Pharmacist and international partner of la Asociación para la Promoción e Investigación científica y cultural de la Lactancia Materna (APILAM) Konstantina Giannioti examines the research on medications in mothers’ breast milk and asks whether it is finding answers or raising questions.

These days, more women are choosing to breastfeed. Scientific research provides the data to support the importance of breastfeeding for the child, the mother, the family and society at large. Breastfeeding mothers (like any women) need medications for acute or chronic diseases (llamola, Bucci-Rechtweg, Costantine, Tsilou, Sherwin, & Zajicek, 2017; Nice & Luo, 2012). Since 2016, the summary of product characteristics of medications used by premenopausal women must contain information regarding lactation, according to the Pregnancy Lactation Labeling Rule, as implemented by the United States Food and Drug Administration (Whyte, 2016). Even though the guidelines have changed, the available information remains inadequate. Many researchers are focusing now on breastfeeding dyads. It is promising to see new data as it becomes available in the literature.

Important parameters in pharmaceutical research during lactation

In order to be able to draw safe conclusions from studies carried out during lactation, there are many aspects that need to be considered. Unfortunately, available studies provide insufficient information because due consideration is not given to the physiology of lactation. For instance, we know that colostrum has a completely different composition to that of transitional or mature milk. 

As a result, drug levels measured in colostrum might vary from the levels measured in the mature milk of the same mother. Studies carried out during the immediate postpartum period,  might show higher concentrations of drugs in breast milk, because the gap junctions between the lactocytes (milk-producing cells in the mammary epithelium) are still open so that medications can easily be transferred in the milk. As the gaps close and the milk matures, it is harder for the drugs to be transferred through the lactocytes (Nice & Luo, 2012; Hale, 2017).

It is also very important to collect as many milk samples as possible in each study. Getting only one or two milk samples from each mother does not give us enough information. A milk sample taken in the morning or at the beginning of a feeding, when the breast might be fuller, results in a low measure of drug concentration. By contrast, measuring drug levels in a sample taken from an empty breast or in the evening could reveal higher concentrations, if the drug is lipid-soluble, for example.

Many studies do not provide us with the necessary data regarding the timing of drug administration and timing of milk sampling. If the milk sample is collected when the drug levels in plasma are highest (Tmax), this will differ significantly from the milk sample that is collected after one or more medication’s half-lives (T1/2) (Nice & Luo; 2012; Hale, 2017).

Is Research on Medications In Mothers' Breast Milk Finding Answers?
Ken Tackett

Medications, labor interventions and other parameters

When we study pharmacotherapy (treatment through administration of drugs) during lactation, we need to examine carefully the effects of medications and other parameters (e.g. labor interventions) on:

  • lactogenesis (the onset of milk secretion),
  • milk production, and
  • the child.

For instance, studies on antidepressants should carefully consider how selective serotonin reuptake inhibitors (SSRIs) used during pregnancy can lead to delayed lactogenesis in some women (Anderson, 2017, Part 1). While some mothers provide samples of transitional milk on the third or fourth day postpartum, some others might still be producing colostrum at that point. So, when milk samples are collected during the immediate postpartum period, it is important to know if the milk has “come in” and exactly when that happened for every participant mother.

Other factors significantly affecting lactogenesis, milk production and infants are:

  • maternal thyroid and metabolic function (Stuebe, Meltzer-Brody, Pearson, Pedersen, & Grewen, 2015)
  • maternal hormonal balance
  • medications that were administered prenatally during labor or postnatally (Anderson, 2017) 
  • length of gestation
  • mode of birth.

Let’s say a mother has a history of gestational diabetes, high body mass index (BMI) or polycystic ovaries syndrome (PCOS), she might then be insulin resistant and the problems of insufficient milk production she could be facing might be due to that hormonal imbalance, rather than the effects of the medications she has received (Kirigin Biloš, 2017).

Many studies do not record whether all the participant mothers have been carefully screened for alcohol consumption, tobacco smoking, herbal medications, over the counter (OTC) drugs or other substances that could interfere with the study results (Sachs, 2013). 

We have known for decades that when administered during labor, synthetic oxytocin and opioid analgesics, like the ones used in epidural analgesia, can affect not only lactogenesis (Anderson, 2017), but also the neurophysiology of the neonate (Ounsted, Boyd, Hendrick, Mutch, Simons, & Good, 1978; Herrera-Gómez, García-Martínez, Ramos-Torrecillas, De Luna-Bertos, Ruiz, & Ocaña-Peinado, 2015; Martin, Vickers, Landau, & Reece-Stremtan, 2018). The effects on the infants of medications used during labor may be apparent not only for the first few hours after birth (Abdoulahi, Hemati, Sadat Mousavi, Delaram, & Namnabati, 2017; Bell, White-Traut, & Rankin, 2013; Brimdyr et al., 2015; Hemati, Abdollahi, Broumand, Delaram, Namnabati, & Kiani, 2018), but often for longer periods (Ounsted, Boyd, Hendrick, Mutch, Simons, & Good, 1978; Gomes, Trocado, Carlos-Alves, Arteiro, & Pinheiro, 2018; Gu et al,. 2015; Brown, & Jordan, 2014).

