2.3 disorders of prematurity Flashcards
highest frequencies of death under 1 year
congenital mlaformation, deformation, and chromosomal abnormalities, disorders related to short gestation and low birth weight, sudden infant death syndrome (SIDS)
congenital anomalies
morphological defects present at birth, may not be expressed until later in life, can or cannot be genetic defect, 3% of newborns have a major anomaly (cosmetic or functional significance), most common cause of death in first year of life, significant cause of mortality and morbidity in all early years of life, in reality, observed anomalies in live births represent the leaset serious that occur
malformations
primary error of morphogenesis with intrinsic abnormal development (anencephaly, congenital heart defects). Multifactorial. Single/multiple
disruptions
secondary destruction of organ/body region that was previously normal in development. Extrinsic distrubance (amniotic bands that compress portions of fetus)
Anencephaly
neural tube defect with absence of cerebral hemisphere, skull, and skin
cleft lip/palate
if isolated - compatible with life, with malformation syndrome - severe cardiac defects
deformations
like disruptions these are due to extrinsic disturbance as a localized/generalized fetal compression by biomechanical forces –> structural anomalies (uterine constraint, oligohydramnios) –>(club feet)
Sequence
cascade of anomalies triggered by one initiating event
Potter sequence of oligohydramnios
renal agenesis, amniotic leak, maternal HTN, toxemia (U/O insff) —-> all lead to oligo hydramnios —–>can lead to amnion nodosom (plaques of squamous cells and fibrin), pulmonary hypoplasia, and fetal compression —-> fetal compression can lead to pulmonary hypoplasia, altered facies, positioning defects of feet and hands, breech presentation
syndrome
a constellation of congenital anomalies that are thought to be pathologically related but unlike a sequence can not be explained by a single initiating event. Can have a single etiology, eg a viral disease or chromosomal alteration that affects different tissues
Causes of anomalies
genetic, environmental and multifactorial (50 - 75% unknown)
genetic causes of congenital anomalies
chromosomal (karyotypic) abberations, single gene mutsionts
karyotypic abberations
10-15% of CA
when do most karyotypic abberations occur
during gametogenesis (not familial)
ex of karyotypic abberation
Down’s a la Robertsonian translocation of 21 with another chromosome (4%)
karyotypic abberations and death
80-90% of chromosomal number abberations die in the uterus
single gene mutations inheritance
90% AD or AR and 10% X-linked
examples of loss of fn genes involved in normal organogenesis
sonic hedgehog - holoprosencephally, HOXGL13 - digit anomalies (polydactyly, syndactyly)
holoprosencephaly
incomplete separation of cerebral hemispheres across the midline
prematurity
gestational age less than 37 weeks
2nd leading cause of neonatal mortality
prematuraty (1st would be congenital anomalies), premature babies have higher rates of morbidity and mortality than full term babies
aga
appropriate for gestational age (btw the 10 and 90 percentile)
sga
small for gestational age
lga
large for gestational age
birthweight and gestational age implications
a premature infant of 2300g may be as large as a term infant at 2300g but still has immature organs esp. lungs, An AGA 1500g infant born at 32wks is better off than an SGA 700g infant born at 32 wks
preterm
before 37 weeks
post term
after 42 weeks
risk factors for prematurity and fetal growth restriction
premature rupture of placental membranes (PPROM, PROM), intrauterine infection, uterine, cervical, placental structural anomalies, multiple gestations, additional factors: immaturity of organs
PPROM
preterm premature rupture of Membranes
PROM
premature rupture of Membranes
PPROM
causes 30-40% of preterm deliveries
PROM
carries far lower risk (spontaneous or induced)
Risks of PPROM
smoking, prior Hx, and vaginal bleeding
intrauterine infection
present in 25% of preterm births, can be a cause of (P)PROM or be a result of (P)PROM
histology of intrauterine infection
chorioamionitis (membranes) and Funisitis (cord)
most common intrauterien infection
Group B strem
how is preterm labor induce by infection
TLR4 activation –> (inflammatory cells drawn into area –> ROM and proteases), (deregulation of prostaglandins –> uterine contractions–> inflammation-induced Preterm Labor)
maternal and placental structural anomalies
fibroids, incompetent cervix, placenta previa (implantationsin lower uterus), abruptio placenta (premature separation) —most common in late preg, placenta accreta (no decidua implantation into uterine wall)
multiple gestation
twin pregnancy
immature organs
lung, kidneys - usually deep glomeruli mature enough for survival, brain -vital brain center OK. Temp reg and respiration control are affected, Liver - generally OK but bilirubin handeled poorly so many are jaundiced
fetal growth restriction (FGR)
same as intrauterine growth restriction (IUGR) - condition in shice a fetus is unable to achieve its genetically determined potential size (shorter)
Asymmetric FGR
(70-80%) - normal head size, dec crown to heel
Symmetric FGR
