Fetal magnetic resonance imaging at 36 weeks predicts neonatal macrosomia: the PREMACRO study.

BACKGROUND: Large-for-gestational-age fetuses are at increased risk of perinatal morbidity and mortality. Magnetic resonance imaging seems to be more accurate than ultrasound in the prediction of macrosomia; however, there is no well-powered study comparing magnetic resonance imaging with ultrasound in routine pregnancies. OBJECTIVE: This study aimed to prospectively compare estimates of fetal weight based on 2-dimensional ultrasound and magnetic resonance imaging with actual birthweights in routine pregnancies. STUDY DESIGN: From May 2016 to February 2019, women received counseling at the 36-week clinic. Written informed consent was obtained for this Ethics Committee-approved study. In this prospective, single-center, blinded study, pregnant women with singleton pregnancies between 36 0/7 and 36 6/7 weeks' gestation underwent both standard evaluation of estimated fetal weight with ultrasound according to Hadlock et al and magnetic resonance imaging according to the formula developed by Baker et al, based on the measurement of the fetal body volume. Participants and clinicians were aware of the results of the ultrasound but blinded to the magnetic resonance imaging estimates. Birthweight percentile was considered as the gold standard for the ultrasound and magnetic resonance imaging-derived percentiles. The primary outcome was the area under the receiver operating characteristic curve for the prediction of large-for-gestation-age neonates with birthweights of ≥95th percentile. Secondary outcomes included the comparative prediction of large-for-gestation-age neonates with birthweights of ≥90th, 97th, and 99th percentiles and small-for-gestational-age neonates with birthweights of ≤10th, 5th, and 3rd percentiles for gestational age and maternal and perinatal complications. RESULTS: Of 2914 women who were initially approached, results from 2378 were available for analysis. Total fetal body volume measurements were possible for all fetuses, and the time required to perform the planimetric measurements by magnetic resonance imaging was 3.0 minutes (range, 1.3-5.6). The area under the receiver operating characteristic curve for the prediction of a birthweight of ≥95th percentile was 0.985 using prenatal magnetic resonance imaging and 0.900 using ultrasound (difference=0.085, P<.001; standard error, 0.020). For a fixed false-positive rate of 5%, magnetic resonance imaging for the estimation of fetal weight detected 80.0% (71.1-87.2) of birthweight of ≥95th percentile, whereas ultrasound for the estimation of fetal weight detected 59.1% (49.0-68.5) of birthweight of ≥95th percentile. The positive predictive value was 42.6% (37.8-47.7) for the estimation of fetal weight using magnetic resonance imaging and 35.4% (30.1-41.1) for the estimation of fetal weight using ultrasound, and the negative predictive value was 99.0% (98.6-99.3) for the estimation of fetal weight using magnetic resonance imaging and 98.0% (97.6-98.4) for the estimation of fetal weight using ultrasound. For a fixed false-positive rate of 10%, magnetic resonance imaging for the estimation of fetal weight detected 92.4% (85.5-96.7) of birthweight of ≥95th percentile, whereas ultrasound for the estimation of fetal weight detected 76.2% (66.9-84.0) of birthweight of ≥95th percentile. The positive predictive value was 29.9% (27.2-32.8) for the estimation of fetal weight using magnetic resonance imaging and 26.2% (23.2-29.4) for the estimation of fetal weight using ultrasound, and the negative predictive value was 99.6 (99.2-99.8) for the estimation of fetal weight using magnetic resonance imaging and 98.8 (98.4-99.2) for the estimation of fetal weight using ultrasound. The area under the receiver operating characteristic curves for the prediction of large-for-gestational-age neonates with birthweights of ≥90th, 97th, and 99th percentiles and small-for-gestational-age neonates with birthweights of ≤10th, 5th, and 3rd percentiles was significantly larger in prenatal magnetic resonance imaging than in ultrasound (P<.05 for all). CONCLUSION: At 36 weeks' gestation, magnetic resonance imaging for the estimation of fetal weight performed significantly better than ultrasound for the estimation of fetal weight in the prediction of large-for-gestational-age neonates with birthweights of ≥95th percentile for gestational age and all other recognized cutoffs for large-for-gestational-age and small-for-gestational-age neonates (P<.05 for all).

