Johan F. Skomsvoll

Anti-inflammatory pharmacotherapy during pregnancy.

NSAIDs or cyclooxygenase inhibitors (COX inhibitors), including aspirin, are widely used to treat pain, fever and the articular symptoms of chronic rheumatic diseases. Manifestations of connective tissue or autoimmune diseases are commonly treated with glucocorticosteroids. The effect and side effects of NSAIDs depend on the isoforms of cyclooxygenases that they preferentially or selectively inhibit. The use of COX inhibitors has recently been associated with infertility and miscarriage. The classical nonselective COX inhibitors, including aspirin, do not increase the risk of congenital malformations in humans but administered in the latter part of gestation, they can affect pregnancy and the fetus. The ability of nonselective and selective COX inhibitors to prolong gestation has been used by obstetricians to inhibit premature delivery. The vascular effects of prostaglandin inhibitors can cause constriction of the fetal ductus arteriosus and reduce renal blood flow. These complications have been described for most nonselective COX inhibitors but are increasingly reported also for the selective COX-2 inhibitors. Aspirin, which causes irreversible inhibition of cyclooxygenases, differs from other NSAIDs with regard to indication, effects and side effects. Prematurity, which is increased in pregnancies of women with connective tissue diseases, is an additional risk factor for adverse effects of antenatal exposure to NSAIDs. Therefore, treatment with COX inhibitors should be discontinued at week 32 of gestation. The ability of NSAIDs to compromise reproductive function by inhibition of ovulation and as causative agents for miscarriage is still under debate. Glucocorticosteroids given in early pregnancy are a risk factor for the development of oral clefts. Therefore, the daily dose should be kept to ≤ 15 mg during the first trimester. High doses of glucocorticosteroids in the second and third trimester are reserved for flares of autoimmune diseases. Intrauterine fetal growth restriction and premature delivery are possible side effects of high doses.

Work disability and health-related quality of life in males and females with psoriatic arthritis

Objectives: To compare health status, demographic variables and work disability (WD) between males and females with psoriatic arthritis (PsA) in the 18–45 age group, and further to compare health status between those with and without WD for each gender and to identify variables associated with WD. Methods: A cross-sectional study was carried out of patients with PsA with peripheral arthritis at the time at which they started disease-modifying antirheumatic drug therapy (DMARD) and/or biological treatment. Patients receiving a permanent national WD pension corresponding to ⩾50% were defined as work disabled. Gender differences were examined with regard to health status, demographic variables and WD. Mann–Whitney U test and Pearson χ2 were applied for group comparisons between males and females and work disabled versus not work disabled for each gender. Multiple logistic regression analyses with adjustments for duration of education, disease duration, age, erosive disease, disability score (Modified Health Assessment Questionnaire; MHAQ), the short form-36 (SF-36) mental health score, and gender were used to identify variables associated with WD. Results: Out of 271 (102 females) patients, the number (%) of work-disabled females/males was 33 (32.7%)/29 (17.4%) (p = 0.004). Work-disabled patients had generally worse health status than non-work-disabled patients, and these differences were generally more pronounced in males than in females. In the multiple logistic regression model, low educational level, increasing disability score (MHAQ), presence of erosive disease, female gender and disease duration were independently associated with WD. Conclusions: WD in patients with PsA below 45 years of age was independently associated with educational level, disability score, erosive disease, female gender and disease duration.

Pregnancy and delivery in women with chronic inflammatory arthritides with a specific focus on first birth.

