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.

Intrapartum pyrexia, cardiotocography traces and histologic chorioamnionitis: a case-control study.

OBJECTIVES: To compare characteristics of labor, cardiotocography traces, and maternal and neonatal outcomes, in a cohort of pregnancies at term complicated by maternal intrapartum pyrexia, with or without a histologic diagnosis of chorioamnionitis. METHODS: This is a retrospective case-control study including pregnancies at term with detection of maternal intrapartum pyrexia, delivered between January 2020 and June 2021. Cardiotocography traces were entirely evaluated, since admission till delivery, and classified according to the International Federation of Obstetrics and Gynecology (FIGO) guideline. Maternal and neonatal outcomes were also recorded as secondary outcomes. Placentas have been studied according to the Amniotic Fluid Infection Nosology Committee. RESULTS: Forty four patients met the inclusion criteria and were included in the study cohort. There was a significant association between the use of oxytocin augmentation in labor and the histologic diagnosis of chorioamnionitis. A significative recurrence of loss and/or absence of accelerations at the point of pyrexia was also documented in women with histological chorioamnionitis compared to the others. CONCLUSIONS: Chorioamnionitis appears to be associated with myometrial disfunction, as suggested by the increased use of oxytocin augmentation during active labor of women at term with intrapartum pyrexia and histologic diagnosis of chorioamnionitis.

Maternal Hemodynamics from Preconception to Delivery: Research and Potential Diagnostic and Therapeutic Implications: Position Statement by Italian Association of Pre-Eclampsia and Italian Society of Perinatal Medicine.

OBJECTIVE: The Italian Association of Preeclampsia (AIPE) and the Italian Society of Perinatal Medicine (SIMP) developed clinical questions on maternal hemodynamics state of the art. STUDY DESIGN: AIPE and SIMP experts were divided in small groups and were invited to propose an overview of the existing literature on specific topics related to the clinical questions proposed, developing, wherever possible, clinical and/or research recommendations based on available evidence, expert opinion, and clinical importance. Draft recommendations with a clinical rationale were submitted to 8th AIPE and SIMP Consensus Expert Panel for consideration and approval, with at least 75% agreement required for individual recommendations to be included in the final version. RESULTS: More and more evidence in literature underlines the relationship between maternal and fetal hemodynamics, as well as the relationship between maternal cardiovascular profile and fetal-maternal adverse outcomes such as fetal growth restriction and hypertensive disorders of pregnancy. Experts agreed on proposing a classification of pregnancy hypertension, complications, and cardiovascular states based on three different hemodynamic profiles depending on total peripheral vascular resistance values: hypodynamic (>1,300 dynes·s·cm-5), normo-dynamic, and hyperdynamic (<800 dynes·s·cm-5) circulation. This differentiation implies different therapeutical strategies, based drugs' characteristics, and maternal cardiovascular profile. Finally, the cardiovascular characteristics of the women may be useful for a rational approach to an appropriate follow-up, due to the increased cardiovascular risk later in life. CONCLUSION: Although the evidence might not be conclusive, given the lack of large randomized trials, maternal hemodynamics might have great importance in helping clinicians in understanding the pathophysiology and chose a rational treatment of patients with or at risk for pregnancy complications. KEY POINTS: · Altered maternal hemodynamics is associated to fetal growth restriction.. · Altered maternal hemodynamics is associated to complicated hypertensive disorders of pregnancy.. · Maternal hemodynamics might help choosing a rational treatment during hypertensive disorders..

Timing of cesarean delivery for fetal heart rate abnormalities in hypertensive pregnancies induced with oral misoprostol or Foley catheter: Secondary analysis of a randomized clinical trial.

