Fetal MR Imaging Anatomy of the Transverse Temporal Gyrus (Heschl Gyrus).

BACKGROUND AND PURPOSE: The human auditory system develops early in fetal life. This retrospective MR imaging study describes the in vivo prenatal anatomic development of the transverse temporal gyrus (Heschl gyrus) site of the primary auditory cortex. MATERIALS AND METHODS: Two hundred seventy-two MR imaging studies of the fetal brain (19-39 weeks' gestational age) acquired from a single institution's 1.5T scanner were retrospectively examined by 2 neuroradiologists. MR imaging with pathologic findings and extreme motion artifacts was excluded. Postnatal Heschl gyrus landmarks were used as a reference on T2-weighted ssFSE sequences in the 3 orthogonal planes. The frequency of the Heschl gyrus was reported for gestational age, hemisphere, and planes. Descriptive statistics and a McNemar test were performed. RESULTS: Two hundred thirty MR imaging studies were finally included. Fetal brains were divided by gestational age (in weeks) into 8 groups (parentheses indicate the number of observations): 19-21 (29), 22-23 (32), 24-25 (21), 26-27 (18), 28-29 (35), 30-31 (30), 32-33 (33) and >34 (32). The Heschl gyrus appeared on MR imaging between 24 and 25 weeks' gestational age (14/21 fetuses, 67%) and was visible in all fetuses after the 28th week of gestation. By its appearance (24-28 weeks' gestational age), the sagittal plane was the most sensitive in its detectability. After 28-29 weeks' gestational age, the Heschl gyrus was evident in all acquisition planes and fetuses. Results did not differ between hemispheres. CONCLUSIONS: The Heschl gyrus appears on MR imaging at 24-25 weeks' gestational age, paralleling the functional activation of the auditory system. We propose the Heschl gyrus as an early additional MR imaging marker of fetal brain development.

Comparison of practice vs theory model training for vacuum-assisted delivery: A randomized controlled trial.

OBJECTIVE: To assess the effect of two modalities of simulation training on acquisition/retention of skills for performing operative vaginal delivery. DESIGN: Randomized, controlled, single-centre study. SETTING: A tertiary referral hospital in Italy. PARTICIPANTS: Twenty residents from a single university programme and two young specialists. INTERVENTION: Group 1 had an individual training session with a single senior specialist using a fixed simulator model. After the session, trainees watched a pre-recorded 1-h lecture on vacuum-assisted operative vaginal delivery. Group 1 repeated the simulator session using the same test after 8-12 weeks and 12 months. Group 2 watched the pre-recorded lecture then undertook the same sessions as Group 1. Video recordings of all test performances were evaluated by five specialists in a blinded manner. MAIN OUTCOME MEASURE: Each procedure was evaluated using a Global Rating Scale (GRS), scored with 0-5 points for each item on an Objective Structured Assessment of Technical Skills (OSATS) dataset with seven items (total 35 points). OSATS were evaluated over time, compared for the whole population, and weighted for route and year of residency. The primary outcome was comparison of the effectiveness of training between the two groups based on year of residency by assessing videos of the baseline test and GRS for OSATS scores. The secondary outcome was overall retention of skills at 8-12 weeks and 12 months. RESULTS: Twenty-two participants were recruited and randomized to either Group 1 (n = 11) or Group 2 (n = 11). Five participants did not complete follow-up. The primary outcome of GRS for OSATS scores at time 0 differed significantly between groups for total GRS score, and 'Call for help' and 'Explanation to woman and relatives' item scores (p = 0.002 and p = 0.007, respectively). In a multiple linear regression analysis, OSATS scores were not independently influenced by year of residency. At 8-12-week follow-up, the 'Call for help' item score showed a significant improvement in Group 1 (p = 0.018), although this was not confirmed when year of residency was included as an independent variable. At 12-month follow-up, none of the item scores demonstrated a significant change (p = 0.033). Year of residency did not influence the difference between groups. One-way analysis of variance found significant differences between the groups for 'Localization of the flexion point' (p = 0.005), 'Traction of vacuum cup' (p = 0.039) and 'Use of second hand of the operator' (p = 0.009) item scores and total GRS score (p = 0.007). The values weighted by year of residency did not demonstrate any significant difference. The secondary outcomes evaluated all the candidates of both groups for retention of technical skills over time. A significant effect of time was found for total GRS score (p < 0.001) and OSATS item scores. CONCLUSIONS: Independent of the sequence of theoretical teaching and simulation training, trainees demonstrated high retention - and, actually, improvement - of technical skills for operative vaginal delivery at 12-month follow-up.

