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Papers by Alessandro Alfei

Ultrasound in Obstetrics and Gynecology, 2007

macroscopic and microscopic appearance of the placenta confirmed the diagnosis: it weighed 1100g;... more macroscopic and microscopic appearance of the placenta confirmed the diagnosis: it weighed 1100g; there were multiple dilated vessels on this surface, each of about 2 cm diameter. The second case : A 31year-old primigravida with normal screening ultrasound at 9 weeks and 11 weeks. The 22 weeks screening ultrasound exam discovered a thickened placenta, with hyperechogenic and hypoechogenic areas and an isoechogenic area of about 2 cm diameter. Fetal morphology, biometry and velocimetry were normal. At present the patient is 32 weeks of gestation. We are presenting these cases to show the importance of a careful ultrasound exam of the placenta and the correlation with the histopathologic findings to discriminate a distinct group of high risk pregnancies.

Ultrasound in Obstetrics and Gynecology, 2007

macroscopic and microscopic appearance of the placenta confirmed the diagnosis: it weighed 1100g;... more macroscopic and microscopic appearance of the placenta confirmed the diagnosis: it weighed 1100g; there were multiple dilated vessels on this surface, each of about 2 cm diameter. The second case : A 31year-old primigravida with normal screening ultrasound at 9 weeks and 11 weeks. The 22 weeks screening ultrasound exam discovered a thickened placenta, with hyperechogenic and hypoechogenic areas and an isoechogenic area of about 2 cm diameter. Fetal morphology, biometry and velocimetry were normal. At present the patient is 32 weeks of gestation. We are presenting these cases to show the importance of a careful ultrasound exam of the placenta and the correlation with the histopathologic findings to discriminate a distinct group of high risk pregnancies.

Nutrition journal, 2014

Bariatric surgery results in decreased food intake and a variable degree of malabsorption. Withou... more Bariatric surgery results in decreased food intake and a variable degree of malabsorption. Without adequate supplementation, the most common complications of this surgery are nutritional disorders. Pregnancy following surgery for obesity is a particular condition requiring strict monitoring of nutrient intake necessary for fetal development and a favourable neonatal prognosis. Malnutrition in pregnancy and congenital neural malformations are reported in three women who had previously undergone bariatric surgery (1, 5 and 18 years before pregnancy, respectively). Two patients underwent the Roux en Y bypass and one bilio-pancreatic diversion with gastroplasty. None of the three received pre-conceptional nutritional counselling. Patients 1 and 2 did not undergo postoperative nutritional surveillance; nutrient supplementation was started at 22 and 20 weeks gestation, respectively. In patient 3, supplementation was stopped at six weeks gestation. Newborns 1 and 2 presented with dorsal my...

Cytometry, 1999

Erythroblasts have been the most encouraging candidate cell type for noninvasive prenatal genetic... more Erythroblasts have been the most encouraging candidate cell type for noninvasive prenatal genetic investigation. We previously showed that human erythroblasts can be recovered from bone marrow and blood bank buffy coats by a physical cell separation. In the present study, we modified our previous methodology, taking into account the peculiar behavior of erythroblasts in response to modifications of pH and osmolality of the separation medium. Twenty to forty milliters of cord blood were initially centrifuged on Ficoll/diatrizoate (1.085 g/ml). The interphase cells were further separated on a continuous density gradient (1.040-1.085 g/ml). Two different gradients were initially compared: the first was iso-osmolar and neutral, whereas the second also contained an ionic strength gradient and a pH gradient (triple gradient). A subsequent monocyte depletion was performed by using magnetic microbeads coated with anti-CD14 monoclonal antibody (mAb), and erythroblasts were purified by sedimentation velocity. Purified cells were investigated by analyses with fluorescence-activated cell sorting (FACS) and fluorescence in situ hybridization (FISH) and immunocytochemistry with mAb against fetal hemoglobin and were cultured in vitro. When nucleated cells were spun on an iso-osmolar and neutral continuous density gradient, two separated bands of nucleated red blood cells (NRBCs) were obtained: a light fraction banding at 1.062 g/ml and an heavy fraction banding at 1.078 g/ml. Conversely, when cells were spun in the triple gradient, NRBCs were shifted to the low-density region. Monocyte depletion by immunomagnetic microbeads and velocity sedimentation provided a pure erythroblast population. FACS and FISH analyses and immunocytochemistry substantiated the purity of the isolated cell fraction, which was successfully cultured in vitro. We have shown that fetal erythroblasts can be purified up to homogeneity from cord blood, but further refinements of the isolation procedure are necessary before the same results can be obtained from maternal peripheral blood.

