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.

Giant leiomyoma management during elective cesarean section: a case report.

We present the unique case of a 44-year-old gravida 3 para 2 woman with complaints of monolateral perception of fetal movements who underwent elective cesarean section and hysterectomy for the presence of an exceptionally voluminous infralegamentary leiomyoma. Cesarean section required in-depth preoperative planning and was possible only after gravid uterus exteriorization. Myomectomy and hysterectomy were then necessary to reestablish the physio-anatomical pelvic environment. The patient was discharged after regular and uncomplicated postoperative time. In recent years, the paradigma of avoiding cesarean myomectomy due to fear of hemorrhage has been questioned by many authors and in certain cases cesarean myomectomy may even be undeferrable. We describe an innovative surgical technique which could be useful to obstetricians approaching similar uterine masses during cesarean sections.

Different management strategies for cesarean scar pregnancy: Short-term outcomes and reproductive prognosis.

PURPOSE: To investigate the impact on future reproductive potential of systemic methotrexate (MTX) administration, uterine artery embolization (UAE) and expectant management as treatments of caesarean scar pregnancy (CSP) and to assess their efficacy and safety. BASIC PROCEDURES: We retrospectively analysed patients with a diagnosis of CSP treated in a five years' period (2014-2018). Hospitalization, hCG normalization, menstrual cycle recovery, ultrasound restitutio ad integrum times, reproductive desire accomplishment after the resolution of the picture, and outcomes of subsequent pregnancies were considered. Only patients for whom complete diagnosis, treatment and follow-up data were available could be considered for study entry. MAIN FINDINGS: A total of 21 patients were included. Three of them were managed expectantly. In two cases spontaneous abortion occurred and one case underwent caesarean delivery at 35 weeks of gestation for complete placenta previa with hysterectomy for post partum haemorrhage. Seven patients were treated with systemic MTX. Median [IQR] times of hospitalization, hCG normalization, menstrual cycle recovery and ultrasound restitutio ad integrum were 21 days [10-26 days], 52 days [18-64 days], 8 weeks [6-10 weeks] and 8 weeks [6-11 weeks] respectively. At the end of follow up, 80% (95%CI [38-96%]) of patients with reproductive desire achieved at least one live birth. Eleven patients were treated with UAE combined with MTX. Median [IQR] times of hospitalization, hCG normalization, menstrual cycle recovery and ultrasound restitutio ad integrum were 14 days [12-20 days], 43 days [30-52 days], 8 weeks [4-12 weeks] and 8 weeks [8-10 weeks], respectively. Of those who expressed a reproductive desire after treatment, 80% (95%CI [49-94%]) achieved at least one live birth. In all included patients, the menstrual cycle was restored. PRINCIPAL CONCLUSIONS: Reproductive potential of women treated for CSP was preserved after both systemic MTX administration and systemic MTX combined with UAE. Both strategies proved to be safe.

An uncommon presentation of Wernicke-Korsakoff's syndrome in pregnancy: Case report.

Wernicke's encephalopathy is an acute neuropsychiatric syndrome resulting from severe thiamine (vitamin B1) deficiency. Symptoms occur with an acute onset and may vary according to the brain area involved. Altered consciousness is the most common clinical feature, together with ocular abnormalities and ataxia. We report the case of a pregnant women affected by pre-gestational hyperthyroidism that caused an uncommon presentation of Wernicke's encephalopathy. Symptoms differed from the classic triad and diagnosis was made possible by a thorough analysis of anamnestic factors and brain MRI. Alongside thiamine supplementation, a multidisciplinary approach which included physiokinesis and a phoniatric support was fundamental for the patient's recovery.

The Prevalence and Clinical Impact of Adenomyosis in Pregnancy-Related Hysterectomy.

BACKGROUND: The epidemiology of adenomyosis has been traditionally based on patients undergoing hysterectomy for gynecological indications, while its prevalence among hysterectomies performed for obstetric complications is unknown. The aim of this study was to assess the prevalence and clinical impact of adenomyosis diagnosed through histology among women undergoing pregnancy-related hysterectomy (PH). METHODS: This was a retrospective cohort study. Women who delivered at a tertiary care regional obstetric hub in Milan between 2009 and 2020 were reviewed to identify cases of PH. Histopathological reports of surgical specimens were examined. Cases with adenomyosis were compared to those without adenomyosis for baseline characteristics, obstetric history and outcomes. RESULTS: During the study period there were 71,061 births and a total of 130 PH, giving a PH incidence of 1.83 per 1000 deliveries. Adenomyosis cases were 18, giving a prevalence of 13.8%. Adenomyosis was associated with placenta previa (77.8 vs. 45.5%, p = 0.01), chorionamnionitis (27.8 vs. 5.4%, p = 0.008), lower gestational age at birth (32 ± 4.6 vs. 35.5 ± 3.6 weeks' gestation, p = 0.0004), and intrauterine fetal demise among twin pregnancies (50 vs. 4.5%, p = 0.048). CONCLUSION: Adenomyosis entails a relevant impact on obstetric and perinatal outcomes related to PH. More evidence is needed on the clinical relevance of an ultrasonographic diagnosis of adenomyosis before conception.

