Opioid Use and Misuse in Pregnancy: Clinical Issues, Alternatives, and Best Practices

By Sara Gottfried, MD | November 20, 2019
Opioids and Pregnancy |Women's Health|Sara Gottfried MD

Refill request. Refill request for opioids. When I practiced as a mainstream obstetrician/gynecologist, my heart would sink every time the opioid refill arrived in my inbox. I’d look up the electronic health record of the patient requesting the opioid, and if I saw “pregnancy” in her chart, my heart would sink further. Why? Because I didn’t have many options available for my pregnant patients with pain, in part due to the massive research gap that exists for pregnancy and lactation. I didn’t know the full downstream cost of prescribing an opioid, such as the effect on the pregnancy, developing fetal brain, possible increased risk of neural tube defects, and neonatal outcomes.1 I had a sense that multiple variables—the mother’s genome, the genome of the fetus, environmental and biological factors—all overlapped to create a very complex network of how opioids and pregnancy interacted.

The number of requests were substantial: one in five Medicaid-enrolled women filled a prescription for an opioid during pregnancy.2 Yet at the time, I didn’t have a way of aggregating various genomic and environmental inputs to predict risk for each pregnant patient. I hadn’t received sufficient training in how to prescribe opioids judiciously, or adequate education in addiction medicine, which made my ability to distinguish between the legitimate prescription of controlled substances versus the prescription potentially used for illegitimate purposes fraught with difficulty and dread. So I muddled through, applying common sense and requesting each patient come in for an evaluation for her pain before agreeing to a refill. 

How did we get here?

In the intervening years, healthcare care professionals have discovered that many more women struggle with opioid use and opioid use disorder than we realized, and we need to be more circumspect about our evaluation of pain, our process for choosing opioids versus non-opioids, our prescription habits, and our approach to the pregnant woman with pain. Opioids are a class of drugs that include pain relievers such as oxycodone, hydrocodone, codeine, morphine, and fentanyl, as well as illegal substances such as heroin. Each of these drugs are biochemically related and bind with opioid receptors in the brain and body in order to relieve pain. 

Importantly, we learned that OB/GYNs are on the front lines of the opioid crisis as primary providers of women’s healthcare. While were shocked to discover that from 2000 to 2007 for Medicaid-enrolled women, the number of women filling an opioid prescription increased from 18 to 23% in 46 states, it was more stunning to realize that there is significant regional variation of up to 42%.3 

The root cause

Why were opioids so commonly prescribed? Usually opioids are written for acute pain, and sometimes chronic pain in pregnancy.4 For some patients, it’s pain before pregnancy, such as migraines, endometriosis, or sickle cell disease. For others, it’s new painful conditions that develop during pregnancy, such as low back pain. For most, it’s the pain of birth. Maternity care is the most common reason for hospitalization in the United States. One third of those births result in a cesarean section, for whom two-thirds receive an opioid prescription.5 Two thirds of births are vaginal, for whom one quarter receive an opioid prescription.6 That’s a lot of opioid prescriptions when you consider that there are nearly 4 million births each year in the US.7 

Woven together, these various threads of the opioid crisis add up to a public health disaster, blamed in part on pharmaceutical companies who intentionally minimized the dangers and may have overstated the benefits of opioids. In our current environment of large settlements against drug companies to hold them accountable for their role in the opioid crisis, such as the recent $572 million judgment against Johnson and Johnson and payable to the state of Oklahoma, we will see more trials and legal settlements—in fact, The New York Times predicts there are 2,000 more trials to come.8

Understanding the crisis

However, there are multiple reinforcing root causes of our opioid epidemic. Back in the 1980s and 1990s, American physicians were criticized for being overly conservative in their prescription of narcotics—with one particularly influential letter by Jick et al. in the New England Journal of Medicine claiming that rates of opioid use disorder were extremely with a short course of opioids, on the order of 4 out of 12,000 (0.03%).9 These data, combined with other reports, were used by vocal advocates to rationalize greatly expanded opioid use, despite the lack of evidence showing that opioids are effective long-term for pain.10

Fortunately, we now have a much better sense of the opioid crisis generally, and how it impacts pregnant women specifically, which are the topics of this article. We will review what is known about maternal and fetal effects of opioids, the role of the gene/environment interface, and what might be reasonable alternatives to the prescription of an opioid for those of us who practice personalized lifestyle medicine. I will provide the latest guidelines for opioid prescribing based on the Centers for Disease Control.11 OB/GYNs as well as other prescribers of opioids have a unique opportunity to stem the tide of the opioid use disorder and the opioid crisis because of our close and intensive relationships with women during pregnancy, and due to the fact that most pregnant women are very motivated to reduce opioid use and use disorder.