Screening for Sex Chromosome Aneuploidy by Cell-Free DNA Testing: Patient Choice and Performance.

OBJECTIVE: To study patient choice regarding testing for sex chromosome aneuploidy (SCA) and the performance of cell-free DNA (cfDNA) screening for SCA. METHODS: Patient choice regarding screening for SCA and factors influencing this choice were evaluated in a single center. In a subsequent two-center study, cases that screened positive for SCA were analyzed to determine the positive predictive value (PPV) for each SCA. RESULTS: In all, 1,957 (61.9%) of the 3,162 patients undergoing cfDNA testing opted for SCA screening. Regression analysis demonstrated that independent predictors of a patient's decision for SCA were earlier gestational age, spontaneous conception, and cfDNA chosen as a primary method of screening. A total of 161 cases screened positive for SCA and follow-up data were available for 118 (73.3%). Forty-six of the 61 cases of 45,X were false-positive results and 15 were concordant with the fetal karyotype (PPV = 24.6%). Seventeen of the 22 cases of 47,XXX were false positive and 5 concordant (PPV = 22.7%). Eleven of the 30 cases of 47,XXY were false positive and 19 concordant (PPV = 63.3%). All 5 cases of 47,XYY were correctly identified, thus yielding a PPV of 100%. CONCLUSION: More than half of the patients undergoing cfDNA aneuploidy screening also opted for SCA testing, but they were less likely to do so in the presence of an increased risk of trisomy. SCAs involving the X chromosome had a lower PPV than those involving the Y chromosome.

Self-Amputation of the Extra Digit in a Fetus with Polydactyly: First Ultrasound Demonstration.

We herein report the first ultrasound evidence of the self-amputation of an extra digit in case of fetal polydactyly. The prenatal evidence of fetal polydactyly is not always followed by postnatal confirmation. This is not always due to ultrasound misdiagnosis, but often to an in utero self-amputation phenomenon. We demonstrate that there is the detachment of part of the digit, leading to the evidence of a neonatal bump on the site of the prenatal extra digit. This demonstration has been possible by the direct visualization of the remnant by ultrasound.

[Importance of the molecular diagnosis in the screening of alpha-thalassemia]. / Importanza della diagnosi molecolare nel riconoscimento delle alfa talassemie. Descrizione di un caso.

The term alpha thalassemia refers to inherited disorders of hemoglobin caused by reduced or absent synthesis of alpha globin chains. This paper highlights that in the presence of a alfa2-Tal (-α/αα), called the silent, the biochemical diagnosis turns out to be insufficient. In these cases, the molecular study of alpha-globin genes is necessary for identification. In reason of this we present the following case report. A woman of 29 years, pregnant at 12(a) weeks, arrived at our observation to undergo prenatal screening test for Down and Edwards syndromes (bitest). The medical history of the couple revealed that both had doubts haematological indices: Mr. T.G. had a biochemical framework related to alpha1-Tal (MCV 58.8fl, MCH 19.8pg, HbA2: 1.9, HbF:0.4, erythrocytes 6.58x10(6)/ul ed Hb 13g/dl), which was confirmed by molecular analysis (genotype alfa(0-20.5Kb)). Particular difficulties of interpretation presented the C.F. patient who had a biochemical phenotype border line (MCV 79.8fl, MCH 27.2pg, HbA2: 2.9, HbF: 0.6, erythrocytes 5.11x10(6)/ul, Hb 12.8 g/dl). Only molecular analysis has found with certainty that Mrs. C.F. appeared to be phenotypically alpha2-TAL (-α/αα) for the presence of the mutation "alfa2 init.Cd(T>C) NcoI". In the event, as in our case, there is a couple where one spouse is alpha2-TAL (-α/αα) and the other alpha1-TAL (--/αα), must have to inform the couple about the possibility of conceiving a child with hemoglobin H (HbH). Far from the authors refer to the idea of prenatal diagnosis for couples at risk to bear children with HbH, but it is worth highlighting the importance of a careful study of the blood parameters and an extensive and precise information about the clinical implications related to complications of alpha thalassemia.

Prediction of fetal macrosomia using two-dimensional and three-dimensional ultrasound.

