23.3 Medical & Surgical Disorders in Pregnancy: Drug Pharmacokinetics, Epilepsy, Thyroid, Heart Disease, SLE & APS, Asthma, Liver Disorders, Anemia, Dermatoses, Appendicitis, Gallstones, Stones and Trauma

Why this area matters

TOS area H asks you to:

• recognize seizure disorders, UTI, thyroid disease, autoimmune disease, heart disease, asthma, pancreatitis, GI disorders and dermatoses in pregnancy;
• describe the effects of pregnancy on these diseases, and of the diseases on pregnancy;
• choose drugs with the pharmacokinetics of pregnancy in mind;
• screen and prevent recurrences.

TOS area I adds appendicitis, trauma, cholelithiasis and urolithiasis, managed with the least harm to the fetus, appropriate anesthesia, and preoperative and postoperative care. Indirect causes, such as heart disease, are a growing share of maternal deaths as direct causes decline.

Drugs and pharmacokinetics in pregnancy

• Volume of distribution increases (more plasma and body water) and albumin falls, raising the free fraction of highly protein-bound drugs such as phenytoin.
• Renal clearance increases with GFR, so renally excreted drugs (penicillins, lithium, enoxaparin) may need higher or more frequent doses.
• Hepatic metabolism changes: CYP3A4 and CYP2D6 activity rises. Lamotrigine levels fall markedly, so doses are adjusted to levels.
• Absorption may be delayed by slower gastric emptying.
• Choose drugs with the longest safety record at the lowest effective dose. Do not withhold necessary treatment, because uncontrolled maternal disease usually harms the fetus more.

Seizure disorders

• Epilepsy:
  • seizure control usually stays the same, but tonic-clonic seizures risk injury, hypoxia and abruption;
  • valproate (neural tube defects, lower IQ), phenytoin, carbamazepine and phenobarbital are teratogenic;
  • lamotrigine and levetiracetam have the lowest risk;
  • give folic acid before conception, usually at a higher dose;
  • schedule an anomaly scan;
  • continue antiepileptic drugs, because stopping them risks status epilepticus.
• A new seizure after 20 weeks is eclampsia until proven otherwise. Treat it with magnesium sulfate.

Endocrine and autoimmune disease

• Hyperthyroidism (Graves disease):
  • use PTU in the first trimester, because methimazole causes aplasia cutis and choanal or esophageal atresia, then switch to methimazole, because PTU is hepatotoxic;
  • TSH-receptor antibodies cross the placenta and can cause fetal or neonatal thyrotoxicosis;
  • thyroid storm is precipitated by labor, infection or cesarean delivery.
• Hypothyroidism: raise levothyroxine by about 25% to 30% as soon as pregnancy is confirmed, and check TSH every 4 weeks in the first half of pregnancy. Untreated hypothyroidism impairs fetal neurodevelopment.
• Systemic lupus erythematosus:
  • plan pregnancy during at least 6 months of remission;
  • continue hydroxychloroquine;
  • distinguish a lupus flare from preeclampsia (low complement and active urine sediment favor lupus);
  • maternal anti-Ro/SSA antibodies cause congenital heart block and neonatal lupus.
• Antiphospholipid syndrome: causes recurrent loss, preeclampsia, growth restriction and thrombosis. Treat with low-dose aspirin plus prophylactic or therapeutic heparin.

Heart disease

• Physiologic burden: blood volume and cardiac output rise most in the late second trimester, and again in labor and immediately postpartum. The postpartum rise comes from autotransfusion.
• Lesions by tolerance:
  • Rheumatic mitral stenosis, common in the Philippines, is the classic decompensating lesion. Tachycardia shortens diastolic filling, causing pulmonary edema and atrial fibrillation. Treat with beta-blockers and diuretics; balloon valvotomy can be done in pregnancy.
  • Regurgitant lesions are well tolerated, because the lower systemic resistance helps.
  • Pregnancy is contraindicated (WHO class IV) in pulmonary arterial hypertension and Eisenmenger syndrome, severe left heart obstruction, severe left ventricular dysfunction and Marfan syndrome with a dilated aorta.
• Peripartum cardiomyopathy: heart failure with LVEF below 45% in the last month of pregnancy or in the 5 months after delivery.
• Mechanical valves: warfarin causes embryopathy in weeks 6 to 12. Many switch to low-molecular-weight heparin in the first trimester and near delivery.
• Delivery: usually vaginal with an epidural and an assisted second stage. Endocarditis prophylaxis is limited to the highest-risk lesions.