The opioid crisis and women

For reasons that we don’t completely understand, women are more likely to develop opioid use disorder compared to men, at lower doses, given over shorter durations, and experience more cravings. Between 1999 and 2015, opioid overdose resulted in 471% increase in deaths for women, more than double the rate of 218% in men.12

Awareness of our iatrogenic role in the opioid crisis has improved the trend, but we still have high rates of new persistent opioid use (defined as pharmacy claims for 1 or more opioid prescription 4 to 90 days after discharge and 1 or more prescription 91 to 365 days after discharge among women who filled peripartum opioid prescriptions). In a national cohort of 308,226 deliveries in the United States, women who received an opioid prescription had rates of new persistent opioid use of 1.7% after a vaginal birth and 2.2% after a cesarean birth.13 Millions of American have opioid use disorder, and many of them are pregnant women who may have benefited from a more-informed prescribing strategy, as we will cover in the guideline section below.

Some stats

Consider the larger epidemic of the opioid crisis in the general population and pregnant women:

  • U.S. overdose deaths has been climbing for the past three decades, and increased more than five-fold since 1999 from opioids (the cause of 2/3 overdose deaths)14
  • 259 million prescriptions were written in 2012 for opioid medication—this is more than one prescription for every adult living in the United States15
  • Approximately 130 people die daily from an opioid overdose in the United States16
  • Prevalence of opioid use disorder at delivery more than quadrupled from 1999 to 2014: 1.5 cases per 1,000 delivery hospitalizations to 6.5 during 1999-201417
  • Tens of thousands of infants are affected by prenatal opioid exposure, sometimes leading to neonatal opioid withdrawal syndrome (NOWS, which replaces the older term “neonatal abstinence syndrome”). NOWS increased 5-fold nationwide as the use of opioids amplified in pregnant women18
  • The national incidence of NAS in infants increased from 3.4 to 5.8 per 1000 hospital births from 2009-201219

Opioid risks to mother and fetus 

In deciding what to do for the pregnant woman with pain, we begin with the known risks of opioids to the mother and fetus.

  • Birth defects: Absolute risk is low — some evidence for increased risk of neural tube defects in studies with small sample sizes and possible confounding20
  • Fetal growth restriction: Increased risk of association based on strong evidence21
  • Preterm birth: Increased risk of association based on strong evidence22
  • Opioid use disorder, defined by the Diagnostic and Statistical Manual of Mental Disorders-5 as a pattern of opioid use that causes significant impairment, and involves repeated occurrence within a 12-month period of 2 or more of 11 problems, such as: craving, tolerance, withdrawal, giving up important life events in order to use opioids, or an inability to cut down or control opioid use.23 Opioid Use Disorder is observed in people from all socioeconomic and educational backgrounds.
  • Developing brain. We know from preclinical and human brain studies that opioids harm the developing brain. Opioid receptors are present in neurons, oligodendrocytes, and astroglia. The specific functions that opioids affect are the developing oligodendrocyte and the processes of myelinization (white matter microstructure), connectivity between parts of the brain, and the size of multiple brain regions, including the basal ganglia, cerebellar white matter., and thalamus.24
  • Neonatal opioid withdrawal syndrome (NOWS, described above and formerly neonatal abstinence syndrome or NAS). Causes of NOWS are diverse and include intrauterine exposure to opioids, whether prescription or illicit, as well as to drugs prescribed for maternal opioid use disorder, NOWS is characterized by post-birth withdrawal as evidenced by excessive crying, tremors, sweating, poor feeding, increased muscle tone, sleep and gastrointestinal disturbances.25
  • Other adverse childhood outcomes such as cognitive or behavioral impairment, disability, autism, and need for special education26
  • Other maternal harms, including fractures, myocardial infarction, and sexual dysfunction.27

