normal and disordered fatal growth Flashcards
What does SGA stand for?
small for gestational age
fetus is <10th weight percentile for age (weeks)
What does IUGR stand for?
intrauterine growth restriction
fetus unable to achieve genetically predetermined size
What does LBW stand for?
low birth weight
birth weight less that 2500g
SGA or prematurity
what are the three classifications of small for gestational age foetuses?
1) normal small fetus - no structural abnormality, normal umbilical doppler and liquor. Not at risk, no special care needed.
2) abnormal small fetus - have chromosomal or structural abnormalities
3) growth restricted fetus - usually results from placental dysfunction. Appropriate treatment or timely delivery may improve prospects.
a significant number of healthy foetuses will be subjected to high-risk protocols and, potentially, iatrogenic prematurity.
what two categories can feral growth restriction be decided into?
symmetrical
asymmetrical
what is symmetrical FGR and what is it caused by?
fatal head and body proportionately small
fatal insults during early development - affect growth process and cell hyperplasia
things like chromosomal disorders
what is asymmetrical FGR and what is it caused by?
fatal brain disproportionally large compared to liver fatal insult during later development usually placental insufficiency normal infant brain:live ratio >3 asymmetrical ratio >6
what are the categories of etiologic factors for IUGR?
maternal
placental
fetal
intrinsic factors
extrinsic factors
what are some intrinsic etiologic factors in FGR?
chromosomal aberrations
congenital structural defects
constitutional (genetic heritage)
what are some extrinsic etiologic factors in FGR?
maternal-placental-fetal infections
uteroplacental perfusion
chronic maternal disease
substrate availability and toxins
what are some maternal causes of fatal growth restriction?
chronic disease (hypertension, renal disease, thyrotoxicosis, advanced DM, cyanotic cardiopulmonary disease, collagen vascular disease, haemoglobinopathies.
pre-eclampsia
malnutrition
infection (toxoplasmosis, malaria, rubella, cytomegalovirus, herpes, syphilis, listeriosis )
what are some drugs and medications associated with fetal growth restriction?
marijuana heroin, methadone cocaine cigarette smoking alcohol aminopterin cytotoxic drugs isotretinoin lithium oaramethadione
what are some fatal risk factors for FGR?
multiple pregnancy infections congenital malformations extrauterine pregnancy e.g. abdominal placental or umbilical cord defects chromosomal abnormalities.
what are some common and rare chromosomal abnormalities associated with FGR?
common - trisomy 13, trisomy 18, trisomy 21
rare - trisomy 22, turners syndrome, 4p and 4q syndromes, 5p and 5q syndromes, trisomy 9 mosaic syndrome, triploidy syndrome, partial trisomy 10q syndrome, ring 1, ring 22.
what are some placental factors in IUGR?
uteroplacental insufficiency
- defective trophoblastic invasion/placentation
- lateral insertion of cord
- reduced blood flow to placental bed e.g. pre-eclampsia
- vascular anomaly of placenta and cord - TTTS
- decrease functioning mass - small placenta, abruptio placenta, placenta praaevia, post term pregnancy.
what are the underlying mechanism of IUGR?
insufficient gas exchange and nutrient delivery to fetus
maternal disease
- decreased oxygen - carrying capacity e.g. cyanotic heart disease, smoking, haemoglobinopathy
- dysfunctional oxygen delivery system - diabetes with vascular, hypertension, autoimmune conditions
- placental damage - smoking, thrombophilia, autoimmune diseases
what stages are most vulnerable to maternal dietary deficiences
peri-implantation and period of rapid placental development.
what are the effects of nutritional insult during critical period of gestation?
Nutritional insult during critical period of gestation may leave permanent “memory” throughout life.
Maternal nutritional status can alter epigenetic state of the fetal genome and imprint gene expression
what are epigenetic alterations?
stable alterations of gene expression through covalent modifications of DNA and core histones
what are the two mechanisms of epigenetic modification?
NA methylation and histone modification (acetylation and methylation)
what are the three main functions of the placenta?
metabolism
transport
endocrine
what does the placenta transport?
- Gases
- O2 and CO2 to and from baby.
- Nutrients (Glucose facilitated diffusion via hexose transporters, Amino acid by active transport, Antibodies IgG not IgM, Bilirubin – conjugated poorly transported, unconjugated from fetus crosses easily
- Drugs (fetal drug addiction)
- infectious agents (cytomegalovirus, rubella, measles, microorganisms)
what can happen to things being transported through the placenta?
transported intact
partially consumed
metabolised
not transported
what can placental dysfunction lead to?
placental dysfunction leads to a reduced nutrient transfer and may cause fatal growth restriction
what are the placental implications of IUGR?
increased fetal morbidity and mortality (iatrogenic prematurity, fetal compromise in labour, increased need for induction of labour and caesarean delivery)
10 fold increase in late fetal deaths among very small foetuses (less that the 3rd percentile)
what are some long term consequences of FGR?
- CV disease
- abnormalities (hypothalamic pituitary axis, the CVS)
- insulin resistance
- metabolic syndrome
what is the thrifty phenotype hypothesis?
A metabolically deprived developing fetus becomes metabolically programmed for insulin resistance and
impaired glucose metabolism
metabolic consequences predispose affected fetus to a wide range of health risks
strong association between FGR and elevated fasting glucose, fasting insulin resistance and prevalence of T2DM
what in the history would you screen for fatal growth restriction?
smoking altitude malnutrition previous FGR medications recreational drugs alcohol chronic maternal disease genetic anomalies (maternal age, fam history, habitual abortion, alpha-fetoprotein first trimester vaginal bleeding parents size
how is FGR diagnosed?
presence of risk factors
clinical - serial maternal weight , symphysio-funal height assessment
USS - inadequate fetal growth, reduced AFI, placental calcification
how good is the symphysio-fundal height at predicting IUGR?
poor
sensitivity 27%
specificity = 88%
what are customised fundal height charts?
SFH charts improve sensitivity to detect SGA
non-customised SFH-sensitivity=27%
customised SFH charts-sensitivity=48%
the charts take into account - maternal height, weight, parity and ethnicity.
what things are looked for on fetus USS
BPD HC TCD FL AC ratios EFW amniotic fluids accurate measurements difficult
what test are done for surveillance of foetuses?
serial scans non-stress test amniotic fluid assessment umbilical doppler biophysical profile assessment
what interventions can prevent IUGR?
LDA and miniheparin
Strategies to reduce maternal smoking,
Antibiotics to prevent/rx UTIs
antimalarial prophylaxis
how is IUGR managed?
Fetal surveillance until the risk of in utero
demise exceeds the risk of delivery and
prematurity
what is large for gestational age defined as?
above the 90th centile for that gestation
what is macrosomia?
BW > 4000g regardless of gestational age
unlike IUGR the morbidity and mortality relate to absolute birth wate rather than centiles
prevalence of macrosomia??
9-10% of neonates have BW > 4kg
1.5% have a weight > 4.5 kg.
Rates vary– 3.6% Bangalore, 15% Denmark.
Implies environmental and genetic factors.
Imprinting of genes (epigenetic process that involves
DNA methylation and histone methylation without
altering the genetic sequence) may play a role e.g. IGF
II gene (only paternal gene is expressed).
risk factors for macrosomia?
• Maternal hyperglycaemia during pregnancy • Previous macrosomic infant • Pre-pregnancy obesity/excessive maternal weight gain • Male fetus • Post-term gestation • Parental height and race • Maternal age < 20 years.
what are problems of fetal overgrowth??
- Maternal diabetes
- Fetal demise
- Birth trauma – shoulder dystocia
- Neonatal hypoglycaemia
