Abstract
Pregnant women with chronic pain present a unique clinical challenge for both chronic pain and obstetrical providers, and clinical guidelines do not exist. The present study describes the prevalence and management of chronic pain during pregnancy in a perinatal mood disorder clinic. A retrospective chart review of pregnant women who presented to the Women's Mental Health Program at the University of Arkansas for Medical Sciences (UAMS) for an initial evaluation from July 2013 to June 2016 was conducted to obtain demographic and medical information, including pharmacological exposures. Data are described using the mean and standard deviation for continuous data and frequency for categorical data. Pain complaints and medications are presented as counts and percentages. Differences between women with and without chronic pain were assessed by t-tests for continuous variables and chi-square analysis for categorical variables. Of the 156 pregnant women, chronic pain conditions were reported by 44 (28.2%). The most common chronic pain complaints included neck and/or back pain (34.1%) and headaches (31.8%). Of subjects with chronic pain, 95.5% were taking at least one prescription medication (mean = 2.6 ± 2.1, range of 0–10). Acetaminophen (43.2%) and opioids (43.2%) were the most common. The complexity of managing maternal benefits of treatment with the risks of fetal exposures presents a uniquely challenging clinical scenario for healthcare providers.
1. Introduction
In 2011, the Institute of Medicine released a report on pain estimating that 100 million adults in the United States live with chronic pain conditions [1]. Physical and mental functioning, quality of life, and professional and personal relationships are negatively affected by chronic pain. Moreover, societal stigma around chronic pain and risks associated with the long-term use of pain medications, such as opioids, exacerbates these problems. Women, in comparison with men, experience a greater burden of disease and functional disability as well as lower therapeutic effects with long-term opioid use [2–4]. The perinatal period presents a particularly vulnerable state for women with chronic pain disorders, and data supporting the prevalence, course, and management of perinatal chronic pain disorders are scarce [5]. Chronic pain and obstetrical providers encounter a complex clinical situation where maternal benefits of treatment must be effectively balanced with the risks of maternal illness and fetal exposure to both treatment and maternal illness.
Treatment options for chronic pain disorders during the perinatal period include both pharmacological and nonpharmacological options (e.g., physical therapy); however, uncertainties around treatment impact both the patient and the provider's medical decision-making. For example, among a sample of pregnant women with low back pain, only 32% discussed these symptoms with their prenatal care providers, and 75% of providers did not make any recommendations to manage symptoms [6]. Many women also discontinue pharmacological options immediately upon knowledge of conception due to fears of teratogenic potential.
Another concerning factor includes the limited and discordant reproductive safety data on pharmacological treatments for chronic pain [7]. For example, acetaminophen is a first-line analgesic for pregnant women as it does not produce classic teratogenic effects. However, recent studies have associated perinatal acetaminophen exposure with an increased risk for attention-deficit/hyperkinetic, respiratory, autism spectrum, and testicular disorders in children [8–17]. Opioids are another example as 14–22% of women fill an opioid prescription during pregnancy [18, 19] despite potential adverse neonatal outcomes [20–24]. Moreover, available data support the use of amitriptyline and/or nortriptyline as first-line agents for both nociceptive and neuropathic pain during pregnancy [25–27]; however, use in nonpregnant populations is limited by underutilization by prescribers [28] and patient intolerability [29]. Potential adverse obstetrical and/or neonatal complications are associated with maternal use of NSAIDs and venlafaxine [30], and the use of pregabalin and duloxetine is limited by insufficient reproductive safety data [31]. Notably, antiepileptic exposure in pregnancy is more common for the treatment of pain than epilepsy [32–34]. However, reproductive safety data of antiepileptic drugs are derived from women with epilepsy as well as mood and pain disorders with the majority of studies being confounded by polypharmacy [33–37].
Collectively, reproductive safety data indicate a high potential for adverse outcomes associated with the most commonly used pharmacological treatments for chronic pain, which supports almost exclusive recommendations to use nonpharmacological treatments (e.g., physical therapy and massage). Unfortunately, access to these options may be limited, ineffective, and/or unaffordable. With limited available data to support medical decision-making in women with chronic pain disorders during pregnancy, treatment optimization may depend on reducing concurrent medication exposures, maintaining the minimal effective dose, and decreasing additional exposures associated with risk.
