lecture 32: diseases and disorders 4: pregnancy Flashcards Preview

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Flashcards in lecture 32: diseases and disorders 4: pregnancy Deck (28):

What happens during early pregnancy?

  • up to 12- 16 weeks placenta invades the inner 1/3 of the uterine myometrium 
  • remodels the maternal spiral aterioles 
    • converts to high capacitance (i.e. accommodates large volumes) and low resistance system 
    • net result - slow moving rivers of blood allowing optimal exchange of nutrients and waste between mother and foetus 


What is spiral arteriole remodelling?

  • normal placental remodelling
  • increased risk of foetal growth restriction and preeclampsia 
  • watch this 


What is miscarriage?

  • spontaneous abortion
  • biology
    • occurs in 10-15% of clinically recognised pregnancies
    • 50% have chromosomal errors 
    • thus about 50% due to genetic errors, possibly 50% due to implantation errors 
    • risk increases with maternal age
  • clinical presentation and diagnosis
    • vaginal bleeding and abdominal pains/cramping
    • clinical investigations:
      • serum hCG does not rise (or falls) when taken 48hrs apart
      • on ultrasounds, absence of foetal cardiac activity (diagnostic if no foetal heart and the gestational sac size is greater than 25mm, or crown-rump length more than 7mm) 
  • overview of management 
    • surgical: suction curettage
    • medical: expectant management ± misoprostol (prostaglandins) to induce uterine contractions 


What is ectopic pregnancy?

  • pregnancy implants outside of the uterus, mainly the fallopian tubes
  • biology
    • occurs in 1-2% of all pregnancies
    • never viable 
    • a serious gynaecological emergency: can rupture through the fallopian tube, causing massive haemorrhage 
  • clinical presentation and diagnosis
    • vaginal bleeding and abdominal pains/cramping
      • thus, can masquerade as miscarriage
      • often pain is far more severe
    • clinical investigations:
      • serum hCG and ultrasound (may see ectopic mass outside uterus) 
      • if hCG is more than 1500 IU/L, a gestational sac should be visible in the uterus if it is a normal pregnancy 
      • if not, there should be a high index of suspicion it is an ectopic pregnancy 


How is ectopic pregnancy managed?

  • surgery 
    • a mainstay of treatment
    • two types:
      • salpingostomy: cut along the top of the ectopic, pull out the sac, leaver rest of tube 
      • salpingectomy: take out the entire tube, including the ectopic 
    • laparoscopic salpingectomy is the most common surgical treatment approach 
  • medical 
    • if the ectopic pregnancy is small (e.g. serum hCG less than 3000 IU/L and sac size on ultrasound smaller than 3-4cm), could treat with methotrexate 
  • expectant management:
    • if the ectopic pregnancy is very small (e.g. serum hCG less than 500 IU/L), can watch and monitor hCG levels 


What are foetal anomalies?

  • structural foetal anomalies 
    • about 2% incidence of major foetal structural anomalies 
      • some associated with chromosomal/genetic abnormalities 
      • increased chance of genetic abnormalities if multiple anomalies 
    • about 4-5% incidence of minor anomalies 
    • possibly minor increase with IVF 
  • approach to management 
    • ultrasound diagnosis 
    • consider amniocentesis for genetic analysis 
      • either cytogenetic analysis (including FISH), or prenatal microarray
    • further management depends on type of abnormality 
      • ranges from postnatal repair (cardiac abnormalities), foetal surgery (diaphragmatic hernia) or termination (multiple abnormalities) 


What is downs syndrome?

  • extra chromosome 21 (three instead of 2)
  • discrete syndrome (intellectual and physical disabilities, characteristic facies)
  • 1 in 600-700
  • significantly increased risk with increasing maternal age 
    • e.g. age 30: 1 in 940
    • age 40: 1 in 85 
  • management 
    • may decide for no testing
    • screening tests
      • e.g. first trimester combined screening (blood test 10 week and ultrasound at 12 weeks), or new Non-invasive prenatal test (blood test, highly accurate)
    • the only way to diagnose for sure is an amniocentesis
    • no curative options
    • either termination of pregnancy or continue with the pregnancy 


At what point in early pregnancy are these complications a risk?

