Syphilis is a sexually transmitted infection that manifests as a chronic systemic disease. Each of the different stages of infection involves specific symptoms that can be overlooked or confused with those of other diseases. Adequate screening for syphilis in women at risk, combined with appropriate treatment and follow-up as indicated, is essential to reduce the risk of transmission and disease complications.
The American College of Obstetricians and Gynecologists (ACOG) published a practice bulletin on gestational diabetes mellitus (GDM) in February 2018,1 just 7 months after publishing a previous bulletin on the same topic.2 According to ACOG, the purpose of the update was to provide additional information on the pharmacologic treatment of gestational diabetes mellitus. This article elucidates the recent changes in ACOG’s bulletin, as well as those in the American Diabetes Association guidelines.3 Continue reading
Recent advances in science and clinical care have changed the characteristics of the population with cystic fibrosis (CF). Half of patients with CF are now adults who want to achieve milestones that were impossible in the past; for women with CF, this may include motherhood. However, these women may have concerns and fears about getting pregnant, being pregnant, and becoming mothers that go beyond those that otherwise healthy women experience. This qualitative study was conducted to ascertain the reproductive health concerns of a small group of women with CF. Continue reading
By 2018, some 76,000 women in the U.S. will freeze their eggs every year to preserve their fertility and increase their odds of getting pregnant later in life. Yet egg freezing is by no means a solid insurance policy. Some estimates suggest that just under 24% of procedures will result in a live birth. The fertility field is looking for other options.
In a new study published in the journal Reproductive Sciences, two fertility experts argue that ovarian tissue freezing—a procedure that removes and freezes ovarian tissue for later use—could offer an alternative, especially for women who can’t undergo egg freezing for medical reasons.
Read more at Time.
|Key words: pregnancy, perinatal period, perinatal anxiety, generalized anxiety disorder, perinatal anxiety screening scale|
Routine assessment for perinatal anxiety disorders, using established diagnostic criteria and standardized tools, can facilitate early diagnosis, guide management, and optimize outcomes for pregnant women and their offspring.
An anxiety disorder can disrupt a woman’s abilities to enjoy life and to self-care. When an anxiety disorder is present during the perinatal period—that is, during pregnancy and/or the first year postpartum—it can change how a woman experiences her pregnancy and how she interacts with and cares for her child.1 Limited data suggest a possible association between severe perinatal anxiety disorders and adverse pregnancy outcomes such as preterm birth, low birth weight, and postpartum depression.2,3 In addition, maternal anxiety disorders have been linked to developmental and mental health problems in offspring.2-4 Healthcare providers (HCPs) who see women during pregnancy and postpartum need to know the risk factors and signs and symptoms associated with perinatal anxiety disorders so that these disorders can be identified early and treated as needed. This article focuses primarily on assessment for and management of a common anxiety disorder—generalized anxiety disorder (GAD)—in this patient population.
Generalized anxiety disorder (GAD) is a mental disorder characterized by frequent and intense worry or anxiety about many aspects of one’s life (e.g., health, work, family), even if these aspects of life are going well.5 A person with GAD has difficulty controlling this anxiety, which can interfere with daily functioning.
Approximately 40 million adults in the United States, or 18% of the adult U.S. population, are diagnosed with an anxiety disorder each year, with 22.8% of these cases classified as severe.6 In addition to GAD, anxiety disorders include phobias, social anxiety disorder, post-traumatic stress disorder (PTSD), panic disorder, and obsessive-compulsive disorder. Many adults have more than one anxiety disorder.6 GAD, with a prevalence of 3.1% and an average age of onset of 31 years, is twice as common in women as in men,7 Anxiety disorders affect 4%-39% of women during pregnancy and up to 18% during the postpartum period.8
Perceived lack of partner and/or social support, a history of intimate partner violence or other abuse, a personal history of mental illness, having an unplanned or unwanted pregnancy, past or present pregnancy complications, and past pregnancy loss are risk factors for perinatal GAD.9 Women experiencing a high-risk pregnancy are also at greater risk for developing GAD.10,11 Other risk factors for perinatal GAD include failure to complete high school, unemployment, and nicotine use.12
Some degree of anxiety is common during pregnancy and postpartum, so HCPs should aim to differentiate between “normal” anxiety and GAD. Persons in the general population with GAD may report trembling, twitching, shakiness, muscle aches, sweating, nausea, diarrhea, and an exaggerated startle response.7 In the perinatal period, GAD may manifest as excessive and persistent nervousness, worry, or even panic about pregnancy and childbirth, the infant’s health, and parenting. Physical features—in addition to those listed for GAD in general—may include stomach pain, headaches, dizziness, palpitations, and shortness of breath.13 GAD can exacerbate sleep disturbances and fatigue in women during the perinatal period. Because anxiety and depressive disorders often co-exist, a pregnant or postpartum woman with GAD may exhibit manifestations of depression as well.14
Routine screening is essential for early recognition of GAD, which may otherwise go undetected and untreated in pregnant and postpartum women. Some of the most common clinical features of GAD may be attributed to normal physiologic changes of pregnancy or expected psychosocial adjustments to pregnancy and child care. A woman may be reluctant to report signs/symptoms of GAD for fear of being perceived as an excessive worrier or a hypochondriac.
The American College of Obstetricians and Gynecologists (ACOG) advises screening women at least once during the perinatal period for anxiety and depression using a standardized, validated tool.15 Although ACOG does not provide a recommendation for timing or frequency of this screening, the organization does advise HCPs to closely monitor women who have a history of, or risk factors for, anxiety or depressive disorders.
Two anxiety screening instruments used in both pregnant and postpartum women are the Generalized Anxiety Disorder-7 (GAD-7) and the Perinatal Anxiety Screening Scale (PASS). The GAD-7 is a 7-item self-report questionnaire created to identify essential areas of anxiety (worry, restlessness, irritability, and fear) and its severity in the previous 2 weeks.16,17 The reported internal consistency of the GAD-7 is excellent (Cronbach’s α, .92), and its test/retest reliability is good (intraclass correlation coefficient [ICC], .83). The PASS is useful throughout the perinatal period to assess for a range of anxiety symptoms.18,19 Principal component analyses suggested a 4-factor structure addressing symptoms of acute anxiety and adjustment; general worry and specific fears; perfectionism, control, and trauma; and social anxiety. The PASS is validated for use in hospital, mental health, and community samples and has excellent reliability (Cronbach’s α, .96) and test/retest reliability (ICC, .74). The Box lists various anxiety screens and provides links to them for easy access.
Validated anxiety screening instruments with a postpartum focus include the Postpartum Worry Scale-R (PWS-R) and the Penn State Worry Questionnaire-10 (PSWQ-10). The PWS-R was developed to identify the degree of uncontrollable worry, a major symptom of GAD in postpartum women.20 This revised format of the original PWS includes items related to the mother’s perception of the infant’s well-being in terms of health and development and the mother’s relationship with her child.21,22 The PSWQ-10 measures worry, often described as the cardinal feature of GAD.23 Although the PSWQ-10 cannot distinguish GAD from major depressive disorder, it can track worry, which may affect both treatment and recovery. The Edinburgh Postnatal Depression Scale (EPDS) has an anxiety subscale (EPDS-3A) and can reliably differentiate between depression and anxiety.24
Establishing rapport with patients facilitates a discussion of the clinical features of anxiety, screening test results, and treatment options.
HCPs need to determine the extent to which anxiety, worry, and/or the physical manifestations of anxiety are causing impairment in social, occupational, or other areas of functioning.
Once perinatal anxiety is identified and diagnosed, the next step is to determine whether an underlying condition might be causing the signs/symptoms or exacerbating their severity (e.g., substance misuse/abuse, a physical health condition), as well as whether co-existing psychiatric conditions such as depression, substance abuse, bipolar disorder, psychosis, schizophrenia, or PTSD might be complicating the picture. Referral to a mental health specialist is imperative when a pregnant woman has suicidal ideation, a co-existing psychiatric condition, or need for a complex medication regimen. HCPs providing perinatal care should have resources available for initiating a multidisciplinary team approach in treating perinatal anxiety.25,26
If perinatal anxiety is determined to be the primary problem, cognitive behavioral therapy (CBT), the first-line treatment for anxiety in the general population, is a reasonable first approach.27 Although less studied in women with perinatal anxiety, CBT has been shown to be effective in treating postpartum depression.28,29 Additional nonpharmacologic options include mindfulness-based cognitive therapy, interpersonal therapy, psychodynamic therapy, acupuncture, and massage.30 When nondrug therapies are ineffective or only partially effective, medication may be indicated. In these cases, HCPs and patients should weigh the risks of not fully treating the anxiety disorder, the potential risks to a fetus exposed to the medications chosen, and the potential benefits of easing the anxiety disorder.
