Pediatric diseases
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Congenital anomalies - MCC of neonatal mortality Errors in morphogenesis Malformations Disruption Deformation Sequence Malformation syndrome Agenesis, aplasia, hypoplasia, & atresia
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Pediatric diseases
- 1. Pediatric Diseases – 1 med_students0 1
- 2. Congenital Anamolies Congenital anomalies - MCC of neonatal mortality Errors in morphogenesis Malformations Disruption Deformation Sequence Malformation syndrome Agenesis, aplasia, hypoplasia, & atresia 2
- 3. Congenital Anamolies Malformations Primary (intrinsic) errors of morphogenesis Multifactorial not a single gene or chromosomal defect Several patterns of presentations Congenital heart diseases Multiple malformations (organs/tissues) 3
- 4. Polydactyly Cleft lip with/without palate palate Trisomy 13 (malformation syndrome) Expired due to severe cardiac defect Stillbirth External dysmorphogenesis with sever internal anomalies Like brain & cardiac defects 4
- 5. Congenital Anamolies Disruptions Secondary destruction of organ or body region that was previously normal in development Extrinsic disturbance in morphogenesis Amniotic bands Rupture of amnion Formation of bands Not inheritable 5
- 6. Amniotic band – encircle the leg of fetus 6
- 7. Congenital Anamolies Deformations Extrinsic disturbance of development 2% of newborn to various degrees Localized or generalized compression of growing fetus by biomechanical forces Structural abnormalities MC Uterine constraint Maternal - first pregnancy, small uterus, malformed uterus, leiomyomas Fetal – multiple fetuses, oligohydramnios, abnormal fetal presentation 7
- 8. Congenital Anamolies Sequence Multiple congenital anomalies Secondary effect of a single localized aberration in organogenesis Initiating event – malformation, deformation, or disruption Example – Oligohydramnios (Potter) sequence 8
- 9. Oligohydramnios (Potter) sequence Causes: maternal, placental, or fetal abnormalities Chronic leakage of amniotic fluid (rupture of amnion) Uteroplacental insufficien – maternal hypertension or severe toxemia Renal agenesis Features: Flattented facial features, deformed foot (talipes equinovarus) 9
- 10. Congenital Anamolies Malformation Syndrome Several defects – not due to single localizing initiating error in morphogenesis Commonly arise from single causative condition (viral infection or a specific chromosomal abnormalities) That affects several organs simultaneously Agenesis - the complete absence of an organ Aplasia - incomplete development of an organ Hypoplasia - underdevelopment of an organ Atresia - absence of an opening – intestine, bile duct 10
- 11. Causes of Congenital Malformations Almost 50% - unrecognized reason Genetic Chromosomal aberration 10-15% All chromosomal syndromes Down syndrome & other trisomies (13 & 18), Turner syndrome, Klinefelter syndrome Arise during gametogenesis – not familial Mendelian inheritance 2-10% Single gene mutation Holoprosencephaly - MC developmental defect of the forebrain and midface in humans Polydactyly 11
- 12. Causes of Congenital Malformations Environmental Maternal/placental infection 2-3% Rubella, Toxoplasmosis, Syphilis, CMV & HIV Maternal diseases 6-8% DM, Phenylketonuria, Endocrinopathies Drugs and chemicals ~ 1% Alcohol, Folic acid antagonists, Androgens, Phenytoin, Thalidomide, Warfarin, 13-cis- Retinoic acid, and others Irradiation ~ 1% 12
- 13. Causes of Congenital Malformations Multifactorial 20-25% Interaction of environmental factors With 2 or more genes of small effect MC genetic cause of congenital malformations Importance of environmental factors - like dramatic decrease in neural tube defects with periconceptual intake of folic acid Unknown 40-60% 13
- 14. Pathogenesis Timing of prenatal insult embryonic period (first 9 weeks) early embryonic period (first 3 weeks) an injurious agent damages enough cells to cause death and abortion OR only a few cells allowing the embryo to recover without developing defects. Between 3rd and 9th weeks embryo is extremely susceptible to teratogenesis organs are being crafted out of the germ cell layers 14
