Tumor Necrosis Factor Inhibitor Use Increases Birthweight in Pregnant Women With Rheumatoid Arthritis Independently of the Soluble Fms-Like Tyrosine Kinase-1/Placental Growth Factor Ratio.

BACKGROUND: To study whether the use of TNF (tumor necrosis factor) inhibitors (TNFi) by pregnant women with rheumatoid arthritis affects sFlt-1 (soluble Fms-like tyrosine kinase-1), PlGF (placental growth factor), or their impact on birthweight. METHODS AND RESULTS: sFlt-1 and PlGF were measured in all trimesters of pregnancy in the Preconception Counseling in Active Rheumatoid Arthritis study and were compared according to the use of TNFi. The association of sFlt-1 and PlGF with birthweight in relation to TNFi was determined. The study included 158 women, of whom 52.5% used TNFi during pregnancy. Both sFlt-1 and PlGF increased during pregnancy, whereas their ratio declined. Taking into consideration the trimester-related variation in levels of sFlt-1 and PlGF, after correction for relevant confounders, the sFlt-1/PlGF ratio was not significantly different between patients who did or did not use TNFi (sFlt-1/PlGF ratio in the second trimester compared with the first trimester: estimated change 8.17 [95% CI, 2.54-26.29], P=0.79; sFlt-1/PlGF ratio in the third trimester compared with the first trimester: estimated change 6.25 [95% CI, 1.73-22.50], P=0.25). In women who did not use TNFi, birthweight was significantly lower (3180 versus 3302 g; P=0.03), and sFlt-1 displayed a negative correlation with birthweight (r=-0.462, P<0.001) and birthweight percentile (r=-0.332, P=0.008). In TNFi users, these correlations were absent. CONCLUSIONS: TNF inhibitor use increases birthweight in pregnant women with rheumatoid arthritis independently of the sFlt-1/PlGF ratio. REGISTRATION: http://clinicaltrials.gov. Unique identifier: NCT01345071.

Maternal and neonatal antibody levels on pertussis vaccination in pregnant women on immune-modulating therapy for rheumatic disease.

OBJECTIVES: While protection against pertussis following maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination was demonstrated in healthy term-born infants, no evidence is available on Tdap vaccination in combination with immune-modulating therapy during pregnancy. In this pilot study, we explored whether treatment with tumour necrosis factor alpha inhibitors (TNFis) in pregnant patients with rheumatic disease interferes with Tdap vaccine responses and affects maternal anti-pertussis IgG antibody levels in newborns. METHODS: Patients were included by a rheumatologist during pregnancy in case they received maternal Tdap vaccination in the late-second or early-third trimester of pregnancy. Blood samples were obtained from mothers during the first pregnancy trimester, 3 months after delivery and from the umbilical cord. IgG antibody levels against Tdap-included antigens were measured using a bead-based multiplex immunoassay. Findings on patients exposed to TNFis were compared with those from TNFi-unexposed patients and with data from a historical comparator study among healthy Tdap vaccinated mother-infant pairs (n=53). RESULTS: 66 patients (46 exposed and 20 unexposed to TNFIs) were enrolled. No major differences in IgG antibody levels were observed between TNFi-exposed and unexposed mothers before maternal Tdap vaccination and 3 months after delivery. In cord sera, however, antibody levels against pertussis toxin were significantly lower after TNFi-treatment (35.94 IU/mL, 95% CI 20.68 to 62.45) compared with no TNFi-treatment of mothers with rheumatic disease (94.61 IU/mL, 95% CI 48.89 to 183.07) and lower compared with a cohort of healthy mothers (125.12 IU/mL, 95% CI 90.75 to 172.50). We observed similar differences for filamentous haemagglutinin, pertactin, tetanus toxoid and diphtheria toxoid. CONCLUSION: These preliminary data indicate no major differences in IgG antibody levels on maternal Tdap vaccination in pregnant women with or without immune-modulating treatment, although our findings suggest that TNFis during pregnancy induce lower maternal anti-pertussis-specific protective antibody levels in newborns.

Patient Care Pathways for Pregnancy in Rare and Complex Rheumatic Diseases: Results From an International Survey.