Chronic pain disorders frequently co-occur with mental illness. For example, rates of depression in individuals with chronic pain are twice as high of those without chronic pain [38]—a difference more impactful when comparing women and men [39, 40]. Psychiatrists are often involved in the treatment of individuals with chronic pain given the high rates of comorbid mental illness. Thus, reproductive psychiatrists may find themselves as part of the team managing pregnant patients with chronic low back pain, depression, and fibromyalgia, to name a few. The first step in establishing evidence-based guidelines for the management of chronic pain during the perinatal period is to establish the severity and acuity of the problem. In the present study, we sought to determine the prevalence and assess preevaluation management of chronic pain during pregnancy in a university-based perinatal mood disorder clinic.
2. Materials and Methods
A retrospective chart review of all pregnant women who presented to the Women's Mental Health Program (WMHP) at the University of Arkansas for Medical Sciences (UAMS) for an initial evaluation from July 1, 2013, to June 30, 2016, was conducted. The WMHP is an academic mental health program specializing in the treatment of neuropsychiatric illnesses during the perinatal period. The referral base of the WMHP includes psychiatric and obstetrical practices within UAMS and the community throughout Arkansas as well as self-referral. For the current study, subjects were excluded if they were not currently pregnant (i.e., postpartum or preconception), less than 18 years of age, and/or did not consent to having their information used for clinical research investigation at their initial visit. Information was obtained from written and electronic medical records and included demographic information, medical and surgical history (including obstetrical and psychiatric), medication use, and other exposures.
Demographic and obstetrical data are described using the mean and standard deviation for continuous data and frequency for categorical data. Missing data were not included in the total. Differences between groups were assessed by t-tests for continuous variables and by chi-square analysis for categorical variables. Chronic pain complaints and current medications are presented as counts and percentages. A p value of <0.05 was considered statistically significant. Data were analyzed using Sigma Plot 12.5.
This study was approved by the institutional review board at UAMS.
3. Results
A total of 222 pregnant women presented to the WMHP at UAMS for an initial evaluation. Of which, 66 respondents declined participation in research. This resulted in 156 participants for the current analysis. Chronic pain conditions were reported by more than a quarter of respondents (n = 44, 28.2%). Table 1 displays the demographic characteristics of respondents, including by the presence or absence of chronic pain complaints. No differences were found between the groups.
Table 1.
Demographic and medical history of pregnant women in a perinatal mood disorder clinic.
| Demographics | All (n = 156) | Chronic pain complaint | p-value | |
|---|---|---|---|---|
| Yes (n = 44) | No (n = 112) | |||
| Age (years ± SD) | 28.3 ± 5.5 | 29.1 ± 4.8 | 27.9 ± 5.8 | 0.205 |
| Education (years ± SD) | 14.3 ± 2.4 | 14.2 ± 2.1 | 14.3 ± 2.5 | 0.606 |
| Race/ethnicity (%) | ||||
| White | 126 (80.8) | 38 (86.4) | 88 (78.6) | 0.376 |
| Nonwhite | 30 (19.2) | 6 (13.6) | 24 (21.4) | |
| Marital status (%) | ||||
| Married | 78 (50.0) | 20 (45.5) | 58 (51.2) | 0.594 |
| Not married | 78 (50.0) | 24 (54.5) | 54 (48.2) | |
| Medical comorbiditya (%) | ||||
| Yes | 50 (32.1) | 14 (31.8) | 36 (32.1) | 0.880 |
| No | 106 (67.9) | 30 (68.2) | 76 (67.9) | |
| Self-reported history of physical, emotional, or sexual abuse (%) | ||||
| Yes | 94 (61.0) | 29 (65.9) | 65 (59.1) | 0.548 |
| No | 60 (39.0) | 15 (34.1) | 45 (40.9) | |
| Tobacco use (%) | ||||
| None | 69 (44.2) | 21 (47.7) | 48 (42.9) | 0.520 |
| Current use | 42 (26.9) | 9 (20.5) | 33 (29.5) | |
| History of use | 45 (28.8) | 14 (31.8) | 31 (27.7) | |
| Alcohol use (%) | ||||
| None | 62 (39.7) | 19 (43.2) | 43 (38.4) | 0.652 |
| Current use | 2 (1.3) | 1 (2.2) | 1 (0.9) | |
| History of use | 92 (59.0) | 24 (54.5) | 68 (60.7) | |
| Self-reported illicit drug use (%) | ||||
| None | 81 (51.9) | 25 (56.8) | 56 (50.0) | 0.383 |
| Current use | 15 (9.6) | 2 (4.5) | 13 (11.6) | |
| History of use | 60 (38.5) | 17 (38.6) | 43 (38.4) | |
| Obstetrical information | ||||
| Severity (number ± SD) | 2.8 ± 1.8 | 3.1 ± 1.9 | 2.7 ± 1.7 | 0.139 |
| Parity (number ± SD) | 1.1 ± 1.2 | 1.4 ± 1.3 | 1.0 ± 1.1 | 0.083 |
| Gestational age (weeks ± SD) | 21.2 ± 8.8 | 21.2 ± 9.5 | 20.3 ± 8.5 | 0.620 |
| Trimester at initial evaluation (%) | ||||
| 1st | 48 (31.0) | 14 (31.8) | 34 (30.6) | 0.138 |
| 2nd | 66 (42.6) | 14 (31.8) | 52 (46.8) | |
| 3rd | 41 (26.5) | 16 (36.4) | 25 (22.5) | |
| Planned pregnancy (%) | ||||
| Yes | 46 (30.5) | 11 (25.6) | 35 (32.4) | 0.531 |
| No | 105 (69.5) | 32 (74.4) | 73 (67.6) | |
| Desired pregnancy (%) | ||||
| Yes | 76 (50.3) | 22 (51.2) | 54 (50.0) | 0.870 |
| No | 15 (9.9) | 5 (11.6) | 10 (9.3) | |
| Mixed feelings | 60 (39.7) | 16 (37.2) | 44 (40.7) | |
aMedical comorbidities include hypertension, diabetes, asthma, and thyroid conditions.
