3 leading causes of death in the first 12 months of lie
1. congenital anomalies 2. d/o related to prematurity and low birth weight 3. SIDS
Definition of a malformation
primary error of morphogenesis in which there is an intrinsically abnormal developmental process Multiple genetic loci
Definition of a disruption
secondary destruction of an organ or body region that was previously normal in development-->extrinsic disturbance in morphogenesis
Classic example of a disruption
amniotic bands--rupture of amnion with resultant formation of "bands" that encircle, compress, or attach to parts of the developing fetus
Definition of a deformation
extrinsic disturbance of development due to localized or generalized compression of fetus by abnormal biomechanical forces
Most common underlying factor for deformation
uterine constraint: rapid increase in size of size outpaces growth of uterus, which relative amount of amniotic fluid decreasing as well. Usually occurs between 35 and 38 weeks
Maternal factors increasing likelihood of deformation
first pregnancy, small or malformed uterus, and leiomyomas
Fetal or placental factors increasing likelihood of deformation
oligohydramnios, multiple fetuses, and abnormal fetal presentation.
Example of deformation
clubfeet, often a component of Potter sequence
Definition of a sequence
cascade of anomalies triggered by one initiating aberration in organogenesis
Example of a sequence
oligohydramnios or Potter sequence--decreased amniotic fluid leading to fetal compression-->flattened facies, positional abnormalities of hands and feet, dislocated hips, nodules in amnion (amnion nodosum), and compromised growth of chest well and hypoplastic lungs-->fetal demise
Causes of oligohydramnios
1.chronic leakage of amniotic fluid due to amnion rupture 2. uteroplacental insufficiency due to maternal HTN or severe toxemia 3. renal agenesis in the fetus
Definition of a syndrome
constellation of congenital anomalies pathologically related that cannot be explained on the basis of a single, localized, initiating defect
Definition of aplasia
absence of an organ due to failure of development of the primordium. Agnesis is complete absence of an organ and its associated primordium
Definition of atresia
failure of an opening, usually in a hollow visceral organ such as the trachea or intestine
Placental causes of FGR tend to produce what type of growth retardation?
asymmetric, with relative sparing of the brain down-regulation of growth in the latter half of gestation due to limited availability of nutrients or oxygen
What is meant by genetic mosaicism confined to the placenta?
up to 15% of preg with FGR-->viable genetic mutations occurring after zygota formation, causes different forms of chromosomal mosaicism. Dependent on timing and cell of origin of mutation. Trisomy 7 most frequently documented
Maternal influences resulting in FGR
maternal conditions resulting in decreased placental blood flow. Vascular dz: preeclampsia (toxemia of preg) and chronic HTN Inherited thrombophilias: factor V leiden mutation narcotic abuse, EtOH, heavy cigarette smoking Dilantin prolonged hypoglycemia
5 causes of respiratory distress in the newborn
1. excessive sedation of mother 2. fetal head injury during delivery 3. aspiration of blood or amniotic fluid 4. intrauterine hypoxia due to umbilical cord coiling about the neck 5. hyaline membrane dz, aka RDS-->deposition of a layer of hyaline proteinacecous material in peripheral airspaces of infants with this condition. Most common cause
Common clinical presentation of RDS
preterm and AGA-->male, maternal DM, C-section resuscitation may be needed, but within a few minutes rhythmic breathing and normal color re-established 30 minutes--dyspnea few hours--cyanosis Bilateral rales CXR: ground-glass picture: uniform minute reticulogranular densities
If therapy staves off death for --- days, infant has excellent chance of recovery
Fundamental defect in RDS
deficiency of pulmonary surfactant causing immaturity of lungs
Components of pulmonary surfactant
dipalmitoyl phosphatidylcholine (lecithin) phosphatidylglycerol hydrophilic glycoproteins SP-A and SP-D hydrophobic surfactant proteins SP-B and SP-C to reduce surface tension
When is surfactant production by type 2 alveolar cells accelerated?
After 35th week of gestation
Deficiency of surfactant: what happens to lungs at birth
Increased surface tension-->lungs collapse with each successive breath, so infants must work as hard with each successive breath as they did with the first.
Normal surfactant--lungs retain their residual air volume after first breath so successive breaths require far lower inspiratory pressures
What compounds problem of stiff atelectatic lungs?
soft thoracic wall pulled in as the diaphragm descends
Consequence of atelectasis in RDS
uneven perfusion and hypoventilation-->hypoxemia and CO2 retention-->acidosis-->pulmonary vasoconstriction-->endothelial/epithelial damage-->plasma leak into alveoli-->fibrin and necrotic cells (hyaline membrane) protein-rich, fibrin-rich exudation in to the alveolar spaces with the formation of hyaline membranes-->vicious cycle
What hormone class is especially important in surfactant synthesis?
glucocorticoids. Therefore, synthesis suppressed by high insulin levels (DM mothers), C-section (labor increases surfactant synthesis)
Morphology of RDS
lungs: normal size, but solid, airless, and reddish purple alveoli: poorly developed, collapsed terminal bronchioles and alveolar ducts: necrotic cellular debris incorporated within eosinophilic hyaline membranes made up of fibrin with cell debris from type 2 pneumocytes
Clinical course of RDS
1.delay labor until lungs reach maturity or induce maturation of lungs 2. analyze pulmonary secretions discharged in the amniotic fluid-->phospholipid analysis 3. prophylactic administration of exogenous surfactant at birth 4. antenatal corticosteroids to mom with threatened premature delivery
Hazards with oxygen therapy of RDS
oxygen toxicity 1. retrolental fibroplasia in the eyes--changes in VEGF expression 2. bronchopulmonary dysplasia--airway epithelial hyperplasia and squamous metaplasia, alveolar wall thickening, and peribronchial and interstitial fibrosis; decrease alveolar septation and dysmorphic capillary configuration
Infants who recover from RDS are at risk for what complications?