OBJECTIVE: To map existing organizational care pathways in clinical centers of expertise that care for pregnant women affected by rare and complex connective tissue diseases (rcCTDs). METHODS: An international working group composed of experts in the field of pregnancy in rcCTDs co-designed a survey focused on organizational aspects related to the patient's pathway before, during, and after pregnancy. The survey was distributed to subject experts through referral sampling. RESULTS: Answers were collected from 69 centers in 21 countries. Patients with systemic lupus erythematosus and/or antiphospholipid syndrome were followed by more than 90% of centers, whereas those with disorders such as IgG4-related diseases were rarely covered. In the majority of centers, a multidisciplinary team was involved, including an obstetrician/gynecologist in 91.3% of cases and other healthcare professionals less frequently. Respondents indicated that 96% of the centers provided routine pre-pregnancy care, whereas the number of patient visits during pregnancy varied across centers. A formalized care pathway was described in 49.2% of centers, and 20.3% of centers had a predefined protocol for the monitoring of pregnant patients. Access to therapies during pregnancy also was heterogeneous among different centers. CONCLUSION: In international referral centers, a high level of care is provided to patients with rcCTDs before, during, and after pregnancy. No significant discrepancies were found between European and non-European countries. However, this work highlights a potential benefit to streamlining the care approaches across countries to optimize pregnancy and perinatal outcomes among patients with rcCTDs.

Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients' offspring.

OBJECTIVES: To study pregnancy outcomes in a closely monitored, well-defined cohort of women with rheumatoid arthritis (RA). In particular, pregnancy outcomes of women that used a TNFi during pregnancy. METHODS: Patients were derived from a prospective study on pregnancy and RA (Preconception Counseling in Active RA study) and treated according to a treatment protocol aimed at minimal disease activity. Multivariate linear regression analysis was used to describe which variables influenced birth weight. RESULTS: 188 patients were included, 92 (48.9%) patients with RA used a TNFi during pregnancy. Disease Activity Score in 28 joints C reactive protein (DAS28CRP) was low at all time points during pregnancy (DAS28CRP in the third trimester: 2.17 (SD 0.73). TNFi use was not associated with an increase of adverse pregnancy outcomes such as low birth weight (<2500 g), (emergency) caesarian section, hypertensive disorders or congenital malformations. TNFi use resulted in less children born small-for-gestational age (p=0.05), however, did not increase the risk of large-for-gestational age (p=0.73). Mean birth weight was 173 g higher in women that used a TNFi during pregnancy (3.344 kg vs 3.171 kg, p=0.03). In the multivariate analysis, maternal age (ß -0.023, 95% CI -0.040 to -0.0065, p=0.007), TNFi use (ß 0.20, 95% CI 0.066, 0.34, p=0.004), diabetes mellitus (ß 0.37, 95% CI 0.12, 0.63, p=0.004) and gestational age (ß 0.18, 95% CI 0.15, 0.2, p<0.001) were statistically significant associated with birth weight. CONCLUSIONS: This is the first study to show that TNFi use during pregnancy is associated with increased birth weight of offspring of women with well-controlled RA. The underlying mechanism of TNF-inhibition on birth weight and the long-term consequences for the offspring should be explored in future research.

Active counselling and well-controlled disease result in a higher percentage of women with rheumatoid arthritis that breast feed: results from the PreCARA study.

OBJECTIVES: Previous research has demonstrated that patients with rheumatoid arthritis (RA) are less likely to breast feed their offspring. Treatment options for RA during lactation have expanded and the importance of counselling is recognised. The aim of the current research was to study breast feeding among women with RA who benefit from these developments. METHODS: Patients were derived from the Preconceptional Counselling in Active Rheumatoid Arthritis (PreCARA) cohort. Patients were treated according to a modified treat-to-target approach aimed at remission and received pregnancy counselling, including counselling on breast feeding. Postpartum visits were scheduled at 4-6, 12 and 26 weeks post partum. Prevalence of breast feeding at each postpartum visit was compared with a historical reference cohort (Pregnancy-induced Amelioration of Rheumatoid Arthritis cohort) and the general population. RESULTS: Data on 171 pregnancies were available for the current analysis. 120 (70.2%) patients with RA initiated breast feeding. 103/171 (60.2%), 68/171 (39.8%) and 45/171 (26.3%) patients with RA breast fed their offspring at 4-6, 12 and 26 weeks post partum, respectively. These percentages were higher at all postpartum visits compared with the historical reference cohort (p<0.001). In comparison with the general population, the rates were similar at each time point. CONCLUSION: Patients with RA in the PreCARA cohort were more likely to breast feed their offspring compared with patients with RA in the historical reference cohort. The breastfeeding rates observed were similar to breastfeeding rates among women in the general population. The increase in breast feeding among patients with RA may be due to the extension of lactation-compatible medication and pregnancy counselling.

