H.-S. Cha

Optimal time interval between a single course of antenatal corticosteroids and delivery for reduction of respiratory distress syndrome in preterm twins

OBJECTIVE The objective of the study was to investigate the effect of a single course of antenatal corticosteroid (ACS) therapy on the incidence of respiratory distress syndrome (RDS) in preterm twins according to the time interval between ACS administration and delivery. STUDY DESIGN We performed a retrospective cohort study of twins born between 24 and 34 weeks of gestation from November 1995 to May 2011. Subjects were grouped on the basis of the time interval between the first ACS dose and delivery: the ACS-to-delivery interval of less than 2 days (n = 166), 2-7 days (n = 114), and more than 7 days (n = 66). Pregnancy and neonatal outcomes of each group were compared with a control group of twins who were not exposed to ACS (n = 122). Multiple logistic regression analysis was used to examine the association between the ACS-to-delivery interval and the incidence of RDS after adjusting for potential confounding variables. RESULTS Compared with the ACS nonexposure group, the incidence of RDS in the group with an ACS-to-delivery interval of less than 2 days was not significantly different (adjusted odds ratio [aOR], 1.089; 95% confidence interval [CI], 0.524-2.262; P = .819). RDS occurred significantly less frequently when the ACS-to-delivery interval was between 2 and 7 days (aOR, 0.419; 95% CI, 0.181-0.968; P = .042). However, there was no significant reduction in the incidence of RDS when the ACS-to-delivery interval exceeded 7 days (aOR, 2.205; 95% CI, 0.773-6.292; P = .139). CONCLUSION In twin pregnancies, a single course of ACS treatment was associated with a decreased rate of RDS only when the ACS-to-delivery interval was between 2 and 7 days.

Autophagy Induced by Tumor Necrosis Factor α Mediates Intrinsic Apoptosis in Trophoblastic Cells

To investigate the interconnection of apoptosis and autophagy in trophoblastic cells, we treated JEG-3 cells with tumor necrosis factor α (TNF-α) after transfecting LC3 or Beclin 1 or calpain small interfering RNA (siRNA), which blocks cleavage of autophagy-related gene 5 (Atg5) into N-terminal truncated Atg5 (tAtg5), a mediator between apoptosis and autophagy, and assessed the changes in LC3-II, caspase 9, caspase 3, and tAtg5. We also assessed the TNF-α-induced changes in LC3-II, caspase 9, and caspase 3 in primary trophoblasts from term placentae after transfecting siRNA for LC3 or Beclin 1. In both types of cells, transfection of LC3 or Beclin 1 siRNA significantly attenuated TNF-α-induced increases in LC3-II and activations of caspase 9 and caspase 3. There was significant abrogation of TNF-α-induced expression of tAtg5 after transfection with LC3 or Beclin 1 siRNA. Moreover, transfection with calpain siRNA significantly decreased TNF-α-induced changes in caspase 3 and caspase 9 in addition to tAtg5 in JEG-3 cells. Our data suggest that TNF-α-induced autophagy mediates intrinsic apoptosis, probably through tAtg5, in trophoblastic cells.

Can a customized standard for large for gestational age identify women at risk of operative delivery and shoulder dystocia

Abstract Objective: To determine whether a customized standard for large for gestational age (LGA) identifies undiagnosed women at risk of operative delivery and shoulder dystocia. Methods: We previously generated customized standards from our institution. We compared the baseline maternal characteristics and neonatal outcomes between LGA and non-LGA births, which were classified by both population-based and customized standards. The risk of operative delivery (vacuum delivery or emergent cesarean section) and shoulder dystocia was compared by logistic regression analysis in LGA pregnancies that were identified by a population-based birth weight standard and a customized standard after adjusting for maternal age, parity, body mass index, and neonatal gender. Results: Multivariable analysis revealed that the pregnancies identified as LGA by a customized standard were associated with an increased risk of emergent cesarean section [odds ratio (OR), 4.09; 95% confidence interval (CI), 3.00–5.74] and shoulder dystocia (OR, 10.56; 95% CI, 5.52–20.19). However, there was no association between an increased risk of vacuum delivery (OR, 1.45; 95% CI, 0.92–2.30) and pregnancies identified as non-LGA, using both standards. In addition, customized LGA infants were at increased risk of admission to neonatal intensive care unit (OR 1.63; 95% CI, 1.09–2.43). Conclusion: A customized standard of LGA is useful in identifying previously unrecognized women at risk of emergent cesarean section and shoulder dystocia.