OBJECTIVE: The study aims to assess how oral misoprostol for cervical ripening affects the time of cesarean delivery (CD) for fetal heart rate (FHR) abnormalities in pre-eclampsia patients. Secondary goals include determining the role of uterine hyperstimulation, comparing misoprostol with Foley catheter, and identifying risk factors for FHR abnormalities associated with CD. METHODS: A previously published randomized clinical trial was subjected to a secondary analysis (NCT01801410). We conducted a time-dependent analysis, stratifying the population based on the final mode of induction used (low-dose oral misoprostol vs Foley catheter). RESULTS: There was no CD for FHR abnormalities within 2 h of starting misoprostol. At 5 h, the cumulative incidence of CD for FHR abnormalities in the misoprostol group was 2.10%, while it was 1.00% in the Foley group (P = 0.565). After 25 h, the CD risk for FHR abnormalities remained constant in both groups at 21.00% (95% confidence interval [CI] 15.00%-28.00%). Within 5 h of misoprostol induction, the risk of uterine hyperstimulation was similar in both groups (0.33% in misoprostol vs 0.34% in Foley group, P = 0.161). The risk of CD for FHR abnormalities was unaffected by newborn weight centiles. CONCLUSION: There was no significant difference in CD risk for FHR abnormalities between misoprostol and Foley catheter induction. Nonetheless, the cumulative incidence of CD for FHR abnormalities increased faster in the misoprostol group, indicating that FHR monitoring timing should be tailored to the induction method.

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.

A strange case of pleuritic pain in the third trimester of pregnancy.

Pulmonary sequestration is an uncommon congenital malformation of the lung, generally diagnosed in childhood or adolescence, corresponding to dysplastic lung tissue not communicating with the rest of vascular or bronchial lung system but receiving an arterial blood supply from systemic arteries. Currently, surgical resection is usually indicated in order to prevent or treat related symptoms or complications, although controversy exists regarding its use in asymptomatic patients and adults. We present the case of a 32-year-old pregnant woman with acute chest pain and vomiting diagnosed with intralobar sequestration at 32+2 weeks of gestation and treated with pulmonary lobectomy after giving birth by cesarean section at 33+0 weeks of gestation.

Aspirin for prevention of preeclampsia and adverse perinatal outcome in twin pregnancies: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate the potential role of aspirin in reducing the risk of preeclampsia and adverse maternal and perinatal outcomes in twin pregnancies. DATA SOURCES: Medline, Embase, Google Scholar, Cochrane, and ClinicalTrial.gov databases were searched. STUDY ELIGIBILITY CRITERIA: The search and selection criteria were restricted to the English language. METHODS: The primary outcome was the incidence of preeclampsia. The secondary outcomes included gestational hypertension; fetal growth restriction; preterm birth, either spontaneous or iatrogenic, before 34 weeks of gestation; gestational age at birth; neonatal birthweight; and adverse events secondary to the administration of aspirin, including antepartum and postpartum hemorrhage. In addition, subgroup analyses according to chorionicity (dichorionic vs monochorionic), aspirin dose, and gestational age at administration of aspirin (<16 vs ≥16 weeks of gestation) and considering only studies with a daily aspirin dose of ≥100 mg/d were performed. Head-to-head meta-analyses reporting results as summary odds ratios and mean differences were used to analyze categorical and continuous variables, respectively. Quality assessment for randomized controlled trials was independently performed by 2 researchers based on the risk of bias that was assessed using the revised Cochrane risk-of-bias tool for randomized trials. The conclusion of the meta-analysis on the primary outcome was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: Overall, 9 studies (2273 twin pregnancies) were included. When considering all studies, the risk of preeclampsia was lower in twin pregnancies treated with aspirin than in those not treated with aspirin (odds ratio, 0.64; 95% confidence interval, 0.48-0.85; P=.003), although there was no significant difference in the risk of gestational hypertension (P=.987), fetal growth restriction (P=.9), or adverse maternal and perinatal events (P=.9) in twin pregnancies treated with aspirin compared with those not treated with aspirin. There was no significant difference in the gestational age at birth (P=.2) and neonatal birthweight (P=.06) between women receiving aspirin and those not receiving aspirin. When considering only studies with an aspirin dose of >100 mg/d, the risk of preeclampsia (odds ratio, 0.45; 95% confidence interval, 0.23-0.86; P=.02) was significantly lower in pregnancies receiving aspirin than in those not receiving aspirin, Conversely, there was no significant difference in the risk of gestational hypertension (P=.20), fetal growth restriction (P=.1), gestational age at birth (P=.06), and neonatal weight (P=.05) between the 2 groups. Furthermore, there was no significant difference in the risk of preeclampsia when considering only studies with an aspirin dose of >80 mg/d (P=.611). The association between the administration of aspirin and preeclampsia persisted when considering an aspirin dose of >100 mg/day or when the medication was started before 16 weeks of gestation. The overall quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation assessment was low. CONCLUSION: The administration of aspirin in women with twin pregnancies reduced the risk of preeclampsia. The findings from this study highlighted the need for randomized controlled trials elucidating the actual role of aspirin in affecting maternal and perinatal outcomes in twin pregnancies.

