normal and disordered fatal growth

Question 1

What does SGA stand for?

Answer 1

small for gestational age

fetus is <10th weight percentile for age (weeks)

Question 2

What does IUGR stand for?

Answer 2

intrauterine growth restriction

fetus unable to achieve genetically predetermined size

Question 3

What does LBW stand for?

Answer 3

low birth weight
birth weight less that 2500g
SGA or prematurity

Question 4

what are the three classifications of small for gestational age foetuses?

Answer 4

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.

Question 5

what two categories can feral growth restriction be decided into?

Answer 5

symmetrical

asymmetrical

Question 6

what is symmetrical FGR and what is it caused by?

Answer 6

fatal head and body proportionately small
fatal insults during early development - affect growth process and cell hyperplasia
things like chromosomal disorders

Question 7

what is asymmetrical FGR and what is it caused by?

Answer 7

fatal brain disproportionally large compared to liver 
fatal insult during later development 
usually placental insufficiency 
normal infant brain:live ratio >3 
asymmetrical ratio >6

Question 8

what are the categories of etiologic factors for IUGR?

Answer 8

maternal
placental
fetal

intrinsic factors
extrinsic factors

Question 9

what are some intrinsic etiologic factors in FGR?

Answer 9

chromosomal aberrations
congenital structural defects
constitutional (genetic heritage)

Question 10

what are some extrinsic etiologic factors in FGR?

Answer 10

maternal-placental-fetal infections
uteroplacental perfusion
chronic maternal disease
substrate availability and toxins

Question 11

what are some maternal causes of fatal growth restriction?

Answer 11

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 )

Question 12

what are some drugs and medications associated with fetal growth restriction?

Answer 12

marijuana 
heroin, methadone 
cocaine 
cigarette smoking 
alcohol 
aminopterin 
cytotoxic drugs 
isotretinoin 
lithium 
oaramethadione

Question 13

what are some fatal risk factors for FGR?

Answer 13

multiple pregnancy 
infections 
congenital malformations
extrauterine pregnancy e.g. abdominal 
placental or umbilical cord defects 
chromosomal abnormalities.

Question 14

what are some common and rare chromosomal abnormalities associated with FGR?

Answer 14

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.

Question 15

what are some placental factors in IUGR?

Answer 15

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.

Question 16

what are the underlying mechanism of IUGR?

Answer 16

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

Question 17

what stages are most vulnerable to maternal dietary deficiences

Answer 17

peri-implantation and period of rapid placental development.

Question 18

what are the effects of nutritional insult during critical period of gestation?

Answer 18

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

Question 19

what are epigenetic alterations?

Answer 19

stable alterations of gene expression through covalent modifications of DNA and core histones

Question 20

what are the two mechanisms of epigenetic modification?

Answer 20

NA methylation and histone modification (acetylation and methylation)

Question 21

what are the three main functions of the placenta?

Answer 21

metabolism
transport
endocrine

Question 22

what does the placenta transport?

Answer 22

• 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)

Question 23

what can happen to things being transported through the placenta?

Answer 23

transported intact
partially consumed
metabolised
not transported

Question 24

what can placental dysfunction lead to?

Answer 24

placental dysfunction leads to a reduced nutrient transfer and may cause fatal growth restriction

Question 25

what are the placental implications of IUGR?

Answer 25

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)

Question 26

what are some long term consequences of FGR?

Answer 26

- CV disease - abnormalities (hypothalamic pituitary axis, the CVS) - insulin resistance - metabolic syndrome

Question 27

what is the thrifty phenotype hypothesis?

Answer 27

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

Question 28

what in the history would you screen for fatal growth restriction?

Answer 28

``` 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 ```

Question 29

how is FGR diagnosed?

Answer 29

presence of risk factors clinical - serial maternal weight , symphysio-funal height assessment USS - inadequate fetal growth, reduced AFI, placental calcification

Question 30

how good is the symphysio-fundal height at predicting IUGR?

Answer 30

poor sensitivity 27% specificity = 88%

Question 31

what are customised fundal height charts?

Answer 31

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.

Question 32

what things are looked for on fetus USS

Answer 32

``` BPD HC TCD FL AC ratios EFW amniotic fluids accurate measurements difficult ```

Question 33

what test are done for surveillance of foetuses?

Answer 33

``` serial scans non-stress test amniotic fluid assessment umbilical doppler biophysical profile assessment ```

Question 34

what interventions can prevent IUGR?

Answer 34

LDA and miniheparin Strategies to reduce maternal smoking, Antibiotics to prevent/rx UTIs antimalarial prophylaxis

Question 35

how is IUGR managed?

Answer 35

Fetal surveillance until the risk of in utero demise exceeds the risk of delivery and prematurity

Question 36

what is large for gestational age defined as?

Answer 36

above the 90th centile for that gestation

Question 37

what is macrosomia?

Answer 37

BW > 4000g regardless of gestational age unlike IUGR the morbidity and mortality relate to absolute birth wate rather than centiles

Question 38

prevalence of macrosomia??

Answer 38

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).

Question 39

risk factors for macrosomia?

Answer 39

``` • 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. ```

Question 40

what are problems of fetal overgrowth??

Answer 40

* Maternal diabetes * Fetal demise * Birth trauma – shoulder dystocia * Neonatal hypoglycaemia