Prescribing in pregnancy

• Teratogen:

  • Cause or contribute to structural or functional anomaly, or abnormal neurological development
  • Either during or after pregnancy
  • Medications, recreational drugs, tobacco, alcohol and infections
• Placental transfer:

  • Interface between mother and baby
  • Almost all drugs cross the placenta - some are beneficial e.g. steroids
  • Transfer depends on molecular weight - <500Da readily cross
  • Heparins and insulin do not cross
• Timing of exposure:

  • Timing is critical as determines nature and extent of adverse effects
  • Greatest risk in 1st trimester
  • Second/third trimester lower risk but are some drugs that can cause harm close to term
• 3 stages of human development:

  1. Pre-embryonic = up to 17 days post conception
  2. Embryonic = day 18 to day 55
  3. Foetal = 8 weeks to term
• Analgesia:

  • Pain is a common problem in pregnancy
  • Paracetamol is generally safe - emerging evidence that link to emotional/behavioural issues
  • NSAIDs are avoided
  • Opioids - codeine can be used
• NSAIDs:

  • Work by blocking prostaglandins - are important in the maintaining of the ductus arteriosus in the foetus and neonate
  • Prostaglandins also soften and stimulate uterine contractions at the time of delivery - use of NSAIDs can delay labour
  • Regular use beyond 30 weeks has been associated with oligohydramnios due to reduced perfusion of the foetal kidneys
  • Use around the time of delivery may increase risk of PPH due to platelet dysfunction
• Opioids:

  • Codeine can be used
  • Other opioids should be avoided towards the end of the third trimester - can result in neonatal respiratory depression and withdrawal symptoms
• Penicillin's and Cephalosporins (Ceftriaxone, cefuroxime) are the antibiotics of choice in pregnancy
• Antibiotics safe in pregnancy and breastfeeding:

  • Penicillin's (except co-amoxiclav in the third trimester)
  • Cephalosporins (Cephalexin, Ceftriaxone)
  • Aciclovir
  • Macrolides (clarithromycin)
  • Metronidazole
• Antibiotics not recommended:

  • Tetracyclines (doxycycline) - stain developing bone and teeth of foetus - avoid in pregnancy and breastfeeding
  • Trimethoprim - avoid in first trimester, can be used while breastfeeding
  • Nitrofurantoin - Avoid in third trimester due to concerns of haemolytic anaemia in new born
  • Quinolones - avoid if possible but can be used under specialist advice
• Immunisations:

  • MMR contraindicated
  • Live vaccines contraindicated
  • Influenza vaccine (inactivated) is recommended to all women
  • Whooping cough recommended after 20 weeks
  • Maternal immunisation has a two-fold infant protective effect
• Warfarin:

  • Crosses the placenta
  • Considered teratogenic
  • Foetal loss
  • Congenital malformations - foetal warfarin syndrome - nasal hypoplasia (craniofacial deformities)
  • Bleeding during pregnancy, PPH, foetal haemorrhage and intracranial bleeding (any time during pregnancy)
• LMWH:

  • Does not cross the placenta
  • No monitoring needed
  • Other heparins associated with reversible osteoporosis and heparin induced thrombocytopenia - lower risk with LMWH
• Antiepileptics that cross the placenta (potentially teratogenic):

  • Phenytoin
  • Primidone
  • Phenobarbitone
  • Carbamazepine
  • Sodium valproate
• Common congenital malformations associated with anti-epileptics:

  • Neural tube defects
  • Congenital heart disorders
  • Cleft palate
  • Skeletal abnormalities
• Sodium valproate:

  • Highly teratogenic
  • Physical and neurodevelopmental defects common
  • Contraindicated in women of childbearing potential unless conditions of pregnancy prevention program are met - including using highly effective contraception e.g. IUD
• Isotretinoin (Roaccutane)

  • Retinoid medication (related to vitamin A) used to treat severe acne
  • Highly teratogenic - miscarriage and congenital defects
  • All conditions of pregnancy prevention program must be met
• Roaccutane effects:

  • CNS abnormalities
  • Cleft palate
  • Craniofacial abnormalities
  • External ear abnormalities
  • Cardiovascular abnormalities
  • Thymic aplasia (absence of the thymus)
• Prescribing in pregnancy principles:

  • Clear indication?
  • Benefits outweigh risk?
  • Try avoiding in 1st trimester
  • Lowest dose, shortest duration
  • Choose medications with good safety tract record
  • Avoid polypharmacy
  • Preconceptual counselling
• Lithium:

  • Antimanic agent - used for bipolar disorder
  • Avoid in pregnancy unless absolutely necessary
  • Particularly avoided in the 1st trimester as this is linked with congenital cardiac abnormalities - particularly Ebstein's anomaly - tricuspid valve is set lower
  • If lithium is used, levels need to be monitored closely
  • Lithium enters breast milk and is toxic to the infant
• ACE inhibitors and ARBs:

  • Medication that block the renin-angiotensin system can cross the placenta and enter the foetus
  • Mainly affects the foetal kidneys and reduce the production of urine and therefore amniotic fluid
  • Oligohydramnios
  • Miscarriage or foetal death
  • Hypocalvaria - incomplete formation of the skull bones
  • Renal failure in the neonate
  • Hypotension in the neonate