Reference Charts for Fetal Cerebellar Vermis Height: A Prospective Cross-Sectional Study of 10605 Fetuses.

OBJECTIVE: To establish reference charts for fetal cerebellar vermis height in an unselected population. METHODS: A prospective cross-sectional study between September 2009 and December 2014 was carried out at ALTAMEDICA Fetal-Maternal Medical Centre, Rome, Italy. Of 25203 fetal biometric measurements, 12167 (48%) measurements of the cerebellar vermis were available. After excluding 1562 (12.8%) measurements, a total of 10605 (87.2%) fetuses were considered and analyzed once only. Parametric and nonparametric quantile regression models were used for the statistical analysis. In order to evaluate the robustness of the proposed reference charts regarding various distributional assumptions on the ultrasound measurements at hand, we compared the gestational age-specific reference curves we produced through the statistical methods used. Normal mean height based on parametric and nonparametric methods were defined for each week of gestation and the regression equation expressing the height of the cerebellar vermis as a function of gestational age was calculated. Finally the correlation between dimension/gestation was measured. RESULTS: The mean height of the cerebellar vermis was 12.7mm (SD, 1.6mm; 95% confidence interval, 12.7-12.8mm). The regression equation expressing the height of the CV as a function of the gestational age was: height (mm) = -4.85+0.78 x gestational age. The correlation between dimension/gestation was expressed by the coefficient r = 0.87. CONCLUSION: This is the first prospective cross-sectional study on fetal cerebellar vermis biometry with such a large sample size reported in literature. It is a detailed statistical survey and contains new centile-based reference charts for fetal height of cerebellar vermis measurements.

Predictive value of pregnancy-associated plasma protein-A (PAPP-A) and free beta-hCG on fetal growth restriction: results of a prospective study.

PURPOSE: Low levels of plasmatic pregnancy-associated plasma protein-A (PAPP-A) and high levels of free-beta human chorionic gonadotropin (beta-hCG) could influence the outcome of pregnancy. The objective of this study is to assess the correlation between PAPP-A and free beta-hCG and birth weight. MATERIALS AND METHODS: Prospective follow-up study performed on 3332 patients in the first trimester of pregnancy who were subjected to a screening test focused on evaluation of fetal aneuploidy (SCA-TEST). The values of PAPP-A and free beta-hCG were both analyzed as raw values and subsequently converted to a multiple of the median (MoM). Statistical analysis was performed using SPSS version 17.0.1 (SPSS Inc., Chicago, USA). RESULTS: The incidence of "small for gestational age" in patients with PAPP-A MoM <1st and <5th ‰ was statistically significant (12 and 9.8 %; p < 0.0001). Also statistically significant data have been highlighted about free beta MoM > 95th ‰ (7 %; p = 0.03). The values of PAPP-A MoM > 99th ‰ are significantly correlated with an increased risk of "large for gestational age" (16.7 %; p < 0.0001). CONCLUSION: Our study demonstrates that specific values of PAPP-A and free beta-hCG could identify the risk of low or high birth weight since the first trimester of pregnancy.

Supplementation with a dietary multicomponent (Lafergin(®)) based on Ferric Sodium EDTA (Ferrazone(®)): results of an observational study.

During pregnancy, iron deficiency anemia is recognized as a specific risk factor for both adverse maternal and perinatal outcome. We decided to test the hypothesis that the daily administration of Lafergin(®), a dietary multicomponent based on Ferrazone(®) (Ferric Sodium EDTA), Lactoferrin, Vitamin C and Vitamin B12, from first trimester of pregnancy until the end of gestation, may significantly reduce, in anemic women, the severity of anemia compared to controls who received ferrous sulfate or liposomal iron.

Comparison between modified Misgav-Ladach and Pfannenstiel-Kerr techniques for Cesarean section: review of literature.

In the last decades cesarean section rates increased in many countries becoming the most performed intraperitoneal surgical procedure. Despite its worldwide spread, a general consensus on the most appropriate technique to use has not yet been reached. The operative technique performed is made chiefly on the basis of the individual experience and preference of operators, the characteristics of patients, timing and urgency of intervention. We compared the two most known and used techniques, modified Misgav-Ladach and traditional Pfannenstiel-Kerr, and analyzed their impact on primary, short- and long-term outcomes and outcome related to health service use.

Tubal primary metastatic choriocarcinoma coexistent with a viable early pregnancy: a case report.

INTRODUCTION: fallopian tube choriocarcinoma coexistent with viable intrauterine pregnancy is an extremely rare condition. CASE REPORT: we present the first case reported in literature of tubal choriocarcinoma coexistent with viable intrauterine pregnancy detected at early gestational age (20 weeks) and successfully managed by seriate monitoring of maternal and fetal health status until 31 weeks, then treated by cesarean section followed by etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) chemotherapy protocol. CONCLUSIONS: the outcome was favorable for both the mother and her fetus.

Retrospective study evaluating the performance of a first-trimester combined screening for trisomy 21 in an Italian unselected population.