Pharmeceutical alternatives to opioids

You may wonder why we can’t just prescribe nonsteroidal anti-inflammatory drugs (NSAID) in pregnancy, or acetylsalicylic acid (ASA, or aspirin). The main reasons are the following: 

  • NSAIDs are associated with reduced fertility, and higher rates of early pregnancy loss and birth defects
  • In the second trimester, NSAIDs and ASA are considered reasonably safe but may be associated with fetal cryptorchism, which is failure of one or both testes to descend into the scrotum. 
  • In the third trimester, both NSAIDS and ASA are avoided because they may cause bleeding as well as significant fetal risks, such as renal injury, oligohydramnios, constriction of the ductus arteriosus (with potential for persistent pulmonary hypertension in the newborn), necrotizing enterocolitis, and intracranial hemorrhage.28 
  • NSAIDs are considered relatively safe post-partum and during lactation.29
  • Furthermore, these anti-inflammatory drugs may decrease the amplitude of inflammation but they actually block the resolution of inflammation.

Natural alternatives to opioids

Beyond the limited use of NSAIDs, the following alternatives have demonstrated efficacy in pain management.

  • Physical therapy, for example, for chronic low back pain in pregnancy30
  • Exercise, such as for the prevention of low back and pelvic girdle pain in pregnancy, is shown to be effective in a Cochrane review as well as other meta-analyses31
  • Hormone therapy, for instance the use of progesterone in the preconception phase or first trimester in patients with endometriosis32
  • Acupuncture, particularly auricular acupuncture, is a powerful adjunct for pain management in pregnant women33
  • Reduction of inflammation with omega-3s, which modulates endogenous specialized proresolving mediators, though data in pregnancy are extremely limited34
  • Mind-body techniques for relaxation have been shown to reduce pain intensity35
  • Cannabis and cannabinoids. The endocannabinoid system is a complex network intimately involved in pain, inflammation, and the regulation of homeostasis. While recreational use of cannabis is not recommended,36 potential risks and safety issues for cannabis as an adjunctive treatment for pain pregnancy is an emerging topic. Further research and outcomes data are needed as there is currently a paucity of dose-response data in pregnancy.37
  • Other bioactives.  Evidence is provided for additional nutritional bioactives that can modulate inflammation, including curcumin (limited data exist in animals but there are insufficient safety data in pregnancy),38 and ginger.39 

Individual use must be discussed with the patient’s obstetrician or other health care professional.

Guidelines for care of pregnant women with pain

Guidelines have been developed with the goal of preventing opioid use disorder, particularly with prescription opioids. Most obstetricians advise that the best strategy is to minimize or abolish opioid prescription in the setting of acute pain. Therefore, patients do not need opioids following discharge after a vaginal birth. However,  if there is severe perineal trauma, limit duration to 3 days or less of opioid. The same is true following cesarean section, with the rate exception of a wound complication—in which case, opioids can be limited to 3 days or less. NSAIDs are the treatment of choice, perhaps alongside nutraceuticals such as omega-3s with the goal of inflammation resolution.

Here are additional guidelines regarding the use of opioids for pain.

  • The Canadian Guideline for the Use of Opioids in the Treatment of Chronic Noncancer Pain recommends the following:
    • (1) opioids should be tapered and discontinued or prescribed at the lowest effective dose;
    • (2) in the postpartum period, codeine use should be avoided or limited to 4 days;
    • (3) women should be managed by perinatologists; and
    • (4) women with opioid use disorders should be referred for appropriate treatment.40
  • When a pregnant women has chronic pain, opioid prescription should be considered a last resort and given after careful risk-benefit-alternative analysis.41 Consider that systematic reviews do not demonstrate a benefit to opioid therapy for chronic pain but definitely increase the risk of Opioid Use Disorder, overdose, and other harms documented previously.42 Therefore, the best approach is to consider alternative treatments for chronic pain such as hormonal therapy, physical therapy, exercise, alternative medicine, behavioral therapy, nonsteroidal anti-inflammatory drugs (NSAIDs—see caveats under the “Alternatives” section) or surgery should be considered depending on the etiology. If none of these alternatives are effective, here are the guidelines recommended by the Centers for Disease Control and Prevention, and the National Academies of Sciences, Engineering, and Medicine:43