Serum hepatic biomarkers in women with obstetric cholestasis and a concurrent SARS-CoV-2 infection.

AIM: The aim of the study was to evaluate the association between SARS-CoV-2 infection and serum hepatic biomarker levels among women with obstetric cholestasis. METHODS: In this prospective study, we recruited all pregnant women admitted in our hospital with obstetric cholestasis. Among those with a concurrent SARS-CoV-2 infection, we evaluated the following serum hepatic biomarkers: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and biliar acids (BA). RESULTS: Among the 88 women enrolled in the study, 20 presented with a SARS-CoV-2 infection while 68 were negative. SARS-CoV-2 infected women were younger (mean age 30.5 ± 5.7 vs. 34.3 ± 5.4; p < 0.01) and in a greater percentage of non-Caucasian ethnicity when compared to noninfected women (60.0% vs. 17.6%; p < 0.01). Regarding levels of hepatic biomarkers, they showed higher levels of AST (111.5 ± 134.1 vs. 37.3 ± 43.4 UI/L; p = 0.02), ALT (132.2 ± 115.7 vs. 50.5 ± 73.173.1 UI/L; p < 0.01), and BA (41.4 ± 46.8 vs. 18.4 ± 13.4 µmol/L; p = 0.04) compared to noninfected patients. No significant differences in maternal or fetal outcomes were found between infected and noninfected women. CONCLUSION: SARS-CoV-2 infection was associated with higher levels of liver enzymes in patients with obstetric cholestasis. This could be the result of a possible hepatic involvement in patients with SARS-CoV-2 infection.

Pregnancy in juvenile idiopathic arthritis: maternal and foetal outcome, and impact on disease activity.

Objective: This retrospective cohort study describes the modulation of disease activity during gestation and in the year following delivery as well as maternal and neonatal outcomes in a monocentric cohort of women with juvenile idiopathic arthritis (JIA). Methods: Disease activity was assessed using DAS28-CRP before conception and every 3 months during pregnancy and in the first year postpartum. The risk of complicated pregnancies was measured applying a generalized estimating equation model. Changes in disease activity during gestation and in the first year postpartum were assessed in a linear mixed model for repeated measures. Results: Thirty-one women (49 pregnancies) with persisting JIA and at least one conception were enrolled. Adjusted DAS28-CRP levels remained stable from preconception through the first trimester, but increased significantly in the second and decreased not significantly in the third. In the postpartum, adjusted disease activity peaked at 3 months after delivery, stabilized at 6 months to decrease at 1 year, although not significantly. Preconceptional DAS28-CRP and number of biological drugs predicted disease activity fluctuation during gestation. The number of biological drugs and the length of gestational exposure to biologics significantly predicted pregnancy morbidity. In particular, JIA women had a higher probability of preterm delivery compared with healthy and disease controls. Adjusted for breastfeeding and DAS28-CRP score in the third trimester, postconceptional exposure to biologics was inversely related with disease activity in the postpartum: the longer the patient continued treatment, the lower the probability of experiencing an adverse pregnancy outcome. Conclusion: These data offer novel insights on how treatment affects disease activity during pregnancy and postpartum as well as obstetric outcomes in women with JIA.

Assessment of post-partum haemorrhage risk among women with moderate thrombocytopenia.

It is unknown whether moderate thrombocytopenia represents a risk factor for post-partum haemorrhage (PPH). We assessed PPH risk among women with a platelet count of between 100 and 50 × 109 /l and stratified the risk for O/non-O blood group. We included consecutive women undergoing vaginal delivery or caesarean section with moderate thrombocytopenia. Women with >150 × 109 /l platelets at delivery were selected as controls and matched for age, type of birth and ethnicity. Odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated as risk estimates. A total of 94 thrombocytopenic women and 94 controls were included in the study. The rate of PPH was significantly higher in thrombocytopenic women than in controls (37% vs. 10%, p < 0.001); there was a higher risk of PPH in the thrombocytopenic group when compared to the control group (adjusted OR 4.7, 95% CI 2.1-10.8, p < 0.01) and this association was stronger in blood group O carriers (adjusted OR 11.0, 95% CI 2.4-49.6, p < 0.01). In conclusion, our study shows that a moderate thrombocytopenia is a risk factor for PPH, especially in blood group O carriers.

