Lec 16- Prescribing in pregnancy and breastfeeding

Question 1

Prescribing medicine in pregnancy

Stages of pregnancy

Answer 1

• Trimester
  
  • 1-3

Question 2

Stages of development and timing of exposure

Answer 2

• Potential harm influenced by the timing of exposure
  
  • <17 days = pre-embryonic period (All or nothing)
  • 18-56 days= Embryonic period (Organ formation)
  • Weeks 8-38/40 = fetal stage
• Different defects occur with drugs in different periods of pregnancy (Phenobarbital)
• Period crucial
  
  • Spina Bifida
  • Cleft palate: MTX, Valporate, teratanoins
  • NSAIDs and pulmonary HTN

Question 3

Teratogenicity

Answer 3

• Teratogen is an agent that interferes with the normal growth and development of the fetus
• Potential effects include
  
  • Chromosomal abnormalities
  • Structural malformations
  • IUGR- intrauterine growth retardation
  • Fetal death
  • Behavioural or intellectual abnormalities
• 2-3% incidence of spontaneous malformations in newborn babies in Europe

Question 4

Medicine handling and pregnancy

Answer 4

• PK changes
  
  • Volume of distribution
    
    • Increase body water and fat- water-soluble drugs will become diluted (water content in maternal plasma is higher)= increase dose
    • Increase cardiac output
  • Protein binding
    
    • Decreased albumin- extensive protein binding, greater concentration free= increase risk of toxicity/effect/side effects
  • Clearance
    
    • Increased GFR by 50% in the first weeks of pregnancy- increased renal perfusion
    • Overall clinical significance minimal

Question 5

Placenta

Answer 5

• The placenta is NOT a barrier- offers no protection
• Role: Nutrient uptake, waste elimination and gas exchange via mother blood supply
• Lipid soluble, unionised medicines cross placenta quicker
  
  • Insulin, Heparin via diffusion

Question 6

Principle of medicine use

Prescribing in pregnancy- factors to consider when choosing medication in pregnancy

Answer 6

• Trimester/ number of weeks
• Past pregnancies
• Previous exposure
• Necessity for therapy
• Duration of therapy
• Drug properties, i.e. half-life, teratogenicity risk
• Also, consider women of childbearing age

Question 7

Principle of medicine use

Answer 7

• Medicines should only be prescribed when benefits to the mother > RISK to the fetus
• Simple rules: Preferably use agents extensively used before; Use the lowest effective dose
• To aid compliance all risks and benefits should be discussed with mothers for each medication and their importance

Question 8

Nutrition in pregnancy

Answer 8

• Folic acid supplementation
  
  • Ensure neural tube closure= Prevent spina bifida
  • Essential Vitamin to ensure neural tube closure
  • Low risk: 400mcg OD pre-conception to Wk12
  • High risk: 5mg OD before conception to Wk12
    
    • Diabetes, epilepsy, previous spina bifida in pregnancy, the partner has spina bifida
• Vit D (10mcg per day)
• No alcohol government advice
• Vit A (restrict 700mcg)
• Vit K Supplementation
  
  • May be required: AED, cholestasis or other liver abnormalities
  • Make sure there are adequate clotting factors for fetus

Question 9

Recap

Answer 9

• Medication use effect to the fetus depends upon many factors
  
  • Timing of exposure
  • Dose- lowest effective dose for the shortest time
  • Maternal disease
  • Genetic susceptibility
• Teratogenicity can be dose dependent
• Can get incidence of spontaneous malformations in normal population

Question 10

National recommendations on breastfeeding

Answer 10

• WHO- exclusive breastfeeding for first 6 months ‘responsive’ breastfeeding
• NICE- HCP to improve the nutrition of pregnant and breastfeeding mothers and children in low-income households
• The NHS long term plan (2019)- All maternity services that do not delivery an accredited, evidence-based infant feeding programme, such as the UNICEF baby friendly initiative, will begin the accreditation process

