Table of Contents Author Guidelines Submit a Manuscript
Journal of Ophthalmology
Volume 2014, Article ID 401915, 10 pages
http://dx.doi.org/10.1155/2014/401915
Review Article

Uveitis and Gender: The Course of Uveitis in Pregnancy

Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, VIC 3002, Australia

Received 25 September 2013; Accepted 9 December 2013; Published 9 January 2014

Academic Editor: H. Nida Sen

Copyright © 2014 Nathalie P. Y. Chiam and Lyndell L. P. Lim. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The hormonal and immunological changes in pregnancy have a key role in maintaining maternal tolerance of the semiallogeneic foetus. These pregnancy-associated changes may also influence the course of maternal autoimmune diseases. Noninfectious uveitis tends to improve during pregnancy. Specifically, uveitis activity tends to ameliorate from the second trimester onwards, with the third trimester being associated with the lowest disease activity. The mechanism behind this phenomenon is likely to be multifactorial and complex. Possible mechanisms include Th1/Th2 immunomodulation, regulatory T-cell phenotype plasticity, and immunosuppressive cytokines. This clearly has management implications for patients with chronic sight threatening disease requiring systemic treatment, as most medications are not recommended during pregnancy due to lack of safety data or proven teratogenicity. Given that uveitis activity is expected to decrease in pregnancy, systemic immunosuppressants could be tapered during pregnancy in these patients, with flare-ups being managed with local corticosteroids till delivery. In the postpartum period, as uveitis activity is expected to rebound, patients should be reviewed closely and systemic medications recommenced, depending on uveitis activity and the patient’s breastfeeding status. This review highlights the current understanding of the course of uveitis in pregnancy and its management to help guide clinicians in managing their uveitis patients during this special time in life.

1. Introduction

Pregnancy is associated with various hormonal and immunological changes that facilitate the survival of the semiallogeneic foetus. These physiological changes influence the course of various maternal autoimmune diseases [1, 2]. The effect of pregnancy on noninfectious uveitis has not been as extensively studied; however, to date it has been well described by a few authors. It is essential to understand the course of uveitis in pregnancy as uveitis has a peak incidence in young adults and it is not uncommon for female patients with known uveitis to become pregnant. This review will examine the literature on the course of uveitis in pregnancy and its management. This summary would hopefully help guide clinicians in the management of uveitis during pregnancy and the postpartum period.

2. Theories on How Pregnancy Influences Uveitis

During pregnancy, the tolerance of the semiallogeneic foetus is made possible by the various hormonal and immunological changes in pregnancy. These physiological changes also have a role in influencing the course of maternal autoimmune diseases [1, 2].

The increased levels of oestrogen and progesterone during pregnancy result in the suppression of Th1 associated immunity but the upregulation of Th2 associated immune responses [35]. As such, pregnancy often ameliorates Th1 associated autoimmune diseases, like rheumatoid arthritis, but exacerbates Th2 associated autoimmune conditions, like systemic lupus erythematosus [29]. The association between uveitis amelioration and Th1 suppression/Th2 upregulation has been demonstrated by serum studies in Chan et al.’s [10] prospective case study on four pregnant uveitis patients. Agarwal et al. [11] have also reported similar findings for experimental autoimmune uveitis (EAU) in mice. When EAU susceptible mice (C57BL/6) were immunised with interphotoreceptor retinoid binding protein, the incidence and severity of EAU were lower in the pregnant mice, as compared to nonpregnant controls. The pregnant mice were also found to have reduced levels of interferon gamma, IL 12 P40 but unchanged levels of TNF alpha, IL4, IL5, and IL10, which suggested a Th2 bias in their immune system [11]. This Th2 bias in pregnancy probably augments the Th1 predominant response in noninfectious uveitis, resulting in disease amelioration [12]. Although still uncertain, the recently discovered subset of T helper cells, Th17, may also play a role in altered autoimmune activity in pregnancy [1317]. Th17 cells are proinflammatory and associated with the pathogenesis of autoimmune diseases like systemic lupus erythematosus [18],Vogt-Koyanagi-Harada (VKH) disease [19], irritable bowel disease [20], rheumatoid arthritis [21], and multiple sclerosis [22]. During pregnancy, Th17 cells are elevated in preeclampsia [9, 23]. The hormonal and associated cytokine changes in pregnancy influence autoimmune disease activity and may inspire future therapeutic options. Interestingly, studies have shown that oral oestradiol may decrease disease activity in multiple sclerosis [24, 25]; however, its implications in uveitis management are uncertain.

Several other pregnancy-associated changes may influence the course of maternal autoimmune conditions. For instance, regulatory T cells demonstrate phenotype plasticity and are able to switch between a tolerant or aggressive phenotype in response to circulating foetal cells or infectious agents accordingly [17, 26]. The elevated levels of immunosuppressive cytokines and hormones, such as melanocyte-stimulating hormone [27, 28], early pregnancy factor [29], and alpha-fetoprotein [30, 31] have also been implicated in the improvement of various autoimmune conditions during pregnancy. The mechanism for altered activity of autoimmune uveitis in pregnancy is likely to be multifactorial.

The available literature seems to suggest that uveitis activity begins to improve in mid pregnancy and reaches its lowest level in the third trimester (see below). This may be due to the various pregnancy-associated changes, such as the Th1/Th2 immune shift, becoming increasingly pronounced with the progress of pregnancy [6, 32]. These findings are in keeping with the accepted theory that most forms of non-infectious uveitis are Th1 mediated diseases [12]. After delivery, the rate of flare-up seems to return to prepregnancy levels. This may be explained by the reversal of various pregnancy-associated changes within one to two months of delivery [33].

3. The Effect of Pregnancy on the Course of Uveitis

There have only been a few studies that investigated pregnancy’s effect on noninfectious uveitis. Previous publications on uveitis in pregnancy include a few case reports [10, 3436], a retrospective case series by Rabiah and Vitale [37] in 2003, and a retrospective cohort study by Kump et al. [38] in 2006. The authors of this review have also recently conducted a retrospective case series on uveitis in pregnancy [39]. As uveitis is an uncommon condition [40], studies on uveitis in pregnancy are constrained by the limited number of eligible patients and are largely restricted to retrospective studies. The general consensus is that uveitis activity improves in pregnancy, with significantly decreased disease activity from the mid pregnancy onwards. However, in the postpartum period, uveitis activity tends to relapse.

The findings from previous case reports and small case series () [10, 3436] have limited generalizability due to the small numbers of patients studied. Even so, they reported that uveitis improves in pregnancy, especially in the mid and late trimesters while postpartum period was associated with activity relapse, which was reflected by other larger studies.

