Left ventricular remodeling in twin pregnancy, noninvasively assessed using hemodynamic forces and pressure-volume relation analysis: prospective, cohort study.

This study was designed to prospectively investigate the pattern of intraventricular hemodynamic forces (HDFs) associated with left ventricular (LV) function and remodeling in women with uncomplicated twin pregnancy. Transthoracic echocardiography was performed on 35 women (aged 35.9 ± 4.7-yr old) during gestation (T1, <14 wk; T2, 14-27 wk; T3, >28 wk) and 6-7 mo after delivery (T0). LV HDFs were computed from echocardiography long-axis data sets using a novel technique based on endocardial boundary tracking, both in apex-base (A-B) and latero-septal (L-S) directions. HDF distribution was evaluated by L-S over A-B HDF ratio (L-S:A-B HDF ratio). At T1, L-S:A-B HDF ratio was higher than in T0 (P < 0.05) indicating HDF misalignment. At T2, a slight impairment of cardiac function was then recorded with a reduction of global longitudinal strain (GLS) and left ventricular end-systolic elastance (Ees) at pressure-volume relationship analysis versus T1 (both P < 0.05). Finally, at T3, when HDF misalignment and LV contractility reduction (GLS and Ees) were all restored, a rightward shift of the end-diastolic pressure-volume relationship (EDPVR) with an increase of ventricular capacitance was documented. In twin pregnancy, HDF misalignment in the first trimester precedes the slight temporary decrease in left ventricular systolic function in the second trimester; at the third trimester, a rightward shift of the EDPVR was associated with a realignment of HDF and normalization of ventricular contractility indexes. These coordinated changes that occur in the maternal heart during twin pregnancy suggest the role of HDFs in cardiac remodeling.NEW & NOTEWORTHY These changes indicate that 1) the misalignment of hemodynamic forces (HDFs) precedes a mild reduction in systolic function in twin pregnancy and 2) the positive left ventricular (LV) response to hemodynamic stress is mainly due to an improved diastolic function with enhanced LV cavity compliance.

The placenta in fetal death: molecular evidence of dysregulation of inflammatory, proliferative, and fetal protective pathways.

BACKGROUND: It is estimated that over 2 million cases of fetal death occur worldwide every year, but, despite the high incidence, several basic and clinical characteristics of this disorder are still unclear. Placenta is suggested to play a central role in fetal death. Placenta produces hormones, cytokines and growth factors that modulate functions of the placental-maternal unit. Fetal death has been correlated with impaired secretion of some of these regulatory factors. OBJECTIVE: The aim of the present study was to evaluate, in placentas collected from fetal death, the gene expression of inflammatory, proliferative and protective factors. STUDY DESIGN: Cases of fetal death in singleton pregnancy were retrospectively selected, excluding pregnancies complicated by fetal anomalies, gestational diabetes, intrauterine growth restriction and moderate to severe maternal diseases. A group of placentas collected from healthy singleton term pregnancies were used as controls. Groups were compared regarding maternal and gestational age, fetal sex and birthweight. Placental messenger RNA expression of inflammatory (interleukin 6), proliferative (activin A, transforming growth factor ß1) and regulatory (vascular endothelial growth factor, vascular endothelial growth factor receptor 2, ATP-binding cassette transporters (ABC) ABCB1 and ABCG2, sphingosine 1-phosphate signaling pathway) markers was conducted using real-time polymerase chain reaction. Statistical analysis and graphical representation of the data were performed using the GraphPad Prism 5 software. For the statistical analysis, Student's t test was used, and P values<.05 were considered significant. RESULTS: Placental mRNA expression of interleukin 6 and vascular endothelial growth factor receptor 2 resulted significantly higher in the fetal death group compared to controls (P<.01), while activin A, ABCB1, and ABCG2 expression resulted significantly lower (P<.01). A significant alteration in the sphingosine 1-phosphate signaling pathway was found in the fetal death group, with an increased expression of the specific receptor isoforms sphingosine 1-phosphate receptor 1, 3, and 4 (sphingosine 1-phosphate1, sphingosine 1-phosphate3, sphingosine 1-phosphate4) and of sphingosine kinase 2, 1 of the enzyme isoforms responsible for sphingosine 1-phosphate synthesis (P<.01). CONCLUSION: The present study confirmed a significantly increased expression of placental interleukin 6 and vascular endothelial growth factor receptor 2 mRNA, and for the first time showed an increased expression of sphingosine 1-phosphate receptors and sphingosine kinase 2 as well as a decreased expression of activin A and of selected ATP-binding cassette transporters, suggesting that multiple inflammatory and protective factors are deranged in placenta of fetal death.

