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The efficacy of low molecular weight heparin (LMWH) is well-established in patients with obstetric antiphospholipid syndrome (O-APS). Their role in women with unexplained recurrent pregnancy loss (U-RPL) and late obstetrical complications (intrauterine growth restriction, IUGR and preeclampsia) is controversial. Here we compared rates of miscarriage and late obstetrical complications in RPL patients diagnosed with O-APS (n = 57) or hereditary thrombophilia (n = 25) (both assuming LMWH from the beginning of pregnancy) and in patients with a history of U-RPL (n = 118), assuming or not LMWH, followed at the 'Pregnancy at risk' and 'Recurrent pregnancy loss' outpatient clinics at the San Raffaele Hospital from April 2010 to April 2020. Patients with systemic autoimmune diseases other than primary O-APS were excluded. We tested for bivariate or multivariate associations among adverse pregnancy outcomes, the presence of thrombophilia and LMWH use by using chi-square test, Anova, propensity score adjusted univariate logistic regression and multivariate analysis as appropriate. U-RPL patients assuming LMWH from the beginning of pregnancy (group A) had a significantly lower rate of miscarriage compared to U-RPL patients who were not treated with LMWH (group B) (13 % vs. 41 % respectively, p 0.001) and similar pregnancy rates compared to both O-APS patients with a history of RPL taking LMWH (group C, 18 %) and RPL patients with thrombophilia and treated with LMWH (group D, 16 %). Our data highlight a protective effect of LMWH on miscarriage in patients with a history of U-RPL. In these patients, LMWH seems as effective as in O-APS and hereditary thrombophilia in reducing RPL.

Systemic lupus erythematosus (SLE) preferentially affects women of childbearing age. Miscarriages or fetal death, intrauterine growth restriction (IUGR), preterm delivery, preeclampsia and disease flares complicate pregnancy in SLE patients. Treatment is challenging due to the need to prevent disease exacerbations and limit obstetrical complications, while showing an acceptable safety profile for both the mother and the fetus. We collected data from 74 pregnancies in 53 SLE patients prospectively followed in a dedicated ‘Pregnancy at risk’ outpatient clinic from 2003 to 2019. Out of 74, 45 pregnancies patients were treated with hydroxychloroquine (HCQ). Mothers under HCQ therapy (HCQ+ patients) and those who did not receive HCQ (HCQ−) were homogeneous in terms of age and comorbidities. Disease activity prior to conception was slightly higher in HCQ+ patients. No significant difference was observed in terms of obstetrical history. In patients achieving a viable pregnancy, the rate of IUGR (4/39, 10% in HCQ+ vs 8/25, 32%, in HCQ− patients, p

Objective.Antibodies that recognize the phosphatidylserine/prothrombin complex (antiphosphatidylserine/prothrombin antibodies; aPS/PT) might reveal enhanced thrombotic risk in patients with systemic lupus erythematosus. Little is known about their association with pregnancy complications in the antiphospholipid syndrome (APS).Methods.We enrolled 55 patients with APS who were seeking pregnancy in 2 Italian hospitals. Antiphospholipid antibodies (aPL), including anticardiolipin antibodies, anti-β2-glycoprotein I antibodies, lupus-like anticoagulant, and aPS/PT antibodies were assessed, and the patients were prospectively followed for 24 months.Results.There were 65% (36/55) of the APS patients who had aPS/PT antibodies. Forty-seven pregnancies were followed, including 33 of aPS/PT+ patients. Forty-one of the 47 patients (87%) who initiated a pregnancy eventually gave birth to a child. The pregnancy duration and the mean newborn weight at delivery were significantly lower in aPS/PT+ than in aPS/PT− patients (33.1 ± 4.7 vs 36.2 ± 3.4 wks of gestation, respectively, and 2058 ± 964 g vs 2784 ± 746 g, respectively, p < 0.05). Late pregnancy complications, including intrauterine fetal death, preterm delivery, preeclampsia, and intrauterine growth restriction (IUGR), were more frequent in aPS/PT+ patients, independent of the therapy. Titers of aPS/PT IgG were significantly inversely correlated with the neonatal weight at delivery. Vascular injury, as reflected by thrombosis, fibrinoid necrosis, ischemic and hemorrhagic areas, and presence of chorangiomas characterized the IUGR placentas in the presence of aPS/PT.Conclusion.The aPS/PT antibodies might represent markers of aPL-related pregnancy complications, IUGR/preeclampsia in particular, and could help identify beforehand patients who may require additional treatment.