The retrospective case series by Rabiah and Vitale [37] was based in Saudi Arabia. It included 76 pregnancies among 50 women. Their subjects had VKH associated uveitis (46%), Behcet’s disease associated uveitis (20%), and idiopathic uveitis (34%), which reflected the regional epidemiology in Saudi Arabia. The study investigated the probability of at least one flare-up in the periods three months before pregnancy, during pregnancy, and up to six months postpartum. They reported that the probability of uveitis flaring-up was lower during pregnancy as compared to three months pre-pregnancy and six months postpartum. It should be noted that the duration of followup in prepregnancy, pregnancy, and postpartum was unequal. As such, a larger number of patients may experience a flare-up when the duration of followup was longer; thus their findings should be interpreted with this in mind.

The retrospective cohort study by Kump et al. [38] was based in the United States of America. It involved 32 pregnant self-controls and 32 nonpregnant female controls who were matched for age, ethnicity, and anatomical location of uveitis. Most subjects had idiopathic uveitis (72%). They reported that the annual rate of flare-up was significantly lower during pregnancy (1.0 per year) as compared to nonpregnant periods (2.4 per year) and non-pregnant controls (3.1 per year), . During pregnancy, rates of flare-up decreased significantly in the second and third trimester (2.3, 0.5, 0.4 per year for the first, second, and third trimesters, resp.).

Chiam et al.’s retrospective study was based in Australia and included 47 subjects [39]. Uveitis activity one year prepregnancy, during pregnancy and one year postpartum was evaluated. The reported flare-up rates were 1.188, 0.540, 0.972 per person year in prepregnancy, gestation, and postpartum, respectively. ( for comparison between pre-pregnancy and pregnancy; for comparison between pregnancy and postpartum). The rate of flare-up was 1.188, 0.264, 0.096 per person year for the first, second, and third trimesters, respectively. Rates in the second trimester were significantly lower than rates in the first trimester, ; meanwhile rates in the third trimester did not differ significantly from the second trimester, . After delivery, rates of flare-up rebounded, as flare-up rates six months postpartum were not significantly different from pre-pregnancy rates ().

Interestingly, the severity of uveitis flare-ups does not seem to be influenced by the course of pregnancy. Chiam et al. reported that when uveitis severity was evaluated based on anterior chamber cell count, the severity of flare-ups was not significantly different between pregnancy and nonpregnant periods [39]. In Rabiah and Vitale’s study [37], surrogate markers of disease severity including flare-up duration and type of therapy prescribed were also not significantly different in pregnancy and nonpregnant periods.

Other factors have also been studied with regard to their possible influence on uveitis activity during this period. These include the effect of breastfeeding, the possible relationship between multiple pregnancies in the same individual and various host factors such as type of uveitis.

Lactation has been suggested to aggravate some autoimmune diseases. After delivery, elevated prolactin levels from pregnancy will decline unless breastfeeding occurs. As prolactin is a proinflammatory hormone that promotes Th1-immune responses [2], Th1-dominant immunopathologies like rheumatoid arthritis have been shown to be aggravated by lactation [8, 4145]. Although breastfeeding has not been found to have a significant influence on the likelihood of uveitis flare-up in the postpartum period, this is likely to be due to the small numbers of subjects available for analysis [3739]. Similarly, although uveitis activity in pregnancy does not seem to be correlated between different pregnancies within multiparous individuals [37, 39], the small numbers of subjects available for analysis in these studies were again limited.

In general, the course of uveitis varies across uveitis aetiologies. However, it is interesting to note that in our study, host variables such as uveitis aetiology, anatomical location of uveitis, course of uveitis activity, medication used, and sex of child were not found to be associated with flare-up rates in pre-pregnancy, gestation, or postpartum period. In particular, it is interesting to note that uveitis activity seems to improve during pregnancy across most uveitis aetiologies. This is supported by other studies that analysed the effect of pregnancy according to uveitis diagnosis, where uveitis activity was found to improve from the second trimester onwards across the various uveitis aetiologies [37, 39]. Uveitis aetiologies analysed in these studies included HLA-B27 associated uveitis, VKH disease, Behcet’s disease, and idiopathic uveitis.

Articles focusing on systemic autoimmune diseases in pregnancy have also suggested that the associated uveitis tends to improve for most of these conditions [3, 4, 7, 41, 42, 4652]; however, the opposite applies to systemic lupus erythematosus, where ocular inflammation has been reported to increase in pregnancy [7, 51]. Meanwhile reports have been contradictory for VKH associated uveitis [5358]. Rabiah and Vitale’s retrospective study reported that their VKH subjects () mostly experienced an early pregnancy flare-up, with approximately half experiencing a postpartum flare-up [37]. However, this has not been a consistent pattern amongst prior studies. Two case reports have described VKH patients experiencing flare-ups in mid and late pregnancy [55, 58]. Meanwhile, other case reports have described VKH activity in early pregnancy, with cases of VKH being first diagnosed between 10 and 16 weeks [56, 57]. There have also been case reports on VKH generally improving during pregnancy [53, 54]. It is therefore difficult to ascertain the course of VKH on pregnancy as the existing literature is restricted to case reports which describe inconsistent experiences.

The use of anti-inflammatory medications has not been found to be associated with rates of flare-up during pregnancy [37, 39]. However, this may be due to selection bias, as patients who did not receive treatment probably had relatively inactive uveitis, whereas those on medication likely had more aggressive disease that required treatment. On the other hand, the lack of association could also be due to the relatively small sample sizes (type II error) in these studies.

4. The Management of Uveitis in Pregnancy

The management of non-infectious uveitis in pregnancy attracts special interest as non-infectious uveitis is often managed with immunosuppressive agents that may affect fertility and the viability of pregnancies. The management of uveitis in pregnant women is therefore an area of uncertainty for clinicians due to the limited information available.

Wakefield et al. [59] recently published a review on the treatment of severe inflammatory eye disease in pregnancy and young patients of reproductive age. They advised that both male and female patients should be informed about the risks of infertility, miscarriage, and foetal abnormalities. Measures to address these adverse effects of immunosuppressants include sperm banking for male patients, oocyte cryopreservation for female patients, the use of double contraception (barrier and hormonal), and enforcing a drug washout period before conception is attempted. Female patients who become pregnant should be encouraged to inform their doctors as soon as possible so that their treatment may be modified if required for the safety of the pregnancy [59]. In general, principles in the management of uveitis in pregnancy include collaboration between the obstetrician, ophthalmologist, and the patient to evaluate the risks and benefit for the mother and child [59, 60].