Guidelines from Centers for Disease Control and Prevention

  1. Opioid therapy should be considered only if benefits, in terms of pain relief and function, outweigh risks.
  2. Before initiating opioid treatment, clinicians should establish treatment goals and treatment should only be continued if there is clinically meaningful improvement in pain and function that outweighs risks.
  3. Before initiating, and periodically while administering opioid treatment, clinicians should review risks and benefits.
  4. When initiating opioid therapy for chronic pain, clinicians should prescribe intermediate-release opioids and NOT extended-release (long-acting) agents which have greater risk of respiratory arrest. 
  5. Clinicians should prescribe the lowest effective dose and carefully reassess evidence of benefit when doses ≥ 50 morphine milligram equivalents (MME)/day are required; clinicians should avoid doses ≥ 90 MME/day.
  6. Since long-term opioid use often begins with treatment of acute pain, adhere to the opioid prescribing recommendations made above for acute pain management (lowest dose, intermediate-release formulations, ≤ 3-day duration). 
  7. Reassess benefits and harms within 1 to 4 weeks of starting treatment and every 3 months thereafter while treatment is continued.
  8. Before starting, and periodically during continuation of opioid therapy, reassess risk factors for possible harm and consider offering naloxone when factors are present that increase risk of overdose (e.g., therapy ≥ 50 MME/day or concomitant benzodiazepine therapy).
  9. Clinicians should review a patient’s history of controlled substance prescriptions using their state’s prescription drug monitoring program (PDMP) data to determine whether she is receiving opioid dosages that put her at risk for an overdose. Review PDMP data when starting opioids for chronic pain and every 3 months while on therapy.
  10. When prescribing opioids for chronic pain obtain urine drug testing before initiating treatment and consider annual testing to assess for prescribed medications as well as other controlled prescriptions and illicit drugs.
  11. Avoid prescribing concomitant benzodiazepines for patients on opioids because of their synergistic effects promoting respiratory arrest.
  12. Arrange for MAT with behavioral therapy for patients with OUD.
  13. Physicians do not have to reverse the opioid epidemic on their own—and most likely, cannot. Fortunately, new regulations at the Food and Drug Administration now allow specially-trained nurse midwives, nurse practitioners, and physician assistants to prescribe and oversee buprenorphine treatment for pregnant women with opioid use disorder.44 Several authors recommend the following: “Opioid agonist pharmacotherapy should replace the continued use of opioids or detoxification. Current guidelines recommend methadone and buprenorphine equally. However, recent studies indicate that buprenorphine has advantages over methadone. Accordingly, we suggest buprenorphine as first-line therapy.”45 Buprenorphine demonstrates better neonatal outcomes compared to methadone therapy, including lower rates of preterm labor and neonatal respiratory distress.46

Conclusion

As I finish writing this article, I was sent the latest journal of my specialty, Obstetrics and Gynecology, and on the cover is an advertisement for bupivacaine lisosome injectible suspension with the headline: “Enhance your opioid-minimizing efforts in c-section with long-lasting, non-opioid Exparel!”  While the pharmaceutical industry is quick to hop on the “non-opioid” bandwagon, I urge caution and remind practitioners that we can play a key role in stemming the epidemic.

And for our beloved patient, please be aware that pregnancy is a risky time with these risky medications. Be prudent, but also don’t suffer unnecessarily. Certainly, a multimodality approach that includes local anesthesia, reduction of inflammation and inflammation resolution, and other alternative approaches are warranted, but we also need more research on opioid exposure on the mother and developing fetus, and to understand better why women are more vulnerable than men when it comes to the downstream effects of opioids use and misuse.

Now it’s your turn. What has your experience been with opioids? If you are a practitioner, what is your approach to pain in women, or pain in pregnancy? If you are a patient, did you have difficulty obtaining pain relief in pregnancy and/or childbirth? Were there nonopioid options that you found particularly helpful? Many other women will benefit from your comments—we hope to hear from you!

