Amber J Tresca

Crohn's disease and ulcerative colitis are the two main forms of inflammatory bowel disease (IBD), which are incurable, chronic, idiopathic autoimmune conditions that primarily affect the digestive tract. IBD presents a number of concerns for women during pregnancy, particularly when it comes to managing medications and any related conditions. However, there have been great strides in making pregnancy and birth safer for mothers and their babies. Women with IBD who become pregnant will need to be followed closely by both their gastroenterologists and their obstetricians.

In previous years, women with IBD were counseled against becoming pregnant and having children. It was thought that women with Crohn's disease, in particular, may experience an unfavorable outcome, such as premature birth, birth defects, and a worsening of the IBD. It was thought that ulcerative colitis was associated with infertility. It is now known that the risks are not as significant as was once thought, especially when the IBD is managed properly.

These misperceptions still exist in the public consciousness, and some women with IBD may delay or forgo pregnancy, thinking that their chances of having a healthy baby are low,

 or that they will be passing their disease on to a child. Women with IBD tend to have smaller families than women who do not have IBD, although this may be attributable in part to the racial and educational status of IBD patients.

Family members of patients with IBD do have a higher risk (anywhere from 3 to 20 times greater) of developing the disease than the general population. Even so, most patients (greater than 80%) have no family members with IBD.

 However, women who have a recent diagnosis of IBD (between 0 and 6 months) should be counseled to delay a pregnancy for about 6 months because of a risk of preterm birth.

IBD is often spoken of as a "disease of young people." There is a spike in the diagnosis of IBD in adolescents and young men and women between the ages of 15 and 25 years. These are some of the prime childbearing years for women, and given that IBD is not an uncommon condition, obstetricians are likely to see young pregnant patients with Crohn's disease and ulcerative colitis.

IBD is characterized by periods of flare-ups and remission, with the goal of treatment being the induction of remission with mucosal healing in the digestive tract. The state of the IBD (the presence of either remission or active disease) at the time of conception is important to the course of the pregnancy.

 Because patients and their babies may do best when IBD is in remission, planning for conception when the IBD is quiescent should be recommended to patients considering a pregnancy.

In general, studies on pregnant women with IBD show that when the disease is active at the time of conception, it tends to continue to be active during the course of the pregnancy.

 For women with IBD who are experiencing remission at the time of conception, the remission tends to continue.

 Women who have severely active Crohn's disease during pregnancy have been shown to have an increased risk of experiencing preterm birth.

 However, pregnant women with active Crohn's disease do not appear to have a higher risk of having a baby with low birth weight, intrauterine growth restriction, or congenital defects.

 Women with IBD should be counseled to avoid a pregnancy within at least 3 months of their last active disease flare-up.

The evidence is conflicting regarding how disease activity during pregnancy affects IBD after delivery, but the largest study done to date reports that women may experience fewer flare-ups after a pregnancy.

 Women with long-standing Crohn's disease and those with ulcerative colitis may have a higher risk of experiencing an IBD flare-up during pregnancy.

 There is also a risk that ulcerative colitis may flare up again after delivery.

Women who experience a flare-up of IBD during pregnancy will need treatment to have the best possible outcome and to avoid complications such as low birth weight and preterm birth. There are several treatments for IBD (with the exception of methotrexate and thalidomide) that can be used relatively safely during pregnancy.

5-Aminosalicylates (sulfasalazine, mesalamine).

 Sulfasalazine and mesalamine are in Pregnancy Category B, and it is generally thought that these medications can safely be used to treat IBD in pregnant women. Several studies done on women with IBD taking sulfasalazine during pregnancy have not been able to discern between the effects of the medication versus the effects of the disease on pregnancy outcome. While a few of these studies have shown a slight increase in stillbirth, preterm birth, congenital malformation, and preterm delivery,

 others have shown no association with poor pregnancy outcomes.

 However, sulfasalazine interferes with the body's ability to absorb folic acid, and both pregnant women with IBD and those women considering pregnancy who take sulfasalazine should receive appropriate folic acid supplements. 

 Some studies have shown that the use of 6-MP and azathioprine in pregnant women with IBD is associated with an increased risk of preterm birth, congenital defects, and perinatal mortality, but the effects of the disease versus the effects of the drug could be confounding the results.

 Several other studies have not found any relationship between 6-MP or azathioprine and preterm birth, low birth weight, neonatal adverse outcomes, or congenital abnormalities.

