transplacental (hematologic) infections:
TORCH (Toxoplasma, Other (Treponema pallidum), Rubella, CMV, Herpes)
Parvovirus: 5th disease
transcervical infections
Most bacterial, some viral (HSV II)
Frequent with preterm delivery
Gonnococcal and Chlamydial infections
post-natal maternal milk
CMV
HIV
HTLV I
Heat-labile E. coli enterotoxin
perinatal infections
Group B strep #1 within 1 week of delivery
hydrops fetalis
Accumulation of edema in fetus
Immune or nonimmune
Erythroblastosis fetalis if accompanied by anemia
immune hydrops
Rh- mother, Rh+ baby
first pregnancy: anti-D IgM (can’t cross placenta)
second pregnancy: anti-D IgG (can cross placenta)
concurrent ABO incompatibility helps prevent sensitization to Rh
Coombs test
tests for presence of anti-RBC Abs on RBCs
non-immune hydrops
Cardiovascular defects
Chromosomal anomalies (Turner, Trisomy 21 and 18)
Lymphatic anomalies
Twin-twin transfusion
Fetal non-immune anemia (homozygous alpha-thalassemia, parvovirus B19 induced aplastic anemia)
self-mutilation
Lesch-Nyhann syndrome
sweaty feet
isovaleric acidemia
mousy or musty
PKU
cataracts
galactosemia
cherry red macula
Tay-Sachs, GM1
dislocated lens
homocysteinuria or Marfans
cystic fibrosis
AR, 1 in 2500 live births, most common lethal genetic disease
Affects transport of fluid secretions in exocrine glands and epithelial lining of respiratory, GI, and reproductive tracts
Viscous mucous secretions, obstruct organ passages
Pancreatic insufficiency, steatorrhea, malnutrition, hepatic cirrhosis, intestinal obstruction, male infertility, recurrent pulmonary infections
hemangiomas
usually skin, most common tumor of infancy, benign
lymphangiomas
skin or deeper (neck, axilla, mediastinum, retroperitoneum), benign
fibrous tumors
t(12;15)(p13;q25) in congenital-infantile fibrosarcoma (ETV6-NTKR3 fusion transcript making tyrosine kinase stimulating RAS and PI3K/AKT oncogenic pathways)
most common malignancy in children
acute lymphoblastic leukemia
1 solid tumor in children
CNS tumors
2 solid tumor in children
neuroblastoma (#1 in infants)
neuroblastoma genes and findings
17q gain, 1p deletion
N-myc amplification
DNA hyperdiploidy, near triploidy
urinary catecholamines
Ewing sarcoma genes
t(11;22)
rhabdomyosarcoma genes
PAX3 and PAX7
Burkitt lymphoma gene
t(8;14)
*Wilms tumor gene
11p13 (WT1)
retinoblastoma gene
13q14 (RB)
neuroblastoma findings
Presents as abdominal mass, most commonly adrenal medulla
90% secrete catecholamines, VMA and HVA in urine
Small blue cell tumor
*Homer-Wright pseudorosettes
neuroblastoma cutaneous metastases
blueberry muffin baby
neuroblastoma stage 4s
localized primary tumor in infants with dissemination limited to skin, liver, and/or bone marrow. Good prognosis.
N-MYC amplification
poor neuroblastoma prognosis
Double minutes
retinoblastoma findings
Malignant eye tumor
Familial (60-70%): germline RB1 mutation
Sporadic (30-40%): somatic RB1 mutation
Flexner-Wintersteiner rosettes
nephroblastoma
#1 primary renal tumor in children, #4 pediatric malignancy Triphasic histology: stroma, tubules, blastemal elements
embryo
implantation to first 8 weeks
fetus
9 weeks to birth
neonatal
first 4 weeks after birth (most hazardous)
perinatal
5 months before to 1 month after birth
infancy
first year after birth
childhood
birth to puberty or legal adult age
most common cause of death from 1-12 months
SIDS
most common cause of death from 1-14 years
accidents
congenital anomalies
Present at birth, may not be expressed until later in life
Up to 3% of newborns
The most severe anomalies cause intrauterine death
most common birth defects
- bicuspid aortic valve
2. Down syndrome
malformation
Primary failure, intrinsically abnormal development > abnormal morphogenesis
E.g. anencephaly, congenital heart defects
Usually multifactorial
disruption
Secondary disruption of previously normal structure
E.g. amniotic bands, environmental cuases
Not heritable!