- 15. Pathogenesis Timing of prenatal insult fetal period (after 9 weeks until birth) Significantly reduced susceptible to teratogenic agents Example: rubella infection first trimester - disruption of the development later pregnancy - viral infection causes tissue injury accompanied by inflammation VSD (teratogen) before 6 weeks of gestation ventricular septum closes at this time 15
- 16. Pathogenesis Genes that regulate morphogenesis Homeobox (HOX) gene: disruption regulates transcription of several other genes Example retinoic acid for severe acne - retinoic acid embryopathy, - CNS, cardiac, and craniofacial defects Na-valproate (anticonvulsant) 16
- 17. Perinatal Infections Transcervical (ascending infections) Most bacterial like α-hemolytic streptococcal Few viral like herpes simplex fetus – inhaling the infected amniotic fluid into the lungs or by passing through an infected birth canal during delivery inflammation of the placental membranes (chorioamnionitis) and the umbilical cord (funisitis) in severe cases - pneumonia to sepsis and meningitis 17
- 18. Perinatal Infections Transplacental infections TORCH toxoplasma, rubella, CMV, herpesvirus and any of the other (O) microbes like Treponema pallidum, Listeria etc evoke similar clinical & pathologic features early in gestation - growth restriction, mental retardation, cataracts, and congenital cardiac anomalies later in pregnancy - encephalitis, chorioretinitis, hepatosplenomegaly, pneumonia, and myocarditis 18
- 19. Perinatal Infections Transplacental infections HBV & HIV maternal-to-fetal transfusion at the time of delivery 19
- 20. Prematurity & Fetal Growth Retardation Prematurity - gestational age < 37 weeks the second MCC of neonatal mortality usually weigh less than normal (<2500 gm) immaturity of organ systems Major risk factors premature rupture of membranes; intrauterine infection (chorioamnionitis); structural abnormalities of the uterus, cervix, and placenta; and multiple gestation (e.g., twin pregnancy) 20
- 21. Conditions Associated with Prematurity Hyaline membrane disease (respiratory distress syndrome) Necrotizing enterocolitis Intraventricular and germinal matrix hemorrhage 21
- 22. Fetal Growth Restriction (FGR) 1/3 infants weigh less than 2500 gm - born at term Undergrown rather than immature small-for-gestational-age (SGA) infants - fetal growth restriction Causes: many cases the specific cause is unknown Fetal Maternal placental abnormalities 22
- 23. Causes of FGR Fetal factors: intrinsically reduce growth potential of the fetus despite an adequate supply of nutrients from the mother chromosomal abnormalities 17% congenital anomalies 66% (of fetuses with documented ultrasonographic malformations) fetal infection (TORCH) – common cause growth retardation is symmetric 23
- 24. Causes of FGR Placental causes: any factor that compromises the uteroplacental supply placenta previa (low implantation of the placenta) placental abruption (separation of placenta from the decidua by a retroplacental clot) placental infarction growth retardation is asymmetric 24
- 25. Causes of FGR Maternal factors: MCC of the growth deficit in SGA infants Growth retardation is asymmetric Causes: preeclampsia (toxemia of pregnancy)c chronic hypertension avoidable influences narcotic abuse, alcohol intake, and heavy cigarette smoking, teratogens (phenytoin), malnutrition (in particular, prolonged hypoglycemia) 25
- 26. Consequences of FGR Handicapped in perinatal period childhood adult life At increased risk for cerebral dysfunction learning disabilities sensory (i.e., visual, hearing) impairment 26
- 27. RESPIRATORY DISTRESS SYNDROME (RDS) OF THE NEWBORN Morbidity/Mortality: 24,000 infants are affected by RDS each year (current stats) little more than 1000 deaths (2002) more than 25,000 deaths each year (1960) 27