The influence of different inositol stereoisomers supplementation in pregnancy on maternal gestational diabetes mellitus and fetal outcomes in high-risk patients: a randomized controlled trial.

Objective: To identify the effects of different dietary inositol stereoisomers on insulin resistance and the development of gestational diabetes mellitus (GDM) in women at high risk for this disorder.Design: A preliminary, prospective, randomized, placebo controlled clinical trial.Participants: Nonobese singleton pregnant women with an elevated fasting glucose in the first or early second trimester were studied throughout pregnancy.Intervention: Supplementation with myo-inositol, d-chiro-inositol, combined myo- and d-chiro-inositol or placebo.Main outcome measure: Development of GDM on a 75 grams oral glucose tolerance test at 24-28 weeks' gestation. Secondary outcome measures were increase in BMI, need for maternal insulin therapy, macrosomia, polyhydramnios, neonatal birthweight and hypoglycemia.Results: The group of women allocated to receive myo-inositol alone had a lower incidence of abnormal oral glucose tolerance test (OGTT). Nine women in the control group (C), one of the myo-inositol (MI), five in d-chiro-inositol (DCI), three in the myo-inositol/D-chiro-inositol group (MI/DCI) required insulin (p = .134). Basal, 1-hour, and 2 hours glycemic controls were significantly lower in exposed groups (p < .001, .011, and .037, respectively). The relative risk reduction related to primary outcome was 0.083, 0.559, and 0.621 for MI, DCI, and MI/DCI groups.Conclusions: This study compared the different inositol stereoisomers in pregnancy to prevent GDM. Noninferiority analysis demonstrated the largest benefit in the myo-inositol group. The relevance of our findings is mainly related to the possibility of an effective approach in GDM. Our study confirmed the efficacy of inositol supplementation in pregnant women at risk for GDM.

Prenatal planning of placenta previa: diagnostic accuracy of a novel MRI-based prediction model for placenta accreta spectrum (PAS) and clinical outcome.

PURPOSE: To investigate the diagnostic accuracy of MRI for placenta accreta spectrum (PAS) and clinical outcome prediction in women with placenta previa, using a novel MRI-based predictive model. METHODS: Thirty-eight placental MRI exams performed on a 1.5T scanner were retrospectively reviewed by two radiologists in consensus. The presence of T2 dark bands, myometrial thinning, abnormal vascularity, uterine bulging, placental heterogeneity, placental protrusion sign, placental recess, and percretism signs was scored using a 5-point scale. Pathology and clinical intrapartum findings were the standard of reference for PAS, while intrapartum/peripartum bleeding and emergency hysterectomy defined the clinical outcome. Receiver-operating characteristic (ROC) analysis and discriminant function analysis were performed to test the predictive power of MRI findings for both PAS and clinical outcome prediction. RESULTS: Abnormal vascularity and percretism signs were the two most predictive MRI features of PAS. The area under the curve (AUC) of the predictive function was 0.833 (cutoff 0.39, 67% sensitivity, 100% specificity, p = 0.001). Percretism signs and myometrial thinning were the two most predictive MRI features of poor outcome. AUC of the predictive function was 0.971 (cutoff - 0.55, 100% sensitivity, 77% specificity, p < 0.001). CONCLUSION: The diagnostic accuracy of MRI, especially considering the combination of the most predictive MRI findings, is higher when the target of the prediction is the clinical outcome rather than the PAS.

Effect of inositol stereoisomers at different dosages in gestational diabetes: an open-label, parallel, randomized controlled trial.

AIMS: Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy. The aim of the study is to compare the effect of different dosages of inositol stereoisomers supplementation on insulin resistance levels and several maternal-fetal outcomes in GDM women. METHODS: Participants were randomly allocated to receive daily: 400 mcg folic acid (control treatment), 4000 mg myo-inositol plus 400 mcg folic acid (MI treatment), 500 mg D-chiro-inositol plus 400 mcg folic acid (DCI treatment) or 1100/27.6 mg myo/D-chiro-inositol plus 400 mcg folic acid (MI plus DCI treatment). The homeostasis model assessment of insulin resistance (HOMA-IR) was measured at the diagnosis of GDM and after 8 weeks of treatment. Secondary outcomes, obstetric outcomes and any maternal or fetal complication at delivery were also collected. RESULTS: Eighty GDM women were assigned to one of the four arms of study (20 per arm). A significant delta decrease in HOMA-IR index was found in subjects of MI group without insulin therapy compared to control group (p < 0.001). A lower variation in average weight gain (at delivery vs pre-pregnancy and OGTT period) was detected in MI group vs control group (p = 0.001 and p = 0.019, respectively). Moreover, women exposed to MI and MI plus DCI required a significantly lower necessity of an intensified insulin treatment. Women of the control group had newborns with higher birth weight compared with women treated with inositol (p = 0.032). CONCLUSIONS: Our study provides interesting but preliminary results about the potential role of inositol stereoisomers supplementation in the treatment of GDM on insulin resistance levels and several maternal-fetal outcomes. Further studies are required to examine the optimal and effective dosages of different inositol supplements. CLINICAL TRIAL REG. NO.: NCT02097069, ClinicalTrial.gov.