 These immunosuppresive drugs are Pregnancy Category D, are known to cross the placenta, and have been found in cord blood. There is some concern that this exposure during pregnancy can result in babies being born anemic.

 It is generally accepted that 6-MP or azathioprine should be continued during pregnancy if these drugs are determined to be effective in keeping the pregnant patient with IBD in remission.

. This class of drugs is in Pregnancy Category C. There has been some concern over the increased risk of cleft palate in women taking corticosteroids during their first trimester,

 but a recent, large, case-control study shows no association.

 These drugs have not been associated with other fetal abnormalities, and they may be helpful in treating IBD flare-ups in pregnant women.

 These two immunosuppressive drugs are in Pregnancy Category X and should not be used during pregnancy. Methotrexate is associated with fetal skeletal abnormalities and fetal loss.

 Thalidomide is well known for causing limb defects and major organ complications.

 Methotrexate should be discontinued in women for at least three months (and more conservatively, 6 months) before attempting a pregnancy. Both of these drugs are available for treating patients with IBD under close supervision by a physician and only in conjunction with rigorous birth control and frequent pregnancy testing. Women who become pregnant while taking methotrexate or thalidomide will need immediate attention to determine the viability of the pregnancy.

 The most recent class of drugs to be utilized in treating IBD are the biologics, or anti-TNF drugs such as infliximab, adalimumab, and certolizumab. TNF-alpha is an important component in the development of a fetus, and there is concern that a TNF blocker could interfere with the growth of the fetus' immune system. These drugs have a much shorter timeframe in the use of IBD, and their safety during pregnancy is still being determined. This class of drugs is in Pregnancy Category B, and infliximab and adalimumab have been found to cross the placenta. Therefore, it is currently recommended that these drugs be stopped in pregnant women with IBD before 30 weeks' gestation.

Certolizumab has not been found to cross the placenta. The largest study to date on women with IBD taking biologics has not shown any association with fetal complications.

 Babies born to women who take biologics (either alone or in combination with immunosuppressive drugs) during pregnancy should not be given any live vaccines until at least 6 months of age.

Today, women with IBD have a greater chance of a healthy pregnancy and baby than ever before. While many women will have concerns about taking any medications while pregnant, they should be urged to consider that keeping IBD quiescent or in remission offers the best possible chance for an uneventful pregnancy and birth. Pregnant patients with IBD should be encouraged to continue their treatment plans during pregnancy, particularly when the plan is effective at preventing flare-ups.

Flare-ups of IBD in pregnant patients should be treated promptly to minimize risks to the fetus. Patients (especially those with ulcerative colitis and long-standing Crohn's disease) should also be counseled that they are at increased risk of a flare-up after delivery.

1. Ban L, Tata LJ, Fiaschi L, Card T. Limited risks of major congenital anomalies in children of mothers with IBD and effects of medications. 

. 2014 Jan;146(1):76-84. doi: 10.1053/j.gastro.2013.09.061.

2. Mountifield R, Bampton P, Prosser R, Muller K, Andrews JM. Fear and fertility in inflammatory bowel disease: a mismatch of perception and reality affects family planning decisions. 

 2009 May;15(5):720-725. doi: 10.1002/ibd.20839.

3. Marri SR, Ahn C, Buchman AL. Voluntary childlessness is increased in women with inflammatory bowel disease. 

4. Heyman MB, Kirschner BS, Gold BD, et al. Children with early-onset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry. 

5. NÃ¸rgÃ¥rd BM. Birth outcome in women with ulcerative colitis and Crohn's disease, and pharmacoepidemiological aspects of anti-inflammatory drug therapy. 

6. Abhyankar A, Ham M, Moss AC. Meta-analysis: the impact of disease activity at conception on disease activity during pregnancy in patients with inflammatory bowel disease. 

 2013 Sep;38(5):460-466. doi: 10.1111/apt.12417. Epub 2013 Jul 15.

7. Khosla R, Willoughby CP, Jewell DP. Crohn’s disease and pregnancy. 

8. Riis L, Vind I, Politi P, et al. Does pregnancy change the disease course? A study in a European cohort of patients with inflammatory bowel disease. 

9. Pedersen N, Bortoli A, Duricova D, et al. The course of inflammatory bowel disease during pregnancy and postpartum: a prospective European ECCO-EpiCom Study of 209 pregnant women. 