Maternal Hemodynamics from Preconception to Delivery: Research and Potential Diagnostic and Therapeutic Implications: Position Statement by Italian Association of Preeclampsia 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..

Stillbirths: results of a pilot population-based surveillance system in Italy (SPItOSS)

OBJECTIVES: to describe the results of a pilot population-based perinatal mortality surveillance system, with regards to stillbirths; to study maternal, obstetric, and foetal characteristics, evaluating risk factors and understanding causes. DESIGN: a cross-sectional study was conducted on incident cases of stillbirths collected by the surveillance system from July 2017 to June 2019 in three Italian Regions (Lombardy, Tuscany, and Sicily). SETTING AND PARTICIPANTS: data on stillbirths, resulting from the in-hospital multidisciplinary audits, organised using the Significant Event Audit methodology, were analysed. According to the World Health Organization (WHO) definitions, the project identified stillbirths as foetuses born dead >=28 weeks of gestation. The WHO International Classification of Diseases-Perinatal Mortality was used to categorise the causes of foetal death. MAIN OUTCOMES MEASURES: maternal characteristics, obstetric and foetal findings were investigated. Unadjusted relative risks and 95% confidence intervals were computed with respect to the background population. Finally, causes of death and contributing maternal conditions have been considered. RESULTS: the maternity and neonatal units of the three participating Regions notified 520 stillbirths, of which 435 cases underwent to the multidisciplinary audit (83.7%); 40.0% of cases occurred in the gestational age range between 36 and 39 weeks. The risk of stillbirth was significantly increased in mothers with foreign citizenship (RR: 1.39; 95%CI: 1.13-1.71), multiple pregnancies (RR: 1.59; 95%CI 1.05-2.42), and pregnancies conceived with assisted reproductive technologies (RR: 2.15; 95%CI 1.45-3.19). The rate of congenital malformations was 6.0%. A diagnosis of foetal growth restriction was reported in 10.3% of cases, although the percentage of dead foetuses weighting <10° centile was at least twice in almost all gestational age periods. Post-mortem and placental histological examinations were carried out in more than 70% and more than 90% of cases, respectively. CONCLUSIONS: the implementation of a population-based surveillance system with high participation rate of maternity units and the use of universally accepted definitions could improve the identification of stillbirth avoidable risk factors and potentially modifiable predisposing maternal conditions, highlighting issues of perinatal assistance in need of improvement.

Difference in cardiac remodeling between female athletes and pregnant women: a case control study.

OBJECTIVES: The aim of this study was to detect possible differences in reversible cardiac remodeling occurring in sport training and twin pregnancy. BACKGROUND: cardiac remodeling occurs in athletes and pregnant women due to training and fetal requirements, respectively. These changes could be apparently similar. METHODS: 21 female elite athletes (23.2 ± 5.3 years), 25 women with twin pregnancies (35.4 ± 5.7 years) and 25 healthy competitive female athletes (controls), age-matched with pregnant women (34.9 ± 7.9 years), were enrolled. This latter group was included to minimize the effect of age on cardiac remodeling. All women evaluated through anamnestic collection, physical examination, 12 leads ECG, standard echocardiogram and strain analysis. Sphericity (SI) and apical conicity (ACI) indexes were also calculated. RESULTS: Pregnant women showed higher LA dimension (p < 0.001) compared to both groups of athletes. LV e RV GLS were significantly different in pregnant women compared to female athletes (p = 0.02 and 0.03, respectively). RV GLS was also different between pregnant women and controls (p = 0.02). Pregnant women showed significantly higher S' wave compared to female athletes (p = 0.02) but not controls. Parameters of diastolic function were significantly higher in athletes (p = 0.08 for IVRT and p < 0.001 for E/A,). SI was lower in athletes in both diastole (p = 0.01) and systole (p < 0.001), while ACIs was lower in pregnant women (p = 0.04). CONCLUSIONS: Cardiac remodeling of athletes and pregnant women could be similar at first sight but different in LV shape and in GLS, highlighting a profound difference in longitudinal deformation between athletes and pregnant women. This difference seems not to be related with age. These findings suggest that an initial maternal cardiovascular maladaptation could occur in the third trimester of twin pregnancies.

