Breastfeeding and medication for long-term conditions

In each general practice there will be women who have a chronic medical condition but who are also breastfeeding their baby. However, we may not know who they are. Contacts with mothers have shown that they may forget to tell their health practitioners. This has been particularly true with increasing numbers of video calls. It is also anecdotally true, according to social media groups, when women are continuing to offer breastfeeds alongside appropriate solid foods to older toddlers and children. Some women may wish to avoid conversations when they anticipate possible criticism, even though this concern may have no foundation at all. How we, as healthcare professionals, have fed our own babies, if we had them, may influence our feelings. Nevertheless, breastfeeding is a health promotion issue and not just a matter of providing milk for babies (Renfrew and Hall, 2008). None of us can know everything but we can take opportunities to increase our knowledge in areas which are important to families but in which we lack experience.

Knowing the benefits of breastfeeding for the mother and baby can help to understand why continuing breastfeeding can be important. We know that for babies, breastfeeding helps protect them against (Victora et al, 2016):

• Ear infections
• Gastro-intestinal infections
• Chest infections
• Urine infections
• Childhood diabetes
• Eczema
• Obesity
• Atopic diseases
• Risk of sudden infant death syndrome (SIDS).
• But it also has the following effects on mothers (Victora et al, 2016):
• Protects against ovarian cancer
• Protects against breast cancer
• Increased likelihood of returning to their pre-pregnancy weight
• Delayed resumption of the menstrual cycle with consequential lower loss of iron stores
• Reduces lifetime risk of cardiovascular disease (Tschiderer et al, 2022).

If we consider just five illnesses (breast cancer in the mother and gastroenteritis, respiratory infections, middle ear infections and necrotising enterocolitis in the baby), moderate increases in breastfeeding would translate into cost savings for the NHS of £40 million and tens of thousands of fewer hospital admissions and GP consultations (2012 data). If half of those mothers who currently do not breastfeed were to do so for up to 18 months of their lifetime, there would be 865 fewer cases of breast cancer, with cost savings to the NHS of over £21 million (Renfrew et al, 2012).

Making decisions about prescribing to lactating mothers

When prescribing to breastfeeding women we need to be aware that some of the drug which she takes is likely to pass to the baby via breastmilk. The British National Formulary (BNF) is not always a useful source of information, as historically it has been led by the summary of product characteristics (SPC) written by the manufacturers. It may have comments such as ‘passage into milk is negligible but the manufacturers advise avoid (breastfeeding)’ or ‘not known to be harmful but consider discontinuing breastfeeding’.

So how can we make an evidence-based decision if a mother needs to be treated and is breastfeeding? How can we support the mother to continue to breastfeed and feel well? Prescribing outside of the product licence involves taking professional responsibility, but there are very few drugs licensed in breastfeeding. The aim of this article is to help prescribing general practice nurses make appropriate decisions using expert resources as recommended in guidance from the National Institute for Health and Care Excellence (NICE, 2014).

We know that breastfeeding affects women's use of drugs. While 65.9% of women have taken a drug while breastfeeding a baby before 6 months, 79.6% of formula feeding mothers have taken a drug in the same period (Jones and Brown, 2000; Schirm et al, 2004).

However, we give most drugs to women in the first few days after birth; mainly analgesics and antibiotics.

Early passage of drugs into milk

In the first few days after delivery, drugs are not restricted in their passage into milk as there are gaps between the milk cells to allow the passage of immunoglobulins to protect the baby (Figure 1).

By day 3 to 5 these gaps have closed so that the drug has to transverse the cell membranes, which dramatically reduces the transfer to the breastmilk (Figure 2) (Hale and Krutsch, 2022). Although, in theory this would make us more cautious about prescribing in the early perinatal period, it is the time when most drugs are used – eg antibiotics, analgesics, laxatives – but with the full experience of the maternity ward team (Jones and Brown, 2000).

Oral bioavailability

When looking at the factors which influence the transfer of the drug from mother to baby, the simplest to understand is the oral bioavailability of a drug. The baby is only exposed to a medication through breastmilk once the drug passes through the maternal gut and liver into plasma, with all the associated pharmacokinetic pathways, and then into breastmilk. In turn, the baby then has to absorb the drug from the milk and metabolise that, usually at a much smaller level.

Any drug that is not orally bioavailable cannot be given to the mother orally but rather by infusion or injection. For the same reason the baby would be unable to absorb any drug which is in maternal milk. Examples include gentamycin, teicoplanin, meropenem, insulin, vaccines and the biological drugs such as adalimumab. In addition, these are all large molecules which cannot pass through the cell membranes, so restricting transfer into breastmilk (Hale and Krutsch, 2022).

