Robbins

Question 1

Two main classes of congenital anomalies and examples for each.

Answer 1

Genetic:
chromosomal aberrations: Down syndrome, Turner syndrome
Mendelian inheritance: holoprosencephaly

Environmental:
Maternal/Placental infections: TORCH
Maternal disease states: Diabetes, obesity, PKU
Drugs and chemicals: alcohol, folic acid antagonists, 13-cis-retinoic acid, phenytoin, thalidomide, warfarin

Question 2

During which weeks of development is the embro/fetus most susceptible to teratogens?

Answer 2

Between weeks 3 - 9, embryo is extremely susceptible to teratogens.
PEAK sensitivity: weeks 4 - 5.

Question 3

Define embryonic & fetal periods (in terms of weeks):

Answer 3

Fetal: first 9 weeks
Embryonic: 9 weeks - birth.
<37 weeks = premature

Question 4

Name 4 environmental teratogens.

Answer 4

Alcohol
Valproic acid
Cyclopamine
Retinoic acid

Question 5

What are the top two causes of neonatal mortality?

Answer 5

Congenital anomalies

Prematurity

Question 6

What are the top 4 major risk factors for prematurity?

Answer 6

PPROM: premature preterm rupture of membranes.
Intrauterine infection.
Uterine, cervical and placental structural abnormalities.
Multiple gestation.

Question 7

List clinical risk factors for PPROM.

Answer 7

Prior hx of preterm delivery.
preterm labor and/or vaginal bleeding during the current pregnancy.
maternal smoking.
Low SES.
poor maternal nutrition.

Question 8

What are the histologic correlates of intrauterine infection?

Answer 8

Chorioamnionitis: inflammation of placental membranes.

Funisitis: inflammation of fetal umbilical cord.

Question 9

What are the 4 main hazards of prematurity?

Answer 9

Neonatal respiratory distress syndrome (hyaline membrane disease).

Necrotizing Enterocolitis (NEC).

Sepsis.

Intraventricular and germinal matrix hemmorrhage.

Question 10

Give at least one example each of maternal, fetal and placental abnormalities that lead to fetal growth restriction.

Answer 10

Maternal: preeclampsia; hypertension; narcotics, alcohol and smoking; chemotherapy, phenytoin; malnutrition.

Fetal: THESE ARE SYMMETRICAL; chromosomal disorders (trisomies); congenital anomalies; congenital infections (TORCH);

Placental: THESE ARE ASYMMETRICAL; vascular anomalies (single umbilical artery, abnormal cord insertion, placental abruption, placenta previa, thrombosis and infarction; chronic villitis of unknown etiology; multiple gestations.

Question 11

List 5 causes of respiratory distress in the newborn

Answer 11

RDS (pulmonary immaturity, deficiency of surfactant –> hyaline membrane disease)

Excessive sedation of the mother

fetal head injury during delivery

aspiration of blood or amniotic fluid

intrauterine hypoxia due to nuchal cord

Question 12

What maternal disease increases the risk of RDS, and briefly explain the mechanism.

Answer 12

Maternal diabetes

Maternal hyperglycemia –> fetal hyperinsulinism –> suppresses surfactant synthesis.

Question 13

List 3 risk factors (associations) for RDS.

Answer 13

male sex

maternal diabetes

cesarean delivery

Question 14

What are the two major complications of RDS?

Answer 14

1. Retinopathy of prematurity: treatment with oxygen leads to hyperoxia –> decrease in VEGF; relative hypoxia during weaning off oxygen leads to increase in VEGF, inducing retinal vessel proliferation (neovascularization).
2. Bronchopulmonary dysplasia:
   - decrease in alveolar septation - large, simple alveolar structures.
   - multifactorial.

Question 15

What are (4) classic histologic features of NEC?

Answer 15

Mucosal or transmural coagulative necrosis
ulceration
bacterial colonization
submucosal gas bubbles

Later: reparative changes - fibrosis and granulation tissue.

