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Objective: To evaluate the impact of preclinical systemic autoimmune rheumatic disorders on pregnancy outcome., Methods: In this longitudinal cohort study, patients were enrolled during the first trimester of pregnancy if they reported having had connective tissue disorder symptoms, were found to be positive for circulating autoantibodies, and on clinical evaluation were judged to have a preclinical or incomplete rheumatic disorder. The incidence of fetal growth restriction (FGR), preeclampsia, and adverse pregnancy outcomes in patients with preclinical rheumatic disorders was compared with that in selected controls, after adjustment for confounders by penalized logistic regression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated., Results: Of 5,232 women screened, 150 (2.9%) were initially diagnosed as having a suspected rheumatic disorder. After a mean ± SD postpartum follow-up of 16.7 ± 5.5 months, 64 of these women (42.7%) had no clinically apparent rheumatic disease and 86 (57.3%) had persistent symptoms and positive autoantibody results, including 10 (6.7%) who developed a definitive rheumatic disease. The incidences of preeclampsia/FGR and of small for gestational age (SGA) infants were 5.1% (23 of 450) and 9.3% (42 of 450), respectively, among controls, 12.5% (8 of 640) (OR 2.7 [95% CI 1.1-6.4]) and 18.8% (12 of 64) (OR 2.2 [95% CI 1.1-4.5]), respectively, among women with no clinically apparent disease, and 16.3% (14 of 86) (OR 3.8 [95% CI 1.9-7.7]) and 18.6% (16 of 86) (OR 2.3 [95% CI 1.2-4.3]), respectively, among those with persisting symptoms at follow-up. Mean ± SD umbilical artery Doppler pulsatility indices were higher among women with no clinically apparent disease (0.95 ± 0.2) and those with persisting symptoms (0.96 ± 0.21) than in controls (0.89 ± 0.12) (P = 0.01 and P < 0.001, respectively)., Conclusion: In our study population, preclinical rheumatic disorders were associated with an increased risk of FGR/preeclampsia and SGA. The impact of these findings and their utility in screening for FGR/preeclampsia need to be confirmed in population studies., (© 2016, American College of Rheumatology.)

Objective: To compare routine first trimester biochemical and ultrasound markers in pregnancies complicated by gestational diabetes with those of a control group., Methods: First trimester data including the screening test for Down syndrome were retrieved from a computer data base. Clinical data were recorded at delivery. A multivariate quantile regression model was used to analyze the association between first trimester data and subsequent clinical outcomes in a case-control study design., Results: In the group of women who developed second trimester gestational diabetes, both first trimester median (1494 vs 2225 mU/L, P < 0.001) and adjusted multiple of median pregnancy-associated plasma protein-A (PAPP-A) concentrations (1.2 vs 0.7, P < 0.001) were significantly lower than in the control group. Differences between observed and expected crown-to-rump length expressed in mm was lower in women destined to develop gestational diabetes than in the control group (0.2 vs 1.4 mm, P < 0.005). In multivariate models, first trimester maternal PAPP-A concentrations correlated independently and inversely to pregestational body mass index (BMI, P = 0.004), subsequent gestational diabetes (P < 0.001) and pregnancy complications (P = 0.036)., Conclusions: First trimester PAPP-A concentrations were lower among pregnant women with subsequent gestational diabetes than in the control group., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: The widespread use of diagnostic breast imaging has yielded an increase in the detection of in situ, microinvasive, and small invasive carcinomas and has provided opportunities to study the earliest stages of breast carcinoma development. The authors of this report analyzed the pathobiologic features of 577 minimal breast carcinomas (MBCs), including in situ carcinomas and invasive carcinomas < or =1 cm, according to the definition given by Hartmann in Cancer (1984;53:681-4)., Methods: Estrogen and progesterone receptors (ER and PR), proliferation index (PI), and p53 and neu expression were studied by immunohistochemical technique and measured by quantitative image analysis in 99 pure in situ carcinomas (ISCp); in 105 mixed invasive/in situ carcinomas, with a separate analysis of in situ (ISCm) and invasive (ICm) components; and in 373 invasive carcinomas < or =1 cm (IC). Follow-up data were available for 164 invasive carcinomas., Results: A progressive increase in the levels of hormone steroid receptors, from the lowest in ISCm to the highest in IC, was observed (ER, P< 0.001; PR, P=0.005). Levels of PI and p53 expression were higher in ISCm than in the other categories (PI, P=0.007; p53, P=0.046). Overexpression of neu was greater in ICm than in IC (P=0.013). Younger women (< or =40 years) with invasive carcinoma had worse biologic profiles, with lower ER (P < 0.001) and higher PI (P=0.021), neu (P=0.008), and p53 (P=0.040). It was demonstrated clinically that PI and neu were the biologic markers with the highest predictive prognostic values in univariate analysis (PI for recurrence, P < 0.015; neu for recurrence and overall survival, P < 0.001 and P < 0.007, respectively) and in multivariate analysis (neu for recurrence and overall survival, P < 0.007 and P < 0.017, respectively)., Conclusions: Biologic phenotypes of MBC can be interpreted as reflecting a dimension of neoplastic progression capacity that is independent of tumor size. This study suggests that biologic markers can be integrated with traditional pathologic indicators for accurate staging of patients.

Background: The biologic profile of 907 infiltrating breast carcinomas was determined considering estrogen receptor (ER) and progesterone receptor (PR), proliferation index (PI) and c-erbB-2/Neu expression. The relationship with pathologic parameters (lymph node status, size, histotype) were studied by a multivariate analysis. The clinical prognostic power of biologic profile also was evaluated for 265 patients., Methods: In 907 infiltrating breast carcinomas, the quantitation of ER, PR, an PI was obtained with an image analysis system (CAS 200, Becton Dickinson Cell Analysis Systems, San Jose, CA); Neu was evaluated semiquantitatively. A clinical study of 265 patients was performed (median follow-up, 42.5 months)., Results: Seventy-seven percent of tumors were ER-positive, 70% were PR-positive, 58% had a high PI, and 35% were Neu-positive. The overall analysis indicated a direct correlation between ER and PR (Spearmans' rho [rs] = 0.47, P < 0.001) and an inverse correlation between PI and ER (rs = -0.39, P < 0.001), PI and PR (rs = -0.32, P < 0.001), Neu and ER (rs = -0.20, P < 0.001), and Neu and PR (rs = -0.21, P < 0.001). Cluster analysis, performed based on the biologic profile (ER, PR, PI, c-erbB-2/Neu expression), identified two final groups of tumors with different pathologic features. This study showed a longer relapse free interval for patients with ER- and PR- positive tumors (P = 0.016 and P = 0.007) and low PI and Neu-negative tumors (P < 0.001 and P = 0.047)., Conclusions: These results stress the importance of the biologic profile for defining tumor behavior and patient management, leading to integration of, and eventually the substitution for, the actual staging system.