lactation Flashcards
when should i child be breastfed?
6m-2y
what is lactogenesis
Lactogenesis: synthesis and secretion of milk from breast alveoli
Composition of breastmilk
Milk consists of simple sugars (carbs), lipids, proteins, vitamins and minerals dissolved in water
Water accounts for >80% of its volume
Changes from colostrum to mature milk
Problems with medicines in lactation
Most drugs are not licensed for use during lactation
Many will have warnings on their packs – e.g. do not take if breastfeeding OR consult GP/pharmacist
This means that the manufacturers have not undertaken research to confirm safety on ethical grounds
However, this does NOT necessarily mean that they can’t be used in breastfeeding women
Pharmacokinetics of drugs must be considered by the HCP and specialist resources should be consulted
Data may also be available on the amount of drug which gets into breast milk
NOT the same as taking drugs in pregnancy!!
What factors affect infant exposure tomaternal drug therapy?
Drug factors
Maternal factors
Infant factors
Drug factors
Molecular weight –
The lower the molecular weight of a medication, the more likely it is to penetrate into human milk – as diffusion through the alveolar epithelial cell is much easier
Medications with molecular weights <300 Da will tend to penetrate to milk in higher concentrations than those with higher molecular weights
Examples of drugs with high molecular weights that are basically excluded from milk would include heparin (30,000), antibodies such as Remicade (144190), and insulin (6000)
Ethanol with a molecular weight of 120 rapidly equilibrates between the plasma and milk compartments
Plasma protein binding – the more highly bound the drug, the less that can transfer into milk ( e.g. ibuprofen >99% bound)
Lipophilicity – alveolar epithelium of breast is a lipid barrier, so lipid soluble drugs pass more freely into breast milk than water-soluble drugs/ ions (e.g. CNS drugs)
Milk composition varies within and between feeds and this may also affect transfer of drugs into breast milk.
For e.g., milk at the end of a feed (hindmilk) contains considerably more fat than foremilk and may concentrate fat-soluble drugs
pKa -The pKa of a drug is the hydrogen ion concentration (pH) at which 50% of the drug exists in its ionized hydrophilic form
Milk has a lower, more acidic pH (6.6-7.2) than blood (7.4)
For basic drugs, a greater fraction will be ionised at an acidic pH, so the milk compartment will tend to ‘trap’ weak bases (ion trapping)
Drugs with higher pKa (weak bases) generally have higher milk:plasma ratios (more will penetrate the breast milk)
Acidic drugs (lower pKa) are more ionised at higher pH values and will be ‘trapped’ in plasma
So drugs with lower pKa are preferable for breastfeeding, - less penetration into milk compartment
Milk:plasma ratio – the lower this value is, the less drug reaches the breastmilk, most drugs have <1
Drugs with higher pKa values (weakly basic) generally have higher milk/ plasma ratios
Iodine has a milk:plasma ratio of 26 – due to an active transport mechanism into the milk – iodine dressings NOT recommended
Oral bioavailability to infant – when ingested in the breastmilk, drugs with low oral bioavailability are poorly absorbed from infant’s GI tract, broken down in their gut or undergo extensive first pass metabolism in their liver. The drug concentration that reaches the systemic circulation is reduced. Insulin is an example of such drug.
Half life (half-life in the maternal and infant’s plasma) - short half life preferable as less likelihood of the drug accumulating
Active metabolites – presence may prolong infant drug exposure and lead to drug accumulation (esp. in neonatal period)
Therapeutic index – some drugs have very narrow ranges and need monitoring (e.g. digoxin, lithium and warfarin)
maternal Factors
Maternal drug regimen – single doses/short courses rarely cause problems, but chronic therapy can be problematic. Multiple medications increase risk, as well as higher doses. Topical/inhalation routes preferred
Maternal plasma concentration - usually, the most important determinant of drug penetration into milk is the mother’s plasma level
As the level of the medication in the mother’s plasma begins its rise, the concentration in milk begins its rise as well. Drugs both enter milk, and in most cases, exit milk as a function of the mother’s plasma level
As soon as the maternal plasma level of a medication has fallen, the milk level soon follows
Pharmacogenetics – sedation and one death occurred in infants of mothers with rare genotypes of the cytochrome P450 enzyme CYP2D6, leading to ultrarapid metabolism of codeine to morphine
Timing of feed – often impractical, especially if infants are feeding frequently, also not useful if drug has long half life or when drug has reached steady state. This technique should be selectively for drugs with short half lives and predictable peaks/troughs
infant factors
The age and maturity of the baby – liver and kidney systems do not work fully for some time after birth. Premature babies may show higher than expected drug levels.
