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Parenteral Pethidine for Labour Pain Relief and Substance Use Disorder: 20-Year Follow-Up Cohort Study in Offspring

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Parenteral Pethidine for Labour Pain Relief and Substance Use Disorder: 20-Year Follow-Up Cohort Study in Offspring Open Access Research BMJ Open: first published as 10.1136/bmjopen-2011-000719 on 30 May 2012. Downloaded from Parenteral Pethidine for labour pain relief and substance use disorder: 20-year follow-up cohort study in offspring Robert Rodrigues Pereira,1,2,3 Humphrey Kanhai,4 Frits Rosendaal,5 Paula van Dommelen,6 Dick Swaab,7 Erik Rodrigues Pereira,8 Ben van de Wetering9 To cite: Rodrigues Pereira R, ABSTRACT ARTICLE SUMMARY Kanhai H, Rosendaal F, et al. Objective: To determine whether use of intrapartum Parenteral Pethidine for Pethidine pain analgesia increases the risk for Article focus labour pain relief and substance use disorder in adult offspring. - substance use disorder: Research question: does perinatal Pethidine for 20-year follow-up cohort Design: Analysis of data from a cohort study. labour pain relief lead to substance use disorder study in offspring. BMJ Open Setting: Academic hospital in Leiden, the Netherlands. in later life? 2012;2:e000719. doi:10. Participants: 133 cases and 164 control individuals, - Is it possible to confirm the published data on an 1136/bmjopen-2011-000719 aged 18e20 years at follow-up. OR of around 5? Main outcome measure: Incidence of substance use - We hypothesise that there is no relationship. < Prepublication history for disorder or use of alcohol and tobacco. this paper is available online. Key messages Results: The lifetime use of addictive substances in To view these files please - We cannot confirm earlier data on the risk of visit the journal online (http:// children exposed to intrapartum Pethidine analgesia substance use disorder after perinatal analgesia. dx.doi.org/10.1136/ was 45% of 133 children versus 48% of 164 not- - We did not find a risk for smoking and drinking bmjopen-2011-000719). ¼ exposed subjects (adjusted OR 0.79, 95% CI 0.48 to alcohol either. 1.29). Recent use of alcohol, tobacco and hard drugs - Perinatal Pethidine analgesia appears not to be http://bmjopen.bmj.com/ Received 5 December 2011 showed no statistical difference either. Accepted 1 May 2012 associated with substance misuse in later life. Conclusion: Pethidine for labour pain medication This final article is available appears not to be associated with substance misuse or Strengths and limitations of this study for use under the terms of smoking in later life. - This is a well-designed large cohort study on the Creative Commons long-term effects of perinatal Pethidine analgesia. Attribution Non-Commercial - The main limitation is the relatively low response 2.0 Licence; see and the possible selective response. http://bmjopen.bmj.com INTRODUCTION After parenteral therapy in the mother, the on September 25, 2021 by guest. Protected copyright. Analgesia during labour is common world- opiates can be detected in cord blood with wide. Methods used include barbiturates, a plasma level of 50% of that of the mother. nitrous oxide, opioids, epidural analgesia, After birth, the child is often sleepy and transcutaneous electric nerve stimulation, slightly respiratory depressed for a few psychoprophylaxis and hypnosis. In the hours.34 Netherlands, opiates had been used in 7%e In 1987, the issue of development of 15% of all deliveries between 2000 and 2007, substance use disorders (SUDs) and behav- which is in 15 000e30 000 mothers a year.1 In ioural problems in the offspring after peri- the 1970s, intramuscular PethidineÒ was the natal analgesic medication was addressed.5 most common drug for pain relief during The authors reported ORs of 4.7 compared labour. In recent years, a rise in the use of with individuals who did not receive perinatal epidural or spinal analgesia and in PCA analgesic drugs. These results were derived (patient-controlled analgesia) with very short from caseecontrol studies in patients with For numbered affiliations see 6e8 end of article. acting opiates intravenously is observed. SUD. However, PethidineÒ is the most commonly The SUD was attributed to the ‘imprinting used opioid worldwide because it is cheap hypothesis’ and was first published in the Correspondence to et al 7 Dr Robert Rodrigues Pereira; and easy to administer. Concerns have been BMJ in 1990 by Jacobson . The brain, pereirar@ raised about its effectiveness and potential when exposed to a noxe during a window in maasstadziekenhuis.nl maternal, fetal and neonatal side effects.2 time before or during birth, could be Rodrigues Pereira R, Kanhai H, Rosendaal F, et al. BMJ Open 2012;2:e000719. doi:10.1136/bmjopen-2011-000719 1 No evidence that Pethidine increases risk SUD BMJ Open: first published as 10.1136/bmjopen-2011-000719 on 30 May 2012. Downloaded from affected permanently by changing neurotransmitter congenital anomalies, born at term after an uncompli- receptors, synaptogenesis, myelination, proliferation, cated delivery and who had not been admitted in the apoptosis, migration of neuronal cells or by stunting of