| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
ORIGINAL RESEARCH |
From the Division of Rheumatology, Immunology and Allergy, Department of Medicine, Georgetown University, Washington, DC.
Address reprint requests to: Virginia D. Steen, MD, Division of Rheumatology, Georgetown University Medical Center, 3800 Reservoir Road, NW, LL Gorman Building, Washington, DC 20007-2197, E-mail: steenv{at}gunet.georgetown.edu
 |
Abstract |
|---|
Top
 Abstract MethodsResultsDiscussionReferences |
|---|
Methods: Women of childbearing age with systemic sclerosis seen at the University of Pittsburgh between 1987 and 1996 were observed prospectively. Pregnancy outcomes included abortion, miscarriage, preterm and term birth, and perinatal death. Complications of pregnancy and scleroderma were determined during and after pregnancy.
Results: Fifty-nine women with systemic sclerosis had 91 pregnancies during the 10-year period. No increase in the frequency of miscarriage was found, except in those with long-standing diffuse scleroderma. Preterm births occurred in 29% of pregnancies, and all but one of the infants survived. Symptoms related to scleroderma, particularly Raynaud phenomenon, improved during pregnancy, but esophageal reflux became worse. After pregnancy, some women with diffuse scleroderma had increased skin thickening. There were three cases of renal crisis during pregnancy, all in women with early diffuse scleroderma. Four women had five healthy infants while taking angiotensin-converting-enzyme inhibitors.
Conclusion: Women with systemic sclerosis can safely have healthy pregnancies. Those with early diffuse scleroderma should wait until their disease stabilizes before becoming pregnant to decrease the risk of renal crisis. High-risk pregnancy management should be standard for all scleroderma pregnancies because of the high frequency of premature births.
Systemic sclerosis is a connective-tissue disease that occurs in women of childbearing age at least five times more frequently than in men. The mean age of symptom onset is in the early 40s, so half the women with it have the potential to become pregnant. Until recently, women usually completed their pregnancies before that age, but in the past decade many women delayed their childbearing, increasing the chances of concomitant pregnancy and illness. Thus, the frequency of concurrent pregnancies and scleroderma during early adulthood has increased. Women and their physicians are in great need of additional information about those pregnancies.
The older literature is filled with individual case reports and case series in which outcomes of both conditions were poor in women with concomitant pregnancy and scleroderma.1,2 On the basis of those reports, it is not unusual for physicians to recommend that scleroderma patients avoid pregnancy or have abortions if pregnancy occurs. Several retrospective case control studies3,4 based on patient questionnaires, including our own study,3 showed much less ominous outcomes. Our earlier study found an increased frequency of preterm births and small full-term infants, compared with controls, and we concluded that those pregnancies should be managed as high-risk, but there was minimal fetal or maternal loss. The objective of the present study was to determine the pregnancy and scleroderma outcomes of women followed prospectively and managed as having high-risk pregnancies. For those with bad outcomes, we searched for risk factors to explain the events.
|
Methods |
|---|
|
Top
AbstractMethodsResultsDiscussionReferences |
|---|
All women had been evaluated previously at the University of Pittsburgh, so the disease subtype, duration of disease, extent of organ involvement, and auto-antibody status were known already. Prior pregnancy outcomes were not included as part of this prospective study. ACOG definitions for pregnancy outcomes were used5: Full-term infants, born at 38 or more weeks’ gestation and weighing more than 2500 g; small full-term infants, full-term weighing less than 2500 g; miscarriage, pregnancy ending spontaneously before 20 weeks’ gestation; preterm birth, live-born before 38 weeks’ gestation; neonatal-perinatal death, fetal death after 20 weeks’ gestation or within the first 28 days of life; and abortion, therapeutic abortion done by choice of women.
Definitions of limited scleroderma and diffuse scleroderma were those used by LeRoy et al.6 Women with limited scleroderma had limited skin thickening with long histories of Raynaud phenomenon. Women with diffuse scleroderma had more acute illness with concurrent onset of Raynaud phenomenon and diffuse skin thickening, more musculoskeletal-tendon symptoms, and greater potential for visceral involvement, particularly lung and kidney disease. Early disease was defined arbitrarily as less than 4 years and late disease as more than 4 years of scleroderma symptoms.
Controls from our earlier study3 were used as a comparison group because they completed similar questionnaires. They were healthy women identified by random-digit dialing. The control-comparison pregnancy data was not ideal because it was not prospective or collected at the same time as the study group; however, control pregnancy outcomes were similar to the normal population.