Among respondents with chronic pain, the most common complaints included neck and/or back pain, headaches, and “other” pain complaints (e.g., pelvic and abdominal pain, neuropathic pain, and fibromyalgia). 95.5% (n = 42) were currently taking at least one prescription medication, and 59.5% (n = 26) were taking two or more medications.
Table 2 lists all medications reported by respondents with chronic pain. The mean number of medications taken was 2.6 ± 2.1 with a range between 0 and 10. More than 20% (n = 10) of subjects with chronic pain were concomitantly taking an opioid and benzodiazepine. Nonpharmacological therapy, including physical therapy and transcutaneous electrical nerve stimulation, was reported by 20.5% (n = 32).
Table 2.
Medication exposures among pregnant women with chronic pain disorders.
| Medication class | N (%) | Individual medications | N (%) |
|---|---|---|---|
| Opioids | 19 (43.2) | Buprenorphine | 1 (2.3) |
| Fentanyl | 1 (2.3) | ||
| Hydrocodone | 13 (29.5) | ||
| Oxycodone | 6 (13.6) | ||
| Tramadol | 4 (9.1) | ||
| Acetaminophen | 19 (43.2) | Acetaminophen | 19 (43.2) |
| Sedative/hypnotic | 16 (36.4) | Alprazolam | 6 (13.6) |
| Clonazepam | 3 (6.8) | ||
| Diazepam | 5 (11.4) | ||
| Lorazepam | 1 (2.3) | ||
| Zolpideim | 6 (13.6) | ||
| Antiepileptic drugs | 13 (29.5) | Gabapentin | 6 (13.6) |
| Lamotrigine | 4 (9.1) | ||
| Pregabalin | 1 (2.3) | ||
| Topiramate | 2 (4.5) | ||
| Muscle relaxant | 7 (15.9) | Carisoprodol | 3 (6.8) |
| Cyclobenzaprine | 3 (6.8) | ||
| Methocarbamol | 1 (2.3) | ||
| Steroid | 7 (15.9) | Steroid | 7 (15.9) |
| Nonsteroidal anti-inflammatory drugs | 3 (6.8) | Etodolac | 1 (2.3) |
| Ibuprofen | 1 (2.3) | ||
| Naproxen | 1 (2.3) | ||
| Selective serotonin reuptake inhibitors | 11 (25.0) | Citalopram | 2 (4.5) |
| Escitalopram | 2 (4.5) | ||
| Fluoxetine | 5 (11.4) | ||
| Sertraline | 2 (4.5) | ||
| Selective norepinephrine reuptake inhibitors | 5 (11.4) | Desvenlafaxine | 1 (2.3) |
| Venlafaxine | 4 (9.1) | ||
| Tricyclic antidepressants | 1 (2.3) | Doxepin | 1 (2.3) |
| Norepinephrine reuptake inhibitor | 1 (2.3) | Bupropion | 1 (2.3) |
4. Discussion
The literature on chronic pain among pregnant women is limited, and this study aimed at determining the prevalence and preevaluation management of chronic pain during pregnancy in a university-based perinatal mood disorder clinic. A chronic pain condition was self-reported by 28.2% of initial evaluations, and the two most common complaints were neck and/or back pain and headaches. The majority were taking more than one medication at initial presentation with nearly half taking acetaminophen and/or opioids. Nonpharmacological therapy was less common contributing in less than one-quarter of respondents.