 2013 Sep;38(5):501-512. doi: 10.1111/apt.12412. Epub 2013 Jul 15.

10. Reddy D, Murphy SJ, Kane SV, Present DH, Kornbluth AA. Relapses of inflammatory bowel disease during pregnancy: in-hospital management and birth outcomes. 

 2008 May;103(5):1203-1209. doi: 10.1111/j.1572-0241.2007.01756.x. Epub 2008 Apr 16.

11. NÃ¸rgÃ¥rd B, Puho E, Pedersen L, Czeizel AE, SÃ¸rensen HT. Risk of congenital abnormalities in children born to women with ulcerative colitis: a population-based, case-control study. 

12. Rahimi R, Nikfar S, Rezaie A, Abdollahi M. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis. 

13. Mogadam M, Dobbins WO, Korelitz BI, Ahmed SW. Pregnancy in inflammatory bowel disease: effect of sulfasalazine and corticosteroids on fetal outcome. 

14. Rahimi R, Nikfar S, Rezaie A, Abdollahi M. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis. 

15. Hutson JR, Matlow JN, Moretti ME, Koren G. The fetal safety of thiopurines for the treatment of inflammatory bowel disease in pregnancy. 

16. Stephansson O, Larsson H, Pedersen L, et al. Congenital abnormalities and other birth outcomes in children born to women with ulcerative colitis in Denmark and Sweden.

17. Moskovitz DN, Bodian C, Chapman ML, et al. The effect on the fetus of medications used to treat pregnant inflammatory bowel-disease patients. 

18. Mahadevan U, Martin CF, Sandler RS, et al. PIANO: A 1000 Patient Prospective Registry of Pregnancy Outcomes in Women with IBD Exposed to Immunomodulators and Biologic Therapy. 

19. Jharap B, de Boer NK, Stokkers P, et al. Intrauterine exposure and pharmacology of conventional thiopurine therapy in pregnant patients with inflammatory bowel disease. 

20. Edwards MJ, Agho K, Attia J, et al. Case-control study of cleft lip or palate after maternal use of topical corticosteroids during pregnancy. 

21. Skuladottir H, Wilcox AJ, Ma C, et al. Corticosteroid use and risk of orofacial clefts. 

22. Nguyen C, Duhl AJ, Escallon CS, Blakemore KJ. Multiple anomalies in a fetus exposed to low-dose methotrexate in the first trimester. 

23. Botting J. The History of Thalidomide. 

24. Gisbert JP, Chaparro M. Safety of anti-TNF agents during pregnancy and breastfeeding in women with inflammatory bowel disease. 

 2013 Sep;108(9):1426-1438. doi: 10.1038/ajg.2013.171. Epub 2013 Jun 11.

Articles

Pregnancy is possible for women with inflammatory bowel disease, but collaboration is needed between gastroenterologists and obstetricians.

IBD and the Pregnant Patient

Do you find that your practice is doing fewer surgeries now than about 10 years ago? If so, your experience is in line with what is happening in OB/GYN surgery at hospitals across the country.

The Agency for Healthcare Research and Quality published their data on the surgeries done on patients in an OR between 2002 and 2013 as part of the Healthcare Cost and Utilization Project (HCUP). The data was stratified a number of different ways to determine which procedures were increasing and which were decreasing amongst patients in the United States. Procedures included were those that were done on inpatients and performed in the OR. Maternal and neonatal hospitalizations were excluded from the analysis. The top 10 surgical procedures in 2012 are shown in the Table.

While certain types of surgeries-including gastrectomy and knee arthroplasty-have increased, some OB/GYN surgeries are on the decline. In fact, of the top 10 procedures that have increased in frequency, none were OB/GYN surgeries. However, of the top 10 procedures that are decreasing at the greatest rate, four of them are OB/GYN-related. Oophorectomy, both unilateral and bilateral, decreased 54% between 2003 and 2012. Hysterectomy, which included procedures done through open surgery and those done vaginally, decreased 51% over the same time period. The two less frequently performed OB/GYN surgeries that were also found to be decreasing are genitourinary incontinence procedures and vaginal obliteration. These procedures decreased at an even greater rate between 2002 and 2013, at 62.5% for genitourinary incontinence and 59% for vaginal obliteration.

