Fausta Beneventi

Prevalence and significance of previously undiagnosed rheumatic diseases in pregnancy

Objectives The objective of this study was to evaluate the rates of previously undiagnosed rheumatic diseases during the first trimester of pregnancy and their impact on the pregnancy outcome. Methods Pregnant women in their first trimester were screened using a two-step approach using a self-administered 10-item questionnaire and subsequent testing for rheumatic autoantibodies (antinuclear antibody, anti-double-stranded DNA, anti-extractable nuclear antigen, anticardiolipin antibodies, anti-β2-glycoprotein I antibodies and lupus anticoagulant) and evaluation by a rheumatologist. Overall, the complications of pregnancy evaluated included fetal loss, pre-eclampsia, gestational diabetes, fetal growth restriction, delivery at less than 34 weeks, neonatal resuscitation and admission to the neonatal intensive care unit. Results Out of the 2458 women screened, the authors identified 62 (2.5%) women with previously undiagnosed undifferentiated connective tissue disease (UCTD) and 24 (0.98%) women with previously undiagnosed definite systemic rheumatic disease. The prevalences were seven (0.28%) for systemic lupus erythematosus and Sjogrens syndrome, six (0.24%) for rheumatoid arthritis, three (0.12%) for antiphospholipid syndrome and one (0.04%) for systemic sclerosis. In multiple exact logistic regression, after adjustment for potential confounders, the OR of overall complications of pregnancy were 2.81 (95% CI 1.29 to 6.18) in women with UCTD and 4.57 (95% CI 1.57 to 13.57) in those with definite diseases, respectively, compared with asymptomatic controls. Conclusions In our population approximately 2.5% and 1% of first trimester pregnant women had a previously undiagnosed UCTD and definite systemic rheumatic disease, respectively. These conditions were associated with significant negative effects on the outcome of pregnancy.

First trimester pregnancy-associated plasma protein-A in pregnancies complicated by subsequent gestational diabetes.

To compare routine first trimester biochemical and ultrasound markers in pregnancies complicated by gestational diabetes with those of a control group.

The Impact of First-Trimester Serum Free β-Human Chorionic Gonadotropin and Pregnancy-Associated Plasma Protein A on the Diagnosis of Fetal Growth Restriction and Small for Gestational Age Infant

Objective: To evaluate the risk of fetal growth restriction (FGR) associated with first-trimester maternal serum concentrations of pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG). Methods: A longitudinal study of 2,178 women who underwent first-trimester evaluation of serum PAPP-A and free β-hCG. FGR was defined as a decrement of the fetal abdominal circumference to below the 10th percentile of our standard growth curve in the presence of Doppler signs of impaired placental perfusion. Logistic regression was used to compute multivariable odds ratios and the estimated prevalences of outcomes associated with first-trimester serum marker concentrations. Results: The prevalences of small for gestational age (SGA, <10th percentile birth-weight) neonates and FGR were significantly higher among women with serum PAPP-A concentrations below the 10th percentile than in controls: 40/206 compared to 183/1,928, for SGA, adjusted odds ratio = 2.1, 95% confidence intervals (CI) 1.4–3.03; 24/75 compared to 182/1,900, for FGR, adjusted odds ratio = 3.9, 95% CI 2.3–6.5. The adjusted prevalences of FGR and SGA among women with simultaneous low first-trimester values of PAPP-A and free β-hCG were 0.21 (95% CI 0.13–0.33) and 0.26 (95% CI 0.17–0.36), respectively. Conclusion: Low first-trimester maternal serum PAPP-A concentrations are significantly associated with reduced fetal size and increased risk of FGR with Doppler signs of impaired placental perfusion.

Gestational diabetes mellitus: including serum pregnancy-associated plasma protein-A testing in the clinical management of primiparous women? A case-control study.

AIMS To assess pregnancy-associated plasma protein A (PAPP-A) correlation with GDM and its usefulness in predicting GDM in primiparous women. METHODS First trimester data related to 307 pregnant women affected by GDM and 366 control pregnant women were retrieved from a computer data base and integrated with ad hoc data. Clinical data were recorded at delivery. A logistic model was used to analyze the association between first trimester data and subsequent clinical outcomes. We derived a risk score using both classical risk factors for GDM and PAPP-A. RESULTS Diabetic and control women were significantly different in terms of age (p<0.001), BMI (p<0.001), weight (p<0.001), family history of diabetes (p<0.001), PAPP-A concentration and PAPP-A corrected multiple of the median (MoM) (p<0.001). The ROC-AUC of the clinical risk score was 0.60 (95%CI 0.56-0.64), the adjusted score including PAPP-A MoM was 0.70 (95%CI 0.66-0.74). CONCLUSIONS Low PAPP-A was strongly associated with GDM and lower values were found in diabetic women needing insulin therapy. Adding PAPP-A to first trimester screening could improve the prediction of women at high risk who will develop GDM. Further studies are needed to validate the applicability of our findings in different populations and settings.