  • miscarriage: high risk at start, decreases with increased time of pregnancy
  • ectopic pregnancy: equal risk over first ten weeks (detection)
  • strucutral anomalies: equal risk over first 10 weeks (detection)
  • downs syndrome: equal risk over first 20 weeks (detection)


What are complications of later pregnancy?

  • spotaneous preterm labour
  • foetal growth restriction
  • preeclampsia 
  • gestational diabetes 


What happens when a complication arises in later pregnancy?

  • the aim of obstetric care is to deliver the baby at a gestation which allows the best chance of a good outcome, while minimising risks to the mother and baby 
  • i.e. the more advanced in gestation, the lower the threshold for delivery 


What is preterm delivery?

  • 5-10% incidence
  • defined as delivery less than 37 weeks: more severe if delivery less than 32-34 weeks
  • threshold of viability around 24 weeks
  • 60% are spontaneous preterm birth (i.e. the uterus starts contracting)
  • remaining 40% are 'iatrogenic', the clinicians had to deliver the baby early for other reasons, mainly preeclampsia or foetal growth restriction
  • the cost: 
    • the preterm foetus is at risk of complications of prematurity
    • more serious complications with earlier gestations 
    • immediate: death, intracerebral bleeding, respiratory distress syndrome bronchopulmonary dysplasia, necrotising enterocolitis 
    • later in life: cognitive delay, mental disability 


How is threatened spontaneous preterm labour managed?

  • give corticosteroids to prepare foetus
    • injected into mother
    • shown to be beneficial in accelerating foetal lung maturation and has other benefits (decreases death by 50%, respiratory distress syndrome by 50% etc) 
  • give agents to try to decrease the contractions
    • nifedipine (blocks caclium receptor)
    • atosiban (blocks oxytocin receptor, not licensed in Australia)
    • we do not know whether these agents work 
  • transfer the mother to a hospital where the paediatric team can care for the preterm foetus 
    • e.g. level 3 (tertiary hospital) if threatened preterm birth at less than 34 weeks gestation 


What is foetal growth restriction?

  • or intrauterine growth restriction 
  • the foetus does not grow to its genetic potential
  • it affects 5-10% of all pregnancies 
  • 80% of foetal growth restriction is due to abnormal placental implantation 
    • placenta in a state of chronic hypoxia 
    • does not supply foetus with sufficient oxygenation and nutrients 
  • the remaining 20% are associated with foetal:
    • structural abnormalities 
    • chromosomal or genetics
    • infections 


What is the normal growth trajectory?


What happens with foetal growth restriction in regards to growth trajectory?


Of what are growth restricted foetuses at higher risk?

  • still birth 


What is the approach to managing foetal growth restriction?

  • overall approach is to time delivery, balancing risks of prematurity and perceived risk of stillbirth to baby 
  • deliver if growth restricted (less than 10th centile) and the foetus has reached term (more than 37 weeks gestation)
  • if preterm growth restriction, perform serial ultrasound tests of foetal wellbeing, and try to leave the foetus in utero for as long as possible before delivery 
  • foetal tests of wellbeing include:
    • measuring blood flows in umbilical artery (more resistance to flow with a sicker, hypoxic baby)
    • measure amniotic fluid around baby (decreased fluid with sicker baby)


What is preeclampsia?

  • factors are released from the placenta into the maternal circulation, causing organ injury
  • defective implantation
  • endothelial dysfunction → release of placental factors
  • end-organ injury 
    • e.g. blood pressure, kidney, brain, liver 


What are maternal organ systems affected by preeclampsia?

