Down's syndrome & maternal age

A woman's risk of having a baby with chromosomal abnormalities increases with her age.  

Down syndrome is the most common chromosomal birth defect, and a woman's risk of having a baby with Down syndrome is:

• At age 25 -  1 in 1,250
• At age 30 - 1 in 1,000
• At age 35 - 1 in 400
• At age 40 - 1 in 100
• At age 45 - 1 in 30
• At age 49 - 1 in 10

Monozygotic twins - Types

Various types of chorionicity and amniosity (how the baby's sac looks) in monozygotic (one egg/identical) twins as a result of when the fertilized egg divides  :  (From wikipedia)


 

Read chart near the diagram in wiki  

SLE

Infections in SLE :

- Patients with SLE may be functionally asplenic and at risk from encapsulated bacterial infections like meningococcemia.
- Immunosuppred patients are at increased risk of sepsis
- Infection can mimic a lupus flare
- ESR and CRP may be raised. CRP changes more acutely, and the ESR lags behind disease changes.
- Measurement of complement may be useful as C3 and C4 levels are reduced in patients with active SLE due to consumption by immune complex–induced inflammation.

Raynaud's phenomenon

- Diagnostic criteria for primary Raynaud phenomenon :

1. Attacks triggered by exposure to cold and/or stress
2. Symmetric bilateral involvement
3. Absence of necrosis
4. No detectable underlying cause
5. Normal inflammatory markers and negative antinuclear factors.

Raynaud's phenomenon

Raynaud phenomenon:

- Recurrent vasospasm of the fingers and toes usually in response to stress or cold exposure.

- Characterised by 3 phases of change:

1. White (vasoconstriction), followed by
2. Blue (cyanosis), and then
3. Red (rapid blood reflow)

- Raynaud disease (primary Raynaud phenomenon) is characterised by the occurrence of the vasospasm alone, with no association with another illness

- Secondary Raynaud phenomenon is vasospasm associated with another illness, usually an autoimmune disease – typically systemic sclerosis, SLE and mixed connective tissue disease

- Diagnostic criteria for primary Raynaud phenomenon :

1. Attacks triggered by exposure to cold and/or stress
2. Symmetric bilateral involvement
3. Absence of necrosis
4. No detectable underlying cause
5. Normal inflammatory markers and negative antinuclear factors.

- Young women with Raynaud phenomenon alone for more than 2 years and no additional manifestations are at low risk for developing an autoimmune disease.

SLE - Challenges in management in pregnancy

1. Differentiating signs and symptoms of normal pregnancy from those of exacerbations SLE
2. Differentiate malar rash from chloasma
3. Differentiate proteinuria secondary to preeclampsia from proteinuria due to lupus nephritis. Lupus nephritis is often associated with proteinuria and cellular casts whereas only proteinuria is seen in patients with preeclampsia.
4. Differentiating renal disease secondary to an exacerbation of SLE from preeclampsia.
5. Differentiating thrombocytopenia in pregnancy from thrombocytopenia of SLE exacerbation

SLE

Pulmonary features of SLE

• Pleurisy with pleuritic chest pain +/- pleural effusions is the commonest feature
• Pulmonary embolism, lupus pneumonitis, chronic lupus interstitial lung disease, pulmonary hypertension, alveolar hemorrhage and infection are other complications

GI features

• Abdominal pain in active SLE may be due to peritonitis, pancreatitis, mesenteric vasculitis or bowel infarction

Cardiac features

• Pericarditis is the most common cardiac feature, presenting with positional chest pain that is relieved on leaning forward.
• Myocarditis and pulmonary hypertension can present with breathlessness and chest pain
• Coronary artery disease presents with angina

Pulmonary embolism - recommended investigations

RCOG Guidelines

1. Where there is clinical suspicion of acute PE a chest X-ray should be performed. 

2. Compression duplex Doppler should be performed where chest X-ray is normal. 

3. If both tests are negative with persistent clinical suspicion of acute PE, a ventilation–perfusion (V/Q) lung scan or a computed tomography pulmonary angiogram (CTPA) should be performed. 

4. Alternative or repeat testing should be carried out where V/Q scan or CTPA and duplex Doppler are normal but the clinical suspicion of PE is high. 

Anticoagulant treatment should be continued until PE is definitively excluded.

SLE - Rx & effects

Maternal effects :
- Treatment with cyclophosphamide may lead to premature ovarian failure and infertility

- Increased risk of hypertensive disorders: Pre-eclampsia occurs in ~15% of women and may be difficult to distinguish from lupus nephritis

- Increased risk of UTI

- Increased risk of gestational diabetes

- VTE – risk especially increased in women with anti-phospholipid antibodies. 

1. Women already on warfarin should be switched to therapeutic LMWH as soon as the pregnancy is recognized. 
2. Women with antiphospholipid syndrome but no previous VTE should be treated with prophylactic LMWH and low-dose aspirin during subsequent pregnancies. 
3. Women with SLE + antiphospholipid antibodies but no past morbidity can be managed with low-dose aspirin +/- hydroxychloroquine.

SLE - preconceptional counselling

Preconception management :

1. Assess disease activity from history, examinations and investigations

2. Risk assessment by checking for antiphospholipid antibodies (for a risk of fetal loss) and for anti-Ro and anti-La antibodies (for a risk of neonatal lupus) should be performed before pregnancy.