- 28. RESPIRATORY DISTRESS in NEWBORN Causes: MCC is RDS (HMD): formation of "membranes" in the peripheral air spaces of infants - fatal Other causes excessive sedation of the mother fetal head injury during delivery aspiration of blood or amniotic fluid intrauterine hypoxia - by coiling of the umbilical cord about the neck 28
- 29. Pathogenesis of RDS RDS - disease of premature infants infants born - < 28 weeks 60% between 32 & 36 weeks 15-20% after 37 weeks < 5% Other contributing influences maternal diabetes C-section before the onset of labor twin gestation 29
- 30. Pathogenesis of RDS Inability of the immature lung to synthesize sufficient surfactant Surfactant is a complex of surface-active phospholipids dipalmitoylphosphatidylcholine (lecithin) at least two groups of surfactant-associated proteins Synthesized by type II pneumocytes In healthy newborn first breath, rapidly coats the surface of alveoli reducing surface tension the pressure required to keep alveoli open 30
- 31. Lung deficient in surfactant alveoli tend to collapse relatively greater inspiratory effort required with each breath to open the alveoli infant rapidly tires from breathing generalized atelectasis sets in hypoxia causes sequence of events lead to epithelial and endothelial damage causing the formation of hyaline membranes 31
- 32. Hyaline membrane disease (RDS) alternating atelectasis and dilation of the alveoli eosinophilic thick hyaline membranes lining the dilated alveoli 32
- 33. Pathogenesis of RDS Surfactant synthesis is regulated by hormones Corticosteroids stimulate the formation of surfactant lipids and associated proteins intrauterine stress and fetal growth restriction increase corticosteroid release lower the risk of developing RDS Surfactant synthesis can be suppressed high blood levels of insulin in infants of diabetic mothers counteracts the effects of steroids Infants of diabetic mothers have a higher risk of developing RDS Labor is known to increase surfactant synthesis C-section before the onset of labor may increase the risk of RDS 33
- 34. Clinical Features of RDS Clinical course and prognosis for RDS vary dependent on the maturity birth weight of the infant promptness of institution of therapy Focused on prevention of RDS delaying labor until the fetal lung matures inducing maturation of the lungs in the fetus at risk prophylactic administration of exogenous surfactant at birth to extremely premature infants (<28 weeks) very beneficial uncommon for infants to die of acute RDS 34
- 35. Clinical Features of RDS Assessing the fetal lung immaturity pulmonary secretions are discharged into the amniotic fluid amniotic fluid phospholipids is a tool to estimate the level of surfactant in the alveolar lining Prognosis uncomplicated cases, recovery begins to occur within 3 or 4 days affected infants oxygen is required high concentration of ventilator-administered oxygen for prolonged periods retrolental fibroplasia (also called retinopathy of prematurity) in the eyes bronchopulmonary dysplasia (BPD). 35
- 36. Clinical Features of RDS Prognosis Infants who recover from RDS At increased risk for patent ductus arteriosus intraventricular hemorrhage necrotizing enterocolitis 36
- 37. Necrotizing Enterocolitis (NEC) MC in premature infants Inversely proportional to the gestational age Occurs in 1 of 10 very-low-birth-weight infants (<1500 gm) Causes controversial multifactorial Intestinal ischemia (pre-requisite) Other predisposing conditions bacterial colonization formula feeds 37
- 38. Necrotizing Enterocolitis Premature infants High perinatal morbidity and mortality Multi-factorial causes Predisposing factors: Intestinal ischemia Hypoperfusion Selective ↓ in blood flow to intestines Worsening mucosal injury in bowel due to: Bacterial colonization of gut Formula feeds
- 39. Necrotizing Enterocolitis Pathological Features Involves terminal ileum, cecum and right colon. Affected segment is distended, friable and congested OR frankly gangrenous. May show intestinal perforation + peritonitis Mucosal or transmural coagulative necrosis Ulceration Bacterial colonization Submucosal gas bubbles.