  • mediated vai maternal endothelial dysfunction
  • maternal blood vessels
    • hypertension always part of the diagnostic criteria
  • kidney
    • most common organ affected
    • if affeted, increased urinary protein, abnormal renal function tests (blood test)
  • liver 
    • more severe form if affected, can cause liver rupture 
    • if affected, abnormal liver function tests, sharp pains 
  • haematological system
    • low platelets, low clotting factors (very dangerous)
    • if affected, abnormal blood tests
  • nervous system/brain
    • can cause the dreaded eclamptic fit, and potentially a stroke (bleed into the brain)
  • foetus
    • preeclampsia can be associated with foetal growth restriction
    • if present, it adds complexity to the management (need to watch both mother and foetus) 
  • factors released from the placenta cause maternal multi-organ injury
    • once there is organ injury, there is usually progression of organ damage
    • other organ systems may become affectyed
    • the only cure is delivery - there is no other treatment 
    • in preterm preeclampsia, the clinician is sometimes forced to deliver the baby early to save the mother 
    • but this inflicts the foetus with 'iatrogenic' prematurity 
    • thus, the need to deliver the mother preterm comes at a cost to the foetus 


How is preeclampsia managed?

  • preterm preeclampsia 
    • try to coast the pregnancy along to a gestation where foetal outcomes can be optimised 
    • to do this, the maternal condition has to be very closely monitored
    • the patient needs delivery if there is signficant deterioration 
    • situations mandating delivery irrespective of foetal gestation include:
      • significant liver or renal injury 
      • occurrence of an eclamptic fit 
  • preeclampsia that has reached term
    • induce and deliver the patient 


What is gestational diabetes?

  • 5-10% of all pregnancies 
  • excessive blood glucose, caused by peripheral insulin resistance 
  • drive in part by 'diabetogenic' proteins released from placenta (e.g. human placental lactogen)
  • worsened in the patient has preexisting metabolic syndrome/obese
  • the complications that can arise:
    • foetal overgrowth: macrosomia, leading to caesarean sections, shoulder dystocia, neonatal problems 
    • foetal growth restriction
    • increased amniotic fluid leading to unstable lie
    • if very poorly controlled sugars, foetus may be at increased risk of still birth 


How is gestational diabetes diagnosed?

  • oral glucose tolerance test: mother given a load of glucose to drink and their blood sugars at 1 and 2 hours tested 
  • diagnosis made if 2 hours sugars are more than 8mmol/L
  • usually performed at 28 weeks gestation 


How is gestational diabetes managed?

  • the mother
    • control of blood sugars
      • regular monitoring of blood sugar levels (BSLs), 4 times a day
      • aim for 2 hours after meals of less than 6.5 mmol/L 
    • otions for sugar control
      • diet control (achieved in 70-80% of cases; low GI foods)
      • insulin (or metformin), if diet cannot lower blood sugar levels to target 
  • the baby 
    • measure foetal growth at around 32-34 weeks by ultrasound 
    • may offer tests of foetal wellbeing 
    • if on insulin, some will offer induction of labour at 39 weeks gestation 
  • the aftermath:
    • the diabetes will immediately end after birth 
    • BUT, mother has a 50% lifetime risk of developing type II diabetes 


What is risk and timing of later pregnancy complications?

  • spontaneous preterm birth from 22 weeks onward increased risk to term
  • foetal growth restriction: from 20 weeks onward increasing risk
  • preeclampsia: same
  • gestational diabetes: continuous risk from around 28 weeks onward


What is timing of clinical care in human pregnancy?

  • first visit: before 10 weeks, ultrasound and blood tests 
  • 10-13 weeks: downs syndrome test offered
  • 20 weeks: foetal anomaly ultrasound 
  • 28 weeks: gestational diabetes test 
  • also:
    • with each antenatal visit we screen for major complications:
      • preeclampsia: blood pressure
      • foetal growth restriction: tape measure on abdomen → refer for an ultrasound if it measures as small
  • for:
    • miscarriage or ectopic pregnancy: presents with symptoms or incidentally at early pregnancy ultrasound
    • spontaneous preterm labour: patient presents with uterine contractions 


What are developing treatments for ectopic pregnancy?

  • medication treatment 
  • phase I trial - GEM study 


What is a new diagnostic method?

  • measuring mRNA in maternal blood
  • circulating RNA from the foetus 


What are developing treatments for preeclampsia?

  • therapeutic strategies: targeting the placental factors
  • nanoparticles to deliver drugs directly to the placenta 
  • therapeutic neutralising antibodies 
  • small molecules (conventional drugs)