Publications by authors named "Leonardo Caforio"

14 Publications

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Pregnancy and viral infections: Mechanisms of fetal damage, diagnosis and prevention of neonatal adverse outcomes from cytomegalovirus to SARS-CoV-2 and Zika virus.

Biochim Biophys Acta Mol Basis Dis 2021 Jun 10;1867(10):166198. Epub 2021 Jun 10.

Fetal and Perinatal Medicine and Surgery Unit, Medical and Surgical Department of Fetus, Newborn and Infant - "Bambino Gesù" Children's Hospital IRCCS, Rome, Italy. Electronic address:

Some maternal infections, contracted before or during pregnancy, can be transmitted to the fetus, during gestation (congenital infection), during labor and childbirth (perinatal infection) and through breastfeeding (postnatal infection). The agents responsible for these infections can be viruses, bacteria, protozoa, fungi. Among the viruses most frequently responsible for congenital infections are Cytomegalovirus (CMV), Herpes simplex 1-2, Herpes virus 6, Varicella zoster. Moreover Hepatitis B and C virus, HIV, Parvovirus B19 and non-polio Enteroviruses when contracted during pregnancy may involve the fetus or newborn at birth. Recently, new viruses have emerged, SARS-Cov-2 and Zika virus, of which we do not yet fully know the characteristics and pathogenic power when contracted during pregnancy. Viral infections in pregnancy can damage the fetus (spontaneous abortion, fetal death, intrauterine growth retardation) or the newborn (congenital anomalies, organ diseases with sequelae of different severity). Some risk factors specifically influence the incidence of transmission to the fetus: the timing of the infection in pregnancy, the order of the infection, primary or reinfection or chronic, the duration of membrane rupture, type of delivery, socio-economic conditions and breastfeeding. Frequently infected neonates, symptomatic at birth, have worse outcomes than asymptomatic. Many asymptomatic babies develop long term neurosensory outcomes. The way in which the virus interacts with the maternal immune system, the maternal-fetal interface and the placenta explain these results and also the differences that are observed from time to time in the fetal‑neonatal outcomes of maternal infections. The maternal immune system undergoes functional adaptation during pregnancy, once thought as physiological immunosuppression. This adaptation, crucial for generating a balance between maternal immunity and fetus, is necessary to promote and support the pregnancy itself and the growth of the fetus. When this adaptation is upset by the viral infection, the balance is broken, and the infection can spread and lead to the adverse outcomes previously described. In this review we will describe the main viral harmful infections in pregnancy and the potential mechanisms of the damages on the fetus and newborn.
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http://dx.doi.org/10.1016/j.bbadis.2021.166198DOI Listing
June 2021

Fetal cardiac dimensions in congenital diaphragmatic hernia: relationship with gestational age and postnatal outcomes.

J Perinatol 2021 Jul 1;41(7):1651-1659. Epub 2021 Mar 1.

Department of Neonatology, Royal Hospital for Children, Glasgow, UK.

Objective: To serially assess fetal cardiac dimensions in congenital diaphragmatic hernia (CDH) and their relation to disease severity.

Study Design: Retrospective analysis of CDH cases and matched controls. Mitral (MVd) and tricuspid (TVd) valve diameters, left (LV) and right (RV) ventricular length and area, Z-scores, were serially assessed at 24-26, 30-32, and 35-37 weeks gestational age (GA).

Results: In CDH cases MVd, MVd Z-score, and LV area were significantly reduced at 24-26 and 35-37 weeks GA. TVd, TVd Z-score, and RV area were significantly reduced at 24-26 weeks. RV area Z-score increased with advancing GA. MVd and MVd Z-score were significantly lower at 24-26 weeks GA in CDH who had a combined outcome of death and/or ECMO.

Conclusions: LV hypoplasia in CDH is characterized by reduced MVd from 24 weeks GA. MVd, and the ratio of mitral and tricuspid valve diameters at later gestations, may be potential predictors of disease severity.
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http://dx.doi.org/10.1038/s41372-021-00986-yDOI Listing
July 2021

Vertical Transmission of SARS-CoV-2 (COVID-19): Are Hypotheses More than Evidences?

