Biology Of Pregnancy Research Articles

Considerations for the Use of Biologics in Pregnancy

Considerations for the Use of Biologics in Pregnancy

The "Bad Father": Paternal Role in Biology of Pregnancy and in Birth Outcome.

Pregnancy is generally studied as a biological interaction between a mother and a fetus; however, the father, with his characteristics, lifestyle, genetics, and living environment, is by no means unrelated to the outcome of pregnancy. The half of the fetal genetic heritage of paternal derivation can be decisive in cases of inherited chromosomal disorders, and can be the result of de novo genetic alterations. In addition to the strictly pathological aspects, paternal genetics may transmit thrombophilic traits that affect the implantation and vascular construction of the feto-placental unit, lead to placenta-mediated diseases such as pre-eclampsia and fetal growth retardation, and contribute to the multifactorial genesis of preterm delivery. Biological aspects of immunological tolerance to paternal antigens also appear to be crucial for these pathologies. Finally, this review describes the biological findings by which the environment, exposure to pathogens, lifestyle, and nutritional style of the father affect fetal pathophysiological and epigenetic definition.

P741 Do gastroenterology services need published standards for provision of antenatal care in patients with Inflammatory Bowel Disease? A local evaluation of UK practice

Abstract Background Inflammatory bowel disease (IBD) is common with 0.5-1% of the UK living with the disease. Poor disease control can result in adverse pregnancy outcomes including low birth weight and preterm labour. It is essential that pregnant patients with IBD receive care from physicians experienced in management of antenatal IBD. Furthermore patients must be equipped with the knowledge to make decisions on their care and the care of their new-born. Audit standards by Selinger et al 20201 for the British Society of Gastroenterology (endorsed by the British Maternal and Fetal Medicine Society) have been published for UK practice but local service standards are unknown. Methods Pregnant patients with Crohn’s disease (CD) and Ulcerative Colitis (UC) between 2017-2020 were identified with ICD-10 and OPSC-4 codes for a hospital with 650 inpatient beds and a catchment area of 450,000 with around 4,600 births per annum. The service was assessed against a 90% compliance standard for documentation of: a decision on biological therapy during pregnancy; discussion on mode of delivery (MoD); antenatal live vaccine counselling; and breast-feeding advice. Results 48 eligible patients were identified. Mean birth weight and delivery date were in line with the national average with no preterm births. 41 of 48 patients (85%) were in remission at the time of conception. 9 of 25 CD pregnancies were on biologics at conception and 7 of 9 (78%) discontinued this by 24-weeks gestation; one continued vedolizumab to 30-weeks and received antenatal vaccine counselling; one continued ustekinumab to 34-weeks. 4 out of 23 UC pregnancies were on biologics at conception; all ceased biologics by 24-weeks and vaccine counselling was not indicated. Only one published standard was achieved, with decision on biologics in pregnancy discussed in 100% (13/13). 3 standards were not met; MoD discussion (23%, 11/48); antenatal vaccine counselling (50%, 1/2); and breast-feeding advice (4%, 2/48). Conclusion Our service did not meet new standards for antenatal IBD care, demonstrating a need for improvement. We recommend that all IBD teams understand the expected service standards, perform a baseline service evaluation and develop clear patient pathways and departmental guidelines to identify pregnant patients with IBD. Clear patient information and close collaboration between obstetricians and gastroenterologists is essential to optimise the outcome for mother and baby. 1) Selinger C et al Standards for the provision of antenatal care for patients with inflammatory bowel disease: guidance endorsed by the British Society of Gastroenterology and the British Maternal and Fetal Medicine Society. Frontline Gastroenterology 2021;12:182-187 BMJ 2020

Bezpečnost biologické léčby vedolizumabem a ustekinumabem podávané v průběhu gravidity pro idiopatický střevní zánět matek – multicentrická retrospektivně-prospektivní observační studie

