Maternal medical conditions Flashcards
SLE - definition, epidemiology, RFs
Idiopathic, systemic connective tissue disease
Periods of disease activity / remission
Heterogeneous with a variety of clinical and antibody patterns
Epidemiology:
Prevalence 1:1000
Average age at diagnosis = 30yo, increased in Afro-Caribbean
Female: male = 10:1; in pregnancy years = 15:1
Risk factors:
Female, family history, other auto-immune disease
SLE - aetiology
- Idiopathic
- Genetic - family history (10% have affected relative), twin concordance >50%
- Autoimmune
-6% have other auto-immune disease
-Circulating non-specific auto-antibodies, polyclonal B cell activation, impaired T cell regulation of immunity, failure to remove immune complexes
-Deposition of immune complexes causes vasculitis - Environmental triggers – UV light, viral infection
- Drugs that bring on SLE – procainamide, quinidine, hydralazine
SLE - diagnostic criteria
4 or more of 11 criteria (American College of Rheumatology)
1. Malar rash
2. Discoid rash (on sun-exposed areas, no itch)
3. Photosensitivity
4. Oral ulcers
5. Arthritis (90%) – non erosive, >2 joints (joint involvement commonest clinical feature)
6. Serositis – pleuritis/pericarditis
7. Renal (lupus nephritis) (50%) – glomerulonephritis with proteinuria, haematuria, pyuria, urinary cellular casts
8. Neurological (lupus cerebritis) (20%) – seizures, headaches, chorea, stroke, transverse myelitis, mood disorder, psychosis
9. Haematological – haemolytic anaemia, leukopenia (<4), lymphopenia, thrombocytopaenia (<100)
10. ANA (present in 96% of SLE patients) (remember, will occur in 30% population at any given time)
11. Immunological
Anti dsDNA – 80-90%; elevated levels precede relapse; highly specific for SLE
Anti Sm – 40%; highly specific
APL (positive test for anticardiolipin or lupus anticoagulant) - 40%
Other tests:
Ab to other ENAs (Ro/SS-A or La/SS-B) in 30%; associated with neonatal lupus
Reduced complement titres (C3/C4), indicate active disease
FBE - normochromic normocytic anaemia, neutropenia, thrombocytopenia
ESR - elevated due to high immunoglobulin levels
CRP - usually normal (although can be raised with pleuritic/pericardial involvement)
What is the most common antibody in SLE?
ANA (present in 96% of SLE patients) (remember, will occur in 30% population at any given time)
What is the most common clinical feature of SLE?
Joint involvement - arthritis in 90%
SLE - effect of pregnancy on condition
- Increased likelihood of flare in pregnancy and particularly puerperium (40%-60%)
- Flares usually mild, occur at any stage, most commonly involve skin or joints
- May be difficult to diagnose due to symptom overlap with normal pregnancy (e.g. hair loss, oedema, palmar and facial erythema, fatigue, anaemia, raised ESR, MSK pain), and difficult to differentiate between lupus nephritis and pre-eclampsia
- Risk is lower when prior quiescent disease
- Lupus nephritis unlikely to manifest first in pregnancy without history pre-existing renal disease
- If pre-existing lupus nephritis
-33% renal flare if pre-existing
-7-10% flare if >6m since last episode
-50-60% flare if active disease at time of conception
-21% experience renal deterioration
-7% permanent deterioration (higher risk if higher baseline creatinine)
SLE - effect of condition on pregnancy
- Normal outcome if remission for >6m, no HTN/lupus nephritis/thrombocytopenia/aPLs
- Adverse outcomes increased if aPLs, lupus nephritis, active disease at conception, first SLE in pregnancy:
-Miscarriage
-HTN/PET
-Fetal death
-IUGR
-Prematurity (approx. 30% risk PTB/LBW <2.5kg)
How can you differentiate between a lupus nephritis flare and pre-eclampsia?
