IMPORTANCEAlthough several studies have provided information on short-term clinical outcomes in children with perinatal exposure to SARS-CoV-2, data on the immune response in the first months of life among newborns exposed to the virus in utero are lacking. OBJECTIVE To characterize systemic and mucosal antibody production during the first 2 months of life among infants who were born to mothers infected with SARS-CoV-2. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study enrolled 28 pregnant women who tested positive for SARS-CoV-2 infection and who gave birth at Policlinico Umberto I in Rome, Italy, from November 2020 to May 2021, and their newborns. Maternal and neonatal systemic immune responses were investigated by detecting spike-specific antibodies in serum, and the mucosal immune response was assessed by measuring specific antibodies in maternal breastmilk and infant saliva 48 hours after delivery and 2 months later. EXPOSURES Maternal infection with SARS-CoV-2 in late pregnancy. MAIN OUTCOMES AND MEASURES The systemic immune response was evaluated by the detection of SARS-CoV-2 IgG and IgA antibodies and receptor binding domain-specific IgM antibodies in maternal and neonatal serum. The mucosal immune response was assessed by measuring spike-specific antibodies in breastmilk and in infant saliva, and the presence of antigenantibody spike IgA immune complexes was investigated in breastmilk samples. All antibodies were detected using an enzyme-linked immunosorbent assay. RESULTSIn total, 28 mother-infant dyads (mean [SD] maternal age, 31.8 [6.4] years; mean [SD] gestational age, 38.1 [2.3] weeks; 18 [60%] male infants) were enrolled at delivery, and 21 dyads completed the study at 2 months' follow-up. Because maternal infection was recent in all cases, transplacental transfer of virus spike-specific IgG antibodies occurred in only 1 infant. One case of potential vertical transmission and 1 case of horizontal infection were observed. Virus spike proteinspecific salivary IgA antibodies were significantly increased (P = .01) in infants fed breastmilk (0.99 arbitrary units [AU]; IQR, 0.39-1.68 AU) vs infants fed an exclusive formula diet (0.16 AU; IQR, 0.02-0.83 AU). Maternal milk contained IgA spike immune complexes at 48 hours (0.53 AU; IQR, 0.25-0.39 AU) and at 2 months (0.09 AU; IQR, 0.03-0.17 AU) and may have functioned as specific stimuli for the infant mucosal immune response. CONCLUSIONS AND RELEVANCEIn this cohort study, SARS-CoV-2 spike-specific IgA antibodies were detected in infant saliva, which may partly explain why newborns are resistant to SARS-CoV-2 infection. Mothers infected in the peripartum period appear to not only passively protect the (continued) Key Points Question What is the association of maternal SARS-CoV-2 infection with immune response in offspring in the first 2 months of life? Findings In this cohort study of 21 mothers who tested positive for SARS-CoV-2 at delivery and their 22 newborns, there was 1 case of potential motherinfant vertical virus transmission and 1...

Aim: To analyze the prognostic value of maternal serum C-reactive protein (CRP) in predicting funisitis in patients with preterm premature rupture of membranes (pPROM). Methods: 66 patients (gestational age 24–33 weeks) hospitalized 1–12 h after pPROM were enrolled. White blood cell count (WBC), platelet count (PLT) and plasma concentration of CRP were assessed every 3 days. Histological evidence of chorioamnionitis and funisitis was obtained post-partum. Receiver operating characteristic (ROC) curves were employed to evaluate the role of maternal CRP in predicting funisitis. Results: Funisitis was found in 24 patients (36.3%); 42 patients (63.7%) without funisitis were considered as controls. PLT and WBC at admission and before delivery did not show significant differences and were not statistically different between the two groups. Patients with funisitis had significantly higher CRP levels both at admission to hospital and 24– 48 h before delivery. ROC curve analysis showed that CRP at admission (area under the curve: 0.671, p = 0.021) and before delivery (area under the curve: 0.737, p = 0.001) are predictive of funisitis. Conclusions: High maternal serum CRP levels (>20,000 µg/l) in pPROM patients at admission to hospital may be an early marker which indicates, with a good diagnostic performance, the presence of funisitis.

