renal failure.
3. Beckwith-Wiedemann syndrome:  Enlargement of body organs, hemihypertrophy, renal medullary cysts, adrenal cytomegaly.

Triphasic histologic features of Wilms’ tumor include:  (1) blastema, (2) immature stroma, and (3) tubules – an attempt to recapitulate nephrogenesis.