pregnancy Flashcards

1
Q

what is the decidua

A

uterine lining (endometrium) during pregnancy which forms maternal part of placenta

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2
Q

balance of pro and anti-inflammation in decidualisation

A
  1. Pro-inflammatory: HESCs release IL-33 upon decidualisation
  2. Anti-inflammatory: HESCs → downregulation of ST2L, upregulation of sST2
    Poor regulation of this in RPL → imbalance between pro & anti-inflammation → pro-inflammatory time in window of receptivity increased → late decidualisation
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3
Q

Endometrial causes of recurrent pregnancy loss (3)

A
  1. Impaired decidualisation of stromal cells → failure of placenta formation
  2. Dysregulation of pro and anti-inflammation → prolonged endometrial receptivity → delayed implantation (in unsupportive uterine environment)
  3. Failure of decidualisation → loss of inhibition of implantation factor secretion → loss of embryo recognition and selection
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4
Q

when does decidualisation occur

A

mid-luteal phase of every menstrual cycle

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5
Q

endocrinology of pregnancy

A

hCG peak during 1st trimester at ~8 weeks GA
All other hormones (placental lactogen, progesterone, oestrogens) hit peak at end of pregnancy, and fall after delivery
Progesterone levels are highest
Steep fall due to delivery of placenta
All require placental activity though have different regulation

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6
Q

where is hCG produced

A

Primarily secreted from syncytiotrophoblasts

Cytotrophoblasts can produce some

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7
Q

hCG functions (2)

A
  1. Major role: maintenance of oestradiol and progesterone in early pregnancy
    hCG → LH receptor on corpus luteum (similar structure to LH) → cAMP → progesterone & oestrogen production from ovary; prevents degeneration of corpus luteum until luteo-placental shift
  2. Stimulation of steroidogenesis in feto-placental unit
    High levels of hCG cross from maternal circulation to fetal → androgen production by developing testis
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8
Q

where is prolactin produced (2)

A
  1. lactotrophs of pituitary

2. decidualising endometrial cells

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9
Q

hormonal control of breast development

A

Oestrogen influences duct development

Progesterone and prolactin influence alveolar development

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10
Q

placental production of oestrogen

A

Placenta lacks key enzyme CYP17 which converts pregnenolone to DHEA
1. Pregnenolone converted to DHEA-S (sulfated form) in fetal adrenals (develop early)
OR DHEA-S produced by maternal adrenals which goes to placenta
DHEA-S inactive as DHEA could affect development in females
2. DHEA-S travels to fetal liver: can either be:
i. Converted to oestrodiol in placenta or
ii. Hydroxylated to 16αOH-DHEA-S, then converted to estriol in placenta

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11
Q

what hormones do the different cells of the placenta produce

A

Cytotrophoblast layer can produce GnRH and CRH

Syncytium can produce hCG, hPL and progesterone

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12
Q

cardiovascular changes in pregnancy

A
  1. ↑cardiac output
  2. ↓peripheral vascular resistance
  3. ↑heart rate
    Can lead to decreased exercise tolerance, dizziness, palpitations
    Parameters begins to return to normal during third trimester
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13
Q

diagnostic criteria for pre-eclampsia

A
  1. New onset hypertension (>140/90mmHg)

2. Proteinuria (>0.5g/day) on 2 separate occasions

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14
Q

symptoms of pre-eclampsia (4)

A
  1. Headache
  2. Visual disturbances (due to oedema in the eye)
  3. Abdo pain (due to stretching of liver capsule)
  4. Swelling (capillaries leaking)
    Can be asymptomatic ∴ screening important
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15
Q

complications of pre-eclampsia (5)

A
  1. Eclampsia (fitting)
  2. Cerebral haemorrhage: due to uncontrolled high BP
  3. Pulmonary oedema
  4. Acute kidney injury
  5. HELLP: haemolysis, elevated liver enzymes, low platelets
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16
Q

cardiovascular changes in preeclampsia

effect of exercise

A

Pre-eclampsia → concentric remodelling → fibrosis, stiffness, ↓diastolic function
Exercise → eccentric remodelling; better able to cope w increased load
∴ exercise may decrease risk

