Maternal opioid treatment after delivery and risk of adverse infant outcomes: population based cohort study
BMJ 2023; 380 doi: https://doi.org/10.1136/bmj-2022-074005 (Published 15 March 2023) Cite this as: BMJ 2023;380:e074005Linked Editorial
Opioid analgesia for breastfeeding mothers
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
Dear Editor,
We thank Dr. Francis for her comments. Our article explicitly discusses breastfeeding, and we acknowledge that we lack data on breastfeeding status.
The discrepancy between the numbers in the text and those in Figure 2 are explained by censoring. We censored mother-infant pairs if a mother who initially did not fill an opioid prescription subsequently filled one in the 30 days of follow-up. The numbers in Figure 2 represent those infants remaining at risk of the outcome at each time interval.
Regarding Dr. Francis’ point on rounding, it is obviously true that 3,038÷85,675 is 3.55, and we presented this in our initial results. This was changed to 3.5 to comply with journal style and does not influence our findings or conclusions.
We disagree with Dr. Francis about the study interpretation. The raw data indicate a slight increase in hospital admissions among infants born to mothers not prescribed opioids following birth. However, this finding corresponded to an absolute risk difference of 0.08% (95% confidence interval −0.06% to 0.22%). We interpret this difference as a null finding that suggests no significant difference in admissions between infants born to mothers prescribed opioids and those born to mothers who were not.
Competing interests: No competing interests
Dear Editors,
I am writing to submit a rapid response to the recent publication titled "Maternal opioid treatment after delivery and risk of adverse infant outcomes: population based cohort study" by Zipursky and colleagues in the British Medical Journal. As a psychiatrist specializing in the treatment of opioid addiction among pregnant women in Taiwan, I would like to emphasize the importance of evidence-based care for pregnant women with opioid addiction.
Healthcare providers have a responsibility to provide safe and effective care for pregnant women with opioid addiction. This involves not only managing addiction during pregnancy but also addressing the social and economic factors that may contribute to adverse outcomes for both mother and child. Evidence-based treatments such as methadone and buprenorphine have been shown to reduce the risk of adverse outcomes, and healthcare providers should prioritize these treatments for pregnant women with opioid addiction.
It is also important to address the social and economic factors that contribute to adverse outcomes. Pregnant women with opioid addiction are often from lower socio-economic backgrounds and may lack the support and resources necessary for adequate parenting. Therefore, healthcare providers should work closely with social services and other community resources to provide support and resources for these mothers.
Furthermore, it is crucial to consider the long-term impact of opioid use disorder on the children born to these mothers. My own case series study conducted 13 years ago found that infants born to pregnant women receiving methadone treatment did exhibit developmental delays. However, these delays were largely due to socio-economic factors and inadequate parenting, rather than the methadone treatment itself. It is therefore crucial that we provide appropriate resources and support to ensure optimal outcomes for these children.
In conclusion, evidence-based care that takes into account socio-economic factors and adequate support for mothers with opioid use disorder is crucial for the well-being of both mother and child. As healthcare providers, it is our responsibility to prioritize these evidence-based treatments and provide the necessary support and resources for pregnant women with opioid addiction.
Sincerely,
Lien-Chung Wei, Master of Public Health
Department of Addiction Psychiatry
Taoyuan Psychiatric Center, Ministry of Health and Welfare, Taiwan
Competing interests: No competing interests
Dear Editor,
I was very interested to read this original research piece in the BMJ physical journal.
Having read it through a number of times, and spoken to others, I can’t help but feel that some clarifications or corrections may need to be made regarding the following:
1) The study question and concluding statement under ‘What this study adds’ in the physical journal do not mention breastfeeding at all unlike the title. As the authors acknowledge that breastfeeding data is lacking and there is no other mention of breastfeeding apart from in that sentence alone, it seems incongruous that the title of this research draws attention to that element..
2) The numbers in the main body of the text in the physical journal don't entirely match the numbers used for the graph: for infants of the mothers who did not fill out an opioid prescription, the numbers show 85,675 - 82,003 = 3672 (4.3%) but the number quoted in the section titled ‘Study answer and limitations’ is 2962 (3.5%).
3) There seems to be a rounding error where 3.55 has been to 3.5 in this same section.
4) The conclusion drawn in 'what this study adds' says the opposite to what the numbers themselves show. The data shows a slight increase in infant admission in mothers who did not fill out an opioid prescription, not those who did.
I appreciate that the overarching conclusion from this study is most likely that there is still no association between maternal opioid prescription after delivery and adverse infant outcomes, but I feel that the article should be quoting the numbers and facts accurately.
If I have misunderstood any of the above, then please do correct me. Otherwise I hope my comments are useful.