- 40. terminal ileum, cecum, and right colon (any part of the small or large intestine) involved segment is distended, friable, and congested, or may be frankly gangrenous intestinal perforation with accompanying peritonitis may be seen. microscopically - mucosal or transmural coagulative necrosis, ulceration, bacterial colonization, and submucosal gas bubbles 40
- 41. Clinical features of NEC Bloody stools Abdominal distention Circulatory collapse Abdominal radiographs gas within the intestinal wall (pneumatosis intestinalis) conservative management if detected early many cases (20% to 60%) require operative intervention resection of the necrotic segments of bowel 41
- 42. Necrotizing Enterocolitis Clinical Features and Management Bloody stools Abdominal distention Circulatory collapse Gas seen in intestinal wall (abdominal radiograph) Treatment: Surgery with resection of necrotic segments of bowel. Complications: Post-NEC strictures from fibrosis during healing.
- 43. Prognosis of NEC NEC - high perinatal mortality Infants who survive often develop post-NEC strictures from fibrosis caused by the healing process may present as intestinal obstruction 43
- 44. Hydrops Fetalis Generalized edema of fetus Due to progressive fluid buildup during IU growth; usually lethal. Causes: Turner Syndrome Trisomies 21, 13, 18 Cardiac anomalies, arrhythmias Twin-twin transfusion syndrome Fetal anemia Rh and ABO hemolysis Homozygous α-thalassemia, parvovirus B19 infection
- 45. Hydrops Fetalis Clinical Features Tissue ischemia Secondary myocardial dysfunction Circulatory failure Secondary liver failure Hypoalbuminemia ↓ed oncotic pressure Edema
- 46. Hydrops Fetalis Clinical Presentation HF due to chromosomal anomaly: Dysmorphic features Cardiac anomaly HF due to fetal anemia: Fetus and placenta are pale Hepatosplenomegaly (due to cardiac failure and congestion) Compensatory hyperplasia of erythroid precursors in BM Extramedullary hematopoiesis in liver, spleen, and possibly kidneys, lungs and heart. High # of immature RBC’s in blood (erythroblastosis fetalis) due to ed hematopoiesis.
- 47. Hydrops Fetalis Clinical Presentation HF due to parvovirus-associated anemia: Same as HF due to fetal anemia EXCEPTION: NO compensatory hyperplasia of erythroid precursors. HF due to Rh or ABO incompatibility: Also shows hyperbilirubinemia May cause kernicterus (CNS damage) Basal ganglia, brain stem and other brain tissue take up bilirubin which is toxic. Adults protected from kernicterus (BBB).
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- 51. Immune Hydrops Due to blood group incompatibility b/w mother and child Leads to Ab-induced hemolytic disease in newborn (immune hydrops) Occurs when paternally inherited RBC antigenic determinants are foreign to mother. MC antigens: Rh (specifically D) and ABO blood group antigens.
- 52. Immune Hydrops Pathogenesis Fetal RBC’s may reach maternal blood during 3rd trimester. Cytotrophoblast absent (no barrier). Fetomaternal bleed (during childbirth). Mother develops Ab’s to fetal RBC’s. Ab’s move thru placenta to fetus and cause hemolysis. Immune hemolysis → progressive anemia in fetus + IU cardiac failure + edema
- 53. Immune Hydrops (contd). Fetal RBC’s that reach maternal blood are coated with isohemagglutinins and removed from maternal blood. Ab response depends on dose of immunizing Ag Hemolytic disease only with major transplacental bleed. IgG can cross placenta (NOT IgM). 1st exposure to Rh antigen: IgM formed. Rh disease uncommon Later pregancies: IgG response → Rh disease
- 54. Immune Hydrops Control Rh Hemolysis: Rh-neg. mothers given anti-D globulin after delivering an Rh-pos. baby. Anti-D Ab’s mask antigenic sites on fetal RBC’s in maternal blood. Mother avoids long-lasting sensitization to Rh-antigens.
- 55. Immune Hydrops – ABO Incompatibility MCC of immune hemolytic disease in newborn. ABO incompatibility occurs in 20-25% of pregnancies, only few infants develop hemolysis; milder disease. Occurs in Group A or B infants born to Group O mothers. Normally, anti-A and anti-B isohemagglutinins are IgM type (can not cross placenta). In some cases, they are IgG types. 1st born affected.