paediatric ward. Information was available on maternal e dendrite growth.9 12 An epidemiological and clinical characteristics and obstetric history including medica- study showed that cannabis exposure before birth is tion as well as the postpartum condition of the newborn. associated with impulsive and psychiatric disorders in later life.13 Conflicting results have been publishes about Data collection the association of autism spectrum disorders, develop- After finding the recent addresses, we were able to send mental delay and learning disorders in offspring after validated questionnaires about lifetime and recent (last e peripartum exposure to analgesics.14 17 month) use of cigarettes, alcohol and drugs. The first is No long-term follow-up study in children born after the National Drugs Questionnaire as a part of the opioid use of the mother during pregnancy or after Permanent National Life Style Inquiry that is used from opioid labour analgesia has been published. A recent 1997 (with computer-assisted personal interviewing or in Cochrane Review has been published looking at the case of drug questions with computer-assisted self-inter- effectiveness and side effects of intrapartum parenteral viewing method) that meet with the European Statistics opioids.18 Short-term follow-up studies did not show Code of Practice. The second questionnaire is a vali- sequelae in children in their development up to dated questionnaire for young adults about life events, e 5 years.19 22 schooling and behaviour.25 We investigated the association between PethidineÒ use and the risk on smoking, drinking alcohol or drug Analysis abuse in offspring 20 years after birth. The primary analysis was a comparison of the prevalence of substance abuse at adult age between the PethidineÒ- METHODS exposed and not-exposed groups. Subsequently, the Sample and study design results were compared with the national drug monitor Power calculation study that was done in the same period. A multivariate Considering the prevalence of drug abuse, smoking and logistic regression model was used to calculate ORs and drinking alcohol, we needed 160 participants in each 95% CIs for the outcome measures with age, sex, reli- group. In total, 85 individuals in each group were suffi- gion and parental education as potential confounders. cient to detect an OR of 4.7 or more between the groups The analyses were performed with SPSS V.11.5 for with 80% power and a type I error of 0.05,7 assuming Windows (SPSS Inc). a prevalence of major drug abuse in the control group of http://bmjopen.bmj.com/ 5%.1 Because of the much more frequent use of tobacco Non-response and alcohol, this sample size was sufficient to detect ORs Non-responders received a short questionnaire about yes around two. or no lifetime or recent use of alcohol, smoking and Data about lifetime prevalence and recent substance drugs. The individuals who responded to the short use are available for Europe23 and for the Netherlands24 questionnaire and those who only partially filled in the (table 1). questionnaire were analysed separately. Identification of the cohort variables RESULTS on September 25, 2021 by guest. Protected copyright. After ethical approval by the Medical Ethical Committee From a total of 715 deliveries, 91% of the addresses were of the Leiden University Medical Center, the birth files found. Of these 651 individuals, 347 (53%) returned the from the Academic Hospital Leiden from 1986 to 1987 questionnaires. One hundred and thirty-three partici- were used to compose two groups of participants: one pants with and 164 without PethidineÒ analgesia could cohort with and the other without labour analgesia by be fully evaluated (n¼297, 46%). After a second call, 26 PethidineÒ. Included were only healthy babies without individuals with and 24 without PethidineÒ analgesia completed the questionnaire and 92 (53 with and 39 without PethidineÒ) completed the short questionnaire. Table 1 Lifetime prevalence and recent tobacco, alcohol All together, 439 children (67% of 651 children) were and drug use in the Netherlands24 analysed. Both the index and the control group showed Lifetime Recent use, the same distribution of age and sex. There were no prevalence (%) last month (%) differences in the distribution of parental education or religion (table 2). These were also similar to national Smoking 72 37 data. The peripartum data of both groups showed no Alcohol 90 79 Cannabis 37 17 differences in birth weight, sex and Apgar scores. All XTC 6.2 2.2 newborns were healthy and none was admitted in the Amfetamine 5 1.9 paediatric ward. Cocaı¨ne 4.3 1.7 No differences were found in lifetime or recent use of drugs, alcohol or tobacco use between both groups. The 2 Rodrigues Pereira R, Kanhai H, Rosendaal F, et al. BMJ Open 2012;2:e000719. doi:10.1136/bmjopen-2011-000719 No evidence that Pethidine increases risk SUD BMJ Open: first published as 10.1136/bmjopen-2011-000719 on 30 May 2012. Downloaded from hard drugs, tranquilisers, hallucinogenics, anabolics or Table 2 Distribution of parental education or religion stratified by PethidineÒ and no PethidineÒ groups soft drugs (including tobacco and alcohol use).
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