(20-30%) -dec birth weight, all organs are similarly affect, small head, short stature
FGR can be detected in utero by
ultrasound
Measurements vs. gestational age
BPD, HC, AC, H/A circumference ratio
causes of FGR
fetal, placental, maternal
fetal causes of FGR
intrinsic problem with fetus despite adequate support, chromosomal abnormalities, congenital infections - TORCH organisms (Toxoplasma, Rubella, CMV, Herpes, Other), congenital anomalies, fetal causes usually have symmetric growth restriction
Placental causes of FGR
during 3rd rim –> vigorous fetal growth –> inc U/P supply, any cause of placental insufficency is critical, abruptio placenta, palcenta previal, thrombosis, infection, infarction, small placenta, cord anomalies, single arter (AA/V), abnormal insertion, usually results in asymmetrical FGR with brain spared
placenta previa
placenta is implanted in cervical os, during labor it dialates and the placenta starts bleeding, but patient has no pain, most common antepartum bleeding
abruptio placenta
complains of pain bc there is blood/hemmoraging on the side of the uterine wall and blood cant get out
most frequnt cause of SGA
maternal causes of FGR
maternal causes of FGR
conditions affecting mothers health/blood flow including Preeclampsia, eclampsia, chroinic HTN, Inherited thrombophilias, Alcohol, heavy smoking, drugs, general malnutrition
preeclapsia
hypertension, proteinuria, edema
eclampsia
progression to seizures and DIC
example of inherited thrombophilia
factor V laiden mutation
Neonatal respiratory Distress Syndrome – hyalin membrane disease
most common cause of respiratory distress, can occur in term infants but most in preterm and AGA, rate inversely proportional to gestational age (60% 34wks), immaturity of lungs means inability to secrete surfactant
Surfactant is secreted by
Type II pneumocytes (approx 35wks gestation)
Surfactant consists of
lipid (dipalmitoyl phosphatidyl choline), phosphatidylglycerol, and hydrophobic proteins SP-B and C (dec surface tension)
the first breath
requires a large inspiratory effort but once inflated the lungs remain 40% inflated
if no surfactant
lungs collapse back and every breath is as hard as the first
what leads to breathing difficulty in RDS
stiff lungs and soft chest wall
what induces surfactant secretion
glucocorticoids and thyroxine
what induces surfactant synthesis
labor
what inhibits surfactant secretion
high levels of insuline
what are predisposing factors for increased risk of RDS
prematurity, maternal diabetes, and cesarean delivery –think about why
immatur lung histology
thick, even at 30 weeks
Pathophysiology of RDS
see pic
gross anatomy of lung with rds.hyaline membrane disease
solid, airless, redish-purple, sink in water
RDS clinical course
rapid, labored respiration, substernal retraction, cyanosis, grunting, nasal flaring at birth, ground glass on xray
how to deal with preventing/treating RDS today
much more favorable today, monitoring amniotic fluid for surfactant for lung maturity, antenatal treatment with steroids, adminstration of surfactant, acute death now unusual, recovery begins at about 4 days
RDS treatmetn risks
therapy with O2 carries risks – retinopathy of prematurity and bronchopulmonary dysplasia
Lecithin:Sphingomyelin ration – L/S ratio
L/S ratio of 2 or more indicates a relatively low risk of infant RDS, and an L/S ratio of less than 1.5 is associated with a high risk of infant RDS
good LS ratio by about
35 weeks –8/2 – ratio of 4
retrolental fibroplasia – aka retinopaty of prematurity
hypoxia leads to increase in VEGF leading to dec in endothelial cell apoptosis, and inc in angiogenesis, O2 therapy and hyperoxia (phase 1) dec VEGF, then ralative hypoxia (room air) inc VEGF (phase 2 - retinal vessel proliferation), even with very careful o2 monitoring, retinopaty can resul suggesting other causes
Bronchopulmonary Dysplasia
now infrequent in infants >1200g and 30 weeks, usually in 28 days
multiple factors associated with bronchopulmonary dysplasia
hyperoxemial, hyperventilation, prematurity, inflammatory cytokines, and vascular maldevelopment
prognosis of RDS babies
infants who recover from RDS are t increased risk for PDA(patent ductus arteriosus), intraventricular hemorrhage, and NEC (necrotizing enterocolitis)
Necrotizing Enterocolitis (NEC)
occurrence inversely related to gestational age (1 in 10 of <1500g)
NEC pathogenesis
multifactorial, prematurity, most cases associated with oral feeding, suggesting infectious organisms, also inflammatory mediators, inflammation leads to mucosal breakdown (necrosis) invasion by bacteria, sepsis, and shock
NEC clinical manifestations
premature, fever, bloody stools, distended abdoment, and vascular collapse
NEC Rx
air in intestinal wall (pneumatosis intestinalis) – usually involves terminal ileum, cecum, and proximal colon
NEC treatment
Early NPO, IV fluids, Orogastric tube, antibiotics; Later surgery to remove fibrotic segments
NEC and mortality
high mortality and post-natal strictures from healing
Germinal Matrix Hemorrhage
subependymal (periventricular) hemorrhage w/ extension into ventricles occurs in preterm infants, microcirculation extremely sensitive to hypoxia and changes in perfusion pressure, common cause for admissions to neonatal ICU in <1500g babies
