[show abstract][hide abstract] ABSTRACT: Umbilical vessels, that provide blood oxygenation and fetal nourishment in utero, are encased and protected against external forces by the umbilical cord. The biomechanics of this peculiar structure has not been deeply investigated so far. The purpose of this study is to investigate the hydraulic behaviour of human umbilical veins (UV) and its changes in presence of an external cord compression. Five umbilical cords were subjected to in vitro tests. UV was accurately cannulated and connected to a perfusion circuit, while the cord was subjected to an external compression. Pressure drops across UV were measured for various venous flow rates and various degrees of cord constriction. Compressive forces were measured, too. The UV hydraulic resistances measured in unloaded cords (0.029 ± 0.016 mmHg min cm−1 L−1) correspond to placenta-abdomen pressure drops well consistent with in utero measurements. As expected, at fixed flow rate, flow resistance augments when cord is compressed. Interestingly, resistance does not substantially change until a 30–50% cord thickness reduction, whereas slightly larger constriction cause a steep increase. Compressive forces becomes critical for values above 0.5-2 N, depending on the length of cord compression and on considered specimen. Moreover, at high cord constriction, hydraulic behaviour of UV is very peculiar. Namely, the slope of the pressure-flow relationship decreases at increasing flow rates and, in few cases, a surprising reduction of pressure drop was even observed. The biomechanical behaviour of the umbilical cord during compression is very complex, with high non-linearity of venous hydraulic behaviour.
Cardiovascular Engineering and Technology. 08/2013; 4(3).
[show abstract][hide abstract] ABSTRACT: Objectives. Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe perinatal morbidity and mortality following early-onset fetal growth restriction based on time of antenatal diagnosis and delivery.
Methods. We report cohort outcomes for a prospective multicenter randomized management study of fetal
growth restriction (Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE)) performed in 20
European perinatal centers between 2005 and 2010. Women with a singleton fetus at 26–32 weeks of
gestation, with abdominal circumference < 10th percentile and umbilical artery Doppler pulsatility index >95th percentile, were recruited. The main outcome measure was a composite of fetal or neonatal death or severe morbidity: survival to discharge with severe brain injury, bronchopulmonary dysplasia, proven neonatal sepsis or necrotizing enterocolitis.
Results Five-hundred and three of 542 eligible women formed the study group. Mean ± SD gestational age at diagnosis was 29 ± 1.6 weeks and mean ± SD estimated fetal weight was 881 ± 217 g; 12 (2.4%) babies died in utero. Gestational age at delivery was 30.7 ± 2.3 weeks, and birth weight was 1013 ± 321 g. Overall,
81% of deliveries were indicated by fetal condition and 97% were by Cesarean section. Of 491 liveborn babies, outcomes were available for 490 amongst whom there were 27 (5.5%) deaths and 118 (24%) babies suffered severe morbidity. These babies were smaller at birth (867 ± 251 g) and born earlier (29.6 ± 2.0 weeks). Death and severe morbidity were signiﬁcantly related to estational age, both at study entry and delivery and also with the presence of maternal hypertensive morbidity. The median time to delivery was 13 days for women without hypertension, 8 days for those with gestational hypertension, 4 days for pre-eclampsia and 3 days for HELLP syndrome.
Conclusions Fetal outcome in this study was better than expected from contemporary reports: perinatal death was uncommon (8%) and 70% survived without severe neonatal morbidity. The intervals to delivery, death and severe morbidity were related to the presence and severity of maternal hypertensive conditions.
Ultrasound in Obstetrics and Gynecology. 01/2013; 42:400-408.
[show abstract][hide abstract] ABSTRACT: Introduction
Early onset placenta Preeclampsia (ePE) with Intrauterine Growth Restriction (IUGR) is associated with insufficient placental function, leading to decreased nutrient and oxygen (O2)O2) availability for the fetus . Mitochondria (mt) are the cell energy producers. Mt dysfunctions could be involved in altered placental metabolism leading to ePE and IUGR. We previously demonstrated higher levels of mtDNA in human IUGR placentas .
Here we investigate mtDNA levels in ePE and PE without IUGR placentas, and we present an innovative technique, High Resolution Respirometry (HRR), on cytotrophoblast cells (CTC) from PE, IUGR and control placentas (C), measuring cell O2O2 consumption which represents respiratory chain efficiency.
mtDNA was measured by Real-Time PCR in 20 PE placentas, with (n = 14) or without (n = 6) IUGR, and 45 C.