Ultrasound in Obstetrics and Gynecology, 2009

K E Y W O R D S: breast ultrasound; multivariate model; precocious puberty; premature thelarche r... more K E Y W O R D S: breast ultrasound; multivariate model; precocious puberty; premature thelarche risk score ABSTRACT Objective To determine the utility of breast ultrasonography in the diagnostic work-up of precocious puberty and to create a prognostic index for early differentiation between non/slowly progressive or transient forms of precocious puberty and rapidly progressive central precocious puberty.

Ultrasound in Obstetrics and Gynecology, 2003

Objectives Treatment with growth hormone (GH), alone or in combination with oxandrolone, is used ... more Objectives Treatment with growth hormone (GH), alone or in combination with oxandrolone, is used in patients affected by Turner syndrome to improve growth velocity and adult height. Since GH interacts with gonadotropins in the stimulation of the human ovary, the aim of our study was to evaluate the possible effects of GH administration on uterine and ovarian characteristics.

Prenatal Diagnosis, 2012

The objective of the study was to evaluate the association between placental histological pattern... more The objective of the study was to evaluate the association between placental histological patterns and umbilical artery (UA) Doppler velocimetry in pregnancies complicated by fetal growth restriction (FGR). A cohort of 126 FGR pregnancies was followed according to a standard protocol. Placental lesions were diagnosed according to consensus nomenclature and standardized criteria. Pulsatility index was normal in 45 (35.7%) and increased in 44 (34.9%) women. End-diastolic UA Doppler flow was absent in 27 (21.4%) and reversed in 10 (7.9%). Fifty-four women (42.9%) had preeclampsia. In preeclampsia, increasing Doppler abnormalities, from normal to reversed UA end-diastolic flow, were directly associated only with an increased number of placental syncytial knots. In normotensive pregnancies, Doppler abnormalities were associated with increased intervillous fibrin deposits, villous hypoplasia, syncytial knots, placental site giant cells, immature intermediate trophoblast, and with pattern of lesions indicating superficial implantation and maternal vascular underperfusion. In the whole cohort, increase of syncytial knots [odds ratio (OR) = 28.7; 95% confidence interval (CI) = 2.75-298.5], intervillous fibrin deposits (OR = 2.1; 95% CI = 1.04-4.28), placental site giant cells (OR = 3.0; 95% CI = 1.05-8.84), and patterns suggesting maternal underperfusion (OR = 2.9; 95% CI = 1.0-7.1) were independently associated with increased rates of absent/reversed UA end-diastolic flow. In pregnancies complicated by FGR, abnormalities of UA Doppler velocimetry were associated with placental lesions indicating superficial implantation and maternal vascular underperfusion.