Nutrigenetic variants and cardio-metabolic risk in women with or without gestational diabetes.

AIM: Gestational diabetes mellitus (GDM) is the most frequent metabolic disorder in pregnancy and it can be considered a silent risk associated to T2DM and CVD later in life. The aim of this study was to investigate the association of clinical parameters with nine single nucleotide polymorphisms (SNPs) involved with nutrients and metabolism in women with or without GDM in order to identify potential routine clinical markers for early prevention. METHODS: Nine gene variants associated with nutrients and metabolism, namely PPARG2 rs1801282 (C > G); PPARGC1A rs8192678 (C > T); TCF7L2 rs7903146 (C > T); LDLR rs2228671 (C > T); MTHFR rs1801133 (C > T); APOA5 rs662799 (T > C); GCKR rs1260326 (C > T); FTO rs9939609 (T > A); MC4R rs17782313 (T > C) were genotyped in 104 GDM cases and 124 controls using High Resolution Melting (HRM) analysis. RESULTS: The genetic variant rs7903146 (C > T) in TCF7L2 gene showed a strong association with GDM risk (OR: 2.56; 95% CI: [1.24-5.29]). Moreover, a significant correlation was observed between lipid parameters and polymorphisms in other genes, namely PPARG2 [p = 0,03], APOA5 [p = 0,02], MC4R [p = 0,03], LDLR [p = 0,04] and FTO [p = 0,03]. In addition, rs17782313 variant, mapped close to MC4R gene, was associated to BMI in pre-pregnancy [p = 0,02] and at the end of pregnancy [p = 0,03] in GDM group. CONCLUSION: In our study, we found significant associations between routine clinical parameters and some gene variants connected with nutrients and metabolism in women with GDM. These results can provide useful information to develop effective tools and possible personalized intervention strategies in a timely manner.

Early Subclinical Atherosclerosis in Gestational Diabetes: The Predictive Role of Routine Biomarkers and Nutrigenetic Variants.

Gestational diabetes mellitus (GDM) can be considered a silent risk for out-of-pregnancy diabetes mellitus (DM) and cardiovascular disease (CVD) later in life. We aimed to assess the predictive role of 3rd trimester lipid profile during pregnancy for the susceptibility to markers of subclinical atherosclerosis (CVD susceptibility) at 3 years in a cohort of women with history of GDM. A secondary aim is to evaluate the usefulness of novel nutrigenetic markers, in addition to traditional parameters, for predicting early subclinical atherosclerosis in such women in order to plan adequate early prevention interventions. We assessed 28 consecutive GDM women in whom we collected socio-demographic characteristics and clinical and anthropometric parameters at the 3rd trimester of pregnancy. In a single blood sample, from each patient, we assessed 9 single nucleotide polymorphisms (SNPs) from 9 genes related to nutrients and metabolism, which were genotyped by High Resolution Melting analysis. All women then attended a 3-year-postpartum follow-up and on that occasion performed an oral glucose tolerance test (OGTT, with 75 g oral glucose), the measurement of carotid artery intima-media thickness (cIMT), and analyses of metabolic parameters. In addition, we evaluated the physical activity level and the adherence to Mediterranean diet (MedDiet) using the International Physical Activity Questionnaire (IPAQ-short version) and PREDIMED questionnaires. We found an association between 3rd trimester triglycerides and cIMT (p = 0.014). We also found significant associations between the APOA5 CC genotype and cIMT after adjustments for age and body mass index (p = 0.045) and between the interaction CC APOA5/CC LDLR and cIMT (p = 0.010). At the follow-up, the cohort also featured a mean BMI in the overweight range and a high mean waist circumference. We found no difference in the MedDiet adherence, physical activity, and smoking but an inverse correlation between the PREDIMED and the IPAQ scores with the IMT. In conclusion, this preliminary study provides insight into the predictive role of lipid profile during pregnancy and of some genetic variants on cIMT taken as a parameter of subclinical CVD susceptibility in GDM.