Although many immunosuppressive agents are not recommended during pregnancy due to the lack of safety data rather than due to proven teratogenicity, some have proven adverse effects on the fetus and must be avoided. Specifically, methotrexate is contraindicated during pregnancy and lactation, as it results in both miscarriage and fetal anomalies. Similarly, cyclophosphamide and mycophenolate mofetil (MMF) should also be avoided in pregnancy. MMF has been associated with a high rate of fetal anomalies and miscarriages and has therefore resulted in the development of a risk evaluation and mitigation strategy (REMS) for this drug as mandated by the Food and Drug Administration [61]. Cyclophosphamide use poses fetal malformation risks and developmental delay and is absolutely contraindicated in early pregnancy [62, 63]. Although azathioprine and cyclosporine can be used with caution during pregnancy [63], there is currently insufficient data regarding the use of tumour necrosis factor blockers, anakinra and rituximab in pregnancy and lactation [59, 62, 63]. Table 1 summarises the current recommendations regarding the use of various immunosuppressive drugs in pregnancy, as advised in previous reviews [59, 6265].

tab1
Table 1: Immunosuppressive drugs in pregnancy and lactation (adapted from reviews on immunomodulatory agents in pregnancy) [59, 6265].

Wakefield et al.’s review proposed a stepwise therapeutic regimen for the management of uveitis in pregnancy according to disease severity. In mild uveitis, treatment could consist of topical or local steroid injections, followed by oral prednisolone (<50 mg/day), azathioprine (2 mg/kg/day), or cyclosporine (2.5–5 mg/kg/day). Higher doses of prednisolone (1 mg/kg/day) were recommended for more severe uveitis, with the addition of azathioprine and/or cyclosporine if needed. In the event where triple therapy with steroids, azathioprine, and cyclosporine was insufficient for the control of inflammation, the addition of intravenous immunoglobulin therapy or biological agents could then be considered [59]. In addition, for those patients taking chronic corticosteroids during pregnancy, Wakefield et al. recommended that the dose should be increased prior to delivery (24, 12, and 1 hour prior to delivery) to counteract the stress of childbirth.

However, as we and others have found that uveitis is generally less active during pregnancy than during the pre-pregnancy and postpartum periods, given the questionable safety of several systemic agents used in the treatment of non-infectious uveitis, an alternative approach would be to taper and/or cease systemic treatments during pregnancy in favour of locally delivered treatment.

The use of locally delivered treatment (such as periocular sustained release corticosteroid injections or intravitreal steroids) in non-infectious uveitis is not new and its use has been extensively described in a large range of non-infectious ocular inflammatory conditions. Periocular corticosteroids of triamcinolone and methylprednisolone have been effective in managing vitritis, posterior segment inflammation, and moderate macular oedema [6673]. They confer the advantages of achieving higher drug levels in the posterior segment of the eye as compared to systemic steroids and lower risks of systemic side effects [74]. However, potential complications include ptosis, orbital fat protrusion, and other steroid induced ocular complications such as cataracts and raised intraocular pressure (IOP) [66, 73, 75, 76].

Intravitreal triamcinolone acetate (IVTA) is commonly used to treat vitritis and associated cystoid macular oedema [7782]. Specifically, IVTA has been effectively used to treat uveitis associated with Behcet’s disease [8385], VKH syndrome [86], serpinginous choroiditis [87], and sympathetic ophthalmia [8891]. These studies have shown that IVTA may be used alone or as an adjuvant to reduce the dose of systemic immunosuppression required. As compared to other forms of steroids, IVTA has been shown to be more effective than orbital floor and sub-Tenon triamcinolone [92, 93] and comparably as effective as oral steroids in managing posterior uveitis. However, side effects associated with IVTA include relatively high risks of steroid induced cataracts (15–30%) and IOP rise (25–45%), particularly in younger patients [81, 94]. This should be kept in mind when considering regionally delivered corticosteroids in uveitis patients during pregnancy. Other less common side effects include postinjection infectious endophthalmitis, pseudoendophthalmitis, and rhegmatogenous retinal detachments [95].

In most of these cases, the use of periocular or intravitreal steroid injections has been for the treatment of acute exacerbations, often in combination with the commencement of systemic treatment to prevent the relapse of disease when the sustained release steroid is exhausted. However, due to their limited duration of effect, this modality of treatment tends not to be used as the sole treatment in chronic disease. However, their use during pregnancy would appear ideal, as they have very little (if any) systemic toxicity and only a limited and finite number of repeated administrations would be needed (if required) during the course of the pregnancy, after which systemic treatments could be reconsidered after delivery. Alternatively, newer forms of sustained release corticosteroid therapy such as Ozurdex (Allergan, Irvine, CA) and Retisert (Bausch and Lomb, Rochester, NY) could also be considered during this time, given their longer durations of effect in chronic active posterior or panuveitis, with similar efficacy to systemic treatment [96, 97].

A suggested approach in the management of patients with chronic uveitis who become pregnant would therefore be the tapering and cessation of systemic treatments during pregnancy, as the activity of the patient’s uveitis would be expected to decrease during this time. Any flare-ups of disease could then be managed locally with either topical, sub-Tenons, or intravitreal sustained release corticosteroid as required until delivery. For those with sight-threatening disease, repeated prophylactic local injections could be considered; however, this would be a more contentious approach, given that disease activity is expected to reduce during pregnancy and common side effects such as raised IOP and cataracts are higher in younger patients [81, 94]. Upon delivery, recommencement of systemic agents (being mindful of the patient’s breastfeeding status) and closer review of patients would then be recommended, given that uveitis activity is likely to rebound back to prepregnancy levels. For patients with chronic, sight-threatening disease where the cessation of systemic treatment is deemed particularly risky, an alternative option is the use of either the Ozurdex or Retisert sustained release corticosteroid devices. In those patients planning for multiple children, Retisert may be particularly advantageous, given its much longer duration of effect [98].

5. Conclusion

The influence of pregnancy on the course of uveitis is a fascinating phenomenon. The general consensus is that uveitis improves during pregnancy, especially from mid pregnancy onwards, while the postpartum period is associated with uveitis activity relapse. This has key implications on the management of pregnant uveitis patients. Clinicians may consider decreasing uveitis medications during pregnancy to minimise medication associated side effects on the foetus. After delivery, followup should also be intensified in anticipation of postpartum relapse. It would be interesting to see if future studies on the mechanisms behind uveitis amelioration in pregnancy would inspire new therapeutic options for uveitis.

Conflict of Interests

The authors have no conflict of interests in any aspect of this paper.

Acknowledgment

CERA receives Operational Infrastructure Support from the Victorian Government.