Biological and Methotrexate Survival after Pregnancy in Patients With a Rheumatic Disease.

Objective: Patients with a rheumatic disease who discontinue their disease-modifying anti-rheumatic drug (DMARD) due to pregnancy often wonder if treatment will be as effective after pregnancy. This study investigates the effect of a temporary discontinuation of DMARDs due to pregnancy on the effectiveness of the same DMARD postpartum in patients with a rheumatic disease. Methods: Pregnant, rheumatic patients were derived from the Preconceptional Counseling in Active Rheumatoid Arthritis (PreCARA) cohort. DMARD-survival after pregnancy, for biological and methotrexate (MTX) therapy, was analyzed and compared to controls with stable DMARD-treatment from a retrospective cohort. Results: In total, 234 patients were included, of whom 114 patients had stable biological or MTX treatment before their pregnancy. After pregnancy, 40 out of 56 (71%) patients restarted their biological, for MTX this was 49%. One year after restart, and censoring for a following pregnancy, 88.9% of patients were still using their biological, and 85% still used their MTX (p = 0.92). Compared to the matched controls the survival after pregnancy was significantly lower 1 year after restart for both biologicals (98.3%) and MTX (99.6%); p = 0.002 and p < 0.001 respectively; 3 years after restart this significant difference was no longer observed (p = 0.50 and p = 0.33, respectively). Conclusion: Effective DMARD (biological or MTX) treatment before pregnancy that was discontinued due to pregnancy seems effective after pregnancy. Although DMARD-survival was higher in the control group 1 year after restart, the percentage of patients with effective treatment was still very good (>85%). In addition, this difference was no longer observed after 3 years.

Paternal inflammatory arthritis is associated with a higher risk of miscarriage: results of a large multicentre study (iFAME-Fertility).

OBJECTIVES: Paternal preconception health is recognized as an important contributor to pregnancy outcomes. Nonetheless, pregnancy outcomes of partners of men with inflammatory arthritis (IA) have never been studied. Our objective was to describe the pregnancy outcomes of partners of men diagnosed with IA. METHODS: We performed a multicentre cross-sectional retrospective study conducted in the Netherlands. Men with IA who were over 40 years old that reported at least one positive pregnancy test were included. To analyse the impact of IA on pregnancy outcomes, pregnancies were classified into two groups: pregnancies conceived after the diagnosis of IA and before the diagnosis of IA. RESULTS: In total, 408 male participants diagnosed with IA reported 897 singleton pregnancies that resulted in 794 live births. Pregnancies conceived after the diagnosis of IA had higher rate of miscarriage (12.27 vs 7.53%, P = <0.05). This increased risk was still present after adjusting for confounders [OR 2.03 (95% CI 1.12, 3.69) P = 0.015]. CONCLUSIONS: This is the largest study to describe the pregnancy outcomes of partners of men diagnosed with IA and the first to demonstrate that paternal IA is associated with a higher risk of miscarriage. Notwithstanding, the overall rate of miscarriage reported in our study could be comparable to previously reported population estimates.

The sFlt-1 to PlGF ratio in pregnant women with rheumatoid arthritis: impact of disease activity and sulfasalazine use.

OBJECTIVES: An elevated sFlt-1/PlGF ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with RA. We explored whether the sFlt-1/PlGFratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since SSZ has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether SSZ could affect sFlt-1 or PlGF levels. METHODS: Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21-42 years, were included, with a median gestational age of 30 + 3 weeks. RESULTS: No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (P = 0.07 and P = 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r = -0.01 and r = -0.05, respectively). Four (2%) women with a sFlt-1/PlGF ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio > 38, corresponding to a negative predictive value of 98.1%. SSZ users (n = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-SSZ users (n = 164, P = 0.91 and P = 0.11). CONCLUSION: Our study shows that in pregnant women with RA, the sFlt-1/PlGF ratio is not altered due to disease activity and a cut-off ≤38 can be used to exclude preeclampsia. Additionally, SSZ use did not affect sFlt-1 or PlGF levels in this population.

