Third-trimester ultrasound for antenatal diagnosis of placenta accreta spectrum in women with placenta previa: results from the ADoPAD study.

OBJECTIVE: To evaluate the performance of third-trimester ultrasound for the diagnosis of clinically significant placenta accreta spectrum disorder (PAS) in women with low-lying placenta or placenta previa. METHODS: This was a prospective multicenter study of pregnant women aged ≥ 18 years who were diagnosed with low-lying placenta (< 20 mm from the internal cervical os) or placenta previa (covering the internal cervical os) on ultrasound at ≥ 26 + 0 weeks' gestation, between October 2014 and January 2019. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs on grayscale ultrasound: (1) obliteration of the hypoechogenic space between the uterus and the placenta; (2) interruption of the hyperechogenic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. Histopathological examinations were performed according to a predefined protocol, with pathologists blinded to the ultrasound findings. To assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprising the need for active management at delivery and histopathological confirmation of PAS was considered the reference standard. PAS was considered to be clinically significant if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation or uterine artery embolization. The diagnostic performance of each ultrasound sign for clinically significant PAS was evaluated in all women and in the subgroup who had at least one previous Cesarean section and anterior placenta. Post-test probability was assessed using Fagan nomograms. RESULTS: A total of 568 women underwent transabdominal and transvaginal ultrasound examinations during the study period. Of these, 95 delivered in local hospitals, and placental pathology according to the study protocol was therefore not available. Among the 473 women for whom placental pathology was available, clinically significant PAS was diagnosed in 99 (21%), comprising 36 cases of placenta accreta, 19 of placenta increta and 44 of placenta percreta. The median gestational age at the time of ultrasound assessment was 31.4 (interquartile range, 28.6-34.4) weeks. A normal hypoechogenic space between the uterus and the placenta reduced the post-test probability of clinically significant PAS from 21% to 5% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 9% in the subgroup with previous Cesarean section and anterior placenta. The absence of placental lacunae reduced the post-test probability of clinically significant PAS from 21% to 9% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 36% in the subgroup with previous Cesarean section and anterior placenta. When abnormal placental lacunae were seen on ultrasound, the post-test probability of clinically significant PAS increased from 21% to 59% in the whole cohort and from 62% to 78% in the subgroup with previous Cesarean section and anterior placenta. An interrupted hyperechogenic interface between the uterine serosa and bladder wall increased the post-test probability for clinically significant PAS from 21% to 85% in women with low-lying placenta or placenta previa and from 62% to 88% in the subgroup with previous Cesarean section and anterior placenta. When all three sonographic markers were present, the post-test probability for clinically significant PAS increased from 21% to 89% in the whole cohort and from 62% to 92% in the subgroup with previous Cesarean section and anterior placenta. CONCLUSIONS: Grayscale ultrasound has good diagnostic performance to identify pregnancies at low risk of PAS in a high-risk population of women with low-lying placenta or placenta previa. Ultrasound may be safely used to guide management decisions and concentrate resources on patients with higher risk of clinically significant PAS. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic accuracy and cost-effectiveness of different strategies to triage women with adnexal masses: a prospective study.