Maternal hemodynamic changes in gestational diabetes: a prospective case-control study.

PURPOSE: The aim of the study is to compare maternal hemodynamic adaptations in gestational diabetes (GDM) versus healthy pregnancies. METHODS: A prospective case-control study was conducted, comparing 69 singleton pregnancies with GDM and 128 controls, recruited between September 2018 and April 2019 in Maternal-Fetal Medicine Unit, Careggi University Hospital, Florence, Italy. Hemodynamic assessment by UltraSonic Cardiac Output Monitor (USCOM) was performed in both groups in four gestational age intervals: 17-20 weeks (only in early GDM cases), 26-30 weeks, 32-35 weeks and 36-39 weeks. We evaluated six hemodynamic parameters comparing GDM cases versus controls: cardiac output (CO), cardiac index (CI), stroke volume (SV), total vascular resistance (TVR), inotropy index (INO) and potential to kinetic energy ratio (PKR). RESULTS: GDM group had significantly lower values of CO and SV than controls from the early third trimester (26-30 weeks) until term (p < 0.001). CI is significantly lower in GDM women already at the first evaluation (p = 0.002), whereas TVR and PKR were significantly higher in GDM (p < 0.001). GDM women showed also lower INO values than controls in all assessments. CONCLUSIONS: A hemodynamic maternal maladaptation to pregnancy can be detected in GDM women. The effect of hyperglycemia on vascular system or a poor pre-pregnancy cardiovascular (CV) reserve could explain this hemodynamic maladaptation. The abnormal CV response to pregnancy in GDM women may reveal a predisposition to develop CV disease later in life and might help in identifying patients who need a CV follow-up.

Perinatal outcomes of pregnant women with severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO): a case series and literature review.

PURPOSE: Pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have a higher risk of hospitalization, admission to intensive care unit (ICU) and invasive ventilation, and of acute respiratory distress syndrome (ARDS). In case of ARDS and critical severe coronavirus disease 2019 (COVID-19), the use of extracorporeal membrane oxygenation (ECMO) is recommended when other respiratory support strategies (oxygen insufflation, non-invasive ventilation [NIV], invasive ventilation through an endotracheal tube) are insufficient. However, available data on ECMO in pregnant and postpartum women with critical COVID-19 are very limited. METHODS: A case series of three critically ill pregnant women who required ECMO support for COVID-19 in pregnancy and/or in the postpartum period. RESULTS: The first patient tested positive for COVID-19 during the second trimester, she developed ARDS and required ECMO for 38 days. She was discharged in good general conditions and a cesarean-section [CS] at term was performed for obstetric indication. The second patient developed COVID-19-related ARDS at 28 weeks of gestation. During ECMO, she experienced a precipitous vaginal delivery at 31 weeks and 6 days of gestation. She was discharged 1 month later in good general conditions. The third patient, an obese 43-year-old woman, tested positive at 38 weeks and 2 days of gestation. Because of the worsening of clinical condition, a CS was performed, and she underwent ECMO. 143 days after the CS, she died because of sepsis and multiple organ failure (MOF). Thrombosis, hemorrhage and infections were the main complications among our patients. Neonatal outcomes have been positive. CONCLUSION: ECMO should be considered a life-saving therapy for pregnant women with severe COVID-19.

Intra- and Interobserver Reproducibility of Third Trimester Middle Cerebral Artery Pulsatility Index Measurement: A Prospective Cross-Sectional Study.