CTC were isolated from 4 PE, 4 IUGR and 6 C and characterized by flow cytometry, staining samples with anti-cytokeratin-7 and anti-vimentin antibodies. Cells were located in chambers with atmospheric O2O2levels; 2 different protocols were used, with or without digitonin permeabilization, allowing to measure the O2O2 consumption of the respiratory chain complexes singularly or all together. Substrates and inhibitors of different respiratory chain complexes were sequentially administered (succinate, ADP, oligomycin, FCCP, rotenone, antimycin A, glutamate, malate, myxothiazol, TMPD, ascorbate, pyruvate, cytochrome C, differently combined depending on the protocol) and O2O2 consumption levels were recorded. Data were normalized by Citrate Synthase (CS) activity and CTC mtDNA content.
PE placentas: mtDNA content was significantly increased in ePE+IUGR (p = 0.02) vs C; opposite to this, mtDNA was decreased in PE without IUGR (p = 0.03).
CTC: single mt O2O2 consumption (obtained by normalizing data both by CS activity and mtDNA) was slightly increased both in PE and IUGR. The global cell respiration was increased, though not significantly. The trend towards higher O2O2 consumption studied on permeabilized cells was confirmed for all the respiratory chain complexes.
Our study showed that mtDNA is increased also in ePE with IUGR and added the novel observation that mtDNA is decreased in PE without IUGR. In both conditions placental mitochondria present an altered respiratory chain activity, with a trend to a higher respiratory capacity. This could lead to higher ATP production likely as an attempt to compensate for other aspects of placental disease due to small or inefficient exchange capabilities.
Further data are needed to confirm these preliminary results, together with specific enzymatic assays to asses the respiratory chain complexes functionality.
Supported by Fondazione Giorgio Pardi, Associazione Studio Malformazion(ASM) and by a Grant COFIN (Italian Ministry of Research) on: New markers for preterm deliveries
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 07/2012; 2(3):203.
[show abstract][hide abstract] ABSTRACT: To estimate the ability to discriminate between benign and malignant adnexal masses of different size using: subjective assessment, two International Ovarian Tumor Analysis (IOTA) logistic regression models (LR1 and LR2), the IOTA simple rules and the risk of malignancy index (RMI).
We used a multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e. the database previously used to prospectively validate the diagnostic performance of LR1 and LR2. The masses were categorized into three subgroups according to their largest diameter: small tumors (diameter < 4 cm; n = 396), medium-sized tumors (diameter, 4-9.9 cm; n = 1457) and large tumors (diameter ≥ 10 cm, n = 592). Subjective assessment, LR1 and LR2, IOTA simple rules and the RMI were applied to each of the three groups. Sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-), diagnostic odds ratio (DOR) and area under the receiver-operating characteristics curve (AUC) were used to describe diagnostic performance. A moving window technique was applied to estimate the effect of tumor size as a continuous variable on the AUC. The reference standard was the histological diagnosis of the surgically removed adnexal mass.
The frequency of invasive malignancy was 10% in small tumors, 19% in medium-sized tumors and 40% in large tumors; 11% of the large tumors were borderline tumors vs 3% and 4%, respectively, of the small and medium-sized tumors. The type of benign histology also differed among the three subgroups. For all methods, sensitivity with regard to malignancy was lowest in small tumors (56-84% vs 67-93% in medium-sized tumors and 74-95% in large tumors) while specificity was lowest in large tumors (60-87%vs 83-95% in medium-sized tumors and 83-96% in small tumors ). The DOR and the AUC value were highest in medium-sized tumors and the AUC was largest in tumors with a largest diameter of 7-11 cm.
Tumor size affects the performance of subjective assessment, LR1 and LR2, the IOTA simple rules and the RMI in discriminating correctly between benign and malignant adnexal masses. The likely explanation, at least in part, is the difference in histology among tumors of different size.