For the OB/GYN procedures on the decline since 2002, the decrease was found across most age groups. Incontinence procedures decreased in the groups aged 18 to 44 years, 45 to 64 years, and 65 to 84 years. Vaginal obliteration surgery also decreased in the same age groups. However, in the 85 years and older group, lumpectomy and mastectomy were the OB/GYN procedures that showed the largest decrease. There were no OB/GYN surgeries that increased in any age group.

Procedures broken out by payer were fairly consistent in respect to OB/GYN surgeries, with hysterectomy being in the top 5 most frequently done in Medicaid, privately insured, and uninsured patients. Vaginal obliteration and incontinence procedures were the only OB/GYN procedures in the top 5 of decreasing procedures. The rate of vaginal obliteration procedures decreased in Medicare and privately insured patients, while incontinence procedures decreased in privately insured patients.

Fingar KR (Truven Health Analytics), Stocks C (AHRQ), Weiss AJ (Truven Health Analytics), Steiner CA (AHRQ). Most Frequent Operating Room Procedures Performed in U.S. Hospitals, 2003-2012. HCUP Statistical Brief #186. December 2014. Agency for Healthcare Research and Quality; Rockville, MD. Available at: 

http://www.hcup-us.ahrq.gov/reports/statbriefs/sb186-Operating-Room-Procedures-United-States-2012.pdf

Of the top 10 surgical procedures that are decreasing at the greatest rate, 4 of them are related to obstetrics and gynecology.

Downward Trends in OB/GYN Procedures

The first stand-alone HPV screening tool, the cobas HPV Test, was approved by the FDA in 2014 to screen for primary cervical cancer in women over the age of 25 years. In 2011, the cobas HPV test was first approved to work in conjunction with a Pap test. Currently, co-testing with a Pap and an HPV test is recommended for women over the age of 30, but the approval of a stand-alone cobas HPV test has the potential to change this practice. A recent cohort study looked at the specificity of the cobas HPV test as a stand-alone screening test for high-grade cervical lesions.

"In women who are older than 30, we are obtaining both a Pap and an HPV test in order to detect disease. And I think you just can't do any better than that right now."

The cobas test is used to identify the presence of HPV 16 and HPV 18, the two types of HPV that are responsible for about 70% of cervical cancer cases, as well as 12 other types of HPV. The test is done using cervical cells taken during a scrape of the cervix. The DNA isolated from those cells is tested for the presence of any HPV DNA, specifically the L1 and L2 genes. If HPV 16 or HPV 18 is present, a follow-up colposcopy is recommended. If another HPV type is found, a Pap test is recommended. If the test comes back negative for any HPV type, no further screening is needed, but the test should be repeated in 3 years.

The effectiveness of the cobas HPV test was put under the microscope during a cohort study at Houston Methodist Hospital. Of the 90,400 Pap tests done at Houston Methodist Hospital between March 2013 and February 2014, 33,875 were included in the study. There were 4,022 patients whose cobas HPV test results returned as positive, and of those, 50.8% also had abnormal cytology. Of the 29,495 patients found to be HPV-negative in the initial cobas test, 10.2% also had abnormal cytology confirmed by biopsy. Researchers found that a total of 59.7% of women who had biopsies that showed abnormal cytology returned a negative result on the cobas HPV test.

The authors of the study concluded that the rates of false-negatives in patients with high-grade cervical lesions screened with the cobas HPV test were "unacceptably high." They further express concern that false-negative results could provide a false sense of confidence for patients and physicians. Believing they are clear of HPV after receiving a negative result on primary screening, women and their physicians may not seek any further tests. The ultimate result could be a delay in diagnosis of and treatment for cervical lesions.

[[{"type":"media","view_mode":"media_crop","fid":"34087","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_2939422500785","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"3610","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.0080003738403px; line-height: 1.538em; float: right;","title":"Juan Felix, MD","typeof":"foaf:Image"}}]]The results of this study may seem alarming, but as Juan Felix, MD, professor of clinical pathology and obstetrics and gynecology and chief of gynecologic pathology at the University of Southern California University and Norris Hospitals pointed out in a phone interview, "We have known from past experiences that the HPV test is not perfect." Dr Felix goes on to say, "The one thing that is incontrovertible and has been present in every single study is that if you use the Pap and an HPV test, your sensitivity will be superior than if you use either HPV or Pap alone."

