Fetal oxygen and glucose consumption in human pregnancy complicated by fetal growth restriction

In healthy pregnancy, glucose and oxygen availability are essential for fetal growth and wellbeing. However, how substrate delivery and fetal uptake are affected in human pregnancy complicated by fetal growth restriction (FGR) is still unknown. Here we show that the human FGR fetus has a strikingly reduced umbilical uptake of both oxygen and glucose. In 30 healthy term and 32 FGR human pregnancies umbilical volume flow (Qumb) and parallel umbilical vein (uv) and artery (ua) blood samples were obtained at elective Caesarean section to calculate fetal glucose and oxygen uptake as Qumb • Δ (uv-ua) differences. Umbilical blood flow was significantly lower in FGR pregnancy (-63%, P<0.001) but not when normalized for fetal body weight. FGR pregnancy had significantly lower umbilical oxygen delivery and uptake, both as absolute values (delivery: –78%; uptake: –78%) and normalized (delivery: –50%; uptake: –48%) for fetal body weight (all P<0.001). Umbilical glucose absolute delivery and uptake were significantly reduced (delivery: –68%; uptake: –72%) but only glucose uptake was decreased when normalized for fetal body weight (–30%, P<0.05). The glucose/oxygen quotient was significantly increased (+100%, P<0.05) while glucose clearance was significantly decreased (71%, P<0.001) in FGR pregnancy (both P<0.05). The human fetus in FGR pregnancy triggers compensatory mechanisms to reduce its metabolic rate, matching the proportion of substrate consumption relative to oxygen delivery as a survival strategy during complicated pregnancy.Financial support was obtained by grants from Fondazione Giorgio Pardi, by ASM (Associazione Italiana per lo Studio delle Malformazioni), and by a Grant of the Italian Ministry of University and Research PRIN 2010-2011 prot. 20102chst5_005

Cervical pessary for preventing preterm birth in twin pregnancies with short cervical length: a systematic review and meta-analysis

OBJECTIVE: To evaluate the effectiveness of cervical pessary for preventing spontaneous preterm birth (SPTB) in twin pregnancies with an asymptomatic transvaginal ultrasound cervical length (TVU CL) in the second trimester. METHODS: We performed a meta-analysis including all randomized clinical trials (RCTs) comparing the use of cervical pessary (i.e. intervention group) with expectant management (i.e. control group). The primary outcome was incidence of SPTB <34 weeks. RESULTS: Three trials, including 481 twin pregnancies with short cervix, were analyzed. Two RCTs defined short cervix as TVU CL ≤25 mm and one as TVU CL ≤38 mm. Pessary was not associated with prevention of SPTB, and the mean gestational age at delivery and the mean latency were similar in the pessary group compared to the control group. Moreover, no benefits were noticed in neonatal outcomes.\ud CONCLUSIONS: Use of the Arabin pessary in twin pregnancies with short TVU CL at 16-24 weeks does not prevent SPTB or improve perinatal outcome

multicenter cohort study

Publisher Copyright: © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.Objective: Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies. Methods: This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin-to-twin transfusion syndrome (TTTS), twin anemia–polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention. Results: Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow-up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity-related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124). Conclusion: Monochorionicity-related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management.publishersversionpublishe

Postmortem Micro-CT of Human Fetal Heart—A Systematic Literature Review

Micro-computed tomography (CT) is a non-invasive alternative to conventional macroscopic dissection for the evaluation of human fetal cardiac anatomy. This paper aims to systematically review the literature regarding the use of micro-CT to examine human fetal hearts, to illustrate its educational and research implications and to explain its possible directions for the future. A systematic literature review was conducted following the PRISMA statement to identify publications concerning micro-CT applications for the isolated human fetal heart. The search strategy identified nine eligible studies. Micro-CT is technically feasible for postmortem examination of the human fetal heart coming from early and late termination of pregnancy. It reaches high diagnostic accuracy, and it seems to perform better than autopsy in small samples or in the case of early termination of pregnancy. Applications derived from micro-CT allow multiple off-time evaluations and interdisciplinary comparisons for educational purposes and research perspectives in biological and bioengineering domains

Micro-computed tomography of isolated fetal hearts following termination of pregnancy: a feasibility study at 8 - 12 week’s gestation.