Background: Inflammatory bowel disease (IBD) is mostly diagnosed in young women of fertile age, and a significant number of patients become pregnant while they have the disease. The remission of the illness, which is often achieved by intensive anti inflammatory treatment, has been found to be the most important factor of a successful pregnancy. Vedolizumab (VDZ) and ustekinumab (UST) are newer types of monoclonal antibodies with different mechanisms of effect when compared to anti-TNF treatment. VDZ is a monoclonal antibody against the α4ß7 integrin receptor, and UST against interleukin 12/23; both have expanded the spectrum of the biological treatment of IBD in recent years. Aims: To present the results of a multicentre observational study. The primary aim was to assess the safety of vedolizumab and ustekinumab for pregnancy, foetal development and the neonatal outcome. The secondary aim was to measure the drug concentration in maternal and cord blood at the time of delivery. Methods: It was a multicentre, retrospective-prospective observational study. Data on patients’ demographics, clinical characteristics and pregnancy were collected by the treating physician using a predefined questionnaire, data on newborn outcome were obtained from medical documentation. The ELISA method was used to measure the VDZ and UST concentrations. Results: The study took place in 15 IBD clinical centres in the Czech Republic. 79 women with 85 completed pregnancies were included in the study, and they were exposed to VDZ or UST during pregnancy. 36 women were treated with vedolizumab (median age 32 years) and 49 with ustekinumab (median age 30.5 years). In the group with VDZ, live births occurred with 32 women (88.9%), and there were two early spontaneous abortions up to the eighth week of gestation in addition to two instrumentally aborted pregnancies (4, 11.1%). 31 children (93.9%) in the group with VDZ were born at term with a median birth weight of 3,097.5 grams. In the ustekinumab group, 39 women (79.6%) had live births, there were nine early abortions and one instrumentally aborted pregnancy (10, 20.4%). 38 (97.4%) children were born at term with a median birth weight of 3,265 grams. The drug levels of VDZ and UST at birth were measured in 44 neonate-mother pairs (21 VDZ, 23 UST). The median level of VDZ in maternal venous blood was 7.2 mg/l, and in cord blood it was 4.7 mg/l (infant / maternal ratio 0.66). With UST, the median maternal level was 4.7 mg/l, and in neonates it was 7.9 mg/l (infant / maternal ratio 1.65). Conclusion: The results found in a group of women that were being treated for IBD and were exposed to at least one dose of biologic treatment with UST or VDZ during pregnancy are consistent with previously published evidence showing no adverse events, and they confirm the safety profile of new biologics in pregnancy. Due to the still limited number of enrolled patients, further studies are needed on the outcomes of pregnancies with new biologics drugs. Keywords vedolizumab, ustekinumab, pregnancy, transplacentární přenos

Comparative fecal steroid profile during pregnancy, parturition, and lactation between natural fertilization and embryo transfer in ocelots (Leopardus pardalis)

Despite the invaluable role that assisted reproduction technologies (ARTs) play in conservation, pregnancy and parturition rates by embryo transfer (ET) are low for most endangered felids. Thus, efforts to expand the knowledge on pregnancy biology and ET are still required. In this context, we examined fecal sex steroid metabolites (i.e., estrogens, glucocorticoids, and progestogens) of eight ocelots submitted to natural fertilization (NF) and ET in 22 pregnancies (19 NF and 3 ET). Fecal samples were collected and assessed for each pregnancy from estrous cycle, pregnancy, and lactation, totaling 155 days. In short, progestogen levels remained high and unchanged (P < 0.05) from conception until parturition for females maintained under NF. On the other hand, females submitted to ET exhibited changes (P > 0.05) in progestogen levels from conception until parturition, with a significant decrease during pregnancy (480.72 ng/day; r2 = 0.81; P < 0.0001). Significant changes between NF and ET also were noted in estrogen levels between the first and last thirds of pregnancy (P < 0.05), in which estrogen levels exhibited a negative correlation (P < 0.01) between themselves. Regarding glucocorticoids, significant changes (P < 0.01) were observed only in the first third of pregnancy between NF and ET, which we believe may be related to the handling for ovarian synchronization and ET. Besides hormonal changes, the pregnancy was more prolonged (2.5 days) and more prone to dystocia in ET than NF. Overall, 24 embryos were transferred into eight females (3/1), with three kittens being born from three distinct deliveries (i.e., 12.5% of embryos and 37.5% of females). Our findings have supported the great potential of production and transfer of long-term frozen embryos in ocelot conservation. However, they reveal possible effects of these biotechnologies on hormonal levels during pregnancy linked with low conception and parturition rates and dystocic cases in felids.