References

  1. J. P. Buyon, J. L. Nelson, and M. D. Lockshin, “The effects of pregnancy on autoimmune diseases,” Clinical Immunology and Immunopathology, vol. 78, no. 2, pp. 99–104, 1996. View at Publisher · View at Google Scholar · View at Scopus
  2. R. L. Wilder, “Hormones, pregnancy, and autoimmune diseases,” Annals of the New York Academy of Sciences, vol. 840, pp. 45–50, 1998. View at Publisher · View at Google Scholar · View at Scopus
  3. J. P. Buyon, “The effects of pregnancy on autoimmune diseases,” Journal of Leukocyte Biology, vol. 63, no. 3, pp. 281–287, 1998. View at Google Scholar · View at Scopus
  4. A. Doria, L. Iaccarino, S. Arienti et al., “Th2 immune deviation induced by pregnancy: the two faces of autoimmune rheumatic diseases,” Reproductive Toxicology, vol. 22, no. 2, pp. 234–241, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. I. J. Elenkov, J. Hoffman, and R. L. Wilder, “Does differential neuroendocrine control of cytokine production govern the expression of autoimmune diseases in pregnancy and the postpartum period?” Molecular Medicine Today, vol. 3, no. 9, pp. 379–383, 1997. View at Publisher · View at Google Scholar · View at Scopus
  6. I. J. Elenkov, R. L. Wilder, V. K. Bakalov et al., “IL-12, TNF-α, and hormonal changes during late pregnancy and early postpartum: implications for autoimmune disease activity during these times,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 10, pp. 4933–4938, 2001. View at Publisher · View at Google Scholar · View at Scopus
  7. S. O. Keeling and A. E. Oswald, “Pregnancy and rheumatic disease: “by the book” or ‘by the doc’,” Clinical Rheumatology, vol. 28, no. 1, pp. 1–9, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. L. J. Jara, O. Vera-Lastra, J. M. Miranda, M. Alcala, and J. Alvarez-Nemegyei, “Prolactin in human systemic lupus erythematosus,” Lupus, vol. 10, no. 10, pp. 748–756, 2001. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Østensen, P. M. Villiger, and F. Förger, “Interaction of pregnancy and autoimmune rheumatic disease,” Autoimmunity Reviews, vol. 11, no. 6-7, pp. A437–A446, 2012. View at Publisher · View at Google Scholar · View at Scopus
  10. C.-C. Chan, G. F. Reed, Y. Kim, E. Agrón, and R. R. Buggage, “A correlation of pregnancy term, disease activity, serum female hormones, and cytokines in uveitis,” British Journal of Ophthalmology, vol. 88, no. 12, pp. 1506–1509, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. R. K. Agarwal, C.-C. Chan, B. Wiggert, and R. R. Caspi, “Pregnancy ameliorates induction and expression of experimental autoimmune uveitis,” Journal of Immunology, vol. 162, no. 5, pp. 2648–2654, 1999. View at Google Scholar · View at Scopus
  12. E. F. Foxman, M. Zhang, S. D. Hurst et al., “Inflammatory mediators in uveitis: differential induction of cytokines and chemokines in Th1- versus Th2-mediated ocular inflammation,” Journal of Immunology, vol. 168, no. 5, pp. 2483–2492, 2002. View at Google Scholar · View at Scopus
  13. M. Akdis, O. Palomares, W. van de Veen, M. van Splunter, and C. A. Akdis, “TH17 and TH22 cells: a confusion of antimicrobial response with tissue inflammation versus protection,” Journal of Allergy and Clinical Immunology, vol. 129, pp. 1438–1449, 2012. View at Google Scholar
  14. E. Bettelli, M. Oukka, and V. K. Kuchroo, “TH-17 cells in the circle of immunity and autoimmunity,” Nature Immunology, vol. 8, no. 4, pp. 345–350, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. J. Furuzawa-Carballeda, M. I. Vargas-Rojas, and A. R. Cabral, “Autoimmune inflammation from the Th17 perspective,” Autoimmunity Reviews, vol. 6, no. 3, pp. 169–175, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. M. B. Torchinsky and J. M. Blander, “T helper 17 cells: discovery, function, and physiological trigger,” Cellular and Molecular Life Sciences, vol. 67, no. 9, pp. 1407–1421, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. J. Ernerudh, G. Berg, and J. Mjösberg, “Regulatory T helper cells in pregnancy and their roles in systemic versus local immune tolerance,” American Journal of Reproductive Immunology, vol. 66, no. 1, pp. 31–43, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. C. K. Wong, C. Y. Ho, E. K. Li, and C. W. K. Lam, “Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus,” Lupus, vol. 9, no. 8, pp. 589–593, 2000. View at Google Scholar · View at Scopus
  19. C. Wang, Y. Tian, B. Lei et al., “Decreased IL-27 expression in association with an increased Th17 response in Vogt-Koyanagi-Harada disease.,” Investigative Ophthalmology & Visual Science, vol. 53, pp. 4668–4675, 2012. View at Google Scholar
  20. D. Yen, J. Cheung, H. Scheerens et al., “IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6,” Journal of Clinical Investigation, vol. 116, no. 5, pp. 1310–1316, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. W. Wang, S. Shao, Z. Jiao, M. Guo, H. Xu, and S. Wang, “The Th17/Treg imbalance and cytokine environment in peripheral blood of patients with rheumatoid arthritis,” Rheumatology International, vol. 32, no. 4, pp. 887–893, 2012. View at Publisher · View at Google Scholar · View at Scopus
  22. L. Klotz, S. Burgdorf, I. Dani et al., “The nuclear receptor PPARγ selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity,” Journal of Experimental Medicine, vol. 206, no. 10, pp. 2079–2089, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. G. Toldi, J. Rigó Jr., B. Stenczer, B. Vásárhelyi, and A. Molvarec, “Increased prevalence of IL-17-producing peripheral blood lymphocytes in pre-eclampsia,” American Journal of Reproductive Immunology, vol. 66, no. 3, pp. 223–229, 2011. View at Google Scholar · View at Scopus
  24. W.-H. Zhu, C.-Z. Lu, Y.-M. Huang, H. Link, and B.-G. Xiao, “A putative mechanism on remission of multiple sclerosis during pregnancy: estrogen-induced indoleamine 2,3-dioxygenase by dendritic cells,” Multiple Sclerosis, vol. 13, no. 1, pp. 33–40, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. S. S. Soldan, A. I. A. Retuerto, N. L. Sicotte, and R. R. Voskuhl, “Immune modulation in multiple sclerosis patients treated with the pregnancy hormone estriol,” Journal of Immunology, vol. 171, no. 11, pp. 6267–6274, 2003. View at Google Scholar · View at Scopus
