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Research on medications during lactation: Getting answers or raising questions?

As time goes by, more women choose to breastfeed. Scientific research provides data supporting that breastfeeding has important benefits for the child, the mother, the family and the society. Mothers who breastfeed often need medications, for acute or chronic diseases1,2. Since 2016, the Summary of Product Characteristics of medications used for premenopausal women, must contain information regarding lactation, according to the Pregnancy Lactation Labeling Rule that the United States FDA implemented3. Even though the guidelines have changed, the available information is inadequate. Nowadays many researchers focus on breastfeeding dyads and it is very promising to see new data available in the literature.

Important Parameters in Pharmaceutical Research During Lactation

In order to be able to draw safe conclusions from studies during lactation though, there are many aspects that need to be considered. Unfortunately available studies provide insufficient information, due to the physiology of lactation. For instance, it is well known that colostrum has a completely different composition, than the composition of transitional or mature milk2. As a result, drug levels measured in colostrum might vary from the levels measured in mature milk of the same mother. As the passage of drugs in breastmilk is much higher during the immediate postpartum period, studies done during this period might show higher concentrations, because the gaps between the lactocytes are still open and medications can easily be transferred in the milk. While the gaps close and the milk matures, it is harder for the drugs to be transferred through the lactocytes.2,4

It is also very important to collect as many milk samples as possible in each study. Getting only one or a couple of milk samples from each mother gives us only a small piece of information. If the milk sample was taken in the morning or at the beginning of a feeding, the breast might be fuller and the drug concentration could be measured lower than it trully is. On the other hand, measuring drug levels in a sample taken from an empty breast or in the evening, could lead to higher concentrations, if the drug is lipid-soluble, for example.

Many studies do not provide us with important data such as timing of drug administration and timing of milk sampling. If the milk sample is collected when the drug levels in plasma are highest (Tmax), it significantly differs from the milk sample that is collected after one or more medication's half-lives (T1/2).2,4


Medications, Labor Interventions and Other Parameters

Another thing we need to carefully examine when we study pharmacotherapy during lactation are the effects of medications and other parameters (e.g. labor interventions) i) on lactogenesis, ii) on milk production and iii) on the child. For instance, studies on antidepressants should carefully consider that SSRIs used during pregnancy can cause delayed lactogenesis in some women.5 While some mothers provide samples of transitional milk on the third or fourth day postpartum, some others might still be producing colostrum. So when milk samples are collected during the immediate postpartum period, it is important to know if the milk "came in" and exactly when that happened for every participant mother.

Other factors significantly affecting lactogenesis, milk production and infants are maternal thyroid and metabolic function6, maternal hormonal balance, medications that were administered prenatally, during labor or postnatally,5,7 length of gestation and mode of birth. For instance, if a mother has a history of gestational diabetes, high Body Mass Index (BMI) or Polycystic Ovaries Syndrome (PCOS) she might be insulin resistant and the problems of insufficient milk production she might be facing could be due to that hormonal imbalance, rather than the effects of the medications she received.8

In many studies it is not mentioned if all mothers were carefully screened for alcohol consumption, tobacco smoking, other substances, herbal medications or Over The Counter (OTC) drugs that could interfere with the study results.9 Furthermore, it is known for decades that synthetic oxytocin and opioid analgesics -like the ones used in epidural analgesia- when administered during labor, can affect not only lactogenesis5, but also the neurophysiology of the neonate10-12. The effects on the infants of medications used during labor, can be apparent not only for the first few hours after birth13-16, but often for longer periods10,17-19.

There are evidence showing that different labor interventions lead to various neonatal effects. The use of forceps or vacuum may cause pain or headache to the neonate20, which could cause more infant crying and irritability. There are evidence showing that the use of synthetic oxytocin may lead to poor infant feeding and depressed neonatal reflexes.13-16,21-24 In animal experiments, central -but not peripheral oxytocin administration- blocked the calls of the rat pups for mother25, 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 neonates26. So it is hard to differentiate the effects of drug exposure via breastmilk, 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? Or when we see poor neonatal neurological scores, how can we tell if it is the effect of a drug in breastmilk, 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 lead to each effect. When there is one or few milk samples collected and the data of a study refer to a small time frame of the postpartum period, we only see a 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, that can answer questions instead of raising them.




1. Illamola S.L., Bucci-Rechtweg C., Costantine M.M., Tsilou E., Sherwin C.M. and Zajicek A. Inclusion of pregnant and breastfeeding women in research - efforts and initiatives. Br J Clin Pharmacol 2018;84(2):215-222

2. Nice F.J. and Luo A. Medications and breast-feeding: Current concepts. J Am Pharm Assoc. 2012;52:86-94

3. Whyte J. FDA Implements New Labeling for Medications Used During Pregnancy and Lactation. Am Fam Phys 2016;94(1):12-5

4. Hale T.W. and Rowe H.E. Medications and Mothers' Milk 2017; 17th Edition. Amarillo TX: Springer Publishing Company LLC

5. Anderson P.O. Drugs that Suppress Lactation, Part 1. Breastfeed Med 2017;12:128-130

6. Stuebe A.M., Meltzer-Brody S., Pearson B., Pedersen C. and Grewen K. Maternal neuroendocrine serum levels in exclusively breastfeeding mothers. Breastfeed Med. 2015;10(4):197-202.

7. Anderson P.O. Drugs that Suppress Lactation, Part 2. Breastfeed Med. 2017;12:199-201

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

9. Sachs H.C. The Transfer of Drugs and Therapeutics Into Human Breast Milk: An Update on Selected Topics. Committee On Drugs. Pediatrics 2013;132(3): e796-e809

10. Ounsted M.K., Boyd P.A., Hendrick A.M., Mutch L.M., Simons C.D. and Good F.J. Induction of labour by different methods in primiparous women. II. Neuro-behavioural status of the infants. Early Hum Dev. 1978;2(3):241-53.