Journal of Perinatal Medicine, 2000

To correlate placental pathologic lesions, as defined by the Society for Pediatric Pathology, to ... more To correlate placental pathologic lesions, as defined by the Society for Pediatric Pathology, to the severity of the ratio of the pulsatility Doppler index (PI) of the fetal middle cerebral artery to that of the umbilical artery (cerebroplacental ratio, CPR). A cohort-study of 176 singleton pregnancies complicated by fetal growth restriction (FGR). The mean values of gestational age, birth weight and CPR of the entire cohort were 33.9±3.6 weeks, 1552±561 g, and 1.33±0.68, respectively. In ordered logistic regression analysis, after adjustment for potential confounders, muscularised arteries (Odds Ratio [OR]=3.14; 95% confidence intervals [CI]=1.58-6.28, P=0.001), mural hypertrophy (OR=2.35; 95% CI=1.26-4.4, P=0.008), immature intermediate trophoblast (OR=2.0; 95% CI=1.07-3.71, P=0.03) and maternal vascular underperfusion (OR=2.32; 95% CI=1.25-4.23, P=0.007) were the only parameters associated with severity of CPR. The correlation between placental histological findings indicating maternal underperfusion and placental occlusion suggest that forced centralization of fetal circulation in FGR could be at least partially attributable to the hemodynamic consequences of increased placental vascular resistance.

International Urogynecology Journal, 2007

We performed a historical cohort study of 62 consecutive patients who underwent abdomino-perineal... more We performed a historical cohort study of 62 consecutive patients who underwent abdomino-perineal vaginal re-construction with a segment of the sigmoid colon during a 25-year period. A dedicated database was reviewed for the aetiology of vaginal malformation, surgical complications and post-operative follow-up. Follow-up visits were scheduled 2, 6 and 12 months after discharge from hospital and annually thereafter. Fifty-eight (93.5%) patients were diagnosed as having Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) and four (6.5%) had undergone previous demolitive surgery for gynaecologic malignancy. The mean operating time was 145 min (range 95 to 250 min). The mean hospital stay was 8.3 days (range 5 to 23 days). Post-operative complications requiring additional surgery occurred in 3 (4.8%) patients and were a case of necrotising fascitiis with leakage of the bowel anastomosis, a case of bowel occlusion and a case of neovaginal prolapse. The mean follow-up was 11.3 years (range 3 months to 24 years). We recorded 5 cases (8.1%) of sigmoid graft shrinkage treated successfully by dilation. The time interval between sigmoid vaginoplasty and first intercourse was 4 months (range 2 months to 4 years). During the follow-up, 32 (51.6%) women reported regular and 30 (48.4%) women reported occasional sexual intercourse; 80.6% (50/62) were "satisfied" with the surgical procedure. In this large series, laparotomic sigmoid vaginoplasty was a safe and acceptable technique to treat congenital absence of the vagina. This procedure allowed early sexual intercourse and was associated with a low incidence of shrinkage and a high rate of patients' satisfaction.

Fetal Diagnosis and Therapy, 2009

To evaluate the risk of fetal growth restriction (FGR) associated with first-trimester maternal s... more To evaluate the risk of fetal growth restriction (FGR) associated with first-trimester maternal serum concentrations of pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG). A longitudinal study of 2,178 women who underwent first-trimester evaluation of serum PAPP-A and free beta-hCG. FGR was defined as a decrement of the fetal abdominal circumference to below the 10th percentile of our standard growth curve in the presence of Doppler signs of impaired placental perfusion. Logistic regression was used to compute multivariable odds ratios and the estimated prevalences of outcomes associated with first-trimester serum marker concentrations. The prevalences of small for gestational age (SGA, <10th percentile birth-weight) neonates and FGR were significantly higher among women with serum PAPP-A concentrations below the 10th percentile than in controls: 40/206 compared to 183/1,928, for SGA, adjusted odds ratio = 2.1, 95% confidence intervals (CI) 1.4-3.03; 24/75 compared to 182/1,900, for FGR, adjusted odds ratio = 3.9, 95% CI 2.3-6.5. The adjusted prevalences of FGR and SGA among women with simultaneous low first-trimester values of PAPP-A and free beta-hCG were 0.21 (95% CI 0.13-0.33) and 0.26 (95% CI 0.17-0.36), respectively. Low first-trimester maternal serum PAPP-A concentrations are significantly associated with reduced fetal size and increased risk of FGR with Doppler signs of impaired placental perfusion.