With high rates of comorbid pain in people with depression [41, 42], it was not surprising that our study found more than a quarter of patients presenting to a perinatal mood disorder clinic had a comorbid chronic pain condition. Previous studies of chronic prescription opioid use among pregnant women for pain management also identify headaches/migraine and back pain as the most frequent complaints [18, 43]. Although the rate of chronic pain conditions during pregnancy is lower than those in the general population, the authors believe it warrants the need for awareness among chronic pain physicians as well as obstetrical providers. The national opioid epidemic has raised awareness of the complexity of patients with chronic pain disorders, chronic opioid treatment, and opioid use disorders. As a result, providers should be aware of the Center for Disease Control and Prevention (CDC) guidelines for the management of chronic pain disorders [44] as well as the American College of Obstetrics and Gynecology guidelines for the management of opioid use disorder during pregnancy [45].
Our previous work has shown that less than a quarter of reproductive-aged women with long-term opioid prescriptions fill prescriptions for contraceptives [46]. The study population had an unplanned pregnancy rate of 69.5%. Given the rate of unplanned pregnancies in the general United States population is nearly 50% [47], women with chronic pain disorders may have an unmet need for family planning. The CDC recently published guidelines for the prescription of opioids for chronic pain, and recommendations include a discussion of family planning with the initial prescription of opioids [44]. This discussion should include family planning as well as the adverse obstetrical and fetal risks associated with pharmacological and nonpharmacological treatment options. If an unintended pregnancy does occur, a realistic goal is the development of a treatment plan at the earliest possible gestational age to maximize the benefit-to-risk ratio.
Primary fetal development occurs in the first trimester (i.e., up to 14 weeks of gestation), and exposures during that time may pose a risk. In this study, pregnant women presented at about 21 weeks of gestation or during the second trimester—past the first trimester. Moreover, the overwhelming majority of women were taking at least one analgesic medication. Notably, up to 10 pharmacological agents were reported in isolated cases. Application of known reproductive safety data is difficult in patients with chronic pain disorders as the impact of polypharmacy on perinatal outcomes is understudied.
Acetaminophen and opioids were the most commonly used agents—a finding that raises numerous questions. First, are these patients receiving optimal care for chronic pain conditions prior to knowledge of pregnancy? First-line pharmacological options for chronic pain include acetaminophen, nonsteroidal anti-inflammatory drugs, topical agents, tricyclic antidepressants, selective norepinephrine reuptake inhibitors, and gabapentinoids [48–52], while opioids are last-line treatment options. Second, the reproductive safety data of acetaminophen have recently been questioned [8, 9, 11, 15, 16, 53, 54]. Moreover, clinical experience raises concerns of appropriate dosing of acetaminophen as patients often report exceeding recommended dosage instructions and are given sparse guidance from healthcare professionals regarding dosing and presence of acetaminophen in preparations of over-the-counter and prescription medications. Third, the specific risks of opioids for chronic pain syndromes during the perinatal period are unknown. Data concerning obstetrical and neonatal outcomes with opioid exposure in utero are often derived from addiction studies and may not be directly applicable to pain disorder management [55]. Lastly, the epidemic of prescription opioid use in the United States population has extended to pregnant women and is of concern secondary to the adverse effects opioids have on maternal and neonatal health [19, 56, 57]. Comparable to this study, previous studies support an increasing trend of opioid use among pregnant women [19, 56, 57]. Changing physiology in pregnancy may require increased daily opiate dose [58], and prenatal exposure may exceed six months. Both duration of use and dose escalation are associated with increased risk of addiction [59, 60].
Only 20.5% of respondents utilized nonpharmacological treatments. Possible explanations for low utilization of nonpharmacological therapies include a lack of access, efficacy, reproductive safety data, and/or inadequate insurance coverage. Our study did not identify rates of cognitive-behavioral therapy use for chronic pain disorders, but cognitive-behavioral therapy is an effective treatment that should be considered for both chronic pain conditions and many psychiatric disorders in the perinatal period.
The current study has limitations warranting consideration. The population is derived from a specialty clinic and may not be generalizable to populations without psychiatric illnesses. Data were primarily collected from self-reported intake forms and are subject to recall bias. Although self-reported measures have been found to be a strong indicator of pain and a patient's psychosocial profile [61], they are only part of the clinical picture and must be used in conjunction with valid observation-based assessment tools in order to accurately evaluate patients. Finally, this was a retrospective chart review in a clinic focused on neuropsychiatric disorders during the perinatal period, and reports of chronic pain disorders may be underreported as the extent of inquiry by providers may have varied.