BACKGROUND: Middle cerebral artery (MCA) pulsatility index (PI) Doppler in the third trimester of pregnancy is increasingly used. OBJECTIVES: The aim of the study was to investigate intra- and interobserver reproducibility of MCA PI in the third trimester. METHOD: Singleton pregnancies between 30+0 and 40+0 weeks were recruited. MCA Doppler velocimetry measurements were performed prospectively, independently, and blindly. Intra- and interobserver reproducibility was assessed by concordance correlation coefficient (CCC) and intraclass correlation coefficient (ICC); Bland-Altman plots were built, and limits of agreement (LoA) were calculated. Results were interpreted according to the cutoff set by the True Reproducibility of Ultrasound Techniques Review. RESULTS: We enrolled 101 patients. ICCs for intraobserver reproducibility were 0.84 and 0.78 for raw values and percentiles, respectively; CCCs were 0.72 and 0.64. For interobserver reproducibility ICCs were 0.84 and 0.78, CCCs 0.72 and 0.63. According to the chosen criteria, these values show a poor-moderate reproducibility of third trimester MCA PI. Cohen's Kappa coefficients were 0.59 and 0.42, indicating a moderate agreement in discriminating normal and abnormal values. CONCLUSIONS: Intra- and interobserver reproducibility of third trimester MCA PI, as assessed by ICC, CCC, and LoA, is far from satisfactory. This should be taken into account before taking clinical decisions.

Intraobserver and interobserver reproducibility of third trimester uterine artery pulsatility index.

OBJECTIVES: The primary aim of the study was to investigate intraobserver and interobserver reproducibility of uterine artery (UtA) pulsatility index (PI) in the third trimester of pregnancy. The secondary aim of the study was to examine whether high maternal body mass index (BMI) or gestational age (GA) influence the reliability of this measurement. METHODS: Singleton pregnancies in women with known BMI were recruited between 30+0 and 40+0  weeks. UtA PI Doppler measurements were performed prospectively, independently, and blindly by 2 Fetal Medicine Foundation-accredited operators. Intraobserver and interobserver reproducibility was assessed by concordance correlation coefficient (CCC) and intraclass correlation coefficient (ICC); Bland-Altman plots were built and limits of agreement (LoA) were calculated. The analysis was performed for both raw numbers and percentiles. To estimate the intraoperator and interoperator agreement in defining normal and pathological measurements, the assessments were divided in 2 categories-UtA PI <95th percentile/ ≥95th percentile-and Cohen's kappa coefficients were calculated. Results were interpreted according to the cutoffs reported by the True Reproducibility of Ultrasound Techniques review. Correlation between maternal BMI and GA and accuracy of UtA measurements was studied with Spearman's correlation coefficient. RESULTS: Measurements were available in 101 women. For intraobserver reproducibility, ICCs and CCCs were calculated for raw values and percentiles and were 0.912 and 0.835, and 0.837 and 0.716, respectively. For interobserver reproducibility, ICCs and CCCs were 0.809 and 0.732, and 0.677 and 0.576, respectively. This indicates a poor-moderate reproducibility of third trimester UtA PI. LoA were also wide (from a minimum of -0.30-0.35 to a maximum of -0.53-0.62). Cohen's kappa coefficients were 0.478 and 0.418, showing a moderate intraoperator and interoperator agreement in distinguishing between normal and pathological values. No correlation was found between maternal BMI and GA and reproducibility of the measurements. CONCLUSIONS: Intraobserver and interobserver reproducibility of third trimester UtA PI as assessed by ICC, CCC, and LoA is only moderate-poor. The agreement between operators in defining pathological and normal measurements is moderate.

Pregnancy in fanconi anaemia with bone marrow failure: a case report and review of the literature.

BACKGROUND: Fanconi anaemia is a rare inherited disease characterized by congenital abnormalities, progressive bone marrow failure and predisposition to malignancy. Successful pregnancies in transplanted patients have been reported. In this paper we will describe the pregnancy of a patient with Fanconi anaemia without transplantation. CASE PRESENTATION: A 34-year-old nulliparous woman with Fanconi anaemia was referred to our institution. Pregnancy was complicated by progressive pancytopenia and two severe infections. C-section was performed at 36 weeks. Both infant and mother are well. CONCLUSION: Successful pregnancy in a Fanconi anaemia patient with bone marrow failure is possible. The mode of delivery in patients with bone marrow failure should be determined by obstetric indications. The case highlights the safe outcome of the pregnancy with strict clinical and laboratory control by a multidisciplinary team.

Area-based study identifies risk factors associated with missed antenatal corticosteroid prophylaxis in women delivering preterm infants.