- 56. Nonimmune Hydrops Causes: CVS defects Chromosomal anomalies (Turner Syndrome, trisomies 21 and 18). Fetal anemia: Homozygous α thalassemia Parvovirus infection 19 Virus enters erythroid precursors (normoblasts), replicates. Leads to erthryocyte maturation arrest + aplastic anemia. Inclusions seen in circulating and marrow erythroid precursors.
- 57. Infant with nonimmune hydrops fetalis Islands of extramedullary hematopoesis Mature hepatocytes 57
- 58. Hydrops Fetalis Clinical Course Stillborn infants or dead in first few days or recover completely (depends on severity). Amniocentesis shows high bilirubin. Human antiglobulin test (Coombs test) is + on fetal cord blod if RBCs are coated with maternal Ab. Treatment: Antenatal exchange transfusion Phototherapy (converts bilirubin to readily excreted dipyrroles). Administering anti-D globulins to mother can prevent Rh erythroblastosis.
- 59. Sudden Infant Death Syndrome (SIDS) Sudden and unexpected death of an infant <1 year of age COD unknown after complete autopsy, examination of scene of death, and case history review. 3000 deaths due to SIDS in US each year Leading COD in 1st year of life in developed countries 90% of cases: infant <6 months of age
- 60. SIDS (contd.) Infant usually dies while asleep, pseudonyms - crib death or cot death SIDS in an earlier sibling is associated with a 5 fold relative risk of recurrence 3rd MCC of death in infancy congenital anomalies (1st) prematurity and low birth weight (2nd)
- 61. Pathogenesis of SIDS Delayed development of arousal and cardiorespiratory control (hypothesis) arcuate nucleus located in the ventral medullary surface - body's "arousal" response to noxious stimuli such as hypercarbia, hypoxia, and thermal stress encountered during sleep The prone position during sleep predisposes an infant to hypoxia hypercarbia thermal stress decreased arousal responsiveness 61
- 62. Diagnosis and Prevention Incosistent anatomical features multiple petechiae vascular engorgement with/without pulmonary edema hypoplasia of the arcuate nucleus or a subtle decrease in brain stem neuronal populations Presence of any other condition would exclude a diagnosis of SIDS Putting baby to sleep in supine position ↓ ed incidence of SIDS by 40%. 62
- 63. Sudden Unexpected Death Causes of Sudden “Unexpected” Death MC COD is infections - viral myocarditis or bronchopneumoniases 2nd - unsuspected congenital anomaly 3rd - genetic aberration 63
Editor's Notes
- Human malformations can range in severity from the incidental to the lethal. A, Polydactyly (one or more extra digits) and syndactyly (fusion of digits), have little functional consequence when they occur in isolation. B, Similarly, cleft lip, with or without associated cleft palate, is compatible with life when it occurs as an isolated anomaly; in this case, however, the child had an underlying malformation syndrome (trisomy 13) and expired because of severe cardiac defects. C, Stillbirth representing a severe and essentially lethal malformation, in which the midface structures are fused or ill-formed; in almost all cases, this degree of external dysmorphogenesis is associated with severe internal anomalies such as maldevelopment of the brain and cardiac defects.
- No risk of recurrence in future pregnancies
- Disruptions occur in a normally developing organ because of an extrinsic abnormality that interferes with normal morphogenesis. Amniotic bands are a frequent cause of disruptions. In the illustrated example, note the placenta at the right of the diagram and the band of amnion extending from the top portion of the amniotic sac to encircle the leg of the fetus.
- Between the 35th and 38th weeks of gestation, rapid increase in the size of the fetus outpaces the growth of the uterus, and the relative amount of amniotic fluid (which normally acts as a cushion) also decreases. Thus, even the normal fetus is subjected to some form of uterine constraint.
- Pathogenesis of the oligohydramnios (Potter) sequence. B, Infant with oligohydramnios (Potter) sequence. Note flattened facial features and deformed foot (talipes equinovarus). Renal agenesis in the fetus also causes oligohydramnios because fetal urine is a major constituent of amniotic fluid.