SLE - pre-conception management
- Confirmation of diagnosis and assessment of severity; rheumatological assessment
- Optimise disease status - aim for disease quiescence for at least 6m prior to conception
- Medications:
- Avoid NSAIDs
- Substitute ACEi
- Discontinue cytotoxic drugs e.g. MTX and cyclophosphamide for > 3 months pre-conception, mycophenolate mofetil for 4-6 months pre-conception
- Continue hydroxychloroquine to avoid increasing flare
- Commence low dose aspirin in pregnancy if nephritis, aPLs, vasculitis - Pre-conception evaluation:
-History / examination / blood pressure
-aPLs: lupus anticoagulant, anticardiolipin ab, anti-b2-glycoprotein ab
-Anti-Ro/SSA and anti-La/SSB ab > risk of fetal complete heart block
-Anti-ds DNA ab
-FBE, UEC (creatinine), LFTs, uric acid, TSH
-Complement levels (C3/4)
-Urinalysis with urine sediment, spot PCR, baseline 24h protein (consider renal bx if lupus nephritis) - Pre-conception counselling:
-Risk to mother: disease flare, PET, preterm birth
-Risk to fetus: fetal loss, IUGR, neonatal lupus syndrome, complications of prematurity; if Anti-Ro/SSA and anti-LA/SSB ab present risk of fetal complete heart block
-Advise against pregnancy IF serum creatinine >177, high risk of renal deterioration and poor fetal outcome
SLE - antenatal management
- Setting: Multidisciplinary team - combined clinic with obstetrician and physician
- Monitor disease activity: monthly anti-ds DNA, complement titre, 24h urinary protein
- Treat SLE: hydroxychloroquine, steroids (improve outcome in women with active SLE / raised anti-dsDNA levels)
- Serial growth ultrasounds (including uterine artery doppler 20-24 weeks)
- If Anti-Ro/La positive - FHR from 16 weeks, TTE if suspected complete heart block
- VTE thromboprophylaxis: if APLS or significant proteinuria
- Diagnosing flare as opposed to PET difficult (dx of lupus nephritis made with renal bx, contraindicated)
- Treat flare with corticosteroids
SLE - treatment of flare in pregnancy
- Treat flare with corticosteroids
Mild-mod = prednisolone 15-30mg/day
Severe without = prednisolone 1.0-1.5mg/kg/day
Severe with CNS/renal involvement = IV methylprednisolone
Lupus nephritis = prednisolone 1.0-1.5mg/kg/day
Can consider other medications: cyclophosphamide, rituximab, tacrolimus in special situations
SLE - intra/postpartum management
Aim for vaginal delivery
Hydrocortisone intrapartum if taking prednisolone >7.5mg >2 weeks
Breastfeeding:
- Contraindication – methotrexate, cyclophosphamide
- Caution with - azathioprine (theoretical immunosuppression), NSAIDs (can theoretically cause jaundice)
- Hydroxychloroquine okay
Neonatal lupus - pathophysiology
- Passively acquired anti-Ro/anti-La
- 75-95% mothers positive anti-Ro, 50-70% positive for anti-La
- Autoantibodies cross the placenta and cause immune damage to the fetus
- Several clinical syndromes including cutaneous neonatal lupus and congenital heart block (rarely co-exist)
Risk factors for having Anti-Ro antibodies
Present in:
- Mothers with SLE 30%
- Sjogren’s, Raynaud’s phenomenon, photosensitivity
- 1% general population
Neonatal lupus - clinical presentation
Cutaneous:
- Erythematous scaling plaques on face and scalp
- 2 weeks to 6 months
- Scarring rare
Cardiac:
Congenital heart block (CHB)
- Specifically related to 52 kDa Ro antibodies which causes fibrosis of conducting system particularly AV node)
- Likely progresses through 1st -> 2nd -> 3rd degree (complete) heart block
- If severe can lead to hydrops and FDIU
- Mortality rate 20% mainly in first 3 months of life; 60% require PPM in early infant life, and all by early teens to avoid risk sudden death
- Recurrence rate 10-20%
