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Safety of Medications During Pregnancy and Breastfeeding: Infants of Drug-Addicted Mothers

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Neonatology

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Abstract

Any decision on maternal pharmacotherapy should be balanced, comparing maternal and fetal/neonatal outcome to withholding any treatment. This is because there is a relevant body of evidence that uncontrolled maternal conditions also affect fetal outcome. The same holds true for breastfeeding.

Drugs are not thoroughly evaluated for use during pregnancy or breastfeeding. Knowledge on safety of drugs exposure during fetal and neonatal (breastfeeding) life is limited. Pregnancy category classifications for drugs are currently used, but have their limitations. Pregnancy exposure registries to build knowledge have been implemented in the recently revised version of the FDA labelling guidelines (Pregnancy and Lactation Labeling Final Rule).

Suggestive indicators of “likely safe during breastfeeding” are (i) drugs commonly administered to infants, (ii) drugs that are not absorbed following oral administration, (iii) not excreted into human milk, and finally (iv) drug considered safe during pregnancy, since fetal exposure is generally longer and more extensive. Aspects of opioids, benzodiazepines, and anti-epileptics use during fetal life or via breastfeeding have been discussed to illustrate the concepts of pregnancy-related clinical pharmacology, followed by a focused discussion on neonatal abstinence syndromes. We hereby aim to provide the practicing clinician with some guidance and sources of information.

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References

  • Allegaert K, van den Anker JN (2015) Maternal analgosedation and breastfeeding: guidance for the pediatrician. JPNIM 4, e04117

    Google Scholar 

  • Allegaert K, Langhendries JP, van den Anker JN (2013) Educational paper: do we need neonatal clinical pharmacologists? Eur J Pediatr 172(4):429–435

    Article  Google Scholar 

  • Amant F, Han SN, Gziri MM et al (2015) Management of cancer in pregnancy. Best Pract Res Clin Obstet Gynaecol 29:741–753

    Article  Google Scholar 

  • Anderson PO, Pochop SL, Manoquerra AS (2003) Adverse drug reactions in breastfed infants: less than imagined. Clin Pediatr (Phila) 42:325–340

    Article  Google Scholar 

  • Asti L, Magers JS, Keels E et al (2015) A quality improvement project to reduce length of stay for neonatal abstinence syndrome. Pediatrics 135:e1494–e1500

    Article  Google Scholar 

  • Bada HS, Sithisam T, Gibson J et al (2015) Morphine versus clonidine for neonatal abstinence syndrome. Pediatrics 135:e383–e391

    Article  Google Scholar 

  • Berlin CM Jr, van den Anker JN (2013) Safety during breastfeeding: drugs, foods, environmental chemicals, and maternal infections. Semin Fetal Neonatal Med 18:13–18

    Article  Google Scholar 

  • Briggs GG, Polifka JE, Wisner KL et al (2015) Should pregnant women be included in phase IV clinical drug trials? Am J Obstet Gynecol 213:810–815

    Article  Google Scholar 

  • Cole AP, Hailey DM (1975) Diazepam and active metabolite in breast milk and their transfer to the neonate. Arch Dis Child 50:741–742

    Article  CAS  Google Scholar 

  • Creanga AA, Sabel JC, Ko JY et al (2012) Maternal drug use and its effect on neonates: a population-based study in Washington State. Obstet Gynecol 119:924–933

    Article  Google Scholar 

  • De Wildt SN, Kearns GL, Hop WC et al (2002) Pharmacokinetics and metabolism of oral midazolam in preterm infants. Br J Clin Pharmacol 53:390–392

    Article  Google Scholar 

  • DeVane CL (2015) An epidemic of opioid prescriptions. Pharmacotherapy 35:241–242

    Article  Google Scholar 

  • Dow K, Ordean A, Murphy-Oikonen J et al (2012) Neonatal abstinence syndrome clinical practice guidelines for Ontario. J Popul Ther Clin Pharmacol 19:e488–e506

    PubMed  Google Scholar 

  • Feghali MN, Mattison DR (2011) Clinical therapeutics in pregnancy. J Biomed Biotechnol 2011:783528

    Article  Google Scholar 

  • Gadot Y, Koren G (2015) The use of antidepressants in pregnancy: focus on maternal risks. J Obstet Gynaecol Can 37:56–63

    Article  Google Scholar 

  • Genung V (2013) Psychopharmacology column: a review of psychotropic medication lactation risks for infants during breastfeeding. J Child Adolesc Psychiatr Nurs 26:214–219

    Article  Google Scholar 

  • Hendrickson RG, McKeown NJ (2012) Is maternal opioid use hazardous to breast-fed infants? Clin Toxicol 50:1–14