Question 16

What are the two main routes of fetal/perinatal infection?

Answer 16

Transplacental (hematogenous)

Transcervical (ascending)

Question 17

What are some consequences to the fetus of ascending infection, and what is the mechanims?

Answer 17

Preterm birth: due to rupture of amniotic sac - either due to inflammation, or release of prostaglandins from neutrophils

Pneumonia, sepsis, meningitis: fetus infected via aspiration of amniotic fluid.

Question 18

Which infections are typically ascending, and which hematologic?

Answer 18

Ascending: HSV2, most bacteria

Hematologic: parasites (toxoplasma), most viral infections, some bacterial (listeria, treponemal)

Question 19

What are the possible sequelae of Parvovirus B19?

Answer 19

Spontaneous abortion

Stillbirth

Anemia

Hydrops fetalis

Question 20

What are the possible clinical presentations of TORCH infections?

Answer 20

Fever

Encephalitis

Hepatosplenomegaly

Pneumonitis

Myocarditis

Vesicular & hemorrhagic skin lesions

Question 21

What organism is the most common cause of early-onset (within first 7 days of life) sepsis?

Answer 21

Group B strep

Question 22

Define immune hydrops.

Answer 22

Autoimmune hemolytic disease due to RBC antigen incompatibility between the mother and fetus.

Question 23

Name two consequences of excessive destruction of RBCs due to immune hydrops in the neonate, and discuss their consequences.

Answer 23

Anemia: directly due to red cell loss. leads to liver and cardiac injury due to HYPOXIA. Decreased liver protein synthesis and cardiac failure lead to decreased plasma oncotic pressure and increased hydrostatic pressure, culminating in hydrops.

Janudice: hemolysis –> unconjugated bilirubin –> passes through infant’s weak blood-brain barrier –> water insoluble but fat soluble, binds to lipids in brain –> kernicterus.

Question 24

list the THREE major causes of NONimmune Hydrops

Answer 24

Cardiovascular defects

Chromosomal anomalies

Fetal anemia

Question 25

List 3 chromosomal anomalies associated with non-immune hydrops

Answer 25

trisomy 21

trisomy 18

Turner 45, X0

Mechanisms: Turner - defect of lymphatic drainage in the neck –> nuchal hydrops

Trisomies: accompanying cardiac structural defects leading to cardiac failure

Question 26

List causes of non-immune anemia leading to hydrops.

Answer 26

Alpha-thalassemia

Parvovirus B19

Monozygotic twinning (with twin-twin transfusion)

Question 27

what is a classic finding in the peripheral blood of a neonate with hydrops ?

Answer 27

Erythroblastosis - large numbers of immature RBCs in the circulation, secondary to extramedullary hematopoesis.

Question 28

Name two inborn errors of metabolism.

Answer 28

Phenylketonuria

Galactosemia

Question 29

List 7 clinical manifestations of cystic fibrosis.

Answer 29

Chronic lung disease (secondary to recurrent infections)

Pancreatic insufficiency

Steatorrhea

Malnutrition

Hepatic cirrhosis

Intestinal obstruction / Meconium Ileus

Male infertility.

Question 30

Define SIDS

Answer 30

Sudden Infant Death Syndrome: sudden, unexplained death of a child <1 year of age that remains unexplained ever after a complete autopsy, examination of the death scene, and review of the clinical history.

Question 31

What is the ‘triple risk’ model of SIDS?

Answer 31

Vulnerable infant
Critical period of development
Environmental/exogenous stressor

Question 32

name some postmortem abnormalities that can be detected in cases of sudden unexplained infant death

Answer 32

Infections

viral myocarditis

unsuspected congenital anomaly

Long QT

Anomalous origin of left coronary artery (from left pulmonary artery)

Traumatic child abuse

Intentional suffocation

Congenital aortic stenosis