OBJECTIVE: The estimation of the fetal weight by three-dimensional (3D) ultrasound (US) with fractional thigh volume (TVol) has been suggested to be more accurate than two-dimensional (2D) US particularly within the context of fetuses at risk of macrosomia. The objective of this study was to compare the accuracy of 2D US and 3D US with two different methods of projection for the identification of fetal macrosomia at term. STUDY DESIGN: Prospective study which included women at risk for fetal macrosomia referred for fetal biometry between 34+0-36+6 weeks. The estimated fetal weight (EFW) was computed using 2D US and the Hadlock Model IV or through 3D US and the Model VI by Lee et al. The projection of the EFW at the time of delivery was performed by using Yudkin's chart percentiles and the gestation-adjusted projection (GAP) method. RESULTS: Overall, 230 patients were included. Paired comparison between 2D-US-EFW and 3D-US-EFW with either method of projection of the EFW at birth suggested different properties of the techniques, being 2D-US-EFW associated with higher sensitivity and 3D-US-EFW with higher specificity, PPV and LR + . At ROC curve no difference was found in the prediction of birthweight ≥90th centile using 2D-US-EFW or 3D-US-EFW (AUC 0.831, 95%CI 0.768-0.894 versus AUC 0.860, 95%CI 0.799-0.920, respectively, p 0.37) nor in the prediction of birthweight >95th centile with 2D-US-EFW compared to 3D-US-EFW (0.803, 95%CI 0.731-0.874 versus 0.866, 95%CI 0.805-0.926, respectively, p 0.07). Similarly, a non-significant difference in the accuracy of the prediction of birthweight >4000 g (AUC 0.788, 95%CI 0.716-0.859 for 2D-US-EFW vs AUC 0.802, 95%CI 0.723-0.880 for 3D-US-EFW, p 0.72) and >4500 g (0.828, 95%CI 0.720-0.936 for 2D-US-EFW vs 0.858, 95%CI 0.759-0.956 for 3D-US-EFW, p 0.71) with the GAP method could be demonstrated. CONCLUSIONS: Within a population at risk of fetal macrosomia the performance of 3D-US-EFW is similar to that of 2D-US-EFW in the prediction of macrosomia at term regardless of the method used for the projection of the EFW, however different properties were noted between the two techniques. Such finding suggests a potential complementary role of the techniques which warrants evaluation in future research.

Analysis of cystic fibrosis gene mutations in children with cystic fibrosis and in 964 infertile couples within the region of Basilicata, Italy: a research study.

INTRODUCTION: Cystic fibrosis is the most common autosomal recessive genetic disease in the Caucasian population. Extending knowledge about the molecular pathology on the one hand allows better delineation of the mutations in the CFTR gene and the other to dramatically increase the predictive power of molecular testing. METHODS: This study reports the results of a molecular screening of cystic fibrosis using DNA samples of patients enrolled from January 2009 to December 2013. Patients were referred to our laboratory for cystic fibrosis screening for infertile couples. In addition, we identified the gene mutations present in 76 patients affected by cystic fibrosis in the pediatric population of Basilicata. RESULTS: In the 964 infertile couples examined, 132 subjects (69 women and 63 men) resulted heterozygous for one of the CFTR mutations, with a recurrence of carriers of 6.85%. The recurrence of carriers in infertile couples is significantly higher from the hypothetical value of the general population (4%). CONCLUSIONS: This study shows that in the Basilicata region of Italy the CFTR phenotype is caused by a small number of mutations. Our aim is to develop a kit able to detect not less than 96% of CTFR gene mutations so that the relative risk for screened couples is superimposable with respect to the general population.

Risk of preterm delivery associated with prior treatment of cervical precancerous lesion according to the depth of the cone.

The aim of this study was to evaluate the impact of the surgical excisional procedures for cervical intraepithelial neoplasia (CIN) treatment both on subsequent fertility (cervical factor) and pregnancy complication (risk of spontaneous preterm delivery). We retrospectively analyzed 236 fertile women who underwent conization for CIN. We included in the study 47 patients who carried on pregnancy and delivered a viable fetus. Patients were asked about postconization pregnancies, obstetrical outcomes, and a possible diagnosis of secondary infertility caused by cervical stenosis. We evaluated the depth of surgical excision, the timing between cervical conization and subsequent pregnancies, surgical technique, and maternal age at delivery. We recorded 47 deliveries, 10 cases of preterm delivery; 8 of them were spontaneous. The depth of surgical excision showed a statistically significant inverse correlation with gestational age at birth. The risk of spontaneous preterm delivery increased when conization depth exceeded a cut-off value of 1.5 cm. Our data do not demonstrated a relation between conization and infertility due to cervical stenosis.