associated with prematurity, enteral feeding, infectious agents, inflammatory mediators (especially PAF increasing mucosal permeability) Ultimately, breakdown of mucosal barrier-->migration of gut bacteria-->inflammation, mucosal necrosis, sepsis, shock
Clinical course of NEC
bloody stools, abd distention, circulatory collapse abd XR: gas within interstinal wall (pneumatosis intestinalis) involves terminal ileum, cecum, and right colon-->distended, friable, congested or gangrenous
What condition is a complication of NEC?
intestinal perforation with accompanying peritonitis
Microscopic findings in NEC
mucosal or transmural coagulative necrosis, ulceration, bacterial colonization, and submucosal gas bubbles
managed conservatively resection of necrotic bowel
Consequences of surviving NEC
post-NEC strictures from fibrosis caused by granulation tissue and fibrosis after an acute episode
What type of infections are acquired by cervicovaginal (transcervical or ascending) route?
most bacterial and a few viral (e.g. herpes simplex II) infections
acquired by inhaling infected amniotic fluid shortly before brith or through an infected birth canal during delivery
Most common sequelae due to infection by inhalation of amniotic fluid
pneumonia, sepsis, and meningitis
Types of infections acquired by transplacental (hematologic) infections
parasitic (toxoplasma, malaria) and viral infections, plus a few bacterial infections (listeria, treponema)
via chorionic villi; occurring at any time during gestation or at time of delivery via maternal-to-fetal transfusion (e.g. hep B and HIV)
Consequences of parvovirus B19 in a minority of intrauterine infections
spont AB (esp second trimester), stillbirth, hydrops fetalis, and congenital anemia.
Infects erythroid cells; diagnostic viral inclusions seen in early erythroid progenitor cells
TORCH group of infections: clinical and pathological manifestations
fever, encephalitis, chorioretinitis, hepatosplenomegaly, pneumonitis, myocarditis, hemolytic anemia, and vesicular or hemorrhagic skin lesions
Chronic sequelae: growth and mental retardation, cataracts, congenital cardiac anomalies, and bone defects
Early onset sepsis: timeline, symptoms, and responsible pathogens
within first 7 days of life; acquired at or shortly before birth, resulting in pneumonia, sepsis, and meningitis symptoms within 4-5 dyas of life
Group B streptococcus
Late-onset sepsis: timeline and pathogens responsible
from 7 days to 3 months; Listeria and Candida
Fetal hydrops refers to:
accumulation of edema fluid in the fetus during intrauterine growth; can be immune or nonimmune hydrops
3 categories of consequences of hydrops
1. progressive, generalized edema of fetus (hydrops fetalis), usually lethal 2. localized degrees of edema (isolated pleural and peritoneal effusions) 3. postnuchal fluid accumulation (cystic hygroma) compatible with life
When may fetal RBC's reach the maternal circulation?
1. during last trimester when the cytotrophoblast is no longer present as a barrier 2. during childbirth
Which Rh antigen is the major cause of Rh incompatibility?
3 factors influencing the immune response to Rh-positive RBC's that reach the maternal circulation
1. ABO incompatibility protects mother against Rh immunization, since fetal RBC's are promptly coated and removed by anti-A or anti-B IgM antibodies that do not cross the placenta 2. dose-dependent; requires mother experience a significant transplacental bleed 3. Rh dz uncommon in first preg (IgM only); during next preg, IgG ab response
Administering ---- to Rh-negative mother decreases risk of hemolytic dz in future pregs
3 reasons why ABO incompatibility causing hemolytic dz is rare
1. anti-A and anti-B abs are IgM so don't cross placenta 2. fetal RBCs express antigens poorly 3. cells other than RBCs express antigens so they absorb some of the transferred ab.
How does the developing infant respond to mild hemolysis?
extramedullary hematopoeisis in spleen and liver
Consequences of severe hemolytic in infant
progressive anemia-->hypoxia to heart and liver. plasma protein synthesis drops cardiac decompensation and failure reduced plasma oncotic pressure and hydrostatic failure-->generalized edema and anasarca-->hydrops fetalis Elevated bilirubin in blood-->lipid soluble-->travels to brain-->kernicterus (CNS damage)
3 major causes of nonimmune hydrops
1. CV defects--congenital cardiac defects and arrhythmias-->intrauterine cardiac failure and hydrops 2. chromosomal anomalies--Turner syndrome and trisomies 21 and 18 3. fetal anemia (not caused by Rh or ABO)--due to thalassemias or Parvovirus B19
Why does Turner syndrome cause hydrops?
Abnl lymph drainage from neck-->postnunchal fluid accumulation (cystic hygromas)
Why do trisomies 21 and 18 cause hydrops?
due to underlying structural cardiac anomalies associated with the chromosomal aberrations
Why does parvovirus B19 cause fetal anemia?
enters into erythroid precursors-->apoptosis of red cell precursors-->red cell aplasia
What is kernicterus?
brain is enlarged, edematous, and when sectioned has a bright yellow color especially in the basal ganglia, thalamus, cerebellum, gray matter, and spinal cord