The aim of the study was to evaluate the body composition and fat distribution in long-term users of hormonal replacement therapy (HRT). 18 healthy menopausal women, long-term users of HRT (transdermal estradiol 50 μg continuously administered and 10 mg/day of medroxyprogesterone acetate for 12 days/month) and 18 healthy menopausal women, who had never used HRT were included in the study. Age, menopausal age, parity, weight and height (body mass index, weight/height²), and lifestyle habits were similar. Waist and hip circumference, body composition and waist/hip ratio were measured and the results were analyzed. No significant difference was demonstrated in fat and water percentage, and waist/hip ratio. Nevertheless, the waist circumference of long-term HRT users was significantly lower than that of non-users. In conclusion, abdominal fat in long-term HRT users is lower than that of non-users of similar age, menopausal age and body mass index.

Objective SLE is an autoimmune disease, mainly affecting women of childbearing age, with possible impact on pregnancy. In this study, we evaluated pregnancy outcomes in all pregnant patients affected by SLE, followed in the context of a rheumatology/gynaecology multi-disciplinary team. Methods Since 2008, we evaluated 70 consecutive pregnancies occurring in 50 SLE patients referring to the Lupus Clinic of Sapienza University of Rome; as controls we evaluated 100 consecutive pregnancies in 100 women without autoimmune diseases. Results By comparing SLE patients and controls, we did not find differences in terms of pregnancy outcomes, except for the occurrence of small for gestational age, which was significantly higher in the SLE group (22.8% vs 11%, P =0.003). Small for gestational age was associated with the positivity for anti-dsDNA, anti-Sm and anti-RNP (P =0.009, P =0.02, P =0.002, respectively). A disease flare was reported in 28 pregnancies (40%) and in 31 puerperium periods (44.3%). Flare during pregnancy was associated with anti-SSA (P =0.02), while puerperium relapse with previous MMF treatment (P =0.01) and haematological flare during pregnancy (P =0.03). Conclusion The present study confirms how pre-gestational counselling and a multi-disciplinary approach could result in positive pregnancy outcomes for SLE patients. The high percentage of disease relapse justifies even more the need for multi-disciplinary management.

Ipriflavone (IP) (7-isopropoxyisoflavone), a synthetic isoflavone derivative, is active in both inhibiting bone resorption and enhancing osteoblast function. This property suggested its clinical use in the treatment of involutional osteoporosis, and in the prevention of postmenopausal bone mass loss. Forty postmenopausal women with low bone mineral content were enrolled and randomly treated for 12 months with IP 600 mg/day or placebo (PL), according to a double-blind, parallel group design. All patients wee also given an oral calcium supplementation (1 g/day). Bone mineral density (BMD) was measured at the spine (L2-L4) by dual-energy X-ray absorptiometry and at the distal radius by single-photon absorptiometry. Bone metabolism markers (serum calcium, phosphate, osteocalcin, and alkaline phosphatase, and urinary calcium, phosphate, and hydroxyproline) were assessed at the same times. After 12 months, a reduction of BMD was evidenced in the PL-treated group, at both the spine (-2.2%, P < 0.01 vs baseline) and the forearm (-1.2%). In the IP-treated group, an increase of BMD was obtained (+1.2%, P < 0.01 vs placebo, at the spine; +3%, not significant, at the forearm). Bone markers were in the normal range for postmenopausal women; no statistically significant modifications were observed during the treatment period. Three patients were withdrawn from the treatment in the IP-treated group, and two in the PL-treated group for gastrointestinal disturbances. In the other women, the tolerance of the drug was good and the compliance with the oral treatment was excellent.