The impact of a multilevel approach to reduce emergency hysterectomy for postpartum haemorrhage: Insights from a tertiary referral centre in Northern Italy.

OBJECTIVE: To assess the effectiveness of the implementation of a multilevel institutional program to reduce the rate of emergency peripartum hysterectomy (EPH) secondary to postpartum haemorrhage (PPH) in a Western world referral centre for obstetrics. STUDY DESIGN: Women who delivered at a tertiary care regional obstetric hub in Milan between 2012 and 2020 were retrospectively reviewed to identify cases of EPH. During the study period, several measures aimed at preventing EPH were progressively implemented: reduction of primary and repeated caesarean, update of PPH treatment protocol, implementation of massive transfusion protocol, dedicated clinical pathway for high-risk patients, regular educational sessions, daily review of critical cases with senior consultant, and periodical review of near miss cases by quality improvement committee. To investigate the possible benefits, we divided the detected cases into two groups based on the historical period (Period I, 2012-2016 vs. Period II, 2017-2020) with the main aim of comparing the rate of EPH calculated as EPH ratio per 1000 deliveries. RESULTS: During Period I and II there were 30,241 and 21,270 births; a total of 60 and 25 EPH were performed, respectively. EPH incidence decreased from 2.0 to 1.2‰ across the study periods (p = 0.027). Between Period I and II, we observed a reduction of institutional caesarean section rate (44.4% vs. 40.4%, p < 0.0001); among cases undergoing EPH, we reported a significant reduction of massive blood transfusion (83.3% vs. 52.2%, p = 0.002), increased use (56.7% vs. 96.0%, p = 0.0004) and appropriate administration (25.0% vs. 88.0%, p < 0.0001) of tranexamic acid, increased use of non-invasive Bakri Balloon tamponade (3.3% vs. 32.0%, p = 0.0002) instead of surgical techniques (38.3% vs. 16.0%, p = 0.043). CONCLUSION: A reduction of EPH incidence as a severe outcome of obstetric haemorrhage is achievable through a multilevel institutional effort. Our study may inspire a larger-scale program to improve the safety of patients experiencing PPH.

sFlt-1/PlGF ratio in hypertensive disorders of pregnancy in patients affected by COVID-19.

OBJECTIVES: To analyze soluble Fms-like tyrosine Kinase 1 (sFlt-1) and Placental Growth Factor (PlGF) ratio concentrations in COVID-19 pregnant patients with and without Hypertensive Disorders of Pregnancy (HDP), compared with non COVID-19 pregnant patients with HDP and a control group. STUDY DESIGN: We recruited and obtained a complete follow-up of 19 COVID-19 pregnant patients with HDP and of 24 COVID-19 normotensive pregnant patients. Demographic, clinical and sFlt-1/PlGF ratio findings were compared with a group of 185 non COVID-19 pregnant patients with HDP and 41 non COVID normotensive patients. Findings were based on univariate analysis and on a multivariate adjusted model, and a case by case analysis of COVID-19 pregnant patients with an abnormal sFlt-1/PlGF ratio > 38 at recruitment. MAIN OUTCOME MEASURES: sFlt-1/PlGF ratio. RESULTS: We confirmed a significant higher prevalence of HDP in women affected by COVID-19 compared to control population. sFlt-1/PlGF ratio was found high in HDP patients, with and without of Sars-Cov2 infection. COVID-19 patients with worse evolution of the disease showed greater rates of obesity and other comorbidities. sFlt/PlGF ratio proved not to be helpful in the differential diagnosis of the severity of this infection. CONCLUSIONS: COVID-19 pregnant patients showed a higher prevalence of HDP compared to non COVID-19 controls, as well as higher comorbidity rates. In spite of the possible common endothelial target and damage, between Sars-Cov-2 infection and HDP, the sFlt1/PlGF ratio did not correlate with the severity of this syndrome.

Prophylactic intraoperative uterine artery embolization for the management of major placenta previa.

