Fetoscopic laser ablation therapy in monochorionic diamniotic twin pregnancies with twin-to-twin transfusion syndrome treated at a single centre over 10 years: a retrospective study.

OBJECTIVES: To review experience with fetoscopic laser ablation of placental anastomoses to treat monochorionic diamniotic (MCDA) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) in a single centre over a ten-year period. METHODS: A retrospective study on 142 MCDA twin pregnancies complicates by TTTS treated with equatorial laser ablation of placental anastomoses (2008-2018). Solomon technique was also applied after 2013. Survival rates, neonatal outcome, intraoperative and post-laser complications were recorded, and prognostic factors analysed. RESULTS: A total of 133 cases were included in the final analysis; 41 patients were at stage II (30.8%), 73 were at stage III (62.9%), while only 12 (9%) at stage I and two patients (1.7%) at stage IV. Solomon technique was applied in 39 cases (29.3%). Survival of both twins was 51.1% (68/133), of a single twin 20.3% (27/133), and of at least one 71.5% (95/133), with an overall survival of 61.3% (163/266). TAPS and recurrent TTTS occurred in 8 (6%) and 15 (11.3%) patients. Survival of both fetuses increased over time (44.6 vs. 57.3%). A posterior placenta (p<0.003) and the use of the Solomon technique (p<0.02) were more frequent in cases with survival of both fetuses, while TTTS recurrence was significantly associated to the loss of one or two fetuses (p<0.01). Such associations were confirmed at logistic regression analysis. CONCLUSIONS: Survival of both twins can improve over time and seems to be favourably associated with a placenta in the posterior location and the use of the Solomon technique.

Maternal functional hemodynamics in uncomplicated twin pregnancies: A longitudinal study using impedance cardiography.

INTRODUCTION: Longitudinal studies of maternal hemodynamics in twin pregnancy are scarce and preload reserve in twin pregnancies has not been studied. Thus, we aimed to investigate serial changes in maternal systemic hemodynamics from the first to third trimester, and cardiovascular response to passive leg raising to evaluate preload reserve using impedance cardiography in a cohort of uncomplicated twin pregnancies. MATERIAL AND METHODS: This was a prospective longitudinal study of 50 twin pregnancies. Maternal hemodynamics was assessed at baseline and 120 seconds after passive leg raising using impedance cardiography, at five time points during gestation. Women were excluded from the analysis if there were pregnancy complications or fewer than three of five planned assessments were available. RESULTS: Data from 37 uncomplicated twin pregnancies were available for analysis. Mean arterial pressure slightly decreased until 17 weeks' gestation, then increased. Systemic vascular resistance was constant in the first half of pregnancy before rising steadily thereafter, whereas the cardiac output increased from the first trimester, peaked by the end of the second trimester and then decreased in the third trimester. The change in stroke volume and cardiac output following passive leg raising during pregnancy ranged from -2.2% to 1.6% and from -3.7% to 3.2%, respectively. Although passive leg raising caused no significant changes in systemic vascular resistance, cardiac output or heart rate, mean arterial pressure decreased in the first and second trimesters. CONCLUSIONS: In uncomplicated twin pregnancies, maternal cardiovascular adaptation is evident from the first trimester. Twin pregnancies show a reduced preload reserve in the second half of gestation.

The use of ultrasound-indicated cerclage or cervical pessary in asymptomatic twin pregnancies with a short cervix at midgestation.

INTRODUCTION: Spontaneous preterm birth in women with a twin pregnancy is one of the main causes of perinatal mortality and morbidity. Our aim was to review the perinatal outcome of asymptomatic twin pregnancies with a sonographic short cervical length during the second trimester treated with an ultrasound-indicated cerclage or cervical pessary. MATERIAL AND METHODS: Retrospective study on asymptomatic twin pregnancies with a short cervix (≤ 25 mm) at transvaginal ultrasound examination during the second trimester treated with a cervical cerclage or pessary (2001-2017). The rate of preterm birth < 28, 32 and 34 weeks of gestation, neonatal mortality, neonatal morbidity and composite adverse neonatal outcome were compared in the groups of women treated with cerclage or pessary. RESULTS: Seventy-four twin pregnancies underwent a cerclage while a cervical pessary was inserted in 34 women with twins at our Department: 36 women with an ultrasound-indicated cerclage and 20 with a pessary were included in the analysis. Median gestational age at delivery was higher in women treated with cerclage compared with those with pessary placement (P = .02) and the rate of preterm birth before 34 weeks of gestation was lower in the cerclage group (P = .03). Admissions to the Neonatal Intensive Care Unit were more frequent in pregnancies with pessary (P = .01), the length of admission was longer (P = .005) and composite adverse neonatal outcome occurred more often (P = .03) compared with the cerclage group. CONCLUSIONS: Ultrasound-indicated cerclage appears to reduce the rate of preterm birth before 34 weeks of gestation in asymptomatic twin pregnancies with a short cervix during the second trimester, and also the composite adverse neonatal outcome compared with pessary.