Am J Perinatol 2020 09 5;37(S 02):S31-S38. Epub 2020 Aug 5.

Neonatal Intensive Care Unit, IRCCS Foundation Policlinico "San Matteo," Pavia, Italy.

In spite of the increasing, accumulating knowledge on the novel pandemic coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), questions on the coronavirus disease-2019 (COVID-19) infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending and have not been addressed so far. SARS-CoV-2, a RNA single-stranded virus, has been detected in the amniotic fluid, in the cord blood and in the placentas of the infected women. In the light of these findings, the theoretical risk of intrauterine infection for fetuses, or of peripartum infection occurring during delivery for neonates, has a biological plausibility. The extent of this putative risk might, however, vary during the different stages of pregnancy, owing to several variables (physiological modifications of the placenta, virus receptors' expression, or delivery route). This brief review provides an overview of the current evidence in this area. Further data, based on national and international multicenter registries, are needed not only to clearly assess the extent of the risk for vertical transmission, but also to ultimately establish solid guidelines and consistent recommendations. KEY POINTS: · Questions on the COVID-19 infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending so far.. · The theoretical risk of intrauterine infection for fetuses, or of neonatal infection during delivery for neonates, has a biological plausibility.. · A caution is recommended in the interpretation of clinical and laboratory data in neonates..
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http://dx.doi.org/10.1055/s-0040-1714346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645815PMC
September 2020

Physiological changes in cardiac dimensions and function in low-risk pregnancies.

J Matern Fetal Neonatal Med 2020 Jul 1:1-4. Epub 2020 Jul 1.

Newborn Surgery Unit, Ospedale Pediatrico Bambino Gesu, Roma, Italy.

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http://dx.doi.org/10.1080/14767058.2020.1786057DOI Listing
July 2020

Comparison of mediastinal shift angles obtained with ultrasound and magnetic resonance imaging in fetuses with isolated left sided congenital diaphragmatic hernia.

J Matern Fetal Neonatal Med 2020 Jan 23:1-6. Epub 2020 Jan 23.

Department of Medical and Surgical Neonatology, Fetal Medicine and Surgery Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.

To compare ultrasound (US) and magnetic resonance imaging (MRI) in the assessment of mediastinal shift angles (MSAs) in fetuses affected by isolated left congenital diaphragmatic hernia (CDH). The use of MRI-MSA and US-MSA as prognostic factor for postnatal survival in fetal left CDH was also explored. This was an observational study of 29 fetuses with prenatally diagnosed isolated left CDH, assessed with both US and MRI examinations between January 2015 and December 2018. The US-MSA measurements performed within 2 weeks from the MRI assessment were considered for the analysis. The primary outcome was the postnatal survival rate. No significant difference between US and MRI MSAs was detected ( = .419). Among the 29 cases, there were 21 alive infants, for an overall postnatal survival rate of 72.41%. After stratifying for postnatal survival, the best cutoffs with the highest discriminatory power in terms of sensibility and specificity were 42.1° for the US-MSA and 39.1° for the MRI-MSA. The performance of MRI-MSA in predicting postnatal survival was close to that of US-MSA in terms of sensitivity (62.5 versus 50.0%), specificity (80.9 versus 90.5%), positive predictive value (55.6 versus 66.7%), negative predictive value (85.0 versus 82.6%) and accuracy (75.9 versus 79.3%). There was no statistically significant difference between the two modalities ( > .05 for all). MRI and US can be interchangeably used for the assessment of MSA in prenatally diagnosed isolated left CDH. Moreover, MSA measured by both US and MRI was confirmed to be correlated with perinatal outcome in terms of survival.
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http://dx.doi.org/10.1080/14767058.2020.1716714DOI Listing
January 2020

Fetal MRI assessment of mediastinal shift angle in isolated left congenital diaphragmatic hernia: A new postnatal survival predictive tool?

Prenat Diagn 2020 01 27;40(1):136-141. Epub 2019 Dec 27.

Department of Imaging, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy.

Objective: To quantify the mediastinal shift angle (MSA) in fetuses with isolated left congenital diaphragmatic hernia (CDH) by magnetic resonance imaging and evaluate survival.