Question 11

Advantages of breastfeeding

Answer 11

• Contains secretary IgA (Sustained benefit if BF >13 wk)
• Child
  
  • Reduces risk of infection
  • GI (diarrhoea), UTI, otitis media, LRTI, NEC
  • Increased cognitive development
  • Protection against development of atopic-disease
  • Reduction in childhood leukaemia’s
  • Reduction in hypertension, diabetes and obesity
• Mother
  
  • Reduction in risk of pre-menopausal breast cancer, ovarian cancer and hip fractures

Question 12

Disadvantages of breastfeeding

Answer 12

• Not enough breast milk
• Sore/cracked nipples
• Breast engorgement
• Blocked duct/mastitis
• Latching problems
• Painful, messy and tiring
• Difficult to establish
• Breast fed babies wake more often during the night–More difficult for mothers to return to work–Mother may need to modify her diet

Question 13

Breast milk v formula milk

Answer 13

• Formulamilknotatruereplica
• Breastmilkcomplex, contains antibodies, enzymes and hormones.
• Colostrum( yellow milk) high in immunoglobulin’s
• Newborninfantshavehighcalorificandfluidrequirements
  
  • Av fluid 150ml/kg/day
  • Calories 110 kcal/kg/day
• 40% of energy comes from carbohydrate (mainly lactose) and 50% from fat.
• Babies require vitamin K to prevent haemorrhagic disease of newborn

Question 14

Prescribing in breast feeding

Answer 14

• Not breastfeeding is NOT a neutral no harm option

Question 15

Consideration of medication choice

Answer 15

• Pharmacokinetic factors influence prescribing the choice
  
  • Size of drug molecule; larger molecules less in breast milk
  • Drug solubility; most passage simple diffusion
  • Fat solubility of the drug; unionised and lipid-soluble drugs have increased concentration in breast milk e.g. BZ’s
  • Plasma protein binding of the drug; higher concentration bound less in milk
  • Half-life; can influence infants excretion.
  • Peak plasma levels; a higher concentration of drug get more drug passage into milk. (2hrs in oral vs 20 mins IV)

Question 16

Consideration on medication choice cont

Answer 16

• Other factors
  
  • Milk: plasma ratio
  • Age of baby
  • The volume of feeds
  • Frequency of feeds
• Generally, manufacturers do not gain a licence for drugs in breastfeeding so are cautious and recommend against it.
• Due to ethics, there are no larger and randomised studies on drugs in breastfeeding

Question 17

Medicines clearance in infants

Answer 17

Question 18

Calculating relevant infant dose

Answer 18

• Infant exposure to the drug is sometimes expressed as a percentage of the weight adjusted the maternal daily dose
• A relative infant dose of <10% is generally considered safe
• Other factors would also need to be considered e.g. gestational age of infant, actual amount of milk ingested, properties of maternal medication, medical conditions and medications of the infant

Question 19

Medicines considered UNSAFE in breast feeding

Answer 19

• Indomethacin => convulsions
• Clindamycin => enterocolitis
• Ginseng => Androgenisation
• Mesalazine => Thrombocytosis /Neutropenia
• Amiodarone => Thyroid dysfunction
• Tetracyclines => Bone and teeth chelation
• Statins => May affect milk ChE levels

Question 20

Medicines use with CAUTION in breast feeding

Answer 20

• Codeine => Risk of morphine toxicity if mother CYP2D6 ultra-rapid metabolizers
• Atenolol => Case report of bradycardia, cyanosis and hypotension
• Diuretics => May supress lactation

Question 21

Medicines SAFE in breastfeeding

Answer 21

• Penicillins
• Erythromycin
• Cefalexin
• Ibuprofen
• Diclofenac
• Senna
• Lactulose
• Loperamide

Question 22

Medicines affecting lactation

Answer 22

• Oestrogens may decrease milk production
  
  • Can use POP
• Dopamine receptor agonists suppress lactation- bromocriptine
• Dopamine antagonists can promote lactation- metoclopramide

Question 23

General principles

Answer 23

• If not necessary avoid drug use
  
  • Limit OTC product use
• Avoid known toxic drugs
• Generally licensed in infant will be ok
• Neonates at greatest risk
• Monitor infants for SEs
• Avoid long acting formulations
• Avoid new medicines
  
  • Limited data
• Most important is Benefit/Risk ratio