Uterus transplantation: the importance of uterine natural killer cells.

Murine studies have established that uterine natural killer (uNK) cells are critical regulators of normal placentation and fetal development in mammals. However, the biology of uNK cells in humans remains poorly understood. This ignorance represents a costly knowledge gap, as disordered placentation is thought to underpin a variety of pregnancy complications that impact maternal and neonatal health. In the context of uterus transplantation (UTx), uNK cells are anticipated to play a critical role within the allograft. Here, we review the current understanding of uNK cells in pregnancy biology and explore how this critically important cell population may contribute to pregnancy and graft outcomes in uterus transplant recipients. Recent studies have characterized differences in NK cell populations between anatomic compartments in humans. In the endometrium, at least five phenotypically and functionally distinct subpopulations of uNK cells have been identified, with research into mechanisms regulating their differentiation and function currently underway. Further elucidating uNK cell biology has the potential to influence the outcomes of pregnancy and UTx and benefit human health. UTx is a unique opportunity to study uNK cell biology and may shed light on mechanisms by which immunological tolerance is established at the maternal-fetal interface.

ELF3 activated by a superenhancer and an autoregulatory feedback loop is required for high-level HLA-C expression on extravillous trophoblasts

HLA-C arose during evolution of pregnancy in the great apes 10 to 15 million years ago. It has a dual function on placental extravillous trophoblasts (EVTs) as it contributes to both tolerance and immunity at the maternal-fetal interface. The mode of its regulation is of considerable interest in connection with the biology of pregnancy and pregnancy abnormalities. First-trimester primary EVTs in which HLA-C is highly expressed, as well as JEG3, an EVT model cell line, were employed. Single-cell RNA-seq data and quantitative PCR identified high expression of the transcription factor ELF3 in those cells. Chromatin immunoprecipitation (ChIP)-PCR confirmed that both ELF3 and MED1 bound to the proximal HLA-C promoter region. However, binding of RFX5 to this region was absent or severely reduced, and the adjacent HLA-B locus remained closed. Expression of HLA-C was inhibited by ELF3 small interfering RNAs (siRNAs) and by wrenchnolol treatment. Wrenchnolol is a cell-permeable synthetic organic molecule that mimics ELF3 and is relatively specific for binding to ELF3's coactivator, MED23, as our data also showed in JEG3. Moreover, the ELF3 gene is regulated by a superenhancer that spans more than 5 Mb, identified by assay for transposase-accessible chromatin using sequencing (ATAC-seq), as well as by its sensitivity to (+)-JQ1 (inhibitor of BRD4). ELF3 bound to its own promoter, thus creating an autoregulatory feedback loop that establishes expression of ELF3 and HLA-C in trophoblasts. Wrenchnolol blocked binding of MED23 to ELF3, thus disrupting the positive-feedback loop that drives ELF3 expression, with down-regulation of HLA-C expression as a consequence.

Biologics During Pregnancy and Breastfeeding Among Women With Rheumatic Diseases: Safety Clinical Evidence on the Road.

Females are generally more affected by autoimmune diseases, a fact that underlines the relationship with pregnancy and the safety of anti-rheumatic drugs in pregnancy and lactation. Biologic therapies are increasingly prescribed to treat and maintain remission in a significant number of systemic autoimmune rheumatic diseases. The experience with the use of biologics during gestation is extremely lacking because of the observational nature of the available studies and the difficulty in designing proper clinical trials in pregnancy. Among the studied biologics, more information was published on TNFα inhibitors and, in particular, on their potential passage through the placenta and impact on the fetus. Currently, a fragment of anti-TNFα monoclonal IgG, certolizumab pegol, is considered safe with almost no placental transfer. Subsequent observations are suggesting a comparable safety for the soluble TNFα receptor etanercept. Another biologic, eculizumab, the anti-C5a antibody used to treat complement-mediated microangiopathies, is also considered safe due to the unique engineered IgG2/4κ formulation that limits its passage through the placental barrier. Still, long-term data about children born to women treated with biologics in pregnancy are not attainable. Data on breastfeeding are currently available for several biologics. This article reviews the literature available about which drugs are considered safe during pregnancy and lactation, which are not, and on future prospects.