Citations

  1. Broussard CS, Rasmussen SA, Reefhuis J, Friedman J, Jann MW, Riehle-Colarusso T, et al. Maternal treatment with opioid analgesics and risk for birth defects. Am J Obstet Gynecol. 2011;204(4):314, e311–311; Yazdy MM, Mitchell AA, Tinker SC, Parker SE, Werler MM. Periconceptional Use of Opioids and the Risk of Neural Tube Defects. Obstet Gynecol. 2013;122(4):838–844.
  2. Desai RJ, Hernandez-Diaz S, Bateman BT, Huybrechts KF. Increase in prescription opioid use during pregnancy among Medicaid-enrolled women. Obstet Gynecol. 2014;123(5):997–1002. doi:10.1097/AOG.0000000000000208
  3. Desai RJ, Hernandez-Diaz S, Bateman BT, Huybrechts KF. Increase in prescription opioid use during pregnancy among Medicaid-enrolled women. Obstet Gynecol. 2014;123(5):997–1002. doi:10.1097/AOG.0000000000000208
  4. Ray-Griffith SL, Wendel MP, Stowe ZN, Magann EF. Chronic pain during pregnancy: a review of the literature. Int J Womens Health. 2018;10:153–164. Published 2018 Apr 9. doi:10.2147/IJWH.S151845
  5. Bateman  BT, Franklin  JM, Bykov  K,  et al.  Persistent opioid use following cesarean delivery: patterns and predictors among opioid-naïve women. Am J Obstet Gynecol. 2016;215(3):353.e1-353.e18; Martin  JA, Hamilton  BE, Osterman  MJK, Driscoll  AK, Drake  P.  Births: final data for 2017.  Natl Vital Stat Rep. 2018;67(8):1-50.
  6. Martin  JA, Hamilton  BE, Osterman  MJK, Driscoll  AK, Drake  P.  Births: final data for 2017. Natl Vital Stat Rep. 2018;67(8):1-50; Prabhu  M, Garry  EM, Hernandez-Diaz  S, MacDonald  SC, Huybrechts  KF, Bateman  BT.  Frequency of opioid dispensing after vaginal delivery.  Obstet Gynecol. 2018;132(2):459-465.
  7. Martin  JA, Hamilton  BE, Osterman  MJK, Driscoll  AK, Drake  P.  Births: final data for 2017. Natl Vital Stat Rep. 2018;67(8):1-50.
  8. https://www.nytimes.com/2019/08/26/health/oklahoma-opioids-johnson-and-johnson.html accessed August 27, 2019.
  9. Porter J, Jick H. Addiction rare in patients treated with narcotics. N Engl J Med. 1980 Jan 10;302(2):123.
  10. Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: report of 38 cases. Pain. 1986 May;25(2):171-86; Van Zee A. The promotion and marketing of oxycontin: commercial triumph, public health tragedy. Am J Public Health. 2009 Feb;99(2):221-7. 
  11. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain–United States, 2016. JAMA. 2016;315(15):1624–1645. doi:10.1001/jama.2016.1464
  12. https://www.womenshealth.gov/files/documents/final-report-opioid-508.pdf
  13. Peahl AF, Dalton VK, Montgomery JR, Lai Y, Hu HM, Waljee JF. Rates of New Persistent Opioid Use After Vaginal or Cesarean Birth Among US Women. JAMA Netw Open.Published online July 26, 20192(7):e197863. doi:10.1001/jamanetworkopen.2019.7863
  14. https://www.cdc.gov/drugoverdose/data/index.html, accessed August 26, 2019.
  15. Krans EE et al. Opioid use disorder in pregnancy: health policy and practice in the midst of an epidemic. Obstet Gynecol. 2016;128(1):4-10.
  16.  https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis. Accessed August 11, 2019.
  17. Kuehn B. Opioid use disorder during pregnancy. JAMA. 2018;320(12):1232; Haight SC, Ko JY, Tong VT, Bohm MK, Callaghan WM. Opioid use disorder documented at delivery hospitals – United States, 1999-2014. MMWR Morb Mortal Wkly Rep.2018;67:845-849.
  18. 18.  Schiff DM et al. Treatment of opioid use disorder during pregnancy and cases of neonatal abstinence syndrome. JAMA. 2017;171(7):707; Piccotti L, et al. Neonatal Opioid Withdrawal Syndrome: A Developmental Care Approach. Neonatal Netw 38, no. 3 (2019):160-169. 