Endocardial fibroelastosis, myocarditis, dilated CM, pericardial effusion, mitral insufficiency
Haematological:
- Rare
- Autoimmune haemolytic anaemia, leukopenia, thrombocytopenia
- Hepatosplenomegaly
Neonatal lupus - risk factors
Mother has SLE = <5% (not related to severity of disease)
Mother has anti-Ro/La – cutaneous lupus = 5%; fetal heart block = 2%
1 Previous child affected – 16-18%; 2 Previous children affected – 50%
Neonatal lupus - diagnosis and management of congenital heart block
Diagnosis:
- Bradycardia during routine scan / check
- Fetal TTE with AV dissociation with structurally normal heart
- Maternal autoantibodies
Antenatal management:
- Maternal autoantibodies
- Close monitoring of fetal heart rate (e.g. weekly from 16 weeks)
- Fetal TTE
- If bradycardia detected at or near term, delivery required
Neonatal management:
- Neonatal FBE, UEC, LFT
- Avoid sunlight/phototherapy
- 60% require PPM in early infancy, otherwise by early teens
Neonatal lupus - recurrence rate of CHB in future pregnancies
10-20%
Epilepsy - AED risks
Risk dependent on type of AED, dose and mono/polytherapy
Risks associated with AEDs:
Major malformations
- NTDs
- Orofacial clefts
- Congenital heart defects
- Urinary tract abn
- Skeletal abn
Minor malformations (fetal anticonvulsant syndrome)
- Dysmorphic features - V shaped eyebrows, low-set ears, broad nasal bridge, irregular teeth
- Hypertelorism
- Hypoplastic nails and distal digits
- Hypoplasia of mid face
Fetal growth restriction
Adverse long-term neurodevelopment outcomes - impaired neurodevelopment, lower IQ, higher rates of autism and ADHD
Lowest risks with lamotrigine, levetiracetam and carbamezapine (especially if low dose and used as monotherapy)
- No evidence for long term adverse neurodevelopmental outcomes
Lamotrigine:
- Conflicting data for increased risk, dose related, malformations increased when >300mg/day (EURAP), particular risk of small isolated oral cleft malformation
- Commonly required to increase dose of lamotrigine in pregnancy, serial drug levels may be required (esp. if regular seizures)
Epilepsy - labour, delivery, postpartum
- Caesarean section only required if recurrent generalised seizures in late pregnancy or labour
- Risk of seizures increases around time of delivery, however absolute risk of seizures in labour is low (1-2% intrapartum)
- Setting - consultant-led unit with facilities for one-to-one midwifery care and maternal and neonatal resuscitation
- Continue regular AEDs in labour - if not tolerated orally, parenteral alternative
- Intrapartum measures to reduce risk
○ Adequate analgesia
○ Appropriate care in labour to reduce insomnia, stress, dehydration
○ Early epidural recommended to limit risk of precipitating a seizure due to pain and anxiety - Management of seizures in labour
○ If not rapidly self-limiting - administer oxygen and IV lorazepam or diazepam (IV or rectal gel)
○ For women who have had seizures during previous deliveries or who are at high risk of seizures peripartum, oral clobazam may be used for short periods of time (e.g. starting day prior to delivery or at onset of labour)
○ Magnesium sulphate should be the initial drug of choice if suspicion of eclampsia - Postpartum
○ Neonate should receive 1mg Vit K IM
○ Encourage breastfeeding - AEDs cross into breast-milk but usually at subtherapeutic levels
○ Encourage changing nappies while on the floor, bathing baby in shallow water or with supervision
○ Woman should not be left unattended in first 24 hours postpartum due to high risk seizures
Contraception: Women taking hepatic enzyme inducing drugs (e.g. carbamezapine) or lamotrigine require higher doses oestrogen to receive adequate contraception (Mirena and depo unaffected)
