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16 Articles in Volume 20, Issue #5
20/20 with Drs. Carmen R. Green and Johnathan Goree: Racial Disparities in Pain Care
A Kratom Primer: Miracle Medicine or Herb of Abuse?
A Pilot Study: Incidence and Prediction of Diversion among Opioid Therapy Patients
Analgesics of the Future: G-Protein Biased Mu-Opioid Receptor Ligands
Application Note: Decellularized Human Placenta in the Treatment of Infracalcaneal Heel Pain
Are Clinicians Effectively Counseling Patients on Safe Opioid Storage and Disposal? Survey Results
Ask the PharmD: How to Manage Pain Meds During Pregnancy?
Behavioral Medicine: Managing Anxiety and Maladaptive Behaviors
Case Report: Spinal Cord Stimulation for the Treatment of Pain Associated with Chronic Pancreatitis
Differential Diagnoses: Inflammatory or Non-inflammatory Chronic Back Pain?
Pelvic Inflammatory Disease: Diagnosis, Education, and Treatment Options
Product Review: Non-Invasive Neuromodulation for the Treatment of the Most Difficult Pain Conditions
Provider Perspective: Carpal Tunnel's Association with Hypothyroidism
Research Insights: Opioid Use During the Peripartum Period – What to Expect
Special Report: Race, Pain Management, and the System
When Patients Become Pregnant: How to Maintain Chronic Pain Management

When Patients Become Pregnant: How to Maintain Chronic Pain Management

The perinatal period presents a particularly vulnerable state for women with chronic pain disorders, and data supporting their prevalence, course, and management are scarce. By collaborating with a patient’s obstetrical team, pain specialists can avoid suboptimal care.

The prevalence of pre-existing chronic pain conditions in pregnant women is unknown. But with the increasing rates of women older than 30 years giving birth, clinicians are likely to see women with complex medical problems, including chronic pain syndromes, experiencing pregnancy while under their care.

Treatment options during pregnancy include pharmacological and nonpharmacological options, but there are many uncertainties around appropriate and effective treatment leaving clinicians without adequate resources to make evidence-based recommendations. Following are considerations for assessment and management of patients with commonly seen chronic pain conditions for which newer treatment strategies may impact clinical care.

Until recently, there were no clinical guidelines for the management of any type of chronic pain during pregnancy - but strides are being made. (Image: iStock)

How to Guide Patients with Rheumatic and Musculoskeletal Diseases through Pregnancy

Until recently, there were no clinical guidelines for the management of any type of chronic pain during pregnancy. But earlier this year, the American College of Rheumatology (ACR) released a Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases, which includes clinical practice guidelines for pregnancy assessment and management in women with lupus, rheumatoid arthritis, and other rheumatic conditions.1

Patient Counseling and Education

The management of reproductive health issues in individuals with rheumatic and musculoskeletal diseases (RMD) differs from that in healthy persons. Patients, like clinicians, may not be aware of the potentially complex interactions between reproductive health and their chronic disease. Thus, understanding and addressing reproductive health-related issues are crucial for rheumatology clinicians. Not only should they counsel their patients about pregnancy and how it affects their condition, but they should also collaborate with specialists in obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology.

While it is true that pregnancy in women with RMD may lead to serious maternal or fetal adverse outcomes, patients’ potentially outsized fears about their disease may color their reproductive decisions. In a survey of 267 women with inflammatory arthritis (79% had rheumatoid arthritis), 40% were affected by infertility, and 58% said they chose to limit childbearing because of fears that their arthritis was heritable, their diseases and medications could directly harm a fetus, they would be incapable of physically caring for a child, or that they may die prematurely.2 Yet a recent review of studies found that disease activity improved in 60% of patients with RA during pregnancy but flared in 46.7% postpartum.3

The availability of biologic agents and treat-to-target paradigms have significantly improved outcomes, although some commonly prescribed drugs, such as methotrexate, may be contraindicated during pregnancy.2 Nevertheless, while patients may perceive disease-related risks as absolute contraindications toward childbearing, clinicians may not find such risks to be insurmountable.2 As clinical outcomes for patients with RMD improve, patients have become stable enough to consider pregnancy, and rheumatologists can help guide them to make well-informed reproductive decisions. 

Rheumatology clinicians should aim to address reproductive health issues at an early visit and follow up in subsequent visits. An understanding of basic pregnancy physiology may be helpful to coordinate care with obstetric providers and pain management specialists. When possible, pregnancy should be planned during periods of quiet disease when the patient is on pregnancy-compatible medications. Women with uncontrolled RA may be at increased risk for preterm birth and babies that are small for their gestational age.