OBJECTIVE: Transvaginal sonography (TVS) and serum biomarkers are used widely in clinical practice to triage women with adnexal masses, but the effectiveness of current biomarkers is weak. The aim of this study was to determine the best method of diagnosing patients with adnexal masses, in terms of diagnostic accuracy and economic costs, among four triage strategies: (1) the International Ovarian Tumor Analysis group's simple rules (SR) for interpretation of TVS with subjective assessment (SA) by an experienced ultrasound operator when TVS results are inconclusive (referred to hereafter as SR ± SA), (2) SR ± SA and cancer antigen 125 (CA 125), (3) SR ± SA and human epididymis protein 4 (HE4) and (4) SR ± SA and the risk of malignancy algorithm (ROMA). Our main hypothesis was that the addition of the biomarkers to SR ± SA could improve triaging of these patients in terms of diagnostic accuracy (i.e. malignant vs benign). As secondary analyses, we estimated the cost effectiveness of the four strategies and the diagnostic accuracy of SR ± SA at the study hospitals. METHODS: Between February 2013 and January 2015, 447 consecutive patients who were scheduled for surgery for an adnexal mass at the S. Anna and Mauriziano Hospitals in Turin were enrolled in this multicenter prospective cohort study. Preoperative TVS was performed and preoperative CA 125 and HE4 levels were measured. Pathology reports were used to assess the diagnostic accuracy of the four triage strategies and the cost of each strategy was calculated. RESULTS: A total of 391 patients were included in the analysis: 57% (n = 221) were premenopausal and 43% (n = 170) were postmenopausal. The overall prevalence of malignancy was 21%. SR were conclusive in 89% of patients and thus did not require SA; the overall performance of SR ± SA showed a sensitivity of 82%, specificity of 92% and positive and negative predictive values and positive and negative likelihood ratios of 74%, 95%, 10.5 and 0.19, respectively. In premenopausal women, mean cost among the four triage strategies varied from €36.41 for SR ± SA to €70.12 for SR ± SA + ROMA. The addition of biomarkers to SR ± SA showed no diagnostic advantage compared with SR ± SA alone and was more costly. Among postmenopausal women, mean cost among the four triage strategies varied from €39.52 for SR ± SA to €73.23 for SR ± SA + ROMA. Among these women, SR ± SA + CA 125 and SR ± SA + ROMA had a higher sensitivity (both 92% (95% CI, 85-99%)) than SR ± SA (81% (95% CI, 71-91%)), but SR ± SA had a higher specificity (84% (95% CI, 77-91%)). SR ± SA + CA 125 and SR ± SA + ROMA improved diagnostic accuracy, each diagnosing a third more malignant adnexal masses. In postmenopausal women, compared with SR ± SA alone, SR ± SA + CA 125 showed a net reclassification improvement (NRI) of 28.8% at an extra cost of €13.00, while the extra cost for SR ± SA + ROMA was €33.71, with a comparable gain, in terms of NRI, as that of SR ± SA + CA 125. CONCLUSIONS: In our study sample, SR ± SA seems to be the best strategy to triage women with adnexal masses for surgical management. Among postmenopausal women, SR ± SA + CA 125 increased the NRI at a reasonable extra cost. Our data do not justify the use of HE4 and ROMA in the initial triage of women with adnexal masses. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Accuracy of ultrasound in antenatal diagnosis of placental attachment disorders.

OBJECTIVES: To evaluate the accuracy of ultrasound in the diagnosis of placenta accreta and its variants, and to assess the impact of prenatal diagnosis in our population. METHODS: A total of 314 women with placenta previa were enrolled prospectively and underwent transabdominal and transvaginal ultrasound examinations. An ultrasound diagnosis (grayscale and color/power Doppler) of placental attachment disorder (PAD) was based on the detection of at least two of the following ('two-criteria system'): loss/irregularity of the retroplacental clear zone, thinning/interruption of the uterine serosa-bladder wall interface, turbulent placental lacunae with high velocity flow, myometrial thickness < 1 mm, increased vascularity of the uterine serosa-bladder wall interface, loss of vascular arch parallel to the basal plate and/or irregular intraplacental vascularization. Definitive diagnosis was made at delivery by Cesarean section. Maternal outcome in cases diagnosed antenatally was compared with that in cases diagnosed at delivery. RESULTS: There were 37/314 cases of PAD (29 anterior and eight posterior). The two-criteria system identified 30 cases of placenta accreta, providing a sensitivity of 81.1% and specificity of 98.9%. When anterior and posterior placentae were considered separately, the detection rates of PAD were 89.7 and 50.0%, respectIvely. Maternal outcome was better in women with prenatal diagnosis of PAD, as seen by less blood loss and shorter hospitalization. CONCLUSIONS: Our data confirmed that grayscale and color Doppler ultrasound have good performance in the diagnosis of PAD and that prenatal diagnosis improves maternal outcome. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Phenotype of five cases of prenatally diagnosed campomelic dysplasia harboring novel mutations of the SOX9 gene.

OBJECTIVES: Campomelic dysplasia is a rare congenital skeletal disorder characterized by bowing of the long bones and a variety of other skeletal and extraskeletal defects, many of which can now be identified prenatally using advanced ultrasound equipment. The disorder is caused by mutations in SRY-box 9 (SOX9), a gene that is abundantly expressed in chondrocytes as well as in other tissues. However, the correlation between genotype and phenotype is still unclear. We report five cases of prenatally detected campomelic dysplasia in which the diagnosis was confirmed by molecular analysis. METHODS: Ultrasound examinations were performed between 12 and 32 weeks. Standard fetal biometric measurements were obtained. Fetal sex was determined sonographically and confirmed by chromosomal analysis. Genomic DNA was obtained in four cases before termination of pregnancy from chorionic villi or amniocytes and in one case postnatally from peripheral blood. RESULTS: Skeletal dysplasia, most often limb shortening and bowed femora, was observed in one case in the first trimester, in three cases in the second trimester and in one case, presenting late for antenatal care, in the third trimester. Four of the pregnancies were terminated and one was carried to term. Postmortem/postnatal physical and radiographic examinations confirmed the presence of anomalies characteristic of campomelic dysplasia. A de novo mutation in the SOX9 gene was detected in all four cases that underwent termination. The father of the proband in the case that went to term was a carrier of a somatic mosaic mutation without clinical or radiographic signs of campomelic dysplasia. CONCLUSIONS: It is likely that the integrated expertise of ultrasonographers, obstetricians, pediatricians and clinical geneticists will markedly improve the likelihood of accurate prenatal clinical diagnoses of campomelic dysplasia. This will, in turn, encourage more specific molecular testing and facilitate comprehensive genetic counseling.