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17
Q

pathophysiology of preeclampsia

2 causes

A
  1. Diminished remodelling of spiral arteries → narrow lumen, smooth muscle hypertrophy → poor blood flow & ↑clotting → release of syncytiotrophoblast microparticles (STBMs) into maternal circulation
  2. Variable blood flow through spiral arteries → oxygen tension in placenta alters → reoxygenation → ↑release of free radicals and STBMs
    STBMs and free radicals:
    a. Damage endothelial cells→ cannot release prostacyclin → ↑vasoconstriction and coagulation → hypertension, proteinuria, procoagulant state
    b. Activate leukocytes → damage of maternal vasculature
    Leads to cycle: high blood flow → coagulation & vasoconstriction → clot breakdown → restoration of blood flow → high blood flow
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18
Q
  1. phases of cervical dilatation

2. ideal rate of contractions + intervention

A
  1. Latent phase: < 3cm dilated, active phase: > 3cm
    Can detect whether labour is failing to progress and if intervention needed
  2. Contractions: aim for 3-4 / 10min
    Undercontracting → oxytocin
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19
Q

normal values on CTG (4)

A
  1. Baseline rate 110-160 (average fetal HR in 10min)
  2. Variability >5 (how much peaks and troughs of HR deviate from baseline)
    Reflection of baby’s autonomic nervous system
  3. Accelerations (abrupt fetal HR increase > 15pbm above baseline for >15s)
  4. No decelerations (opposite of accelerations)
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20
Q

causes of abnormal CTG

A
Maternal:
1. Sepsis
2. Placental abruption
3. Uterine scar rupture
4. Spinal/ epidural hypotensive  episode
5. Hyperstimulation>5:10
Fetal: 
6. Intrauterine growth  restriction
7. Cord around neck
8. Cord prolapse
9. Rapid descent
10. Prolonged cord compression
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21
Q

effects of pregnancy on pre-existing diabetes (5)

A
  1. More insulin needed
  2. Nephropathy worsens
  3. Retinopathy occurs/worsens
  4. Hypoglycaemia common; ↓awareness of hypos
  5. Neuropathy/gastroparesis (delayed gastric emptying) may worsen
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22
Q

effect of pre-existing diabetes on pregnancy (6)

also same effects as gestational diabetes

A
  1. ↑risk of miscarriage
  2. ↑risk of pre-eclampsia: varies w HbA1c
  3. ↑perinatal/neonatal mortality
  4. ↑glucose supplies from mother → ↑hyperplasia of pancreas → fetus hyperinsulinaemic → risk of hypoglycaemia after birth
  5. Ketones cross placenta → ketoacidosis
  6. Insulin acts as growth factor → macrosomia → shoulder dystocia (shoulder stuck behind pubic bone → nerve damage: Erb’s palsy)
23
Q

interventions for gestational diabetes (3)

A
  1. diet and exercise
  2. metformin
  3. insulin
24
Q

risks of multiple pregnancy (2)

A
  1. perinatal mortality

2. cerebral palsy

25
Q

monozygotic vs dizygotic twins

A
dizygotic = two separate oocytes fertilised by two separate sperm (genetically distinct as siblings)
monozygotic = single oocyte fertilised by single sperm splits to give two embryos (genetically identical)
26
Q

how does different chorionicity and amnionicity occur in twins?

A

splitting of monozygotic embryo at
1. day 3 (2 cell stage) -> dichorionic diaminiotic twins
can also get DCDA by fertilisation of two separate by oocytes by two separate sperm (dizygotic)
2. day 4-8 -> two ICMs -> monochorionic diamniotic twins
3. day 8-13 -> two embryos from one ICM -> monochorionic monoamniotic twins
4. incomplete separate of embryo by day 15-17 -> conjoined twins

27
Q

how is chorionicity determined pre-conception

A

USS at 10-13 weeks ->

  1. Lambda sign = dichorionic
  2. T (twin-peak) sign = monochorionic
28
Q

complications of multiple pregnancy (7)

