Discussion of Specific Conditions Encountered During Infant and Child Development PDF

## Discussion of Specific Conditions Encountered During Infant and Child Development ### Congenital Anomalies - Anomalies present at birth. - Some may not become clinically apparent until years later. - **Congenital** does not imply or exclude a genetic basis. - Approximately 120,000 babies are born...

## Discussion of Specific Conditions Encountered During Infant and Child Development ### Congenital Anomalies - Anomalies present at birth. - Some may not become clinically apparent until years later. - **Congenital** does not imply or exclude a genetic basis. - Approximately 120,000 babies are born with a birth defect each year in the United States (1 in 33). - Important cause of infant mortality. - Significant source of illness, disability, and death throughout the early years of life. ### Terms Used to Describe Errors in Morphogenesis #### Malformations - Primary errors of morphogenesis. - Intrinsically abnormal developmental process. - Usually multifactorial. - May manifest in multiple patterns: - Single body systems may be involved. - Multiple malformations involving many organs and tissues may coexist. #### Disruptions - Result from secondary destruction of an organ or body region that was previously normal in development. - Stem from an extrinsic disturbance in morphogenesis. - Amniotic bands are a classic example. - Rupture of the amniotic membrane leads to bands that encircle, compress, or attach to parts of the developing fetus. - Not heritable. #### Deformations - Represent an extrinsic disturbance of development rather than an intrinsic error of morphogenesis. - Common, affecting approximately 2% of newborn infants. - Caused by localized or generalized compression of the growing fetus by abnormal biomechanical forces. - Most common cause: uterine constraint. - Between weeks 35 and 38 of gestation, the rapid increase in size of the fetus outpaces the growth of the uterus. - Decreases in amniotic fluid lead to increased constraint. ### Terms Used to Describe Errors in Morphogenesis #### Sequence - Multiple congenital anomalies that result from the secondary effects of a single localized aberration in organogenesis. - Initiating event may be a malformation, deformation, or disruption. - **Oligohydramnios (Potter) sequence** is an excellent example: - Decreased amniotic fluid may be due to: - Rupture of the amniotic membrane. - Uteroplacental insufficiency. - Renal agenesis in the fetus. - Classic phenotype of the newborn: flattened face, positional abnormalities of the hands and feet, and hip dislocation. - Complicated by chest wall and lung growth compromise. #### Malformation Syndrome - Several defects that cannot be explained on the basis of a single localizing initiating error in morphogenesis. - Often arise from a single causative condition (e.g. viral infection or a specific chromosomal abnormality) that simultaneously affects several tissues. #### Organ-Specific Malformations - **Agenesis:** complete absence of an organ - **Aplasia and Hypoplasia:** incomplete development and underdevelopment, respectively - **Atresia:** absence of an opening ### Etiology - **Genetic:** - Chromosomal aberrations - Mendelian inheritance - **Environmental:** - Maternal/placental infections - Maternal disease states - Drugs and chemicals - Irradiation - **Multifactorial:** - Unknown ### Pathogenesis - **Timing of the prenatal teratogenic insult:** - **Embryonic period (first 9 weeks):** injury may damage only a few cells and allow for recovery or cause death and abortion. - **Fetal period (weeks 9 to birth):** embryo is extremely susceptible to teratogenesis, with peak sensitivity between weeks 4 and 5. - **Complex interplay between environmental insults and intrinsic genetic defects:** - **Valproic acid:** antiepileptic drug that disrupts expression of HOX proteins, resulting in anomalies in limbs, vertebrae, and craniofacial structures. - **Vitamin A (retinol):** essential for normal development and differentiation. - Deficiency can result in a constellation of malformations. - Excessive exposure can also be teratogenic. ### Perinatal Infections - **Transcervical (ascending):** microbial spread from the cervicovaginal canal. - Occurs in utero or during birth. - Common cause of preterm birth. - **Transplacental (hematogenous):** organism crosses the placenta via the chorionic villi. - Can occur at any time. ### Prematurity and Fetal Growth Restriction #### Prematurity - Gestational age less than 37 weeks. - Second most common cause of neonatal mortality. - Infants born before completion of gestation weigh less than normal (<2500 gm). - Major risk factors: - Preterm premature rupture of membranes (PPROM) and premature rupture of membranes (PROM). - Intrauterine infection. - Uterine, cervical, and placental structural abnormalities. - Complications: - Neonatal respiratory distress syndrome. - Necrotizing enterocolitis. - Sepsis. - Intraventricular and germinal matrix hemorrhage. #### Fetal Growth Restriction - Infants weigh less than 2500 gm but are born at term. - Causes: - **Maternal:** - Vascular diseases (e.g., preeclampsia, chronic hypertension). - Hypercoagulability. - Narcotic use, alcohol intake, heavy cigarette smoking. - Maternal malnutrition. - **Fetal:** - Chromosomal disorders. - Congenital anomalies. - Congenital infections. - **Placental:** - Placenta previa. - Placental abruption. - Placental infarction. ### Neonatal Respiratory Distress Syndrome (RDS) - Most common cause of respiratory insufficiency in the newborn. - Primarily a disorder of premature infants. - Fundamental defect: inability of the immature lung to synthesize sufficient surfactant. - Surfactant: complex of surface-active phospholipids that reduces surface tension in the alveoli, making it easier to breathe. - Deficiency leads to collapse of the alveoli, requiring increased effort to breathe. - Rapidly tires the infant, resulting in atelectasis, hypoxia, and epithelial and endothelial damage. - Hormones regulate surfactant synthesis: - Corticosteroids stimulate production. - Insulin suppresses production. - Labor stimulates surfactant release. - Morphology: - Lungs are of normal size but heavy and airless with a mottled purple color. - Microscopic examination reveals poorly developed and generally collapsed alveoli. - Hyaline membranes line the respiratory bronchioles, alveolar ducts, and alveoli. - Clinical Features: - Classic presentation prior to surfactant treatment included respiratory distress, tachypnea, and cyanosis. - Treatment focuses on prevention (delayed labor until the fetal lung reaches maturity or inducing maturation with antenatal steroids) and prompt therapy. - Prognosis: - Improved due to the development of exogenous surfactant. - Uncomplicated cases: recovery begins within 3 or 4 days. ### Necrotizing Enterocolitis (NEC) - Most commonly occurs in premature infants. - Incidence is inversely proportional to the gestational age. - Pathogenesis: - Immaturity of the intestinal mucosal barrier and immune system. - Alterations in the gut microbiome. - Exaggerated inflammatory host response. - Morphology: - Typically involves the terminal ileum, cecum, and right colon. - Intestinal segment is distended, friable, and congested. - May become gangrenous, leading to perforation and peritonitis. - Clinical Features: - Bloody stools, abdominal distention, and circulatory instability. - Abdominal radiographs often demonstrate gas within the intestinal wall (pneumatosis intestinalis). - Management: - Early detection allows for conservative management. - More severe cases require surgery. - High perinatal mortality rate for those who survive, often developing post-NEC strictures. ### Sudden Infant Death Syndrome (SIDS) - Sudden death of an infant under 1 year of age that remains unexplained after a thorough investigation. - Leading cause of death between 1 month and 1 year in U.S. infants. - Factors associated with increased risk: - **Parental:** - Maternal cigarette smoking. - Paternal drug use. - Short intergestational intervals. - Low socioeconomic status. - **Infant:** - Brain stem abnormalities. - Prematurity. - Male sex. - Product of a multiple birth. - **Environmental:** - Prone or side sleep position. - Sleeping on a soft surface. - Hyperthermia. - Pathogenesis: - **Vulnerable infant:** - Delayed development of cardiorespiratory control. - May be specific to the infant or the parent(s). - **Exogenous stressors:** - Prone sleeping. - Soft surfaces. - Thermal stress. - **Prone sleeping:** - Increases infants' vulnerability to hypoxia, hypercarbia, and thermal stress. - Decreases arousal responsiveness. - **Postmortem findings:** - Often reveal an unsuspected cause of death. - Multiple petechiae. - Lung congestion. - Vascular engorgement. - Brain stem abnormalities (e.g., hypoplasia of the arcuate nucleus). ### Fetal Hydrops - Accumulation of edema fluid in at least two serous cavities combined with subcutaneous edema during