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are first-line drugs for the treatment of moderate or severe anxiety disorders.31 The Table lists commonly prescribed SSRIs and SNRIs, as well as their recommended daily doses and side effects.31 Taken together, data obtained over several years suggest that SSRIs and SNRIs are not teratogenic or associated with adverse pregnancy outcomes. Studies of the use of the SSRIs sertraline, fluoxetine, and citalopram during pregnancy provide the largest databases indicating no teratogenic effects.32,33 Although study results are conflicting, some reports have suggested a small increased risk for congenital heart defects associated with use of paroxetine during pregnancy.34,35 No teratogenic effects have been reported with use of SNRIs during pregnancy, although these agents may be associated with a small increased risk for pre-eclampsia.36
The SSRIs fluoxetine and paroxetine and the SNRI venlafaxine, if taken around the time of birth, have been most closely associated with postnatal adaptation syndrome (PNAS).37 However, a recent study found that these agents did not cross the placenta to a greater extent than other antidepressants.37 Maternal use of SSRIs in late pregnancy may also be associated with a potentially increased risk of persistent pulmonary hypertension of the newborn.38 The absolute risk is small, and, according to a recent study, the increased risk appears more modest than that suggested in previous studies.38
Both SSRIs and SNRIs may be used for treatment of an anxiety disorder in a woman who is breastfeeding.34,39 Infants whose mothers are using the SSRIs fluvoxamine, paroxetine, or sertraline or the SNRI venlafaxine have been found to have low or undetectable serum drug levels, and no adverse effects have been reported.40
In the general population, use of benzodiazepines should be reserved for acute anxiety on a short-term basis because of the multiple associated risks: worsening of depressive symptoms, possible dependence, and possible overdose.32 Benzodiazepine use should be avoided in pregnancy because of these risks. Some data show a small increased risk for preterm birth, low birth weight, and floppy infant syndrome (hypotonia) in infants whose mothers used benzodiazepines during pregnancy. Data are inconclusive in terms of any teratogenic effect. If benzodiazepines are considered for women who are breastfeeding, those with a shorter half-life such as lorazepam and oxazepam are preferred because they are reported to result in low levels in breast milk and because they do not cause adverse effects in breastfed infants.34,41 Alprazolam and diazepam, with longer half-lives than some of the other benzodiazepines, should be avoided because of reports of infant sedation.34,41
Perinatal anxiety is fairly common, and, when severe, has been linked to adverse pregnancy outcomes and to developmental and mental health problems in offspring. Early identification of and intervention for perinatal anxiety can help alleviate signs and symptoms, improve the perinatal experience, and reduce the risk for adverse outcomes. HCPs need to screen women for anxiety both during pregnancy and postpartum. When anxiety is identified, HCPs should conduct further assessment to determine whether the patient has a co-existing psychiatric disorder that merits referral and collaboration with a mental health specialist. Nonpharmacologic treatments such as CBT should be considered as first-line treatment, although some women may require medication to manage symptoms adequately. Risks and benefits of using medications to treat anxiety during the perinatal period should be considered on an individualized and ongoing basis.
Marian L. Farrell is Professor of Nursing at the University of Scranton in Scranton, Pennsylvania. She is also in private practice as a psychiatric nurse practitioner and clinical nurse specialist. The author states that she does not have a financial interest in or other relationship with any commercial product named in this article.
1. Ross LE, McLean LM. Anxiety disorders during pregnancy and the postpartum period: a systematic review. J Clin Psychiatry. 2006; 67(8):1285-1298.
2. Bauer A, Knapp M, Parsonage M. Lifetime costs of perinatal anxiety and depression. J Affect Disord. 2016;192:83-90.
3. Bayrampour H, Al E, McNeil DA, et al. Pregnancy-related anxiety: a concept analysis. Int J Nurs Stud. 2015;55:115-130.
4. Rubertsson C, Hellström J, Cross M, Sydsjö G. Anxiety in early pregnancy: prevalence and contributing factors. Arch Womens Ment Health. 2014;17(3):221-228.
5. National Institute of Mental Health (NIMH). Generalized Anxiety Disorder Among Adults.
6. National Institute of Mental Health. Any Anxiety Disorder Among Adults.
7. American Psychiatric Association. Anxiety disorders. In: Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington, VA: APA; 2013:222-226.
8. Marchesi C, Ossola P, Amerio A, et al. Clinical management of perinatal anxiety disorders: a systematic review. J Affect Disord. 2016;190:543-550.
9. Biaggi A, Conroy S, Pawlby S, Pariante CM. Identifying the women at risk of antenatal anxiety and depression: a systematic review. J Affect Disord. 2016;191:62-77.
10. O’Hara MW, Stuart S, Watson D, et al. Brief scales to detect postpartum depression and anxiety symptoms. J Womens Health. 2012;21(12):1237-1243.
11. Zadeh MA, Khajehei M, Sharif F, Hadzic M. High-risk pregnancy: effects on postpartum depression and anxiety. Br J Midwifery. 2012;20(2):104-113.
12. Fairbrother N, Janssen P, Antony MM, et al. Perinatal anxiety disorder prevalence and incidence. J Affect Disord. 2016;200:148-155.
13. Hoang S. Pregnancy and anxiety. Int J Childbirth Educ. 2014;29(1):67-70.
14. Grigoriadis S, de Camps Meschino D, Barrons E, et al. Mood and anxiety disorders in a sample of Canadian perinatal women referred for psychiatric care. Arch Womens Ment Health. 2011;14(4):325-333.
15. American College of Obstetricians and Gynecologists. Screening for perinatal depression. Washington, DC: ACOG; 2015.
16. Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092-1097.
17. Simpson W, Glazer M, Michalski N, et al. Comparative efficacy of the generalized anxiety disorder 7-item scale and the Edinburgh Postnatal Depression Scale as screening tools for generalized anxiety disorder in pregnancy and the postpartum period. Can J Psychiatry. 2014;59(8):434-440.
18. Somerville S, Dedman K, Hagan R, et al. The perinatal anxiety screening scale: development and preliminary validation. Arch Womens Ment Health. 2013;17(5):443-454.
19. Somerville S, Byrne SL, Dedman K, et al. Detecting the severity of perinatal anxiety with the Perinatal Anxiety Screening Scale (PASS). J Affect Disord. 2015;186:18-25.
20. Wenzel A, Haugen EN, Jackson LC, Robinson K. Prevalence of generalized anxiety at eight weeks postpartum. Arch Womens Ment Health. 2002;6(1):43-49.
21. Moran TE, Polanin JR, Wenzel A. The Postpartum Worry Scale-Revised: an initial validation of a measure of postpartum worry. Arch Womens Ment Health. 2014;17(1):41-48.
22. Moran TE, Polanin JR, Segre L, Wenzel A. The Postpartum Worry Scale-Revised: continuing validation with a sample of NICU mothers. Arch Womens Ment Health. 2015;18(2):221-228.
23. Yao B, Sripada RK, Klumpp H, et al. Penn State Worry Questionnaire-10: a new tool for measurement-based care. Psychiatry Res. 2016;239:62-67.
24. Matthey S, Fisher J, Rowe H. Using the Edinburgh postnatal depression scale to screen for anxiety disorders: conceptual and methodological consideration. J Affect Disord. 2013;146(2):224-230.
25. Ali NS, Azam IS, Ali BS, et al. Frequency and associated factors for anxiety and depression in pregnant women: a hospital-based cross-sectional study. Scientific World Journal. 2012;2012:653098.
26. Dunkel Schetter C, Tanner L. Anxiety, depression and stress in pregnancy: implications for mothers, children, research, and practice. Curr Opin Psychiatry. 2012;25(2):141-148.
27. Otte C. Cognitive behavior therapy in anxiety disorders: current state of the evidence. Dialogues Clin Neurosci. 2011;13(4):413-421.
28. Sockol LE, Epperson CN, Barber JP. A meta-analysis of treatments for perinatal depression. Clin Psychol Rev. 2011;31(5):839-849.
29. Stuart S, Koleva H. Psychological treatments for perinatal depression. Best Pract Res Clin Obstet Gynaecol. 2014;28(1):61-70.
30. Kittel-Schneider S, Reif A. Treatment of mental disorders in pregnancy and lactation: psychotherapy and other non-drug therapies. Neurologist. 2016;87(9):967-973.
31. Stahle S. Stahl’s Essential Psychopharmacology Prescriber’s Guide. 5th ed. New York, NY: Cambridge University Press; 2014.
32. Woo TM, Robinson MV. Pharmacotherapeutics for Advanced Practice Nurse Prescribers. Philadelphia, PA: F.A. Davis; 2016.
33. Rubinchik SM, Kablinger AS, Gardner JS. Medications for panic disorder and generalized anxiety disorder during pregnancy. Prim Care Companion J Clin Psychiatry. 2005;7(3):100-105.
34. Malm H, Artama M, Gissler M, Ritvanen A. Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstet Gynecol. 2011;118(1):111-120.
35. Stephansson O, Kieler H, Haglund B, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality. JAMA. 2013;309(1):48-54.
36. Palmsten K, Setoguchi S, Margulis AV, et al. Elevated risk of preeclampsia in pregnant women with depression: depression or antidepressants? Am J Epidemiol. 2012;175(10):988-997.
37. Ewing G, Tatarchuk Y, Appleby D, et al. Placental transfer of antidepressant medications: implications for postnatal adaptation syndrome. Clin Pharmacokinet. 2015;54(4):359-370.
38. Huybrechts KF, Bateman BT, Palmsten K, et al. Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn. JAMA. 2015;313(21):2142-2151.
39. Ellfolk M, Malm H. Risks associated with in utero and lactation exposure to selective serotonin reuptake inhibitors. Reprod Toxicol. 2010;30(2):249-260.
40. LactMed: A Toxnet Database.
41. Brucker MC, King TL. Pharmacology for Women’s Health. 2nd ed. Burlington, MA: Jones & Bartlett Learning; 2017.
All pregnant women should be screened for preeclampsia with blood pressure measurements throughout their pregnancy, according to the U.S. Preventive Services Task Force (USPSTF).
There is “adequate evidence” that screening for preeclampsia has a “substantial benefit” for both mother and infant and that any harms resulting from screening and treatment are “no greater than small,” stated Kristen Bibbins-Dimingo, PhD, MD, of the USPSTF, and colleagues.
Read more at MedPage Today.
Researchers at the University of Montreal Hospital Research Center (CRCHUM) have discovered a possible new explanation for female infertility. Thanks to cutting-edge microscopy techniques, they observed for the first time a specific defect in the eggs of older mice. This defect may also be found in the eggs of older women. The choreography of cell division goes awry, and causes errors in the sharing of chromosomes. These unprecedented observations are being published today in Current Biology. Read more.
WHEAT RIDGE — When Megan Wiedel was pregnant with her second child, she did just as her doctor told her to.
No raw fish. No soft cheeses. No lunch meat.
All along, a much bigger risk — one that her doctor never told her about — loomed.
So, unaware, when Wiedel’s first daughter sniffled, she held her. When Wiedel herself caught a cold in the second trimester, she shrugged it off. And when her second daughter, Anna, was born — at only 5 pounds, full term — and then failed the newborn hearing test, Wiedel and her husband tried not to worry as the pediatrician ordered more tests.
Two weeks later, the results came back. Anna would be deaf for the rest of her life. She might never be able to walk or even hold her head up. It was because she had a virus called CMV.