Ultrasound in Obstetrics and Gynecology 05/2012; 40(3):345-54. · 3.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study aimed to assess the feasibility and the short- and long-term efficacy of hysteroscopic myomectomy for submucous
myomas with intramural development [grade 1 (G1) and grade 2 (G2)] by using non-electrical “cold” loops and to verify the
role of preoperative variables on surgical outcomes. Symptomatic (bleeding and infertility) premenopausal patients with the
diagnosis of submucous myoma at transvaginal sonography, and with G1 and G2 grading at sonohysterography, were included in
this prospective study. Hysteroscopic myomectomy was performed by the combined monopolar electrical slicing and traction-and-leverage
manoeuvres by non-electrical “cold” loops. One hundred fifty-nine patients were recruited, and 169 procedures were performed.
Operating time, fluid deficit, complications and complete resection at first procedure (perioperative outcomes) and persisting
symptoms and additional surgery for persisting symptoms (long-term outcomes) were not significantly different for G1 vs. G2
myomas. Perioperative outcomes were significantly different when comparing myoma mean diameter <3.0 vs. ≥3.0cm (75th percentile).
Multivariate analysis and multiple regression analysis proved that myoma mean diameter was the only significant variable for
surgical outcomes. Hysteroscopic myomectomy by non-electrical “cold” loops is an effective and efficient treatment for submucous
myomas with intramural development. Myoma mean diameter is the only significant preoperative variable for perioperative outcome,
while myoma grading loses its role as a prognostic factor.
KeywordsHysteroscopic myomectomy–Non-electrical “cold” loops–Submucous myoma–Long-term follow-up–Hysteroscopic complications
[show abstract][hide abstract] ABSTRACT: To report the incidence of fetal and maternal complications after selective fetoscopic laser surgery for twin-to-twin transfusion syndrome (TTTS).
A total of 150 cases of TTTS were treated from January 2004 to June 2009 (period 1, 2004-2006, 62 cases; period 2, 2007 to June 2009, 88 cases). Fetal complications (double and single intrauterine fetal death, recurrence of TTTS, twin anemia-polycythemia sequence (TAPS), reversal of TTTS, cerebral lesions in one twin) and maternal complications were recorded, and retrospectively analyzed.
Nineteen (12.6%), 58 (38.7%), 61 (40.7%) and 12 cases (8.0%) were classified preoperatively as Quintero stage I, II, III and IV, respectively. The anterior placenta was described in 73 cases (48.6%). Double and single fetal death occurred overall in 7.3 and 36.0% of cases, respectively. The rate of recurrence was 11.3%, of TAPS 3.3%, and of reversal of TTTS 1.3%. Cerebral lesions were diagnosed in 3 donors (2.0%). Eighteen cases (12.0%) of fetal complications had a second procedure (6 repeat laser, 4 serial amnioreduction, 8 bipolar cord coagulation). Pregnancies undergoing a second procedure delivered at a median gestational age of 30.2 weeks compared to 32.1 weeks for those not repeating (p = 0.04). Perinatal survival of at least one twin improved from 66.1 to 79.5% (p = 0.06) in the two consecutive periods. For every 10 laser surgeries performed, there was an average improvement of 1.5% in the predicted percentage of survival of at least one twin (OR 1.09, 95% CI 1.00-1.19). Major maternal complications occurred in 9 cases (6.0%), 3 of which required admission to intensive care unit.
Fetal complications are common after fetoscopic laser surgery. In this experience, an increasing number of procedures improved the performance of a new fetoscopic laser center.
Fetal Diagnosis and Therapy 03/2012; 31(3):170-8. · 1.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to assess and compare uterine artery (UtA) blood flow volume in pregnant patients with an abnormal uterine Doppler pulsatility index (PI) who delivered fetuses with an appropriate weight for gestational age (AGA) or with intrauterine growth restricted (IUGR). We prospectively recruited singleton pregnancies with abnormal uterine arteries P.I. between 18 and 38 weeks of gestation regardless of estimated fetal weight (EFW). Vessel diameter and blood flow velocity were measured along the UtA upstream to the vessel bifurcation in both the right and left UtAs. Uterine blood flow volumes measured in these pregnancies were compared to historical Control-pregnancies. Forty-three patients delivered at term a normal weight newborn (AGA-pregnancies). Thirty patients delivered growth restricted newborns at 32 weeks (i.r. 29-36w) with a median weight of 1160 gr (i.r. 1000-2065 gr) (IUGR-pregnancies). At mid-gestation (18 + 0 - 25 + 6 weeks + days of gestation) a significantly lower uterine blood flow volume per unit weight was observed between the two study groups and compared to controls: 142 ml/min/kg in IUGR-pregnancies, 217 ml/min/kg in AGA-pregnancies and 538 ml/min/kg in Control-pregnancies. These striking differences in blood flow volume were already present at mid-gestation, at a time when EFW was still normal. In late gestation (27 + 0 - 37 + 6 weeks + days of gestation), pregnancies with an abnormal uterine P.I. showed persistently low UtA flow (<50% of controls) even when corrected for fetal weight: 81 ml/min/kg in IUGR-pregnancies, 105 ml/min/kg in AGA-pregnancies, and 193 ml/min/kg in Control-pregnancies; p < 0.0001. Our findings are consistent with other recent studies regarding the association between reduced uterine blood flow volume and fetal growth restriction. However, the study brings new insight into the finding of abnormal uterine P.I. in normally grown fetuses typically dismissed as "falsely abnormal" or "false positive" findings. Our study suggests that blood flow volume measurement may serve as a new tool to assess this group of patients and possibly those with ischemic placental diseases that may provide some basis for therapeutic interventions.