Copyright ©2015 Canti V. This is an open access article distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Volume 2 : Issue 5 Article Ref. #: 1000GOROJ2122 Pregnancy in Takayasu Arteritis Patients Exposed to Anti-Tumour Necrosis Factor (Anti-TNF)-α Therapy

The impact of maternal systemic autoimmune diseases on pregnancy outcome is not unequivocally defined. We analysed the pregnancy outcome of 221 pregnancies from 181 autoimmune patients, consecutively followed in a single Italian reference centre from 2001 to 2009. All patients were prospectively followed with monthly visits. Pregnancy outcome was compared with the previous obstetrical history. The patient population comprised five groups: primary antiphospholipid syndrome (PAPS, 39 pregnancies), antiphospholipid syndrome associated with a rheumatic disease (APS/RD, 17 pregnancies), other RD (92 pregnancies), isolated autoantibodies (autoAbs) in the absence of a definite autoimmune disease (aAbs, 38 pregnancies) and reactive arthritis or spondyloarthropathies (35 pregnancies). Of these patients, 50.6% had previous pregnancy complications with an anamnestic live-birth rate of 43.4%. In these patients, complications dropped to 28.2% (44/156). This percentage was very similar to that observed in the 221 pregnancies (29.9%, 66/221) with a live-birth rate of 87.3%. Mean neonatal weight was 3018 ± 611 g; mean gestational age at delivery was 38.17 ± 2.79 weeks. Thus, 10.4% of pregnancies resulted in preterm delivery and 10.9% newborns had low weight at delivery. APS/RD patients had the worse outcome: 17.6% resulted in miscarriage, 14.3% resulted in growth restriction and 50% resulted in preterm delivery. This result was mainly due to patients with APS/systemic lupus erythematosus (SLE) that had the lowest gestational age at delivery (30.8 ± 3.56 weeks) and the lowest newborn weight (1499 ± 931 g). Results confirm that a strict follow-up and targeted treatments significantly improve pregnancy outcomes in autoimmune patients with PAPS, SLE and isolated autoAbs. The pregnancy outcome in patients with APS/SLE remains unsatisfactory.

Human Leukocyte Antigen (HLA)-G is involved in reprogramming immune responses at fetal-maternal interface during pregnancy. We evaluated the genetic diversity of the 3′ Un-Translated Region (UTR) of HLA-G, previously associated with HLA-G mRNA post-transcriptional regulation, in women with unexplained Recurrent Pregnancy Loss (RPL), with 2 pregnancy losses (RPL-2, n=28), or 3 or more pregnancy losses (RPL-3, n=24), and in 30 women with a history of successful pregnancy. Results showed in RPL-2, but not in RPL-3, women compared to controls: i) higher frequency of the 14bp Ins allele, in single and in double copy; ii) significantly lower frequency of DelG/X genotype, iii) reduced frequency of the UTR-2, and UTR-3 haplotypes; iv) higher frequencies of the UTR-5, UTR-7, and UTR-8 haplotypes. This pilot study supports the relevance of performing 3′UTR HLA-G genetic screening, not limited to a specific polymorphism, but considering the extended haplotypes, as a possible predictor of pregnancy outcome.