Noninvasive inferring expressed genes and in vivo monitoring of the physiology and pathology of pregnancy using cell-free DNA

Noninvasive monitoring of fetal development and the early detection of pregnancy-associated complications is challenging, largely because of the lack of information about the molecular spectrum during pregnancy. Recently, cell-free DNA in plasma was found to reflect the global nucleosome footprint and status of gene expression and showed potential for noninvasive health monitoring during pregnancy. We aimed to test the relationships between plasma cell-free DNA profiles and pregnancy biology and evaluate the use of a cell-free DNA profile as a noninvasive method for physiological and pathologic status monitoring during pregnancy. We used genome cell-free DNA sequencing data generated from noninvasive prenatal testing in a total of 2937 pregnant women. For each physiological and pathologic condition, features of the cell-free DNA profile were identified using the discovery cohort, and support vector machine classifiers were built and evaluated using independent training and validation cohorts. We established nucleosome occupancy profiles at transcription start sites in different gestational trimesters, demonstrated the relationships between gene expression and cell-free DNA coverage at transcription start sites, and showed that the cell-free DNA profiles at transcription start sites represented the biological processes of pregnancy. In addition, using cell-free DNA data, nucleosome profiles of transcription factor binding sites were identified to reflect the transcription factor footprint, which may help to reveal the molecular mechanisms underlying pregnancy. Finally, by using machine-learning models on low-coverage noninvasive prenatal testing data, we evaluated the use of cell-free DNA nucleosome profiles for distinguishing gestational trimesters, fetal sex, and fetal trisomy 21 and highlighted its potential utility for predicting physiological and pathologic fetal conditions by using low-coverage noninvasive prenatal testing data. Our analyses profiled nucleosome footprints and regulatory networks during pregnancy and established a noninvasive proof-of-principle methodology for health monitoring during pregnancy.

P447 No severe neonatal and maternal complications in inflammatory bowel diseases patients treated with ustekinumab or vedolizumab during pregnancy

Abstract Background Inflammatory bowel diseases (IBD) have a high incidence in the female population of childbearing age. Ustekinumab (UST) and vedolizumab (VDZ) are used in IBD after failure of immunosuppressants and//or anti-TNF therapy. Data on the use and safety of these novel biologics in pregnancy are rare. Methods We conducted a retrospective cohort study in the GETAID and identified female IBD patients who received at least one injection of UST or VDZ during pregnancy or within the 2 months before conception. The aims of the study were to assess the maternal and neonatal complications in these patients and to assess the management of VDZ or UST during pregnancy. Results Seventy-three pregnancies in 68 patients were reported in 21 centres. The median time between UST or VDZ introduction and pregnancy was 11.8 months (IQR: 5.2–17.6) and 10 months (IQR: 5.7–19.5), respectively. Twenty-nine pregnancies occurred in 27 patients on UST resulting in 26 (90%) live births, two (7%) spontaneous abortions, and one (3%) elective termination. Maternal complications were reported in two patients (gestational diabetes and threat of preterm birth). Five (19%) neonatal complications were reported (3 preterm deliveries, one low birth weight and one cardiac malformation). Six (21%) patients received UST in the 2 months before conception and stopped UST with a relapse in one patient (17%). UST was maintained during pregnancy in 22 (79%) patients: 13 patients discontinued UST in the first trimester with a relapse in 4 (31%) patients and 9 patients maintained UST during all pregnancy with a relapse in 3 (33%) patients. Forty-four pregnancies occurred under VDZ resulting in 38 (86%) live births, 5 (11%) spontaneous abortions and one (3%) medical interruption. Maternal complications were reported in 5 women (4 pre-eclampsia and one pregnancy cholestasis). Fourteen (37%) neonatal complications were reported: 7 (18%) premature births, 6 (16%) low birth weights and one (3%) congenital corpus callosum hypoplasia. Fifteen (34%) patients received VDZ in the 2 months before conception and discontinued VDZ with a relapse in 8 (53%) patients. VDZ was maintained during pregnancy in 29 (66%) patients: 16 patients discontinued VDZ in the 1st trimester with a relapse in 8 (50%) patients and 13 patients maintained VDZ during all the pregnancy with a relapse in one (8%) patient. Conclusion We reported 73 pregnancies under VDZ or UST. Except one cardiac malformation on UST and one congenital corpus callosum hypoplasia on VDZ, no serious neonatal or maternal complications were observed. However, additional prospective evaluations regarding pregnancy outcomes with new biologics are needed.