  26. Z. Williams, “Inducing tolerance to pregnancy,” The New England Journal of Medicine, vol. 367, pp. 1159–1161, 2012. View at Google Scholar
  27. J. M. Lipton and A. Catania, “Anti-inflammatory actions of the neuroimmunomodulator α-MSH,” Immunology Today, vol. 18, no. 3, pp. 140–145, 1997. View at Publisher · View at Google Scholar · View at Scopus
  28. J. M. Lipton, “Modulation of host defense by the neuropeptide α-MSH,” Yale Journal of Biology and Medicine, vol. 63, no. 2, pp. 173–182, 1990. View at Google Scholar · View at Scopus
  29. J. Harness, A. Cavanagh, H. Morton, and P. McCombe, “A protective effect of early pregnancy factor on experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein,” Journal of the Neurological Sciences, vol. 216, no. 1, pp. 33–41, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. T. B. Tomasi Jr., “Structure and function of alpha-fetoprotein,” Annual Review of Medicine, vol. 28, pp. 453–465, 1977. View at Google Scholar · View at Scopus
  31. E. Matsuura, Y. Kang, H. Kitakawa et al., “Modulation of T cell function by alpha-fetoprotein: an in vivo study on porcine thyroid peroxidase-induced experimental autoimmune thyroiditis in transgenic mice producing human alpha-fetoprotein,” Tumor Biology, vol. 20, no. 3, pp. 162–171, 1999. View at Publisher · View at Google Scholar · View at Scopus
  32. S. Vassiliadis, A. Ranella, L. Papadimitriou, A. Makrygiannakis, and I. Athanassakis, “Serum levels of pro- and anti-inflammatory cytokines in non-pregnant women, during pregnancy, labour and abortion,” Mediators of Inflammation, vol. 7, no. 2, pp. 69–72, 1998. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Ostensen, R. Lundgren, G. Husby, and O. P. Rekvig, “Studies on humoral immunity in pregnancy: immunoglobulins, alloantibodies and autoantibodies in healthy pregnant women and in pregnant women with rheumatoid disease,” Journal of Clinical and Laboratory Immunology, vol. 11, no. 3, pp. 143–147, 1983. View at Google Scholar · View at Scopus
  34. C. Taguchi, E. Ikeda, N. Hikita, and M. Mochizuki, “A report of two cases suggesting positive influence of pregnancy on uveitis activity,” Nippon Ganka Gakkai zasshi, vol. 103, no. 1, pp. 66–71, 1999. View at Google Scholar · View at Scopus
  35. A. Kubicka-Trz̧ska, “Endogenous uveitis during pregnancy—a report of 4 cases,” Klinika Oczna, vol. 106, no. 3, pp. 328–331, 2004. View at Google Scholar · View at Scopus
  36. K. Yamada, K. Kimoto, J. Ikewaki, K. Nakatsuka, and H. Yatsuka, “A case of recurrent uveitis with remission during pregnancies,” Japanese Journal of Clinical Ophthalmology, vol. 57, no. 3, pp. 311–315, 2003. View at Google Scholar · View at Scopus
  37. P. K. Rabiah and A. T. Vitale, “Noninfectious uveitis and pregnancy,” American Journal of Ophthalmology, vol. 136, no. 1, pp. 91–98, 2003. View at Publisher · View at Google Scholar · View at Scopus
  38. L. I. Kump, R. A. Cervantes-Castañeda, S. N. Androudi, C. S. Foster, and W. G. Christen, “Patterns of exacerbations of chronic non-infectious uveitis in pregnancy and puerperium,” Ocular Immunology and Inflammation, vol. 14, no. 2, pp. 99–104, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. N. P. Chiam, A. J. Hall, R. J. Stawell, L. Busija, and L. L. Lim, “The course of uveitis in pregnancy and postpartum,” The British Journal of Ophthalmology, vol. 97, no. 10, pp. 1284–1288, 2013. View at Publisher · View at Google Scholar
  40. D. A. Jabs, “Epidemiology of uveitis,” Ophthalmic Epidemiology, vol. 15, no. 5, pp. 283–284, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. J. H. Barrett, P. Brennan, M. Fiddler, and A. Silman, “Breast-feeding and postpartum relapse in women with rheumatoid and inflammatory arthritis,” Arthritis & Rheumatism, vol. 43, pp. 1010–1015, 2000. View at Google Scholar
  42. J. H. Barrett, P. Brennan, M. Fiddler, and A. J. Silman, “Does rheumatoid arthritis remit during pregnancy and relapse postpartum? Results from a nationwide study in the United Kingdom performed prospectively from late pregnancy,” Arthritis & Rheumatism, vol. 42, pp. 1219–1227, 1999. View at Google Scholar
  43. L. Matera, M. Mori, M. Geuna, S. Buttiglieri, and G. Palestro, “Prolactin in autoimmunity and antitumor defence,” Journal of Neuroimmunology, vol. 109, no. 1, pp. 47–55, 2000. View at Publisher · View at Google Scholar · View at Scopus
  44. S. E. Walker, D. Miller, D. Hill, and G. R. Komatireddy, “Prolactin, a pituitary hormone that modifies immune responses. Proceedings of the Mini-symposium on Prolactin and SLE, held at the 5th International Conference on Systemic Lupus Erythematosus, Cancun, Mexico.,” Lupus, vol. 7, no. 6, pp. 371–375, 1998. View at Publisher · View at Google Scholar · View at Scopus
  45. K. B. Elbourne, D. Keisler, and R. W. McMurray, “Differential effects of estrogen and prolactin on autoimmune disease in the NZB/NZW F1 mouse model of systemic lupus erythematosus,” Lupus, vol. 7, no. 6, pp. 420–427, 1998. View at Publisher · View at Google Scholar · View at Scopus
  46. J. L. Nelson and M. Ostenson, “Pregnancy and rheumatoid arthritis,” Rheumatic Disease Clinics of North America, vol. 23, no. 1, pp. 195–212, 1997. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Østensen and P. M. Villiger, “Immunology of pregnancy—pregnancy as a remission inducing agent in rheumatoid arthritis,” Transplant Immunology, vol. 9, no. 2–4, pp. 155–160, 2002. View at Publisher · View at Google Scholar · View at Scopus
  48. S. H. Zrour, R. Boumiza, N. Sakly et al., “The impact of pregnancy on rheumatoid arthritis outcome: the role of maternofetal HLA class II disparity,” Joint Bone Spine, vol. 77, no. 1, pp. 36–40, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. E. Musiej-Nowakowska and R. Ploski, “Pregnancy and early onset pauciarticular juvenile chronic arthritis,” Annals of the Rheumatic Diseases, vol. 58, no. 8, pp. 475–480, 1999. View at Google Scholar · View at Scopus
  50. M. Ostensen, “Pregnancy in patients with a history of juvenile rheumatoid arthritis,” Arthritis and Rheumatism, vol. 34, no. 7, pp. 881–887, 1991. View at Google Scholar · View at Scopus
  51. C. Gordon, “Pregnancy and autoimmune diseases,” Best Practice & Research Clinical Rheumatology, vol. 18, pp. 359–379, 2004. View at Google Scholar