Ultrasound in Obstetrics and Gynecology, 2007

macroscopic and microscopic appearance of the placenta confirmed the diagnosis: it weighed 1100g;... more macroscopic and microscopic appearance of the placenta confirmed the diagnosis: it weighed 1100g; there were multiple dilated vessels on this surface, each of about 2 cm diameter. The second case : A 31year-old primigravida with normal screening ultrasound at 9 weeks and 11 weeks. The 22 weeks screening ultrasound exam discovered a thickened placenta, with hyperechogenic and hypoechogenic areas and an isoechogenic area of about 2 cm diameter. Fetal morphology, biometry and velocimetry were normal. At present the patient is 32 weeks of gestation. We are presenting these cases to show the importance of a careful ultrasound exam of the placenta and the correlation with the histopathologic findings to discriminate a distinct group of high risk pregnancies.

Ultrasound in Obstetrics and Gynecology, 2007

macroscopic and microscopic appearance of the placenta confirmed the diagnosis: it weighed 1100g;... more macroscopic and microscopic appearance of the placenta confirmed the diagnosis: it weighed 1100g; there were multiple dilated vessels on this surface, each of about 2 cm diameter. The second case : A 31year-old primigravida with normal screening ultrasound at 9 weeks and 11 weeks. The 22 weeks screening ultrasound exam discovered a thickened placenta, with hyperechogenic and hypoechogenic areas and an isoechogenic area of about 2 cm diameter. Fetal morphology, biometry and velocimetry were normal. At present the patient is 32 weeks of gestation. We are presenting these cases to show the importance of a careful ultrasound exam of the placenta and the correlation with the histopathologic findings to discriminate a distinct group of high risk pregnancies.

Nutrition journal, 2014

Bariatric surgery results in decreased food intake and a variable degree of malabsorption. Withou... more Bariatric surgery results in decreased food intake and a variable degree of malabsorption. Without adequate supplementation, the most common complications of this surgery are nutritional disorders. Pregnancy following surgery for obesity is a particular condition requiring strict monitoring of nutrient intake necessary for fetal development and a favourable neonatal prognosis. Malnutrition in pregnancy and congenital neural malformations are reported in three women who had previously undergone bariatric surgery (1, 5 and 18 years before pregnancy, respectively). Two patients underwent the Roux en Y bypass and one bilio-pancreatic diversion with gastroplasty. None of the three received pre-conceptional nutritional counselling. Patients 1 and 2 did not undergo postoperative nutritional surveillance; nutrient supplementation was started at 22 and 20 weeks gestation, respectively. In patient 3, supplementation was stopped at six weeks gestation. Newborns 1 and 2 presented with dorsal my...

Cytometry, 1999

Erythroblasts have been the most encouraging candidate cell type for noninvasive prenatal genetic... more Erythroblasts have been the most encouraging candidate cell type for noninvasive prenatal genetic investigation. We previously showed that human erythroblasts can be recovered from bone marrow and blood bank buffy coats by a physical cell separation. In the present study, we modified our previous methodology, taking into account the peculiar behavior of erythroblasts in response to modifications of pH and osmolality of the separation medium. Twenty to forty milliters of cord blood were initially centrifuged on Ficoll/diatrizoate (1.085 g/ml). The interphase cells were further separated on a continuous density gradient (1.040-1.085 g/ml). Two different gradients were initially compared: the first was iso-osmolar and neutral, whereas the second also contained an ionic strength gradient and a pH gradient (triple gradient). A subsequent monocyte depletion was performed by using magnetic microbeads coated with anti-CD14 monoclonal antibody (mAb), and erythroblasts were purified by sedimentation velocity. Purified cells were investigated by analyses with fluorescence-activated cell sorting (FACS) and fluorescence in situ hybridization (FISH) and immunocytochemistry with mAb against fetal hemoglobin and were cultured in vitro. When nucleated cells were spun on an iso-osmolar and neutral continuous density gradient, two separated bands of nucleated red blood cells (NRBCs) were obtained: a light fraction banding at 1.062 g/ml and an heavy fraction banding at 1.078 g/ml. Conversely, when cells were spun in the triple gradient, NRBCs were shifted to the low-density region. Monocyte depletion by immunomagnetic microbeads and velocity sedimentation provided a pure erythroblast population. FACS and FISH analyses and immunocytochemistry substantiated the purity of the isolated cell fraction, which was successfully cultured in vitro. We have shown that fetal erythroblasts can be purified up to homogeneity from cord blood, but further refinements of the isolation procedure are necessary before the same results can be obtained from maternal peripheral blood.