On the trail of steroid aromatase: The work of Kenneth J. Ryan

On the trail of steroid aromatase: The work of Kenneth J. Ryan

The use of biologics for autoimmune rheumatic diseases in fertility and pregnancy.

In an age where autoimmune rheumatic diseases are successfully managed with biologics, their discontinuation in pregnancy is inadvisable without careful forethought; maternal disease activity is associated with adverse pregnancy outcomes, which has long-term implications for both mother and offspring. We aim to provide clinicians with the necessary tools to facilitate decision-making - when a biologic should be used, when it can be discontinued in pregnancy if appropriate. The pathophysiology of these biologic molecules and their effect on fertility, pregnancy and parturition are discussed. A summary of the 2016 international guidelines (European League Against Rheumatism and British Society in Rheumatology) on biologics in pregnancy has been tabulated; more recent publications are discussed in depth. Data on transplacental-transfer ratios and breastmilk excretion rates are also included. Biologic effects on organogenesis, their implications for the exposed infant in terms of infection risks and vaccination requirements are included, and future directions for research proposed.

Immunosuppressives and biologics during pregnancy and lactation : Aconsensus report issued by the Austrian Societies of Gastroenterology and Hepatology and Rheumatology and Rehabilitation.

SummaryAn increasing and early-onset use of immunosuppressives and biologics has become more frequently seen among patients with inflammatory bowel diseases (IBD) and rheumatic disorders. Many women in their childbearing years currently receive such medications, and some of them in an interdisciplinary setting. Many questions arise in women already pregnant or wishing to conceive with respect to continuing or discontinuing treatment, the risks borne by the newborns and their mothers and long-term safety. Together with the Austrian Society of Rheumatology and Rehabilitation, the IBD working group of the Austrian Society of Gastroenterology and Hepatology has elaborated consensus statements on the use of immunosuppressives and biologics in pregnancy and lactation. This is the first Austrian interdisciplinary consensus on this topic. It is intended to serve as a basis and support for providing advice to our patients and their treating physicians.

591: The obstetric and neonatal outcomes of inflammatory bowel disease in pregnancy and associated medication use

The available inflammatory bowel disease (IBD) literature in pregnancy points to an increased risk of preterm birth (PTB), small for gestational age (SGA), and low birth weight, however there is little data regarding the effects of disease severity and use of biologics in pregnancy and postpartum. Our objective was to evaluate maternal, neonatal, and infectious outcomes categorized by disease severity and effect of immunomodulators in pregnancies affected by IBD. This was a retrospective cohort study of patients with IBD who were pregnant and delivered at a single tertiary care institution from 2012 to 2017. Controls were randomly selected from a set of pregnant patients without IBD during the same time frame. Rates of SGA and PTB were compared between cases and controls using logistic regression controlling for maternal age, BMI, history of PTB and race. Within cases, the incidence of maternal and neonatal composite outcomes were compared between groups defined by disease severity, flares in pregnancy, use of biologics, and use of infliximab postpartum using Chi-square and Fisher’s exact tests. There were 219 patients included for analysis (101 with IBD and 118 without). Patients with IBD were more likely to be older (p=0.0004), had a lower BMI (p=0.0002), and were more likely to be Caucasian (p<0.0001) (Table 1). The rate of PTB was significantly higher in cases (10.5%) compared to controls (1.7%), p=0.01. This remained statistically significant in adjusted analysis (p=0.03). SGA rates were comparable between cases (5.4%) and controls (5.9%), p=0.86. Moderate-severe/severe disease was associated with an increased risk of maternal adverse outcome as compared to mild-moderate disease (88.2% versus 52.8%, p=0.007). In addition, having a flare in pregnancy was associated with increased maternal adverse outcomes (90% versus 55.7%, p=0.04). There was a trend towards significance for increased composite maternal adverse outcomes in patients using biologics (71.4% versus 50.9%, p=0.06, Table 2). The use of infliximab postpartum was not associated with a statistically significant increased risk of maternal infectious outcome (33.3% versus 16.7%, p=0.16). As one would expect, more severe IBD disease and IBD flares during pregnancy are associated with adverse pregnancy outcomes. Additionally, although there was no difference in infectious outcomes using infliximab postpartum, larger studies are needed to confirm these findings.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