Wiedel hung up the phone and thought to herself: Why had she never heard about CMV?
“When you talk about it, it seems like it’s really rare,” Wiedel said. “But it’s not. A lot of kids have CMV.”
“That’s the hardest piece for me is that this is a preventable, prevalent, quiet disease.”
But, now, a small community of mothers and medical workers are trying to make CMV awareness a little less quiet.
At Children’s Hospital Colorado, physician assistant Shannon Hughes has developed an outpatient clinic for kids dealing with the aftereffects of CMV. The clinic has served about 40 kids in the past two years. Nearly all of the parents she meets had never heard of CMV before finding out that it would forever alter their children’s lives.
“Obviously, that has a big impact on them emotionally that they think they did something wrong and should have prevented it,” she said.
Neonatal nurse practitioner Erin Mestas, who also works at Children’s as well as at Poudre Valley Hospital, is also trying to raise awareness among both mothers and health care workers about CMV.
In some ways, CMV’s ubiquity accounts for its invisibility.
Most adults have been exposed to CMV at some point in their lifetimes, meaning they have antibodies to fight off a new CMV infection. For women with CMV antibodies, then, being exposed to the virus while pregnant is usually no big deal.
How can a nurse practitioner help a young woman addicted to heroin safely carry her pregnancy to term and deliver a healthy infant?
AT, a 23-year-old woman, presents to the obstetrician’s office in her rural hometown. As a nurse practitioner (NP) enters the examination room, AT cries out to her, “I can’t lose another baby!”
Three weeks previously, after learning that she was pregnant, AT voluntarily admitted herself to an inpatient treatment program at a regional medical center located 50 miles from her home. AT had been injecting heroin daily for the past 1.5 years. At the inpatient treatment program, AT insisted on undergoing detoxification from heroin because she knew that she would not be able to keep appointments for maintenance medication management.
She underwent medicated detoxification over 2.5 days. After a 5-day stay, she was discharged from the medical center and instructed to follow up with counseling services nearer to her home.
At the office visit, AT acknowledges to the NP that she has thought about heroin every minute since her discharge from the inpatient treatment program, and that her boyfriend, with whom she lives, is still using heroin. She admits that she has relapsed twice since the discharge, taking a hydrocodone/acetaminophen tablet one time and injecting methamphetamine one time. The NP wonders how she can best help AT safely carry her pregnancy to term and deliver a healthy infant.
Most heroin addictions begin with prescription opioid abuse. In 2010, approximately 210 million prescriptions were written for opioids in the United States.1 Twenty percent of the U.S. population have admitted using prescription opioids for nonmedical reasons. Opioid users who become addicted to the drugs but can no longer get them legally may turn to heroin because it is less costly on the black market.1 In 2013, more than 500,000 persons in this country admitted using heroin, an increase of 100% since 2006.1
Heroin has infiltrated small rural areas as well as urban areas because of its easy availability and relatively low cost.1-5 In fact, data indicate that heroin use has increased significantly in recent years among rural adolescents and young adults, with a report from the National Institute on Drug Abuse and the CDC describing a shift in heroin use from urban to rural areas.6-8
The demographics of heroin users are changing in other ways. Nowadays, a typical user may be a woman in a high income bracket living in a suburban area with private health insurance or she may be a woman living in poverty in a rural or urban area.1,5,8 In 2012, 34% of persons receiving treatment for heroin addiction in the U.S. were women.2,9 Women fortunate enough to be treated for heroin addiction will likely undergo psychological counseling, with or without maintenance therapy with an opioid agonist.2, 9-11 By contrast, many women living in rural areas have limited access to treatment.7
The NP reviews AT’s health history, including her recent hospitalization information. She asks AT if they can have an honest conversation about her heroin use and her life situation so that they can plan for the best care for her and the fetus.
AT has complex health and social problems that have led to and complicated her current situation. Her health history includes depression and anxiety. She was the victim of a sexual assault at age 14. Her parents were both heavy drinkers, and her three siblings have addictions to alcohol, drugs, or both. At age 20, AT was prescribed hydrocodone/acetaminophen after a back injury and became addicted to the opioid, which eventually led to her heroin use. She has had many failed attempts to quit using heroin on her own. As a result, AT has not been able to get or keep a job. She has no home or car and has been charged with two felony possessions in the past year. The year before, the Division of Family Services removed her two children from her care because of her addiction—prompting her outcry to the NP about her fear of losing another child.
When she learned she was pregnant with her third child, AT and her boyfriend were homeless. It was only after AT’s detoxification and hospital stay that her boyfriend’s mother agreed to let them stay with her as long as they both remained drug free. Her boyfriend, who is the father of her other two children as well, can hold odd jobs, but he spends most of his income on drugs.
AT’s initial physical examination and routine prenatal laboratory test findings are all normal. Test results for HIV, hepatitis C, chlamydia, gonorrhea, and syphilis are negative. AT completed the hepatitis B vaccination series with her previous pregnancy. A urine drug screen is negative. Ultrasonography (USG) confirms that she is at 10 weeks’ gestation.
The NP tells AT about an outpatient treatment program at the local hospital that provides free transportation to and from visits. AT agrees to be evaluated at the program and to consider maintenance therapy. An appointment is made for the next day. The NP also describes the healthcare providers (HCPs) who will be important team members in AT’s care. She will receive chemical dependency counseling, other mental health counseling, and management of her maintenance medication dosage at the outpatient treatment program. The NP will collaborate with the obstetrician at the office to provide her prenatal care and will consult regularly with maternal–fetal healthcare specialists at the regional medical center where she was previously hospitalized. AT provides written consent for all healthcare team members to have access to her electronic health record so that her care can be coordinated.
Chronic heroin use during pregnancy is associated with spontaneous abortion, placental insufficiency, intrauterine growth restriction, premature labor and/or birth, chorioamnionitis, preeclampsia, abruption placentae, oligohydramnios, premature rupture of membranes, intrauterine death, higher rates of cesarean sections, postpartum hemorrhage, and longer hospital stays. Newborns are at risk for neonatal abstinence syndrome (NAS).12-14
Opioid-assisted maintenance therapy (OAMT), the standard treatment for heroin addiction during pregnancy, can reduce the risks for obstetric and neonatal complications.15 In addition, the use of OAMT during pregnancy can prevent complications of illicit opioid use, narcotic withdrawal, and relapse; encourage prenatal care and drug treatment; reduce criminal activity; and avoid risks to the patient of associating with a drug culture.15, 16
Methadone, a full opioid agonist, is the most commonly used medication for OAMT during pregnancy. Methadone maintenance must be prescribed and dispensed on a daily basis by an addiction treatment specialist in a registered methadone treatment program. Buprenorphine, a partial opioid agonist, is another option for treatment during pregnancy. Buprenorphine may be prescribed in an office setting by a physician or NP who has undergone specific credentialing and in accordance with federal and state regulations. Advantages of treatment with buprenorphine over methadone include lower risk of overdose, ability to have outpatient treatment without required daily visits to a treatment program, and evidence of less severe NAS.15,16 Disadvantages include higher discontinuation rates, risks for sharing or selling the drug, and lack of long-term data on the effects of the medication on children exposed to it in utero.15,16
Medication dosages may need to be adjusted during pregnancy to avoid withdrawal symptoms that can cause fetal stress and may lead to maternal heroin use relapse. This need is especially true in the third trimester, when the woman may have a more rapid metabolism.15,16
The NP sees AT every 2 weeks over the next 6 weeks to establish rapport, offer support, and evaluate concerns. The NP consults with maternal– fetal healthcare specialists at the regional medical center to discuss a plan to monitor fetal well-being throughout the pregnancy. A USG schedule is established to evaluate fetal anatomy at 19 weeks and then every 6 weeks in the third trimester to monitor fetal growth.
AT and her addiction specialist decide that buprenorphine is an appropriate maintenance medication for her. AT attends individual and group counseling sessions at the outpatient treatment program 5 days a week and sees the addiction specialist weekly for her buprenorphine prescription for the first month of her treatment. The psychiatrist at the treatment center evaluates AT for depression and anxiety and prescribes sertraline to treat depression and quetiapine to aid sleeping. Over time, AT is able to reduce her counseling sessions to 3 days a week and her appointments for buprenorphine prescription to once monthly.
After the first few weeks of frequent visits, AT sees the NP every 4 weeks until 26 weeks’ gestation, every 2 weeks until 36 weeks’ gestation, and then weekly. The USG at 19 weeks shows normal fetal anatomy and growth. USGs at 28 and 34 weeks show fetal growth within normal limits. All routine laboratory test results are normal.
The NP and obstetrician discuss birthing plans with AT. She decides to remain on buprenorphine through labor and delivery, with a planned epidural for pain management. The pediatrician is available to oversee management of any NAS in the newborn. The maternal–fetal healthcare specialists at the regional medical center remain available for consultation.
At 38 weeks’ gestation, AT has an uncomplicated labor and vaginal birth of a baby girl weighing 6 lb 15 oz. Although breastfeeding is encouraged, AT decides to bottle feed. A social worker from the division of family services approves AT to take her baby home. AT and her daughter are discharged after 48 hours to stay with her boyfriend at his mother’s home. She decides she will use an intrauterine contraceptive so that she can continue to get her life in order without worrying about another pregnancy.
Breastfeeding is encouraged for mothers receiving OAMT as long as they abstain from the use of illicit substances.15,17 Breastfeeding supports mother–infant bonding and may reduce the severity and duration of NAS symptoms.18,19 Minimal levels of methadone or buprenorphine are found in breast milk, regardless of the maternal dosage.15,16 Both medications are considered safe during breastfeeding.15
The safety of illicit substances during breastfeeding is not possible to determine. Maintaining open lines of communication between the mother and her HCPs is essential so that she feels comfortable letting them know if she does relapse. If relapse does occur, the mother should be provided with assistance to transition to bottle feeding and guidance on how to taper milk production to prevent mastitis.17
Although AT was successful in stopping heroin and staying drug free for most of her pregnancy, she admitted having two occasions of illegal drug use during treatment. Her boyfriend initiated treatment, but he stopped after 2 weeks and started using heroin again. AT moved into a shelter for homeless pregnant women for a month, until her boyfriend returned to treatment. The motivation to have a healthy baby she could keep and easy access to a treatment center near home were vital to AT’s success.