Ultrasound in Obstetrics and Gynecology, 2009

K E Y W O R D S: breast ultrasound; multivariate model; precocious puberty; premature thelarche r... more K E Y W O R D S: breast ultrasound; multivariate model; precocious puberty; premature thelarche risk score ABSTRACT Objective To determine the utility of breast ultrasonography in the diagnostic work-up of precocious puberty and to create a prognostic index for early differentiation between non/slowly progressive or transient forms of precocious puberty and rapidly progressive central precocious puberty.

Ultrasound in Obstetrics and Gynecology, 2003

Objectives Treatment with growth hormone (GH), alone or in combination with oxandrolone, is used ... more Objectives Treatment with growth hormone (GH), alone or in combination with oxandrolone, is used in patients affected by Turner syndrome to improve growth velocity and adult height. Since GH interacts with gonadotropins in the stimulation of the human ovary, the aim of our study was to evaluate the possible effects of GH administration on uterine and ovarian characteristics.

Prenatal Diagnosis, 2012

The objective of the study was to evaluate the association between placental histological pattern... more The objective of the study was to evaluate the association between placental histological patterns and umbilical artery (UA) Doppler velocimetry in pregnancies complicated by fetal growth restriction (FGR). A cohort of 126 FGR pregnancies was followed according to a standard protocol. Placental lesions were diagnosed according to consensus nomenclature and standardized criteria. Pulsatility index was normal in 45 (35.7%) and increased in 44 (34.9%) women. End-diastolic UA Doppler flow was absent in 27 (21.4%) and reversed in 10 (7.9%). Fifty-four women (42.9%) had preeclampsia. In preeclampsia, increasing Doppler abnormalities, from normal to reversed UA end-diastolic flow, were directly associated only with an increased number of placental syncytial knots. In normotensive pregnancies, Doppler abnormalities were associated with increased intervillous fibrin deposits, villous hypoplasia, syncytial knots, placental site giant cells, immature intermediate trophoblast, and with pattern of lesions indicating superficial implantation and maternal vascular underperfusion. In the whole cohort, increase of syncytial knots [odds ratio (OR) = 28.7; 95% confidence interval (CI) = 2.75-298.5], intervillous fibrin deposits (OR = 2.1; 95% CI = 1.04-4.28), placental site giant cells (OR = 3.0; 95% CI = 1.05-8.84), and patterns suggesting maternal underperfusion (OR = 2.9; 95% CI = 1.0-7.1) were independently associated with increased rates of absent/reversed UA end-diastolic flow. In pregnancies complicated by FGR, abnormalities of UA Doppler velocimetry were associated with placental lesions indicating superficial implantation and maternal vascular underperfusion.