Cushing syndrome in pregnancy secondary to adrenal adenoma.

We report a case of Cushing syndrome secondary to adrenal adenoma presenting with hypertension and oligohydramnios during pregnancy. The tumor was confirmed by magnetic resonance imaging at 28 week 3 day weeks of pregnancy and was removed surgically at 29 week 1 day weeks of gestation. After surgery, hypertension subsided and amniotic fluid volume returned to normal range. The gravid woman subsequently delivered a healthy infant at term.

Amniopatch treatment for spontaneous previable, preterm premature rupture of membranes associated or not with incompetent cervix.

Objective: We reviewed women with previable spontaneous premature rupture of membranes (sPPROM) in whom an amniopatch was performed and compared their pregnancy outcomes with a conservative management group. Methods: Amniopatch, an amnioinfusion of autologous platelet concentrate followed by cryoprecipitate, was performed in 7 women with sPPROM diagnosed at 17–23 weeks’ gestation, including one twin pregnancy. Three patients had incompetent cervices and the other 4 patients had sPPROM without incompetent cervices. Pregnancy outcomes of the cases were compared with the controls who were managed conservatively (n = 22). Results: Amniopatch treatment was successful in 1 of 7 cases (14.3%), in which the ruptured membranes were completely sealed and the patient delivered a healthy baby at 39 weeks’ gestation. No procedure-related complications were observed. Overall, neonatal outcome was similar in the amniopatch and conservatively managed groups, although the incidences of early neonatal sepsis and respiratory distress syndrome were lower in the amniopatch group. Conclusion: The overall success rate of amniopatch among our small number of cases was low. However, if successful, amniopatch may prolong a pregnancy with previable sPPROM to term.

SAT0346 Anti-Drug Antibodies as A Predictor for the Discontinuation of Anti-TNF Agents in Patients with Spondyloarthrtis

Background Tumor necrosis factor (TNF) blocking agent has shown to be effective in patients with axial spondyloarthritis (SpA) including ankylosing spondylitis (AS) as up to 60-70%. However, the other 30-40% of patients fails to respond. This non-responsiveness to TNF blocking agent has been suggested as the result of the development of antibodies against it, anti-drug antibodies (ADA), which have been described well in patients with rheumatoid arthritis and Crohns disease. Objectives The aim is to assess whether ADA is related to the clinical efficacy in SpA patients on anti-TNF agents. Methods According to the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA, consecutive patients were recruited at a single tertiary hospital who received treatment with adalimumab (Ada) or infliximab (Ifx): 86 AS, 11 inflammatory bowel disease associated SpA, 3 psoriatic SpA and 2 undifferentiated SpA. Serum samples were collected at the enrolment for the drug and ADA levels, which were measured by ELISA. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at baseline (at the beginning of the current anti-TNF agents), at 3 month and then every 6 months. The reactivation of tuberculosis infections, side-effects or infusion reactions, and the cause for discontinuation of therapy were assessed prospectively. Results A total of 102 patients were studied (89.2% male; mean age at sampling 35.2±18.0 years; mean disease duration 11.3±7.9 years). HLA-B27 was positive in 65 of 76 patients (85.5%). Among 102 patients, 74 were treated with Ada and 28 with Ifx. Eighteen patients (17.6%) had switched from other kinds of anti-TNF agents including Ada, Ifx and etanercept. Latent tuberculosis (TB) infection was detected in 22 patients (21.6%) before starting anti-TNF agents and the treatment regimen with isoniazid and rifampin was commenced by a TB expert. ADA was demonstrated in 8 patients (7.8%) (5 of Ada and 3 of Ifx) and all of them were anti-TNF naïve patients. Patients who developed ADA had lower levels of the corresponding drugs (Ada level: 0.45±0.68 vs 4.42±2.12, p<0.0001; Ifx level 0.91±1.36 vs 3.38±2.24, p=0.076). At baseline, no differences in BASDAI were found in patients with or without ADA, and neither ESR nor CRP was different. The median period under prospective observation was 15 months (range 0 – 17, mean 12.7±7.8). ADA-positive patients had a significantly higher cumulative drug discontinuation rate due to inefficacy and adverse events (37.5% vs 6.4%, p=0.022). There was no reactivation of tuberculosis during anti-TNF treatment. Conclusions Our result suggests that in SpA patients the presence of ADA to current Ada or Ifx can predict the drug discontinuation in future due to inefficacy or adverse events. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3465