AIM: All women delivering a preterm infant should receive antenatal corticosteroid prophylaxis, but many miss this opportunity. We determined the risk factors associated with missed prophylaxis in a geographically defined area of Italy. METHODS: We prospectively studied all mothers who delivered babies between 24 and 31 completed weeks of gestation, from 2009 to 2013, in all maternity units in Tuscany. RESULTS: Of 1232 mothers, 186 (15.1%) did not receive prophylaxis. The risk was higher in migrant mothers, with an adjusted risk ratio (RR) of 1.28 and 95% confidence interval (95% CI) of 1.04-1.56, and in mothers hospitalised for less than 24 hours (RR 4.09, 95% CI: 2.90-5.78). Preterm prelabour rupture of membranes (RR 0.63, 95% CI: 0.41-0.96) and maternal antepartum transfer (RR 0.24, 95% CI: 0.18-0.32) were protective. Hospital level at birth and gestational age did not influence the prophylaxis rate. The population-attributable fractions were 50.4% for late hospital admissions and 10.2% for migrant status. CONCLUSION: In a highly organised network of hospitals, neither level of care nor gestational age influenced prophylaxis. Timely arrival of women in hospital, better recognition of the imminence of delivery and tighter steroids administration guidelines are the most relevant targets to further increase prophylaxis.

Management of osteogenesis imperfecta type I in pregnancy; a review of literature applied to clinical practice.

PURPOSE: Osteogenesis imperfecta (OI) is a rare heritable heterogenous disorder characterized by bone fragility and susceptibility to fractures with a wide spectrum of clinical expression due to defects in collagen type I biosynthesis. The purpose of the review is to highlight the practical norms in pregnancies with osteogenesis imperfecta. METHODS: We carried out a literature review in MEDLINE on OI during pregnancy, focusing on diagnosis, therapy and delivery. We reviewed 28 articles (case reports, original articles and reviews). RESULTS: Pregnant women affected by type I OI should be closely monitored to assess fetal well-being and detect pregnancy-related complications associated with an increased risk for osteoporosis, restrictive pulmonary disease, cephalopelvic disproportion and other problems related to connective tissue disorders. Mode of delivery remains controversial and should be determined on an individual basis. CONCLUSION: In conclusion, women affected by type I OI represent a subset of patients whose pregnancies should be considered high risk and warrant a multidisciplinary approach in a referral center.

Therapy and differential diagnosis of posterior reversible encephalopathy syndrome (PRES) during pregnancy and postpartum.

PURPOSE: Posterior reversible encephalopathy syndrome (PRES) is an usually reversible neuro-radiological clinical entity characterized by headache, confusion, visual disturbances or blindness and seizures. It rarely occurs without seizures. METHODS: We conducted a literature review in MEDLINE about PRES during post partum and pregnancy, focusing on differential diagnosis and therapy. We reviewed 28 articles (case reports, original articles and reviews) describing PRES as well as a case of a severe, immediate postpartum HELLP syndrome (haemolysis, elevated liver enzyme levels, low platelet count) with PRES without generalized seizure. RESULTS: The development of PRES after delivery is unusual. Magnetic resonance imaging represents the gold standard for the diagnosis of this condition. White matter oedema in the posterior cerebral hemispheres is typical on neuroimaging. PRES is reversible when early diagnosis is established and appropriate treatment is started without delay. The pathogenesis of PRES is discussed and the importance of a prompt diagnosis is emphasized, as the crucial role of rapid blood press reduction. CONCLUSION: MRI is the diagnostic gold standard and it may be useful in the differential diagnosis. The goal of the therapy is to control elevated blood pressure and to prevent seizures or promptly manage it.

Successful obstetric management of arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic myocardial disorder characterized by the replacement of myocardium by fibro-adipose tissue. The proper obstetric management of this disease remains unclear due to the lack of an adequate number of cases reported in the literature. We report the successful management of a pregnant patient with ARVC. A female patient with ARVC presented to our hospital at 9 weeks of gestation. Before pregnancy, she was treated with bisoprolol, which resulted in a reduction in extrasystoles and she never developed palpitations. Periodical cardiological examinations showed clinical stability, and the only therapeutic change consisted of an increase in the bisoprolol dosage. She delivered at term by elective cesarean section. We decided that avoiding changes in the chronic therapy of our patient was the best management because she had reached clinical stability before pregnancy and discontinuation of therapy may pose an addition risk. In our opinion, cesarean section was the best mode of delivery in our ARVC patient to avoid the stress of labor, which may raise heart rate and cause arrhythmia. Our experience and the case reports in the literature suggest that pregnancy is tolerated in female patients with ARVC, but they need to be monitored during pregnancy by a multidisciplinary team.