213. The use of biologics in pregnant women with chronic conditions and adverse maternal outcome: A systematic review and meta-analysis

Introduction The increased availability and awareness of biologics safety has led to an increase in their use over the past decade. Previous concern regarding adverse pregnancy outcome resulted in the discontinuation of biologics before carefully planned conception. With the greater appreciation of the safety of a number of these agents, in addition to the need to control the underlying disease activity, many physicians now maintain patients on treatment for at least a portion of their pregnancy. However, conflicting opinions remain and there is little data to the safety of certain biologics in pregnancy. There are multiple systematic reviews that have studied foetal/infant outcomes but not maternal outcomes. Objectives Primarily; to study the effect of biologics during pregnancy on the rate of miscarriage. Secondary outcomes include the rate of maternal infections, C-sections and hypertensive disorders in pregnancy. Methods We performed a comprehensive search to identify potentially relevant published studies on the use of biologics 3-months before or during pregnancy and their effect on maternal outcomes from 1998 to December 2017 in all languages. Databases including PubMed, EMBASE and Cochrane were searched using a detailed strategy. We potentially selected studies and retrieved their full-text. We performed data extraction and currently in the process of quality and risk of bias appraisal and heterogeneity assessment. Incidence data will be combined where feasible in a meta-analysis using Stata software and fixed-effects or random-effects models as appropriate. This systematic review will be reported according to the PRISMA guidelines. Results The search resulted in 1244 studies. 16 studies included (11 TNF-inhibitors, 3 tocilizumab, 1 tofacitinib and 1 abatacept) for the qualitative analysis after excluding other studies from title and abstract and after removing duplicates. We are currently in the process of quality assessment and risk of bias appraisal. In the symposium we will present the final results.

Research to knowledge: promoting the training of physician-scientists in the biology of pregnancy

Common disorders of pregnancy, such as preeclampsia, preterm birth, and fetal growth abnormalities, continue to challenge perinatal biologists seeking insights into disease pathogenesis that will result in better diagnosis, therapy, and disease prevention. These challenges have recently been intensified with discoveries that associate gestational diseases with long-term maternal and neonatal outcomes. Whereas modern high-throughput investigative tools enable scientists and clinicians to noninvasively probe the maternal-fetal genome, epigenome, and other analytes, their implications for clinical medicine remain uncertain. Bridging these knowledge gaps depends on strengthening the existing pool of scientists with expertise in basic, translational, and clinical tools to address pertinent questions in the biology of pregnancy. Although PhD researchers are critical in this quest, physician-scientists would facilitate the inquiry by bringing together clinical challenges and investigative tools, promoting a culture of intellectual curiosity among clinical providers, and helping transform discoveries into relevant knowledge and clinical solutions. Uncertainties related to future administration of health care, federal support for research, attrition of physician-scientists, and an inadequate supply of new scholars may jeopardize our ability to address these challenges. New initiatives are necessary to attract current scholars and future generations of researchers seeking expertise in the scientific method and to support them, through mentorship and guidance, in pursuing a career that combines scientific investigation with clinical medicine. These efforts will promote breadth and depth of inquiry into the biology of pregnancy and enhance the pace of translation of scientific discoveries into better medicine and disease prevention.