Method: Fetuses from singleton pregnancies with isolated left CDH were matched for gestational age with controls without thoracic malformations. For all fetuses the MSA was determined by two operators and inter-operator variability and differences between cases and controls were investigated. For all cases total fetal lung volume (TFLV) was calculated and the correlation between MSA and TFLV was assessed, and its predictive value towards survival was determined.

Results: Thirty-four fetuses were included as cases and 42 as controls. The mean gestational age for assessment of CDH fetuses was 32 weeks (range 27-38). Twenty-four fetuses survived until discharge and 10 did not. There was an excellent inter-operator reliability for measuring the MSA and a significant difference between MSA in cases and controls. There was an inverse correlation between MSA values and survival, a correlation between TFLV and survival and an inverse correlation between MSA and TFLV. The area under the ROC curve for MSA in predicting survival was 0.931 (95% CI 0.851-1.000).

Conclusion: The MSA measured late in gestation correlates with postnatal survival in patients with isolated left CDH.
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http://dx.doi.org/10.1002/pd.5619DOI Listing
January 2020

Cerebral blood flow autoregulation and congenital heart disease: possible causes of abnormal prenatal neurologic development.

J Matern Fetal Neonatal Med 2011 Oct 20;24(10):1208-11. Epub 2011 Jan 20.

Department of Obstetrics and Gynecology, Santa Maria della Misericordia University Hospital, Perugia, Italy.

Objective: To determine whether the major congenital heart diseases (CHDs) can modify the cerebrovascular flow dynamics and the biometrical parameters in fetuses at third trimester of pregnancy.

Methods: We studied 60 fetuses with CHD. Data included prenatal versus postnatal cardiac diagnosis, cerebral and umbilical artery doppler, fetal biometrical parameters, fetal weight, and gestational age. The pulsatility index (PI) was used to determine blood flow velocities in the umbilical artery (UA) and middle cerebral artery (MCA), while the cerebro/placental ratio (CPR) was assessed as a measure of cerebral autoregulation. Fetuses with CHD were compared to normal controls and then analyzed after being divided into groups based on specific defects.

Results: Compared with control fetuses, those with CHD showed a decrease of resistance blood flow in the middle cerebral artery (1.76 vs 1.92 PI) especially considering the CPR (1.66 vs 2.03 PI) (p < 0.01). Furthermore, fetuses with CHD also had smaller head circumferences (30.6 cm vs 31.5 cm p < 0.01) and head/abdominal (HC/AC) ratio (1 vs 1.05 p < 0.01). When stratified for single cardiac diseases, fetuses with hypoplasic left heart syndrome showed a lower CPR and HC/AC ratio.

Conclusions: Cerebrovascular resistance is significantly lower in fetuses with CHD, especially in cases of left side obstruction. The cerebro/placental hemodynamic changes are similar to that described in fetuses with placental insufficiency and may contribute to their abnormal neurologic development.
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http://dx.doi.org/10.3109/14767058.2010.547961DOI Listing
October 2011

Neonatal emergencies associated with cardiac rhabdomyomas: an 8-year experience.

Fetal Diagn Ther 2011 27;29(2):169-77. Epub 2010 Nov 27.

Paediatric Cardiology, Catholic University, A. Gemelli Hospital, Largo Gemelli 8, Rome, Italy.

During the foetal-neonatal period, rhabdomyomas represent the majority of cardiac tumours and are closely associated with tuberous sclerosis. Cardiac rhabdomyomas may be completely asymptomatic and are incidentally discovered during an echocardiogram, or may cause cardiac dysfunctions requiring medical and/or surgical intervention. During foetal life and the early neonatal period, life-threatening conditions, mostly due to arrhythmias, cardiac failure or obstruction, do occur on rare occasions. We reviewed the medical records of all cases of cardiac rhabdomyomas diagnosed prenatally or postnatally over an 8-year period. The present study reviews 7 cases of life-threatening conditions. Arrhythmic episodes were described in 5 patients, and blood flow obstruction was reported in 2 cases. Antiarrhythmic agents successfully controlled the clinical and electrophysiological conditions. Obstructive conditions were associated with poor outcomes. In conclusion, when prenatal diagnosis of rhabdomyoma is made, appropriate planning at delivery for the management of potential haemodynamic complications may prevent adverse neonatal outcomes. The clinical outcome is more influenced by obstructive rather than by dysrhythmic complications. Appropriate antiarrhythmic treatment is of primary importance. In all cases discovered through prenatal and/or neonatal life-threatening conditions, an accurate follow-up should always be performed to anticipate the development of tuberous sclerosis.
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http://dx.doi.org/10.1159/000320483DOI Listing
June 2011