Early Fetal Growth Restriction with or Without Hypertensive Disorders: a Clinical Overview.

Early onset fetal growth restriction (FGR) is one of the main adverse pregnancy conditions, often associated with poor neonatal outcomes. Frequently, early onset FGR is associated with early onset hypertensive disorders of pregnancy (HDP), and in particular preeclampsia (PE). However, to date, it is still an open question whether pregnancies complicated by early FGR plus HDP (FGR-HDP) and those complicated by early onset FGR without HDP (normotensive-FGR (n-FGR)) show different prenatal and postnatal outcomes and, consequently, should benefit from different management and long-term follow-up. Recent data support the hypothesis that the presence of PE may have an additional impact on maternal hemodynamic impairment and placental lesions, increasing the risk of poor neonatal outcomes in pregnancy affected by early onset FGR-HDP compared to pregnancy affected by early onset n-FGR. This review aims to elucidate this poor studied topic, comparing the clinical characteristics, perinatal outcomes, and potential long-term sequelae of early onset FGR-HDP and early onset n-FGR.

P-glycoprotein expression is decreased in placenta accreta and placenta previa disorders.

BACKGROUND: P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are multidrug resistance (MDR) transporters that function as placental gatekeepers, lowering the fetal levels of diverse xenobiotics and toxins that may be circulating in the maternal blood throughout pregnancy. Placenta accreta spectrum (PAS) and the placenta previa (PP) disorders are obstetric pathologies encompassed by an abnormal invasion of chorionic villous tissue in the uterine wall or at the endocervical os, respectively. Given the fact that MDR transporters are involved in placentation and are highly responsive to inflammation, we hypothesized that immunostaining of P-gp and BCRP would be altered in PAS and in PP specimens. METHODS: A total of 32 placental histological specimens, sorted in control (N.=8; physiological pregnancies), PAS (N.=14), and PP (N.=10), were subjected to immunohistochemistry for P-gp and BCRP transporters. Semi-quantitative scoring of the resulting immunostained area and intensity was undertaken. RESULTS: Decreased P-gp staining intensity in the syncytiotrophoblast of the PAS compared to the control group (P<0.05) and in the PP compared to the PAS group was detected (P<0.05). Fetal blood vessel P-gp immunostaining was decreased in PAS and PP groups (P<0.001). CONCLUSIONS: We conclude that PAS and PP histological specimens exhibit decreased immunostaning of the drug transporter P-gp, and that fetuses born from these pregnancies may be exposed to greater levels of drugs and toxins present at the maternal circulation. Futures studies should attempt to investigate the mechanisms underlying P-gp down-regulation in these obstetric pathologies.

Impact of pregnancy on the natural history of women with hypertrophic cardiomyopathy.

AIMS: Whether pregnancy is a modifier of the long-term course and outcome of women with hypertrophic cardiomyopathy (HCM) is unknown. We assessed the association of pregnancy with long-term outcomes in HCM women. METHODS AND RESULTS: Retrospective evaluation of women with HCM from 1970 to 2021. Only women with pregnancy-related information (pregnancy present or absent) and a follow-up period lasting ≥1 year were included. The peri-partum period was defined as -1 to 6 months after delivery. The primary endpoint was a composite for major adverse cardiovascular events [MACE: cardiovascular death, sudden cardiac death, appropriate defibrillator shock and heart failure (HF) progression]. Overall, 379 (58%) women were included. There were 432 pregnancies in 242 (63%) patients. In 29 (7.6%) cases, pregnancies (n = 39) occurred after HCM diagnosis. Among these, three carrying likely pathogenic sarcomeric variants suffered MACEs in the peri-partum period. At 10 ± 9 years of follow-up, age at diagnosis [hazard ratio (HR) 1.034, 95% confidence interval (CI) 1.018-1.050, P < 0.001] and New York Heart Association (NYHA) class (II vs. I: HR 1.944, 95% CI 0.896-4.218; III vs. I: HR 5.291, 95% CI 2.392-11.705, P < 0.001) were associated with MACE. Conversely, pregnancy was associated with reduced risk (HR 0.605; 95% CI 0.380-0.963, P = 0.034). Among women with pregnancy, multiple occurrences did not modify risk. CONCLUSIONS: Pregnancy is not a modifier of long-term outcome in women with HCM and mostly occurs before a cardiac diagnosis. Most patients tolerate pregnancy well and do not show a survival disadvantage compared to women without. Pregnancy should not be discouraged, except in the presence of severe HF symptoms or high-risk features.