deformation
Extrinsic disturbance from abnormal biomechanical forces > structural abnormalities
Maternal (uterine constraint) or fetal/placental (oligohydramnios) cause
2% of newborns
E.g. breech presentation
sequence
Cascade of anomalies set off by one initiating aberation
May be a “complex”
E.g. Potter sequence
malformation syndrome
Constellation of congenital anomalies thought to be pathologically related but cannot be explained by a single initiating event
May be a “complex”
E.g. viral disease or chromosomal alteration that affects different tissues
Potter sequence (oligohydramnios)
renal agenesis > oligohydramnios > amnion nodosum pulmonary hypoplasia, fetal compression > altered facies, positioning defects, breech presentation
Potter facies
Ocular hypertelorism (increased space btw eyes)
Low-set ears
Receding chin
Flattening of nose
TORCH organism
Toxoplasma Other (T. pallidum) Rubella CMV Herpes simplex
Cataracts, conjunctivitis, pneumonitis, HSM, petechiae and purpura
Early infection: heart problems
agenesis
complete absence of an organ an primordium (nothing formed)
aplasia
absence of an organ d/t primordium development failure
atresia
block in something with a lumen
dysplasia
abnormal organization of cells (malformation context only)
omphalocele
abdominal musculature fails to form, covered by peritoneum, easier to repair
gastroschisis
part of abdominal wall fails to form, not covered by peritoneum
causes of congenital anomalies
- 40-60% unknown
2. 20-25% multifactorial
most sensitive period of fetal development
4-5 weeks (heart forms first 6 weeks)
most sensitive period for teratogenicity
3-9 weeks
Rubella embryopathy
Worst of TORCH, usually 1st trimester Tetrad of: Cataracts Deafness Heart defects Mental retardation
CMV
Later in pregnancy (2nd trimester)
CNS involvement
Microcephaly, mental retardation, deafness, HSM
Does not affect organogenesis much, primarily affects growth of organs
thalidomide
limb developmental problems
Vit A/13-cis-retinoic acid/accutane(isotretinoin)
disrupts HOX genes
valproic acid (antiepilectic)
disrupts HOX genes
fetal alcohol syndrome (FAS)
atrial septal defects, #1 cause of mental retardation, growth retardation, microcephaly
phthalates
Added to PVC and used in flexible plastics
Exposure to in lab animals causes endocrine disruption and testicular dysgenesis syndrome
Some concern for BPA effects on brain, behavior, and prostate glands in fetuses, infants, and children
maternal diabetes
Diabetic embryopathy
Hyperglycemia in mother induces hyperinsulinemia in infant > decreased surfactant
Fetal macrosomia (birth weight > 4000g)
Heart problems, brain and spinal defects, oral clefts, kidney and GI defects, limb deficiencies
caput succedaneum
scalp edema, extremely common (vaginal delivery > cone head)
cephalhematoma
hemorrhage (more problematic), 25% will have skull fracture
HOX 1-4
face
HOX 9-13
extremeties
HOXD13
syndactyly/polydactyly
HOXA13
hand-foot-genital syndrome (distal limb and distal urinary tract malformations)
PAX2
renal-coloboma syndrome (developmental defects of kidneys, ears, eyes, brain)
PAX3
Waardenburg syndrome (congenital pigment abnormalities and deafness)
PAX6
aniridia (congenital absence of iris)
Robertsonian translocation
2 copies of gene on 1 chromosome, none on the homolog
Trisomies or monosomies in progeny
B9
lowers incidence of neural tube defects
2 requirements for congenital dislocation of hip
- shallow acetabulum (genetic)
2. breech presentation (environment)
probability of neonate mortality (APGAR)
0-1: 50% mortality
4: 20%
7 or better: almost 0%
premature (pre-term)
Before 37 weeks
2nd leading cause of neonatal mortality behind congenital anomalies
Risk factors: premature rupture of placental membranes, intrauterine infection, uterine, cervical, or placental structural abnormalities, multiple gestaion
postmature (post-term)
after 42 weeks
PROM
Premature rupture of membranes (after 37 weeks)
Okay to deliver baby
PPROM
Pre-term premature rupture of membranes (before 37 weeks)
Administer anti-labor meds to delay deliver
intrauterine infection
Present in 25% of preterm births
Choriamnitis (membranes)
Funisitis (cord)
U. urealyticum, M. hominis, G. vaginalis, T. vaginalis, N. gonorrheae, C. trachomatis
fetal causes of FGR
Usually symmetric growth
Chromosomal disorders
Congenital anomalies
Infection by a TORCH
placental causes of FGR
Usually asymmetric
Uteroplacental insufficiency
Confined placental mosaicism (trisomy 7)
maternal causes of FGR
Most frequent causes of FGR Hypertension Hypercoagulable states Alcohol, narcotics, heavy smoking, drugs (dilantin) Malnutrition
hyaline membrane disease
Most are preterm
Surfactant deficiency
More common in males, maternal DM, multiple gestation, C-section
surfactant
Mature type II pneumocytes Dipalmitoyl phosphatidylcholine (lecithin) SP-B and SP-C (surface tension) L/S ratio > 2 lungs are mature L/S ratio
retinopathy of prematurity (retrolental fibroplasia)
Phase I: O2 therapy > decreased VEGF > endothelial cell apoptosis
Phase II: relative hypoxia (room air) > increased VEGF > angiogenesis
bronchopulmonary dysplasia
alveolar hypoplasia
necrotizing enterocolitis (NEC)
intestinal ischemia
platelet activating factor elevated in stool
germinal matrix hemorrhage
Subependymal (periventricular) hemorrhage with extension into ventricles in preterm infants