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About POPP

The Prescription Opioids in the Perinatal Period (POPP) Program harnesses the power of ‘big data’ to generate real-world evidence regarding the use and safety of prescription opioids before, during and after pregnancy (also known as the perinatal period).

Opioids can be used for two main therapeutic purposes. Opioids such as codeine, oxycodone, tramadol, and morphine are used to manage pain. Conversely, opioids including methadone and buprenorphine, are used as part of a treatment known as opioid agonist therapy (OAT) for people with opioid dependence. The treatment for both these conditions requires careful monitoring and adherence to medical guidelines.Ìý

Opioid use has increased worldwide over the last 20 years, including among pregnant women*, raising concerns about the health impacts during the perinatal period. Opioids can cause a condition known as neonatal withdrawn syndrome in newborn babies. Although the risk of this syndrome following opioid use during pregnancy is low (less than 1 case per 1000 babies delivered, in women with no risk factors), it increases with long-term use.1ÌýHowever, a few studies have found a connection between prescription opioid useÌýfor pain managementÌýduring pregnancy and other harms such as specific birth defects or preterm birth. Still, it remains unclear whether opioid use directly causes these problems. For women with opioid dependence, current recommendations are to commence or continue OAT during pregnancy as it leads to better outcomes for the mother and infant compared to no treatment. However, questions remain about which OAT medicine is best to use during pregnancy.ÌýÌý

Our research addresses these lingering knowledge gaps by examining the extent to which prescription opioids are used among women of reproductive age and pregnant women and determining any short-term and long-term consequences of opioid use during pregnancy on both the child and the mother.ÌýGiven that half of pregnancies are unplanned, women may receive treatment for pain or for opioid dependence before becoming aware of their pregnancy. Therefore, these questions about safety and risk are relevant for all women of reproductive age and should be considered when prescribing to women who may become pregnant.Ìý

We are also interested in opioid use in the year after pregnancy. Women often take pain-relieving medicines during this period, which might lead to ongoing or persistent opioid use. Long-term opioid use can lead to dependence or an overdose. Understanding the patterns of medicine use during this time can help healthcare professionals identify risks of persistent use, provide appropriate support, and ensure the well-being of both the mother and her baby.

To answer these questions, our research group applies advanced epidemiological techniques to ‘big health data’, that is, large, routinely collected health-related datasets.ÌýMost of our planned work will be carried out in the ‘Early Life Course Data Platform', which contains data for all children born in New South Wales between 2001 and 2019, and their family health records.ÌýThe Early Life Course Data PlatformÌýincludes rich data from 20 data collections, including information on the antenatal period and birth, medicine dispensings and clinical outcomes for both mothers and babies.

*Please note that although we use terms which describe gender throughout the webpage content, including woman, mother, and maternal, our focus is on the biological sex. The information provided here should be considered inclusive of individuals who are pregnant or who have given birth but may not identify as women.

1. Desai RJ, Huybrechts KF, Hernandez-Diaz S, Mogun H, Patorno E, Kaltenbach K, et al. Exposure to prescription opioid analgesics in utero and risk of neonatal abstinence syndrome: population based cohort study. BMJ. 2015;350:h2102.

Significance

Our findings will help clinicians and patients make informed decisions about whether to use prescription opioids to manage pain and determine the safest therapies for opioid dependence.Ìý

Investigators

Ms Bianca Varney

School of Population Health, UNSW Sydney
Researcher

Dr Danielle Tran

National Drug & Alcohol Research Centre, UNSW Sydney
Research Fellow

Dr Jonathan Brett

School of Population Health, UNSW Sydney
Senior Research Fellow

Dr Alys Havard

National Drug & Alcohol Research Centre and School of Population Health, UNSW Sydney
Senior Research Fellow

A/Prof Helga Zoega

School of Population Health, UNSW Sydney; Centre of Public Health Sciences, University of Iceland
Associate Professor

Dr Malcolm Gillies

School of Population Health, UNSW Sydney
Senior Biostatistician

Ms Claudia Bruno

School of Population Health, UNSW Sydney
Researcher

Prof Sallie Pearson

School of Population Health, UNSW Sydney
Professor

Collaborators

National

  • Ms Ximena Camacho, Researcher, School of Population Health, University of New South Wales
  • , Obstetrician and Gynaecologist, Department of Maternal Fetal Medicine, Royal Hospital for Women
  • , Research Fellow, School of Population and Global Health, The University of Western Australia