Relative risks (RRs) and 95% confidence intervals (CIs), means and standard errors (SEs), along with other descriptive statistic measures were calculated for comparisons between groups. Data were analyzed per pregnancy, per subject, and per first pregnancy.
|
Results |
|---|
|
Top
AbstractMethodsResultsDiscussionReferences |
|---|
The 59 women had a total of 91 pregnancies during the present study. Twenty of those women had pregnancies before the study. The outcomes of those pregnancies were 19 term infants, nine miscarriages, five preterm infants, and three neonatal deaths. The three women with neonatal deaths had come specifically to request information about future pregnancies. All three later had at least one healthy infant and no further fetal losses.
Tables 1
and 2 summarize the demographics and pregnancy outcomes in the entire scleroderma group, retrospective controls (Table 1), and the scleroderma subsets (Table 2). The number of pregnancies and women with the different outcomes are shown, but the RRs are for frequencies per pregnancy. The frequency of miscarriages, all but one of which occurred in the first trimester, was similar in scleroderma women and retrospective controls when evaluated per pregnancy, per subject, or per first pregnancy. It was similar also between limited and diffuse scleroderma subjects, except that all but one of the miscarriages in the diffuse scleroderma group occurred in women with more than 4 years of illness. Forty-two percent of the late, diffuse scleroderma subjects had miscarriages compared with 13% of all other subjects (RR 2.8; 95% CI 1.23, 6.37, P < .05). Renal insufficiency and severe malabsorption were associated with miscarriages in two women. Only one women with long-standing, limited scleroderma was a recurrent aborter experiencing four miscarriages and no healthy infants.
|
|
Seven women had preterm labor without any obvious explanations or problems with them or their infants. Using tocolytic therapy, labor and delivery was delayed from 1–6 weeks in four women, although two had pulmonary edema from the tocolytics. Three women had premature rupture of membranes, and two had unexplained placental bleeding. Four other women, all with early, diffuse scleroderma, had an elevated blood pressure (BP) with normal renal function and were believed to have mild preeclampsia, which resulted in preterm delivery. One woman with renal crisis delivered a 900-g female infant at 28 weeks’ gestation. Four patients had labor induced at 37 weeks’ gestation.
Forty-three full-term infants were born to 34 systemic sclerosis subjects (mean 3230 ± 70 g). Although that number was fewer than in controls, the percentage of live births was 82% in both groups. Unlike the retrospective study, there were no small full-term infants in this study. Of the 65 preterm and full-term infants born, only one had a significant birth defect—a severe cleft palate.
Table 3 shows a variety of clinical and laboratory features that could be predictive of specific pregnancy outcomes. Some women had pregnancies in more than one category, so the analysis was based on findings at the time of the specific pregnancy. The single neonatal death was not included in analysis. No differences in demographics, laboratory features, or medications taken between the three pregnancy outcomes were found. Four subjects (five infants) were taking angiotensin-converting-enzyme inhibitors throughout most of their pregnancies and their fetuses did not have any problems associated with those drugs.7
|
). Three had pregnancies 1–5 years after renal crisis, one of whom had a miscarriage shortly after discontinuing dialysis; however, those three women had four successful pregnancies. Two women had renal crises during pregnancy. One who had early, diffuse scleroderma was aborted at 19 weeks’ gestation to control renal crisis, but she still needed dialysis. The other woman, also with early, diffuse scleroderma, had renal crisis during the 28th week of gestation. She needed temporary dialysis for 8 months but has been off dialysis for 2 years with a recent serum creatinine level of 1.4 mg/dL. Another woman who we believed had preeclampsia at the time of her preterm birth at 34 weeks’ gestation had persistent hypertension postpartum. Four weeks after delivery, her BP was 180/120 mmHg, and her serum creatinine 6.7 mg/dL. Five women had severe scleroderma pulmonary fibrosis, none of whom required oxygen. Three women with forced vital capacities less than 65% predicted had three preterm but healthy infants. The fourth woman with severe fibrosis developed aspiration pneumonia and adult respiratory distress syndrome necessitating therapeutic abortion at 20 weeks’ gestation. She died 3 months later from respiratory failure, malabsorption, and multiorgan failure. The fifth woman, who had a forced vital capacity of 55% predicted, elected to have two therapeutic abortions.
The woman with severe gastrointestinal problems was poorly nourished, had malabsorption, and had three unsuccessful pregnancies: A 23-week fetal death, an ectopic pregnancy, and a first-trimester miscarriage. She was given hyperalimentation and antibiotic therapy for malabsorption, and in the following 3 years she delivered two term male infants weighing more than 3500 g each.
Deliveries usually were uncomplicated. Some women had tight abdominal skin, but it did not interfere with them carrying pregnancies to term or having vaginal deliveries. Seven women had cesarean deliveries (nine infants) because of histories of cesarean delivery, failure of labor to progress, or cephalic-pelvic disproportion. None of the women who had cesarean deliveries had any problems with healing or infections.