Analysing cord blood levels of TNF inhibitors to validate the EULAR points to consider for TNF inhibitor use during pregnancy.

BACKGROUND: To minimise placental transfer of tumour necrosis factor inhibitors (TNFi), the European League Against Rheumatism (EULAR) created points to consider (PtC) for the use of TNFi during pregnancy. We are the first to validate the EULAR-PtC by analysing TNFi concentrations in cord blood. METHODS: Patients were derived from the Preconceptional Counselling in Active Rheumatoid Arthritis Study. TNFi was stopped at the time points recommended by the EULAR. Maternal blood and cord blood were collected and analysed for the concentration of TNFi. RESULTS: 111 patients were eligible for the analysis. Median stop time points were gestational age (GA) 37.0 weeks for certolizumab pegol, GA 25.0 weeks for etanercept, GA 19.0 weeks for adalimumab and GA 18.4 weeks for infliximab. Certolizumab pegol (n=68) was detectable in 5.9% of cord blood samples, with a median concentration of 0.3 µg/mL (IQR: 0.2-1.3) and a median cord/maternal concentration ratio of 0.010. Etanercept (n=30) was not detected in any cord blood samples. Adalimumab (n=25) was detectable in 48.0% of cord blood samples, with a median concentration of 0.5 µg/mL (IQR: 0.2-0.7) and a median concentration ratio of 0.062 (IQR: 0.018-0.15). Infliximab (n=14) was detectable in 57.1% of cord blood samples, with a median concentration of 0.4 µg/mL (IQR: 0.1-1.2) and a median concentration ratio of 0.012 (IQR: 0.006-0.081). CONCLUSION: Compliance with the EULAR-PtC results in absence or low levels of TNFi in cord blood.

Impaired fertility in men diagnosed with inflammatory arthritis: results of a large multicentre study (iFAME-Fertility).

OBJECTIVES: The impact of inflammatory arthritis (IA) on male fertility remains unexplored. Our objective was to evaluate the impact of IA on several male fertility outcomes; fertility rate (number of biological children per man), family planning, childlessness and fertility problems. METHODS: We performed a multicentre cross-sectional study (iFAME-Fertility). Men with IA 40 years or older who indicated that their family size was complete were invited to participate. Participants completed a questionnaire that included demographic, medical and fertility-related questions. To analyse the impact of IA on fertility rate, patients were divided into groups according to the age at the time of their diagnosis: ≤30 years (before the peak of reproductive age), between 31 and 40 years (during the peak) and ≥41 years (after the peak). RESULTS: In total 628 participants diagnosed with IA were included. Men diagnosed ≤30 years had a lower mean number of children (1.32 (SD 1.14)) than men diagnosed between 31 and 40 years (1.60 (SD 1.35)) and men diagnosed ≥41 years (1.88 (SD 1.14)).This was statistically significant (p=0.0004).The percentages of men diagnosed ≤30 and 31-40 years who were involuntary childless (12.03% vs 10.34% vs 3.98%, p=0.001) and who reported having received medical evaluations for fertility problems (20.61%, 20.69% and 11.36%, p=0.027) were statistically significant higher than men diagnosed ≥41 years. CONCLUSIONS: This is the first study that shows that IA can impair male fertility. Men diagnosed with IA before and during the peak of reproductive age had a lower fertility rate, higher childlessness rate and more fertility problems. Increased awareness and more research into the causes behind this association are urgently needed.

Low prevalence of anti-SSA (anti-Ro) and anti-SSB (anti-La) autoantibodies in female patients with rheumatoid arthritis with a wish to conceive.