PURPOSE: Placenta previa is a major cause of maternal morbidity and mortality, associated to a high risk of peripartum hemorrhage and hysterectomy. We aimed to verify if prophylactic intraoperative uterine artery embolization in patients with placenta previa and at least one additional risk of bleeding (major placenta previa), can reduce hemorrhage, need for blood transfusions, peripartum hysterectomy and maternal morbidity. MATERIALS AND METHODS: We enrolled 76 patients with major placenta previa; a specific multidisciplinary protocol was designed for management, including ultrasound evaluation, hospitalization at 34 weeks, antenatal corticosteroids and scheduled cesarean section at 35-36 weeks. 44 patients (control group or CTR) were treated with elective cesarean section, 32 patients (embolized group or EMB) underwent selective catheterization of bilateral uterine arteries before cesarean section and subsequent uterine embolization. In both cases cesarean section was performed by a senior surgeon. RESULTS: Significant differences were found in term of intraoperative blood loss (CTR: 1431 ml; EMB: 693 ml); despite an high percentage of CTR patients had a bleeding greater than 1000 ml (56%), the need for blood transfusion was not significantly different between the two groups. Time of surgery was higher in the EMB group, considering that embolization procedure required approximatively 30 min. Three patients from the CTR group needed hysterectomy and ICU admission, compared to none in the EMB group. Duration of hospitalization and neonatal outcome were similar. Uterine embolization was not related to any short or long-term complications; return to normal menses and preservation of fertility were confirmed at follow up. CONCLUSIONS: Our results are promising, although we believe that a major contribution is referable to the multidisciplinary approach rather than the procedure itself. Nevertheless, we demonstrated the feasibility and safety of preventive uterine embolization in patients with placenta previa; in order to establish its prophylactic role in the prevention of peripartum hemorrhage, randomized trial should be carried out, on a larger population.

Maternity ward management and COVID-19 pandemic: Experience of a single center in Northern Italy during lockdown.

INTRODUCTION: The aim of our study is to describe the management of a maternity ward in a referral center during the COVID-19 pandemic and 2020 lockdown. METHODS: This is a retrospective single-center study. We analyzed the records of all women consecutively admitted to our delivery ward during lockdown and compared them with those of women admitted in the same period in 2019. RESULTS: The number of patients (1260) admitted to our department in 2020 was similar (1215) to that in 2019. Among patients admitted during lockdown, 50 presented with a Sars-CoV-2 infection (3.9%). In 2020, the number of antenatal check-ups was lower than in 2019 [7.9 (1.5) vs 8.2 (1.3), p<0.001] and the rate of labor inductions was higher [436 (34.6) vs 378 (31.1), p=0.008] although no difference in delivery mode was found. Moreover, women admitted during lockdown were more likely to give birth alone [140 (11.1) vs 50 (4.1), p<0.001]. However, during 2020, the rate of mother and newborn skinto-skin contact [1036 (82.2) vs 897 (73.8), p<0.001] and that of breastfeeding within 2 hours from birth [1003 (79.6) vs 830 (68.3), p<0.001] was higher. We found no significant differences in maternal or neonatal outcomes. CONCLUSIONS: Despite the COVID-19 pandemic, we were able to guarantee a safe birth assistance to all pregnant women, both for those infected and those not infected by Sars-CoV-2.

Sociodemographic characteristics of pregnant women tested positive for COVID-19 admitted to a referral center in Northern Italy during lockdown period.

INTRODUCTION: We investigated association between sociodemographic characteristics and COVID-19 disease among pregnant women admitted to our unit, the largest high-risk maternity unit in the Milan metropolitan area. METHODS: Between March 1, 2020 and April 30, 2020, 896 pregnant women were admitted to our Institution and tested for COVID-19. We collected information regarding their sociodemographic characteristics. Additional information on geographical area of residence, number of family members, number of family members tested positive for COVID-19, and clinical data was collected for women tested positive for COVID-19. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of developing COVID-19 according to sociodemographic characteristics were estimated by unconditional logistic regression models. RESULTS: Among the 896 women enrolled, 50 resulted positive for COVID-19. Pregnant women aged ≥35 years had a significantly lower risk of developing the infection (crude OR = 0.29; 95% CI:0.16-0.55). Conversely, foreign women (crude OR = 3.32; 95% CI:1.89-5.81), unemployed women (crude OR = 3.09; 95% CI: 1.77-5.40), and women with an unemployed partner (crude OR = 3.16; 95% CI: 1.48-6.79) showed a significantly higher risk of infection. Ethnicity was positively associated with the risk of developing COVID-19 (mutually adjusted OR = 2.15; 95% CI:1.12-4.11) in the multivariate analysis. Foreign women with COVID-19 were more likely to have a lower education level (p < 0.01), to be unemployed (p < 0.01), and to live in larger families (p < 0.01) compared to Italian pregnant women. CONCLUSIONS: The socioeconomic conditions described are characteristic of immigration patterns in our metropolitan area. These factors may increase the risk of viral transmission, reducing the effectiveness of lockdown and social distancing.