  19. Gressler LE et al. Association of criminal statutes for opioid use disorder with prevalence and treatment among pregnant women with commercial insurance in the US.  JAMA Netw Open. 2019;2(3):e190338.
  20. Larson JJ, Graham DL, Singer LT, Beckwith AM, Terplan M, Davis JM, Martinez J, Bada HS. Cognitive and Behavioral Impact on Children Exposed to Opioids During Pregnancy.
  21. Opioid use. https://www.drugabuse.gov/publications/treating-opioid-use-disorder-during-pregnancy/treating-opioid-use-disorder-during-pregnancy. Accessed August 11, 2019.
  22. Opioid use. https://www.drugabuse.gov/publications/treating-opioid-use-disorder-during-pregnancy/treating-opioid-use-disorder-during-pregnancy. Accessed August 11, 2019.
  23. American Psychiatric Association, DSM-5 Task Force. Diagnostic and statistical manual of mental disorders : DSM-5. Fifth. Arlington, VA: American Psychiatric Association; 2013. [Google Scholar] [Ref list]
  24. Caritis SN, et al. Opioids affect the fetal brain: reframing the detoxification debate. Am J Obstet Gynecol. 2019 Jul 16. pii: S0002-9378(19)30906-8. doi: 10.1016/j.ajog.2019.07.022. [Epub ahead of print]
  25. McQueen K. et al. Neonatal Abstinence Syndrome. New Engl J Med 375 (2016):2468-2479; Piccotti L, et al. Neonatal Opioid Withdrawal Syndrome: A Developmental Care Approach. Neonatal Netw 38, no. 3 (2019):160-169. 
  26. Reddy UM, Davis JM, Ren Z, Greene MF; Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes Workshop Invited Speakers. Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes: Executive Summary of a Joint Workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, American College of Obstetricians and Gynecologists, American Academy of Pediatrics, Society for Maternal-Fetal Medicine, Centers for Disease Control and Prevention, and the March of Dimes Foundation. Obstet Gynecol. 2017;130(1):10–28. doi:10.1097/AOG.0000000000002054
  27. Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, Dana T, Bougatsos C, Deyo RA. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015 Feb 17;162(4):276-86.  
  28. Kallen B., Ongoing Pharmacological Management of Chronic Pain in Pregnancy. Drugs.2016 Jun;76(9):915-24. doi: 10.1007/s40265-016-0582-3; Bloor M, Peach M. Nonsteroidal anti-inflammatory drugs during pregnancy and the initiation of lactation. Anesth Analg. 2013 May;116(5):1063-75. doi: 10.1213/ANE.0b013e31828a4b54. Epub 2013 Apr 4.
  29. Bloor M, Peach M. Nonsteroidal anti-inflammatory drugs during pregnancy and the initiation of lactation. Anesth Analg.2013 May;116(5):1063-75. doi: 10.1213/ANE.0b013e31828a4b54. Epub 2013 Apr 4.
  30. Stuge B. Evidence of stabilizing exercises for low back- and pelvic girdle pain – a critical review. Braz J Phys Ther. 2019;23(2):181–186. doi:10.1016/j.bjpt.2018.11.006
  31. Eur J Pain. 2018 Jan;22(1):19-27. doi: 10.1002/ejp.1096. Epub 2017 Sep 4.
  32. Cochrane Database Syst Rev. 2014 Mar 10;(3):CD009590. doi: 10.1002/14651858.CD009590.pub2.
  33. Park J, Sohn Y, White AR, Lee H. The safety of acupuncture during pregnancy: a systematic review. Acupunct Med. 2014;32(3):257–266. doi:10.1136/acupmed-2013-010480;
  34. Elliott E, Hanson CK, Anderson-Berry AL, Nordgren TM. The role of specialized pro-resolving mediators in maternal-fetal health. Prostaglandins Leukot Essent Fatty Acids. 2017;126:98–104. doi:10.1016/j.plefa.2017.09.017; Nordgren TM, Anderson Berry A, Van Ormer M, et al. Omega-3 Fatty Acid Supplementation, Pro-Resolving Mediators, and Clinical Outcomes in Maternal-Infant Pairs. Nutrients. 2019;11(1):98. Published 2019 Jan 5. doi:10.3390/nu11010098