Agreement between anatomical M-mode and tissue Doppler imaging in the assessment of fetal atrioventricular annular plane displacement in uncomplicated pregnancies: A prospective longitudinal study.

AIM: To evaluate the level of agreement between M-mode and pulsed-wave tissue Doppler imaging (PW-TDI) techniques in assessing fetal mitral annular plane systolic excursion (MAPSE), tricuspid annular plane systolic excursion (TAPSE) and septal annular plane systolic excursion (SAPSE) in a low-risk population. METHODS: This prospective longitudinal study included healthy fetuses assessed from 18 to 40 weeks of gestation. Tricuspid annular plane systolic excursion, MAPSE and SAPSE were measured using anatomical M-mode and PW-TDI. The agreement between the two diagnostic tests was assessed using Bland-Altman analysis. RESULTS: Fifty fetuses were included in the final analysis. Mean values of TASPE were higher than that of MAPSE. There was a progressive increase of TAPSE, MAPSE and SAPSE values with advancing gestation. For each parameter assessed, there was an overall good agreement between the measurements obtained with M-mode and PW-TDI techniques. However, the measurements made with M-mode were slightly higher than those obtained with PW-TDI (mean differences: 0.03, 0.05 and 0.03 cm for TAPSE, MAPSE and SAPSE, respectively). When stratifying the analyses by gestational age, the mean values of TAPSE, MAPSE and SAPSE measured with M-Mode were higher compared to those obtained with PW-TDI, although the mean differences between the two techniques tended to narrow with increasing gestation. Tricuspid annular plane systolic excursion, MAPSE and SAPSE measurements were all significantly, positively associated with gestational age (all P < 0.001). CONCLUSION: Fetal atrioventricular annular plane displacement can be assessed with M-mode technique, or with PW-TDI as the velocity-time integral of the myocardial systolic waveform. Atrioventricular annular plane displacement values obtained with M-mode technique are slightly higher than those obtained with PW-TDI.

Longitudinal reference ranges for serial measurements of myocardial performance index (MPI) by conventional and pulsed-wave tissue Doppler in monochorionic diamniotic twins at 17 to 26 weeks of gestation.

OBJECTIVE: To describe the longitudinal changes of fetal myocardial performance index (MPI) measured by conventional Doppler (MPI) and by pulsed-wave tissue Doppler (MPI') based on a prospective cohort of uncomplicated monochorionic diamniotic twin. METHOD: Single-center observational study. We measured MPI and MPI' in the right and left ventricles 3 times between 17 and 26 weeks of gestation. Second-degree fractional polynomials were built to obtain the best fitting curves in relation to gestational age (weeks) for each parameter. Gestational age-specific reference values were estimated by using two-level hierarchical models. RESULTS: Eighty-three uncomplicated monochorionic pregnancies were included in our study with a total of 249 observations. Fetal cardiac function was measured as MPI RV and LV, MPI' RV and LV at a mean gestational age of 18+3 (range 17+1 to 19+2 ), 22+3 (21+1 to 23+5 ), and 24+3 (22+6 to 26+2 ) weeks. The reference ranges for MPI LV, MPI RV, MPI' LV, and MPI' RV at 17 to 26 weeks were constructed and conditional percentiles calculated. CONCLUSION: The present study provides additional data on fetal cardiac function in uncomplicated monochorionic diamniotic twin gestations, describing the evolution of MPI and MPI' in both ventricles in uncomplicated monochorionic diamniotic pregnancies.

Rapid cervical phIGFBP-1 test in asymptomatic twin pregnancies: role in mid-pregnancy prediction of spontaneous preterm delivery.