EUREKA algorithm predicts obstetric risk and response to treatment in women with different subsets of anti-phospholipid antibodies.

OBJECTIVES: aPL, the serum biomarkers of APS, are the most common acquired causes of pregnancy morbidity (PM). This study investigates the impact of aPL positivity fulfilling classification criteria ('criteria aPL') and at titres lower than thresholds considered by classification criteria ('low-titre aPL') on PM and assesses the effectiveness of low-dose aspirin (LDASA), low molecular weight heparin (LMWH) and HCQ in reducing the probability of PM (PPM). METHODS: Longitudinal data on 847 pregnancies in 155 women with persistent aPL at any titre and 226 women with autoimmune diseases and negative aPL were retrospectively collected. A generalized estimating equations model for repeated measures was applied to quantify PPM under different clinical situations. RESULTS: EUREKA is a novel algorithm that accurately predicts the risk of aPL-associated PM by considering aPL titres and profiles. aPL significantly impact PPM when at low titres and when fulfilling classification criteria. PPM was further stratified upon the aPL tests: aCL IgG/IgM and anti-ß2-glycoprotein I (ß2GPI) IgM, alone or combined, do not affect the basal risks of PPM, an increase occurs in case of positive LA or anti-ß2GPI IgG. LDASA significantly affects PPM exclusively in women with low-titre aPL without anti-ß2GPI IgG. The LDASA + LMWH combination significantly reduces PPM in all women with low-titre aPL and women with criteria aPL, except those carrying LA and anti-ß2GPI IgG. In this group, the addition of HCQ further reduces PPM, although not significantly. CONCLUSION: EUREKA allows a tailored therapeutic approach, impacting everyday clinical management of aPL-positive pregnant women.

Anti-phospholipid antibodies and reproductive failures.

Anti-phospholipid syndrome (APS) recapitulates the link between autoimmunity and pregnancy failure: Acquired anti-phospholipid antibodies (aPL) play a pathogenic role in pregnancy complications. The diagnosis of obstetric APS can easily be pursued when women present with laboratory and clinical features fulfilling the international classification criteria. Standard therapeutic approach to obstetric APS consists in the association of anti-platelet agents and anticoagulants. Most patients achieve a live birth thanks to conventional treatment; however, approximately 20% fail to respond and are managed with additional therapeutic tools added on the top of conventional treatment. Surely, a refinement of risk stratification tools would allow early identification of high-risk pregnancies that warrant tailored treatment. In real life, obstetricians and rheumatologists face complex diagnostic scenarios including women with pregnancy morbidities other than those mentioned in classification criteria such as one or two early losses and premature birth after 34 weeks due to preeclampsia or placental insufficiency, women with low-titer aPL not fulfilling criteria laboratory requirements, women with positive non-criteria aPL, asymptomatic aPL carriers, and infertile women found to be aPL-positive. This review focuses on some of the several unanswered questions related to diagnostic, prognostic, and therapeutic aspects in obstetric APS.

Impact of different stages of intrauterine inflammation on outcome of preterm neonates: Gestational age-dependent and -independent effect.