    Article  CAS  Google Scholar 

  • http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm093307.html. Accessed 8 July 2015

  • Hudak ML, Tan RC, Committee on Drugs, Committee on Fetus and Newborn, American Academy of Pediatrics (2012) Neonatal drug withdrawal. Pediatrics 129:e540–e560

    Article  Google Scholar 

  • Ito S, Blajchman A, Stephenson M, Eliopoloulos C, Koren G (1993) Prospective follow up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol 168:1393–1399

    Article  CAS  Google Scholar 

  • Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ (2006) Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet 368:704

    Article  Google Scholar 

  • Lam J, Kelly L, Ciszkowski C et al (2012) Central nervous system depression of neonates breastfed by mothers receiving oxycodone for postpartum analgesia. J Pediatr 160:33.e2–37.e2

    Article  Google Scholar 

  • Lefevere J, Allegaert K (2015) Question: is breastfeeding useful in the management of neonatal abstinence syndrome? Arch Dis Child 100:414–415

    Article  Google Scholar 

  • MacMullen NJ, Dulski LA, Blobaum P (2014) Evidence-based interventions for neonatal abstinence syndrome. Pediatr Nurs 40:165–172

    PubMed  Google Scholar 

  • Marsot A, Brevaut-Malaty V, Vialet R (2014) Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach. Fundam Clin Pharmacol 28:465–471

    Article  CAS  Google Scholar 

  • Meador KJ, Baker GA, Browning N et al (2009) Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med 360:1597–1605

    Article  CAS  Google Scholar 

  • Meador KJ, Baker GA, Browning N et al (2014) Breastfeeding in children of women taking antiepileptic drugs. Cognitive outcomes at age 6 years. JAMA Pediatr 168:729–736

    Article  Google Scholar 

  • Ng CM, Dombrowsky E, Lin H et al (2015) Population pharmacokinetic model of sublingual buprenorphine in neonatal abstinence syndrome. Pharmacotherapy 35(7):670–680

    Article  CAS  Google Scholar 

  • Nitsun M, Szokol JW, Saleh HJ et al (2006) Pharmacokinetics of midazolam, propofol, and fentanyl transfer to human breast milk. Clin Pharmacol Ther 79:549–557

    Article  CAS  Google Scholar 

  • O’Donnell M, Nassar N, Leonard H et al (2009) Increasing prevalence of neonatal withdrawal syndrome: population study of maternal factors and child protection involvement. Pediatrics 123:e614–e621

    Article  Google Scholar 

  • Ornoy A, Koren G (2014) Selective serotonin reuptake inhibitors in human pregnancy: on the way to resolving the controversy. Semin Fetal Neonatal Med 19:188–194

    Article  Google Scholar 

  • Patrick SW, Schumacher RE, Benneyworth BD et al (2012) Neonatal abstinence syndrome and associated health care expenditures: United States, 2000–2009. JAMA 307:1934–1940

    Article  CAS  Google Scholar 

  • Patrick SW, Davis MM, Lehman CU, Cooper WO (2015) Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to 2012. J Perinatol 35:650–655

    Article  CAS  Google Scholar 

  • Pavek P, Ceckova M, Staud F (2009) Variation of drug kinetics in pregnancy. Curr Drug Metab 10:520–529

    Article  CAS  Google Scholar 

  • Pressler RM, Mangum B (2013) Newly emerging therapies for neonatal seizures. Semin Fetal Neonatal Med 18:216–223

    Article  Google Scholar 

  • Ramoz LL, Patel-Shori NM (2014) Recent changes in pregnancy and lactation labeling: retirement of risk categories. Pharmacotherapy 34:389–395

    Article  Google Scholar 

  • Reefhuis J, Devine O, Friedman JM et al (2015) Specific SSRIs and birth defects bayesian analysis to interpret new data in the context of previous reports. BMJ 351:h3190

    Google Scholar 

  • Rivers CM, Olsen D, Nelson LS (2012) Breastfeeding and oxycodone. J Pediatr 161:174

    Article  Google Scholar 

  • Rowe H, Baker T, Hale TW (2013) Maternal medication, drug use, and breastfeeding. Pediatr Clin North Am 60:275–294

    Article  Google Scholar 

  • Saadeh RJ (2012) The Baby-Friendly Hospital Initiative 20 years on: facts, progress, and the way forward. J Hum Lact 28:272–275

    Article  Google Scholar 

  • Sachs HC, Committee on Drugs (2013) The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics 132:e796–e809