OBJECTIVES: Guidelines advise to test for anti-Sjögren's-syndrome-related antigen A (anti-SSA) and anti-Sjögren's-syndrome-related antigen B (anti-SSB) antibodies in all patients with rheumatoid arthritis (RA) who wish to conceive. Our objective was to determine the prevalence and titres of anti-SSA and anti-SSB autoantibodies in patients with RA with a wish to conceive or pregnant. METHODS: Patients were derived from two large cohorts on RA and pregnancy (PARA cohort and PreCARA cohort). In addition, to determine the clinical relevance of searching for anti-SSA and anti-SSB in patients with RA, we studied the prevalence of the maternal diagnosis of RA in the French national registry of neonatal lupus syndrome (NLS) and congenital heart block (CHB). RESULTS: 26 out of 647 patients with RA had detectable anti-SSA and/or anti-SSB. Anti-SSA was detected in 25 out of 647 patients (3.9%) (Ro-52, n=17; Ro-60, n=19), anti-SSB in 7 out of 647 (1.1%). Thirteen women had a titre of >240 units/mL of anti-SSA antibodies. The prevalence of anti-SSA and/or anti-SSB was higher in rheumatoid factor (RF)-positive patients compared with RF-negative patients (5.1% vs 1.6%, p=0.04). No cases of CHB and/or NLS in the offspring were observed. In the French national register, the prevalence of RA in mothers with SSA related CHB was 1.5%. CONCLUSION: Anti-SSA and anti-SSB have a low prevalence in patients with RA who wish to conceive. Especially for RF-negative patients, the current advise to test for anti-SSA and anti-SSB should be reconsidered.

Systemic lupus erythematosus and COVID-19 during pregnancy.

Background: The ongoing corona virus disease 2019 (COVID-19) pandemic is having a worldwide impact. Valuable information on the clinical characteristics of COVID-19 in pregnant patients with an autoimmune disease, such as systemic lupus erythematosus (SLE), is currently lacking. Methods: Herein, we describe the clinical presentation of 2 pregnant patients with SLE and mild symptomatic COVID-19 infection. Results: In both pregnant SLE patients, a watchful-waiting approach without initiation of treatment for COVID-19 was taken. No adverse outcomes were reported and both pregnancies resulted in healthy neonates born at term. In one patient we observed a flare in SLE disease activity, most likely attributed to discontinuing SLE treatment. Conclusion: Our report highlights the importance of multidisciplinary collaboration between health care professionals as well as individualized treatment decisions during unprecedented periods such as the current COVID-19 pandemic. Discontinuation of immunosuppressive drugs during the acute phase of a COVID-19 infection should be considered on a case-by-case basis. Maternal treatment decisions should be in line with current recommendations for treatment of rheumatic and musculoskeletal diseases during COVID-19 infection and in line with treatment of COVID- 19 during pregnancy.

Modern treatment approach results in low disease activity in 90% of pregnant rheumatoid arthritis patients: the PreCARA study.

OBJECTIVES: In patients with rheumatoid arthritis (RA), high disease activity impairs fertility outcomes and increases the risk of adverse pregnancy outcomes. The aim of this study was to determine the feasibility of a modern treatment approach, including treat-to-target (T2T) and the prescription of tumour necrosis factor (TNF) inhibitors, in patients with RA with a wish to conceive or who are pregnant. METHODS: Patients were derived from the Preconception Counseling in Active RA (PreCARA) cohort. Patients with a wish to conceive or who are pregnant were treated according to a modified T2T approach, in which the obvious restrictions of pregnancy were taken into account. Results of the PreCARA study were compared with results of the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study, a historic reference cohort on RA during pregnancy. Patients in the PARA cohort were treated according to the standards of that time (2002-2010). Differences in disease activity over time between the two cohorts were tested using a linear mixed model. RESULTS: 309 patients with RA were included in the PreCARA study, 188 children were born. 47.3% of the patients used a TNF inhibitor at any time during pregnancy. Mean disease activity over time in the PreCARA cohort was lower than in the reference cohort (p<0.001). In the PreCARA cohort, 75.4% of the patients were in low disease activity (LDA) or remission before pregnancy increasing to 90.4% in the third trimester, whereas in the PARA cohort, these percentages were 33.2% and 47.3%, respectively. CONCLUSIONS: This first study on a modern treatment approach in pregnant patients with RA shows that LDA and remission are an attainable goal during pregnancy, with 90.4% of patients achieving this in the third trimester.

IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive.

