Women's health

• Stages of pregnancy


  1. First trimester (weeks 1-12)

  2. Fertilised egg travels along fallopian tube dividing constantly until it reaches the uterus and implants in the lining

  3. Organs begin to develop

  4. Second trimester (weeks 13-27)

  5. Muscles and bones continue to develop

  6. Growth occurs rapidly

  7. All essential organs have formed

  8. Third trimester (weeks 28-41)

  9. Movement increases and babies begin to practice breathing by moving their diaphragm

  10. Weight increases significantly

  11. Bones harden and skin thickens
• Use of drugs in pregnancy

  • The need for drugs in pregnancy can be due to pre existing conditions or those developed as a result of pregnancy itself
  • Drugs can have harmful effects on a developing foetus at any point during the 9 months of pregnancy
  • These effects vary depending on the stage of pregnancy
  • The use of drugs in women of child bearing age is always important to consider even if they are not currently pregnant – for women who must take a potentially teratogenic drug they must be advised on suitable methods of contraception
  • For some drugs, it is also relevant to men since some drugs should also be avoided by men who wish to father a child (e.g. griseofulvin)
• Effect of drugs in different trimesters

  1. First trimester

  2. Often thought of as the main time of concern when using drugs since some drugs used in the first trimester can cause structural congenital malformations or be teratogenic

  3. A teratogen is something that causes structural or functional abnormalities in a foetus or child

  4. Second and third trimester

  5. Use of drugs at this stage can lead to effects on the growth and functional development of the foetus

  6. Some drugs given very late in pregnancy can lead to adverse effects after delivery including withdrawal symptoms (e.g. opiates)
• Teratogens


  • Any drug or substance that can cross the placenta and cause a congenital malformation is known as a teratogen
  • Teratogens can cause structural or functional abnormalities in a foetus or child after birth
  • Teratogens will not always cause an issue – e.g. thalidomide caused abnormalities in less than half of foetuses exposed during the critical period
  • Only 1-2% of major congenital malformations are thought to be caused by drugs
  • Teratogenicity is usually dose dependent
• Physiological changes during pregnancy

  • Physiological changes occur in the mother in order to meet foetal growth requirements and to prepare for labour and delivery
  • These changes can impact on the pharmacokinetics and pharmacodynamics of drugs which can then impact on their effectiveness and toxicity
• Examples of physiological changes during pregnancy

  • BP initially decreases and increases back to pre pregnancy levels at term. There is an associated increase in heart rate and stroke volume
  • Changes in the coagulation cascade can lead to increased risk of a VTE
  • Increase in renal blood flow means renally excreted drugs may be cleared more rapidly
  • Plasma volume increases and albumin levels decrease affecting drug levels of highly protein bound drugs
  • Altered activity of hepatic enzymes can affect drugs metabolised in the liver
  • A decrease in lower oesophageal sphincter pressure and a decrease in GI motility can lead to bloating, reflux and constipation
• Safety of drugs in pregnancy

  • Drugs are very rarely tested on pregnant women
  • Most manufacturers will be cautious and may contraindicate the drug for use in pregnancy or attach special warnings for its use
  • Animal studies can reveal effects on foetal development
  • Evidence for safety in pregnancy usually comes from post authorisation drug safety data which looks at case reports, registry data, birth monitoring services and clinical studies
  • Absence of a warning does not imply safety
  • Avoid all drugs if possible in first trimester and if drugs must be used, use one drug at the lowest effective dose for the shortest possible time, using a drug that has been used extensively and appears to be safe
  • Avoid newer, untested drugs
• Sodium Valproate (Epilim ® Depakote ®)


  • Sodium valproate is a known teratogen and is associated with foetal malformations and developmental delays
  • In addition, many other antiepileptic drugs can lead to folate deficiency which is linked to the development of neural tube defects such as spina bifida
  • In 2018, warnings were strengthened and now must be present on boxes
  • However, it is important to control epilepsy during pregnancy since frequent or prolonged maternal seizures can cause miscarriage and premature labour and deprive the foetus of oxygen and nutrients
  • Initiated only if two specialists independently agree for patients under 55 years old
  • Women of child bearing age MUST be on a pregnancy prevention programme (PPP)
• Isotretinoin (Roaccutane ®)


  • Retinoids, including isotretinoin are contraindicated in pregnancy due to a high risk of serious congenital abnormalities and life threatening birth defects
  • It should only be used for severe acne resistant to standard therapy and given under specialist supervision
  • Women of child bearing age who are using isotretinoin should be enrolled on a pregnancy prevention programme
• Antidepressants


  • Women with mental health conditions may receive conflicting advice on how to manage their condition and whether or not they should continue to take medicines
  • Women who become pregnant may suddenly stop taking their medication since they may feel this is the safest thing to do
  • Leaving a condition such as severe depression untreated can have adverse effects on the pregnancy outcome and can affect the developing relationship between the mother and child
  • TCAs and SSRIs have not been associated with a significant risk of foetal abnormalities
  • If patient is willing and suitable, consider talking therapies
• Analgesics


  • Pain is common in pregnancy
  • Paracetamol is safe and effective and recommended first line for mild to moderate pain
  • Use of NSAIDs in late pregnancy can lead to premature closure of the ductus arteriosus which can lead to congestive heart failure
  • Use of opiates in late pregnancy can lead to respiratory depression and withdrawal symptoms in the neonate but are not linked to an increased risk of congenital abnormalities
  • Codeine is first choice if an opiate must be used
  • Strong opioids used during labour can lead to neonatal issues
  • Opioids can also exacerbate constipation, nausea and vomiting which are already common during pregnancy
• Breastfeeding