A
  1. TTTS
  2. Fetal growth restriction
  3. Cord entanglement
  4. Conjoined twins
  5. Congenital malformations
  6. Single intrauterine death
  7. Preterm delivery
29
Q

twin-to-twin transfusion syndrome

  1. occurs in which type of twins
  2. features
A
  1. Occurs in monochorionic twins sharing a placenta:
    2a. Unbalanced sharing of blood via placenta vascular anastomoses
    b. Deep unidirectional flow through arterio-venous communications
    c. Minimal or absent superficial bidirectional flow
    - > smaller donor twin + larger recipient twin
30
Q

consequences of TTTS for donor and recipient twin (4 each)

A
Donor twin
1. Oligohydramnios
2. Hypovolaemia
3. Uteroplacental insufficiency
4. Oligouria (smaller bladder on USS)
Recipient twin 
1. Polyhydramnios
2. Hypervolaemia
3. Cardiac dysfunction → heart failure 
4. Polyuria (larger bladder on USS)
31
Q

management of TTTS (2)

A
  1. Laser ablation of arterio-venous anastomoses
  2. Serial amnioreduction: small hole created in amniotic sac (seals naturally afterwards) under USS guidance -> normalises amniotic fluid levels
32
Q

greatest risk of cord entanglement in which type of twin

management

A

monochorionic monoamniotic

early delivery at 32 weeks by C-section

33
Q

consequences of single intrauterine death (3)

A
  1. necrotic neurological and renal problems in surviving twin
  2. subsequent death of initially healthy twin
  3. sudden drop in BP in surviving twin, due to blood redirected to dead twin
34
Q

timing and mode of delivery for multiple pregnancy

A
  1. MCMA: 32 weeks, by C-section
  2. MCDA: by 37 weeks
  3. DCDA: by 38 weeks
    Delaying delivery beyond these times raises risk of death even if pregnancy has been uncomplicated
35
Q

maternal complications of multiple pregnancy (4)

A
  1. Hypertension and pre-eclampsia
  2. Gestational diabetes (placental hormones promote insulin resistance)
  3. Anaemia
  4. Venous thromboembolism
36
Q

definition of miscarriage

A

loss of an intrauterine pregnancy before 24 weeks of gestation

37
Q

causes of recurrent miscarriage (10)

A
  1. thrombophilia e.g. antiphospholipid syndrome
  2. increased uterine natural killer cells
  3. PCOS
  4. thyroid disorders
  5. failure of decidualisation -> inability to recognise and prevent implantation of low quality embryos
  6. sperm DNA fragmentation
  7. karyotypic disorders
  8. failure of trophoblast hCG secretion (CGB mutation) -> inadequate progesterone to maintain pregnancy
  9. MTHFR mutation -> reduced folate production
  10. uterine malformations
38
Q

antiphospholipid syndrome diagnosis + treatment

A

thromboelastogram as bedside test for assessing coagulation
2 positive tests at least 12 weeks apart
1. Lupus anticoagulant
2. Anti-cardiolipin Abs
3. Anti-B2 glycoprotein-l Abs
Treatment: aspirin + unfractionated heparin

39
Q

uterine malformation example, diagnosis, Tx

A

failure of septal reabsorption -> septate/arcuate malformations
1. USS
2. laparoscopy or hysteroscopy; can resect septum and restore normal shape (metroplasty)
however many pts w malformations still able to have normal successful pregnancy

40
Q

sperm DNA fragmentation in recurrent miscarriage

investigations + treatment

A

assays e.g. sperm chromatin structure assay (SCSA)

antioxidants e.g. zinc may be useful

41
Q

hCG mutation (in recurrent miscarriage)

  1. gene
  2. treatment + evidence
A
  1. CGB
  2. Multicentre placebo-controlled study of hCG supplementation in early pregnancy failed to show any benefit in pregnancy outcome
42
Q

folate deficiency

  1. mechanism for recurrent miscarriage
  2. evidence for supplementation
A
  1. MTHFR mutation -> decreased folic acid → increased plasma homocysteine levels -> risk of miscarriage
  2. no evidence whether supplementation decreases risk of a new miscarriage
43
Q

evidence for

  1. oestrogen supplementation in recurrent miscarriage
  2. progesterone supplementation
A
  1. RCTs found no benefit