Respiratory, renal, GI and hepatic disorders

• Asthma: about one-third of patients improve, one-third worsen and one-third stay the same. Continue inhaled corticosteroids and bronchodilators, because poorly controlled asthma causes fetal hypoxia. In PPH, avoid carboprost in asthmatics.
• Urinary tract infection: treat asymptomatic bacteriuria. Pyelonephritis needs admission and IV ceftriaxone, because of the risk of sepsis, ARDS and preterm labor. Avoid fluoroquinolones, and avoid nitrofurantoin near term.
• Intrahepatic cholestasis of pregnancy:
  • occurs in the third trimester;
  • generalized itching, worst on the palms and soles, without a rash;
  • raised serum bile acids;
  • risk of sudden stillbirth;
  • treated with ursodeoxycholic acid and delivery at about 36 to 37 weeks, or earlier if bile acids are very high.
• Acute fatty liver of pregnancy:
  • occurs in the third trimester;
  • nausea and vomiting, then liver failure with hypoglycemia, coagulopathy and renal failure;
  • linked to fetal LCHAD deficiency;
  • managed with immediate delivery.
• Hyperemesis gravidarum is covered with early pregnancy problems.
• Acute pancreatitis is usually caused by gallstones or hypertriglyceridemia.
• Anemia: iron deficiency is most common. Thalassemia trait is common in the Philippines, so a microcytosis that does not respond to iron needs hemoglobin studies.

Dermatoses of pregnancy

• Polymorphic eruption of pregnancy (PUPPP):
  • itchy urticarial papules starting in the abdominal striae and sparing the umbilicus;
  • usually in a first pregnancy in the third trimester;
  • harmless.
• Pemphigoid gestationis:
  • autoimmune blisters that involve the umbilicus;
  • can cause neonatal blisters and prematurity;
  • treated with corticosteroids.
• Atopic eruption of pregnancy is the most common dermatosis of pregnancy and appears early.

Surgical disorders in pregnancy

• Acute appendicitis:
  • the most common nonobstetric surgical emergency;
  • the appendix is pushed upward and laterally by the uterus, so pain may be in the right flank or right upper quadrant;
  • leukocytosis is less specific in pregnancy;
  • diagnose with graded-compression ultrasound, then MRI (no ionizing radiation) if ultrasound is inconclusive;
  • operate promptly in any trimester (laparoscopy is acceptable), because perforation greatly raises fetal loss.
• Cholelithiasis and cholecystitis: pregnancy promotes gallstones. Uncomplicated biliary colic is managed conservatively, but recurrent attacks, cholecystitis or gallstone pancreatitis are treated with cholecystectomy, ideally in the second trimester.
• Urolithiasis: causes flank pain and hematuria. Use renal ultrasound, remembering that right-sided hydronephrosis is physiologic. Most stones pass with hydration and analgesia. Stent or nephrostomy for obstruction with infection.
• Adnexal torsion and ovarian masses: most adnexal masses are functional cysts or dermoids. Torsion needs urgent laparoscopy and detorsion.
• Trauma:
  • resuscitate the mother first, with left uterine displacement after 20 weeks;
  • monitor the fetus for at least 4 hours after significant blunt trauma, because placental abruption may follow even minor trauma;
  • give anti-D to Rh-negative women, with a Kleihauer-Betke test;
  • in maternal cardiac arrest after 20 weeks, begin perimortem (resuscitative) cesarean delivery within 4 minutes, so that delivery occurs by 5 minutes.
• Elective surgery is postponed until after delivery. Necessary surgery is best done in the second trimester.
• Anesthesia: regional anesthesia is preferred. With general anesthesia, guard against aspiration and hypoxemia. Keep the patient in left uterine displacement and use thromboprophylaxis.