During 57 pregnancies, women said their scleroderma symptoms were unchanged. Eighteen pregnancies were associated with some improvement, usually in their symptoms of Raynaud phenomenon. In 16 pregnancies, esophageal reflux (n = 10), cardiac arrhythmias (n = 3), arthritis (n = 3), skin thickening (n = 2), and renal crisis (n = 2) occurred or became aggravated.
After delivery, a third of the women had increased severity of their symptoms including Raynaud phenomenon (n = 8), arthritis (n = 5), skin thickening (n = 7), and renal crisis (n = 1). The seven women who had skin thickening after pregnancy had diffuse scleroderma and stabilized soon after reinstitution of their medications. Only seven women noticed improvement in esophageal reflux and arthritis postpartum. Most of the women noticed no changes in their symptoms postpartum.
|
Discussion |
|---|
|
Top
AbstractMethodsResultsDiscussionReferences |
|---|
Although the controls in this study were younger, had pregnancies 10 years earlier, and were not managed as high-risk pregnancies, their outcomes were similar to more recent reports. It seemed unlikely that using a more closely matched control group would substantially change our significant findings. Although the decreased number of pregnancies in the scleroderma group suggested that infertility might be an issue, as suggested by Silman and Black,9 our recent report did not find infertility to be a problem.10
Increased numbers of miscarriages have been seen in several series1,11 before8,9 and after onset of disease.12 In our retrospective study, there was no increase in frequency of miscarriages.3 In the present study, only the subset of women with long-standing, diffuse scleroderma had an increased frequency of miscarriages. Those women did not have serious internal organ involvement, were of similar ages, and were not taking any more medications than were the women without miscarriages. None of the late, diffuse scleroderma subjects who had miscarriages were taking calcium-channel blockers. Although those findings are not statistically significant, decreased blood flow early in the pregnancy might have contributed to the miscarriages.
Prematurity was the major problem in the scleroderma subjects. Although not emphasized in the earlier literature, the present study clearly showed that scleroderma subjects had an increased frequency of preterm births compared with the controls. Most of those infants were normal-sized and able to go home with their mothers. Fifteen of 23 preterm infants weighed more than 2300 g at birth. Only three infants weighed less than 1500 g.
We were not able to identify any unique feature or problem potentially related to scleroderma to explain the causes of preterm births. All of the probable explanations appeared to be standard obstetric problems. Preterm births occurred in 29% of the scleroderma pregnancies even though they were monitored as high-risk pregnancies. All pregnant women with scleroderma should be monitored particularly closely and taught how to recognize early signs of labor so their physicians can try to delay delivery or prepare their infants for early birth.13
Our earlier retrospective study found a high frequency of full-term small infants,3 but in the present study, no small full-term infants were born. Only one of the preterm infants was small for date (actual weight less than expected for the week of gestation). Some women were taking calcium-channel blockers during pregnancy; perhaps that had an effect.
Scleroderma symptoms during pregnancy usually were unchanged or improved. Although seven of 26 (27%) of the diffuse scleroderma subjects noticed temporary increases in their skin thickening, there was little overall change postpartum. We did not observe any significant deterioration in lung or other organ function. Renal crisis was reported during pregnancy in many case reports.14,15 Our earlier retrospective study was unable to determine whether that was a chance occurrence or if pregnancy precipitated renal crisis.3 Subjects in this current study also had several episodes of renal crisis, during and after pregnancy. It is impossible to determine the effect that pregnancy had on the development of that complication, although most patients have early diffuse scleroderma, which is when most renal crisis usually occurs.
Renal crisis is difficult to diagnose and treat during pregnancy; it presents as an acute onset of severe hypertension, often with thrombocytopenia and daily increases of serum creatinine in women who have had diffuse scleroderma for less than 5 years, which mimics preeclampsia. Elevated liver function tests, which should be normal in renal crisis, and serum creatinine, which increases daily in renal crisis, are the best ways to differentiate between it and preeclampsia. Despite the association of angiotensin-converting-enzyme inhibitors with birth defects and infant kidney dysfunction,7 angiotension-converting-enzyme inhibitors must be used urgently in renal crisis because they are the only drugs that successfully control hypertension in renal crisis. No evidence was revealed to suggest that aborting a pregnancy will reverse renal problems; angiotensin-converting-enzyme inhibitors are the only lifesaving treatment.