An 11.4-Mb Interstitial Deletion in a Fetus with No Apparent Phenotypic Alterations.

A prenatal case of a de novo interstitial deletion distal to 8q24 was reported. Ultrasound examination and postmortem evaluation demonstrated no apparent phenotypic alterations. Array CGH showed an 11.4-Mb loss in chromosome 8 ranging from 8q24.13 to 8q24.23. This case partially overlaps the 2 cases previously described in the literature.

Molecular Analysis of a Genetic Variants Panel Related to Nutrients and Metabolism: Association with Susceptibility to Gestational Diabetes and Cardiometabolic Risk in Affected Women.

Gestational diabetes mellitus (GDM) is the most frequent metabolic disorder in pregnancy. Women with a GDM history are at increased risk of developing diabetes and cardiovascular diseases. Studies have demonstrated a significant correlation between several genes involved in the metabolic pathway of insulin and environmental factors. The aim of this study was to investigate the relationship between clinical parameters in GDM and variants in genes involved with nutrients and metabolism. Several variants PPARG2 rs1801282 (C>G); PPARGC1A rs8192678 (C>T); TCF7L2 rs7903146 (C>T); LDLR rs2228671 (C>T); MTHFR rs1801133 (C>T); APOA5 rs662799 (T>C); GCKR rs1260326 (C>T); FTO rs9939609 (T>A); MC4R rs17782313 (T>C) were genotyped in 168 pregnant Caucasian women with or without GDM by High Resolution Melting (HRM) analysis. A significant correlation was observed between TT genotype of TCF7L2 gene and increased risk of GDM (OR 5.4 [95% CI 1.5-19.3]). Moreover, a significant correlation was observed between lipid parameters and genetic variations in additional genes, namely, PPARG2 [p = 0,02], APOA5 [p = 0,02], MC4R [p = 0,03], LDLR [p = 0,01], and FTO [p = 0,02]. Our findings support the association between TCF7L2 rs7903146 variant and an increased GDM risk. Results about the investigated genetic variants provide important information about cardiometabolic risk in GDM and help to plan future prevention studies.

Aneuploidy screening using circulating fetal cells in maternal blood by dual-probe FISH protocol: a prospective feasibility study on a series of 172 pregnant women.

BACKGROUND: A long sought goal in medical genetics has been the replacement of invasive procedures for the detection of chromosomal aneuploidies by isolating and analyzing fetal cells or free fetal DNA from maternal blood, avoiding risk to the fetus. However, a rapid, simple, consistent, and low-cost procedure suitable for routine clinical practice has not yet been achieved. The purpose of this study was to assess the feasibility of predicting fetal aneuploidy by applying our recently established dual-probe FISH protocol to fetal cells isolated and enriched from maternal blood. METHODS: A total of 172 pregnant women underwent prospective testing for fetal aneuploidy by FISH analysis of fetal cells isolated from maternal blood. Results were compared with the karyotype determined through invasive procedures or at birth. RESULTS: Seven of the samples exhibited fetal aneuploidy, which was confirmed by invasive prenatal diagnosis procedures. After enrichment for fetal cells, the frequency of trisomic cells was at least double in samples from aneuploid pregnancies (range 0.38-0.90%) compared to samples from normal pregnancies (≤0.18%). One false negative result was also obtained. CONCLUSIONS: Noninvasive prenatal aneuploidy screening using fetal cells isolated from maternal blood is feasible and could substantially reduce the need for invasive procedures.

Myo-Inositol Supplementation to Prevent Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a common complication characterized by increased insulin resistance, and by increased risk for adverse pregnancy outcomes affecting both the mother and the fetus. International guidelines describe optimal ways to recognize it, and the recommended treatment of patients affected to reduce adverse outcomes. Improving insulin resistance could reduce incidence of GDM and its complications. Recently, a few trials have been published on the possible prevention of GDM. Inositol has been proposed as a food supplement that might reduce gestational diabetes incidence in high-risk pregnant women.

Effect of dietary myo-inositol supplementation in pregnancy on the incidence of maternal gestational diabetes mellitus and fetal outcomes: a randomized controlled trial.