Objective This study aimed to assess the accuracy of a second-trimester rapid cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) test to predict spontaneous preterm delivery in asymptomatic twin pregnancies. Method During the second trimester, a rapid test to detect phIGFBP-1 in cervical secretions was performed on consecutive twin pregnancies between 2009 and 2011, to evaluate its predictive value for spontaneous preterm delivery at <28, <30, <32 and <34 weeks' gestation. Excluded were patients with cerclage, pessary or undergoing indicated preterm delivery. Results A total of 197 pregnancies fulfilled the study criteria and were tested at a median gestational age of 20.3 weeks (interquartile range: 20-20.6). Median gestational age at delivery was 36.4 weeks. Spontaneous preterm delivery at <34 weeks occurred in 21 (10.7%) cases, at <32 weeks in 9 (4.5%), at <30 weeks in 6 (3%) and at <28 weeks in 4 (2%). Seventeen patients (8.7%) were test positive: In this group, three patients delivered before 34 weeks' gestation, whereas none delivered at <32 weeks. The sensitivity, specificity, positive and negative predictive value of the test for spontaneous preterm delivery <34 weeks were 14% (95% confidence interval, 3-37%), 92% (86-95%), 17% (4-44%) and 90% (84-93%), respectively, with a positive and negative likelihood ratio of 1.79 (0.56-5.74) and 0.93 (0.78-1.10). Conclusions In the second trimester, rapid cervical phIGFBP-1 testing in asymptomatic twin pregnancies has a poor performance in predicting spontaneous preterm delivery.

Sleep-disordered breathing and pregnancy outcomes: The impact of maternal oxygen saturation.

OBJECTIVE: To investigate pathological associations between sleep-disordered breathing (SDB) and pregnancy outcomes. METHODS: From May 2016 to September 2019, obese women during their uncomplicated singleton pregnancies underwent screening sleep questionnaires, oxygen saturation monitoring, and, in proper cases, complete overnight polysomnography. Their medical records were also recorded. RESULTS: In all, 112 pregnant women were included in the study cohort; 44 showed an oxygen desaturation index ≥10, and their newborns had a significantly higher rate of congenital abnormalities and respiratory distress syndrome compared with the women with normal pulse oximetry. Stepwise multivariate regression analysis showed that basal oxygen saturation was independently associated with the occurrence of fetal growth restriction. CONCLUSION: Among obese pregnant women, the rate of congenital abnormalities is higher in the ones with altered pulse oximetry. Maternal basal oxygen saturation in the first trimester of pregnancy predicts fetal growth restriction independently of maternal age, ethnicity, body mass index, gravidity, and hypertensive disorders of pregnancy.

Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study.

OBJECTIVES: To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. METHODS: Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. RESULTS: We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. CONCLUSIONS: Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

Cervical cerclage in twin pregnancies.

PURPOSE: To evaluate the outcomes of cervical cerclage (CC) in twin pregnancies. METHODS: Retrospective analysis of twin pregnancies undergoing CC between January 2001 and December 2009 at our Institution. CC was offered in case of a cervical length measurement ≤ 20 mm (ultrasound-indicated CC) or in case of cervical dilatation with membranes at or beyond the external cervical os (physical examination-indicated CC). Cervicovaginal and rectal swabs were obtained preoperatively. Perioperative antibiotics and tocolysis were administered. RESULTS: There were 28 cases of ultrasound-indicated and 14 of physical examination-indicated CC. Positive swab cultures were observed in 21 % of cases. The incidence of preterm delivery <34 weeks was 32 % [95 % confidence interval (CI) 16-52 %] and 50 % (95 % CI 23-77 %) in the ultrasound-indicated and physical examination-indicated CC group, respectively. The incidence of premature rupture of membranes <34 weeks was 21 % (95 % CI 8-41 %) and 29 % (95 % CI 8-58 %) in the ultrasound-indicated and physical examination-indicated CC group, respectively. Perinatal survival was 96 % (95 % CI 88-100 %) in the ultrasound-indicated CC group, and 86 % (95 % CI 67-96 %) in the physical examination-indicated CC group. CONCLUSIONS: We showed a high-risk of preterm delivery in both groups, but with a high overall perinatal survival. Our data stress the importance of re-evaluating the efficacy of CC in twin pregnancies by properly designed clinical trials, particularly if it is physical examination indicated.