Kind regards
Dr Tabitha Francis
Competing interests: No competing interests
Dear Editor
Opioids are routinely prescribed for postoperative pain management in many countries. Thus, surgery is among the most common indications for opioid initiation. Data from the United States suggest that there has been an increase in the amount of opioids dispensed following minor surgical procedures3 and that many US patients receive more opioids than necessary to treat their short-term pain. According to a recent study United States and Canada have a 7-fold higher rate of opioid prescriptions filled in the immediate postoperative period compared with Sweden. (1)
The belief that newborns can develop opioid toxicity from breastfeeding is widely held but supported by very little data. Based largely on a single, highly publicized case report (the "Toronto case"), major health agencies worldwide now caution against codeine use by nursing mothers. Although steps were taken to replace codeine with other opioids yet the notion of adverse effects are hard to believe due to the exceedingly small amount of opioids passed into breastmilk irrespective of maternal CYP genotype, the observation that significant neonatal opioid accumulation can only occur in the setting of severely impaired renal function, and the previously unreported finding of a markedly elevated codeine concentration in postmortem blood. (2)
Safety of maternal drug therapy during breastfeeding may be assessed from estimated levels of drug exposure of the infant through milk. Pharmacokinetic (PK) principles predict that the lower the clearance is, the higher the infant dose via milk will be. Drugs with low clearance (<1 mL/[kg·min]) are likely to cause an infant exposure level greater than 10% of the weight-adjusted maternal dose even if the milk-to-plasma concentration ratio is 1. Substantial individual variations of drug clearance exist in both mother and infant, potentially causing drug accumulation over time in some infants even if an estimated dose of the drug through milk is small (3). it has also been reported that overall, opioid use for pain management during labor and delivery and subsequent short-term use for 2-3 days are compatible with breastfeeding.
Another important decisive factor for adverse impact of maternal opioid use is the frequency of breast feeding or use of formula milk instead of breast feeding. Although breast feeding is considered as best feeding for infants however lesser frequency of breast feeding, donor human milk and use of standard formula milk powder instead of complete breast feeding may lower the risk factors for adverse opioid therapy outcomes in infants. A recent meta-analysis yielded convincing data indicating that breastfeeding is beneficial for newborns and infants with Neonatal Abstinence Syndrome (NAS). (4)
Hence an overall monitoring of neonates is important with respect to frequency of breast milk, renal function of neonate, pharmacokinetic properties of the opioid use, use of standard formula milk etc. for additional data on monitoring of risk outcomes related to maternal opioid therapy.
1. Ladha KS, Neuman MD, Broms G, et al. Opioid Prescribing After Surgery in the United States, Canada, and Sweden. JAMA Netw Open. 2019;2(9):e1910734.
2. Zipursky J, Juurlink DN. The Implausibility of Neonatal Opioid Toxicity from Breastfeeding. Clin Pharmacol Ther. 2020;108(5):964-970.
3. Ito S. Opioids in breast milk: pharmacokinetic principles and clinical implications. The Journal of Clinical Pharmacology. 2018;58:S151-63.
4. Chu L, McGrath JM, Qiao J, Brownell E, Recto P, Cleveland LM, Lopez E, Gelfond J, Crawford A, McGlothen-Bell K. A meta-analysis of breastfeeding effects for infants with neonatal abstinence syndrome. Nursing research. 2022;71(1):54.
Competing interests: No competing interests
Re: Maternal opioid treatment after delivery and risk of adverse infant outcomes: population based cohort study
Dear Editor,
I thank the authors of this research for their reply to my initial response. I believe there may have been a bit of confusion. My response to the clarifications needed were specifically in regards to the summarised version in the physical copy of the journal.
I noted that the article does state that breastfeeding data is lacking; my question was about why the summary of the research bears the title '...for breastfeeding mothers' at all, as no link can be drawn to breastfeeding.
I appreciate the explanation about censored data, and that may explain why the key in the graph, again, in the summarised version in the physical journal, appears to be labelled the opposite way round to the figures quoted directly beneath it.
Finally, with regards to my statement about the conclusion, this once again relates to the physical journal summary. I was not disputing there is no significant difference in admissions whether mothers filled out opioid prescriptions or not, I agree with that. I was merely commenting on the concluding sentence that says '...visits was marginally increased in infants of mothers who filled an opioid prescription...'. The author's response agrees with my interpretation of the summary, that the data showed '...a slight increase in hospital admissions among infants born to mothers not prescribed opioids following birth.' I wonder if this concluding sentence was simply written incorrectly.
All in all, my main concern was that the summary of the research printed in the physical BMJ 18 March 2023 edition might have had some incorrect statements written in it, hence my initial rapid response querying these.
Many thanks.
Competing interests: No competing interests