The evidence shows that different labor interventions lead to various neonatal effects. The use of forceps or vacuum extraction may cause pain or headache in the neonate (Rakza, Butruille, Thirel, Houfflin-Debarge, Logier, Storme, & De Jonckheere, 2018), which could cause more infant crying and irritability. There is evidence that the use of synthetic oxytocin may lead to poor infant feeding and depressed neonatal reflexes (Abdoulahi, Hemati, Sadat Mousavi, Delaram, & Namnabati, 2017; Bell, White-Traut, & Rankin, 2013; Brimdyr et al., 2015; Hemati, Abdollahi, Broumand, Delaram, Namnabati, & Kiani, 2018; French, Cong, & Chung, 2016; Olza Fernández, Marín Gabriel, Malalana Martínez, Fernández-Cañadas Morillo, López Sánchez, & Costarelli, 2012; Marín Gabriel, 2015; Odent, 2013).

In animal experiments, central but not peripheral oxytocin administration blocked the calls of rat pups for their mother (Insel, & Winslow, 1991), so there could be a chance that externally administered synthetic oxytocin during labor affects infant crying, among other parameters. The use of fentanyl in maternal epidural analgesia during labor may cause less quiet sleep, heart rate alterations and poor neurological adaptation in neonates (Nikkola, Jahnukainen, Ekblad, Kero, & Salonen, 2000). It is hard to differentiate the effects of drug exposure via breast milk from the effects of placental drug exposure and labor interventions in the early postpartum period.

Questions raised

In studies regarding lactation, where the effects on neonates of maternal central nervous system (CNS) medications are measured, how do we know that symptoms such as irritability, poor feeding or less quiet sleep are not caused, for instance, by pain that the baby is experiencing because of the forceps used during labor or because of other labor interventions? When we see poor neonatal neurological scores, how can we tell if it is the effect of a drug in breast milk that might be affecting the central nervous system rather than the exposure to synthetic oxytocin or epidural narcotic analgesics that were used during labor? Even by assessing infantile symptoms using standardized tools, it is very difficult to tell which specific intervention or substance led to which effect. When a single milk sample or just a few are collected and the data of a study refer to a small time frame of the postpartum period, we only see a small part of the whole picture.    


In order to get answers and valid data from research during lactation, it is critical to design carefully every aspect of each study and put every single detail under the microscope. Safe use of medications for mothers and babies is not just about having a lot of questionable information. The best choices regarding pharmacotherapy are made by collecting and using valid and accurate data, which can answer questions instead of raising them.

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Abdoulahi, M., Hemati, Z., Sadat Mousavi, As., F., Delaram, M., & Namnabati, M. (2017). Association of using oxytocin during labor and breastfeeding behaviors of infants within two hours after birth. Iran J Neonat, 8(3):48-52

Anderson, P. O. (2017). Drugs that suppress lactation, Part 1. Breastfeeding Medicine, 12(3), 128–130. doi:10.1089/bfm.2017.0012

Anderson, P. O. (2017). Drugs that suppress lactation, Part 2. Breastfeeding Medicine, 12(4), 199–201. doi:10.1089/bfm.2017.0029

Bell, A. F., White-Traut, R., & Rankin, K. (2013). Fetal exposure to synthetic oxytocin and the relationship with prefeeding cues within one hour postbirth. Early Human Development, 89(3), 137–143. doi:10.1016/j.earlhumdev.2012.09.017

Brimdyr, K., Cadwell, K., Widström, A.-M., Svensson, K., Neumann, M., Hart, E. A., … Phillips, R. (2015). The association between common labor drugs and suckling when skin-to-skin during the first hour after birth. Birth, 42(4), 319–328. doi:10.1111/birt.12186

Brown, A., & Jordan, S. (2014). Active management of the third stage of labor may reduce breastfeeding duration due to pain and physical complications. Breastfeeding Medicine, 9(10), 494–502. doi:10.1089/bfm.2014.0048

French, C. A., Cong, X., & Chung, K. S. (2016). Labor epidural analgesia and breastfeeding. Journal of Human Lactation, 32(3), 507–520. doi:10.1177/0890334415623779

Gomes, M., Trocado, V., Carlos-Alves, M., Arteiro, D., & Pinheiro, P. (2018). Intrapartum synthetic oxytocin and breastfeeding: a retrospective cohort study. Journal of Obstetrics and Gynaecology, 1–5. doi:10.1080/01443615.2017.1405924

Gu, V., Feeley, N., Gold, I., Hayton, B., Robins, S., Mackinnon, A., … Zelkowitz, P. (2015). Intrapartum synthetic oxytocin and its effects on maternal well-being at 2 months postpartum. Birth, 43(1), 28–35. doi:10.1111/birt.12198

Hale, T. W. (2017) Medications and mothers’ milk, 17th edition. Amarillo, TX: Springer Publishing Company LLC.