  52. R. L. Mayock, R. D. Sullivan, R. R. Greening, and R. Jones Jr., “Sarcoidosis and pregnancy,” Journal of the American Medical Association, vol. 164, no. 2, pp. 158–163, 1957. View at Google Scholar · View at Scopus
  53. D. A. Snyder and H. H. Tessler, “Vogt-Koyanagi-Harada syndrome,” American Journal of Ophthalmology, vol. 90, no. 1, pp. 69–75, 1980. View at Google Scholar · View at Scopus
  54. L. P. Steahly, “Vogt-Koyanagi-Harada syndrome and pregnancy,” Annals of Ophthalmology, vol. 22, no. 2, pp. 59–62, 1990. View at Google Scholar · View at Scopus
  55. Z. Friedman, M. Granat, and E. Neumann, “The syndrome of Vogt-Koyanagi-Harada and pregnancy,” Metabolic Ophthalmology, vol. 4, no. 3, pp. 147–149, 1980. View at Google Scholar · View at Scopus
  56. M. Nohara, K. Norose, and K. Segawa, “Vogt-Koyanagi-Harada disease during pregnancy,” British Journal of Ophthalmology, vol. 79, no. 1, pp. 94–95, 1995. View at Google Scholar · View at Scopus
  57. M. Doi, H. Matsubara, and Y. Uji, “Vogt-Koyanagi-Harada syndrome in a pregnant patient treated with high-dose systemic corticosteroids,” Acta Ophthalmologica Scandinavica, vol. 78, no. 1, pp. 93–96, 2000. View at Publisher · View at Google Scholar · View at Scopus
  58. N. Miyata, M. Sugita, S. Nakamura et al., “Treatment of Vogt-Koyanagi- Harada's disease during pregnancy,” Japanese Journal of Ophthalmology, vol. 45, no. 2, pp. 177–180, 2001. View at Publisher · View at Google Scholar · View at Scopus
  59. D. Wakefield, A. Abu El-Asrar, and P. McCluskey, “Treatment of severe inflammatory eye disease in patients of reproductive age and during pregnancy,” Ocular Immunology and Inflammation, vol. 20, pp. 277–287, 2012. View at Google Scholar
  60. C. Y. Chung, A. K. H. Kwok, and K. L. Chung, “Use of opthalmic medications during pregnancy,” Hong Kong Medical Journal, vol. 10, no. 3, pp. 191–195, 2004. View at Google Scholar · View at Scopus
  61. Mycophenolate REMS, “Food and Drug Administration,” 2012, https://www.mycophenolaterems.com/HCPOverview.aspx.
  62. M. Barbhaiya and B. L. Bermas, “Evaluation and management of systemic lupus erythematosus and rheumatoid arthritis during pregnancy,” Clinical Immunology, vol. 149, pp. 225–235, 2013. View at Google Scholar
  63. K. K. Temprano, R. Bandlamudi, and T. L. Moore, “Antirheumatic drugs in pregnancy and lactation,” Seminars in Arthritis and Rheumatism, vol. 35, no. 2, pp. 112–121, 2005. View at Publisher · View at Google Scholar · View at Scopus
  64. A. B. Elliott and E. F. Chakravarty, “Immunosuppressive medications during pregnancy and lactation in women with autoimmune diseases,” Women's Health, vol. 6, no. 3, pp. 431–442, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. M. Petri, “Immunosuppressive drug use in pregnancy,” Autoimmunity, vol. 36, no. 1, pp. 51–56, 2003. View at Publisher · View at Google Scholar · View at Scopus
  66. S. R. J. Taylor, H. Isa, L. Joshi, and S. Lightman, “New developments in corticosteroid therapy for uveitis,” Ophthalmologica, vol. 224, supplement 1, pp. 46–53, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. P. Ferrante, A. Ramsey, C. Bunce, and S. Lightman, “Clinical trial to compare efficacy and side-effects of injection of posterior sub-Tenon triamcinolone versus orbital floor methylprednisolone in the management of posterior uveitis,” Clinical and Experimental Ophthalmology, vol. 32, no. 6, pp. 563–568, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. P. Riordan-Eva and S. Lightman, “Orbital floor steroid injections in the treatment of uveitis,” Eye, vol. 8, part 1, pp. 66–69, 1994. View at Google Scholar · View at Scopus
  69. C. J. Helm and G. N. Holland, “The effects of posterior subtenon injection of triamcinolone acetonide in patients with intermediate uveitis,” American Journal of Ophthalmology, vol. 120, no. 1, pp. 55–64, 1995. View at Google Scholar · View at Scopus
  70. I. G. M. Duguid, R. L. Ford, S. E. Horgan, H. M. A. Towler, and S. L. Lightman, “Combined orbital floor betamethasone and depot methylprednisolone in uveitis,” Ocular Immunology and Inflammation, vol. 13, no. 1, pp. 19–24, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. M. L. Dafflon, V. T. Tran, Y. Guex-Crosier, and C. P. Herbort, “Posterior sub-Tenon's steroid injections for the treatment of posterior ocular inflammation: indications, efficacy and side effects,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 237, no. 4, pp. 289–295, 1999. View at Publisher · View at Google Scholar · View at Scopus
  72. V. Tanner, J. J. Kanski, and P. A. Frith, “Posterior sub-Tenon's triamcinolone injections in the treatment of uveitis,” Eye, vol. 12, part 4, pp. 679–685, 1998. View at Google Scholar · View at Scopus
  73. M. Roesel, M. Gutfleisch, C. Heinz, B. Heimes, B. Zurek-Imhoff, and A. Heiligenhaus, “Orbital floor triamcinolone acetonide injections for the management of active non-infectious uveitis,” Eye, vol. 23, no. 4, pp. 910–914, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. S. Raghava, M. Hammond, and U. B. Kompella, “Periocular routes for retinal drug delivery,” Expert Opinion on Drug Delivery, vol. 1, no. 1, pp. 99–114, 2004. View at Publisher · View at Google Scholar · View at Scopus
  75. Y. S. Byun and Y.-H. Park, “Complications and safety profile of posterior subtenon injection of triamcinolone acetonide,” Journal of Ocular Pharmacology and Therapeutics, vol. 25, no. 2, pp. 159–162, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Roesel, M. Gutfleisch, C. Heinz, B. Heimes, B. Zurek-Imhoff, and A. Heiligenhaus, “Intravitreal and orbital floor triamcinolone acetonide injections in noninfectious uveitis: a comparative study,” Ophthalmic Research, vol. 42, no. 2, pp. 81–86, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. R. J. Antcliff, D. J. Spalton, M. R. Stanford, E. M. Graham, T. J. Fytche, and J. Marshall, “Intravitreal triamcinolone for uveitic cystoid macular edema: an optical coherence tomography study,” Ophthalmology, vol. 108, no. 4, pp. 765–772, 2001. View at Publisher · View at Google Scholar · View at Scopus
  78. S. Young, G. Larkin, M. Branley, and S. Lightman, “Safety and efficacy of intravitreal triamcinolone for cystoid macular oedema in uveitis,” Clinical and Experimental Ophthalmology, vol. 29, no. 1, pp. 2–6, 2001. View at Publisher · View at Google Scholar · View at Scopus