Risk Mitigation & Medication Management

The risk in pregnancy for women with RMD relates primarily to diagnosis, level of disease activity and damage, medications, and the presence of anti-Ro/SSA, anti-La/SSB, and antiphospholipid (aPL) antibodies.1 Therefore, pre-pregnancy assessment is crucial for a successful pregnancy with good maternal and fetal/neonatal outcomes. Recommendations regarding analgesics and other drugs commonly used for RMD patients are also available.4

The ACR guideline includes several recommendations for pregnancy assessment and management, including a strong recommendation to counsel women with RMD who are considering pregnancy on the improved maternal and fetal outcomes associated with entering pregnancy during low disease activity.1

In addition, the ACR strongly recommends that women with active disease requiring medical therapy be given a pregnancy-compatible steroid-sparing medication, as glucocorticoid treatment has the potential for maternal and fetal harm. Testing for anti-Ro/SSA, anti-La/SSB antibodies before or early in pregnancy is also recommended in women with lupus, Sjögren’s syndrome, systemic sclerosis, and rheumatoid arthritis.  

A conditional recommendation is to treat lupus patients with low-dose aspirin daily (81 mg to 100 mg) starting in the first trimester. For women testing positive for aPL who do not meet the criteria for obstetric or thrombotic antiphospholipid syndrome (APS), it is conditionally recommended to preventatively treat with a daily low-dose aspirin starting early in pregnancy and continuing through delivery. Additional recommendations can be found in the ACR guidelines.1

 

How to Guide Patients with Migraine through Pregnancy

Migraine occurs in as many as 24% of women of reproductive age, a rate three times higher than that in men, which is mainly due to sex hormone differences.5,6 Migraine without aura may improve during pregnancy because of increasing estrogen levels, although migraine with aura often remains the same or worsens.5 Pregnant women with headaches have been reported to have a greater rate of preterm delivery, gestational hypertension, and preeclampsia.7

Quality of Life Issues

Migraine adversely affects a patient’s quality of life both during and between attacks, impacting careers, social activity, and relationships. The American Registry for Migraine Research collected data on future reproductive life plans from 607 women classified by headache specialists as having migraine who completed questionnaires between February 2016 and September 2019.8 Overall, 20% reported that they avoid pregnancy to some extent because of their migraine disorder. Compared to those who reported that migraine had no impact on their reproductive decisions, they had a higher proportion of depression, more headache days, and higher disability scores. Moreover, 73% believed their migraine would be worse during or just after pregnancy, and 68% believed that their migraine attacks would make pregnancy more difficult. These inconsistencies, coupled with previous observations that migraine improves during pregnancy,5 underscore the importance of educating women with migraine on the impact of pregnancy on their disease.

Nevertheless, alterations to sleep, stress level, and mood do play a major role in exacerbating headache among pregnant women, but these symptoms are potentially modifiable if identified and treated.

Migraine Management Approaches

Nonpharmacological approaches to migraine management include avoidance of triggers, stress management, sleep optimization, massage, biofeedback, yoga, and acupuncture. Nerve blocks to the scalp using local anesthetics may also be safely given during pregnancy.

Based on a review of 144 articles in the current literature, Ray-Griffith and colleagues noted that pharmacological options for acute migraine management include acetaminophen, triptans, antiemetics, and opioids.7 Preventive treatments recommended during pregnancy include tricyclic antidepressants, topiramate, magnesium, and botulinum toxin, which is the only drug indicated for the treatment of chronic migraine.7 Ray-Griffith and colleagues further recommend that, in general, pharmacological management should focus on the minimizing exposures to the fetus by simplifying medication regimens and eliminating those that may have limited efficacy or excessive risk.7

The safety of onabotulinumtoxin-A (Botox) given during pregnancy has not been well studied, although a 29-year safety database indicates that the prevalence of fetal defects in botulinum toxin-exposed mothers before or during pregnancy is comparable with rates in the general population.9 More recently, a review of nine women (10 pregnancies) treated with botulinum toxin for chronic migraine during pregnancy at doses ranging from 155 units to 185 units showed that all pregnancies resulted in live full-term births of healthy babies.10

The newer calcitonin gene-related peptide (CGRP) antagonists are potentially beneficial options for migraine prevention. However, because of the role CGRP plays in mediating the adrenal glucocorticoid response to acute stress in the mature fetus as well as its role in cervical ripening prior to delivery, longitudinal surveillance in women during pregnancy is required.11 Neurologist Lawrence Robbins, MD, urges caution in recommending one of these agents. In a commentary for clinicians involved in the treatment of chronic headache and migraine published in this journal, he noted that CGRP antagonists could negatively affect pregnancy, particularly during the latter stages, and need additional study before recommendations can be made.

Overall, counseling women with migraine who are considering pregnancy can help prevent deleterious effects of certain pharmacologic options on the health of both mother and fetus. The risk/benefit ratio for any medication should be discussed with patients and the lowest effective dose and frequency taken.

