Pregnancy + Lactation

What are the three areas of medicines in pregnancy?

Emesis - aka morning sickness - can happen any time of day/24 hours a day

Hyperemesis - uncontrollable N+V - may be admitted to hospital for IV fluids

• If extreme - TPN potentially

 

Pregnancy induced HTN - didn't have before pregnancy

• Can progress to pre-eclampsia

 

Pre-eclampsia - rare - but serious - stage before eclampsia

 

Eclampsia - can have seizures during pregnancy - dangerous for foetus

• Expectant mother may have to undergo emergency C-section

 

VTE - risk of developing blood clot e.g., DVT - higher risk in pregnancy

 

Gestational diabetes - e.g., due to hormones in placenta

• Insulin resistance as pregnancy progresses

• Usually tested with oral glucose tolerance test

• Usually resolves post pregnancy - as hormonal

• Increased risk of developing T2DM later in life/post-pregnancy

• Important to manage - e.g., diet + exercise and/or medication

 

Infection - amnionitis (infection in the amniotic fluid)

• Monitor infection markers

 

Postnatal:

Pain - e.g., tear, stitches, C-section etc.

When is term?

37 weeks

What are commonly used medicines in pregnancy?

• Folate/folic acid - reduces risk of neural tube defects in developing foetus

  • Advised in first trimester (esp. first 12 weeks)

• Vitamins - esp. vitamin D.

  • Also multivitamins (iron can be in these)

• Iron - may have dilutional anaemia during pregnancy

• Aspirin - if have risk of pre-eclampsia or other conditions e.g., migraines (since other meds may not be safe)

• Metformin and/or insulin

• Labetalol + nifedipine - for HTN in pregnancy

• Anti-sickness, antacids, PPIs - for GI symptoms during pregnancy

• Vaccinations - may be seasonal e.g., flu and COVID

  • Whooping cough + RSV vaccine recommended - antibodies pass onto the baby - baby protected - when gets to about 8, 12, 16 weeks - start receiving own vaccinations after this point

What is teratogenicity?

The ability of a drug/ agent to cause foetal abnormalities or deformities.

• teratogens cross placenta

• directly or indirectly cause structural abnormalities in foetus or child after birth

• may not be apparent until later in life

Foetal response to a teratogen depends on dose, route, timing of exposure, genetic and environmental factors, number of concomitant drugs.

• dose dependent teratogen = carbamazepine (higher dose = high risk to foetus)

E.g. thalidomide, alcohol, chemicals, some infections

What are the phases in human development?

Pre-embryonic:

• First few weeks

• Harmful exposures of teratogenic medications - interfere with embryo ability to attach to uterus - greatest risk of miscarriage (all or nothing period)

 

Embryonic phase

• Up to ~8 weeks of foetal development

• Greatest vulnerability

Foetal phase:

• 8 weeks to rest of term

When are medicines generally avoided in pregnancy?

Generally advise AVOID using medicines in first trimester where possible.

• Structural defect risk.

 

2nd + 3rd trimester - growth + functional defects risk.

 

Meds even during labour/end of pregnancy

• Can affect neonate after delivery.

• E.g., withdrawal effects with opioids.

What properties of drugs allows them to cross the placenta?

• Non-ionised, lipid-soluble drugs (e.g. labetalol) will cross into the placenta, in preference to more polar, ionised, hydrophilic compounds (e.g. atenolol)

• High MW drugs tend not to cross placenta (e.g. insulin, heparin), but there are exceptions (e.g. infliximab)

N.b. some drugs do not cross placenta but can still cause harm e.g. by causing vasoconstriction of placental vasculature

• constricts blood supply - needed for foetal growth for nutrients + oxygen for the baby

What is some potential harm in pregnancy (e.g., conditions)?

What are the mechanisms of harm?

Give examples of known teratogens?

Tetracyclines - can affect teeth and foetal bones

Some teratogens - benefit may outweigh risk

What update has there been on valproate (i.e., requirements)?

• Negative pregnancy test - monthly basis

• Must meet PPP requirements

• Annual review - to explain risks

• Packs have warning sticker

• Annual risk acknowledgement form - must sign this

• Advised potential infertility risk in men

• Two specialists required to initiate valproate in male or female pts that are younger than 55 years old

• Risk of neurodevelopmental disorders in babies where father was on valproate - effective contraception recommended during and for 3 months after Tx has stopped

• Inform pts to not stop taking without specialist advise - risk of epilepsy or bipolar disorder if suddenly stop

How does absorption change in pregnancy? Effect?