Plasma protein binding

The more that a drug is bound to the plasma proteins in the mother's bloodstream, the less of the drug that there is to pass into milk. In an ideal world, we would choose drugs which are highly protein bound, eg ibuprofen 99%, as these produce very low levels in milk. This information cannot be found in the BNF, but is available in the specialised texts and databases referred to later in the article.

Half-life of the drug

Drugs with long half-lives (the time taken for half of the drug to be metabolised by the body) can accumulate in the blood and, therefore, the milk. Some have longer half lives in neonates, as their renal and hepatic function is not fully mature for the first 6 weeks of life (Rodieux et al, 2015). After five half lives the drug has reached such a low level that it is assumed to have left the body (Figure 3).

However, any drug which is taken chronically rather than acutely, takes 5 half lives to reach a steady state, at which it remains. For example, an antidepressant will remain at the same level in milk throughout 24 hours and timing feeds to avoid peak levels adds stress to the mother and does not achieve any reduction in the level of the drug to which the baby is exposed (Figure 4).

Relative infant dose

The most widely used indicator of compatibility of medication with breastfeeding, used by lactation and medication experts, is the relative infant dose. This is a calculation based on the dose that the mother consumes compared to the dose passed to the baby. A relative infant dose (RID) less than 10% is usually regarded as compatible. However, it is not always that simple and all the data and studies need to be taken into account. Methotrexate has a RID 0.11–0.95% (Hale and Krutsch, 2022) but is one of the few drugs contraindicated in lactation on a chronic basis (if used to treat an ectopic pregnancy breastfeeding needs to be interrupted for 24 hours only, then resumed as normal). Figure 5 shows how relative infant dose is calculated.

Medications licensed for children

Any medication which is licensed for a baby/child is unlikely to reach the paediatric dose when transferred through breastmilk. This includes antibiotics, analgesics and antihistamines. Table 1 shows the data on antibiotics.

Supporting women to make a decision on taking medication when breastfeeding

According to Jølving et al (2016), during the past 25 years to 2013 the prevalence of maternal chronic disease during pregnancy has increased four-fold, reaching 15.76%. Scime et al (2021) recorded an incidence of 10–12% maternal chronic diseases in a Canadian population. As chronic disease specialists, general practice nurses may be at the forefront of professionals supporting breastfeeding women needing regular medication for a chronic disease.

Sources of information on prescribing in lactation:

• Specialist pharmacy service (UKDILAS). Provides training and guidance on the use of medicines in breastfeeding: https://www.sps.nhs.uk/home/guidance/safety-in-breastfeeding/
• Hale TW. Medications and Mothers Milk. Available as a book or via paid online access. https://www.halesmeds.com
• LactMed: part of the National Library of Medicine USA. Free online access: https://www.ncbi.nlm.nih.gov/books/NBK501922/
• Jones W. Breastfeeding and Medication. 2018; Routledge
• Brown A and Jones W (eds). A Guide to Supporting Breastfeeding for the Medical Profession. 2019; Routledge
• The Breastfeeding Network Factsheets written by the author. Covering many commonly used drugs: https://www.breastfeedingnetwork.org.uk/drugs-factsheets/
• Breastfeeding and Medication Factsheets written by the author: https://breastfeeding-and-medication.co.uk/

When helping families (and professionals), a polarity map (Johnson, 1996) can be a useful decision-making aid. We are aware of the disadvantages of not breastfeeding, which have been identified earlier. However, it may be thought that when prescribing ‘would it be safer to suggest that she stops breastfeeding temporarily or permanently, and that the baby is given artificial milk supplements' based solely on the information in the BNF. Nevertheless, each mother and baby pair are individuals and it is key to ask:

• How old is the baby?
• How much milk is the baby/toddler/child consuming?
• What are the potential risks to the baby of consuming any of the drug via breastmilk?
• What are the wishes of the mother?
• What are the risks of interrupting breastfeeding, even temporarily?

The two polarities of the dilemma could be to continue breastfeeding in the presence of the medication or cease breastfeeding and use formula. There is, in fact, an intermediate solution which is to temporarily express breastmilk to maintain the supply while substituting with formula. However, for the purposes of this article long-term medication will be assumed, so this is not possible (see Table 2 for an example of a polarity map). The Case study also provides an example of supporting a mother to make an informed decision.