Fertility issues are common amongst women with rheumatoid arthritis (RA). Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα), known key players in RA pathogenesis, have been associated with reproductive disorders. This study investigates the role of these cytokines in decreased fertility in women with active RA. Preconception cytokine measurements of 61 patients from the PARA-cohort, a prospective study on RA and pregnancy, were studied in relation to time to pregnancy as a measure for fertility. IL-6 levels were higher in patients with a time to pregnancy longer than 1 year (p = 0.016). Survival analysis of patients stratified by high or low serum IL-6 levels, shows a prolonged time to pregnancy in the high IL-6 group (p = 0.045). Univariate cox regression analysis of IL-6 in relation to time to pregnancy as well as multivariate cox regression analysis correcting for age, disease activity, nulliparity, NSAID use and prednisone use were performed, with hazards ratios for log transformed IL-6 of 0.68 (95% CI: 0.51-0.93, p = 0.015) and 0.66 (95% CI: 0.43-0.99, p = 0.044), respectively. For TNFα, no association with time to pregnancy was found. This study shows that high IL-6, but not TNFα, is associated with decreased fertility in women with RA. This finding provides a rationale to therapeutically target the IL-6 pathway in the time period before pregnancy. More research in the form of large cohort studies on drug safety and the effect of bDMARDS on fertility is needed for implementation of treatment strategies directed at fertility issues in women with RA.

Parenting problems postpartum can be detected early in pregnancy in patients with rheumatoid arthritis.

OBJECTIVE: To describe parenting disability postpartum in patients with rheumatoid arthritis (RA) using the Parenting Disability Index and to determine early in pregnancy which patients will face parenting problems postpartum. METHODS: Data were collected from a prospective study on pregnancy and RA (Pregnancy induced Amelioration of Rheumatoid Arthritis study). Postpartum visits were performed at 6, 12 and 26 weeks after delivery. Domains causing parenting difficulties were identified. A multivariate logistic regression model to identify which patients develop parenting disabilities postpartum with patient characteristics in the first trimester as covariates was performed. RESULTS: 148 patients were eligible for this study. The domains carrying, hygiene, feeding, getting up and down, and household/shopping were frequently scored as difficult. Maintaining discipline, taking care of the children when sick, listening and having other children over caused the least problems. 30.1% of patients with RA report low parenting disability, 30.9% reports intermediate disability and 39.0% reports high disability. Patients with a low Health Assessment Questionnaire (HAQ)-score in the first trimester (OR 9.2, 95% CI 3.0 to 27.7, p<0.001) and low disease activity in the first trimester (Disease Activity Score 28-joint count C reactive protein<3.2) (OR 4.8, 95% CI 1.8 to 12.9, p=0.002) were likely to report low parenting disability postpartum. Patients with a longer disease duration (OR 0.87, 95% CI 0.79 to 0.95, p=0.003) were less likely to report low parenting disability postpartum. A high HAQ-score in the first trimester (OR 4.54, 95% CI 1.99 to 10.34, p<0.001) and erosive disease (OR 2.32, 95% CI 1.00 to 5.35, p=0.049) increased the risk of high parenting disability postpartum. CONCLUSION: Physical domains of parenting postpartum are most commonly affected in patients with RA. When counselling patients with RA, a HAQ-score in the first trimester is the most reliable marker to identify patients that develop parenting disability after delivery.

Cam Deformity and Acetabular Dysplasia as Risk Factors for Hip Osteoarthritis.

OBJECTIVE: Cam deformity and acetabular dysplasia have been recognized as relevant risk factors for hip osteoarthritis (OA) in a few prospective studies with limited sample sizes. To date, however, no evidence is available from prospective studies regarding whether the magnitude of these associations differs according to sex, body mass index (BMI), and age. METHODS: Participants in the Rotterdam Study cohort including men and women ages 55 years or older without OA at baseline (n = 4,438) and a mean follow-up of 9.2 years were included in the study. Incident radiographic OA was defined as a Kellgren/Lawrence grade of ≥2 or a total hip replacement at follow-up. Alpha and center-edge angles were measured to determine the presence of cam deformity and acetabular dysplasia/pincer deformity, respectively. Odds ratios (ORs) were calculated to assess the associations between both deformities and the development of OA. RESULTS: Subjects with cam deformity (OR 2.11, 95% confidence interval [95% CI] 1.55-2.87) and those with acetabular dysplasia (OR 2.19, 95% CI 1.50-3.21) had a 2-fold increased risk of developing OA compared with subjects without deformity, while pincer deformity did not increase the risk of OA. Stratification analyses showed that the associations of cam deformity and acetabular dysplasia with OA were driven by younger individuals, whereas BMI did not influence the associations. Female sex appears to modify the risk of hip OA related to acetabular dysplasia. CONCLUSION: Individuals with cam deformity and those with acetabular dysplasia are predisposed to OA; these associations were independent of other well-known risk factors. Interestingly, both deformities predisposed to OA only in relatively young individuals. Therefore, early identification of these conditions is important.