- The fetal period that follows organogenesis is marked chiefly by further growth and maturation of the organs, with greatly reduced susceptibility to teratogenic agents. Instead, the fetus is susceptible to growth retardation or injury to already-formed organs. It is therefore possible for the same teratogenic agent to produce different effects if exposure occurs at different times of gestation. For example, viral infections such as rubella produce disruption of the developmental program in the first trimester, but later during pregnancy, the result of viral infection is usually tissue injury accompanied by inflammation. The approximate timing of the insult can be gauged from the pattern of disruption that is present at birth or in the abortus. Thus, a ventricular septal defect resulting from exposure to a teratogen must have occurred before 6 weeks of gestation, because the ventricular septum closes at this time.
- Infants born to mothers treated with retinoic acid for severe acne develop retinoic acid embryopathy, including CNS, cardiac, and craniofacial defects
- Most parasitic (e.g., toxoplasma, malaria) and viral infections, and a few bacterial infections (i.e., Listeria, Treponema) demonstrate this mode of hematogenous transmission.
- Most parasitic (e.g., toxoplasma, malaria) and viral infections, and a few bacterial infections (i.e., Listeria, Treponema) demonstrate this mode of hematogenous transmission.
- When the causation is intrinsic to the fetus, growth retardation is symmetric (i.e., affects all organ systems equally).
- With placental (and maternal) causes of growth restriction, the growth retardation is asymmetric (i.e., the brain is spared relative to visceral organs such as the liver).
- With placental (and maternal) causes of growth restriction, the growth retardation is asymmetric (i.e., the brain is spared relative to visceral organs such as the liver).
- The growth-restricted infant is handicapped not only in the perinatal period but also in childhood and adult life. These individuals are at increased risk for cerebral dysfunction, learning disabilities, and sensory (i.e., visual, hearing) impairment.
- Pathophysiology of respiratory distress syndrome
- Hyaline membrane disease (H&E stain). There is alternating atelectasis and dilation of the alveoli. Note the eosinophilic thick hyaline membranes lining the dilated alveoli. The lungs in RDS infants are of normal size but are heavy and relatively airless. They have a mottled purple color, and microscopically the tissue appears solid, with poorly developed, generally collapsed (atelectatic) alveoli. If the infant dies within the first several hours of life, only necrotic cellular debris is present in the terminal bronchioles and alveolar ducts. Later in the course, characteristic eosinophilic hyaline membranes line the respiratory bronchioles, alveolar ducts, and random alveoli. These "membranes" contain necrotic epithelial cells admixed with extravasated plasma proteins. There is a remarkable paucity of neutrophilic inflammatory reaction associated with these membranes. The lesions of hyaline membrane disease are never seen in stillborn infants or in live-born infants who die within a few hours of birth. If the infant dies after several days, evidence of reparative changes, including proliferation of type II pneumocytes and interstitial fibrosis, is seen
- Surfactant synthesis is regulated by hormones. Corticosteroids stimulate the formation of surfactant lipids and associated proteins. Therefore, conditions associated with intrauterine stress and fetal growth restriction that increase corticosteroid release lower the risk of developing RDS. Surfactant synthesis can be suppressed by the compensatory high blood levels of insulin in infants of diabetic mothers, which counteracts the effects of steroids. This may explain, in part, why infants of diabetic mothers have a higher risk of developing RDS. Labor is known to increase surfactant synthesis; hence, cesarean section before the onset of labor may increase the risk of RDS.
- The classic clinical presentation before the era of treatment with exogenous surfactant was described earlier. Currently, the actual clinical course and prognosis for neonatal RDS vary, dependent on the maturity and birth weight of the infant and the promptness of institution of therapy. A major thrust in the control of RDS focuses on prevention, either by delaying labor until the fetal lung reaches maturity or by inducing maturation of the lung in the fetus at risk. Prophylactic administration of exogenous surfactant at birth to extremely premature infants (gestational age <28 weeks) has been shown to be very beneficial, such that it is now uncommon for infants to die of acute RDS.
