Elena Locatelli

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.

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).

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.

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.

Effects of uncomplicated vaginal delivery and epidural analgesia on fetal arterial acid–base parameters at birth in gestational diabetes

AIM To investigate the effects of uncomplicated vaginal delivery and epidural analgesia on fetal acid-base parameters in women with gestational diabetes (GDM) compared with controls. METHODS A retrospective case-control study of 142 women with gestational diabetes and 284 controls. To evaluate the effect of diabetes and analgesia on acid-base status correcting for potential confounders we used ordered logistic equations including quartiles of fetal arterial acid-base parameters collected at birth as outcomes and categories of diabetes and epidural analgesia as explanatory variables. RESULTS In the GDM group cord base deficit (-2.63 mmol/l, interquartile range [IQR]=4.2 to -0.65 mmol/l vs. -1.9 mmol/l, IQR=-3.3 to -0.2 mmol/l, p=0.009, odds ratio (OR)=1.51, 95% confidence interval (CI)=1.04-2.18) was lower and concentration of calcium higher (1.49 mmol/l, IQR=1.42-1.56 mmol/l vs. 1.47 mmol/l, IQR=1.41-1.51 mmol/l, p=0.009, OR=1.69, 95% CI=1.12-2.56) compared with controls. Epidural analgesia in the GDM group was associated with reduced cord concentration of glucose (84.0mg/dl [4.7 mmol/l], IQR=70-103.3mg/dl vs. 92.5mg/dl [5.1 mmol/l], IQR=76.5-121.8 mg/dl, p=0.004), lactate (2.65 mmol/l (IQR=1.80-4.20) vs. 3.70 mmol/l (IQR=2.90-5.55 mmol/l), p=0.002) and less pronounced base deficit (-2.05 mmol/l, IQR=-3.90 to -0.17 mmol/l vs. -2.8, IQR=-5.57 to -1.05 mmol/l, p=0.01, OR=0.7, 95% CI=0.49-0.99). CONCLUSIONS In uncomplicated pregnancies and deliveries, well-controlled gestational diabetes mellitus has potentially significant detrimental effects on fetal acid-base status at birth. Epidural analgesia reduces cord arterial glucose and lactates.

Soluble HLA-G concentrations in maternal blood and cervical vaginal fluid of pregnant women with preterm premature rupture of membranes

OBJECTIVE To evaluate soluble HLA-G (sHLA-G) concentrations in maternal blood serum and cervical vaginal fluid in pregnancies complicated by preterm premature rupture of membranes (PPROM) compared to controls. STUDY DESIGN Case-control study of 24 women with PPROM and 40 controls. MAIN OUTCOME MEASURES Vaginal and serum sHLA-G and IL-6 concentrations. FINDINGS Women with PPROM had significantly higher serum and vaginal sHLA-G concentrations compared to controls (respectively median 31.48U\ml versus 13.9U\ml p<0.001 and 1.7U\ml versus 0.1U\ml p<0.001). Vaginal expression of IL-6 was higher in PPROM cases compared to controls (respectively, median 31.19pg\ml versus 6.67pg\ml; p<0.001). Higher serum and vaginal sHLA-G were associated with both a shorter length of pregnancy and histological chorioamnionitis in the PPROM group. CONCLUSIONS Higher vaginal and serum sHLA-G in PPROM cases may be a sign of local and systemic inflammation.

Early, Incomplete, or Preclinical Autoimmune Systemic Rheumatic Diseases and Pregnancy Outcome.

To evaluate the impact of preclinical systemic autoimmune rheumatic disorders on pregnancy outcome.

Association between previously unknown connective tissue disease and subclinical hypothyroidism diagnosed during first trimester of pregnancy

OBJECTIVE To investigate the presence of autoimmune rheumatic disorders among women with autoimmune thyroid disorders diagnosed during the first trimester of pregnancy and subsequent pregnancy outcomes. DESIGN Case-control study. SETTING Tertiary obstetric and gynecologic center. PATIENT(S) Pregnant women in the first trimester of pregnancy. INTERVENTION(S) Clinical, laboratory, ultrasonographic evaluations. MAIN OUTCOME MEASURE(S) Thyroid-stimulating hormone (TSH) level; antibodies against thyroperoxidase, thyroid globulin and TSH receptor detection; screening for rheumatic symptoms and antinuclear antibodies (ANA); uterine artery pulsatility index evaluation; pregnancy complication onset. RESULT(S) Out of 3,450 women enrolled, 106 (3%) were diagnosed with autoimmune thyroid disorders. ANA were present in 18 (16.9%) of 106 cases and 26 (12.6%) of 206 controls. Of the cases, 28 (26.4%) of 106 reported rheumatic symptoms, 5 of these were diagnosed with Sjögren syndrome or with undefined connective tissue disease. Autoimmune thyroid diseases are statistically significantly associated with a higher risk of preeclampsia, fetal growth restriction, and overall pregnancy complications compared with controls, with a higher uterine artery pulsatility index, suggesting a defective placentation in thyroid disorders. The effect of ANA-positivity on moderate/severe adverse pregnancy outcomes was statistically significant among the patients with thyroid disorders (9 of 18 as compared to 8 of 88, odds ratio 9.65; 95% confidence interval, 2.613-7.81). CONCLUSION(S) Connective tissue diseases are frequently associated with autoimmune thyroid disorders diagnosed during the first trimester of pregnancy. Thyroid autoimmunity and ANA positivity independently increased the risk of adverse pregnancy outcomes.