5. Conclusion
Chronic pain conditions among pregnant women with psychiatric illness are common and likely confer a significant burden of disease to both mother and fetus. The complexity of managing maternal benefits of treatment with the risks of fetal exposures presents a uniquely challenging clinical scenario for both chronic pain and obstetrical providers. Current guidelines for the management of chronic pain emphasize the importance of multimodal approaches, and progress towards effective and safe chronic pain management in pregnancy will require a multidisciplinary, biopsychosocial approach. Future research should examine both independent and dependent effects of pain and its treatment on perinatal outcomes in neuropsychiatric populations.
Acknowledgments
Dr. Ray's work was supported by the University of Arkansas for Medical Sciences Translational Research Institute (Grants UL1TR000039 and KL2TR000063) through the National Institute of Health, National Center for Research Resources, and the National Center for Advancing Translational Sciences and T32 DA022981-06. Ms. Morrison's work was supported by T32 DA022981/DA/NIDA HIH HHS (2T32DA022981-06).
Data Availability
The clinical data used to support the findings of this study have not been made available due to patient privacy.
Disclosure
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health.
Conflicts of Interest
Dr. Ray-Griffith currently receives clinical trial support from Neuronetics and has received clinical trial support from Sage Therapeutics. She has never served on a speaker's bureau or advisory board. Neither she nor her family members have every held equity positions in biomedical or pharmaceutical corporations. Dr. Stowe has received research support from Eli Lilly, Glaxo SmithKline (GSK), Janssen, Sage Therapeutics, the National Institutes of Health (NIH), and Wyeth. He has served on speakers' bureaus and/or received honoraria from Eli Lilly, GSK, Pfizer, and Wyeth. He has served on advisory boards for GSK and BSM. Neither he nor family members have ever held equity positions in biomedical or pharmaceutical corporations. Ms. Morris declares that she has no competing financial interests.
References
- 1.Simon L. S. Relieving pain in America: a blueprint for transforming prevention, care, education, and research. Journal of Pain & Palliative Care Pharmacotherapy. 2012;26(2):197–198. doi: 10.3109/15360288.2012.678473. [DOI] [Google Scholar]
- 2.Darnall B. D., Stacey B. R. Sex differences in long-term opioid use. Archives of Internal Medicine. 2012;172(5):431–432. doi: 10.1001/archinternmed.2011.1741. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Amris K., Wæhrens E. E., Jespersen A., Bliddal H., Danneskiold-Samsøe B. Observation-based assessment of functional ability in patients with chronic widespread pain: a cross-sectional study. Pain. 2011;152(11):2470–2476. doi: 10.1016/j.pain.2011.05.027. [DOI] [PubMed] [Google Scholar]
- 4.LeResche L., Saunders K., Dublin S., et al. Sex and age differences in global pain status among patients using opioids long term for chronic noncancer pain. Journal of Women’s Health. 2015;24(8):629–635. doi: 10.1089/jwh.2015.5222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Ray-Griffith S., Wendel M., Stowe Z., Magann E. Chronic pain during pregnancy: a review of the literature. International Journal of Women’s Health. 2018;10:153–164. doi: 10.2147/ijwh.s151845. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Wang S.-M., Dezinno P., Maranets I., Berman M. R., Caldwell-Andrews A. A., Kain Z. N. Low back pain during pregnancy. Obstetrics & Gynecology. 2004;104(1):65–70. doi: 10.1097/01.aog.0000129403.54061.0e. [DOI] [PubMed] [Google Scholar]
- 7.Coluzzi F., Valensise H., Sacco M., Allegri M. Chronic pain management in pregnancy and lactation. Minerva Anestesiologica. 2014;80(2):211–224. [PubMed] [Google Scholar]
- 8.Liew Z., Ritz B., Rebordosa C., Lee P.-C., Olsen J. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatrics. 2014;168(4):313–320. doi: 10.1001/jamapediatrics.2013.4914. [DOI] [PubMed] [Google Scholar]
- 9.Liew Z., Ritz B., Virk J., Olsen J. Maternal use of acetaminophen during pregnancy and risk of autism spectrum disorders in childhood: a Danish national birth cohort study. Autism Research. 2016;9(9):951–958. doi: 10.1002/aur.1591. [DOI] [PubMed] [Google Scholar]
