Introduction

Acatchy phrase that expectant and newly delivered moms will typically hear is “breast is best.” Although breast milk is best for newborn babies, this is especially true for premature babies in the neonatal intensive care unit (NICU). It is important for pharmacists to be aware of the advantages of mother’s milk for these vulnerable babies so that they can adequately assess the risk−benefit scenario when faced with whether or not it is safe to use a mother’s milk. There are very few contraindications to breastfeeding, but there are definite risks in not providing mother’s milk.

Mother’s Milk

Composition

Mother’s milk is produced based on the law of supply and demand. The hormones oxytocin and prolactin work in a positive feedback loop to establish the breastfeeding cycle.¹ A suckling baby or a breast pump empties the breasts, stimulating the creation of more milk. This is not always as simple as it sounds. In the early days following delivery, some women fight to produce drops of milk. This milk should not be taken for granted!

Colostrum, the first milk a new mother produces, is usually somewhat thick and yellow in color and lasts for 1 to 3 days. Drugs pass more readily into colostrum; however, due to the nature of the very small volume produced, exposure to any substance is minimal and clinically neglible.²

Benefits

Mother’s milk has been associated with reduced incidence of necrotizing enterocolitis (NEC), a potentially fatal disease in premature babies (see Chapter 13).³ In addition to fat, protein, carbohydrates, and vitamins, mother’s milk provides immune globulins and probiotics to colonize the newborn intestine. These properties protect babies from other infections besides NEC, such as otitis media and respiratory tract infections. Breastfed babies also have a lower risk for sudden infant death syndrome as well as a decreased risk of some childhood cancers (e.g., leukemia, lymphoma). The effects reach into adolescence and adulthood with formerly breastfed babies having lower incidence of diabetes and asthma.

Another advantage of mother’s milk is that the protein in human milk is better tolerated than the cow protein in infant formulas because it is easier for babies to digest.³

Length of Breastfeeding

Experts recommend exclusive breastfeeding for the first 6 months of life.³ Even as solid foods begin to be added to the diet, breastfeeding is recommended during the first year of life. The Healthy People 2020 Goals include a goal to increase the number of mothers who are breastfeeding at hospital discharge to 80% and for at least 60% to breastfeed through the first 6 months of the child’s life.⁴

Contraindications

Maternal contraindications to breastfeeding include human immunodeficiency virus, herpes simplex virus lesion on the breast, exposure to radioactive materials, antimetabolites or other chemotherapy, active tuberculosis, and human T-cell lymphocyctic virus infection.³ Additionally, infants who have galactosemia should not receive maternal milk. There are very few medications that are absolute contraindications to breastfeeding. Women frequently stop breastfeeding secondary to medication use, although that may not be the optimal decision.² Pharmacists can play a role in meeting the Healthy People 2020 goal by providing accurate, reliable information that may allow the mother to continue to provide milk safely to her infant.

Donor Milk

Prior to the invention of artificial feedings, women who could not provide milk for their babies relied on wet nurses. Since the early twentieth century, this practice has fallen out of favor due to understanding about the passage of communicable diseases. Interestingly, we have come full circle with several milk banks across the United States that provide pasteurized donor breast milk to NICUs. Donors are screened and are preferred not to be taking any medications regularly; however, specific medications (e.g., prenatal vitamins, human insulin, asthma inhalers) are allowed due to their proven safety.⁵

Additives to Mother’s Milk

Premature babies miss much of the nutrient accretion that occurs normally during the third trimester. To help them catch up, a supplement known as human milk fortifier is added in the NICU to maternal milk. This product adds protein and minerals such as phosphorus and calcium to the milk. Mother’s milk has low concentrations of iron, which has poor bioavailability. For this reason, premature babies receiving the majority of their calories from breast milk also require iron supplementation with at least 2 mg/kg/day. The American Academy of Pediatrics (AAP) recommends that all babies receive 400 units of vitamin D daily regardless of diet.⁶ For additional calories in babies who are not gaining adequate amounts of weight, medium chain triglycerides oil or a protein supplement (e.g., Beneprotein) may be added to increase caloric density. Oat cereal may be added to thicken feeds in babies who are experiencing symptomatic reflux. Rice cereal has fallen out of favor due to concerns over potential arsenic contamination.

Drug Transfer into Milk

Many properties affect the transfer of medications into human milk. Primarily, drugs pass into breast milk by passive diffusion from the mother’s blood stream.² If the drug is not present in the systemic circulation, then it cannot pass into milk. A few drugs have active transport mechanisms into breast milk. The most commonly used drugs that can pass via active transport include acyclovir, cimetidine, and iodine. Of these, iodine poses the greatest concern because large quantities of iodine can affect thyroid function. Normal dietary intake of iodine is not problematic, but supplements rich in iodine should be avoided during lactation. Even with active transport, the amount of acyclovir and cimetidine passed into milk is not clinically significant.

Understanding the pharmacokinetic and pharmacodynamic properties that affect drug transfer and sequestration into milk can assist and reassure pharmacists as they assess medication safety in lactation and make recommendations related to medication use in lactation.

Molecular Weight

The smaller the molecular weight, the more easily the drug will pass into milk.² For example, medications that are less than 200 daltons are most likely to pass into milk. Proteins such as insulin are very large molecules and would, therefore, not be expected to pass into milk at all.

Bioavailability

Bioavailability is an important factor to consider in assessing a medication’s safety in milk.² First, consider if the medication is absorbed by the mother. For example, if gastrointestinal (GI) contrast is administered during radiologic imaging of the GI tract, it is not absorbed. Because the contrast is not absorbed by the mother, it cannot pass into her milk. Second, consider if the medication has oral bioavailability. Enoxaparin is a large molecule that would not be expected to pass into milk. Even if it were passed into milk, the baby would not absorb it orally from the milk.

Volume of Distribution

Volume of distribution is important to consider because, as previously stated, substances that are not in the blood stream cannot pass into milk.² An example is the bisphosphonate zoledronic acid (Zometa) that is sometimes used to treat hyperparathyroidism. This medication distributes immediately to bone and does not remain in the serum, so it cannot be expected to pass into breast milk.

Peak Serum Concentration

Medications can sometimes be administered to avoid feeding or pumping milk during the time that a medication is at its peak serum concentration.² Just as medications diffuse into milk, they can also diffuse back into serum as the concentration decreases. This strategy can reduce the exposure that an infant has to a medication via lactation.

Acid Ionization Constant

Another factor that affects concentration of medications in breast milk is the acid ionization constant also known as the pK_a. Although most pharmacists have not thought about pK_a since pharmacy school, it is helpful to have an appreciation for the effect known as ion trapping. As a reminder, pK_a is the pH at which half the drug is ionized and half is unionized. Medications with a pK_a greater than 7.2 are at higher risk to become sequestered in milk.²

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