Think about effect on prodrugs - form of ionisation may need to change for them to turn into the active drug wanted.

How does distribution change in pregnancy? Effect?

How does hepatic metabolism and elimination change in pregnancy? Effect?

How does renal elimination change in pregnancy? Effect?

What should be done to doses changed post-delivery?

Adjust doses back post-delivery.

How long does effective contraception (± barrier methods) need to be used for cytotoxic agents before planning?

• During exposure until treatment is finished

• For cytotoxic agents, usually wait 2 spermatogenic cycles (6 months)

• Cyclophosphamide (3 months), rituximab (12 months)

What questions should be asked to a pregnant/planning pregnancy patient when information gathering?

What are the key principles for medication use in pregnancy?

How should risk vs. benefit be weighed in pregnancy?

What should be mentioned when counselling on medication in pregnancy?

• Potential consequences of using a medicine during pregnancy?

• Likely benefits of treating the maternal condition and risks if not treated?

• How likely the woman and her child are to be affected?

• What can be done to manage any risks?

What are the benefits of breastfeeding?

WHO recommends exclusive BF for first 6 months

• With supplemental BF continuing for 2 years and beyond

Formula can be hard to obtain at times/expensive

Composition of breastmilk changes based on babies needs

• If mother or baby exposed to infection - milk produced during BF will have more antibodies

• Or e.g., composition incl. melatonin in BF - helps babies during sleep during night feed.

• Reduces risks of allergies developing

What are the issues with breastfeeding?

Can make it more difficult for babies to breastfeed.

What is the composition of breastmilk?

“ a suspension of fat droplets in an aqueous phase containing proteins, lactose and electrolytes”

Medicines can be present in:

• Lipid phase

• Aqueous phase

• Bound to milk proteins

Composition of milk changes with:

• Duration of feed

• Time of day

• Needs of baby

Why do we need to look at medicines in lactation?

Explain the pharmacokinetics in lactation in the first few days after birth?

Reason - to protect baby from infection - it is a way of passing on immunity

Also means medications enter from bloodstream into breastmilk more easily.

Explain the pharmacokinetics in lactation after the first few days after birth?

After few days

• Gaps start to close

• Harder for meds to pass membrane + enter breast milk

Explain how other pharmacokinetics are affected in lactation?

Try choose shorter acting medicines - to reduce toxic effect - as neonate kidneys not well functioning yet right after birth

How is toxicity of the drug affected by lactation?

What is the relative infant dose?

How can we information gather in a breastfeeding mother?

Corrected age - e.g., age if they went through to full term if born prematurely.

Feed much more when newborn rather than couple months old.

How can we manage the risk in a breastfeeding mother?

Is it essential? Are there non-pharmacological options?

• Avoid if not essential

• Disease might be worse than medicine – more important to treat.

Consider alternative drugs

• Choice primarily depends on suitability for patient and their condition, then assess compatibility with breastfeeding

Can BF be interrupted temporarily?

• only for very short courses, otherwise can be difficult to resume

• avoid this option if possible – may not have any other option

Timing – unhelpful if course exceeds 5 half-lives and reaches steady state

If a drug with potential neonatal side effects is still used while breastfeeding:

• Monitor the baby carefully

• Avoid multiple drugs with similar potential adverse effects

• Use minimum doses needed

• Use dosage forms that limit systemic exposure if possible

• Avoid new drugs with limited information if possible

• Avoid medicines with long half-lives if possible

What should be considered about codeine for BF mothers?

Avoid in breastfeeding.

Codeine - can be metabolised (ultra-rapid metabolisers) into morphine

• Can happen in a breastfed infant

• Try avoid codeine

Dihydrocodeine preferred

What should be considered about drowsy medicines and antibiotics for BF mothers?

Medicines that may cause drowsiness (e.g. chlorpheniramine) can pass through the BBB → sedative effect (avoid)

Antibiotics:

• may cause temporary lactose intolerance but not a reason to interrupt bf

• antibiotics that are licensed to give in children can be given to breastfeeding mother (level reaching baby through milk will be lower than licensed dose)

What should be considered about SSRIs for BF mothers?

SSRIs:

• sertraline and citalopram are well-studied - little passes into breast milk

• lithium is contraindicated

• stopping breastfeeding may exacerbate symptoms of depression due to loss of oxytocin

What should be considered about methadone and herbal remedies for BF mothers?

Methadone – highly plasma protein-bound

• RID 1.9-6.5%

• Can be used if prescribed by a specialist service

Herbal remedies – limited data (avoid)