Nurse practitioners providing care for reproductive-aged women may encounter some with heroin addiction, including during a pregnancy. NPs need to screen all women for alcohol and drug abuse at least annually and all pregnant women early in pregnancy. A nonjudgmental and supportive approach is important. Goals for pregnant women are to encourage regular prenatal care and drug treatment that includes OAMT and counseling. A collaborative approach includes prenatal care providers, addiction treatment specialists, mental health professionals, maternal–fetal healthcare specialists, and neonatal specialists. Using this collaborative approach, NPs in rural health settings can safely manage the care of pregnant women with heroin or opioid addiction.
Corinne Ann Coppinger is a women’s health nurse practitioner atMercy Hospital-Washington in Washington, Missouri. The author states that she does not have a financial interest in or other relationship with any commercial product named in this article.
1. Kane-Willis K, Schmitz SJ, Bazan M, Narloch VF. A multiple indicator analysis of heroin and opiate use in Missouri: 2001-2011. Missouri Recovery Network. March 2013.
2. Substance Abuse and Mental Health Services Administration. Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health. September 2015.
3. Kane-Willis K, Schmitz SJ, Bazan M, Narloch VF. Heroin use: National and Illinois Perspectives, 2008-2010. Roosevelt University. Institute for Metropolitan Affairs. August 2012.
4. U.S. Department of Justice Drug Enforcement Administration. National Drug Threat Assessment Summary. November 2014. info.
5. Substance Abuse and Mental Health Service Administration. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. September 2014.
6. Havens JR, Young AM, Havens CE. Nonmedical prescription drug use in a nationally representative sample of adolescents: evidence of greater use among rural adolescents. Arch Pediatr Adolesc Med. 2011;165(3):250-255.
7. Keyes KM, Cerdá M, Brady JE, et al. Understanding the rural-urban differences in nonmedical prescription opioid use and abuse in the United States. Am J Public Health. 2014;104(2):e52-e59.
8. CDC. Today’s Heroin Epidemic. Updated July 7, 2015.
9. Substance Abuse and Mental Health Service Administration. Substance Abuse Treatment Admissions by Primary Substance of Abuse, According to Sex, Age Group, Race, and Ethnicity. 2013.
10. Kampman K, Jarvis M. American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. J Addict Med. 2015;9(5):358-367.
11. National Institute on Drug Abuse. Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition). Updated December 2012.
12. Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Rockville, MD: Substance Abuse and Mental Health Services Administration (US); 2004.
13. Kaltenbach K, Berghella V, Finnegan L. Opioid dependence during pregnancy. Effects and management. Obstet Gynecol Clin North Am. 1998;25(1):139-151.
14. Maeda A, Bateman BT, Clancy CR, et al. Opioid abuse and dependence during pregnancy: temporal trends and obstetrical outcomes. Anesthesiology. 2014;121(6):1158-1165.
15. American College of Obstetricians and Gynecologists. Committee Opinion. Opioid Abuse, Dependence, and Addiction in Pregnancy. May 2012.
16. Wong S, Ordean A, Kahan M;Society of Obstetricians and Gynecologists of Canada. SOGC clinical practice guideline: substance use in pregnancy. Int J Gynaecol Obstet. 2011;114(2):190-202.
17. Reece-Stremtan S, Marinelli KA.ABM clinical protocol # 21: guidelines for breastfeeding and substance use or substance use disorder, revised 2015. Breastfeed Med. 2015;10(3):135-141.
18. McQueen KA, Murphy-Oikonen J, Gerlach K, Montelpare W. The impact of infant feeding method on neonatal abstinence scores of methadone- exposed infants. Adv Neonat Care. 2011;11(4):282-290.
19. Pritham UA. Breastfeeding promotion for management of neonatal abstinence syndrome. J Obstet Gynecol Neonat Nurs. 2013;42(5):517-526.
In June 2015, the FDA updated its recommendations for the labeling of drugs with respect to their use by pregnant women, lactating women, and females and males of reproductive potential. Healthcare providers caring for these populations, many of whom are taking prescription medications and biologics, need to be alert to these labeling changes.
Between 64% and 94% of pregnant women use a prescribed medication during their gestation.1,2 Among pregnant women who take prescribed medications, 80% do so during the first trimester,3 when fetal organ systems and structures are being formed. For many women who are managing chronic diseases, discontinuing the medications is not an option. In addition, because more than 50% of pregnancies in the United States are unintended,4 a large group of women are exposing their fetus to medications before they even realize that they are pregnant.
For postpartum patients on medications for chronic conditions, the choice to breastfeed their infant may pose a dilemma. Many of these women are advised to bottle-feed their infants instead, even if they are using medications safely taken by lactating women.5 Likewise, women who become ill during the lactation period may be counseled to stop breastfeeding their child if they need to take certain medications. According to the Centers for Disease Control and Prevention, 77% of infants born in the United States in 2010 were breastfed.6 During the same year, breastfeeding rates were 49% at 6 months and 27% at 1 year. Because many breastfeeding mothers are using prescription medications, these statistics translate to hundreds of thousands of infants potentially being exposed to these same medications for prolonged periods of time.
For reproductive-aged women who could become pregnant, counseling with regard to the potential impact of prescription or over-the-counter medications on pregnancy is often lacking. In the case of drugs that are known teratogens, past research indicates that women who had them prescribed, compared with women for whom safer medications were prescribed, did not receive contraceptive counseling in greater numbers.7 The impact of certain drugs on fertility, including chemotherapeutic medications, may not be discussed unless the effects are catastrophic. Finally, there is scant information on the need for reproductive health counseling for men in terms of medication use. Available counseling has often focused on the impact of illicit drugs on male factor infertility.8
The thalidomide tragedy, as it developed in the late 1950s and early 1960s in Europe, provided the impetus for tighter regulation of drugs by the FDA in the United States. In 1979, the FDA adopted a labeling system hat rated drugs for pregnant women using the well-known letter system: A, B, C, D, or X. At the time, the FDA did not provide a risk classification system for drugs taken during lactation. Pregnant women and nursing mothers were considered under the precaution areas of the counseling for medication use.9
Early in 1996, the FDA determined that the letter system was too simplistic.3 In addition, many drugs were allocated to different risk categories, depending on how the results of safety studies were being interpreted,10 resulting in confusion for healthcare providers (HCPs) and patients alike. The Teratology Society asked the FDA to develop a more comprehensive risk counseling strategy that would encompass all stages of the childbearing process.1 Changes to the system were proposed in 2008, and multiple public hearings and comment periods ensued. The Pregnancy and Lactation Labeling Rule (PLLR) was adopted and published in December 2014. Immediate compliance with the labeling rule has been required for all prescription drug and biologic products submitted to the FDA after June 30, 2015; phased-in compliance over 3-5 years is required for previously approved prescription drugs and biologics.11
The PLLR requires changes to the content and format for information presented in prescription drug labeling in the Physician Labeling Rule format to assist HCPs in assessing benefit versus risk and in subsequent counseling of pregnant women and nursing mothers who need to take medication, thereby enabling them to make informed decisions for themselves and their children. Subsections for pregnancy, lactation, and females and males of reproductive potential are required in the Use in Specific Populations section. Pregnancy letter categories have been removed.
Specific subheadings required in the pregnancy subsection include contact information for a pregnancy exposure registry for the drug (if one is available), a risk summary, clinical considerations, and available human and animal data. Some subheadings may be excluded if no relevant information is available.
This subheading is always required. If a drug is contraindicated in pregnancy, this fact must be listed first. Statements that describe risks for adverse developmental outcomes based on relevant human data, animal data, and the drug’s pharmacology are required. A cross-reference to additional details in the data subheading is included when applicable. Drugs not absorbed systemically following a particular route of administration include a statement that maternal use is not expected to result in fetal exposure to the drug. Drugs with more than one route of administration must include information related to each route.
This subheading provides information to further assist HCPs in prescribing decisions and risk–benefit counseling. When relevant, this subheading includes information about disease-associated maternal and/or embryo/fetal risk, dose adjustments during pregnancy and postpartum, maternal adverse reactions, fetal/neonatal adverse reactions, and labor/delivery. Inclusion of any disease -associated maternal and/or embryo/fetal risks is important for patient counseling and informed decision making. After all, HCPs and patients need to weigh the risks and benefits of not treating a disease/condition in pregnancy (e.g., depression, hyperlipidemia) versus the risks and benefits of taking a given drug during pregnancy.
When pharmacokinetic data support dose adjustment during pregnancy and/or postpartum, a summary of this information is provided. When applicable, cross-referencing to other labeling sections (e.g., Clinical Pharmacology, Dosage and Administration) for additional information is included.
Drug-associated adverse reactions that are unique to pregnancy or that occur with increased frequency or severity in pregnant women are described. When available, information on any clinical interventions to monitor or reduce maternal drug-associated adverse reactions is provided.
The fetal/neonatal adverse reactions described in this subsection are those based on the drug’s pharmacologic activity. The potential severity and reversibility of the adverse reaction, as well as interventions for monitoring and mitigation of the adverse reaction, are included.
If a drug is expected to affect labor or delivery, the labeling must provide available information about the drug’s effects on the mother, the fetus/neonate, and the duration of labor and delivery. An example is the use of an opioid during labor that may cause respiratory depression in the neonate. The labeling information includes the effect of dose, timing, and duration of exposure on the risk to the neonate and the use of naloxone to mitigate the reaction.
Data that provide the scientific basis for the information in the risk summary and clinical consideration subheadings are included. Human and animal data are presented separately. Data regarding adverse developmental outcomes, adverse reactions, and other adverse events related to the drug must be included.
This subsection must include a risk summary, applicable clinical considerations, and any available human and animal data. The term lactation refers to the biologic state during which the body produces and excretes milk. The term breastfeeding is used to refer to all human milk, whether received directly from the breast or as expressed milk.