Case study

Amy has delivered a baby, Susie, at term following an uneventful pregnancy and delivery. Susie is breastfeeding well now. Initially Amy had problems with latching her baby and needed support from the local hospital infant feeding team as well as local peer supporters. Amy has had a history of depression for which she was treated with 50 mg sertraline for several years until she decided to stop before planning a pregnancy. She has also had cognitive behavioural therapy (CBT) via the local Improving Access to Psychological Therapies (IAPT) team.

Amy has reported feeling low to her health visitor who suggests that she needs to consult a clinician with a view to restarting her sertraline. Although the health visitor has done her best to reassure Amy, she is very anxious.

Amy is desperate to continue to breastfeed as there is a history of atopy in the family and Amy's partner has asthma. She has had to work hard to achieve pain-free breastfeeding but she is now enjoying seeing Susie thriving and happy. However, she is very anxious that baby Susie should not be harmed by any medication which she takes and passes through breastmilk. She has used internet searches and asked on breastfeeding social media groups which have somewhat fuelled her anxiety.

In the BNF the entry for sertraline (October 2022) states ‘Not known to be harmful but consider discontinuing breast-feeding’. Consulting LactMed (https://www.ncbi.nlm.nih.gov/books/NBK501191/), it says ‘Because of the low levels of sertraline in breastmilk, amounts ingested by the infant are small and is usually not detected in the serum of the infant, although the weakly active metabolite norsertraline (desmethylsertraline) is often detectable in low levels in infant serum. Most authoritative reviewers consider sertraline a preferred antidepressants during breastfeeding.’

Hale Medications and Mother's Milk says that it is 98% plasma protein bound, with a milk plasma ratio of 0.89 and a relative infant dose of 0.4–2.2%. It states that many studies generally confirm that the transfer of sertraline and its metabolite to the infant is minimal, and that attaining clinically relevant plasma levels in infants is remote at maternal doses less than 150 mg/day.

The specialist pharmacist service says that it is one of the SSRIs of choice in breastfeeding (https://www.sps.nhs.uk/articles/safety-in-lactation-antidepressants/)

Among the information in Hale is a 2015 review of sertraline levels in breastfed infants confirmed that drug levels in breast milk are low (Pinheiro et al, 2015). This review reported that of 167 infant sertraline levels, 87% were undetectable. The authors of this analysis reported that no adverse events occurred in the 167 infants included in the drug level analysis, even in those with detectable levels (median 5 ng/ml for both sertraline and its metabolite).

Using the information earlier in this article, this is reassuring to you as the prescriber, even though it is outside the manufacturer's licence application. You explain to Amy your decision making evidence along with the fact that the patient information leaflet may say that it is not recommended in breastfeeding. The SPC (https://www.medicines.org.uk/emc/product/3501/smpc#PREGNANCY) says that published data concerning sertraline levels in breast milk show that small quantities of sertraline and its metabolite are excreted in milk. Generally negligible to undetectable levels were found in infant serum, with one exception of an infant with serum levels about 50% of the maternal level (but without a noticeable health effect in this infant). To date, no adverse effects on the health of infants nursed by mothers using sertraline have been reported, but a risk cannot be excluded. Use in nursing mothers is not recommended unless, in the judgment of the physician, the benefit outweighs the risk.

You show all the information to Amy and suggest that she might like to take time to look at the information and make an appointment next week to discuss starting the drug. She is reassured that you have provided sufficient information, respected her concerns and that she is happy to take the medication and continue to breastfeed but will monitor any changes in baby Susie's behaviour. She will also contact the IAPT team for some follow up support.

Conclusion

Prescribing for a lactating mother may not be easy. The disadvantages of not breastfeeding are known, as is increasing prevalence of chronic disease. Using pharmacokinetic data and studies, which are limited in size, we can make professional decisions in consultation with the parents. Rather than say ‘the mother needs medication x, can she continue to breastfeed?’, might we change the emphasis to ask which medication can a mother take for her condition which enables her to continue to breastfeed as normal? The latter maintains the mother and baby dyad at the centre of the consultation.

Key Points

• When prescribing to breastfeeding women prescribers need to be aware that some of the drug which she takes is likely to pass to the baby via breastmilk
• As chronic disease specialists, general practice nurses may be at the forefront of professionals supporting breastfeeding women needing regular medication for a chronic disease
• The more that a drug is bound to the plasma proteins in the mother's bloodstream, the less of the drug that there is to pass into milk
• Drugs with long half-lives can accumulate in the blood and, therefore, the milk
• Prescibers need to be aware of sources they can use to find more information on this topic

CPD reflective questions

• Can you describe the benefits of breastfeeding to women and their babies?
• How confident are you advising breastfeeding mothers on medications? Where could you get more information?
• Which questions should you consider when helping women to make informed decisions?