Reproductive Issues and Pregnancy Implications in Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare systemic autoimmune disease that can influence reproductive health. SSc has a strong female predominance, and the disease onset can occur during fertility age in almost 50% of patients. Preconception counseling, adjustment of treatment, and close surveillance during pregnancy by a multidisciplinary team, are key points to minimize fetal and maternal risks and favor successful pregnancy outcomes. The rates of spontaneous pregnancy losses are comparable to those of the general obstetric population, except for patients with diffuse cutaneous SSc and severe internal organ involvement who may carry a higher risk of abortion. Preterm birth can frequently occur in women with SSc, as it happens in other rheumatic diseases. Overall disease activity generally remains stable during pregnancy, but particular attention should be paid to women with major organ disease, such as renal and cardiopulmonary involvement. Women with such severe involvement should be thoroughly informed about the risks during pregnancy and possibly discouraged from getting pregnant. A high frequency of sexual dysfunction has been described among SSc patients, both in females and in males, and pathogenic mechanisms of SSc may play a fundamental role in determining this impairment. Fertility is overall normal in SSc women, while no studies in the literature have investigated fertility in SSc male patients. Nevertheless, some considerations regarding the impact of some immunosuppressive drugs should be done with male patients, referring to the knowledge gained in other rheumatic diseases.

Immunology of pregnancy and reproductive health in autoimmune rheumatic diseases. Update from the 11th International Conference on Reproduction, Pregnancy and Rheumatic Diseases.

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as "unmet needs", such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.

Frequency of positive antiphospholipid antibodies in pregnant women with SARS-CoV-2 infection and impact on pregnancy outcome: A single-center prospective study on 151 pregnancies.

Background: At the beginning of the SARS-CoV-2 pandemic, there was a lack of information about the infection's impact on pregnancy and capability to induce de novo autoantibodies. It soon became clear that thrombosis was a manifestation of COVID-19, therefore the possible contribution of de novo antiphospholipid antibodies (aPL) raised research interest. We aimed at screening SARS-CoV-2 positive pregnant patients for aPL. Methods: The study included consecutive pregnant women who were hospitalized in our Obstetric Department between March 2020 and July 2021 for either a symptomatic SARS-CoV-2 infection or for other reasons (obstetric complications, labour, delivery) and found positive at the admission nasopharyngeal swab. All these women underwent the search for aPL by means of Lupus Anticoagulant (LA), IgG/IgM anti-cardiolipin (aCL), IgG/IgM anti-beta2glycoprotein I (aB2GPI). Data about comorbidities, obstetric and neonatal complications were collected. Results: 151 women were included. Sixteen (11%) were positive for aPL, mostly at low titre. Pneumonia was diagnosed in 20 women (5 with positive aPL) and 5 required ICU admission (2 with positive aPL). Obstetric complications occurred in 10/16 (63%) aPL positive and in 36/135 (27%) negative patients. The occurrence of HELLP syndrome and preeclampsia was significantly associated with positive aPL (p=0,004). One case of maternal thrombosis occurred in an aPL negative woman. aPL positivity was checked after at least 12 weeks in 7/16 women (44%): 3 had become negative; 2 were still positive (1 IgG aB2GPI + IgG aCL; 1 IgM aB2GPI); 1 remained positive for IgG aCL but became negative for aB2GPI; 1 became negative for LA but displayed a new positivity for IgG aCL at high titre. Conclusions: The frequency of positive aPL in pregnant women with SARS-CoV-2 infection was low in our cohort and similar to the one described in the general obstetric population. aPL mostly presented as single positive, low titre, transient antibodies. The rate of obstetric complications was higher in aPL positive women as compared to negative ones, particularly hypertensive disorders. Causality cannot be excluded; however, other risk factors, including a full-blown picture of COVID-19, may have elicited the pathogenic potential of aPL and contributed themselves to the development of complications.

Stopping bDMARDs at the beginning of pregnancy is associated with disease flares and preterm delivery in women with rheumatoid arthritis.