    Article  Google Scholar 

  • Salman S, Sy SK, Ilett KF, Page-Sharp M, Paech MJ (2011) Population pharmacokinetic modeling of tramadol and its O-desmethyl metabolite in plasma and breast milk. Eur J Clin Pharmacol 67:899–908

    Article  CAS  Google Scholar 

  • Sistonen J, Madadi P, Ros CJ et al (2012) Prediction of codeine toxicity in infants and their mothers using a novel combination of maternal genetic markers. Clin Pharmacol Ther 91:692–699

    Article  CAS  Google Scholar 

  • Siu A, Robinson CA (2014) Neonatal abstinence syndrome: essentials for the practitioner. J Pediatr Pharmacol Ther 19:147–155

    PubMed  PubMed Central  Google Scholar 

  • Thomas SH, Yates LM (2012) Prescribing without evidence – pregnancy. Br J Clin Pharmacol 74:691–697

    Article  Google Scholar 

  • Turner SD, Gomes T, Camacho X et al (2015) Neonatal opioid withdrawal and antenatal opioid prescribing. CAMJ Open 13:E55–E61

    Article  Google Scholar 

  • Van den Anker JN (2012) Is it safe to use opioids for obstetric pain while breastfeeding? J Pediatr 160:4–6

    Article  Google Scholar 

  • Veiby G, Engelsen BA, Gilhus NE (2013) Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding: a prospective cohort study on children of women with epilepsy. JAMA Neurol 70:1367–1374

    Article  Google Scholar 

  • Veiby G, Bjork M, Engelsen BA, Gilhus NE (2015) Epilepsy and recommendations for breastfeeding. Seizure 28:57–65

    Article  Google Scholar 

  • Verreault N, Da Costa D, Marchand A et al (2014) Rates and risk factors associated with depressive symptoms during pregnancy and with postpartum onset. J Psychosom Obstet Gynaecol 35:84–91

    Article  Google Scholar 

  • Wachman EM, Hayes MJ, Brown MS et al (2013) Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome. JAMA 309:1821–1827

    Article  CAS  Google Scholar 

  • Zaijcek A, Giacoia GP (2007) Obstetric clinical pharmacology: coming of age. Clin Pharmacol Ther 81:481–482

    Article  Google Scholar 

  • Zimmermann-Baer U, Nötzi U, Rentsch K, Bucher HU (2010) Finnegan neonatal abstinence scoring system: normal values for first 3 days and weeks 5–6 in non-addicted infants. Addiction 105:524–528

    Article  Google Scholar 

Download references

Acknowledgments

Karel Allegaert is supported by the Fund for Scientific Research, Flanders (fundamental clinical investigatorship 1800214 N), and the research activities are further facilitated by the agency for innovation by Science and Technology in Flanders (IWT) through the SAFEPEDRUG project (IWT/SBO 130033). John van den Anker is supported by NIH (K24DA027992, R01HD048689, U54HD071601) and the European Commission (TINN [223614], TINN2 [260908]. NEUROSIS [223060]).

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Authors and Affiliations

  1. Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium

    Karel Allegaert

  2. Department of Development and Regeneration, KU Leuven, Leuven, Belgium

    Karel Allegaert & Tim van Mieghem

  3. Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium

    Tim van Mieghem

  4. Division of Pediatric Clinical Pharmacology, Children’s National Health System, Washington, DC, USA

    John N. van den Anker

  5. Departments of Pediatrics, Integrative Systems Biology, Pharmacology and Physiology, George Washington University, School of Medicine and Health Sciences, Washington, DC, USA

    John N. van den Anker

  6. Intensive Care and Department of Pediatric Surgery, Erasmus MC – Sophia Children’s Hospital, Rotterdam, The Netherlands

    Karel Allegaert & John N. van den Anker

Authors
  1. Karel Allegaert
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  2. Tim van Mieghem
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  3. John N. van den Anker
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Corresponding author

Correspondence to Karel Allegaert .

Editor information

Editors and Affiliations

  1. Department of Pediatrics Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy

    Giuseppe Buonocore

  2. Department of Pediatrics Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy

    Rodolfo Bracci

  3. Liverpool Women’s Hospital Neonatal Unit, Liverpool, UK

    Michael Weindling

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Allegaert, K., van Mieghem, T., van den Anker, J.N. (2018). Safety of Medications During Pregnancy and Breastfeeding: Infants of Drug-Addicted Mothers. In: Buonocore, G., Bracci, R., Weindling, M. (eds) Neonatology. Springer, Cham. https://doi.org/10.1007/978-3-319-29489-6_192

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  • DOI: https://doi.org/10.1007/978-3-319-29489-6_192

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-29487-2

  • Online ISBN: 978-3-319-29489-6

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