Fetal midgut volvulus: report of eight cases.

OBJECTIVE: To evaluate whether prenatal diagnosis of intestinal midgut volvulus (a rare condition due to the small bowel loops twisting) can improve the prognosis of the newborns. METHODS: In our Prenatal Diagnosis Center, eight cases of intestinal volvulus observed between 2007 and 2014 were retrospectively considered. Ultrasonographic signs can be direct and specific (whirlpool sign, coffee bean sign) or indirect and non-specific (abdominal mass, dilated bowel loops, pseudocysts, ascites, polyhydramnios). RESULTS: Prenatal diagnosis was performed at 20-34 weeks of gestation. All newborns were exposed to an emergency surgery: the major complication was due to cystic fibrosis. CONCLUSIONS: An early suspicion of intestinal volvulus allows the clinician to refer the patient to a tertiary center so to confirm the diagnosis and perform an appropriate follow-up in order to identify the proper time of delivery. The prognosis of the babies with prenatal intestinal volvulus depends on the length of the segment involved, on the level of intestinal obstruction, on the presence of meconium peritonitis and on the gestational age at birth. Our experience, according with the literature, suggests that ascites and absence of abdominal peristalsis are ultrasonographic signs that, in the third trimester of pregnancy, correctly lead to an immediate delivery intervention.

Feasibility study for a microchip-based approach for noninvasive prenatal diagnosis of genetic diseases.

Fetal DNA in maternal plasma may represent a source of genetic material for prenatal noninvasive diagnosis of genetic diseases. We evaluated a cohort of physiological pregnancies to determine if fetal DNA can be retrieved at any gestational week in sufficient quantity to be analyzed with advanced mutation detection technologies. We performed fetal DNA quantification by real-time polymerase chain reaction (PCR) on the SRY gene in 356 women sampled from 6 to 40 gestational weeks. Fetal DNA was retrieved at any week. All female fetuses were correctly identified. In 5 of 188 (2.6%) male-bearing pregnancies, no amplification was obtained. For noninvasive testing, complete clearance of fetal DNA after delivery is mandatory. Long-term persistence was not detected in women with previous sons or abortions. These findings confirm that maternal plasma may represent the optimal source of fetal genetic material. For noninvasive diagnosis of genetic diseases, we evaluated microchip technology. The detection limit for a minority allele determined by diluting a mutated DNA into a wild-type plasma sample was 5 genome equivalents, indicating that the test might be applied to the identification of paternally inherited fetal alleles in maternal plasma. The addition of peptide nucleic acids (PNAs) to either the PCR reaction or the chip hybridization mixture allowed approximately 50% inhibition of wild-type allele signals.

Trisomy 18: Fetal ultrasound findings at different gestational ages.

The aim of this article is evaluate the sonograhic findings in fetuses with trisomy 18 at different gestational ages. The cases were recruited from pregnant women, who underwent to prenatal diagnosis in the period from October 1995 to September 2006. Seventy-one fetuses with trisomy 18 were diagnosed. On review of the sonograms the majority of these cases had ultrasound anomalies (sensitivity of 91.5%). The most frequent anomalies were abnormalities of extremities (40.8%) and fetal growth restriction (35.2%). More frequently (54.9%) two or more anomalies were present. Nearly all fetuses with trisomy 18 had sonographic abnormalities. Likely improved high-resolution equipment and attention to details by skilled operators led to the detection of most anomalies to trisomy 18. Knowledge of types of specific ultrasound findings can improve prenatal diagnosis in order to provide invasive procedures only when indicated, and to avoid amniocentesis when ultrasound signs are not observed in women at high risk from positive biochemical testing.

First-trimester fetal heart block and increased nuchal translucency: an indication for early fetal echocardiography.

Prevalence of congenital heart disease increases with nuchal translucency (NT) thickness. First-trimester fetal bradycardia may result from heart block associated with complex congenital heart disease. We report two cases detected in the first trimester of pregnancy, in which both fetuses showed an increased nuchal translucency and bradycardia. Fetal karyotype was normal in both fetuses. First-trimester fetal echocardiography was performed and, in both cases, complex congenital heart disease was diagnosed. We discuss the added role of fetal heart rate in first-trimester ultrasound screening, in fetuses with increased nuchal translucency and normal karyotype. We stress, as well, the importance of echocardiography performed in the first trimester as a potential tool for early diagnosis in selected cases.

Fetal nasal bone and trisomy 21 in the second trimester.