Outcome of isolated fetal renal pyelectasis diagnosed during midtrimester screening ultrasound and cut-off value to predict a persistent or progressive pyelectasis in utero.

Abstract Aim: To define a better cut-off value of the renal pelvis anteroposterior diameter (RPAPD) to predict persistent or progressive pyelectasis during pregnancy. Methods: We retrospectively reviewed 8873 women whose fetal RPAPD was measured. Midtrimester pyelectasis was defined as a RPAPD of ≥4 mm. Persistent/progressive pyelectasis was defined as a RPAPD of ≥10 mm before delivery. A RPAPD cut-off value to predict a persistent/progressive pyelectasis was determined by receiver operating characteristic curve analysis. Results: Among 249 isolated cases of pyelectasis, persistent/progressive pyelectasis was found in 6.9% before delivery. The midtrimester RPAPD cut-off value that best predicted persistent/progressive pyelectasis before delivery was ≥6 mm with sensitivity, specificity, positive and negative predictive values of 64.3%, 88.7%, 30.0%, and 97.1%, respectively. Conclusions: Although most cases of midtrimester fetal pyelectasis regress to normal during pregnancy, those with a RPAPD of ≥6 mm in the midtrimester are at higher risk for persistent or progressive pyelectasis.

EP05.04: How to measure amniotic fluid index? Comparison of two methods (vertical to abdominal contour or floor): Electronic Poster Abstracts

Objectives: The transabdominal probe (TP) is recommended to be positioned usually vertical to floor and parallel to maternal sagittal plane when measuring amniotic fluid index (AFI). However, many examiners report AFI measured in different ways. This study was performed to investigate the difference of AFI according to the positioning of TP. Methods: AFI was measured in 105 gravidas without fetal abnormalities from 20 to 40 weeks of gestation by four experienced examiners according to the technique proposed by Phelan et al. Maternal abdomen was divided into four quadrants using the umbilicus and linea nigra as landmarks. AFI was generated by the sum of these four values without umbilical cord or fetal parts. In each patient, AFI was measured by four different ways. Group 1: TP kept vertical to floor and parallel to maternal sagittal plane, Group 2: TP kept vertical to abdominal contour and parallel to maternal sagittal plane, Group 3: TP kept vertical to floor and parallel to maternal transverse plane, Group 4: TP kept vertical to abdominal contour and parallel to maternal transverse plane. Repeated Measures Analysis of Variance (RMANOVA) was used for statistical analysis. Results: Mean gestational age at measure of AFI was 30.1 ± 5.7 weeks. AFI was different among four groups (15.24 ± 3.74 versus 16.93 ± 4.75 versus 14.75 ± 3.77 versus 15.98 ± 4.62, p<0.001). Post hoc analysis showed the difference in AFI existed between group 1 and 2 (p<0.001), group 2 and 4 (p=0.003) and group 3 and 4 (p<0.001). There was no difference in AFI between group 1 and 3 (p=0.385). Conclusions: AFI was overestimated when TP was positioned vertical to abdominal contour compared to which acquired by positioning TP vertical to floor. We need to use different reference values according to the positioning of TP. When we kept TP vertical to abdominal contour to measure AFI, the direction of TP also influenced on determination of AFI. This was not the case in TP kept vertical to floor.