Hemati, Z., Abdollahi, M., Broumand, S., Delaram, M., Namnabati , M., & Kiani, D. (2018). Association between newborns’ breastfeeding behaviors in the first two hours after birth and drugs used for their mothers in labor. Iranian Journal of Child Neurology, 12(2), 33–40.

Herrera-Gómez, A., García-Martínez, O., Ramos-Torrecillas, J., De Luna-Bertos, E., Ruiz, C., & Ocaña-Peinado, F. M. (2015). Retrospective study of the association between epidural analgesia during labour and complications for the newborn. Midwifery, 31(6), 613–616. doi:10.1016/j.midw.2015.02.013

Illamola, S. M., Bucci-Rechtweg, C., Costantine, M. M., Tsilou, E., Sherwin, C. M., & Zajicek, A. (2017). Inclusion of pregnant and breastfeeding women in research – efforts and initiatives. British Journal of Clinical Pharmacology, 84(2), 215–222. doi:10.1111/bcp.13438

Insel, T. R., & Winslow, J. T. (1991). Central administration of oxytocin modulates the infant rats response to social isolation. European Journal of Pharmacology, 203(1), 149–152. doi:10.1016/0014-2999(91)90806-2

Kirigin Biloš, L.S. (2017). Polycystic ovarian syndrome and low milk supply: Is insulin resistance the missing link? Endocr Oncol Metab, 3(2), 49–55.

Marín Gabriel, M. A., Olza Fernández, I., Malalana Martínez, A. M., González Armengod, C., Costarelli, V., Millán Santos, I., … García Murillo, L. (2015). Intrapartum synthetic oxytocin reduce the expression of primitive reflexes associated with breastfeeding. Breastfeeding Medicine, 10(4), 209–213. doi:10.1089/bfm.2014.0156

Martin, E., Vickers, B., Landau, R., & Reece-Stremtan, S. (2018). ABM Clinical Protocol #28, Peripartum analgesia and anesthesia for the breastfeeding mother. Breastfeeding Medicine, 13(3), 164–171. doi:10.1089/bfm.2018.29087.ejm

Nice, F. J., & Luo, A. C. (2012). Medications and breast-feeding: Current concepts. Journal of the American Pharmacists Association, 52(1), 86–94. doi:10.1331/japha.2012.10139

Nikkola, E. M., Jahnukainen, T. J., Ekblad, U. U., Kero, P. O., & Salonen, M. A. O. (2000). Journal of Clinical Monitoring and Computing, 16(8), 597–608. doi:10.1023/a:1012268617009

Odent, M. R. (2013). Synthetic oxytocin and breastfeeding: Reasons for testing an hypothesis. Medical Hypotheses, 81(5), 889–891. doi:10.1016/j.mehy.2013.07.044

Olza Fernández, I., Marín Gabriel, M., Malalana Martínez, A., Fernández-Cañadas Morillo, A., López Sánchez, F., & Costarelli, V. (2012). Newborn feeding behaviour depressed by intrapartum oxytocin: a pilot study. Acta Paediatrica, 101(7), 749–754. doi:10.1111/j.1651-2227.2012.02668.x

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Ken Tackett

Ounsted, M. K., Boyd, P. A., Hendrick, A. M., Mutch, L. M. M., Simons, C. D., & Good, F. J. (1978). Induction of labour by different methods in primiparous women II. Neuro-behavioural status of the infants. Early Human Development, 2(3), 241–253. doi:10.1016/0378-3782(78)90028-2

Rakza, T., Butruille L., Thirel, L., Houfflin-Debarge, V., Logier, R., Storme, L. & De Jonckheere, J. (2018). Short-term impact of assisted deliveries: Evaluation based on behavioral pain scoring and heart rate variability. Clin J Pain. 34(5), 445–449.

Sachs, H. C. (2013). The transfer of drugs and therapeutics into human breast milk: An update on selected topics. PEDIATRICS, 132(3), e796–e809. doi:10.1542/peds.2013-1985

Stuebe, A. M., Meltzer-Brody, S., Pearson, B., Pedersen, C., & Grewen, K. (2015). Maternal neuroendocrine serum levels in exclusively breastfeeding mothers. Breastfeeding Medicine, 10(4), 197–202. doi:10.1089/bfm.2014.0164

Whyte, J. (2016). FDA Implements new labeling for medications used during pregnancy and lactation. Am Fam Phys, 94(1),12–15.