Medications and the breastfeeding mother

4.1

Medication use by the breastfeeding mother

Mothers may need medication both during and after pregnancy. In both cases, it is important not only to protect the infant but also to provide the mother with necessary drug treatment. The infant may be born having been exposed to maternal medication during gestation. It is important to remember, in addition to drug exposure of the infant during breastfeeding, that previous exposure during pregnancy may potentiate any adverse effects during lactation. This would especially be true in the immediate postnatal period, but for some drugs, the window of adverse reactions in the infant may be longer (e.g., antidepressants).

4.2

Clinical pharmacology of drug transfer into breast milk

The determining factors for the transport of drugs from maternal circulation to the alveolar lumen in the mammary cell are as follows [ ]: molecular weight [ ], binding to maternal plasma proteins [ ], lipid solubility, and [ ] degree of ionization. Drugs which are transferred most rapidly and/or in the highest amount are those with high lipid solubility, no electrical charge, low molecular weight, and low or no binding to maternal plasma proteins. There are four diffusion mechanisms for drug transfer into the mammary cell alveolar lumen: transcellular, intercellular, passive, and ionophore (transfer of polar compounds bound to carrier proteins) [ ]. Transcellular diffusion probably accounts for most drug transfer. The intercellular diffusion route, which avoids the interior of the cell, may account for the appearance in milk of high-molecular weight compounds such as immunoglobulins (from maternal plasma) and monoclonal antibody drugs such as etanercept (Enbrel, molecular weight 52,000). High-molecular weight compounds do appear in milk. Most obvious are antibodies from maternal plasma. Many of the newer pharmacological agents are high-molecular weight entities such as monoclonal antibodies. For drugs like etanercept, the amount appearing in milk is extremely small (2–5 ng/mL) compared to the maternal serum level of 1450–2000 ng/mL [ ]. Such a small amount of a protein is most likely pharmacologically inactive both because of the extremely small dose and also because of lack of absorption from the infant's gastrointestinal tract. Because virtually all drugs of a molecular weight below 200 or 300 Da will cross into milk, the dose that the child receives (concentration × volume) is usually pharmacologically insignificant. For most drugs, less than 1%–2% of the maternal dose is potentially available to be excreted into breast milk [ ].

4.3

During delivery

The obvious concern in this period of time is the type and anesthesia/analgesia that the mother may have received. This drug exposure may delay the onset of lactogenesis, may affect the mother's mentation and ability to nurse, and the infant may show effects from transplacental transfer that interfere with latch and ingestion. An important concept is that regardless of the type of anesthesia and/or analgesia used after delivery, the amount of any agent potentially transferred to the infant would be less than the amount transferred during labor and delivery via the placenta.

4.4

General anesthesia