Which of the following are the first-, second-, and third-line drugs to use in pregnancy-induced hypertension with no other problems?
No drugs have been subjected to randomized controlled trials in pregnant women so safety data are based on observational data in humans and animal fetuses. FDA categorization is helpful. Briefly, Category A drugs are proven to be safe in clinical trials; no drugs are in this category. Category B drugs are those in which there has been no evidence of harm from animal or human observational studies. Category C drugs are those in which abnormalities have been shown in animals given the drug but not seen in humans. Category D indicates evidence of risk to human fetuses, but benefit to the mother may still outweigh risk to the fetus. Category X drugs are harmful to the human fetus and benefit to the mother does not outweigh risk to the fetus. Methyldopa (Category B) is safe in pregnancy and is the first-line drug used for hypertension. Beta-blockers (Categories B and C) can cause intra-uterine growth retardation and neonatal hypoglycaemia, but are frequently used with four-weekly growth scans. Nifedipine (Category C) has not been shown to cause problems in humans. ACE inhibitors (category D) are teratogenic and later cause renal abnormalities, oligohydramnios, and limb contractures. Thiazides are not safe in pregnancy as they result in neonatal thrombocytopenia, jaundice, hyponatraemia, and bradycardia. Doxazosin is Category C but is not often used as there are other alternatives.
A 24-year-old woman who has a mechanical mitral valve replacement and requires warfarin 4 mg od comes to your clinic, seeking advice about becoming pregnant. She has heard that warfarin is dangerous in pregnancy.
What is the best anticoagulation regime in pregnancy to protect her from valve thrombosis?
Warfarin crosses the placenta and can cause spontaneous abortion, stillbirth, neonatal death, and prematurity. In addition, warfarin is teratogenic, particularly in weeks 6–9, resulting in warfarin embryopathy (nasal hypoplasia, saddle-shaped nasal bridge, skeletal defects, short fingers and toes, low birth weight, and developmental delay). However, the incidence of embryopathy in fetuses where the mother has been given warfarin in doses <5 mg daily is zero. Therefore the risk for this particular patient, who is on 4 mg of warfarin, is low. Heparin does not cross the placenta and so is safe for the fetus, but there is an increased incidence of valve thrombosis which can result in death. Low molecular weight heparin has not been shown to avoid this problem, although the incidence of valve thrombosis is lower. The position of the valve should also be considered. The mitral valve is more likely to thrombose than the aortic valve, and pregnancy is a hypercoagulable state with increased activation of prothrombin 1 and 2, TAT (thrombin–antithrombin complex), and D-dimer. Therefore the safest option for this patient is to continue warfarin throughout pregnancy. Warfarin should be stopped several weeks before delivery to reduce the risk of neonatal intracranial haemorrhage. Warfarin takes several weeks to be metabolized by the fetal liver.
A 28-year-old woman with Marfan syndrome presents 28 weeks pregnant, having been lost to follow-up, with a 47 mm sinus of Valsalva measurement on her echocardiogram (see below).
There is a family history of aortic dissection.
Which one of the following would be the best recommended mode of delivery?
The risk of dissection in pregnant Marfan patients is high (approximately 10% with sinus of Valsalva measuring >40 mm, compared with 1% if <40 mm). All patients should be on beta-blockers throughout pregnancy. Aortic dissection is one of the four major causes of death in pregnancy (which is rare) and can occur in women with normal aortas. Hormonal changes result in histological changes in the aorta and an increased risk of dissection. A patient with a family history of dissection has an additional high risk of dissection. Even though Caesarean section results in greater haemodynamic shifts than vaginal birth, the safest mode of delivery in this case would be to perform a Caesarean section in controlled circumstances with cardiothoracic standby in case aortic surgery is required as an emergency. Patients with significant aortopathy associated with other conditions, such as a bicuspid aortic valve, should also be treated with caution. Epidural anaesthesia results in hypotension, but if it is done by a careful titration technique with IV fluids and invasive monitoring by an experienced anaesthetist this can be overcome. In this case a combined spinal/epidural using the technique described would be recommended.
A 25-year old woman who is 35 weeks pregnant is referred to your clinic because of increasing shortness of breath, palpitations on exertion, and a murmur. A soft non-radiating ejection systolic murmur is heard loudest in expiration at the left sternal edge. Pulse is 90 bpm and normal in character. Blood pressure in the right arm is 104/62 mmHg. Non-pitting ankle oedema is present. The ECG shows sinus rhythm with left axis deviation and Q waves in lead III. The ST segments are quite flat inferolaterally with widespread T-wave inversion. There are several premature ventricular complexes. Echocardiography does not show the aortic valve clearly, but peak velocity across the LV outflow tract is 1.8m/s.
Which one of the following is the most appropriate next investigation?
History and examination can be misleading as dyspnoea, palpitations, and peripheral oedema are common in pregnant women and hypotension and a collapsing pulse are the norm. Over >90% of pregnant women will have an ejection systolic murmur. Sinus tachycardia, right bundle branch block, and premature ventricular and atrial complexes are common in pregnancy, and in the third trimester the ECG often shows left axis deviation, Q III, T III, and inferolateral ST depression, and T-wave inversion. Velocities across the outflow tract in pregnancy are usually increased because of the increased volume load, and chamber sizes on the echocardiogram are increased.
A 42-year-old woman presents 38 weeks pregnant with her fourth child with a 1 hour history of severe sudden-onset dull central chest pain associated with sweating and dyspnoea. She is diabetic, obese, and a smoker. The ECG shows 4 mm of ST elevation in the anterior leads.
What is the ideal management?
Myocardial infarction in pregnancy is rare but is increasing because mothers are tending to be older with increased incidences of obesity, diabetes, and smoking. Coronary dissection can occur, but now myocardial infarction due to coronary atheroma is more common. The adverse haemodynamics in pregnancy plus increased oxygen consumption and hypercoagulability increase the risk. Mortality is high (around 11%, although it is now decreasing in the primary PCI era). The aim should be to save the mother’s life and so radiation is not a concern. The life of the baby depends on survival of the mother (fetal mortality is approximately 9%, mostly due to maternal death). Conservative management is not appropriate. Interventional strategies and the subsequent need for antiplatelet agents are complicated and depend on a number of factors. The need for Clopidogrel precludes regional anaesthesia which is desirable post infarct. The Genous stent would currently require the shortest duration of dual antiplatelet treatment for around a week compared to 28 days for a bare metal stent.
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