Objectives: Women with Rheumatoid Arthritis (RA) can experience flares during pregnancy that might influence pregnancy outcomes. We aimed at assessing the disease course during pregnancy and identifying risk factors for flares. Methods: Data about prospectively-followed pregnancies in RA were retrospectively collected before conception, during each trimester and in the post-partum period. Clinical characteristics, disease activity (DAS28-CRP3), medication use, and pregnancy outcomes were analysed with regard to disease flares. Results: Among 73 women who had a live birth, 64 (88%) were in remission/low disease activity before conception. During pregnancy, a flare occurred in 27 (37%) patients, mainly during first and second trimester. Flares during pregnancy were associated with the discontinuation of bDMARDs at positive pregnancy test (55% of patients with flare vs. 30% of patients with no flare, p 0.034, OR 2.857, 95% CI 1.112-8.323) and a previous use of >1 bDMARDs (33% of patients with flare vs. 10% of patients with no flare, p 0.019, OR 4.1, 95%CI 1.204-13.966). Preterm pregnancies were characterised by higher values of CRP [10 mg/L (5-11) vs. 3 mg/L (2.5-5), p 0.01] and DAS28-CRP3 [4.2 (1.9-4.5) vs. 1.9 (1.7-2.6), p 0.01] during the first trimester as compared with pregnancies at term. Preterm delivery was associated with the occurrence of flare during pregnancy (flare 27% vs. no-flare 7%, p 0.034, OR 4.625, 95%CI 1.027-20.829). Conclusion: Preterm delivery in RA patients was associated with flares during pregnancy. Flares occurred more frequently after the discontinuation of bDMARDs at positive pregnancy test. Women with aggressive RA on treatment with bDMARDs should be considered as candidates for continuing bDMARDs during pregnancy in order to reduce the risk of flare and adverse pregnancy outcomes.

Pregnancy outcome of monochorionic twins: does amnionicity matter?

OBJECTIVE: To compare the fetal loss rate of monochorionic (MC) twin pregnancies according to their amnionicity. METHODS: A retrospective review of all MC pregnancy outcomes in a tertiary centre. Pregnancy outcomes were compared for monochorionic monoamniotic (MCMA) versus monochorionic diamniotic (MCDA) pregnancies. RESULTS: 29 MCMA and 117 MCDA twin pregnancies were identified. The overall fetal loss rate was significantly higher in MCMA (23/52, 44.2%) compared to MCDA pregnancies (28/233, 12%, Chi squared = 30.03, p < .001). Kaplan-Meier analysis showed that fetal survival rate in MCDA twins were significantly higher than in MCMA twins (Log-rank Chi-squared = 27.9, p < .0005). Early pregnancy ultrasound identified the causes for these fetal losses in some MCMA twins. After exclusion of identifiable causes, the difference in fetal survival was not significant in the two groups (Log-rank chi-squared = 0.373, p = .54). CONCLUSION: The loss rate for MCMA twins is high and occurs mainly due to discordant congenital abnormality, conjoint twins or twin reversed arterial perfusion (TRAP) sequence. Although the fetal loss rate in MCDA is lower than in MCMA pregnancies, the majority of fetal loss in MCDA pregnancies cannot be predicted at the first scan at presentation. The data of this study questions the widespread policy of a difference in the scheduling of elective delivery for MCMA and MCDA twins.

Disease course and obstetric outcomes of pregnancies in juvenile idiopathic arthritis: are there any differences among disease subtypes? A single-centre retrospective study of prospectively followed pregnancies in a dedicated pregnancy clinic.

To study disease activity during pregnancy and obstetric outcomes in patients with juvenile idiopathic arthritis (JIA) upon different subsets and with focus on medication use. Retrospective observational study of 22 pregnancies in 16 JIA patients (95.5% Caucasian) who were followed between 2010 and 2018. Disease activity, flares and medications were recorded before conception, during each trimester and postpartum period. Pregnancies occurred in 10 (45.5%) oligoarticular extended (OLA-E), 6 (27.3%) in polyarticular (PLA), 4 in (18.2%) systemic (SYS), 1 (4.5%) in oligoarticular persistent (OLA-P) and 1 (4.5%) in enthesitis-related arthritis (ERA) JIA patients. The median age at disease diagnosis and at conception was 5.5 and 28 years (respectively). The median disease duration was 20 years. Nineteen (95%) pregnancies started in a period of stable disease remission. Among the 22 pregnancies, 20 ended with a live birth (90.9%). No spontaneous miscarriages occurred; two voluntary interruption of pregnancy were performed. There were 7 flares in 6/20 pregnancies (35%) and 8 flares (8/22, 36.4%) occurred in postpartum period, all of them in OLA-E and PLA patients. Seven patients (35%) were taking biological disease-modifying anti-rheumatic drugs (bDMARDs) at conception, and 6 of them stopped this treatment at positive pregnancy test. Five patients resumed bDMARDs either during pregnancy (3 exposed during the third trimester) or puerperium due to a flare. Four preterm deliveries (20%) were recorded, all in patients who had a flare during pregnancy. The preconception counselling should include the evaluation of disease subset, as OLA-E and PLA may flare more than other subsets, especially if bDMARDs are discontinued at positive pregnancy test. Continuation of bDMARDs during pregnancy should be considered to minimize the risk of adverse pregnancy outcomes, particularly preterm delivery. Key Points • In our cohort, all the flares during pregnancy and 75% of postpartum flares were observed in patients who withdrew bDMARDs and cDMARDs at the beginning of pregnancy. • Flares were observed only in PLA and OLA-E patients. • Preterm delivery occurred in 20% of the pregnancies; all of these patients had a disease flare during pregnancy.