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.

Maternal Left Ventricular Function in Uncomplicated Twin Pregnancies: A Speckle-Tracking Imaging Longitudinal Study.

OBJECTIVE: The knowledge of maternal cardiovascular hemodynamic adaptation in twin pregnancies is incomplete. We aimed to longitudinally investigate maternal left ventricular (LV) function in uncomplicated twin pregnancies. METHODS: 30 healthy and uncomplicated twin pregnant women and 30 controls with normal singleton pregnancies were prospectively enrolled to undergo transthoracic echocardiography at 10-15 week's gestation (w) (T1), 19-26 w (T2) and 30-38 w (T3). LV dimensions and volumes, as well as LV ejection fraction (LVEF), mass (LVM) and diastolic parameters (at transmitral pulsed wave Doppler and mitral annular plane tissue Doppler), were calculated. Speckle-tracking imaging was also applied to evaluate LV global longitudinal (GLS), radial and circumferential 2D strains. RESULTS: During twin pregnancy, maternal LV dimensions, volumes and LVM had an increasing trend from T1 to T3, similar to singletons, while LVEF remained stable. There was LV remodeling/hypertrophy in 50% of women at T2 and T3 in both groups. Diastolic function had a worsening trend from T1 to T3 with no differences between twins and singletons, except for higher LV filling pressure (i.e., E/E') at T2 in twins. Two-dimensional strains did not vary during gestation in either group, except for a linear trend to increase (i.e., worsen) GLS in singletons. Radial and circumferential 2D strains were impaired in about half of the women at each trimester, while GLS was altered in one-fourth/one-third of them in both groups. CONCLUSION: Maternal LV geometry, dimensions and function are significantly impaired during twin pregnancies, in particular in the second half of gestation, with no significant differences compared to singletons.

Maternal Right Ventricular and Left Atrial Function in Uncomplicated Twin Pregnancies: A Longitudinal Study.

Objective: The knowledge regarding maternal cardiovascular hemodynamic adaptation in twin pregnancies is incomplete. We performed a longitudinal investigation of maternal right ventricular (RV) and left atrial (LA) function in a cohort of uncomplicated twin pregnancies compared to singleton pregnancies. Study design: Healthy women with uncomplicated twin pregnancies were prospectively enrolled and assessed by transthoracic echocardiography at 10−15 weeks' (w) gestation (T1), 19-26 w gestation (T2), and 30−38 w gestation (T3). Subjects with uneventful singleton pregnancies were selected as controls at the same gestational ages. Cardiac findings were compared to those of women with uneventful singleton gestations. RV systolic and diastolic functions were assessed by conventional echocardiography (FAC, TAPSE, sPAP, E, A, DT) and tissue Doppler imaging (TDI) (E', A', S', IVA, IVCT, IVRT, ET, MPI), and LA dimensions were calculated. Speckle-tracking imaging was also applied to evaluate RV global longitudinal strain and LA 2D strains (at LV end-systole (LAS) and at atrial contraction (LAA)). Results: Overall, 30 uncomplicated twin and 30 uncomplicated singleton pregnancies were included. Regarding maternal RV function in twins, all the parameters (FAC, TAPSE, sPAP, E, A, E/A, DT, E/E', IVA, IVCT, MPI and 2D longitudinal strain) were almost stable throughout gestation, with the exception of the TDI findings (E' decreased from T1 to T3 (p = 0.03), while E'/A' increased from T1 to T2 and then decreased (p = 0.01); A' and basal S' increased (p = 0.04 and p = 0.03, respectively), while IVRT and ET significantly decreased (p = 0.009 and p = 0.007, respectively)). These findings were similar to those found for singleton pregnancies. LA dimensions significantly increased throughout gestation in both twins and singletons (p < 0.001), without intergroup difference. LA strains did not vary during either twin or singleton pregnancies, except for LAA in T1, which was higher among twins than among singletons. Conclusion: Maternal RV and LA function in uncomplicated twin pregnancies does not seem to undergo more significant changes than in singletons, being characterized by similar findings in RV systolic and diastolic functions, as well as LA dimensions and strains.

Inappropriate left ventricular mass after HELLP syndrome inappropriate LVM after HELLP syndrome.