When a woman with scleroderma becomes pregnant after a prior renal crisis episode, control of BP with other medications can be tried. However, if BP or serum creatinine increases, then angiotensin-converting-enzyme inhibitors will be necessary to save the lives of mother and infant. Trying to balance the risks of problems for infants from the use of angiotensin-converting-enzyme inhibitors and the risks of serious kidney damage in the mother if they are not used can be difficult. Women with scleroderma should be encouraged to delay pregnancy until their disease has stabilized and the risk of renal crisis is less, which is usually 3–5 years from onset of symptoms.
|
Footnotes |
|---|
Received July 30, 1998. Received in revised form December 3, 1998. Accepted December 30, 1998.
|
References |
|---|
|
Top
AbstractMethodsResultsDiscussionReferences |
|---|
2. Weiner SR. Organ function: Sexual function and pregnancy. In: Clements PJ, Furst, eds. Systemic sclerosis. New York: Williams and Wilkins, Ltd., 1995:483–99.
3. Steen VD, Conte C, Day N, Ramsey-Goldman R, Medsger TA Jr. Pregnancy in women with systemic sclerosis. Arthritis Rheum 1989;32:151–7.[Medline]
4. Siamopoulou-Mavridou A, Manoussakis MN, Mavridis AK, Moutsopoulos HM. Outcome of pregnancy in patients with autoimmune rheumatic disease before the disease onset. Ann Rheum Dis 1988;47:982–7.
5. Standard terminology for reporting of reproductive health statistics in the United States. American College of Obstetricians and Gynecologists, 1987.
6. LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, et al. Scleroderma (systemic sclerosis): Classification, subsets and pathogenesis. J Rheumatol 1988;15:202–5.[Medline]
7. Mastrobattista JM. Angiotensin converting enzyme inhibitors in pregnancy. Semin Perinatol 1997;21:124–34.[Medline]
8. Englert H, Brennan P, McNeil D, Black C, Silman AJ. Reproductive function prior to disease onset in women with scleroderma. J Rheumatol 1992;19:1575–9.[Medline]
9. Silman AJ, Black C. Increased incidence of spontaneous abortion and infertility in women with scleroderma before disease onset: A controlled study. Ann Rheum Dis 1988;47:441–4.
10. Steen V, Brodeur M, Conte C, Medsger TA. Fertility in patients with systemic sclerosis. Arthritis Rheum 1999.
11. Slate WG, Graham AR. Scleroderma and pregnancy. Am J Obstet Gynecol 1968;101:335–41.[Medline]
12. Scarpinato L, Mackenzie AH. Pregnancy and progressive systemic sclerosis. Case report and review of literature. Cleve Clin Q 1985;52:207–11.[Medline]
13. Katz M, Gill PJ, Newman RB. Detection of preterm labor by ambulatory monitoring of uterine activity for the management of oral tocolysis. Am J Obstet Gynecol 1986;154:1253–6.[Medline]
14. Karlen JR, Cook WA. Renal scleroderma and pregnancy. Obstet Gynecol 1974;44:349–54.
15. Traub YM, Shapiro AP, Rodnan GP, Medsger TA, McDonald RH Jr, Steen VD, et al. Hypertension and renal failure (scleroderma renal crisis) in progressive systemic sclerosis. Review of a 25-year experience with 68 cases. Medicine (Baltimore) 1983;62:335–52.[Medline]
This article has been cited by other articles:
|
|
 |
|
  I. Miniati, S. Guiducci, F. Mecacci, G. Mello, and M. Matucci-Cerinic Pregnancy in systemic sclerosis Rheumatology, June 1, 2008; 47(suppl_3): iii16 - iii18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. F. Chakravarty, D. Khanna, and L. Chung Pregnancy Outcomes in Systemic Sclerosis, Primary Pulmonary Hypertension, and Sickle Cell Disease Obstet. Gynecol., April 1, 2008; 111(4): 927 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gayed and C. Gordon Pregnancy and rheumatic diseases Rheumatology, November 1, 2007; 46(11): 1634 - 1640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. TEIXEIRA, A. MAHR, A. BEREZNE, L.-H. NOEL, L. GUILLEVIN, and L. MOUTHON Scleroderma Renal Crisis, Still a Life-Threatening Complication Ann. N.Y. Acad. Sci., June 1, 2007; 1108(1): 249 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Chung, R L. Flyckt, I Colon, A A Shah, M Druzin, and E F Chakravarty Outcome of pregnancies complicated by systemic sclerosis and mixed connective tissue disease Lupus, September 1, 2006; 15(9): 595 - 599. [Abstract] [PDF]
|
|
|
|
|
|
M. Basso, M. Ghio, G. Filaci, M. Setti, and F. Indiveri A case of successful pregnancy in a woman with systemic sclerosis treated with cyclosporin Rheumatology, October 1, 2004; 43(10): 1310 - 1311. [Full Text] [PDF]
|
|
|
|
 |
|
 V. D. Steen and T. A. Medsger Jr. Long-Term Outcomes of Scleroderma Renal Crisis Ann Intern Med, October 17, 2000; 133(8): 600 - 603. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
