pregnancy Flashcards
what is the decidua
uterine lining (endometrium) during pregnancy which forms maternal part of placenta
balance of pro and anti-inflammation in decidualisation
- Pro-inflammatory: HESCs release IL-33 upon decidualisation
- 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
Endometrial causes of recurrent pregnancy loss (3)
- Impaired decidualisation of stromal cells → failure of placenta formation
- Dysregulation of pro and anti-inflammation → prolonged endometrial receptivity → delayed implantation (in unsupportive uterine environment)
- Failure of decidualisation → loss of inhibition of implantation factor secretion → loss of embryo recognition and selection
when does decidualisation occur
mid-luteal phase of every menstrual cycle
endocrinology of pregnancy
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
where is hCG produced
Primarily secreted from syncytiotrophoblasts
Cytotrophoblasts can produce some
hCG functions (2)
- 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 - Stimulation of steroidogenesis in feto-placental unit
High levels of hCG cross from maternal circulation to fetal → androgen production by developing testis
where is prolactin produced (2)
- lactotrophs of pituitary
2. decidualising endometrial cells
hormonal control of breast development
Oestrogen influences duct development
Progesterone and prolactin influence alveolar development
placental production of oestrogen
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
what hormones do the different cells of the placenta produce
Cytotrophoblast layer can produce GnRH and CRH
Syncytium can produce hCG, hPL and progesterone
cardiovascular changes in pregnancy
- ↑cardiac output
- ↓peripheral vascular resistance
- ↑heart rate
Can lead to decreased exercise tolerance, dizziness, palpitations
Parameters begins to return to normal during third trimester
diagnostic criteria for pre-eclampsia
- New onset hypertension (>140/90mmHg)
2. Proteinuria (>0.5g/day) on 2 separate occasions
symptoms of pre-eclampsia (4)
- Headache
- Visual disturbances (due to oedema in the eye)
- Abdo pain (due to stretching of liver capsule)
- Swelling (capillaries leaking)
Can be asymptomatic ∴ screening important
complications of pre-eclampsia (5)
- Eclampsia (fitting)
- Cerebral haemorrhage: due to uncontrolled high BP
- Pulmonary oedema
- Acute kidney injury
- HELLP: haemolysis, elevated liver enzymes, low platelets
cardiovascular changes in preeclampsia
effect of exercise
Pre-eclampsia → concentric remodelling → fibrosis, stiffness, ↓diastolic function
Exercise → eccentric remodelling; better able to cope w increased load
∴ exercise may decrease risk
pathophysiology of preeclampsia
2 causes
- Diminished remodelling of spiral arteries → narrow lumen, smooth muscle hypertrophy → poor blood flow & ↑clotting → release of syncytiotrophoblast microparticles (STBMs) into maternal circulation
- 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
- phases of cervical dilatation
2. ideal rate of contractions + intervention
- Latent phase: < 3cm dilated, active phase: > 3cm
Can detect whether labour is failing to progress and if intervention needed - Contractions: aim for 3-4 / 10min
Undercontracting → oxytocin
normal values on CTG (4)
- Baseline rate 110-160 (average fetal HR in 10min)
- Variability >5 (how much peaks and troughs of HR deviate from baseline)
Reflection of baby’s autonomic nervous system - Accelerations (abrupt fetal HR increase > 15pbm above baseline for >15s)
- No decelerations (opposite of accelerations)
causes of abnormal CTG
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
effects of pregnancy on pre-existing diabetes (5)
- More insulin needed
- Nephropathy worsens
- Retinopathy occurs/worsens
- Hypoglycaemia common; ↓awareness of hypos
- Neuropathy/gastroparesis (delayed gastric emptying) may worsen
effect of pre-existing diabetes on pregnancy (6)
also same effects as gestational diabetes
- ↑risk of miscarriage
- ↑risk of pre-eclampsia: varies w HbA1c
- ↑perinatal/neonatal mortality
- ↑glucose supplies from mother → ↑hyperplasia of pancreas → fetus hyperinsulinaemic → risk of hypoglycaemia after birth
- Ketones cross placenta → ketoacidosis
- Insulin acts as growth factor → macrosomia → shoulder dystocia (shoulder stuck behind pubic bone → nerve damage: Erb’s palsy)
interventions for gestational diabetes (3)
- diet and exercise
- metformin
- insulin
risks of multiple pregnancy (2)
- perinatal mortality
2. cerebral palsy
monozygotic vs dizygotic twins
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)
how does different chorionicity and amnionicity occur in twins?