This subheading is always required. If a drug is contraindicated during breastfeeding (e.g., radioisotopes), this fact must be stated first. Drugs not absorbed systemically by the mother following a particular route of administration must include a statement that maternal use is not expected to result in the child’s exposure to the drug during breastfeeding. Drugs with more than one route of administration must include information related to each route. For drugs absorbed systemically, available information on whether the drug and/or its active metabolites are present in human milk, effects of the drug on the breastfed child, and effects of the drug on milk production and/or excretion must be included. If a drug and/or its active metabolites are present in human milk, detailed information on actual or estimated infant daily dose based on exclusive breastfeeding must be provided. The risk summary must acknowledge when data are lacking.
A description of ways to minimize exposure of the breastfed child to systemically absorbed drugs that are used intermittently, in a single dose, or short term must be included. This description may include information on timing of administration of the drug relative to feeding, pumping sessions, or expressing for discarding. Specified time periods are based on the half-life of the drug and/or its active metabolite(s). Information on monitoring for adverse reactions must be included if available.
As with the pregnancy subheading, data on which the risk summary and clinical considerations are based for lactation and breastfeeding are provided.
This subsection is included if there are human or animal study data of potential drug-associated effects on fertility and/or pre-implantation loss. Recommendations for pregnancy testing and/or contraception may be based on concerns for adverse developmental outcomes if the drug is taken during pregnancy.
Healthcare providers can use the information provided in the new labeling to be better informed and enhance discussions about the benefits and risks of specific drugs with women who are pregnant or lactating or with patients of reproductive potential. The information contained in the PLLR may or may not be the same as that included in patient drug information.
Providers can utilize websites, mobile apps, and reference texts to focus counseling or answer patients’ questions (Table). These resources may be especially useful until the PLLR changes are fully implemented, as well as for supplemental information. As always, HCPs can consult with pharmacists regarding the pharmacokinetics and pharmacodynamics of a drug.
Kathleen M. Mahoney is a perinatal clinical nurse specialist at Robert Wood Johnson University Hospital in New Brunswick, New Jersey. The author states that she does not have a financial interest in or other relationship with any commercial product named in this article.
1. Ramoz LL, Patel-Shori NM. Recent changes in pregnancy and lactation labeling: retirement of risk categories. Pharmacotherapy. 2014;34(4):389-395.
2. Fantasia H, Harris A. Changes to pregnancy and lactation risk labeling for prescription drugs. Nurs Womens Health. 2015;19(3):266-270.
3. Mazur-Amirshahi M, Samiee-Zafarghandy S, Gray G, Van den Anker JN. Trends in pregnancy labeling and data quality for US-approved pharmaceuticals. Am J Obstet Gynecol. 2014;211(6):690e1-11.
4. Guttmacher Institute. Unintended Pregnancy in the United States. March 2016.
5. Saha MR, Ryan K, Amir LH. Postpartum women’s use of medicines and breastfeeding practices: a systemic review. Int Breastfeed J. 2015;10(28):1-10.
6. Centers for Disease Control and Prevention. Breastfeeding Report Card, 2013.
7. Schwartz EB, Postlethwaite DA, Hung YY, Armstrong MA. Documentation of contraception and pregnancy when prescribing potentially teratogenic medications for reproductive age women. Ann Intern Med. 2007;147(6): 370-376.
8. Fronczak CM, Kim ED, Barqawi AB. The insults of illicit drug use on male fertility. J Androl. 2012;33(4):515- 528.
9. Mosley JF 2nd, Smith LL, Dezan MD. An overview of upcoming changes in pregnancy and lactation labeling information. Pharm Pract (Granada). 2015;13(2):605.
10. Addis A, Sharabi S, Bonati M. Risk classification systems for drug use during pregnancy: are they a reliable source of information? Drug Saf. 2000;23(3):245-253.
11. Food and Drug Administration. Pregnancy and Lactation Labeling (Drugs) Final Rule. December 3, 2014.
12. Food and Drug Administration. Pregnancy, Lactation, and Reproductive Potential: Labeling for Human Prescription Drug and Biological Products — Content and Format. Washington, DC: Food and Drug Administration; 2015.
Thyroid disorders are fairly common in pregnancy, with the most common being hypothyroidism. Undiagnosed or inadequately treated hypothyroidism during pregnancy can have devastating consequences on the developing fetus. By contrast, early recognition and effective management of thyroid disorders in pregnancy can minimize risk for both maternal and neonatal complications.
Approximately 4% of women seeking prenatal care have previously been diagnosed with hypothyroidism.1 In iodine-sufficient areas such as the United States, the major cause of hypothyroidism in women of childbearing age is chronic autoimmune thyroiditis (Hashimoto’s disease).2 However, worldwide, iodine deficiency remains the most important cause of thyroid insufficiency.2,3 In addition, prior thyroidectomy; radioiodine therapy; use of medications such as amiodarone, anti-thyroid drugs, or lithium; and pituitary or hypothalamic disease can result in hypo-thyroidism.2
The prevalence of hypothyroidism diagnosed during pregnancy is 0.3%-0.5% for overt hypothyroidism and 2%-3% for subclinical hypothyroidism.2 Unrecognized or inadequately treated hypothyroidism during pregnancy has been associated with spontaneous abortion, preeclampsia, intrauterine fetal demise, preterm birth, low birth weight, postpartum hemorrhage, and irreversible detrimental effects on fetal neurodevelopment.2,4 The degree of neurocognitive deficit is related to the severity, duration, and gestational age at which hypothyroidism occurs.2,4,5
To reduce pregnancy complications and enhance optimal pregnancy outcomes, nurse practitioners (NPs) need to understand normal thyroid physiology, changes in thyroid physiology and laboratory values during pregnancy, fetal thyroid development and functioning, and strategies for effective pharmacologic management and thyroid monitoring for women with hypothyroidism during pregnancy. The purpose of this article is to increase this understanding.
The follicular cells are the functional cells of the thyroid gland. The follicular cells, in combination with iodine and the amino acid tyrosine, synthesize and secrete thyroid hormone (TH). TH synthesis is also controlled by serum iodide levels. The first step in TH synthesis is the concentration of iodide within the thyroid. Iodide is the inorganic form of iodine and the form in which iodine enters the thyroid. Iodide is oxidized to iodine by the enzyme thyroidal peroxidase (TPO) in the follicular cells.6
Thyroglobulin, a large glycoprotein synthesized by the follicular cells, is the precursor of TH. Thyroglobulin contains the amino acid tyrosine and is joined with one or two iodine molecules within the follicular cells. This joining, facilitated by TPO, results in the formation of iodotyrosine complexes.6 Two of these iodotyrosine complexes form the active THs: tri-iodothyronine (T3), which has three iodine molecules, and thyroxine (T4 ), which has four iodine molecules.
Thyroid hormone is stored in the thyroid as a colloid compound until needed. Of the TH that is synthesized, 90% is T4 , although T3 is physiologically more potent. Only a small amount of T3 is synthesized in the thyroid, with about 80% formed in the liver, kidneys, and muscles from de-iodination of T4 . T3 and T4 are transported in the circulation for the most part bound to thyroxine-binding globulin (TBG) and other plasma proteins such as albumin.6 Proteinbound TH acts as a reservoir, with free TH released as needed. Only free TH can enter target receptor cells, where it then influences a variety of metabolic processes in the body.
Thyroid hormone is regulated through a negative feedback loop involving the hypothalamus-pituitary- thyroid (HPT) axis. Thyrotropin-releasing hormone (TRH), synthesized in the hypothalamus, circulates via the hypothalamic-pituitary portal system to the anterior pituitary, where it stimulates release of thyroid-stimulating hormone (TSH).6 TRH is released in response to cold, stress, and decreased levels of free T4 (FT4 ). TSH, in turn, binds with receptors on the plasma membrane of the thyroid follicular cells and causes an immediate release and increase in synthesis of TH (Figure).6
In response to increased metabolic needs during pregnancy, thyroid activity and hormone production increase. The thyroid typically enlarges moderately due to hyperplasia of glandular tissue and increased vascularity. Human chorionic gonadotropin (hCG) secreted by the placenta, similar in structure to TSH, directly stimulates the maternal thyroid to produce TH. TBG levels increase beginning at about 20 weeks’ gestation as a result of increased estrogen levels. These two changes—that is, hCG stimulation of TH synthesis and increased TBG levels—lead to a decrease in TSH levels in the first trimester, with a return to baseline in the second trimester, and an increase in total TH levels* throughout pregnancy. Table 1 shows the physiologic changes in thyroid function during pregnancy.4,8,9
*Total TH includes both free and protein-bound forms; the increase in total TH is due mainly to the increased protein-bound forms of the hormone. The free circulating form of TH remains relatively unchanged throughout pregnancy.7,8
Nurse practitioners should note that non-pregnancy laboratory reference ranges do not apply to pregnant women. In fact, reference ranges change throughout pregnancy to reflect the physiologic changes occurring in thyroid function. Therefore, NPs should use trimester-specific, assay-specific normal ranges. If these ranges are unavailable, then these ranges for TSH should be used:3,4
• First trimester: 0.1-2.5 mIU/L
• Second trimester: 0.2-3.0 mIU/L
• Third trimester: 0.3-3.0 mIU/L
In addition, the elevated TBG seen in pregnancy interferes with immunoassays for FT4 levels. TSH is the most sensitive indicator of thyroid status in pregnant women.7
Fetal thyroid development and function can be divided into three overlapping phases: embryogenesis (phase I), functional development (phase II), and maturation (phase III) (Table 2).5,9,10 The thyroid is the first fetal endocrine gland to develop. It starts as a thickening at the base of the tongue and migrates down the neck to reach its final position in front of the trachea by 7 weeks’ gestation.9,10 Follicle cells form and begin thyroglobulin production by 8 weeks’ gestation. Although the fetal thyroid is able to start concentrating iodine and synthesizing iodothyronines by about 10 weeks’ gestation, little TH synthesis occurs until about 18 weeks’ gestation.9 During fetal development, T4 is the major TH being produced; T3 is not detected until the third trimester.9,10
The fetal hypothalamus is visible by 7 weeks’ gestation, with levels of TRH detectable by 9 weeks.10 The fetal pituitary is visible by 4 weeks, with TSH starting to become detectable at 10-12 weeks.10 The fetal HPT axis begins to function mid-gestation (18-20 weeks), with the fetus beginning to implement feedback mechanisms for TH production.9,10 During this time, fetal receptors for TRH and TSH become responsive. Further maturation of the HPT axis continues throughout the remainder of pregnancy.10
Maternal hypothyroidism is particularly harmful to the fetal brain in the first half of pregnancy, when fetal T4 production is low. TH is critical for neuron development and neural pathway organization.5,9 It is the transplacental transfer of T4 and iodine in the first trimester that promotes fetal brain development until the fetal thyroid becomes functional.5 Even during the second and third trimesters, when the fetal thyroid is producing T4 , much of the T4 needed for development is still of maternal origin.5,9
Overt hypothyroidism (OH) in pregnancy, evidenced by elevated TSH and low serum FT4, is linked to adverse fetal/obstetric outcomes. Stillbirth, preterm delivery, postpartum hemorrhage, and infants with neuropsychological and cognitive impairment have been reported in women with inadequately treated OH.2,4,5 OH should be treated with levothyroxine (LT4), with the goal of normalizing trimester-specific TSH values.4 Women who have been euthyroid on their LT4 dosages pre-pregnancy will need dosage changes throughout pregnancy in order to maintain the euthyroid state.