- Critical to these objectives is the ability to assess fetal lung maturity accurately. Because pulmonary secretions are discharged into the amniotic fluid, analysis of amniotic fluid phospholipids provides a good estimate of the level of surfactant in the alveolar lining. In uncomplicated cases, recovery begins to occur within 3 or 4 days. In affected infants oxygen is required. However, high concentration of ventilator-administered oxygen for prolonged periods is associated with two well-known complications: retrolental fibroplasia (also called retinopathy of prematurity) in the eyes, and bronchopulmonary dysplasia (BPD). Fortunately, both complications are now significantly less common as a result of gentler ventilation techniques, antenatal glucocorticoid therapy, and prophylactic surfactant treatments. Retinopathy of prematurity has a two-phase pathogenesis. During the hyperoxic phase of RDS therapy (phase I), expression of the pro-angiogenic vascular endothelial growth factor (VEGF) is markedly decreased, causing endothelial cell apoptosis; VEGF levels rebound after return to relatively hypoxic room air ventilation (phase II), inducing retinal vessel proliferation (neovascularization) characteristic of the lesions in the retina. The major abnormality in BPD is a decrease in the number of mature alveoli, referred to as alveolar hypoplasia. Thus, the current view is that BPD is most likely caused by an arrested development of alveolar septation at the so-called saccular stage of development. The levels of a variety of proinflammatory cytokines (TNF, macrophage inflammatory protein-1 and IL-8) are increased in the alveoli of infants who develop BPD, suggesting a role for these cytokines in arresting pulmonary development.
- Infants who recover from RDS are also at increased risk for developing a variety of other complications associated with preterm birth; most important among these are patent ductus arteriosus, intraventricular hemorrhage, and necrotizing enterocolitis. Thus, although technologic advances help save the lives of many infants with RDS, it also brings to the surface the exquisite fragility of the immature neonate.
- The cause of NEC is controversial, but in all likelihood it is multifactorial. Intestinal ischemia is a prerequisite and may result from either generalized hypoperfusion or selective reduction of blood flow to the intestines to divert oxygen to vital organs such as the brain. Other predisposing conditions include bacterial colonization of the gut and administration of formula feeds, both of which aggravate mucosal injury in the immature bowel.
- Necrotizing enterocolitis. A, Postmortem examination in a severe case shows that the entire small bowel is markedly distended with a perilously thin wall (usually this implies impending perforation). B, The congested portion of the ileum corresponds to areas of hemorrhagic infarction and transmural necrosis seen on microscopy. Submucosal gas bubbles (pneumatosis intestinalis) can be seen in several areas (arrows). NEC typically involves the terminal ileum, cecum, and right colon, although any part of the small or large intestine may be involved. The involved segment is distended, friable, and congested, or it can be frankly gangrenous; intestinal perforation with accompanying peritonitis may be seen. Microscopically, mucosal or transmural coagulative necrosis, ulceration, bacterial colonization, and submucosal gas bubbles are all features associated with NEC. Reparative changes, such as granulation tissue and fibrosis, may be seen shortly after the acute episode.
- Hydrops fetalis. A, Generalized accumulation of fluid in the fetus. B, Fluid accumulation particularly prominent in the soft tissues of the neck. This condition has been termed cystic hygroma. Cystic hygromas are characteristically seen with, but not limited to, constitutional chromosomal anomalies such as 45,X karyotypes.
- Bone marrow from an infant infected with parvovirus B19. The arrows point to two erythroid precursors with large homogeneous intranuclear inclusions and a surrounding peripheral rim of residual chromatin.
- Kernicterus. Severe hyperbilirubinemia in the neonatal period-for example, secondary to immune hydrolysis-results in deposition of bilirubin pigment (arrows) in the brain parenchyma. This occurs because the blood-brain barrier is less well developed in the neonatal period than it is in adulthood. Infants who survive develop long-term neurologic sequelae.
- With control of Rh hemolysis, ABO incomaptibility is MCC of immune hemolytic disease in newborn.
- Nonimmune hydrops due to structural cardiac anomalies in most cases. Turner Syndrome due to abnormality of lymphatic drainage from neck causing postnuchal fluid build-up (cystic hygroma).
- Numerous islands of extramedullary hematopoiesis (small blue cells) are scattered among mature hepatocytes in this infant with nonimmune hydrops fetalis.