[show abstract][hide abstract] ABSTRACT: To identify fetal cord blood prognostic markers of symptomatic congenital human cytomegalovirus infection (HCMV).
Retrospective observational study.
Fetal medicine unit in Milan and Medical virology unit in Pavia, Italy.
HCMV-infected and -uninfected fetuses of mothers with primary HCMV infection during the period 1995-2009.
Overall, 94 blood samples from as many fetuses of 93 pregnant women experiencing primary HCMV infection were examined for multiple immunological, haematological and biochemical markers as well as virological markers. Congenital HCMV infection was diagnosed by detection of virus in amniotic fluid, and symptomatic/asymptomatic infections were determined by ultrasound scans, nuclear magnetic resonance imaging, histopathology or clinical examination at birth. Blood sample markers were retrospectively compared in symptomatic and asymptomatic fetuses with congenital infection.
A statistical analysis was performed to determine the value of each parameter in predicting outcome.
Univariate analysis showed that most nonviral and viral markers were significantly different in symptomatic (n = 16) compared with asymptomatic (n = 31) fetuses. Receiver operator characteristics analysis indicated that, with reference to an established cutoff for each marker, the best nonviral factors for differentiation of symptomatic from asymptomatic congenital infection were β(2) -microglobulin and platelet count, and the best virological markers were immunoglobulin M antibody and DNAaemia. β(2) -Microglobulin alone or the combination of these four markers reached the optimal diagnostic efficacy.
The determination of multiple markers in fetal blood, following virus detection in amniotic fluid samples, is predictive of perinatal outcome in fetuses with HCMV infection.
BJOG An International Journal of Obstetrics & Gynaecology 03/2011; 118(4):448-56. · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Increasing numbers of pregnant HIV-positive women are receiving combination antiretroviral regimens for preventing mother-to-child virus transmission or for treating the infection itself. Several studies have demonstrated that nucleoside reverse transcriptase inhibitors (NRTIs) induce mitochondrial toxicity by several mechanisms, including depletion of mitochondrial DNA (mtDNA). By the quantification of mtDNA levels, we studied mitochondrial toxicity in HIV-positive women at delivery and the possible correlations with antiretroviral regimens, viroimmunological and metabolic parameters.
We analysed 68 HIV-positive women enrolled in the Italian Prospective Cohort Study on Efficacy and Toxicity of Antiretroviral in Pregnancy (TARGET Study); all were taking ≥1 NRTI. We quantified mtDNA copies per cell in subcutaneous fat samples collected during delivery. At the 3rd, 6th and 9th month of pregnancy, we collected data concerning CD4(+) T-cell count, plasma HIV RNA, total and high-density lipoprotein (HDL) cholesterol, fasting plasma glucose and triglycerides. As a control, we analysed mtDNA levels in abdominal subcutaneous fat samples from 23 HIV-seronegative women at delivery.
mtDNA content was significantly lower in HIV-infected women when compared with HIV-negative controls. mtDNA content varied independently from viroimmunological, lipid and glucose parameters at the different months, with the exceptions of triglycerides at the 9th month and of HDL at the 6th month of pregnancy.
In subcutaneous tissue from women taking NRTI-based antiretroviral regimens, we observed a significant decrease of mtDNA content, compared with uninfected women not on antiviral treatment. Moreover, a significant correlation was noted between mtDNA content and HDL cholesterol and triglycerides.