Temporal Variation in Soluble Human Leukocyte Antigen‐G (sHLA‐G) and Pregnancy‐Associated Plasma Protein A (PAPP‐A) in Pregnancies Complicated by Gestational Diabetes Mellitus and in Controls

To target gestational diabetes mellitus (GDM) by means of temporal variation in pregnancy‐associated plasma protein A (PAPP‐A) and soluble human leukocyte antigen‐G (sHLA‐G).

Prevalence of undiagnosed autoimmune rheumatic diseases in the first trimester of pregnancy. Results of a two-steps strategy using a self-administered questionnaire and autoantibody testing

Objective  To evaluate the prevalence of undiagnosed rheumatic diseases in the first trimester of pregnancy.

Uterine artery Doppler velocimetry and obstetric outcomes in connective tissue diseases diagnosed during the first trimester of pregnancy.

To evaluate the effect of connective tissue disease (CTD) diagnosed during the first trimester on uterine arteries (UtA) Doppler velocities and on pregnancy outcomes.

The effect of newly diagnosed undifferentiated connective tissue disease on pregnancy outcome

OBJECTIVE The purpose of this study was to evaluate pregnancy outcome in a cohort of patients with newly diagnosed undifferentiated connective tissue disease (UCTD). STUDY DESIGN We conducted a nested case-control study that compared 41 patients who had early UCTD that was diagnosed at 11-14 weeks of pregnancy with 82 healthy control subjects. RESULTS During pregnancy, UCTD progressed to a definite connective tissue disease in 2 of 41 patients (4.9%). Sixteen of the 41 patients (39%) with UCTD tested positive for anti-Ro (SSA) antibodies. Compared with the control subjects, the women with UCTD had higher rates of small for gestational age (SGA; 12/40 vs 11/80; P = .05). The rate of complications of pregnancy (preterm delivery at </= 37 weeks of gestation, SGA, preeclampsia, late fetal loss) was 39% (16/41) among cases and 13.4% (11/82) in control subjects (adjusted odds ratio, 3.98; 95% CI, 1.59-9.49). CONCLUSION Pregnant patients with UCTD are at increased risk of SGA and complications of pregnancy.

Gonadal and uterine function in female survivors treated by chemotherapy, radiotherapy, and/or bone marrow transplantation for childhood malignant and non‐malignant diseases

To evaluate gonadal function and uterine volume in a cohort of female survivors treated by chemotherapy, radiotherapy, and/or stem cell transplantation (SCT) for childhood malignant and non‐malignant diseases.

Connective tissue diseases and autoimmune thyroid disorders in the first trimester of pregnancy

OBJECTIVE To investigate the rates and coexistence of autoimmune thyroid and connective tissue diseases (CTD) during the first trimester of pregnancy and their influence on pregnancy outcome. STUDY DESIGN A cohort study of 150 women with CTD diagnosed during first trimester of pregnancy and 150 negative controls. MAIN OUTCOME MEASURES Screening of CTD by a self-reported questionnaire, rheumatic and thyroid autoantibody detection, clinical rheumatological evaluation and obstetric outcomes. RESULTS Out of 3852 women screened, 61 (1.6%) were diagnosed with undefined connective tissue disease (UCTD), 28 (0.7%) with major CTD (six rheumatoid arthritis, five systemic lupus erythematosus, eight Sjogren syndrome, five anti-phospholipid syndrome, two systemic sclerosis, one mixed CTD and one monoarticular arthritis) and 61 (1.6%) had insufficient criteria for a diagnosis of a rheumatic disease. The overall prevalence of either thyroid peroxidase (TPO-a) or thyroglobulin (TG-a) autoantibodies detection was 8% (12/150) among controls, 62.3% (38/61) among UCTD and 60.7% (17/28) in women with a major CTD (p<.001 compared to controls for both comparisons). After adjustment for confounders, overall CTDs (major or undefined) (OR=3.54, 95% CI; 1.61-7.78) and TPO-a plus TG-a positivity (OR=2.78, 95% CI;1.29-5.98) were independently associated with increased risks of moderate-severe complications of pregnancy (miscarriage, fetal growth restriction, preeclampsia, delivery before 34 weeks). CONCLUSIONS Rheumatic and thyroid autoantibodies during pregnancy are closely associated. Thyroid antibodies could add to the risk of adverse pregnancy outcome associated with connective tissue diseases.