  79. S. Androudi, E. Letko, M. Meniconi, T. Papadaki, M. Ahmed, and C. S. Foster, “Safety and efficacy of intravitreal triamcinolone acetonide for uveitic macular edema,” Ocular Immunology and Inflammation, vol. 13, no. 2-3, pp. 205–212, 2005. View at Publisher · View at Google Scholar · View at Scopus
  80. R. I. Angunawela, C. J. Heatley, T. H. Williamson et al., “Intravitreal triamcinalone acetonide for refractory uveitic cystoid macular oedema: longterm management and outcome,” Acta Ophthalmologica Scandinavica, vol. 83, no. 5, pp. 595–599, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. H. Kok, C. Lau, N. Maycock, P. McCluskey, and S. Lightman, “Outcome of intravitreal triamcinolone in uveitis,” Ophthalmology, vol. 112, no. 11, pp. 1916.e1–1916.e7, 2005. View at Publisher · View at Google Scholar · View at Scopus
  82. M. C. Gillies, J. M. Simpson, F. A. Billson et al., “Safety of an intravitreal injection of triamcinolone: results from a randomized clinical trial,” Archives of Ophthalmology, vol. 122, no. 3, pp. 336–340, 2004. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Tuncer, S. Yilmaz, M. Urgancioglu, and I. Tugal-Tutkun, “Results of Intravitreal Triamcinolone Acetonide (IVTA) injection for the treatment of panuveitis attacks in patients with Behçet disease,” Journal of Ocular Pharmacology and Therapeutics, vol. 23, no. 4, pp. 395–401, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. M. Kramer, R. Ehrlich, M. Snir et al., “Intravitreal injections of triamcinolone acetonide for severe vitritis in patients with incomplete Behcet's disease,” American Journal of Ophthalmology, vol. 138, no. 4, pp. 666–667, 2004. View at Publisher · View at Google Scholar · View at Scopus
  85. M. Karacorlu, B. Mudun, H. Ozdemir, S. A. Karacorlu, and E. Burumcek, “Intravitreal triamcinolone acetonide for the treatment of cystoid macular edema secondary to Behçet disease,” American Journal of Ophthalmology, vol. 138, no. 2, pp. 289–291, 2004. View at Publisher · View at Google Scholar · View at Scopus
  86. M. Karacorlu, S. Arf Karacorlu, and H. Ozdemir, “Intravitreal triamcinolone acetonide in Vogt-Koyanagi-Harada syndrome,” European Journal of Ophthalmology, vol. 16, no. 3, pp. 481–483, 2006. View at Google Scholar · View at Scopus
  87. S. Karacorlu, H. Ozdemir, and M. Karacorlu, “Intravitreal triamcinolone acetonide in serpiginous choroiditis,” Japanese Journal of Ophthalmology, vol. 50, no. 3, pp. 290–291, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. H. Ozdemir, M. Karacorlu, and S. Karacorlu, “Intravitreal triamcinolone acetonide in sympathetic ophthalmia,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 243, no. 7, pp. 734–736, 2005. View at Publisher · View at Google Scholar · View at Scopus
  89. R. V. P. Chan, B. D. Seiff, H. A. Lincoff, and D. J. Coleman, “Rapid recovery of sympathetic ophthalmia with treatment augmented by intravitreal steroids,” Retina, vol. 26, no. 2, pp. 243–247, 2006. View at Publisher · View at Google Scholar · View at Scopus
  90. J. B. Jonas, “Intravitreal triamcinolone acetonide for treatment of sympathetic ophthalmia,” American Journal of Ophthalmology, vol. 137, no. 2, pp. 367–368, 2004. View at Publisher · View at Google Scholar · View at Scopus
  91. J. B. Jonas and U. H. M. Spandau, “Repeated intravitreal triamcinolone acetonide for chronic sympathetic ophthalmia,” Acta Ophthalmologica Scandinavica, vol. 84, no. 3, p. 436, 2006. View at Publisher · View at Google Scholar · View at Scopus
  92. M. Roesel, C. Tappeiner, C. Heinz, J. M. Koch, and A. Heiligenhaus, “Comparison between intravitreal and orbital floor triamcinolone acetonide after phacoemulsification in patients with endogenous uveitis,” American Journal of Ophthalmology, vol. 147, no. 3, pp. 406–412, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Choudhry and S. Ghosh, “Intravitreal and posterior subtenon triamcinolone acetonide in idiopathic bilateral uveitic macular oedema,” Clinical and Experimental Ophthalmology, vol. 35, no. 8, pp. 713–718, 2007. View at Publisher · View at Google Scholar · View at Scopus
  94. A. Sallam, R. M. Comer, J. H. Chang et al., “Short-term safety and efficacy of intravitreal triamcinolone acetonide for uveitic macular edema in children,” Archives of Ophthalmology, vol. 126, no. 2, pp. 200–205, 2008. View at Publisher · View at Google Scholar · View at Scopus
  95. Y. Tao and J. B. Jonas, “Intravitreal triamcinolone,” Ophthalmologica, vol. 225, no. 1, pp. 1–20, 2011. View at Publisher · View at Google Scholar · View at Scopus
  96. J. H. Kempen, M. M. Altaweel, J. T. Holbrook et al., “Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial,” Ophthalmology, vol. 118, no. 10, pp. 1916–1926, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. C. Lowder, R. Belfort Jr., S. Lightman et al., “Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis,” Archives of Ophthalmology, vol. 129, no. 5, pp. 545–553, 2011. View at Publisher · View at Google Scholar · View at Scopus
  98. L. L. Lim, J. R. Smith, and J. T. Rosenbaum, “Retisert Bausch & Lomb/control delivery systems,” Current Opinion in Investigational Drugs, vol. 6, no. 11, pp. 1159–1167, 2005. View at Google Scholar · View at Scopus
  99. M. Østensen, “Antirheumatic therapy and reproduction. The influence on fertility, pregnancy and breast feeding,” Zeitschrift fur Rheumatologie, vol. 65, no. 3, pp. 217–224, 2006. View at Publisher · View at Google Scholar · View at Scopus
  100. L. Park-Wyllie, P. Mazzotta, A. Pastuszak et al., “Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies,” Teratology, vol. 62, pp. 385–392, 2000. View at Google Scholar
  101. P. A. Rosandich, J. T. Kelley III, and D. L. Conn, “Perioperative management of patients with rheumatoid arthritis in the era of biologic response modifiers,” Current Opinion in Rheumatology, vol. 16, no. 3, pp. 192–198, 2004. View at Publisher · View at Google Scholar · View at Scopus
  102. P. A. Greenberger, Y. K. Odeh, M. C. Frederiksen, and A. J. Atkinson Jr., “Pharmacokinetics of prednisolone transfer to breast milk,” Clinical Pharmacology and Therapeutics, vol. 53, no. 3, pp. 324–328, 1993. View at Google Scholar · View at Scopus