OBJECTIVE To examine possible associations between chronic inflammatory arthritides and pregnancy outcomes with separate analyses of first and subsequent births before and after diagnosis. METHODS Linkage of data from a registry of patients with chronic inflammatory arthritides and the Medical Birth Registry of Norway enabled a comparison of pregnancy outcomes in women with chronic inflammatory arthritides and pregnancy outcomes in reference subjects. Outcomes of first birth and subsequent births before and after diagnosis were analyzed separately. Associations between chronic inflammatory arthritides and the womens health during pregnancy and delivery as well as perinatal outcomes were assessed in logistic regression analyses with adjustments for maternal age at delivery and gestational age. RESULTS We analyzed 128 first births and 151 subsequent births after diagnosis and 286 first births and 262 subsequent births before diagnosis in patients and compared them with first and subsequent births in reference subjects. Firstborn children of women diagnosed as having chronic inflammatory arthritides were more often preterm (odds ratio [OR] 1.85 [95% confidence interval (95% CI) 1.09-3.13]) and small for gestational age (OR 1.60 [95% CI 1.00-2.56]). They also had lower mean birth weight (P=0.01) and higher perinatal mortality (OR 3.26 [95% CI 1.04-10.24]). Birth by caesarean section (all classifications) was more frequent in patients than in reference subjects, and elective caesarean section was 2-fold more frequent in patients, both in first birth (OR 2.60 [95% CI 1.43-4.75]) and in subsequent births (OR 2.18 [95% CI 1.33-3.58]). No excess risks of clinical importance were observed prior to diagnosis of chronic inflammatory arthritides. CONCLUSION Excess risks were related to first birth in women diagnosed as having chronic inflammatory arthritides, including a higher rate of perinatal mortality. A higher caesarean section rate was related to all patient deliveries. Mainly, pregnancy outcomes before diagnosis did not differ from those in reference subjects.

Obstetrical and neonatal outcome in pregnant patients with rheumatic disease

Possible associations between inflammatory rheumatic and connective tissue disease and adverse pregnancy outcome were assessed by using the Medical Birth Registry of Norway during the years 1967-95. All women with rheumatic disease were compared to women without such disease. Data on pregnancy outcome and deliveries were analyzed after adjustment for possible confounding factors. Women with rheumatic disease had significantly higher rates of preeclampsia, premature delivery and cesarean section as well a significantly increased relative risk of SGA children in all diagnostic groups in 1967-95. These findings emphasize the importance of close monitoring of pregnancy and delivery not only in patients with connective tissue disease, but also in patients with other inflammatory rheumatic disease.

Pregnancy complications and delivery practice in women with connective tissue disease and inflammatory rheumatic disease in Norway

Objective. To assess possible associations between inflammatory rheumatic disease and pregnancy complications/delivery practice.

Drug insight: Anti-tumor necrosis factor therapy for inflammatory arthropathies during reproduction, pregnancy and lactation.

Tumor necrosis factor (TNF) antagonists are widely used to reduce disease activity and joint damage, and to improve health-related quality of life in patients suffering from rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis. To date, no increased risk of embryotoxicity or teratogenicity, or adverse pregnancy outcome (such as birth defects, premature birth, and low birth weight) has been reported in patients with inflammatory arthropathies treated with anti-TNF therapy, compared with the general population. However, the available data are limited, and methotrexate, which is commonly used in combination with anti-TNF drugs, is teratogenic. Until more data are available, no firm conclusions can be reached regarding the safety of anti-TNF therapy in pregnancy. Nevertheless, in selected cases where there is high disease activity, anti-TNF therapy might be recommended, depending on the results of individual risk–benefit analyses. Fully informed consent from the mother is needed in such cases. Anti-TNF agents are not usually used during lactation, although the risk of toxicity is probably negligible.

Validity of a rheumatic disease diagnosis in the Medical Birth Registry of Norway

Background.  In our population‐based study of pregnancy outcome in women with rheumatic disease we based our assessment on the Medical Birth Registry of Norway (MBRN). We evaluated the MBRN as a source of data for such epidemiologic research by assessing the validity of a diagnosis of rheumatic disease in the MBRN against a gold standard. The validity may also be interpreted as a quality indicator, reflecting an obstetricians attention to rheumatic diseases in pregnancy.