Conservative management of placenta previa-accreta by prophylactic uterine arteries ligation and uterine tamponade.

Fetal Diagn Ther 2009 30;25(4):400-3. Epub 2009 Sep 30.

Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.

Background: Placenta previa-accreta is associated with severe hemorrhage occurring while separating the placenta during cesarean delivery and hysterectomy is considered the treatment of choice. Conservative management has recently been proposed.

Case: A 26-year-old woman had pregnancy complicated by placenta previa with suspected accreta. During elective cesarean section a prophylactic double bilateral ligation of uterine arteries was performed before removal of the placenta; subsequently, the continuous small bleeding from the placental bed was stopped by tamponade with a balloon catheter filled with saline solution. The patient was discharged 5 days later. An ultrasonographic color Doppler follow-up demonstrated a renewed uterine vascularization.

Conclusion: Double bilateral ligation of uterine arteries can be used as a prophylactic surgical treatment when a severe bleeding because of placenta previa-accreta is expected, in order to avoid hysterectomy.
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http://dx.doi.org/10.1159/000236154DOI Listing
December 2009

Predictors of pregnancy outcome in antiphospholipid syndrome: a review.

Clin Rev Allergy Immunol 2010 Apr;38(2-3):116-24

Department of Obstetrics and Gynecology, Catholic University of Sacred Hearth, Rome, Italy.

In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk of preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In the last two decades, several studies were performed to identify the predictive role of some parameters in relation to obstetric outcome in APS patients. Among these, the uterine velocimetry Doppler is the most studied. It provides a non-invasive method for the study of uteroplacental blood flow, being able to detect a condition of impaired placental perfusion, due to the presence of circulating antiphospholipid antibodies (aPL). To date, the uterine artery Doppler velocimetry resulted to be a useful tool to identify APS pregnancies at higher risk of adverse pregnancy outcome. False-positive IgM for toxoplasmosis, others, rubella, cytomegalovirus, herpes viruses (TORCH) complex is associated to a worse pregnancy outcome because it reflects a dysregulation of the immune system which may amplify placental autoimmune damage. Moreover low levels of complement components are related to an increased incidence of obstetrical complications, suggesting that placental deposition of immune complexes and activation of complement cascade may contribute to placental failure APS related. The abnormal uterine Doppler velocimetry, false-positive TORCH IgM and low levels of complement components can be considered prognostic indexes of poor pregnancy outcome in APS.
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http://dx.doi.org/10.1007/s12016-009-8144-zDOI Listing
April 2010

Uterine artery velocity waveforms as predictors of pregnancy outcome in patients with antiphospholipid syndrome: a review.

Ann N Y Acad Sci 2007 Jun;1108:530-9

Department of Obstetrics and Gynecology, Catholic University, Rome, Italy.

In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk for preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation, as the likely consequence of the physiologic change of spiral arteries into low-resistance vessels. The presence of antiphospholipid antibodies can impair this vascular adaptation, resulting in a reduced placental perfusion. Doppler investigation provides a noninvasive method for the study of uteroplacental blood flow. Several studies were performed to detect the predictive role of uterine artery Doppler velocimetry in relation to pregnancy outcome in APS patients. In some studies, a high resistance index in the uterine arteries strongly predicted the subsequent development of obstetric complications. In other studies, persistent bilateral uterine artery notches identified the risk of preeclampsia and fetal intrauterine growth restriction. To date, the uterine artery Doppler velocimetry resulted to be a useful tool for identifying APS pregnancies at risk for adverse pregnancy outcome. These findings might have important implications for the management of these patients.
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http://dx.doi.org/10.1196/annals.1422.056DOI Listing
June 2007

Resistin regulates human choriocarcinoma cell invasive behaviour and endothelial cell angiogenic processes.