Biologics in pregnancy-for the obstetrician

Key content The authors discuss commencing biologics in pregnancy and the potential side effects. Infection is a particular risk, which may be atypical or present atypically. While there is no evidence of teratogenicity, these drugs cross the placenta and neonatal cord drug levels may exceed those of maternal drug levels. If possible, anti-tumour necrosis factor (TNF) agents should be discontinued midtrimester but the gestation to which each drug can be used is slightly different. Neonates exposed in utero to anti-TNF agents beyond the recommended gestation should not be given live attenuated vaccines for the first 6 months of life and any infections promptly treated. Data are lacking on the long-term effects of biologics on children exposed in utero. However, the benefits of controlling active autoimmune disease in the mother often outweigh the small risk to the exposed infants. Learning objectives To know the biologics most commonly used in pregnancy. To understand the literature regarding safety of the common biologics in pregnancy. To be able to counsel a woman taking a biologic about the potential benefits and risks of taking it at different gestations. To be able to counsel a woman receiving biologics in pregnancy about vaccinations for her baby after birth. Ethical issues Biologic agents are relatively new drugs that are being increasingly used in young women because of their perceived ‘fertility sparing’ benefits despite a lack of high quality evidence. Most women who have been prescribed biologics are often refractory to other treatments, and therefore these agents are required for disease control. The decision to continue or discontinue these drugs in pregnancy, especially late pregnancy, is particularly contentious. The long-term effect of biologics on infants exposed in utero is not known and the decision to use these drugs has to be balanced against the risk of severe maternal flares.

Fertility and Pregnancy in Inflammatory Bowel Disease

Inflammatory bowel diseases (IBDs) commonly affect women in their reproductive years; 25% of women with IBD become pregnant after the diagnosis. The relation of IBD to reproductive function often manifests in issues concerning fertility, antepartum pregnancy management, mode of delivery, and lactation as these can be influenced by disease activity, medications, perianal disease, and previous ileoanal pouch surgery. As disease location, activity, and complications can vary between patients, an individualized approach with multidisciplinary management is recommended. Pregnancy outcomes, recommended medication, nursing, managing IBD flares during pregnancy, and immune pathways are also discussed. Figures show issues discussed in preconception counseling and pregnancy guidelines. Tables list medication recommendations, Food and Drug Administration categories for the use of medications in pregnancy, adverse pregnancy outcomes PIANO registry, pregnancy and biological recommendations, thiopurine recommendations, safety of biologics in pregnancy, biologic guidelines, and sick pregnant patient recommendations. This review contains 2 highly rendered figures, 8 tables, and 29 references.

High-risk pregnancy and the rheumatologist.

Rheumatologists are increasingly involved in the care of young women who, in the age of biologic therapy, are now gaining control of their rheumatic diseases and attempting pregnancy. With careful planning, most women with rheumatic diseases have successful pregnancies. This article focuses specifically on the highest-risk pregnancies and controversial areas. We discuss the women at risk of complications, the types of maternal and fetal complications, the treatments that can be used in pregnancy (and breastfeeding) and longer-term outcomes that could affect the mother. SLE, RA, ANCA-associated vasculitides, large vessel vasculitis (e.g. Takayasu's) and other CTDs (e.g. scleroderma) are among the conditions covered. The evidence and controversies regarding the recommendations for the use of biologics in pregnancy are discussed. The role of the rheumatologist in pregnancy planning and caring for the pregnant and post-partum woman as part of the multidisciplinary team is discussed.

Management of moderate to severe plaque psoriasis in pregnancy and lactation in the era of biologics.

Psoriasis is not uncommon in the reproductive years and therefore in pregnant patients. There are limited data about the impact of psoriasis on the course and prognosis of pregnancy and about the impact of pregnancy on the course of psoriasis. Usually the disease improves during pregnancy and patients experience worsening between 4 and 6 weeks after delivery. A safe option for patients with limited disease is topical therapy, including moisturizers and topical steroids as well as UVB phototherapy. In the case of active psoriasis or even psoriasis worsening during pregnancy, there might be a need for continuation or even introduction of systemic therapy. Methotrexate and acitretin are known teratogens and mutagens, and they must be avoided. Ciclosporin may be regarded as a possible rescue therapy for pregnant psoriasis patients in the case of severe disease. Post-marketing experience regarding the safety of biologics is accumulating, with largely reassuring results. All four biologics approved for the treatment of moderate to severe psoriasis--etanercept, infliximab, adalimumab, and ustekinumab--are not currently recommended in pregnant psoriasis patients. The existing evidence implies that the risk of biologics in pregnancy is relatively low and that the risk of fetal drug exposure may be outweighed by the benefits for the mother.