OBJECTIVES: To assess the feasibility of measuring nasal bone length in the second trimester of pregnancy and to confirm if fetal nasal bone absence or hypoplasia is a marker for Down syndrome. METHODS: Fetal nasal bone assessment was performed in 439 consecutive singleton pregnancies at high risk of Down syndrome between 15 and 21 weeks. All ultrasound examinations were performed transabdominally by five skilled sonographers. If the nasal bone was present, its length was measured. The biparietal diameter: nasal bone length ratio (BPD/NBL) was also calculated. RESULTS: Nasal bone assessment was successfully achieved in all fetuses. The nasal bone was absent in 2(0.47%) of the 417 unaffected fetuses and in 10(55.5%) of the 18 fetuses with trisomy 21. Of the 8 Down syndrome cases with a nasal bone present, 4 had nasal bone hypoplasia and 4 had a normal nasal bone. BPD/NBL was 9 or greater in 7 of the 8 fetuses affected by trisomy 21 with nasal bone present and in 86 (20.6%) of the 417 normal fetuses; it was 10 or greater in 5 of the 8 (62.5%) fetuses affected by trisomy 21 and in 41 of the 417 (9.8%) euploid fetuses. CONCLUSIONS: Nasal bone absence is a marker for Down syndrome in the second trimester of pregnancy. Inclusion of nasal bone length into the second-trimester screening protocol could potentially obviate the false-negative cases from other screening tests. The measurement of nasal bone length in the second trimester seems to provide additional benefits beyond the assessment of the presence or absence of the nasal bone.

[Different therapies in 2 cases of hyperdivergent monozygotic twins]. / Conisiderazioni su differenti terapie in due casi di gemelli omozigoti iperdivergenti.

An interesting case of hyperdivergent homozygotic twins is examined. Both required dental treatment involving extractions: in one case of 15, 25, 35, 45 and in the other of 16, 26, 36, 46. The inherent problem is examined in the light of the extreme similarity of the twins.

[Correction of a dental and basal Class II with accentuated overjet using traction]. / Correzione di una II Classe dentale e basale con accentuato overjet con impiego di trazioni.

Correction of a dental and basal 2nd class with accentuated overjet using extraoral traction and programmed extractions of 17-27, 38-48 according to Armstrong's technique. The paper reports a case of dental and basal 2nd class with accentuated overjet treated using the extraction of 17-27, 38-48 and extraoral traction only, according to Armstrong's technique. Results obtained after 117 days of combined extraoral traction are reported in order to illustrate the reasons behind the choice of this apparatus and to demonstrate its evident efficacy in this case of 2nd class, 1st subdivision.

[Use of a functional appliance in initial orthodontic treatment of a case of dental and basal Class II with dental biprotrusion at age 12]. / Impiego di una placca funzionale nel trattamento ortodontico iniziale di un caso di II Classe dentale e basale con biprotrusione dentale all'età di 12 anni.

Use of functional plaque in the initial orthodontic treatment of a case of dental and basal 2nd class with dual dental protrusions in a 12-year-old patient. The use of a functional plaque is described in a 12-year-old male patient in dental and basal 2nd class, following the extraction of 1.6-2.5-2.6-3.6-4.6 due to caries. Biprotrusion was observed together with an overjet of 8 mm and an overbite of 6 mm. Results of the therapy are reported after 21 months.

[Disturbances of craniofacial growth in cleft lip and palate. Local and general factors]. / Gli squilibri di crescita cranio-facciale nei portatori di esiti di LPS. Fattori locali e fattori generali.

The Authors describe and analyze the anomaly of the cranio-facial growth in cleft lip and palate patients and emphasize the importance of proper surgical timing.

[Possibility of cephalometric superimposition on a single point after Steiner, Ricketts and Cervera]. / Possibilità di sovrapposizione cefalometrica su un solo punto secondo Steiner, Ricketts e Cervera.

Following a brief introduction to the various methods of cephalometric superimposition proposed by different authors and school, the paper examines Cervera's system of cephalometric superimposition on a single point. The letter identified a single point, OcC point (Cervera's occlusal point), as the primary fulcrum from which to perform a correct cephalometric superimposition in order to examine the patient's anticipated growth. It is clear that initial anthropological interest, which was focused on the anterior cranial fossa, has gradually moved down to the lower third of the face, the anatomo-functional region in which the functions of the stomatognathic apparatus are mainly performed.

[Fractures of the mandibular condyle in the pediatric age group. Clinical considerations and therapeutic procedures]. / Le fratture del condilo mandibolare in età pediatrica. Considerazioni cliniche e procedure terapeutiche.

The paper analyses the post-traumatic pathology of the T.M. joint in patients in a dynamic growth phase with reference to prognostic and therapeutic factors. After a critical review of the literature, the lack of a common viewpoint and the importance of personal experience are underlined.