OBJECTIVE: To test the hypothesis that dietary myo-inositol may improve insulin resistance and the development of gestational diabetes mellitus (GDM) in women at high risk of this disorder. DESIGN: A prospective, randomized, double-blind, placebo controlled clinical trial, pilot study. PARTICIPANTS: Non-obese singleton pregnant women with an elevated fasting glucose in the first or early second trimester were studied throughout pregnancy. INTERVENTION: Supplementation with myo-inositol or placebo during pregnancy. MAIN OUTCOME MEASURE: Development of GDM on a 75 g oral glucose tolerance test at 24-28 weeks' gestation. Secondary outcome measures were increased in BMI, need for maternal insulin therapy, macrosomia, polyhydramnios, neonatal birthweight and hypoglycemia. RESULTS: Thirty-six women were allocated to receive myo-inositol and 39 placebo. The incidence of GDM in mid-pregnancy was significantly reduced (p = 0.001) in women randomized to receive myo-inositol compared to placebo (relative risk 0.127). Women randomized to receive myo-inositol also required less insulin therapy, delivered at a later gestational age, had significantly smaller babies with fewer episodes of neonatal hypoglycemia. CONCLUSIONS: Myo-inositol supplementation in pregnancy reduced the incidence of GDM in women at high risk of this disorder. The reduction in incidence of GDM in the treatment arm was accompanied by improved outcomes.

Elevated maternal serum α-fetoprotein level in a fetus with Beckwith-Wiedemann syndrome in the second trimester of pregnancy.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a rare disorder characterized by macrosomia, macroglossia, visceromegaly, and omphalocele and an increased risk of growing tumors. Prenatal and postnatal high levels of serum alpha-fetoprotein are associated with several diseases and neoplasms including hepatoblastomas and other hepatic tumors. The diagnosis of BWS is usually made in the postnatal period on the basis of physical exam features and hypermethylation of the H19 gene. CASE: A 30-year-old woman gravida 3, para 2, underwent maternal serum screening at 15 weeks' gestation. The screening was negative for Down's syn drome (risk 1/6085), but positive for NTDs. Further ultrasound examination at 20 and 30 weeks' evidenced a fetal overgrowth and a 3-D scan at 33 weeks' gestation presented a protruding tongue, and a fixed opened mouth caused by macroglossia. CONCLUSIONS: BWS was suspected on the basis of clinical features, and molecular analysis of critical region 11p15.5 revealing the hypermethylation of H19 gene supported the diagnosis.

Rhombencephalosynapsis in a severely polymalformed fetus with non-mosaic tetrasomy 9p, in intracytoplasmic-sperm-injection pregnancy.

CASE REPORT: A fetus with rhombencephalosynapsis and prenatally diagnosed tetrasomy 9p is reported. Chromosomal analysis from amniocyte culture revealed non-mosaic supernumerary chromosome identified as isochromosome 9p (9p24-->q13::q13-->p24). Ultrasound scan revealed intrauterine growth retardation, renal anomalies, cardiac anomalies, ventriculomegaly, and agenesis of cerebellar vermis with fusion of the cerebellar hemispheres. CONCLUSION: Although most cases of cerebellar vermis agenesis in tetrasomy 9p are described with cystic malformation such as Dandy-Walker anomaly, our case indicates that this chromosomal disorder should be taken into account in fetuses with the development of cystic and non-cystic malformations of cerebellar vermis and posterior fossa.

Two cases of vaginitis caused by itraconazole-resistant Saccharomyces cerevisiae and a review of recently published studies.

Genitourinary infections caused by non-Candida yeasts are uncommon, and especially due to Saccharomyces cerevisiae. We describe the cases of two adult females with vulvovaginal infections caused by itraconazole-resistant S. cerevisiae who made a full recovery after oral fluconazole therapy. We also provide a concise review of recently published studies on this topic.

Fetal facial profile in Pallister-Killian syndrome.

Pallister-Killian syndrome (PKS) is a sporadic chromosomal anomaly, caused by a tissue-specific mosaic distribution of an additional isochromosome 12p. About 60 cases of prenatal diagnosis of PKS have been reported. Only 1 case of PKS is described on the basis of prenatal screening, presenting increased nuchal translucency. An abnormal fetal facial profile is described prenatally as sonographic evidence of PKS. We report a case of prenatal diagnosis in a fetus undergoing second-level scan due to positive triple screen with ultrasound features of PKS.

Reversible acute fetal renal failure due to maternal exposure to angiotensin receptor blocker.

We report on a case of fetal toxicity due to maternal treatment with olmesartan medoxomil. At 29 weeks' gestation, oligohydramnios was found, although the fetus had normal kidneys on ultrasound evaluation. Withdrawal of olmesartan medoxomil, maternal rehydration, and a single dose of furosemide reversed the renal impairment. After term delivery, the neonate was confirmed to have normal renal function. The case suggested that fetal renal impairment due to olmesartan medoxomil may be reversible.