- 10.Bakkeheim E., Mowinckel P., Carlsen K. H., Håland G., Carlsen K. C. L. Paracetamol in early infancy: the risk of childhood allergy and asthma. Acta Paediatrica. 2011;100(1):90–96. doi: 10.1111/j.1651-2227.2010.01942.x. [DOI] [PubMed] [Google Scholar]
- 11.Perzanowski M. S., Miller R. L., Tang D., et al. Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban, low-income cohort. Thorax. 2010;65(2):118–123. doi: 10.1136/thx.2009.121459. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Eyers S., Weatherall M., Jefferies S., Beasley R. Paracetamol in pregnancy and the risk of wheezing in offspring: a systematic review and meta-analysis. Clinical & Experimental Allergy. 2011;41(4):482–489. doi: 10.1111/j.1365-2222.2010.03691.x. [DOI] [PubMed] [Google Scholar]
- 13.Snijder C. A., Kortenkamp A., Steegers E. A. P., et al. Intrauterine exposure to mild analgesics during pregnancy and the occurrence of cryptorchidism and hypospadia in the offspring: the generation R study. Human Reproduction. 2012;27(4):1191–1201. doi: 10.1093/humrep/der474. [DOI] [PubMed] [Google Scholar]
- 14.Kristensen D. M., Hass U., Lesné L., et al. Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat. Human Reproduction. 2011;26(1):235–244. doi: 10.1093/humrep/deq323. [DOI] [PubMed] [Google Scholar]
- 15.Jensen M. S., Rebordosa C., Thulstrup A. M., et al. Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism. Epidemiology. 2010;21(6):779–785. doi: 10.1097/ede.0b013e3181f20bed. [DOI] [PubMed] [Google Scholar]
- 16.Becker K. G., Schultz S. T. Similarities in features of autism and asthma and a possible link to acetaminophen use. Medical Hypotheses. 2010;74(1):7–11. doi: 10.1016/j.mehy.2009.08.033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Bauer A. Z., Kriebel D. Prenatal and perinatal analgesic exposure and autism: an ecological link. Environmental Health. 2013;12(1):p. 41. doi: 10.1186/1476-069x-12-41. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Bateman B. T., Hernandez-Diaz S., Rathmell J. P., et al. Patterns of opioid utilization in pregnancy in a large cohort of commercial insurance beneficiaries in the United States. Anesthesiology. 2014;120(5):1216–1224. doi: 10.1097/aln.0000000000000172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Desai R. J., Hernandez-Diaz S., Bateman B. T., Huybrechts K. F. Increase in prescription opioid use during pregnancy among medicaid-enrolled women. Obstetrics & Gynecology. 2014;123(5):997–1002. doi: 10.1097/aog.0000000000000208. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Broussard C. S., Rasmussen S. A., Reefhuis J., et al. Maternal treatment with opioid analgesics and risk for birth defects. American Journal of Obstetrics and Gynecology. 2011;204(4):314.e1–314.e11. doi: 10.1016/j.ajog.2010.12.039. [DOI] [PubMed] [Google Scholar]
- 21.Patrick S. W., Schumacher R. E., Benneyworth B. D., et al. Neonatal abstinence syndrome and associated health care expenditures: United States, 2000–2009. JAMA. 2012;307(18):1934–1940. doi: 10.1001/jama.2012.3951. [DOI] [PubMed] [Google Scholar]
- 22.Hardt N., Wong T. D., Burt M. J., Harrison R., Winter W., Roth J. Prevalence of prescription and illicit drugs in pregnancy-associated non-natural deaths of Florida mothers, 1999–2005. Journal of Forensic Sciences. 2013;58(6):1536–1541. doi: 10.1111/1556-4029.12219. [DOI] [PubMed] [Google Scholar]
- 23.Yazdy M. M., Mitchell A. A., Tinker S. C., Parker S. E., Werler M. M. Periconceptional use of opioids and the risk of neural tube defects. Obstetrics & Gynecology. 2013;122(4):838–844. doi: 10.1097/aog.0b013e3182a6643c. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Taylor J. L., McKibben R. A., DeCamp M., Chisolm M. S., et al. Putting a face on the prescription opioid epidemic: a case report. General Hospital Psychiatry. 2014;36(4):449.e1–449.e2. doi: 10.1016/j.genhosppsych.2014.03.007. [DOI] [PubMed] [Google Scholar]
- 25.Altshuler L., Cohen L. Year Book of Psychiatry and Applied Mental Health. Maryland Heights, MI, USA: Mosby; 1997. Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines; p. p. 491. [DOI] [PubMed] [Google Scholar]
- 26.McElhatton P. R., Garbis H. M., Eléfant E., et al. The outcome of pregnancy in 689 women exposed to therapeutic doses of antidepressants: a collaborative study of the European network of teratology information services (ENTIS) Reproductive Toxicology. 1996;10(4):285–294. doi: 10.1016/0890-6238(96)00057-3. [DOI] [PubMed] [Google Scholar]