Ìý

International

  • , Professor of Anaesthesiology, Perioperative and Pain Medicine, Department of Anaesthesiology, Perioperative and Pain Medicine, Stanford University, United States
  • , Senior Researcher, Norwegian Institute of Public Health, Norway
  • , Researcher, Norwegian Institute of Public Health, Norway
  • , Assistant Professor, Centre for Pharmacoepidemiology, Karolinska Institutet, Sweden

Project List

  • Project lead: Bianca Varney; Project status: Published

    We examined the number of women of reproductive age who use opioids and how long they have been using them. We found that one in eight women of reproductive age use opioid each year, although the number of women using opioids decreased between 2013 and 2020. Most opioid use appeared short term, with over two-thirds of this opioid use in only one month of each year.

    The link to the article can be foundÌý.

  • Project lead: Bianca Varney; Project status: Published

    We investigated opioid use in women who had just given birth. We found that around 20% of women that had undergone a caesarean section were dispensed opioids following discharge after leaving the hospital following childbirth. In contrast, only around 1.5% of women were dispensed an opioid after a vaginal birth. Encouragingly, out of the 95,000 women giving birth each year, only 350 women used opioids long term in the year after childbirth. We found that characteristics including a history of opioid use disorder, other substance use disorders, a mental health diagnosis or prior use of prescription opioids, non-opioid painkillers or benzodiazepines were strongly linked with this ongoing, long-term opioid use.Ìý

    The link to the article can be foundÌý

    A plain-language summary of the study can be foundÌý

  • Project lead: Bianca Varney; Project status: Ongoing

    We will systematically search databases to identify previous studies examining opioid use during pregnancy and the risk of congenital malformations. We will combine the results to address whether the use of opioids to manage pain in the first trimester of pregnancy increases the risk of congenital malformations.Ìý

    The link to the protocol registration can be foundÌý.

  • Project leads: Dr Jonathan Brett and A/Prof Helga Zoega, Project status: Ongoing

    We will compare how the use of opioids used to manage pain during pregnancy compare across different geographical regions including Australia, New Zealand, the United States, Canada, Taiwan, Hong Kong, South Korea, Iceland, Norway, Sweden, Denmark, Finland, and the United Kingdom.

  • Project leads: Dr Jonathan Brett and A/Prof Helga Zoega, Project status: Ongoing

    We will examine the link between opioid use during different periods in pregnancy and preterm birth, and diseases resulting from placental insufficiency, including preeclampsia, placental abruption, and small for gestational age infants.

  • Project lead: Bianca Varney; Project status: Ongoing

    We will perform an exploratory study to examine the impact of opioids used to manage pain on a range of potential adverse outcomes for women and their infants such as stillbirth, congenital malformations, emergency caesarean section, and postpartum haemorrhage.

  • Project lead: Dr Danielle Tran; Project status: Ongoing

    We will quantify the number of women who used methadone and buprenorphine during pregnancy for management of opioid dependence. Additionally, we will examine socio-demographic and health status of mothers based on their use of each medicine.

  • Project leads: Dr Jonathan Brett and A/Prof Helga Zoega; Project status: Ongoing

    We will examine the link between opioid use during pregnancyÌýandÌýpoor child neurodevelopment,Ìýincluding autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and poor academic performance.

Funding

This work is supported by the Australian National Health and Medical Research Council (NHMRC) Ideas Grant (GNT2010778), an NHMRC Project Grant (GNT1138442) and by NHMRC Centre of Research Excellence in Medicines Intelligence Grant (GNT1196900). The National Drug and Alcohol Research Centre, UNSW Sydney, is supported by funding from the Australian Government Department of Health under the Drug and Alcohol Program. Bianca Varney is supported by a UNSW Scientia Scholarship. Danielle Tran and Bianca Varney are supported by a UNSW Neuroscience, Mental Health & Addiction Theme 2023 Collaborative Grant. Danielle Tran is supported by the NHMRC ASCEND Programme (GNT1150078). Jonathan Brett is supported by an NHMRC Investigator Grant (GNT1196560). Helga Zoega is supported by UNSW Scientia Program Awards. Malcolm Gillies is supported by an NHMRC Project Grant (GNT1138442). Claudia Bruno is supported by an Australian Government Research Training Program (RTP) Scholarship. The Early Life Course Data Platform was funded through a UNSW Research Infrastructure Scheme grant.