Journal of Perinatal Medicine, 2000

To correlate placental pathologic lesions, as defined by the Society for Pediatric Pathology, to ... more To correlate placental pathologic lesions, as defined by the Society for Pediatric Pathology, to the severity of the ratio of the pulsatility Doppler index (PI) of the fetal middle cerebral artery to that of the umbilical artery (cerebroplacental ratio, CPR). A cohort-study of 176 singleton pregnancies complicated by fetal growth restriction (FGR). The mean values of gestational age, birth weight and CPR of the entire cohort were 33.9±3.6 weeks, 1552±561 g, and 1.33±0.68, respectively. In ordered logistic regression analysis, after adjustment for potential confounders, muscularised arteries (Odds Ratio [OR]=3.14; 95% confidence intervals [CI]=1.58-6.28, P=0.001), mural hypertrophy (OR=2.35; 95% CI=1.26-4.4, P=0.008), immature intermediate trophoblast (OR=2.0; 95% CI=1.07-3.71, P=0.03) and maternal vascular underperfusion (OR=2.32; 95% CI=1.25-4.23, P=0.007) were the only parameters associated with severity of CPR. The correlation between placental histological findings indicating maternal underperfusion and placental occlusion suggest that forced centralization of fetal circulation in FGR could be at least partially attributable to the hemodynamic consequences of increased placental vascular resistance.

International Urogynecology Journal, 2007

We performed a historical cohort study of 62 consecutive patients who underwent abdomino-perineal... more We performed a historical cohort study of 62 consecutive patients who underwent abdomino-perineal vaginal re-construction with a segment of the sigmoid colon during a 25-year period. A dedicated database was reviewed for the aetiology of vaginal malformation, surgical complications and post-operative follow-up. Follow-up visits were scheduled 2, 6 and 12 months after discharge from hospital and annually thereafter. Fifty-eight (93.5%) patients were diagnosed as having Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) and four (6.5%) had undergone previous demolitive surgery for gynaecologic malignancy. The mean operating time was 145 min (range 95 to 250 min). The mean hospital stay was 8.3 days (range 5 to 23 days). Post-operative complications requiring additional surgery occurred in 3 (4.8%) patients and were a case of necrotising fascitiis with leakage of the bowel anastomosis, a case of bowel occlusion and a case of neovaginal prolapse. The mean follow-up was 11.3 years (range 3 months to 24 years). We recorded 5 cases (8.1%) of sigmoid graft shrinkage treated successfully by dilation. The time interval between sigmoid vaginoplasty and first intercourse was 4 months (range 2 months to 4 years). During the follow-up, 32 (51.6%) women reported regular and 30 (48.4%) women reported occasional sexual intercourse; 80.6% (50/62) were "satisfied" with the surgical procedure. In this large series, laparotomic sigmoid vaginoplasty was a safe and acceptable technique to treat congenital absence of the vagina. This procedure allowed early sexual intercourse and was associated with a low incidence of shrinkage and a high rate of patients' satisfaction.

Fetal Diagnosis and Therapy, 2009

To evaluate the risk of fetal growth restriction (FGR) associated with first-trimester maternal s... more To evaluate the risk of fetal growth restriction (FGR) associated with first-trimester maternal serum concentrations of pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG). A longitudinal study of 2,178 women who underwent first-trimester evaluation of serum PAPP-A and free beta-hCG. FGR was defined as a decrement of the fetal abdominal circumference to below the 10th percentile of our standard growth curve in the presence of Doppler signs of impaired placental perfusion. Logistic regression was used to compute multivariable odds ratios and the estimated prevalences of outcomes associated with first-trimester serum marker concentrations. The prevalences of small for gestational age (SGA, <10th percentile birth-weight) neonates and FGR were significantly higher among women with serum PAPP-A concentrations below the 10th percentile than in controls: 40/206 compared to 183/1,928, for SGA, adjusted odds ratio = 2.1, 95% confidence intervals (CI) 1.4-3.03; 24/75 compared to 182/1,900, for FGR, adjusted odds ratio = 3.9, 95% CI 2.3-6.5. The adjusted prevalences of FGR and SGA among women with simultaneous low first-trimester values of PAPP-A and free beta-hCG were 0.21 (95% CI 0.13-0.33) and 0.26 (95% CI 0.17-0.36), respectively. Low first-trimester maternal serum PAPP-A concentrations are significantly associated with reduced fetal size and increased risk of FGR with Doppler signs of impaired placental perfusion.