- 27.Vasilakis-Scaramozza C., Aschengrau A., Cabral H., Jick S. S. Antidepressant use during early pregnancy and the risk of congenital anomalies. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2013;33(7):693–700. doi: 10.1002/phar.1211. [DOI] [PubMed] [Google Scholar]
- 28.Reed C., Birnbaum H. G., Ivanova J. I., et al. Real-world role of tricyclic antidepressants in the treatment of fibromyalgia. Pain Practice. 2012;12(7):533–540. doi: 10.1111/j.1533-2500.2011.00526.x. [DOI] [PubMed] [Google Scholar]
- 29.Liu W.-Q., Kanungo A., Toth C. Equivalency of tricyclic antidepressants in open-label neuropathic pain study. Acta Neurologica Scandinavica. 2014;129(2):132–141. doi: 10.1111/ane.12169. [DOI] [PubMed] [Google Scholar]
- 30.Briggs G. G., Freeman R. K., Yaffe S. J. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. Philadelphia, PA, U.S.A: Lippincott Williams & Wilkins; 2012. [Google Scholar]
- 31.Hoog S. L., Cheng Y., Elpers J., Dowsett S. A. Duloxetine and pregnancy outcomes: safety surveillance findings. International Journal of Medical Sciences. 2013;10(4):413–419. doi: 10.7150/ijms.5213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Bobo W. V., Davis R. L., Toh S., et al. Trends in the use of antiepileptic drugs among pregnant women in the US, 2001–2007: a medication exposure in pregnancy risk evaluation program study. Paediatric and Perinatal Epidemiology. 2012;26(6):578–588. doi: 10.1111/ppe.12004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Fujii H., Goel A., Bernard N., et al. Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study. Neurology. 2013;80(17):1565–1570. doi: 10.1212/wnl.0b013e31828f18c1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Winterfeld U., Merlob P., Baud D., et al. Pregnancy outcome following maternal exposure to pregabalin may call for concern. Neurology. 2016;86(24):2251–2257. doi: 10.1212/wnl.0000000000002767. [DOI] [PubMed] [Google Scholar]
- 35.Chambers C., Kao K. K., Fekix R. J., et al. Pregnancy outcome in infants prenatally exposed to newer anticonvulsants. Birth Defects Research Part A: Clinical and Molecular Teratology. 2005;73:p. 316. [Google Scholar]
- 36.Morrow J., Russell A., Guthrie E., et al. Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK epilepsy and pregnancy register. Journal of Neurology, Neurosurgery & Psychiatry. 2006;77(2):193–198. doi: 10.1136/jnnp.2005.074203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Hunt S., Russell A., Smithson W. H., et al. Topiramate in pregnancy: preliminary experience from the UK epilepsy and pregnancy register. Neurology. 2008;71(4):272–276. doi: 10.1212/01.wnl.0000318293.28278.33. [DOI] [PubMed] [Google Scholar]
- 38.Meana M., Cho R., DesMeules M. Chronic pain: the extra burden on Canadian women. BMC Women’s Health. 2004;4(1):p. S17. doi: 10.1186/1472-6874-4-s1-s17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Munce S. E. P., Stewart D. E. Gender differences in depression and chronic pain conditions in a national epidemiologic survey. Psychosomatics. 2007;48(5):394–399. doi: 10.1176/appi.psy.48.5.394. [DOI] [PubMed] [Google Scholar]
- 40.Calvó-Perxas L., Vilalta-Franch J., Turró-Garriga O., López-Pousa S., Garre-Olmo J. Gender differences in depression and pain: a two year follow-up study of the survey of health, ageing and retirement in Europe. Journal of Affective Disorders. 2016;193:157–164. doi: 10.1016/j.jad.2015.12.034. [DOI] [PubMed] [Google Scholar]
- 41.Bair M. J., Robinson R. L., Katon W., Kroenke K. Depression and pain comorbidity. Archives of Internal Medicine. 2003;163(20):2433–2445. doi: 10.1001/archinte.163.20.2433. [DOI] [PubMed] [Google Scholar]
- 42.Lindsay P. G., Wyckoff M. The depression-pain syndrome and its response to antidepressants. Psychosomatics. 1981;22(7):571–577. doi: 10.1016/s0033-3182(81)73478-9. [DOI] [PubMed] [Google Scholar]
- 43.Kellogg A., Rose C. H., Harms R. H., Watson W. J. Current trends in narcotic use in pregnancy and neonatal outcomes. American Journal of Obstetrics and Gynecology. 2011;204(3):259.e1–259.e4. doi: 10.1016/j.ajog.2010.12.050. [DOI] [PubMed] [Google Scholar]