Mode of birth in women with low-lying placenta: protocol for a prospective multicentre 1:3 matched case-control study in Italy (the MODEL-PLACENTA study).

INTRODUCTION: The term placenta praevia defines a placenta that lies over the internal os, whereas the term low-lying placenta identifies a placenta that is partially implanted in the lower uterine segment with the inferior placental edge located at 1-20 mm from the internal cervical os (internal-os-distance). The most appropriate mode of birth in women with low-lying placenta is still controversial, with the majority of them undergoing caesarean section. The current project aims to evaluate the rate of vaginal birth and caesarean section in labour due to bleeding by offering a trial of labour to all women with an internal-os-distance >5 mm as assessed by transvaginal sonography in the late third trimester. METHODS AND ANALYSIS: The MODEL-PLACENTA is a prospective, multicentre, 1:3 matched case-control study involving 17 Maternity Units across Lombardy and Emilia-Romagna regions, Italy. The study includes women with a placenta located in the lower uterine segment at the second trimester scan. Women with a normally located placenta will be enrolled as controls. A sample size of 30 women with an internal-os-distance >5 mm at the late third trimester scan is needed at each participating Unit. Since the incidence of low-lying placenta decreases from 2% in the second trimester to 0.4% at the end of pregnancy, 150 women should be recruited at each centre at the second trimester scan. A vaginal birth rate ≥60% in women with an internal-os-distance >5 mm will be considered appropriate to start routinely admitting to labour these women. ETHICS AND DISSEMINATION: Ethical approval for the study was given by the Brianza Ethics Committee (No 3157, 2019). Written informed consent will be obtained from study participants. Results will be disseminated by publication in peer-reviewed journals and presentation in international conferences. TRIAL REGISTRATION NUMBER: NCT04827433 (pre-results stage).

Primary Hyperparathyroidism in Pregnancy: A Case Report.

Primary hyperparathyroidism (PHP) is the third most common endocrine disorder. We report the case of a 28-year-old woman who experienced general weakness, hyperemesis gravidarum and hypercalcemia at 11 weeks of gestation. Corresponding to hypercalcemia, we found inappropriately elevated parathyroid hormone levels. Through neck computed tomography a solitary adenoma of the parathyroid gland, measuring 6 × 2.9 × 11 mm has been documented. An ultrasound-guided fine needle aspiration from the mass confirmed the suspicious of a benign tumor. Left superior parathyroidectomy resulted in immediate and permanent resolution of hypercalcemia. The postoperative course was uneventful. Histopathological and immunohistochemical analyses were consistent with parathyroid adenoma. The diagnostic approach to hypercalcemia in pregnancy represents a challenge for multidisciplinary teamwork.

Insulinoma Identified in Puerperium: Association with Pregnancy and Literature Review.

Postpartum hypoglycemia in non-diabetic women is a rare condition. We report the case of a 34-year-old woman who experienced neuroglycopenia 2 days after delivery. Corresponding to severe hypoglycemia, we found inappropriately elevated insulin and C-peptide levels. Following magnetic resonance imaging a lesion of 10×8 mm was detected in the head of the pancreas. An ultrasound-guided fine needle aspiration of the mass confirmed the diagnostic suspicion of a pancreatic neuroendocrine tumor. Complete surgical enucleation of the insulinoma resulted in immediate and permanent resolution of the hypoglycemia. The postoperative course was uneventful. Histopathological and immunohistochemical analyses were consistent with insulinoma. The diagnostic approach to postpartum hypoglycemia represents a challenge for multidisciplinary teamwork. LEARNING POINTS: Although insulinomas are extremely rare during pregnancy, most cases are recognized or become symptomatic during the first trimester.Symptoms of insulinomas may be initially masked due to changes in glucose metabolism and insulin resistance associated with pregnancy.In pregnancy, surgical treatment should be avoided whenever possible because of the risks to both mother and fetus; conservative treatment, including dietary intake, intravenous glucose and glucagon, should be initiated to control the hypoglycemia symptoms.