intrauterine growth. - Causes: - **Immune hydrops:** - Caused by blood group incompatibility between mother and fetus. - Most common cause: Rh incompatibility. - Fetal red cells reach the maternal circulation during the last trimester or during birth. - Mother becomes sensitized to the foreign antigen and produces anti-Rh IgG antibodies. - Antibodies cross the placenta and cause red cell destruction. - Secondary effects of hemolysis include tissue ischemia, intrauterine cardiac failure, and peripheral edema. - ABO incompatibility can also cause hemolysis. - **Nonimmune hydrops:** - Structural cardiovascular defects. - Chromosomal anomalies. - Fetal anemia. - Parvovirus B19 infection. - **Morphology:** - Generalized edema of the fetus (hydrops fetalis) or more localized edema (e.g., pleural and peritoneal effusions, cystic hygroma). - Findings vary depending on the severity and underlying etiology. - Most severe: hydrops fetalis. - May be stillborn, die within a few days, or recover completely. - Often have dysmorphic features, suggesting underlying constitutional chromosomal abnormalities. - Hemolysis due to Rh or ABO incompatibility: - Liver and spleen are enlarged. - Bone marrow shows compensatory hyperplasia of erythroid precursors, except in cases of parvovirus-associated red cell aplasia. - CNS may be damaged when hyperbilirubinemia is marked. ### Tumors and Tumorlike Lesions of Infancy and Childhood #### Benign Neoplasms - Hemangioma: most common neoplasm of infancy. - Cavernous and capillary hemangiomas. - Typically located on the skin. - May spontaneously regress. - Lymphangioma: lymphatic counterpart of hemangioma. - Cystic and cavernous spaces lined by endothelial cells. - Often encountered in deeper regions of the neck, axilla, mediastinum, and retroperitoneum. - May enlarge after birth and encroach on mediastinal structures or nerve trunks. - Teratoma: neoplasms that include tissues derived from all three germ cell layers: ectoderm, endoderm, and mesoderm. - Mature teratomas: benign, well-differentiated cystic lesions. - Immature teratomas: lesions of indeterminate potential. - Malignant teratomas: unequivocally malignant tumors. - Most common teratomas of childhood: sacrococcygeal teratomas. #### Malignant Neoplasms - Most common in the hematopoietic system, nervous system, and soft tissues. - Differences from malignancies in adults: - Frequent demonstration of a close relationship between abnormal development and tumor induction. - Prevalence of germline mutations that predispose to cancer. - Tendency of fetal and neonatal malignancies to regress spontaneously or undergo differentiation into mature elements. - Improved survival or cure rate. - Often exhibit a primitive microscopic appearance. - Frequently exhibit features of organogenesis. #### Types of Childhood Tumors - **Neuroblastoma:** - Most common solid malignancy of childhood. - Arises from primordial neural crest cells that populate sympathetic ganglia and adrenal medulla. - Demonstrates spontaneous regression and spontaneous or therapy-induced maturation. - Germline mutations in the ALK基因have been linked to the familial predisposition to neuroblastoma. - Somatic gain-of-function ALK mutations are also observed in 8% to 10% of sporadic neuroblastomas. - Clinical trials using inhibitors that target the mutated ALK tyrosine kinase are underway. - **Retinoblastoma:** - Most common primary intraocular malignancy of children. - Approximately 40% are associated with a germline mutation in the RB基因and are therefore heritable. - **Wilms tumor (nephroblastoma):** - Most common primary tumor of the kidney in children. - Occurs between 2 and 5 years of age. - Increased risk with WAGR syndrome, Denys-Drash syndrome, and Beckwith-Wiedemann syndrome. - Features: - Relationship between congenital malformation and increased risk of tumors. - Histologic similarity between the tumor and the developing organ. - Remarkable success in treatment. - Groups of congenital malformations associated with an increased risk: - **WAGR syndrome:** Wilms tumor, aniridia, genital abnormalities, and mental retardation. - **Denys-Drash syndrome:** gonadal dysgenesis and early onset nephropathy. - **Beckwith-Wiedemann syndrome:** enlargement of individual body organs or entire body segments. #### Tumorlike Lesions - **Heterotopia:** microscopically normal cells or tissues present in abnormal locations. - **Hamartoma:** excessive but focal overgrowth of cells and tissues native to the organ in which it occurs.