Subclinical hypothyroidism (SH) is by far the most frequent thyroid dysfunction occurring during pregnancy.11 SH is associated with elevated TSH and normal FT4. SH represents early, mild thyroid dysfunction. Sixty percent to 80% of these cases demonstrate the presence of antithyroid peroxidase antibodies, a marker of chronic thyroiditis (Hashimoto’s disease).12 Because of limited and conflicting data, controversy exists regarding the effects of SH on fetal/obstetric outcomes, including the need to screen or treat women with SH. Several obstetric complications have been associated with SH, with pregnancy loss being one of the most frequent.11,12 Other reported complications include gestational hypertension, preeclampsia, low birth weight, placental abruption, and postpartum hemorrhage, albeit at lower frequencies than those recorded in pregnant women with untreated OH.11,12
Early studies reported impaired cognitive development in infants born to mothers whose SH was inadequately treated, but not in infants born to women with adequately treated SH.12,13 However, in 2012, a large randomized controlled trial, the Controlled Antenatal Thyroid Screening Study, revealed no difference in the neurocognitive development of infants born to women who were screened and treated for SH versus those whose SH status was not revealed until after delivery.14 As a result, the American Congress of Obstetricians and Gynecologists (ACOG), the Endocrine Society, and the American Thyroid Association (ATA) do not recommend universal screening for thyroid disease in pregnancy.4,7 Instead, screening is recommended only in women who are at increased risk for OH, those with symptoms of thyroid disease, and those with a personal history of thyroid disease.
However, a lack of consensus exists regarding the need to treat SH in pregnant women. ACOG recommends against treatment for pregnant woman with SH because of a lack of research showing benefit.7 However, the Endocrine Society and the ATA recommend LT4 therapy for all women with SH.4,7
Levothyroxine, a Pregnancy Category A medication, remains the drug of choice for the treatment of all types of hypothyroidism. In typical cases, the LT4 dosage is increased as the pregnancy advances because of the hypermetabolic state that pregnancy induces.3,4 In fact, dosage requirements may increase by as much as 30%-50% during pregnancy, and these increases may be needed as early as the fifth week of gestation.3 Replacement therapy in dosages of 1-2 mcg/kg/day, or about 100 mcg/day, is recommended.12,137 NPs should check patients’ TSH levels every 4-6 weeks during pregnancy so that dosages can be adjusted as necessary. The goal is to maintain maternal serum TSH in the trimester-specific range.3,4 Because only minimal amounts of LT4 cross the placenta after the first trimester, the fetus is not at risk for thyrotoxicosis from maternal LT4 replacement.4,8
Because of differences, albeit subtle, in bioavailability among LT4 formulations, patients should stay with one formulation when possible. NPs should educate patients to take LT4 on an empty stomach—45 minutes before consumption of food, beverages, or other medications—for optimal absorption.3,15 Prenatal vitamins, calcium, and iron can interfere with the absorption of LT4 and should be avoided within 4 hours of taking LT4.3 Likewise, medications used to treat gastroesophageal reflux, including histamine-2 blockers, proton pump inhibitors, and antacids, can decrease LT4 absorption.15 Finally, NPs need to ascertain whether pregnant women are using any herbal products that contain lemon balm, also known as bee balm, honey plant, or sweet balm.16 Lemon balm, used as a tea or oil to treat anxiety, insomnia, and indigestion, is known to have anti-TSH effects, and can prevent T4 absorption from the small intestine.15,16
After delivery, the LT4 requirement drops immediately; women who were on LT4 prior to pregnancycan revert to their pre-pregnancy dosage.3,5 Women who were started on LT4 to treat OH during their pregnancy can likely reduce their dosage to half that taken just before delivery.3,4,7 If they were receiving LT4 to treat SH, the medication can be stopped and thyroid function tests performed in 6 weeks to determine whether further treatment is required.3,4,7 LT4 is considered safe to use during lactation.3,17
Iodine is a critical trace element required for TH synthesis; both maternal and fetal TH production depends on an adequate dietary intake of iodine.7 Iodine deficiency may be a factor contributing to concurrent maternal and fetal hypothyroidism. In the United States, iodized salt is an important source of iodine. (About 70% of salt sold for household use is iodized.) Other common dietary sources of iodine in the U.S. are dairy products, seafood, eggs, meat, and poultry.4 The prevalence of iodine deficiency is lowest in the Americas (10%) and highest in Europe (59.9%).3,8
In pregnancy, because of an increase in renal excretion of iodine and transfer of iodine to the placenta and fetus, the thyroid triples its uptake of iodine.8 Dietary iodine requirements are therefore increased during pregnancy. Although most U.S. women have adequate iodine intake to meet the increased demand for both maternal and fetal TH production, it is difficult to identify those who are at risk for or who may have mild to moderate iodine deficiency.4
In cases of mild to moderate iodine deficiency, the thyroid decreases synthesis of T4 in favor of T3 , the T3 levels remain normal, and circulating TSH does not rise. Thyroid function tests may indicate euthyroidism even though the amount of T4 available to the fetus may be insufficient.3 Severe iodine deficiency in pregnancy can cause hypothyroidism, poor pregnancy outcome, irreversiblemental retardation, and cretinism. Recent studies show that even mild iodine deficiency has been associated with impaired neurologic outcomes in children.3,8,9
The World Health Organization recommends an intake of 250 mcg/day of iodine during pregnancy and breastfeeding.4,18,19 To achieve this level, the ATA recommends that women in North America who are planning pregnancy or are pregnant or breastfeeding take a daily supplement containing 150 mcg of iodine.1,4 Among the roughly 200 prenatal vitamin brands marketed in the U.S., only half contain iodine, and among the products that do contain iodine, not all contain the recommended dose.4 In addition, studies have shown about 20% of pregnant woman do not take their prenatal vitamin supplement.1,4 NPs need to educate their pregnant patients about why they need to take all the supplements that are prescribed for them.
The normal physiologic changes in the thyroid during pregnancy occur to compensate for increased maternal metabolic demands and to provide adequate TH and iodine for fetal brain development. Hypothyroidism in pregnant women presents unique challenges related to these changes. The physiologic changes affect both interpretation of thyroid studies and dosing of LT4 during pregnancy. The goal of treatment is to restore euthyroidism as soon as possible and to maintain TSH in the trimester-specific reference range. NPs need to consider these key practice points:
• Thyroid disease is the second most common endocrine disorder of pregnancy (following diabetes).
• Iodine requirements increase in pregnancy and lactation. Women should be advised to take a prenatal vitamin that contains 150 mcg of iodine in its formulation.
• Under ideal circumstances, women with hypothyroidism should have their LT4 dose optimized prior to pregnancy and then reviewed each trimester.
• The dosage of LT4 needed to maintain a euthyroid state increases during pregnancy.
• Women with OH should be treated to maintain serum TSH in the trimester-specific goal range.
• Controversy exists regarding whether SH in pregnant women should be treated.
• T4 drops immediately following delivery; the LT4 dosage will need to be readjusted.
Carol A. Botwinski is Director/Chair of the Department of Nursing at the University of Tampa in Tampa, Florida. The author states that she does not have a financial interest in or other relationship with any commercial product named in this article.
1. Haddow JE. The new American Thyroid Association Guidelines for thyroid disease during pregnancy and postpartum: a blueprint for improving prenatal care. Thyroid. 2011;21(10): 1047-1048.
2. Negro R, Mestman JH. Thyroid disease in pregnancy. Best Pract Res Clin Endocrinol Metab. 2011; 25(6):927-943.
3. Klubo-Gwiezdzinska J, Burman K, Van Nostrand D, Wartofsky L. Levothyroxine treatment in pregnancy: indications, efficacy, and therapeutic regimen. J Thyroid Res. 2011;1-12.
4. Stagnaro-Green A, Abalovich M, Alexander E, et al; American Thyroid Association Taskforce on Thyroid Disease during Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081-1104.
5. Mann N. Congenital hypothyroidism – what’s new? Paediatr Child Health. 2011;21:295-300.
6. Matfin G. Disorders of endocrine control of growth and metabolism. In: Porth C, ed. Essentials of Pathophysiology. 4th ed. Philadelphia, PA: Wolters Kluwer; 2015:767-792.
7. American College of Obstetricians and Gynecologists. Practice bulletin No. 148: Thyroid disease in pregnancy. Obstet Gynecol. 2015; 125(4):996-1005.
8. Girling J, Sykes L. Thyroid disorders and other endocrinological disorders in pregnancy. Obstet Gynaecol Reprod Med. 2013;23:171-179.