Identification of patients with defects in the globin genes.

INTRODUCTION: hemoglobinopathies constitute a major health problem worldwide. These disorders are characterized by a clinical and hematological phenotypic heterogeneity. The increase of HbA2 is an invaluable hematological marker of the beta-thalassemia heterozygosis and of double heterozygosis for the alleles of delta and alpha globin genes or for the alleles of delta and beta globin genes which can cause the increase of HbA2 up to normal or borderline values. CASE REPORT: we report the case of a 30-year-old woman (first pregnant) who was admitted to our Unit at 12 weeks for a screening for thalassemia. The outcomes of the biochemical and haematological exams (MCV, MCH, HbA2, HbF) highlighted that the patient was a carrier of a beta-thalassemic trait. Molecular analysis of the beta globin genes highlighted a ß(0)39C>T heterozygous mutation. Biochemical and hematological parameters of the husband (MCV, MCH, HbA2, HbF) were normal except for the level of HbA2 (3,6%). The molecular analysis of the beta globin genes highlighted a IVS2 nt844 C>G heterozygous mutation. Furthermore, the heterozygous mutation δ(+)cod.27G>T was detected in his δ globin gene. For this reason, he was diagnosed a δ+ß Thal. CONCLUSIONS: the aim of this paper is to highlight that biochemical diagnosis could not exhaustive and a molecular diagnostic widening is required to detect the genetic deficiency causing the thalassemic trait.

Clinical correlation between premature ovarian failure and a chromosomal anomaly in a 22-year-old Caucasian woman: a case report.

INTRODUCTION: Premature ovarian failure is defined as the cessation of ovarian activity before the age of 40 years. It is biochemically characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (luteinizing hormone and follicle-stimulating hormone). CASE PRESENTATION: Our patient, a 22-year-old Caucasian woman under evaluation for infertility, had experienced secondary amenorrhea from the age of 18. No positive family history was noted regarding premature menopause. An examination of our patient's karyotype showed the presence of a reciprocal translocation, apparently balanced, which had the X chromosome long arm (q13) and the 14 chromosome short arm (p12) with consequent karyotype: 46, X, t(X; 14)(q13;p12). CONCLUSIONS: Our study has underlined that karyotyping is one of the fundamental investigations in the evaluation of amenorrhea. It highlighted a genetic etiology, in the form of a chromosomal abnormality, as the causal factor in amenorrhea.

Study of a family in the province of Matera presenting with glucose-6-phosphate dehydrogenase deficiency and Gilbert's syndrome.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a recessive X-linked trait, is the most common enzyme deficiency in the world. The most devastating clinical consequence of this deficit is severe neonatal jaundice, which results in sensorineural deficit, and severe haemolytic anemia. However, patients may be asymptomatic. The most common clinical sign is hyperbilirubinemia (h↑), that is also related to Gilbert's syndrome, a condition associated with the promoter polymorphism of the UDP-glucuronosyltransferase 1 (UGT1A1) gene. The aim of this study was to underline (as is usually done by DNA molecular analysis) to detect and to clarify the genetic deficiency that is the reason of the disorder in question. In this study, different techniques were applied to analyse a family of four individuals presenting with hyperbilirubinemia: bilirubinic dosage, electrophoresis and enzymatic activity dosage of G6PD; molecular analysis of the UGT1A promoter to detect a thymine-adenine (TA) insertion, that causes the [A(TA)7TAA] mutation. The results showed that in certain cases, the presence of hyperbilirubinemia is not only associated with G6PD deficiency, but may be caused by the co-presence of a mutation in the UGTA1 promoter related to Gilbert's syndrome. As being affected by these two conditions predisposes to adverse effects towards certain drug treatments, it is advisable to study the UGTA1 gene before prescribing drugs for specific antineoplastic or retroviral treatment. We emphasize that investigating both the UGT1A gene and G6PD activity is the most reliable way to make a correct differential diagnosis.