Hypertrophic cardiomyopathy (HCM) is the most common genetic disorder of the myocardium and is characterized by important gender-related differences: women are typically 5 years older than men at diagnosis, over half are diagnosed >50 years of age and consistently show greater propensity than men for heart failure (HF)-related complications and adverse outcome. Whether pregnancy is a modifier of the long-term course and outcome of women with HCM is unknown. In this study, pregnancy was not a modifier of long-term outcome in women with HCM. In particular: At 10 ± 7 years, most patients tolerated pregnancy well and did not show a survival disadvantage compared to women without pregnancies. Only baseline heart failure symptoms and age were associated with adverse outcome.Pregnancy should not be discouraged, except in the presence of severe HF symptoms or high-risk features. Nevertheless, cardio-obstetric counselling and close supervision are key in all instances, particularly in the peri-partum period.

The "Preeclampsia and Hypertension Target Treatment" study: a multicenter prospective study to evaluate the effectiveness of the antihypertensive therapy based on maternal hemodynamic findings.

BACKGROUND: Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values. OBJECTIVE: This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings. STUDY DESIGN: This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output [≤5 L/min] and/or high systemic vascular resistance [≥1300 dynes/second/cm2]) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output [>5 L/min] and/or low systemic vascular resistances [<1300 dynes/second/cm2]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically appropriate therapy and women treated with an inappropriate therapy. RESULTS: A total of 152 women with hypertensive disorders of pregnancy were included in the final analysis. Most women displayed a hypodynamic profile (114 [75.0%]) and received a hemodynamically appropriate treatment (116 [76.3%]). The occurrence of severe hypertension before delivery was significantly lower in the group receiving an appropriate therapy than in the group receiving an inappropriately treated (6.0% vs 19.4%, respectively; P=.02). Moreover, the number of women who achieved target values of blood pressure within 48 to 72 hours from the treatment start was higher in the group who received an appropriate treatment than in the group who received an inappropriate treatment (70.7% vs 50.0%, respectively; P=.02). CONCLUSION: In pregnant individuals with de novo hypertensive disorders of pregnancy, a lower occurrence of severe hypertension was observed when the first-line antihypertensive agent was tailored to the correct maternal hemodynamic profile.

Neonatal Outcomes of Term Infants Born with Meconium-Stained Amniotic Fluid.

Background Meconium-stained amniotic fluid (MSAF) is considered an alarming sign of possible fetal compromise and it has recently been reported that neonatal outcome correlates with the degree of meconium thickness. Methods We retrospectively studied 400 term infants allocated in clear amniotic fluid and grade 1, 2, and 3 MSAF groups on the basis of color and thickness of AF. Multivariable logistic regression analysis was performed to evaluate the potential independent effect of delivery with MSAF of different severity on the risk of a composite adverse neonatal outcome. Results We found that delivery with grade 2 (OR 16.82, 95% Cl 2.12-33.52; p = 0.008) and 3 (OR 33.79, 95% Cl 4.24-69.33; p < 0.001) MSAF is independently correlated with the risk of adverse neonatal outcome, such as the occurrence of at least one of the following: need of resuscitation in the delivery room, blood cord pH < 7.100, occurrence of meconium aspiration syndrome (MAS), persistent pulmonary hypertension (PPH), transient tachypnea of the newborn (TTN), acute respiratory distress syndrome (ARDS), hypoxic-ischemic encephalopathy (HIE), and sepsis. Conclusions There is a positive correlation between the severity of amniotic fluid meconium staining and thickness and the outcomes of term infants. Therefore, the evaluation and grading of MSAF during labor is useful in order to plan for the presence of a neonatologist at delivery for immediate and proper neonatal care.