Enrico Ferrazzi

Background/Objectives: Clinical risk measures such as pre-pregnancy body mass index (BMI) and gestational weight gain do not distinguish the expansion of fluid, lean, and adipose compartments. Standardized obstetric reference curves for bioelectrical impedance analysis (BIA) are lacking. This study aimed to establish longitudinal, trimester-specific BIA reference curves in uncomplicated pregnancies. Methods: This multicenter, prospective, longitudinal cohort study was conducted at three Italian tertiary research hospitals from September 2020 to September 2025. BIA assessments (InBody 270^®) were performed at 10–15, 23–25, and 34–37 gestational weeks. Generalized additive models for location, scale, and shape were used to derive reference centiles and BMI-conditioned contour plots for total body water, lean mass, fat mass, and visceral fat level. Pregnancies with complications or incomplete longitudinal data were excluded from the primary reference cohort. Results: Among 442 healthy pregnant women, all parameters increased progressively across gestation. Each 1-unit increase in pre-pregnancy BMI was associated with a larger shift in fat mass (1.88 kg; 95% CI, 1.77–1.99) than in total body water (0.47 L; 95% CI, 0.38–0.57). Conclusions: These multicenter, BMI-conditioned, trimester-specific BIA reference curves provide normative benchmarks for maternal hydration and body composition and may support the identification of early deviations from physiological gestational trajectories.

Objective: Pathogenic or likely pathogenic copy‐number variants (p/lpCNVs) are a significant cause of perinatal morbidity and mortality. Current prenatal screening based on cell‐free DNA (cfDNA) fails to detect the majority of microimbalances (microdeletions/microduplications), leaving a significant residual risk of undetected chromosomal abnormalities. This study evaluated the clinical performance of a novel single‐cell‐sequencing‐based non‐invasive prenatal testing (scsbNIPT) method utilizing circulating extravillous trophoblasts (cEVTs) for the detection of fetal p/lpCNVs, particularly microimbalances < 8 Mb. Methods: This was a prospective, blinded, observational multicenter cohort study of 1390 high‐risk pregnant women undergoing prenatal invasive diagnostic testing between November 2021 and December 2023. A 20‐mL maternal blood sample was collected from each subject between 11 + 0 and 22 + 6 weeks' gestation prior to invasive sampling. cEVTs were isolated and subjected to whole‐genome sequencing, using a proprietary workflow. scsbNIPT results were compared with standard invasive prenatal diagnostic results obtained by karyotyping and/or chromosomal microarray analysis. Results: scsbNIPT showed a sensitivity of 92.9% (95% CI, 76.5–99.1%) and a specificity of 98.2% (95% CI, 97.0–99.0%) for the detection of genome‐wide microimbalances measuring ≥ 300 kb to < 8 Mb. The sensitivity for p/lpCNVs ≥ 300 kb in pregnancies screened at 11 + 0 to 14 + 6 weeks was 100% (95% CI, 83.9–100%). For trisomy 21, the sensitivity of scsbNIPT was 98.0% (95% CI, 92.9–99.8%) and the specificity was 99.7% (95% CI, 99.0–99.9%). Conclusions: This study demonstrates the scientific validity and clinical utility of scsbNIPT for the non‐invasive detection of genome‐wide fetal p/lpCNVs, particularly microimbalances, with high sensitivity and a resolution comparable to that of chromosomal microarray analysis. scsbNIPT may offer more complete screening for genome‐wide p/lpCNVs, markedly lowering the residual risk early in pregnancy compared with existing cfDNA‐based methods. © 2026 Menarini Silicon Biosystems. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Pregnancy-associated plasma protein-A (PAPP-A) is a glycoprotein produced by the syncytiotrophoblast and the decidua during pregnancy, and other tissues, including vascular smooth muscle cells and fibroblasts. Type 2 diabetes is associated with chronically low PAPP-A levels. These low values contribute to vascular dysfunction and impaired metabolic health This retrospective study investigated whether PAPP-A levels are correlated with glycated hemoglobin (HbA1c), a marker of glycometabolic control, in pregnant women with type 1 and type 2 pre-GD who underwent first-trimester combined screening. Among the 96 women analyzed, a significant inverse correlation was observed in type 1 pre-GD between PAPP-A and both pregestational and first trimester HbA1c values (R = –0.69 and –0.49; p < 0.01). In type 2 pre-GD, multivariate analysis revealed that for each unit increase in HbA1c, PAPP-A decreased by 0.03 units in Caucasian women, but increased by 2.7 units in South American women. These findings suggest that glycometabolic compensation influences PAPP-A levels and should be considered when calculating aneuploidy risk. Rather than categorizing pre-GD history as a binary variable, incorporating HbA1c as a continuous parameter may improve the accuracy of risk assessment in first trimester screening for aneuploidies.

Normal pregnancy is characterized by changes in lipid metabolism with significant implications for the health of both mother and offspring. When these changes develop into maternal dyslipidemia, a significant association with adverse pregnancy outcomes has been observed, including the development of gestational diabetes (GD), modulation of the inflammatory response, and excessive fetal growth. In the present study, we performed a lipidomic assessment of patients at GD diagnosis (24–28 weeks of gestation) and 12 weeks after diagnosis. We found higher levels of esterified oleic acid in plasma at the time of GD diagnosis in women who subsequently required pharmacological therapy to control blood glucose levels compared to those who did not require additional treatment, suggesting that the measurement of plasma oleic acid might be an additional tool for the early identification of patients with a more severe form of gestational diabetes. Moreover, plasma oleic acid levels showed a positive correlation with fetal growth in the context of adequate glycemic control, supporting a metabolic dysregulation of other pathways whose identification could help clinicians to discriminate different cases within the spectrum of severity of the disease. Finally, the correlation between plasma oleic acid and circulating BAFF levels at the time of diagnosis and 12 weeks later adds a possible mechanism to support the pro-inflammatory and pro-diabetic state in the metabolic set of GD. Overall, these findings strongly support the role of plasma oleic acid as a possible early marker for GD severity stratification during pregnancy.