9. Blackburn S. Maternal, Fetal, & Neonatal Physiology: A Clinical Perspective, 4th ed. St. Louis, MO: Saunders; 2012.
10. Rose S. Thyroid disorders. In: Martin R, Fanaroff A, Walsh M, eds. Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. 9th ed. St. Louis, MO: Elsevier; 2011:1556-1584.
11. McLeod D, McIntyre H. Subclinical hypothyroidism and related biochemical entities in pregnancy: implication and management. Obstet Med. 2010;3:139-144.
12. Cooper D, Biondi B. Subclinical thyroid disease. Lancet. 2012; 379(9821):1142-1154.
13. Behrooz HG, Tohidi M, Mehrabi Y, et al. Subclinical hypothyroidism in pregnancy: intellectual development of offspring. Thyroid. 2011;21(10): 1143-1147.
14. Lazarus JH, Bestwick JP, Channon S, et al. Antenatal thyroid screening and cognitive function. N Engl J Med. 2012:366(6):493-501.
15. Eligar P, Eligar V. Levothyroxine: factors affecting its intestinal absorption and metabolism. W London Med J. 2011;3:9-14.
16. University of Maryland Medical Center. Lemon Balm. Updated May 7, 2013.
17. National Institute of Health. Toxnet. Substance Name: Levothyroxine.
18. World Health Organization. Iodine Supplementation in Pregnant and Lactating Women. 2015.
19. World Health Organization. Joint statement by the WHO and UNICEF: Reaching optimal iodine nutrition in pregnant and lactating women and young children. 2007.
About 68% of invasive cervical cancer cases diagnosed in the United States involve women of childbearing age. Current treatment options for young patients with cervical cancer may cause hormonal and/or structural modifications to the reproductive system that could compromise pregnancy potential. Although clinical guidelines are available to help preserve fertility in these patients, gaps in practice remain, suggesting that the fertility-sparing needs of cervical cancer survivors are not routinely met. The authors provide nurse practitioners with current evidence about fertility-sparing treatments and with counseling considerations for young cervical cancer survivors.
Key words: cervical cancer survivor, fertility-sparing treatment, pregnancy, infertility, conization, trachelectomy
Cervical cancer was once the leading cause of gynecologic cancer in the United States. Following introduction of the use of the Pap smear in the 1940s, the incidence of cervical cancer has declined dramatically.<sup.1 Because use of the Pap smear is so effective and so widespread, the diagnosis of cervical cancer, when it is found, is usually made when a woman is younger (and still fertile) and when the disease is at an earlier stage (and therefore more easily treated).
In 2014, the American Cancer Society projected that 12,360 new cases of cervical cancer would be diagnosed in the U.S.2 Approximately 68% of cervical cancer cases are diagnosed in women of childbearing age.3,4 For young women, a diagnosis of cervical cancer once meant a hysterectomy and loss of the ability to bear a child. Today, fertility-sparing treatment (FST) options exist for women with early-stage cervical cancer, as well as more advanced fertility preservation and assisted reproductive technology (ART) approaches for those who are not candidates for FST.5
Young cervical cancer survivors may not know about FST options, and thus fear that treatment for cancer may compromise their future ability to conceive.6 Survivors also tend to be anxious about pregnancy outcomes after completing cancer treatment.7,8 Evidence suggests that they will want to discuss future fertility options with their healthcare provider (HCP).9 The American Society of Clinical Oncology (ASCO) and the American Society of Reproductive Medicine have published guidelines recommending that, prior to treatment, HCPs educate patients diagnosed with cervical cancer about the treatment’s potential effects on their fertility, along with fertility-preservation options.10,11 However, many HCPs are uninformed themselves and do not routinely offer fertility-preservation counseling prior to cancer treatment.12,13 The purpose of this article is to provide HCPs with current evidence about FST for cervical cancer and with counseling recommendations for young cervical cancer survivors.
A Pap smear is used to screen for cervical cancer but not to make the diagnosis. A histology report from a cervical biopsy confirms the diagnosis and type of cervical cancer. After diagnosis, a workup is done to determine disease stage (Table 1).5
A clinical staging system is used for cervical cancer (rather than the surgical criteria used for most other gynecologic cancers). Two different staging systems are available. The International Federation of Gynecology and Obstetricsn (FIGO) staging system is based on a physical examination, diagnostic procedures, and imaging studies. Stages IA1, IA2, and IB1 are considered early stages of cervical cancer.5,14 In stages IA1 and IA2, cancer is confined to the cervix and diagnosed only microscopically. Stage IB1 describes cancer confined to the cervix with a clinically visible tumor ?4 cm, stromal invasion that further describe tissue involvement (Table 2).5,15,16
The National Comprehensive Cancer Network (NCCN) recommends cone biopsy or radical trachelectomy for treatment for up to cervical cancer stage IB1 in women who want to preserve their fertility.5 This recommendation has not always existed; trends in surgical management of low-risk early-stage lesions have changed over the past 20 years. Hysterectomy was the only cure for cervical cancer stage IB1 until Dargent developed the fertility-sparing radical vaginal trachelectomy (RVT) technique in 1994.,sup>17 Prior to RVT, women with stage IA1 or IA2 lesions were the only cervical cancer survivors able to preserve their fertility.15
This term refers to a wedge-shaped excision of cervical tissue for both diagnostic evaluation and removal of abnormal tissue. Two methods of obtaining a cone biopsy with fertility sparing in mind are cold knife conization (CKC) and the loop electrosurgical excision procedure (LEEP). Cone biopsy is used to treat small lesions when there is no risk of dissecting across a gross neoplasm.5 Given that adequate margins and correct orientation are obtained, CKC and LEEP are appropriate measures for cervical cancer stage IA1 without lymphovascular space invasion.5 Negligible risks exist for cervical cancer stage IA1 recurrence following this treatment.5
Potential risks regarding future fertility following a cone biopsy include cervical stenosis and preterm delivery.18,19 Cervical stenosis occurs in 2%-3% of patients after CKC and in 3%-4% post-LEEP.19 Because of scar tissue formation that can occur after a cone biopsy, fertility may be compromised until the tissue is removed from the cervix. Long and Leeman19 reported that a history of a cone biopsy increased the odds of a preterm delivery by 2.19 (95% confidence interval, 1.93-2.49); risk correlated with the depth of the transformation zone removed. In this study, a greater risk existed for preterm delivery when a cone biopsy sample was thicker than 1.2 cm and larger than 6 cm2. However, Bevis and Biggio18 reported that evidence for the effects of conization procedures on fertility was conflicting because of the different types of procedures performed and the varying quality of control groups.
Fanfani et al20 performed a multicenter retrospective analysis of reproductive outcomes in 23 early-stage cervical cancer survivors who had undergone conization treatment. Among 10 patients who tried to conceive, 6 achieved a spontaneous pregnancy and 4 received conception assistance via in vitro fertilization and embryo transfer (1 of whom achieved a pregnancy). In total, 70% of the young survivors achieved a pregnancy after cone biopsy treatment.
This fertility-sparing surgical procedure is performed to eradicate cervical cancer. In an RVT, the uterine corpus, ovaries, and Fallopian tubes are preserved, but the cervix, upper portion of the vagina, and the supporting ligaments are removed. A cerclage is placed at the location of the isthmus to close the opening of the uterus.7 RVT is an option for patients with stage IA2 or IB1 lesions 2 cm and ?4 cm, and provides a larger resection of the parametria.5
Most women who undergo RVT are able to conceive spontaneously, but a small number will require conception assistance.21 The 5-year cumulative pregnancy rate for women trying to conceive post-RVT is 52.8%; the cervical cancer recurrence rate after the procedure continues to be low.7 Potential risks of either trachelectomy procedure with regard to future fertility include miscarriage, preterm delivery, anovulation, and isthmic stenosis.7,21
Koh et al5 reported that, worldwide, more than 300 pregnancies have been confirmed following a trachelectomy for cervical cancer. Risk for second trimester miscarriage following a trachelectomy is 10%. However, 72% of women have carried a pregnancy to term. Park et al22 conducted a retrospective chart review of 55 young early-stage cervical cancer survivors who underwent laparoscopic abdominal trachelectomy. Ten of 18 patients attempting a pregnancy conceived; 6 of the 10 experienced preterm delivery. Overall, 55.6% of the survivors achieved a pregnancy, with 60% delivering preterm.
Most women with cervical cancer at stage IB2 or greater are not candidates for FST. Radiation therapy is most often used for patients with higher stage IB disease, often called bulky disease. Radiation therapy is also used following a primary radical hysterectomy or in conjunction with chemotherapy in advanced disease. Radiation that includes the ovaries can damage oocyte quality and sex hormone production. Chemotherapy is not used in patients with milder forms of cervical cancer who are considering FST options.
Women planning to undergo radiation still have fertility preservation options, including the ART procedures of oocyte or embryo cryopreservation prior to cancer treatment.23 Cryopreservation of unfertilized oocytes, as opposed to embryos, may be considered for patients who do not have a male partner, do not wish to use donor sperm, or have religious or ethical reasons for avoiding embryo freezing. Because oocytes are highly sensitive to radiation injury, a procedure called oophoropexy (ovarian transposition) may be used. With oophoropexy, ovaries are sutured to the posterior uterus to protect them during pelvic radiation.
Before or after cancer treatment, survivors may benefit from ovarian stimulation medications that help promote follicular development. However, guidelines from both the American Congress of Obstetricians and Gynecologists and ASCO indicate insufficient evidence regarding the effectiveness of gonadotropin-releasing hormone analogs to suppress and protect ovarian function during cytotoxic treatment.24
These counseling recommendations concerning fertility preservation were issued by ASCO: (1) Assume that patients with cancer want to discuss fertility preservation; address the possibility of infertility before cancer treatment starts and work with an interdisciplinary team to formulate a plan and make appropriate referrals; (2) Present oocyte and embryo cryopreservation as established fertility preservation methods; (3) Discuss the option of oophoropexy when pelvic radiation will be performed; (4) Inform patients of their individual risk for infertility, based on disease stage and treatment, as high, medium, low, or nonexistent; and (5) Inform patients about the use of conservative gynecologic surgery and radiation options.11
Several organizations and advocacy groups are available for young cervical cancer survivors with fertility concerns both before and after treatment (Table 3). ASCO created a video that can educate young patients about fertility preservation options and support networks.