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
how is chorionicity determined pre-conception
USS at 10-13 weeks ->
- Lambda sign = dichorionic
- T (twin-peak) sign = monochorionic
complications of multiple pregnancy (7)
- TTTS
- Fetal growth restriction
- Cord entanglement
- Conjoined twins
- Congenital malformations
- Single intrauterine death
- Preterm delivery
twin-to-twin transfusion syndrome
- occurs in which type of twins
- features
- 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
consequences of TTTS for donor and recipient twin (4 each)
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)
management of TTTS (2)
- Laser ablation of arterio-venous anastomoses
- Serial amnioreduction: small hole created in amniotic sac (seals naturally afterwards) under USS guidance -> normalises amniotic fluid levels
greatest risk of cord entanglement in which type of twin
management
monochorionic monoamniotic
early delivery at 32 weeks by C-section
consequences of single intrauterine death (3)
- necrotic neurological and renal problems in surviving twin
- subsequent death of initially healthy twin
- sudden drop in BP in surviving twin, due to blood redirected to dead twin
timing and mode of delivery for multiple pregnancy
- MCMA: 32 weeks, by C-section
- MCDA: by 37 weeks
- DCDA: by 38 weeks
Delaying delivery beyond these times raises risk of death even if pregnancy has been uncomplicated
maternal complications of multiple pregnancy (4)
- Hypertension and pre-eclampsia
- Gestational diabetes (placental hormones promote insulin resistance)
- Anaemia
- Venous thromboembolism
definition of miscarriage
loss of an intrauterine pregnancy before 24 weeks of gestation
causes of recurrent miscarriage (10)
- thrombophilia e.g. antiphospholipid syndrome
- increased uterine natural killer cells
- PCOS
- thyroid disorders
- failure of decidualisation -> inability to recognise and prevent implantation of low quality embryos
- sperm DNA fragmentation
- karyotypic disorders
- failure of trophoblast hCG secretion (CGB mutation) -> inadequate progesterone to maintain pregnancy
- MTHFR mutation -> reduced folate production
- uterine malformations
antiphospholipid syndrome diagnosis + treatment
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
uterine malformation example, diagnosis, Tx
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
sperm DNA fragmentation in recurrent miscarriage
investigations + treatment
assays e.g. sperm chromatin structure assay (SCSA)
antioxidants e.g. zinc may be useful
hCG mutation (in recurrent miscarriage)
- gene
- treatment + evidence
- CGB
- Multicentre placebo-controlled study of hCG supplementation in early pregnancy failed to show any benefit in pregnancy outcome
folate deficiency
- mechanism for recurrent miscarriage
- evidence for supplementation
- MTHFR mutation -> decreased folic acid → increased plasma homocysteine levels -> risk of miscarriage
- no evidence whether supplementation decreases risk of a new miscarriage
evidence for
- oestrogen supplementation in recurrent miscarriage
- progesterone supplementation
- RCTs found no benefit
2. Meta-analysis did not reduce sporadic miscarriage rate
treatment for uterine natural killer cells in recurrent pregnancy
- MOA
- evidence
- disadvantages
- IV immunoglobulin downregulates NK killing
- Meta-analysis: IVIG → ↑rates of live birth in secondary recurrent miscarriage, but insufficient evidence for its use in primary recurrent miscarriage
- Expensive, serious adverse effects incl transfusion reaction, anaphylactic shock and hepatitis
changes in maternal immune system during pregnancy (5)
- Uterine NK cells dominant in decidua; have inhibitory receptors to MHC I ∴ do not attack cytotrophoblasts
- Few T cells in endometrium as would attack allogenic paternal HLA Ags
- ↑Th2 (anti-inflammatory), ↓Th1 → ↑immunity against bacteria, ↓against viruses
- Maternal IgG passes selectively to fetal circulation via Fc-γ receptors, to provide passive immunity
- “Placental sink”: Abs towards paternal antigens are trapped in placental stroma as immune complexes via unknown mechanism
anatomical immune defences in pregnancy
- Physical barrier: vaginal, cervix (long and closed to prevent ascending infection), amniotic sac
- Chemical barrier: pH of vagina (lactobacilli), cervical mucous plug (antibacterial properties)
important features of fetal immune system (4)
- Trophoblasts lack expression of classical HLA class I A and B, and HLA class II
- Expression of Fas ligand (FasL) causes apoptosis of invading lymphocytes
- At term, IgG reach adult levels (passive immunity)
- After birth IgG levels drop; fetus also obtains antibodies from breast milk
haemolytic disease of the newborn definition prevention diagnosis treatment consequences (3)
SAQ 2012
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
effect of pregnancy on autoimmune conditions
Th2 autoimmune conditions worsen e.g. SLE, scleroderma, thyroid
Th1 autoimmune conditions improve e.g. rheumatoid arthritis, multiple sclerosis
route of fetal infection (3)
- Haematogenous route (mostly viruses)
- Iatrogenic: amniocentesis/CVS
- Ascending (most common route)
features of fetal inflammatory response syndrome
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)
diagnosis of miscarriage (2)
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
management of miscarriage (3)
advs + disadvs
2017 SAQ
- 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 - Medical: vaginal Misoprostol
○ Less invasive
○ 1% experience excessive bleeding needing medical attention - 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