Fertility in women with chronic inflammatory arthritides

OBJECTIVE To compare fertility rates in women with RA, other chronic arthritides (OCAs) and JIA with reference women from the general population. METHODS Each woman from a Norwegian patient registry was matched by year of birth with 100 reference women randomly selected from the National Population Registry. Data linkage of patients and references with the Medical Birth Registry of Norway (MBRN) identified all offspring in patients and references until October 2007, and indirectly also nulliparous (childless) women. Groups were compared with Mann-Whitney U-test for continuous variables and chi-squared tests for categorical variables. Poisson regression analysis was applied to calculate relative fertility rates in the diagnostic groups vs references. RESULTS Among 631 patients 849 children were registered in MBRN. Of these, 289 children (34.0%) were born after time of diagnosis vs 44.3% in references. Altogether, 206 of 631 patients (32.6%) were nulliparous vs 26.4% in references (P < 0.001). Among RA patients, 28.4% (96 of 338) were nulliparous vs 24.5% in references (P = 0.09), 30.7% (67 of 218) in OCA patients vs 24.5% in references (P = 0.03) and 57.3% (43 of 75) in JIA patients vs 40.9% in references (P = 0.004). Adjusted relative fertility rates in RA, OCA and JIA after diagnosis were 0.88, 0.84 and 0.84, respectively, compared with references. CONCLUSION A higher proportion of women with chronic inflammatory arthritides were nulliparous compared with references, and relative fertility rates were reduced in all patient groups.

Perinatal outcome in pregnancies of women with connective tissue disease and inflammatory rheumatic disease in Norway

Perinatal outcome in infants of women with rheumatic disease notified between 1967 95 to the Medical Birth Registry of Norway was compared to women without such disease. Logistic regression provided odds ratios for associations between rheumatic disease and perinatal outcome for 3 time periods: 1967-76, 1977-86, and 1987-95. Women with rheumatic disease had significantly higher rates of preterm birth than references and this was only partly correlated to the increased occurrence of preeclampsia. The risk of small for gestational age (SGA) infants was significantly higher both in women with connective tissue disease (CTD) and inflammatory arthritides. The proportion of infants with Apgar score < = 6 after 1 minute and 5 minutes was significantly increased in the CTD group indicating moderate to severe fetal asfyxia. The rate of perinatal mortality was high in the CTD group and postperinatal mortality was increased in infants born to mothers with rheumatic disease. Thus, rheumatic disease not only comprises pregnancy outcome, but increases the risk of adverse perinatal outcome.

Postpartum onset of rheumatoid arthritis and other chronic arthritides: results from a patient register linked to a medical birth registry

Background: It is known that onset of rheumatoid arthritis (RA) is increased post partum. Objective: To compare incidence rates between RA and other chronic arthritides (OCA) 0–24 months after delivery, and to compare the incidence rates within each group 0–24 versus 25–48 months post partum. Methods: Premenopausal women from a Norwegian patient register were linked with the Medical Birth Registry of Norway to study the interval between delivery and time of diagnosis. Cox regression analysis with adjustments for age at delivery and birth order was applied to compare proportions of incident cases of RA and OCA with onset 0–24 months post partum. Poisson regression analysis with adjustment for the population at risk was applied to estimate the incidence rate ratio (IRR) 0–24 versus 25–48 months post partum. Results: Of 183 RA and 110 patients with OCA diagnosed after delivery, 69 (37.7%) had RA and 31 (28.2%) OCA during the first 24 months post partum (p = 0.09). The IRR (95% CI) for diagnosis during 0–24 months versus 25–48 months was 1.73 (1.11 to 2.70) (p = 0.01) for RA, 1.05 (0.59 to 1.84) (p = 0.86) for OCA. The IRR was 2.23 (1.06 to 4.70) and 1.87 (0.67 to 5.21), respectively, when only considering diagnoses after the first pregnancy. Clinical characteristics were similar within each diagnostic group. Conclusion: The proportions of incident cases with onset 0–24 months after delivery were not different between RA and OCA. A peak in incidence during 0–24 months was seen in the RA group, both when considering all pregnancies and only the first pregnancy.