- 44.Dowell D., Haegerich T. M., 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. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Committee on Obstetric Practice. Committee opinion no. 711: opioid use and opioid use disorder in pregnancy. Obstetrics & Gynecology. 2017;130(2):e81–e94. doi: 10.1097/aog.0000000000002235. [DOI] [PubMed] [Google Scholar]
- 46.Ray-Griffith S. L., Chopra D., Stowe Z. N., Martin B. C. Claims for contraceptive services among young women filling chronic opioid prescriptions. Contraception. 2019;99(5):296–299. doi: 10.1016/j.contraception.2019.01.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Finer L. B., Zolna M. R. Unintended pregnancy in the United States: incidence and disparities, 2006. Contraception. 2011;84(5):478–485. doi: 10.1016/j.contraception.2011.07.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Chou R., Fanciullo G. J., Fine P. G., et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. The Journal of Pain. 2009;10(2):113–130. doi: 10.1016/j.jpain.2008.10.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49.Nuckols T. K., Anderson L., Popescu I., et al. Opioid prescribing: a systematic review and critical appraisal of guidelines for chronic pain. Annals of Internal Medicine. 2014;160(1):38–47. doi: 10.7326/0003-4819-160-1-201401070-00732. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50.Moulin D. E., Clark A. J., Gilron I., et al. Pharmacological management of chronic neuropathic pain—consensus statement and guidelines from the Canadian pain society. Pain Research and Management. 2007;12(1):13–21. doi: 10.1155/2007/730785. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.O’Connor A. B., Dworkin R. H. Treatment of neuropathic pain: an overview of recent guidelines. The American Journal of Medicine. 2009;122(10):S22–S32. doi: 10.1016/j.amjmed.2009.04.007. [DOI] [PubMed] [Google Scholar]
- 52.Attal N., Cruccu G., Baron R., et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. European Journal of Neurology. 2010;17(9):1113–e88. doi: 10.1111/j.1468-1331.2010.02999.x. [DOI] [PubMed] [Google Scholar]
- 53.Becquet O., Bonnet D., Ville Y., Allegaert K., Lapillonne A. Paracetamol/acetaminophen during pregnancy induces prenatal ductus arteriosus closure. Pediatrics. 2018;142(1) doi: 10.1542/peds.2017-4021.e20174021 [DOI] [PubMed] [Google Scholar]
- 54.Ystrom E., Gustavson K., Brandlistuen R. E., et al. Prenatal exposure to acetaminophen and risk of ADHD. Pediatrics. 2017;140(5) doi: 10.1542/peds.2016-3840.e20163840 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Jones H. E., Friedman C. J., Starer J. J., Terplan M., Gitlow S. Opioid use during pregnancy. Addictive Disorders & Their Treatment. 2014;13(1):8–15. doi: 10.1097/adt.0b013e318271c437. [DOI] [Google Scholar]
- 56.Epstein R. A., Bobo W. V., Martin P. R., et al. Increasing pregnancy-related use of prescribed opioid analgesics. Annals of Epidemiology. 2013;23(8):498–503. doi: 10.1016/j.annepidem.2013.05.017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57.Mitchell A. A., Gilboa S. M., Werler M. M., Kelley K. E., Louik C., Hernández-Díaz S. Medication use during pregnancy, with particular focus on prescription drugs: 1976–2008. American Journal of Obstetrics and Gynecology. 2011;205(1):51.e1–51.e8. doi: 10.1016/j.ajog.2011.02.029. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 58.Bogen D. L., Perel J. M., Helsel J. C., et al. Pharmacologic evidence to support clinical decision making for peripartum methadone treatment. Psychopharmacology. 2013;225(2):441–451. doi: 10.1007/s00213-012-2833-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 59.Alam A., Gomes T., Zheng H. Long-term analgesic use after low-risk surgery. Archives of Internal Medicine. 2012;172(5):425–430. doi: 10.1001/archinternmed.2011.1827. [DOI] [PubMed] [Google Scholar]
- 60.Piazza P. V., Deroche-Gamonet V. A multistep general theory of transition to addiction. Psychopharmacology. 2013;229(3):387–413. doi: 10.1007/s00213-013-3224-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 61.Amris K., Wæhrens E., Stockmarr A., Bliddal H., Danneskiold-Samsøe B. Factors influencing observed and self-reported functional ability in women with chronic widespread pain: a cross-sectional study. Journal of Rehabilitation Medicine. 2014;46(10):1014–1021. doi: 10.2340/16501977-1878. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The clinical data used to support the findings of this study have not been made available due to patient privacy.