OBJECTIVE: To investigate the impact of different stages of intrauterine inflammation (IUI) on neonatal outcomes, before and after adjusting for gestational age (GA) and other perinatal confounders. METHODS: This was an observational, prospective, single-center cohort study including all eligible neonates with GA < 35 weeks and/or birth weight ≤ 1500 g born at a 3rd level Neonatal Intensive Care Unit between 2011 and 2014. Pathological patterns of placenta, membranes and cord were classified according to Redline's criteria. Multivariable linear and logistic regression models were applied, either including or not GA among the covariates. RESULTS: Of the 807 enrolled neonates, 134 (16.6%) had signs of IUI: among these, 54.5% showed just histological chorioamnionitis (HCA), 25.4% had HCA + funisitis (FUN) stage 1, and 20.1% had HCA + FUN stage 2-3. At univariate analysis, HCA increased the risk for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia, while FUN (any stage) had a deleterious impact on all outcomes investigated. After adjustment for covariates not including GA, HCA was a risk factor only for ROP (OR = 2.8, CI: 1-7.8), while FUN (any stage) was still associated with increased ORs for all outcomes (p <0.01). Upon inclusion of GA in the regression model, the results differed remarkably. HCA was associated with lower risk for mechanical ventilation (OR = 0.3, CI: 0.1-0.7) and need for surfactant (OR = 0.5, CI: 0.2-0.9), while FUN (any stage) worsened clinical conditions at birth (p <0.05), increased the risk for early-onset sepsis (p <0.01), and increased the length of mechanical ventilation (FUN stage 2-3 only, RC = 6.5 days, CI: 2-11). No other outcome was affected. CONCLUSIONS: IUI, especially FUN, negatively impact most neonatal morbidities, but its effect is partially reverted adjusting for GA. Considered that GA is an intermediate variable interposed between prenatal causes of prematurity and outcomes, the appropriateness of adjusting for GA may be questionable.

Acute myeloid leukemia and pregnancy: clinical experience from a single center and a review of the literature.

BACKGROUND: Acute myeloid leukemia (AML) accounts for more than two thirds of leukemia during pregnancy and has an incidence of 1 in 75,000 to 100,000. Its clinical management remains a challenging therapeutic task both for patient and medical team, given to the therapy-attributable risks for mother and fetus and the connected counseling regarding pregnancy continuation. METHODS: We provided a review of updated literature and a comprehensive description of five maternal/fetal outcomes of AML cases diagnosed concomitantly to pregnancy and treated at our Institution from 2006 to 2012. RESULTS: Median age at AML diagnosis was 32 years (31-39). One diagnosis was performed in first trimester and the patient asked for therapeutic abortion before starting chemotherapy. Three cases were diagnosed in second/third trimester; in one case leukemia was diagnosed concomitantly with intrauterine fetal death, while the remaining two patients continued pregnancy and delivered a healthy baby by cesarean section. In only one of these two cases chemotherapy was performed during pregnancy (at 24 + 5 weeks) and consisted of a combination of daunorubicine and cytarabine. Therapy was well tolerated and daily fetus monitoring was performed. After completion of 30 weeks of gestation a cesarean section was carried out; the newborn had an Apgar score of 5/1'-7/5'-9/10', oxygen therapy was temporarily given and peripheral counts displayed transient mild leukopenia. One patient had diagnosis of myelodysplastic syndrome rapidly progressed to AML after delivery. Four out of the 5 described women are currently alive and disease-free. Three children were born and long-term follow-up has shown normal growth and development. CONCLUSIONS: The treatment of AML occurring during pregnancy is challenging and therapeutic decisions should be taken individually for each patient. Consideration must be given both to the immediate health of mother and fetus and to long-term infant health. Our series confirmed the literature data: fetal toxicity of cytostatic therapy clusters during the first trimester; while chemotherapy can be administered safely during second/third trimester and combination of daunorubicin and cytarabine is recommended for induction.

Fetoscopic Endoluminal Tracheal Occlusion in Fetuses with Severe Diaphragmatic Hernia: A Three-Year Single-Center Experience.

OBJECTIVE: To report on our experience in the prenatal treatment of severe congenital diaphragmatic hernia (CDH) by fetoscopic endoluminal tracheal occlusion (FETO). METHODS: Between 2012 and 2014, FETO was performed at our center in 21 cases of CDH considered to be severe based on sonographic measurement of observed/expected lung-to-head ratio (O/E LHR) and side of the defect. We reported pre- and postoperative ultrasound findings, procedure-related complications, pregnancy outcome and survival at 1-3 years of age. RESULTS: The median gestational age (GA) at balloon insertion was 28.1 weeks (range 26.0-31.1) and the median GA at delivery 34.7 weeks (range 31.6-39.0); delivery before 32 and 34 weeks occurred in 2 (9.5%) and 7 (33.3%) cases, respectively. Postnatal survival at 1-3 years of age in the 17 cases with isolated unilateral CDH was 47.1%. The percentage difference between pre-balloon removal O/E LHR and pre-FETO O/E LHR was significantly higher in survivors compared to neonates who died (40.8 vs. 21.2%, respectively; p < 0.05). CONCLUSIONS: In this study, FETO was associated with an infant survival of 47% in cases with isolated unilateral severe CDH. The post-FETO increase in O/E LHR was higher in fetuses that survived compared to those who died.