Objectives:To assess the feasibility of retrieval of intact human fetal hearts after first trimester surgical termination of pregnancy (TOP) and subsequent anatomical assessment by postmortem micro-computed tomography (micro-CT). Methods:In a cohort of consenting women undergoing surgical TOP between 8 and 13 weeks’ gestation, we attempted the retrieval of the fetal heart from the suction material. Specimens were immersion fixed in 10% formaldehyde, scanned by Iodine enhanced micro-CT and cardiac anatomy assessed by a multidisciplinary team using 3D-multiplanar analysis. Results:The median gestational age at TOP was 10.7weeks (range 8.3–12.9). In 57 (95.0%) out of 60 suction specimens, the heart could be retrieved. The median cardiac length was 5mm (range 2- 8mm), in three (5.3%), the heart was too damaged to assess cardiac anatomy and in five (8.7%) only the four chambers could be examined. In the remaining 49 (86.0%) cases, a detailed assessment of cardiac anatomy was possible, showing a major defect in two (4.1%) and a minor defect in four (8.2%). Conclusions:Fetal hearts can be retrieved after first trimester TOP being intact in the vast majority of cases. Iodine enhanced, post-mortem micro-CT can be used to assess cardiac anatomy from as early as 8 weeks and to describe heart abnormalities. Page 3 of 19 http://mc.status: accepte

Il DNA fetale

Nel circolo materno è presente materiale genetico di origine fetale sotto forma di una miscela di frammenti di acidi nucleici aventi due distinte origini: materna e fetale. La quantità di DNA fetale rilevata nel campione di plasma analizzato rispetto al DNA plasmatico totale (materno + fetale) viene espressa in termini di frazione fetale (FF). Per poter fornire risultati attendibili è necessaria una frazione fetale di almeno il 4%. Le principali tecniche di sequenziamento utilizzate per l’analisi del cfDNA sono tecniche quantitative di seconda generazione (Next Generation Sequencing - NGS) dell’intero genoma (Massively Parallel Shotgun Sequency - MPSS) o di specifiche regioni (CSS, Chromosome Selective Sequencing). Un approccio alternativo di tipo qualitatitvo è basato sull'analisi dei polimorfismi a singolo nucleotide (Single-nucleotide polymorphysm- SNPs). Nessuna delle tecniche di analisi del cfDNA attualmente in uso è in grado di fornire una percentuale di falsi positivi (FPR) pari a 0% e sensibilità (DR) del 100%, configurandosi, di fatto, come test di screening e non diagnostici. Alcune delle applicazioni del cfDNA riguardano l’indagine non invasiva di microdelezioni e altre malattie monogeniche, tuttavia, allo stato attuale non sono disponibili dati sufficientemente validati per porre indicazione al loro utilizzo nella pratica clinica. Una valutazione ecografica accurata nel primo trimestre dovrebbe essere offerta a tutte le donne che richiedono uno screening prenatale indipendentemente dalla scelta di sottoporsi al test del cfDNA. L’esito del cfDNA test viene espresso in forma di due possibili risultati per ciascuna delle aneuploidie cromosomiche prese in esame: basso rischio (&gt; 1 su 10.000) o alto rischio (&gt; 99%). Un risultato di basso rischio consente di ridurre il rischio a priori di circa 300 volte per la trisomia 21 e di 50 volte per la trisomia 18 e 13. Un risultato di alto rischio prevede una conferma diagnostica mediante villocentesi o amniocentesi. In una percentuale variabile tra l’1% e il 5% delle gravidanze, il test del cfDNA può non fornire alcun risultato al primo prelievo. Tentativi successivi forniscono un risultato nel 60-70% dei casi. Il fallimento della metodica nella maggior parte dei casi è attribuibile ad una bassa frazione fetale. L’implementazione del cfDNA nella pratica clinica può essere realizzata attraverso due possibili percorsi: in sostituzione all’attuale Test Combinato (“screening universale”) oppure come screening di seconda linea dopo Test Combinato (“screening contingente”). Il modello contingente appare il più vantaggioso

Dural Sinus Arteriovenous Malformation in the Fetus. Case Report and Discussion of the Literature

Sonographic findings of cerebral arteriovenous malformations in the fetus are uncommon and usually regard aneurysm of the Galen vein. Outcome of arteriovenous malformations is usually severe. We report a case of a fetus at 21 weeks’ gestation with a rarer arteriovenous malformation, referred to us for echocardiography on account of a suspicious cardiomegaly at obstetrical scan. Upon examination, we found cardiomegaly, together with an associated moderate tricuspid regurgitation, however, there were no clear features of tricuspid dysplasia. Considering an unusually dilated superior vena cava, we found via color Doppler imaging a systodiastolic flow at Color Doppler progressing. Subsequent MRI of the central nervous system determined the localization in the sinus dura mater. Due to an already evident hemodynamic impact, the parents opted for the termination of the pregnancy. Autopsy confirmed a voluminous arteriovenous malformation of the transverse sinus of the dura mater, severe cardiomegaly, mainly of the ventricles, and hypoplasia of the lungs