 

How to Guide Patients with Mental Health Disorders through Pregnancy

Chronic pain conditions among pregnant women with psychiatric illness are common and likely confer a significant burden of disease to both mother and fetus.12 Rates of depression in individuals with chronic pain are twice as high of those without chronic pain. As a result, reproductive psychiatrists may become a welcome part of the management team for pregnant patients with chronic low back pain, depression, and fibromyalgia, among other conditions.12

Clinical Considerations

The effects of mental health on pregnancy outcomes, whether related to chronic pain or not, is a relatively new area of study. Research has shown that severe obstetrical and neonatal outcomes are associated with perinatal mood and anxiety disorders and serious mental illness.13 Trauma and stress related to military deployment has also been shown to influence reproductive health.14

Mental health issues during pregnancy may also affect the treatment a woman receives. In a retrospective chart review of 156 pregnant women presenting for an initial evaluation to a mental health clinic, 28.2% reported a chronic pain condition, with neck and/or back pain and headache the most common.12 Of those with chronic pain, 95.5% were taking at least one prescription medication, most commonly acetaminophen (43.2%) or opioids (43.2%). Only 20.5% of women were utilizing nonpharmacological therapy, most likely because of a lack of access or inadequate insurance coverage.

Based on these findings, the researchers questioned whether these patients were receiving optimal care prior to their knowledge of pregnancy.12

Further concerns about excess acetaminophen dosing and recent reports in the literature about its links to autism, asthma, and ADHD, among other conditions, led the research team to consider whether patients receive adequate guidance on chronic pain management from their healthcare professionals. Moreover, they concluded, while specific risks of opioids for chronic pain syndromes during the perinatal period are unknown, the increase in opioid use among pregnant women raises concerns about adverse effects on maternal and neonatal health as well as the risk of addiction.

Newborn cryingDespite concerns about the use of opioids during pregnancy, they may be safe when taken as prescribed, despite the risk of neonatal abstinence syndrome (Image: iStock)

Opioids, Pregnancy, and Neonatal Abstinence Syndrome

Exposure to opioids in utero poses risks for fetuses and newborns because of the drugs’ ability to cross placental and blood-brain barriers.15 Prenatal opioid exposure may lead to obstetric complications, adverse neonatal outcomes, neonatal abstinence syndrome (NAS), neurodevelopmental impairments, and teratogenic effects.16 Congenital malformations are a leading cause of infant mortality or can result in lifelong developmental challenges.

Studies have linked opioid use during early pregnancy to congenital malformations and fetal death, reporting a twofold increased risk for some congenital heart defects, neural tube defects, and gastroschisis.17,18 A review of published studies has shown significant positive associations between maternal opioid use during pregnancy and congenital malformations, such as oral clefts and ventricular septal defects/atrial septal defects, but authors allow that uncertainty remains regarding opioids’ teratogenicity.16

Opioid-Naïve Patients

Therefore, when considering opioid therapy for a patient contemplating pregnancy, careful risk assessment is warranted. The CDC Guideline for Prescribing Opioids for Chronic Pain recommends that healthcare providers discuss family planning as well as the effects of long-term opioid use on future pregnancy with women considering opioids to manage chronic pain.19

A large claims database shows that less than one-quarter of reproductive-aged women with long-term opioid prescriptions fill prescriptions for contraceptives, resulting in an unplanned pregnancy rate of 69.5% versus a rate of 50% in the general population.20

Patients on Opioid Therapy

For those practitioners caring for pregnant women already taking opioids, the CDC guideline recommends:

offering a tapering plan

offering medication-assisted therapy with methadone or buprenorphine to those with opioid use disorder

arranging for delivery at a facility prepared to deal with NAS, sometimes referred to as neonatal opioid withdrawal syndrome (NOWS).19

Of note, NAS is related to opioid exposure in utero and is characterized by difficulties with feeding and sleeping as well as central nervous system dysfunction.21 Although some risk factors for NAS, such as maternal and neonatal characteristics and genetics are non-modifiable, practices such as breastfeeding and rooming-in are associated with a reduced risk of the syndrome.

Despite concerns about the use of opioids during pregnancy, they may be safe when taken as prescribed, despite the risk of NAS. Studies have shown the rates of NAS were lower in infants born to mothers taking prescription opioids than in those born to mothers in opioid treatment programs on maintenance medications.22,23

More on opioid use disorder in pregnant patients.

Conclusion

Women with chronic pain conditions who are considering pregnancy face numerous challenges for themselves and their infants. This is compounded on the part of clinicians by a lack of research and resources for making decisions about appropriate and effective treatment. However, by educating themselves and their patients, and by collaborating with other healthcare professionals, pain management specialists can increase their confidence and competence in providing effective care for patients planning a pregnancy or who become pregnant.

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Ask the PharmD: How to Manage Pain Meds During Pregnancy?
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