J Endocrinol 2006 Jun;189(3):691-9

Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Largo Gemelli 8, 00168 Rome, Italy.

Resistin is a novel hormone that is secreted by human adipocytes and mononuclear cells and is probably associated with insulin resistance. Recently, resistin has been postulated to play a role in pregnancy, and resistin gene expression has been observed in placental tissues. However, it is still not known if resistin is able to affect trophoblast functions and development. Therefore, we investigated the hypothesis that resistin might regulate trophoblast production of matrix metalloproteinases (MMPs), the tissue inhibitors of metalloproteinases (TIMPs), trophoblast invasive behavior and the angiogenic processes. In human choriocarcinoma cells (BeWo), resistin (10-100 ng/ml) enhanced both MMP-2 protein and mRNA expression, significantly reduced TIMP-1 and TIMP-2 and increased trophoblast-like cell invasiveness. We analyzed the effect of resistin on an in vitro angiogenesis system for endothelial cells (HUVEC) and we evaluated its ability to modulate the secretion of an angiogenic factor, vascular endothelial growth factor (VEGF). Our data showed that resistin induced VEGF production and we observed that the addition of resistin stimulated endothelial cell tube formation. These findings suggest that resistin might be able to induce BeWo cell invasiveness and to contribute to the control of placental vascular development.
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http://dx.doi.org/10.1677/joe.1.06610DOI Listing
June 2006

Successful treatment of post-cesarean hemorrhage related to placenta praevia using an intrauterine balloon. Two case reports.

Fetal Diagn Ther 2006 ;21(3):277-80

Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Rome, Italy.

The authors report a positive experience in controlling severe postpartum hemorrhage after cesarean section performed for placenta praevia by using an inflated intrauterine balloon and avoiding any further invasive surgery.
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http://dx.doi.org/10.1159/000091356DOI Listing
August 2006

Cardiovascular risk factors in healthy women with previous gestational hypertension.

J Clin Endocrinol Metab 2006 Apr 24;91(4):1233-8. Epub 2006 Jan 24.

Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Via Servilio IV 4, 00178 Rome, Italy.

Context: Epidemiological studies indicate that gestational hypertension (Gh) during pregnancy is associated with increased risk of cardiovascular disease in later life. However, it is unclear whether particular metabolic and hemodynamic characteristics are related to this risk.

Objective: The objective of this study was to investigate endothelial function and carbohydrate and lipid metabolism in healthy, normotensive women with previous pregnancy complicated by Gh.

Design, Setting, And Participants: Brachial artery flow-mediated dilatation (FMD; endothelium dependent) and nitroglycerin-induced dilatation (endothelium independent) were measured in 15 subjects with previous Gh and in 15 controls with previous normal pregnancies. Lipid panel, glucose, insulin, homocysteine, and androgens were also measured.

Results: FMD was significantly reduced in women with previous Gh compared with controls (P < 0.0001), whereas nitroglycerin-induced dilatation was comparable in both groups. Gh women showed increased fasting insulin (P = 0.011), insulin resistance measured by homeostasis model assessment (P = 0.018), free fatty acids (P = 0.0018), and testosterone (P = 0.0012) and decreased high-density lipoprotein cholesterol (P = 0.0017) compared with controls. Across all subjects, FMD showed a strong independent negative correlation with testosterone and homeostasis model assessment and a positive correlation with high-density lipoprotein cholesterol (r = -0.60, P = 0.0003; r = -0.43, P = 0.016; and r = 0.58, P = 0.0005, respectively).

Conclusions: Endothelial dysfunction and early alteration of carbohydrate and lipid metabolism are present in otherwise healthy women with previous Gh. These abnormalities along with a relative hyperandrogenism could explain, at least in part, the increased risk for cardiovascular disease in later life in these women.
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http://dx.doi.org/10.1210/jc.2005-1337DOI Listing
April 2006
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