If the stand-alone HPV test is known for being less specific than co-testing, perhaps the driver behind its use is for cost-effectiveness. However, Dr Felix says that when compared with the prior screening recommendations of a Pap every year, co-testing with Pap and HPV every 3 years has "already achieved a level of cost-efficacy that's outstanding, I don't see a reason to sacrifice, currently, sensitivity, to make it even more cost-effective."

The American Cancer Society has not changed their screening recommendations with the availability of this test, but the data is under review. For women between the ages of 30 and 65, current recommendations are either Pap alone every 3 years, or co-testing with HPV and Pap every 5 years. A Pap test is recommended every 3 years, with follow-up and HPV test in the case of an abnormal result, for women between the ages of 21 and 29.

"In women who are older than 30, we are obtaining both a Pap and an HPV test in order to detect disease. And I think you just can't do any better than that right now," Dr. Felix said.

Zhou HS, Mody R, Luna E, et al. The Sensitivity of the Cobas HPV Test in Detecting Biopsy-confirmed CIN2/3 Cervical Lesions: Analysis of 33,857 Cases with Cytology and HPV Co-testing. 

Now that stand-alone HPV tests have been approved, is it worth changing cervical cancer screening recommendations? Juan Felix, MD, weighs in.

Is It Time for Stand-Alone HPV Testing?

When it comes to pay inequality in the nursing profession, would you assume that female nurses make more than male nurses? You wouldn't be the first to think that in a traditionally female-dominated profession, women would earn more than-or at least the same as-men. However, the opposite is actually true: male RNs make more money than female RNs.

A research letter published in the March 24 issue of 

The Journal of the American Medical Association 

highlighted the differences in pay between male and female registered nurses. The authors pointed out that previous research has come to the same conclusion but that many of those studies were done with older data and were limited because they did not take the potential differences for the pay discrepancy into consideration. 

This recent study used two surveys: the National Sample Survey of Registered Nurses (NSSRN) and the American Community Survey (ACS). The NSSRN ended in 2008, and the ACS was used to fill in the data for the interim years until 2013. To determine whether some RNs were paid more for a quantifiable reason, the study authors took into consideration factors that affect salary, such as education, specialty, work hours, and geographic location. With a total of almost 300,000 RNs included from both surveys, the results showed a clear difference in pay between male and female RNs. In fact, male RNs made, on average, about $5000 more every year than female RNs. The wage difference varied by specialty, with the greatest inequality found in nurse anesthetists, where the gap reached an average high of $17,000 (Table). The only specialty where there was not an inequality was orthopedics.

The difference is staggering, and it's not improved today than over previous years: male and female RN salaries have maintained the same gap all the way back to 1988 and straight through to 2013. The implications go beyond the justification that a fair day's work deserves a fair day's pay: according to the United States Department of Labor, there are 2.7 million nurses in the United States, and 90% of them are women. The lost wages in such a large group has a dramatic effect on the economy as well as on the financial well-being of female nurses and their families.

In addition, the demand for nurses over the next decade is expected to increase by 19%, an estimate that outpaces other occupations. Factors feeding the increase in demand for health care professionals are the aging population, coupled with more people having access to insurance and more patients using the healthcare system.

With the RN wage gap now studied, quantified, and making headlines, it may be more difficult to recruit women into nursing and, in particular, the specialties for which RN pay for women lags so far behind that of men. The authors of the study don’t have any answers as to why female RNs are paid less, but they call on those who employ nurses to take their study into consideration and "eliminate inequalities."

Bureau of Labor Statistics, U.S. Department of Labor. Occupational Outlook Handbook, 2014-15 Edition, Registered Nurses. Available at: 

http://www.bls.gov/ooh/healthcare/registered-nurses.htm

Muench U, Sindelar J, Busch SH, Buerhaus PI. Salary differences between male and female registered nurses in the United States. 

 2015;313:1265-1267. doi: 10.1001/jama.2015.1487.

National Center for Health Workforce Analysis. The U.S. Nursing Workforce: Trends in Supply and Education. Department of Health and Human Services. April 2013. Available at: 

http://bhpr.hrsa.gov/healthworkforce/reports/nursingworkforce/nursingworkforcefullreport.pdf

Gender-based pay inequality in female-predominant fields, such as nursing, may not be what you think. Find out what new research has uncovered.

Amber J Tresca

Articles

IBD and the Pregnant Patient

Downward Trends in OB/GYN Procedures

Is It Time for Stand-Alone HPV Testing?

10% of RNs Are Paid More for the Same Work