OBJECTIVES: Excessive left ventricular mass (LVM) results in inefficient LV work with energy waste leading to a negative prognostic effect. We aimed at investigating the presence of inappropriate LVM and calculating the myocardial mechano-energetic efficiency index (MEEi) in former pre-eclamptic (PE) women (with or without HELLP syndrome) compared to women who experienced HELLP syndrome without PE. STUDY DESIGN: In this cross-sectional study, women with a history of normotensive HELLP (n = 32), PE without HELLP (n = 59), and PE with HELLP (n = 101) underwent echocardiography as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity. MAIN OUTCOME MEASURES: LVM excess was calculated as the ratio between observed LVM and predicted LVM (by sex, stroke work and height), while MEEi was considered as the ratio between stroke work and "double product" (to approximate energy consumption), indexed to LVM. RESULTS: LV hypertrophy was present in 8-14% and concentric remodeling in 31-42% of women, without intergroup difference. LVM was inappropriate in one-third of normotensive former HELLP and in about one-half of PE with or without HELLP, with no difference among groups. Accordingly, without nominal difference, MEEi showed a tendency towards lower values in former pre-eclamptic individuals. CONCLUSIONS: Women with a history of HELLP syndrome, independently from the presence/absence of PE, showed inappropriate LVM in the first 4 years after delivery, which may partially explain the elevated CV risk in these women compared to the general female population.

Uterine artery Doppler for the prediction of outcome in pregnancies complicated by hypertensive disorders of pregnancy.

OBJECTIVES: To evaluate, in pregnancies complicated by hypertensive disorders of pregnancy (HDP), the predictive role of uterine artery (UtA) Doppler for pregnancy outcome compared to the definition of preeclampsia (PE) established by ISSHP recommendations. STUDY DESIGN: Retrospective cohort study including singleton pregnancies diagnosed with HDP, who underwent UtA Doppler assessment at admission in 2011-2017. The study population was classified considering the presence or absence of PE and according to the presence or absence of abnormal UtA Doppler (mean pulsatility index > 95th percentile). MAIN OUTCOME MEASURES: Pregnancy outcome, maternal and fetal complications, evaluated as composite outcomes (CO), and duration of pregnancy (from admission to delivery). RESULTS: A total of 311 mother-infant couples was included.The diagnostic ability of the two classifications was analysed comparing the relative likelihood ratio in the Biggerstaff graph. ISSHP definition turned out to be more efficient in detecting maternal adverse CO in comparison to UtA Doppler, relative positive likelihood ratio 1.50 (1.35-1.66) and 1.31 (1.07-1.60). UtA Doppler classification resulted more efficient in predicting adverse neonatal CO than PE definition, relative positive likelihood ratio 2.21 (1.77-2.75) and 1.61 (1.37-1.90). UtA Doppler was significantly associated with delivery at earlier gestational ages both for patients affected by PE and for women affected by HDP without superimposed PE (respectively p = 0.009 and p = 0.037). CONCLUSIONS: UtA Doppler at HDP diagnosis is a useful bedside marker of fetal/neonatal complications, and is associated with pregnancy duration.

Maternal myocardial dysfunction after hemolysis, elevated liver enzymes, and low platelets syndrome: a speckle-tracking study.

OBJECTIVES: Pregnancy complicated by pre-eclampsia (PE) and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is associated with an increased risk of cardiovascular (CV) diseases later in life. Subclinical cardiac alterations precede eminent CV diseases. Speckle-tracking echocardiography (STE) is an effective method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to investigate the prevalence of subclinical myocardial dysfunction in former PE patients (with and without HELLP syndrome) compared to normotensive women affected by HELLP syndrome. METHODS: In this cross-sectional retrospective study, women with a history of normotensive HELLP (n = 32), PE without HELLP (n = 59), and PE with HELLP (n = 101) underwent conventional and STE as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity. RESULTS: Women with a history of PE with HELLP syndrome were characterized by a higher prevalence of altered left ventricular circumferential and global longitudinal two-dimensional (2D) strain (74 and 20%, respectively), altered right ventricular longitudinal 2D strain (37%), and left atrial (LA) 2D strain (57%). Moreover, a higher proportion of alterations of biventricular and LA strains was also present in former PE without HELLP as well as in the normotensive HELLP group. CONCLUSIONS: In the first years after a pregnancy complicated by HELLP syndrome, irrespective of whether there was concomitant PE, a higher rate of abnormal STE myocardial function is observed. Therefore, these women may benefit from CV risk management.