  35. Smith CA, Levett KM, Collins CT, Armour M, Dahlen HG, Suganuma M. Relaxation techniques for pain management in labour. Cochrane Database Syst Rev. 2018;3(3):CD009514. Published 2018 Mar 28. doi:10.1002/14651858.CD009514.pub2
  36. Prev Med. 2017 Nov;104:46-49. doi: 10.1016/j.ypmed.2017.05.012. Epub 2017 May 18.
  37. Grant KS, Petroff R, Isoherranen N, Stella N, Burbacher TM. Cannabis use during pregnancy: Pharmacokinetics and effects on child development. Pharmacol Ther. 2018;182:133–151. doi:10.1016/j.pharmthera.2017.08.014; Addict Behav. 2019 Aug 7;99:106082. doi: 10.1016/j.addbeh.2019.106082. [Epub ahead of print]
  38. Phytother Res. 2018 Jun;32(6):985-995. doi: 10.1002/ptr.6054. Epub 2018 Feb 26.
  39. Viljoen E, Visser J, Koen N, Musekiwa A. A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting. Nutr J. 2014;13:20. Published 2014 Mar 19. doi:10.1186/1475-2891-13-20
  40. Kahan M, Wilson L, Mailis-Gagnon A, Srivastava A, National Opioid Use Guideline Group Canadian guidelines for safe and effective use of opioids for chronic noncancer pain: clinical summary for family physicians. Part 2: special populations. Canadian Family Physician. 2011;57(11):1269–1276. [PMC free article] [PubMed] [Google Scholar]
  41. Ray-Griffith SL, Wendel MP, Stowe ZN, Magann EF. Chronic pain during pregnancy: a review of the literature. Int J Womens Health. 2018;10:153–164. Published 2018 Apr 9. doi:10.2147/IJWH.S151845
  42. Chou R, Turner JA, Devine EB, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015 Feb 17;162(4):276-86. 
  43. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Committee on Pain Management and Regulatory Strategies to Address Prescription Opioid Abuse; Phillips JK, Ford MA, Bonnie RJ, editors. Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use. Washington (DC): National Academies Press (US); 2017 Jul 13. Available from: https://www.ncbi.nlm.nih.gov/books/NBK458660/ doi: 10.17226/24781
  44. Roper V, Cox KJ.Opioid Use Disorder in Pregnancy. J Midwifery Womens Health. 2017 May;62(3):329-340. doi: 10.1111/jmwh.12619. Epub 2017 May 31.
  45. Rausgaard NLK1, Ibsen IO1, Jørgensen JS1, Lamont RF1, Ravn P1. Management and monitoring of opioid use in pregnancy. Acta Obstet Gynecol Scand. 2019 Jun 14. doi: 10.1111/aogs.13677. [Epub ahead of print]
  46. Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. The New England journal of medicine. 2010 Dec 9;363(24):2320–31. [PMC free article] [PubMed]; Holbrook AM, Baxter JK, Jones HE, Heil SH, Coyle MG, Martin PR, et al. Infections and obstetric outcomes in opioid-dependent pregnant women maintained on methadone or buprenorphine. Addiction. 2012 Nov;107(Suppl 1):83–90. [PMC free article] [PubMed]; Gaalema DE, Scott TL, Heil SH, Coyle MG, Kaltenbach K, Badger GJ, et al. Differences in the profile of neonatal abstinence syndrome signs in methadone- versus buprenorphine-exposed neonates. Addiction. 2012 Nov;107(Suppl 1):53–62. [PMC free article] [PubMed]; Gaalema DE, Heil SH, Badger GJ, Metayer JS, Johnston AM. Time to initiation of treatment for neonatal abstinence syndrome in neonates exposed in utero to buprenorphine or methadone. Drug and alcohol dependence. 2013 Nov 1;133(1):266–9. [PMC free article] [PubMed] 
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