Background/Aim: The aim of this prospective controlled study was to compare the effects of two therapies for menopause on factor VII (FVII) and hemostatic variables. Methods: Postmenopausal women were assigned to receive one of the following treatments: transdermal estradiol (TTS E2; 50 μg) combined in a continuous sequential regimen with oral medroxyprogesterone acetate (MPA; 10 mg/day for 12 days) (group A; n = 20), tibolone (2.5 mg/day) (group B; n = 21) or placebo (group C; n = 19). Sixty women completed the 1-year treatment and underwent follow-up examinations after 3, 6 and 12 months. Results: TTS E2/MPA induced various changes in procoagulatory factors. At 12 months, fibrinogen, activated FVII (FVIIa) and coagulative FVII (FVIIc) had increased by 10.7, 12.9 and 3.7%, respectively. Among the fibrinolytic factors, plasminogen and α2-antiplasmin increased by 11.3 and 7.2%, respectively. Lipoprotein(a) [Lp(a)] and antithrombin III (ATIII) did not show any significant variation. Tibolone induced some changes toward a more homogeneous antithrombotic profile. Fibrinogen, FVIIa and FVIIc decreased significantly by 7.5, 8.1 and 21.3%, respectively. Plasminogen increased (by 11.8%) and Lp(a) decreased (by 28.4%). ATIII was unchanged with tibolone therapy. Conclusion: Our results show that tibolone induces a significant reduction in FVIIc and Lp(a) and a greater enhancement of factors promoting fibrinolysis than the TTS E2/MPA regimen.

We present the case of a stillbirth in a paucisymptomatic mother affected by SARS-CoV-2. At gross examination, the placenta showed a diffuse marbled appearance and a focal hemorrhagic area. Multiple areas of hemorrhagic/ischemic necrosis with central and peripheral villous infarctions and thrombosis of several maternal and fetal vessels with luminal fibrin and platelet deposition was observed. All the lesions appeared to be synchronous. Virus particles were identified by Electron Microscopy within the cytoplasm of endothelial cells whereas, by real time rRT-PCR assay, SARS-CoV-2 RNA was detected in placental tissue. In this case, fetal vascular malperfusion was likely casually associated with the infection; indeed, our EM images clearly showed that the marked SARS-CoV-2 endotheliotropism involved the intravillous fetal capillaries. We confirmed that syncytiotrophoblast is the major target cell type for SARS-CoV-2 infection of the placenta. In conclusion, the possible consequences of the action of the placentotropic SARS-CoV-2 include the occurrence of vertical transmission, as reported in literature, and/or stillbirth: this latter possibility may be triggered by a hampered maternal and/or fetal perfusion of the placenta. The diffuse thrombosis and subsequent ischemia of fetal capillaries induced by COVID-19 cannot be predicted by standard clinical surveillance.

Background: Prescriptions for hormone replacement therapy (HRT) declined following the publication of the Women's Health Initiative study. The number of women who experience recurrence of menopausal symptoms after discontinuation of long-term HRT (LT-HRT), the length of time these symptoms last and the preferred alternative treatments remain unknown. Methods: This prospective 3-year follow-up study analyses the prevalence and intensity of menopausal symptoms that occur in young postmenopausal women who discontinued LT-HRT. Symptoms were evaluated using the Menopause Rating Scale. Results: Women (254) who discontinued LT-HRT (mean use: 6.9 ± 2.3 years) were recruited. Mean age at menopause was 48.1 ± 3.4 years. Mean age at discontinuation was 56.8 ± 3.7 years. 23% of the women were lost to follow-up. Of the remaining 196 women, 93% experienced a recurrence of menopausal symptoms within the first year, 25% resumed low-dose HRT, 62% used vaginal estrogens, 54% used phytoestrogens, and 2% used alternative therapies. A decrease in symptom prevalence and intensity was observed during the 3-year follow-up. Conclusions: Symptoms re-appeared in a significant proportion of patients within the first year after discontinuation of LT-HRT. However, after 3 years, the majority of these women were asymptomatic. Patients who discontinue LT-HRT may require a more detailed follow-up immediately after the discontinuation of treatment.