OBJECTIVES: to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. METHODS: a retrospective validation of first-trimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free ß-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11(+0) and 13(+6) weeks of gestation, between April 2007 and December 2008. RESULTS: of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2-100; false-positive rate (FPR) 4.7%, 95% CI 3.9-5.4; false-negative rate (FNR) 17.6%, 95% CI 0-35.8%]. CONCLUSION: in our study population the detection rate for trisomy 21, using the combined risk calculation based on maternal age, fetal NT, maternal PAPP-A and free ß-hCG levels, was superior to the application of either parameter alone. The algorithm has been validated for first trimester screening in the Italian population.

Comparative study of aCGH and Next Generation Sequencing (NGS) for chromosomal microdeletion and microduplication screening.

BACKGROUND: prenatal genetic diagnosis of rare disorders is undergoing in recent years a significant enhancement through the application of methods of massive parallel sequencing. Despite the quantity and quality of the data produced, just few analytical tools and software have been developed in order to identify structural and numerical chromosomal anomalies through NGS, mostly not compatible with benchtop NGS platform and routine clinical diagnosis. METHODS: we developed technical, bioinformatic, interpretive and validation pipelines for Next Generation Sequencing to identify SNPs, indels, aneuploidies, and CNVs (Copy Number Variations). RESULTS: we show a new targeted resequencing approach applied to prenatal diagnosis. For sample processing we used an enrichment method for 4,813 genes library preparation; after sequencing our bioinformatic pipelines allowed both SNPs analysis for approximately thirty diseases or diseases family involved in fetus development and numerical chromosomal anomalies screening. CONCLUSIONS: results obtained are compatible with those obtained through the gold standard technique, aCGH array, moreover allowing identification of genes involved in chromosome deletions or duplications and exclusion of point mutation on allele not affected by chromosome aberrations.

Placental mesenchymal dysplasia, a case of intrauterine sudden death in a normal-sized fetus.

INTRODUCTION: placental mesenchymal dysplasia (PMD) is a rare placental anomaly characterized by placentomegaly and grape-like vesicles which resemble molar pregnancy. CASE: we report the case of 33-year-old woman (1-gravid) who visited our clinic at 11 weeks of gestation due to a suspected molar pregnancy. Ultrasound examination showed an enlarged placenta with multiple vesicular lesions. Maternal human chorionic gonadotropin level was normal and chorionic villus sampling showed a normal male karyotype (46 XY). The fetus exhibited no specific anomalies and fetal growth was normal during pregnancy with no signs of fetal suffering. At 31 weeks, the pregnancy ended owing to intrauterine fetal death (IUFD). The patient delivered a normal-sized male fetus (1800 g) with no definite anomalies. A pathological examination led to a diagnosis of placental mesenchymal dysplasia. CONCLUSION: in the presence of placental ultrasound anomalies with no other sign of fetal suffering, the pregnancy should be considered at risk and, therefore, should be monitored carefully including the option of hospitalization.

Uterine fibroids and risk for complications following second-trimester amniocentesis.

OBJECTIVE: To compare the abortion rate and preterm premature rupture of membranes (PPROM) after amniocentesis in women who have undergone antibiotic prophylaxis with uterine fibroids and control. STUDY DESIGN: Retrospective study using the Antibiotic Prophylaxis before Second-Trimester Genetic Amniocentesis trial database carried out between January 1999 and December 2005 at the Artemisia Fetal-Maternal Medical Center (Rome, Italy). All women underwent antibiotic prophylaxis before amniocentesis. A follow-up within 4 weeks from the procedure was available. RESULTS: A total of 2,497 of 21,219 (11.8%) women with uterine fibroids were identified. The rate of abortion was 2 of 2,497 (0.08%) in women with fibroids and 4 of 18,722 (0.03%) in women without fibroids (p = 0.42). The rate of PPROM was 4 of 2,497 (0.16%) in women with fibroids and 10 of 18,722 (0.05%) in women without fibroids (p = 0.12). CONCLUSION: The risk for abortion and PPROM does not increase in the presence of uterine fibroids in women who have undergone antibiotic prophylaxis.

Pharmacotherapy of haemophilia A.

INTRODUCTION: Haemophilia A is due to factor VIII (FVIII) deficiency. The main treatment is replacement therapy with FVIII concentrates. However, these concentrates carried a high risk of blood-borne viral infections and still have a high risk of inducing anti-FVIII inhibitors. AREAS COVERED: An overview of products available and therapeutic options for haemophilia A management in order to help in decision making. A literature search using Medline with the keywords: 'haemophilia', 'factor VIII', 'therapy', 'inhibitor', 'concentrate', 'bleeding', 'prophylaxis', 'on demand', 'plasma-derived', 'recombinant', 'coagulation factors', 'immunotolerance' was performed. The years 1960 - 2010 are included. EXPERT OPINION: Progress in management of patients with haemophilia A has allowed increased life expectancy and quality of life. There is evidence that prophylaxis prevents or, at least, slows down arthropathy development when started early in childhood. FVIII concentrates have achieved high levels of blood-borne pathogen safety. However, treatment is frequently complicated by development of FVIII-neutralizing inhibitors, which prevent control of bleeding and predispose to a high morbidity and mortality risk. Bypassing agents are effective in bleeding treatment in a high percentage of cases. Prophylaxis with bypassing agents and their use in combination are offering opportunities in management of inhibitor patients. More evidence is necessary to understand how to prevent and manage this complication.