3. If active disease, advise to defer pregnancy and continue effective contraception

4. Discuss effect of SLE on pregnancy management and outcome. 

5. Women with anti-phospholipid antibody syndrome will require more frequent monitoring than those with SLE alone

6. Discuss effect of pregnancy on SLE

7. Discuss terratogenic effects of drugs such as methotrexate, cyclophosphamide and mycophenolate. 
Due to long half-lives, these drugs should be stopped at least 3 months before the planned conception.

8. Women should use contraception while on immunosuppressive disease-modifying drugs such as mycophenolate and cyclophosphamide. 
 Cyclophosphamide is absolutely contraindicated during pregnancy.

9. Discuss drugs that need to be stopped as soon as pregnancy is detected, such as warfarin.

10. Discuss general measures including folic acid supplementation, screening for rubella immunity

LMWH & regional anasthesia

Regional techniques should not be used until 12 hours after prophylactic & 24 hours after therapeutic dose of LMWH.

Catheter should not be removed within 10-12h of the most recent injection. 

Delivery by C/S -

Prophylactic dose LMWH day before surgery, 
omit morning dose on day of surgery and 
administer prophylactic dose by 3 hours post-op or 4h after insertion or removal of catheter

Cardiac murmur in pregnancy

• Systolic murmurs are common 
- prevalence over 90% 
- vast majority are flow murmurs. 
- Over 90% of patients have normal cardiac structure and function on ECHO
• Left sternal border area is most frequently the area of maximal intensity

• Diastolic mumurs are uncommon and should be considered abnormal as should pansystolic and long and loud systolic murmurs

Acute cortical necrosis

• Characterised by renal cortical cell death with sparing of the medullary portion of the kidney

• Rare complication and almost always associated with pregnancy especially in association with placental abruption in older multiparous women

• If the entire renal cortex is involved, renal failure is irreversible

• Renal failure from acute tubular necrosis is more common (75% of acute renal failure) and is reversible

Medical disorders in pregnancy

• Sickle cell disease - complications are more common in pregnancy and ~35% of pregnancies will develop crises
• Eisenmenger's syndrome - atrial or ventricular septal defect with pulmonary hypertension and right-to-left shunt.

- Cyanotic heart disease with ~50% mortality in pregnancy
• Multiple sclerosis is less likely to present for the first time and less likely to relapse during pregnancy

Anticoagulation in pregnancy

- LMWH should be given daily in two subcutaneous divided doses (in view of recognised alterations in the pharmacokinetics of dalteparin and enoxaparin during pregnancy) titrated against the woman’s booking or most recent weight. 
 
- Tinzaparin may be administered once daily. 

- Routine measurement of peak anti-Xa activity for patients on LMWH is not recommended except in women at extremes of body weight (< 50 kg and > 90 kg) or with other complicating factors (for example with renal impairment or recurrent VTE) putting them at high risk. 

- Peak anti-Xa (3 hours post-injection) should be 0.5–1.2 units/ml.

- Routine platelet count monitoring should not be carried out (unless unfractionated heparin has been given).

Pulmonary embolism - Investigations

Chest X-ray - may identify other pulmonary disease such as pneumonia, pneumothorax or lobar Collapse. 

If the X-ray is abnormal with a high clinical suspicion of PE, CTPA should be performed.

If the X-ray is normal, bilateral Doppler ultrasound leg studies should be performed. 

A diagnosis of DVT may indirectly confirm a diagnosis of PE and, since anticoagulant therapy is the same for both conditions, further investigation may not be necessary.

This would limit the radiation doses given to the mother and her fetus.

The choice of technique for definitive diagnosis (V/Q scan or CTPA) will depend on local availability and should be made after discussion with a radiologist.

(RCOG recommendations)

D-dimers

D-dimers are elevated in normal pregnancy and post-partum and also in complications of pregnancy such as pre-eclampsia. 

However, low level in pregnancy decreases index of suspicion of VTE

Previous VTE with No thrombophilia:

• Low molecular weight heparin for 6 weeks after delivery is recommended


• Value of antenatal thromboprophylaxis is controversial.


• However, if the previous VTE was oestrogen-related (pregnancy or OCP) or high BMI, antenatal thromboprophylaxis should be considered


• Women with more than one VTE, one VTE plus VTE in a first degree relative or VTE in an unusual site(e.g. - axillary) should receive antenatal thromboprophylaxis continued for 6 weeks post-partum


• Most VTE occurs antenatally but the risk per day is greatest in the weeks immediately following delivery


• Previous VTE is not contra-indication to regional anaesthesia in labour

Pituitary micro-adenomas

• Tumour less than 10mm diameter

• Microadenomas enlarge during pregnancy but <2% of women will develop signs / symptoms - headache usually preceeds visual disturbance
• Serum prolactin levels are not useful in assessing tumour size in pregnancy
• Bromocriptine can safely be used in the first trimester. 

• Breast-feeding is permitted without fear of stimulating tumour growth

Immune diseases & pregnancy

• Rheumatoid arthritis typically improves in pregnancy
• Sarcoidosis is unaffected or may improve during pregnancy
• Asthma may improve, worsen (typically severe disease) or remain unchanged

• Eczema often, but not invariably improves in pregnancy