  103. L. Ost, G. Wettrell, I. Bjorkhem, and A. Rane, “Prednisolone excretion in human milk,” Journal of Pediatrics, vol. 106, no. 6, pp. 1008–1011, 1985. View at Google Scholar · View at Scopus
  104. B. Nørgård, L. Pedersen, K. Fonager, S. N. Rasmussen, and H. T. Sørensen, “Azathioprine, mercaptopurine and birth outcome: a population-based cohort study,” Alimentary Pharmacology and Therapeutics, vol. 17, no. 6, pp. 827–834, 2003. View at Publisher · View at Google Scholar · View at Scopus
  105. C. Dejaco, C. Mittermaier, W. Reinisch et al., “Azathioprine treatment and male fertility in inflammatory bowel disease,” Gastroenterology, vol. 121, no. 5, pp. 1048–1053, 2001. View at Google Scholar · View at Scopus
  106. C. B. Coulam, T. P. Moyer, N. S. Jiang, and H. Zincke, “Breast-feeding after renal transplantation,” Transplantation Proceedings, vol. 14, no. 3, pp. 605–609, 1982. View at Google Scholar · View at Scopus
  107. V. T. Armenti, J. S. Radomski, M. J. Moritz et al., “Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation,” Clinical transplants, pp. 97–105, 2001. View at Google Scholar · View at Scopus
  108. P. E. Pergola, A. Kancharla, and D. J. Riley, “Kidney transplantation during the first trimester of pregnancy: immunosuppression with mycophenolate mofetil, tacrolimus, and prednisone,” Transplantation, vol. 71, no. 7, pp. 994–997, 2001. View at Google Scholar · View at Scopus
  109. C. Le Ray, A. Coulomb, E. Elefant, R. Frydman, and F. Audibert, “Mycophenolate mofetil in pregnancy after renal transplantation: a case of major fetal malformations,” Obstetrics and Gynecology, vol. 103, no. 5, pp. 1091–1094, 2004. View at Google Scholar · View at Scopus
  110. S. Di Paolo, A. Schena, L. F. Morrone et al., “Immunologic evaluation during the first year of life of infants born to cyclosporine-treated female kidney transplant recipients: analysis of lymphocyte subpopulations and immunoglobulin serum levels,” Transplantation, vol. 69, no. 10, pp. 2049–2054, 2000. View at Google Scholar · View at Scopus
  111. M. E. Moretti, M. Sgro, D. W. Johnson et al., “Cyclosporine excretion into breast milk,” Transplantation, vol. 75, no. 12, pp. 2144–2146, 2003. View at Publisher · View at Google Scholar · View at Scopus
  112. J. A. Katz, C. Antoni, G. F. Keenan, D. E. Smith, S. J. Jacobs, and G. R. Lichtenstein, “Outcome of pregnancy in women receiving infliximab for the treatment of Crohn's disease and rheumatoid arthritis,” American Journal of Gastroenterology, vol. 99, no. 12, pp. 2385–2392, 2004. View at Publisher · View at Google Scholar · View at Scopus
  113. U. Mahadevan, S. Kane, W. J. Sandborn et al., “Intentional infliximab use during pregnancy for induction or maintenance of remission in Crohn's disease,” Alimentary Pharmacology and Therapeutics, vol. 21, no. 6, pp. 733–738, 2005. View at Publisher · View at Google Scholar · View at Scopus
  114. B. P. Giroir, K. Peppel, M. Silva, and B. Beutler, “The biosynthesis of tumor necrosis factor during pregnancy: studies with a CAT reporter transgene and TNF inhibitors,” European Cytokine Network, vol. 3, no. 6, pp. 533–538, 1992. View at Google Scholar · View at Scopus
  115. K. L. Hyrich, D. P. M. Symmons, K. D. Watson, and A. J. Silman, “Pregnancy outcome in women who were exposed to anti-tumor necrosis factor agents: results from a national population register,” Arthritis and Rheumatism, vol. 54, no. 8, pp. 2701–2702, 2006. View at Publisher · View at Google Scholar · View at Scopus
  116. D. J. Wallace and M. H. Weisman, “The use of etanercept and other tumor necrosis factor-α blockers in infertility: it's time to get serious,” Journal of Rheumatology, vol. 30, no. 9, pp. 1897–1899, 2003. View at Google Scholar · View at Scopus
  117. G. M. Enns, E. Roeder, R. T. Chan, Z. Ali-Khan Catts, V. A. Cox, and M. Golabi, “Apparent cyclophosphamide, (cytoxan) embryopathy: a distinct phenotype?” American Journal of Medical Genetics, vol. 86, pp. 237–241, 1999. View at Google Scholar
  118. J. Penso, B. Lippe, R. Ehrlich, and F. G. Smith, “Testicular function in prepubertal and pubertal male patients treated with cyclophosphamide for nephrotic syndrome,” Journal of Pediatrics, vol. 84, no. 6, pp. 831–836, 1974. View at Google Scholar · View at Scopus
  119. W. H. B. Wallace, S. M. Shalet, M. Lendon, and P. H. Morris-Jones, “Male fertility in long-term survivors of childhood acute lymphoblastic leukaemia,” International Journal of Andrology, vol. 14, no. 5, pp. 312–319, 1991. View at Google Scholar · View at Scopus
  120. V. Papadakis, E. Vlachopapadopoulou, K. van Syckle et al., “Gonadal function in young patients successfully treated for Hodgkin disease,” Medical and Pediatric Oncology, vol. 32, pp. 366–372, 1999. View at Google Scholar
  121. P. H. Wiernik and J. H. Duncan, “Cyclophosphamide in human milk,” The Lancet, vol. 1, no. 7705, article 912, 1971. View at Google Scholar · View at Scopus
  122. R. Rahimi, S. Nikfar, A. Rezaie, and M. Abdollahi, “Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis,” Reproductive Toxicology, vol. 25, no. 2, pp. 271–275, 2008. View at Publisher · View at Google Scholar · View at Scopus
  123. B. Nørgård, A. E. Czeizel, M. Rockenbauer, J. Olsen, and H. T. Sørensen, “Population-based case control study of the safety of sulfasalazine use during pregnancy,” Alimentary Pharmacology and Therapeutics, vol. 15, no. 4, pp. 483–486, 2001. View at Publisher · View at Google Scholar · View at Scopus
  124. M. Mogadam, W. O. Dobbins III, B. I. Korelitz, and S. W. Ahmed, “Pregnancy in inflammatory bowel disease: effect of sulfasalazine and corticosteroids on fetal outcome,” Gastroenterology, vol. 80, no. 1, pp. 72–76, 1981. View at Google Scholar · View at Scopus
  125. E. Esbjorner, G. Jarnerot, and L. Wranne, “Sulphasalazine and sulphapyridine serum levels in children to mothers treated with sulphasalazine during pregnancy and lactation,” Acta Paediatrica Scandinavica, vol. 76, no. 1, pp. 137–142, 1987. View at Google Scholar · View at Scopus
  126. G. Jarnerot and M.-B. Into-Malmberg, “Sulphasalazine treatment during breast feeding,” Scandinavian Journal of Gastroenterology, vol. 14, no. 7, pp. 869–871, 1979. View at Google Scholar · View at Scopus