Short- and long-term neonatal outcomes according to differential exposure to antenatal corticosteroid therapy in preterm births prior to 24 weeks of gestation

Aim To assess the effects of differential exposure to antenatal corticosteroid (ACS) on short- and long-term outcomes of infants born before 24 weeks of gestation. Methods This is a retrospective cohort study of 147 infants delivered by 116 women at 21–23 weeks of gestation between January 2001 and December 2016 at a tertiary referral hospital in Seoul, Korea. Eligible subjects were categorized into the following three groups according to ACS exposure: non-user (n = 53), partial-course (n = 44), and complete-course (n = 50). Univariable and multivariable analyses were used to compare neonatal mortality, neonatal morbidities including intraventricular hemorrhage (IVH), and neurodevelopmental impairment including cerebral palsy among the three groups. Results Neonatal mortality rate was significantly lower in the ACS-user groups (non-user, 52.8%; partial-course, 27.3%; complete-course, 28.0%; P = 0.01), but complete-course of ACS therapy had no advantages over partial-course. A lower incidence of IVH was observed in the complete-course group (non-users, 54.8%; partial-course, 48.6%; complete-course, 20.5%; P = 0.003). Multiple logistic regression analysis showed that ACS therapy, either partial- or complete-course, was associated with a lower rate of neonatal mortality (adjusted odds ratio (aOR) 0.375; 95% confidence interval (CI) 0.141–0.996 in partial-course; aOR 0.173; 95% CI 0.052–0.574) in complete-course). IVH (aOR 0.191; 95% CI 0.071–0.516) was less likely to occur in the complete-course group than in the non-user group. Neurodevelopmental impairment of survivors at 18–22 month after birth was not significantly different among the three groups. Conclusion ACS therapy in preterm births at 21–23 weeks of gestation was associated with significantly reduced rates of neonatal mortality and IVH, especially with complete administration.

FRI0080 Effects of IL-6 Receptor Inhibition Therapy on The Serum Levels of IL-33 and IL-6 in Patients with Rheumatoid Arthritis

Background Several pro-inflammatory cytokines such as TNF-α, IL-1, IL-6, IL-8 and IL-15 are known to be critical in synovial inflammatory process in RA and successful results have been obtained in RA treatment with targeting pro-inflammatory cytokines including TNF-α, IL-1 and IL-6. Objectives This study sought to investigate the role of IL-33 and IL-6 in RA patients receiving IL-6 receptor inhibition therapy. Methods We analyzed the association of the IL-33 and IL-6 level with disease activity and serologic features in 83 patients with RA. We also measured the serum level of IL-33 and IL-6 before and after the administration of tocilizumab for 24 weeks in 40 patients. Results Serum IL-33 level showed significant correlation with RF (rho =0.660, p<0.001) but did not correlate with DAS28, ESR, hsCRP or RA duration. IL-6 level was significantly correlated with hsCRP (rho =0.482, p<0.001) but not correlate with DAS28, ESR, RF or RA duration. There was no correlation between serum IL-6 and IL-33 levels. Serum IL-33 level significantly decreased after 24 weeks of IL-6 receptor inhibition in patients with RA (p<0.001). When comparing subgroups according to ACR20 response, serum IL-33 levels were significantly decreased after 24 weeks of IL-6 receptor inhibition therapy in ACR20 responders (p<0.001) but not in the non-responders (p=0.084). Baseline IL-33 levels were not significantly different between the two subgroups (p=0.765). Serum IL-6 levels were not significantly changed after 24 weeks of IL-6 receptor inhibition therapy (median 7.1 to 8.9 pg/mL, p=0.503). Changes of IL-6 levels were insignificant both in ACR20 responders and non-responders after 24 weeks of IL-6 receptor inhibition therapy. Baseline IL-6 levels were not different between ACR20 responders and non-responders. Conclusions The use of IL-6 receptor inhibitor decreased the serum level of IL-33 and this effect seems to be led by the responder group. IL-33 could be a useful indicator to monitor the response in IL-6 receptor inhibition therapy. Disclosure of Interest None declared