  • Breastfeeding offers a range of health benefits for both the mother and child
  • The chance of an adverse reaction to a drug that has transferred through breast milk is very low
  • Most drugs are unlicensed for use during breastfeeding since there is usually no clinical data available since it is unethical to expose an infant to potential harm
• Use of drugs during breastfeeding


  • There is little information available about the effect of drugs taken by a mother on a breastfed infant
  • The amount of drug transferred via breast milk is usually very low
  • Outcome depends on how much of the drug or active metabolite is transferred, the pharmacokinetics of this in the infant and the effect of the drug on the infant
  • The BNF provides information on drugs that should be avoided or used with caution in breastfed infants and drugs that are known to be safe either because they the amount transferred is too low to be harmful or the drug itself is not harmful
• Use of drugs during breastfeeding

  1. Avoid unnecessary use of drugs

  2. Assess risk vs benefit

  3. Consider the greater risk in neonates and premature infants due to underdeveloped hepatic and renal function leading to reduced excretion and a risk of drug accumulation

  4. If drugs must be used choose a route of administration and regime that minimises the risk to the infant – e.g. topical products for hay fever rather than oral antihistamines

  5. Avoid drugs with long half life if possible due to risk of accumulation

  6. If appropriate, consider taking drug immediately after infant has been fed, aiming to avoid feeding at peak milk concentrations
• Factors to consider if drug is compatible with breastfeeding

  • Is the treatment really needed?
  • Is there a drug option that is licensed for use in infants?
  • How old is the baby and were they full term?
  • The hepatic and renal function of an infant takes some time to develop fully
  • Infant that were premature can be more susceptible to drugs
  • How much breast milk is being given?
  • Younger infants who have not been weaned and are exclusively breastfed will consume more milk than older children
• Factors to consider if drug is compatible with breastfeeding

  • Can you choose a drug which is highly protein bound? If so, less drug is free to enter milk
  • Choose a drug that has a low plasma:milk ratio since less will be found in breastmilk
  • Drugs with a shorter half life are more suitable since they are less likely to accumulate
  • If infant also being actively treated for a condition, consider accumulation of drugs through maternal milk supply exposure in addition to treatment infant receiving directly to reduce additive side effects
• Codeine


  • Use of codeine is not recommended in breastfeeding women due to a fatal case of morphine toxicity in a breastfed infant – codeine is metabolised into morphine in the body
  • Ultrarapid metabolisers convert more codeine into morphine leading to potential toxicity
  • Alternative opioids may be safer e.g. dihydrocodeine and tramadol but should be used under close supervision and the mother and infant monitored
  • Replace opioid with non-opioid analgesic if adverse effects develop in infant and withhold breastfeeding
  • Neonates and young infants are most at risk due to immature hepatic enzyme function
• Ibuprofen and Paracetamol


  • Ibuprofen
  • Ibuprofen is one of the analgesics of choice when breastfeeding
  • Only very small amounts pass into breast milk which are lower than the doses that would be given to infants directly
  • Does not accumulate
  • Paracetamol
  • Paracetamol is the simple analgesic of choice
  • Very small amounts pass into breast milk and again are lower than the dose that would be given directly
  • Does not accumulate
  • Avoid co-codamol and caffeine containing combination products
  • Avoid decongestant combination products
• Antihypertensives


  • Beta blockers
  • Labetalol, metoprolol and propranolol are first choice when breastfeeding
  • Only very small amounts pass into breast milk
  • They have shorter half lives of drugs meaning there is a lower risk of accumulation in the infant
  • Labetalol and propranolol are used therapeutically in neonates, and metoprolol in infants over 1 month old
  • No need to change beta blocker treatment in breastfeeding if already used successfully in pregnancy as long as the infant is born full term and healthy
  • Not known to have an effect on breastfeeding, some non-selective beta blockers (labetalol) can cause nipple pain or Raynaud's phenomenon of the nipple
• Metronidazole


  • Consider for all antimicrobials whether concentration of antimicrobial in breastmilk sufficient enough to cause a bactericidal effect in infant?
  • Short courses of metronidazole considered compatible with breastfeeding
  • No interruptions to breastfeeding needed unless longer term treatment over a few weeks required
  • Low molecular weight, low protein binding so transfer into milk likely
  • Metronidazole and active metabolite hydroxymetronidazole have short half lives so accumulation unlikely
  • Infant monitoring required for adverse reactions e.g. loose stools and oral thrush
• Aspirin


  • Aspirin passes into breast milk in small amounts
  • No adverse effects when used at low dose (75-150mg) when used as an antiplatelet agent
  • Data is limited and therefore should be used with caution and infants monitored
  • Unknown whether small amounts of aspirin present in breast milk could cause Reye's syndrome in a breastfed infant
  • Withhold breastfeeding if infant develops a fever or stop aspirin
• Antidepressants


  • Consider non pharmacological interventions first, e.g. talking therapies, guided self help
  • The SSRI sertraline is a suitable choice since it has a short half life and low levels of the drug transfer into breast milk but use is off licence
  • Fluoxetine has a longer half life leading to a risk of accumulation in the infant
  • There is a risk of maternal toxicity and significant adverse effects with tricyclic antidepressants therefore these are generally prescribed less for post natal depression
• Contraception


  • Lactational amenorrhoea can be up to 98% effective in preventing pregnancy if the mother is fully breastfeeding, the baby is under 6 months and the mother has no periods
  • Contraceptives can be used during breastfeeding and progesterone only methods are the preferred hormonal contraceptive
  • There is a low risk of inhibition of early lactation if they are started before 6 weeks after delivery
  • Combined hormonal contraceptives can be used from 6 weeks after childbirth but have a significant suppressant effect on milk production so should only be used once the infant is weaned or from 6 months post partum