Aim To estimate the incidence of preeclampsia (PE) among nulliparous and multiparous patients with type 1 diabetes and to study predictors of PE. Methods We prospectively collected data on all pregnancies of patients with pregestational type 1 diabetes, followed at our Prenatal Medicine Unit between 1993 and 2008. Medical records were prospectively reviewed by two obstetricians for maternal demographics, pregnancy data, maternal and fetal outcomes. Data were analyzed according to the development of PE and parity. Results We identified and collected data on 291 eligible pregnancies (195 among nulliparae and 96 among multiparae). The incidence of PE was 9.2% (95% CI: 5.6–14.2) among nulliparae and 9.4% (95% CI: 4.4–17.0) among multiparae. Patients who developed PE had higher HbA1c during pregnancy compared to patients who did not ( p =0.026 among nulliparae and p =0.032 among multiparae). Chronic hypertension [OR 17.12 (3.22, 91.00)], microalbuminuria at the beginning of the pregnancy [OR 3.77 (1.22, 11.61)], weight gain during pregnancy [OR 1.13 (1.04, 1.23)] and HbA1c in the first trimester [2.81 (1.12, 7.05)], but not parity, were significant predictors of PE. Conclusions Among patients with type 1 diabetes the incidence of PE was similar among nulliparae and multiparae, unlikely in the general population where PE is a disease of the first pregnancy. An increased risk of PE should be assumed for both nulliparous and multiparous women with pregestational diabetes.

The impact of hypertension in the pregnancies from autoimmune patients is not unequivocally defined. We have prospectively followed 168 pregnancies from 135 patients from four Italian centres to verify the potential impact of hypertension in the antiphospholipid syndrome (APS). The rate of preeclampsia, mean neonatal weight and gestational age at delivery were significantly lower in patients with both APS and hypertension than in patients with hypertension or APS alone. This information may be relevant for counselling and care of these patients.

Pregnancy complications, such as preeclampsia (PEc), have an increased incidence among patients with type 1 diabetes (T1DM), possibly because of maternal vascular involvement. The prototypic long pentraxin, pentraxin 3 (PTX3) is an acute phase reactant critically associated with vascular injury. PTX3 concentrations selectively increase in pregnant women with PEc. Here, we measured PTX3 levels in 37 consecutive pregnant patients with T1DM. Compared with PTX3 levels in healthy pregnant women at identical gestational ages, PTX3 was significantly elevated in pregnant women with diabetes. Patients with pre-existing nephropathy, a well-characterized microvascular complication of diabetes, have even higher PTX3 concentrations and worse maternal and fetal outcomes. Six/thirty-four diabetic non-nephropatic patients developed PEc: PTX3 levels rose abruptly weeks before PEc manifested (p = 0.0375). PTX3 may represent a valuable marker for early detection and prediction of PEc in patients with T1DM.

OBJECTIVE To evaluate whether the presence of insulin antibodies (IAs) may preclude the optimization of metabolic control during pregnancy and affect outcome in women with IDDM. RESEARCH DESIGN AND METHODS IAs were measured by radiobinding assay in 44 women with IDDM referred to the Diabetes and Pregnancy Outpatients' Clinic during 46 pregnancies. Age, duration of IDDM, metabolic control (HbA1c, mean pre- and postprandial capillary blood glucose, frequency of hypo- or hyperglycemia), insulin requirement at 1st and 3rd trimester of pregnancy, BM1, and weight gain were recorded. Neonatal variables such as gestational age, weight, length, and the presence at birth of either hypoglycemia, hypocalcemia, or jaundice requiring phototherapy were also considered. RESULTS IAs correlated positively with insulin requirement (P < 0.05) and negatively with HbA1c at term (P < 0.01). Patients with IA levels ≥ 40% insulin binding (8 of 46) had a higher insulin requirement and lower preprandial capillary blood glucose at the beginning of pregnancy but not at term (P < 0.005), whereas they had lower HbA1c at term than did patients with low IA levels (P < 0.01). IA levels decreased slightly at term (P = 0.007). IA levels ≥ 40% were not associated with a higher rate of hypo- or hyperglycemic episodes or with diabetic complications or thyreopathy. No correlation was found between LA levels and any of the neonatal variables considered. CONCLUSIONS The presence of IAs does not preclude optimization of metabolic control during pregnancy and is compatible with a favourable outcome.