11. Herrera-Gomez A., García-Martínez O., Ramos-Torrecillas J., De Luna-Bertos E., Ruiz C. and Ocaña-Peinado F.M. Retrospective study of the association between epidural analgesia during labour and complications for the newborn. Midwifery 2015;31(6):613-616

12. Martin E., Vickers B., Landau R., Reece-Stremtan S. and the Academy of Breastfeeding Medicine. Academy of Breastfeeding Medicine Clinical Protocol #28: Peripartum analgesia and Anesthesia for the Breastfeeding Mother. Breastfeed Med 2018;13(3):164-71

13. Abdoulahi M., Hemati Z., Sadat Mousavi As F., Delaram M. and Namnabati M. Association of Using Oxytocin during Labor and Breastfeeding Behaviors of Infants within Two Hours after Birth. Iran J Neonat 2017;8(3):48-52

14. Bell A.F., White-Traut R. and Rankin K. Fetal exposure to synthetic oxytocin and prefeeding cues within one-hour postbirth. Early Hum Dev 2013;89(3):137-43

15. Brimdyr K., Cadwell K., Widström A.M., Svensson K., Neumann M., Hart E.A., Harrington S. and Phillips R. The Association Between Common Labor Drugs and Suckling When Skin-to-Skin During the First Hour After Birth. Birth 2015;42(4):319-28.

16. Hemati Z., Abdollahi M., Broumand S., Delaram M., Namnabati M. and Kiani D. Association between Newborns' Breastfeeding Behaviors in the First Two Hours After Birth and Drugs Used For Their Mothers in Labor. Iran J Child Neurol 2018;12(2):33-40.

17. Gomes M. Trocado V., Carlos-Alves M., Arteiro D. And Pinheiro P. Intrapartum synthetic oxytocin and breastfeeding: a retrospective cohort study. J Obstet Gynaecol. 2018; 9:1-5

18. Gu V., Feeley N., Gold I., Hayton B., Robins S., Mackinnon A., Samuel S., Carter C.S. and Zelkowitz P. Intrapartum Synthetic Oxytocin and Its Effects on Maternal Well-Being at 2 Months Postpartum. Birth. 2016;43(1):28-35.

19. Brown A and Jordan S. Active Management of the Third Stage of Labor May Reduce Breastfeeding Duration Due to Pain and Physical Complications. Breastfeed Med 2014;9(10):494-502

20. Rakza T., Butruille L., Thirel L., Houfflin-Debarge V., Logier R., Storme L. and De Jonckheere J. Short-term Impact of Assisted Deliveries: Evaluation Based on Behavioral Pain Scoring and Heart Rate Variability. Clin J Pain. 2018;34(5): 445-449.

21. French C.A., Cong X. and Chung K.S. Labor Epidural Analgesia and Breastfeeding: A Systematic Review. J Hum Lact 2016;32(3):507-520

22. Ibone Olza F., Marín Gabriel M., Malalana Martínez A., Fernández-Cañadas Morillo A., López Sánchez F., and Costarelli V. Newborn feeding behaviour depressed by intrapartum oxytocin: a pilot study. Acta Paediatrica 2012;101(7):749-754

23. Marin Gabriel MA., Ibone Olza F, Malalana Martínez A., González Armengod C., Costarelli V., Millán Santos I., Fernández-Cañadas Morillo A., Pérez Riveiro P., López Sánchez F. and García Murillo L. Intrapartum Synthetic Oxytocin Reduce the Expression of Primitive Reflexes Associated with Breastfeeding. Breastfeed Med 2015;10(4):209-213

24. Odent M.R. Synthetic oxytocin and breastfeeding: Reasons for testing an Hypothesis, Medical Hypotheses 2013;81:889–891

25. Insel T.R. and Winslow J.T. Central administration of oxytocin modulates the infant rats response to social isolation. Eur J Pharmacol 1991;203(1):149-152

26. Nikkola E.M., Jahnukainen T.J., Ekblad U.U., Kero P.O. and Salonen M.A. Neonatal monitoring after maternal fentanyl analgesia in labor. J Clin Monit Comput 2000;16(8):597-608.


Article published in Womens Health Today Blog 


Κωνσταντίνα Γιαννιώτη
Κωνσταντίνα Γιαννιώτη

Είμαι η Κωνσταντίνα Γιαννιώτη.
Σύζυγος, μητέρα δύο παιδιών, Φαρμακοποιός, Διεθνώς Πιστοποιημένη Σύμβουλος Γαλουχίας IBCLC, Διεθνής Συνεργάτιδα της APILAM ( και Εθελοντρια Σύμβουλος Θηλασμού του Συνδέσμου Θηλασμού Ελλάδος - La Leche League Greece / La Leche League International.
Γεννήθηκα και μεγάλωσα στη Ζάκυνθο. Απολαμβάνω τη μουσική, τη συντροφιά, τα βιβλία και τη συγγραφή. Είμαι ανήσυχο πνεύμα. Μου αρέσει να δημιουργώ, να κινούμαι και να ταξιδεύω. Αγαπώ τους ανθρώπους, τα ζώα και τη φύση. Χαίρομαι να συνδυάζω και να χρησιμοποιώ γνώσεις, δεξιότητες και εμπειρίες, για το καλό όλων.
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Κωνσταντίνα Γιαννιώτη PharmD IBCLC  - Υπηρεσίες Συμβουλευτικής Γαλουχίας & Φαρμάκων