Pharmacogenetics - Infants with certain enzyme deficiencies (e.g. G6PD) deficiency may experience adverse effects with even small amounts of certain drugs
Allergies - Possibility of allergic reaction in infant exposed to drug in breast milk, even minimal exposure could cause this response; rare in practice
Volume of breast milk ingested – higher volume = higher drug exposure. Volume may depend on child age
Relative infant dose - a level <10% is probably safe but inherent toxicity/ adverse effect profile of drug needs to be taken into account
what is relative infant dose
Infant plasma levels are most accurate indicator of drug exposure but are seldom available
The Relative Infant Dose (RID) estimates infant drug exposure via breast milk
The daily dose received via breast milk is compared to the dose used therapeutically for an infant of the same age
When the medication is not used in infants or does not have an accepted infant dosage, a weight-adjusted maternal dose is used
Ideal pharmacokinetic properties for breast feeding
Licensed for use in children
Wide therapeutic index
Highly plasma protein bound (<90%)
Low milk:plasma ration (<1)
Low pKa
Poor oral bioavailability
Large molecular weight
Half life < 24 hrs
Low relevant infant dose (RID)
commonly reccommended otc
Many OTC medicines are compatible with breastfeeding (e.g. paracetamol, oral/topical NSAIDs, bulk and osmotic laxatives, loperamide)
Otc medicines to avoid
Codeine should NOT be recommended as metabolism varies between individuals and some breastfeeding mothers may concentrate the drugs into milk
Aspirin as a painkiller (high dose) - aspirin is associated with Reye’s syndrome in children under 16 yrs
Medicines that have the potential to cause drowsiness (e.g. diphenhydramine) should be avoided - they can pass the blood-brain barrier, causing sedation in the child.
These medicines may also have the potential to reduce milk supply
Herbal remedies are best avoided during breastfeeding, due to lack of data
prescribed medicines compatible with breastfeeding
Antibiotics
Antibiotics are given to many breastfeeding mothers for uterine infections, mastitis or infections that affect the general population
Antibiotics passing through breast milk damages the gut villae of the baby, causing temporary lactose intolerance - loose, runny bowel motions - not a reason to interrupt breastfeeding
Any antibiotic that is licensed to be given to a child can be given to a breastfeeding mother (e.g. penicillin)
Antidepressants
Sertraline or citalopram (SSRIs) are the first-line drugs of choice during breastfeeding to treat maternal anxiety and depression - well studied and little passes into breast milk
These are just some examples
prescribed medicines -Contraindications
Contraindicated medicines include:
Cytotoxic agents
Amiodarone
Lithium
Isotretinoin
These are medicines with inherent toxicity or high infant exposure and therefore potential for significant toxicity
Radiopharmaceutical administration also requires temporary cessation of breastfeeding
alcohol whilst breastfeeding
Significant amounts of alcohol pass into milk – not normally harmful if quantity and duration of intake are limited
An occasional alcoholic drink is acceptable – breastfeeding should be avoided for about 2 hours after the drink to avoid exposing the baby to any alcohol in the milk
Chronic or heavy users of alcohol should not breastfeed
High intake of alcohol:
decreases milk let down and disrupts feeding
cause sedation, fluid retention and hormonal imbalances in breastfed infants
Mother can plan ahead by expressing some milk before a social function
They can skip the first breastfeed after the function and feed the baby with the expressed milk instead
The mother does not need to express to clear the milk of alcohol. The level of alcohol in the milk falls as the level of alcohol in the blood falls
vaccines
Neither inactivated nor live vaccines affect the safety of breast feeding for women or their infants
Breast feeding does not adversely affect immunization and is not a contraindication for any UK-licensed vaccine
Breast-fed infants should be vaccinated according to recommended schedules
Considerations for the prescriber
Avoid unnecessary maternal drug use
HCP will consider the need of the mother for treatment and any particular drug – benefit/risk assessment for mother and child
HCPs will use the evidence available and their professional judgement to recommend whether:
A medication is suitable for the breastfeeding mother
An alternative would be preferable
To suspend breastfeeding or decide to wait rather than treat the mother
No baby should be exposed to risk by the mother taking a drug which is contra-indicated in breastfeeding
Breast feeding should be suspended/stopped as a last option
Drug regimen and route of administration which presents minimum amount of drug to the infant via breast milk should be chosen
The minimum clinically effective dose should be used for shortest possible time
Avoid new drugs if there is a therapeutic equivalent with data to support use in lactation
Monitor the infant for unusual signs or symptoms
Recognise risk factors, e.g. prematurity, infant morbidity and multiple maternal medication
Pharmacokinetics – drug transfer into breastmilk
Most drugs pass into breast milk to some extent – although transfer usually low
Amount of drug ingested by infant rarely causes adverse effects
Almost all drugs enter milk by passive diffusion of unionised, unbound drug through the lipid membranes of the alveolar cells of the breast
Although early on, drugs may pass between the alveolar cells (first 72 hours postpartum)
Babies most vulnerable to the effects of drugs in the first few days after delivery as intercellular gaps in the milk ducts
This allows large molecules such as antibodies (Igs) to pass through into the breast milk
Antibodies important to protect baby from infection (passive immunity)
However, this is also when the most medication is given to lactating women
Over 50% of women given medication in first few days after birth (mainly painkillers and antibiotics)