2. Meta-analysis did not reduce sporadic miscarriage rate

44
Q

treatment for uterine natural killer cells in recurrent pregnancy

  1. MOA
  2. evidence
  3. disadvantages
A
  1. IV immunoglobulin downregulates NK killing
  2. Meta-analysis: IVIG → ↑rates of live birth in secondary recurrent miscarriage, but insufficient evidence for its use in primary recurrent miscarriage
  3. Expensive, serious adverse effects incl transfusion reaction, anaphylactic shock and hepatitis
45
Q

changes in maternal immune system during pregnancy (5)

A
  1. Uterine NK cells dominant in decidua; have inhibitory receptors to MHC I ∴ do not attack cytotrophoblasts
  2. Few T cells in endometrium as would attack allogenic paternal HLA Ags
  3. ↑Th2 (anti-inflammatory), ↓Th1 → ↑immunity against bacteria, ↓against viruses
  4. Maternal IgG passes selectively to fetal circulation via Fc-γ receptors, to provide passive immunity
  5. “Placental sink”: Abs towards paternal antigens are trapped in placental stroma as immune complexes via unknown mechanism
46
Q

anatomical immune defences in pregnancy

A
  1. Physical barrier: vaginal, cervix (long and closed to prevent ascending infection), amniotic sac
  2. Chemical barrier: pH of vagina (lactobacilli), cervical mucous plug (antibacterial properties)
47
Q

important features of fetal immune system (4)

A
  1. Trophoblasts lack expression of classical HLA class I A and B, and HLA class II
  2. Expression of Fas ligand (FasL) causes apoptosis of invading lymphocytes
  3. At term, IgG reach adult levels (passive immunity)
  4. After birth IgG levels drop; fetus also obtains antibodies from breast milk
48
Q
haemolytic disease of the newborn
definition 
prevention
diagnosis
treatment
consequences (3) 

SAQ 2012

A

Rh- mother produces Abs against rhesus antigens of Rh+ baby
Prevention: anti-D injections
Diagnosis: history, maternal serum Ab titres, USS
Treatment: intrauterine blood transfusion/exchange transfusion, early delivery
Consequences:
1. Anaemia; severe → hydrops fetalis (heart failure)
2. Jaundice
3. Enlarged spleen and liver

49
Q

effect of pregnancy on autoimmune conditions

A

Th2 autoimmune conditions worsen e.g. SLE, scleroderma, thyroid
Th1 autoimmune conditions improve e.g. rheumatoid arthritis, multiple sclerosis

50
Q

route of fetal infection (3)

A
  1. Haematogenous route (mostly viruses)
  2. Iatrogenic: amniocentesis/CVS
  3. Ascending (most common route)
51
Q

features of fetal inflammatory response syndrome

A

Defined by ↑IL-6 level in fetal plasma
Systemic activation of the fetal innate immune system
1. Adrenal gland: ↑cortisol
2. Lungs: ↑chronic lung disease
3. Brain: ↑PVL (periventricular leukomalacia), IVH (intraventricular haemorrhage)

52
Q

diagnosis of miscarriage (2)

A

USS:
1. Mean gestation sac diameter ≥25mm (w no obvious yolk sac)
2. Fetal pole w crown–rump length ≥7mm (w/o evidence of fetal heart activity)
Not diagnostic alone; need to repeat scans

53
Q

management of miscarriage (3)
advs + disadvs

2017 SAQ

A
  1. Expectant management: wait for natural passage of conceptus (can be at home)
    ○ First line treatment for 7-14 days
    ○ No increased risk of infection or pain
    ○ Safe, though unpleasant
  2. Medical: vaginal Misoprostol
    ○ Less invasive
    ○ 1% experience excessive bleeding needing medical attention
  3. Surgical
    ○ Manual vacuum aspiration of products of conception in outpatient setting under local anaesthetic
    ○ Evacuation of retained production of conception (ERPC) under general anaesthetic (dilation & curettage) → Asherman’s syndrome: intrauterine adhesions caused by excessive curretting