We thank the authors for the interest in our paper

Objective: To investigate the relationship of umbilical vein flow (UVF) measured close to term with abnormal fetal growth and adverse perinatal outcome in a cohort of pregnancies at low risk of placental insufficiency.Methods: This was a prospective multicenter observational study conducted across two tertiary maternity units. Patients with a singleton appropriate‐for‐gestational‐age fetus between 35 and 38 weeks' gestation were included. Pregnancies at higher risk of placental insufficiency or with fetal anomalies were excluded. At ultrasound examination, the abdominal circumference (AC), umbilical vein diameter and peak velocity of the umbilical vein were measured, and, using these variables, a new variable, UVF/AC, was calculated. The primary outcome was the occurrence of severely stunted fetal growth, defined as a greater than 40‐percentile drop between estimated fetal weight at the third‐trimester ultrasound and birth weight. The occurrence of adverse perinatal outcome (defined as one of the following: neonatal acidosis (umbilical artery pH < 7.15 and/or base excess > 12 mmol/L) at birth, 5‐min Apgar score < 7, neonatal resuscitation or neonatal intensive care unit admission) was analyzed as a secondary outcome.Results: Between April 2021 and March 2023, 365 women were included in the study. The mean UVF/AC at enrolment was 6.4 ± 2.6 mL/min/cm, and 35 (9.6%) cases were affected by severely stunted fetal growth. Severely stunted fetal growth was associated with a lower mean UVF/AC (5.4 ± 2.6 vs 6.5 ± 2.6 mL/min/cm; P = 0.02) and a higher frequency of UVF/AC < 10^th percentile (8/35 (22.9%) vs 28/330 (8.5%); P = 0.01). Moreover, UVF/AC showed an area under the receiver‐operating‐characteristics curve (AUC) of 0.65 (95% CI, 0.55–0.75; P = 0.004) in predicting the occurrence of severely stunted fetal growth, and the optimal cut‐off value of UVF/AC for discriminating between normal and severely stunted fetal growth was 7.2 mL/min/cm. This value was associated with a sensitivity and specificity of 0.77 (95% CI, 0.60–0.90) and 0.33 (95% CI, 0.28–0.39), and positive and negative predictive values of 0.11 (95% CI, 0.07–0.15) and 0.93 (95% CI, 0.87–0.97), respectively. Regarding the occurrence of adverse perinatal outcome, this was associated independently with maternal age (adjusted odds ratio (aOR), 0.93 (95% CI, 0.87–0.99); P = 0.04), UVF/AC Z‐score (aOR, 0.53 (95% CI, 0.30–0.87); P = 0.01) and augmentation of labor (aOR, 2.69 (95% CI, 1.28–5.69); P = 0.009). UVF/AC showed an AUC of 0.65 (95% CI, 0.56–0.73; P = 0.005) in predicting the occurrence of adverse perinatal outcome, and the optimal cut‐off value of UVF/AC for discriminating between normal and adverse perinatal outcome was 6.7 mL/min/cm. This value was associated with a sensitivity and specificity of 0.70 (95% CI, 0.54–0.83) and 0.40 (95% CI, 0.34–0.45), and positive and negative predictive values of 0.14 (95% CI, 0.09–0.19) and 0.91 (95% CI, 0.85–0.95), respectively.Conclusions: Our data demonstrate an association between reduced UVF close to term, severely stunted fetal growth and adverse perinatal outcome in a cohort of low‐risk pregnant women, with a moderate ability to rule out and a poor ability to rule in either outcome. Further studies are needed to establish whether the assessment of UVF can improve the identification of fetuses at risk of subclinical placental insufficiency and adverse perinatal outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

We present the case of a 36-year-old primigravida who gave birth to a 3200 g baby by vacuum-assisted (Kiwi OmniCup™) operative vaginal delivery with mediolateral episiotomy. A “y”-shaped perineal tear with a grade IIIC obstetric anal sphincter injury (OASI) was diagnosed and repaired. Two days after delivery, in the absence of suture dehiscence, she started experiencing complete anal incontinence. A decision was made in association with a proctologic surgeon for an early secondary repair. Before surgery, a Three-dimensional transperineal ultrasound (TPUS) was performed. The exam revealed a major defect of the external anal sphincter at the 11 o’clock position. This allowed for the reopening of only a circumscribed area of the perineal suture and repair of the sphincters using the end-to-end technique. The symptoms regressed completely, and follow-up TPUS demonstrated the gradual wound healing process. Anal incontinence, secondary to obstetric anal sphincter injury (OASI), has a severe negative impact on women’s quality of life. TPUS is an effective method to detect sphincter defects and monitor the healing process. This report investigates the feasibility of identifying the sphincter tear in an incontinent puerperal patient without suture dehiscence in order to target early secondary repair while minimizing its extent. TPUS has proven a safe and effective tool to guide early secondary repair of symptomatic OASI complications while minimizing the invasiveness of the procedure. Multidisciplinary management is crucial to ensure the adequate standard of care.