Antibiotic prophylaxis before second-trimester genetic amniocentesis (APGA): a single-centre open randomised controlled trial.

OBJECTIVE: To compare procedure-related pregnancy loss after second-trimester genetic amniocentesis in women given an antibiotic prophylaxis and controls. METHODS: Prospective, open randomised controlled single-centre study between January 1999 and December 2005 at Artemisia Fetal Maternal Medical Centre. A follow-up within 4 weeks after the procedure was done.Of 36,347 eligible women, 1424 refused to participate and 34,923 were enrolled and randomised with unequal chance of selection, 21,991 were assigned to treatment group and 12,932 were assigned to the control group, and did not receive any placebo. Oral azithromycin, 500 mg per day, was administered 3 days before amniocentesis. The primary endpoint was the procedure-related pregnancy loss. The secondary endpoint was the rate of preterm premature rupture of membranes. RESULTS: The rate of abortion related to the amniocentesis was 7/21 219 women (0.03%, 95% CI 0.009-0.057) in the intervention group, and 36/12 529 (0.28%, 0.28-0.30) in controls (p = 0.0019). The rate of preterm premature rupture of membranes was 14/21 219 (0.06%, 0.031-0.101) in the intervention group, and 140/12 529 (1.12%, 0.94-1.30) in the control group (p = 0.001). CONCLUSIONS: Antibiotic prophylaxis before second-trimester amniocentesis reduced the risk of abortion and of rupture of the membranes.

Prenatal screening of Cystic Fibrosis: a single centre experience.

OBJECTIVE: The gene responsible for the pathogenesis of cystic fibrosis has been known for over 15 years and represent the most common autosomal recessive disease in the european population. We aimed to investigate the incidence of this condition during fetal life. METHODS: In the past 10 years we examined in our centre 25393 fetuses of women underwent to amniocentesis. We carried out the examination of the most frequent mutations which enable, according to the literature data, the identification of almost 80% of the affected alleles. RESULT: We identified 922 heterozygous and 9 homozygous for the mutation. The frequency of heterozygousin the examined sample was 1/27,5 while that of the affected was 1/2821. CONCLUSION: We encourage new thoughts regarding the diagnostic validity of the most frequent panel of mutations among the italian population in order to exclude never encountered mutations and the insertion of other more significant mutations.

Two-dimensional fetal echocardiography: where we are.

Congenital Heart Disease (CHD) is the most common severe congenital abnormality in the newborn and the cause of over half the deaths from congenital anomalies in childhood. Prenatal diagnosis, possible as early as 15 weeks of gestation, allows physicians and families the greatest number of therapeutic options, and can improve the postnatal outcome. There are several potential indications for performing such examination. Evaluation of the heart in the setting of restricted fetal growth or fetal distress is often recommended. Whenever extracardiac anomalies are detected during fetal ultrasound examination or in presence of chromosomal abnormalities detected with amniocentesis, cardiac assessment is mandatory. The test should also be performed as part of the assessment of fetal arrhythmias. Finally, whenever congenital heart disease is suspected for other reasons, such as maternal exposure to teratogenic substances or a parental history of previous children with congenital lesions, the examination should be considered. The performance of a fetal echocardiogram requires experience and a systematic approach. Guidelines for training have been formulated, and only qualified individuals should perform this highly specialized examination. A description of the techniques of heart examination is presented below.

Prenatal Aneuploidies Computerized Screening (SCA TEST): a pilot study on 1000 women.

The SCA-TEST, Prenatal Aneuploidies Screening, is an innovating program with very articulated and differentiated calculation potentials. It is a software which allows executing a sequence-like rational screening involving the ultrasound study of the first and second trimester. The program enables to execute a complete and different- levels combined screening, through very sophisticated mathematic analysis methods. In particular, it enables to make: a first trimester screening combining it with nuchal translucency, and biochemical parameters of free beta-hCG and PAPP-A; a second trimester screening by the evaluation of up to 6 biometric parameters (biparietal diameter, cranial circumferentia, femur, humerus, pyelectasis and plica nucalis), and up to 7 associated morphologic parameters (hyperechogenic bowel, cardiac foci, interventricular defect, pericardial effusion, tricuspid valve regurgitation, right/left heart disproportion, and structural abnormalities). The purpose of the study was to present the performance of the SCA TEST in the second trimester of pregnancy through the evaluation of a prospective study performed in the period between April 2007 and December 2007 on 1000 women who underwent the SCA TEST followed by amniocentesis. Studying all the cardiovascular and non-cardiovascular markers, SCA TEST made it possible to identify 62.5% fetuses affected by Trisomy 21 with a specificity of 94.6%, and a 5.4% of false positive. Considering only women older than 35 years the detection rate reaches 80% with a 7.8% of false positive. The statistical analysis confirmed that the second trimester screening gives essential information regarding the aneuploidia risks in particular in high risk women, and in those who did not perform first trimester screening.