A woman who has undergone FST for cervical cancer faces many challenges. She may experience distress, depression, anxiety, and/or fear, and, depending on her own innate coping ability and her support system, may require psychological assessment and referral. HCPs can evaluate patients for these psychological reactions with tools such as the Functional Assessment of Cancer Therapy-Cervical Cancer Subscale and the NCCN Distress Thermometer for Patients, and make referrals as needed.
Cervical cancer and its treatment can adversely affect sexual health, causing problems such as decreased libido, fatigue, vaginal stenosis, and dyspareunia (Table 4).25-27 Many women hesitate to mention sexual problems on their own, so HCPs need to inquire about them and make referrals to a counselor who specializes in sex therapy, a gynecologist, or a physical therapist who specializes in pelvic pain and sexual dysfunction.* Many of the physical and psychological complaints involving sexual function resolve with-in the first year after treatment but may last up to 2 years or longer.25,26
With regard to dyspareunia in particular, asking patients whether they experience it is the first step in helping resolve the problem. Nonpharmacologic and pharmacologic treatments, along with alternate positioning during intercourse, can be offered. HCPs can recommend over-the-counter vaginal moisturizers and lubricants to assist with vaginal dryness, dyspareunia, and sexual stimulation. In addition, prescription-strength topical lidocaine, estradiol vaginal cream, or ospemifene may help.
Undergoing ART can be arduous for women who endure painful and costly treatments. As of 2008, only 15 states have mandates that require health insurance carriers to provide full or partial coverage of costs related to infertility treatments.28 Most couples or individual women pay for infertility treatments out of pocket. Each ART cycle requires a woman to invest her body, mind, time, and money to realize her dream of motherhood, and she may be placing herself at risk for developing anxiety and depression.29-31
Even if a woman succeeds in achieving pregnancy through ART, the process is often fraught with anxiety.32,33 Young female cancer survivors have reported that they have a hopeful yet worried outlook on fertility and motherhood.34 This worry is especially true for cervical cancer survivors who have had trachelectomy surgery, as reported by Lloyd et al,7 wherein several participants described how they were fearful during pregnancy and attempted to be “model” pregnant women who followed every recommendation to reduce risks associated with preterm labor and miscarriage.
Consultations with specialists in reproductive endocrinology and/or high-risk obstetrics may be helpful. Pregnancy loss after infertility treatment can be devastating to these women, who view their pregnancy as “precious” and a “miracle,” and can have a profound impact on their psychological well-being.7 HCPs should promptly refer these cancer survivors to mental health counselors who specialize in infertility and pregnancy loss.
Sixty-eight percent of cervical cancer cases diagnosed in the U.S. involve reproductive-aged women.2 Many of these women desire future pregnancies and want to discuss treatment options and future fertility. An interdisciplinary care approach for these women is necessary, with an emphasis placed on both successful cancer treatment and fertility preservation. FST options are available for women with early-stage cancer up to IB1. Fertility preservation procedures are available for women who are not candidates for FST. National guidelines are available regarding treatment and counseling for reproductive-age women with cervical cancer. The role of HCPs such as women’s health nurse practitioners is to educate young cervical cancer patients and survivors about their treatment options, manage pre- and post-treatment care, and provide referrals to specialists as needed.
Aimee Chism Holland is Assistant Professor, Coordinator of the Dual Adult/Gerontology Primary Care and Women’s Health Nurse Practitioner Specialty Track; Deborah Kirk Walker is Assistant Professor; Sigrid Ladores is Assistant Professor; and Karen Meneses is Professor and Associate Dean for Research, all at the School of Nursing at The University of Alabama at Birmingham. The authors state that they do not have a financial interest in or other relationship with any commercial product named in this article.
1. American Cancer Society. What is cervical cancer? October 2014. www.cancer.org/cancer/cervicalcancer/detailedguide/cervical-cancer-what-is-cervical-cancer
2. American Cancer Society. What are the key statistics about cervical cancer? October 2014. www.cancer.org/
3. Centers for Disease Control and Prevention. Gyencological Cancers: What are the Risk Factors? March 2014. www.cdc.gov/cancer/cervical/basic_info/risk_factors.htm
5. Koh WJ, Greer BE, Abu-Rustum NR, et al. Cervical cancer. J Natl Compr Canc Netw. 2013;11(3):320-343.
6. Kola S, Walsh JC. Patients’ psychological reactions to colposcopy and LLETZ treatment for cervical intraepithelial neoplasia. Eur J Obstet Gynecol Reprod Biol. 2009;146(1):96-99.
7. Lloyd PA, Briggs EV, Kane N, et al. Women’s experiences after a radical vaginal trachelectomy for early stage cervical cancer. A descriptive phenomenological study. Eur J Oncol Nurs. 2014;18(4):362-371.
8. Wenzel L, Dogan-Ates A, Habbal R, et al. Defining and measuring reproductive concerns of female cancer survivors. J Natl Cancer Inst Monogr. 2005(34):94-98.
9. Maltaris T, Seufert R, Fischl F, et al. The effect of cancer treatment on female fertility and strategies for preserving fertility. Eur J Obstet Gynecol Reprod Biol. 2007;130(2):148-155.
10. Ethics Committee of American Society for Reproductive Medicine. Fertility preservation and reproduction in patients facing gonadotoxic therapies: a committee opinion. Fertil Steril. 2013;100(5):1224-1231.
11. Loren AW, Mangu PB, Beck LN, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31(19):2500-2510.
12. Gorman JR, Usita PM, Madlensky L, Pierce JP. Young breast cancer survivors: their perspectives on treatment decisions and fertility concerns. Cancer Nurs. 2011;34(1):32-40.
13. Kim SS, Klemp J, Fabian C. Breast cancer and fertility preservation. Fertil Steril. 2011;95(5):1535-1543.
14. Lea JS, Lin KY. Cervical cancer. Obstet Gyncol Clin North Am. 2012;39(2):233-253.
15. American Joint Committee on Cancer. What is Cancer Staging? 2014. https://cancerstaging.org/references-tools/Pages/What-is-Cancer-Staging.aspx
16. Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 2009;105(2):103-104.
17. Dargent D, Mathevet P. Schauta’s vaginal hysterectomy combined with laparoscopic lymphadenectomy. Baillieres Best Pract Res Clin Obstet Gynaecol. 1995;9(4):691-705.
18. Bevis KS, Biggio JR. Cervical conization and the risk of preterm delivery. Am J Obstet Gynecol. 2011;
19. Long S, Leeman L. Treatment options for high-grade squamous intraepithelial lesions. Obstet Gynecol Clin North Am. 2013;40(2):291-316.
20. Fanfani F, Landoni F, Gagliardi ML, et al. Sexual and reproductive outcomes in early stage cervical cancer patients after excisional cone as a fertility-sparing surgery: an Italian experience. J Reprod Infertil. 2014; 15(1):29-34.
21. Wong I, Justin W, Gangooly S, et al. Assisted conception following radical trachelectomy. Hum Reprod. 2009;
22. Park JY, Kim DY, Suh DS, et al. Reproductive outcomes after laparoscopic radical trachelectomy for early-stage cervical cancer. J Gynecol Oncol. 2014;25(1):9-13.
23. Wang ET, Pisarska MD. Preserving fertility in women facing cancer. Contemporary OB/GYN. 2013;58(12):22-32.
24. American Congress of Obstetricians and Gynecologists. Committee opinion no. 607: gynecologic concerns in children and adolescents with cancer. Obstet Gynecol. 2014; 124(2 pt 1):403-408.
25. Carter J, Sonoda Y, Baser RE, et al. A 2-year prospective study assessing the emotional, sexual, and quality of life concerns of women undergoing radical trachelectomy versus radical hysterectomy for treatment of early-stage cervical cancer. Gynecol Oncol. 2010;119(2):358-365.
26. Froeding LP, Ottosen C, Rung-Hansen H, et al. Sexual functioning and vaginal changes after radical vaginal trachelectomy in early stage cervical cancer patients: a longitudinal study. J Sex Med. 2014;11(2):595-604.
27. Miller M. Sexual Dysfunction in Women. March 2014. www.clinicalkey.com
28. Henne MB, Bundorf MK. Insurance mandates and trends in infertility treatments. Fertil Steril. 2008;89(1): 66-73.
29. Gonzalez LO. Infertility as a transformational process: a framework for psychotherapeutic support of infertile women. Issues Ment Halth Nurs. 2000;21(6):619-633.
30. Sandelowski M. A theory of the transition to parenthood of infertile couples. Res Nurs Health. 1995;18(2): 123-132.
31. Su TJ, Chen YC. Transforming hope: the lived experience of infertile women who terminated treatment after in vitro fertilization failure. J Nurs Res. 2006;14(1):46-54.
32. Hammarberg K, Fisher JR, Wynter KH. Psychological and social aspects of pregnancy, childbirth and early parenting after assisted conception: a systematic review. Hum Reprod Update. 2008;14(5):395-414.
33. Ladores S. The early postpartum experience of previously infertile mothers. Podium presentation at: 25th International Research Congress, Sigma Theta Tau International: Engaging Colleagues – Improving Global Health Outcomes; July 2014; Hong Kong.
34. Gorman JR, Bailey S, Pierce JP, Su HI. How do you feel about fertility and parenthood? The voices of young female cancer survivors. J Cancer Surviv. 2012;6(2):200-209.
*Editor’s Note: In the current issue of Women’s Healthcare: A Clinical Journal for NPs, Tammy M. DeBevoise, PT, DPT; Angela F. Dobinsky, PT, DPT; Caitlin B. McCurdy-Robinson, PT, DPT; Christina M. McGee, PT, DPT, ATC, LAT; Cody E. McNeely, PT, DPT; Sara K. Sauder, PT, DPT; and Kimberlee D. Sullivan, PT, DPT, WCS, BCB-PMD present a feature-length article on pelvic floor physical therapy.