Midline structures and cortical development in fetuses with late growth restriction according to Doppler status: prospective study.

OBJECTIVE: Fetuses with late growth restriction (FGR) have a higher risk of sub-optimal neurocognitive performance after birth. Previous studies have reported that impaired brain and cortical development can start in utero. The primary aim of this study was to report midline structures and cortical development in fetuses with late growth restriction according to its severity; the secondary aim was to elucidate whether the severity of FGR, as defined by the presence of abnormal Doppler findings, plays a role in affecting brain growth and maturation. METHODS: Prospective cross-sectional study including fetuses with late FGR undergoing neurosonography between 32 and 34 weeks of gestation. Midline structures (corpus callosum (CC) and cerebellar vermis (CV) length) and cortical development, including the depth of Sylvian (SF), parieto-occipital (POF) and calcarine (CF) were compared between FGR, small (SGA) and appropriate for gestational age (AGA) fetuses, defined upon the Delphi criteria. Sub-group analysis according to the severity of FGR (normal vs abnormal fetal Dopplers) was also performed. Univariate analysis was used to analyze the data. RESULTS: 52 FGR with normal, 60 with abnormal Dopplers, 64 SGA and 100 AGA fetuses were included in the analysis. SGA and FGR fetuses showed significant differences in absolute values of CC (median (interquartile range) control 43.47 (28.9-56.05), vs SGA 41.85 (27.82-51.79), vs FGR ND 38.54 (29.12-50.53), vs FGR AD 31.72 (23.8-40.19) K= 26.68; p<0.0001), CV (control 24.85 (17.55-29.21), SGA K=16.71; p=0.0008), SF (control 14.52 (10.65-16.76) vs SGA 12.71 (9.8-15.10) vs FGR ND 11.93 (9.12-13.43) VS FGR A 8.30 (6.72-10.33) K=75.82; p<0.0001), POF (control 8.56 (6.31-11.09) vs SGA 8.11 (5.58-10.43) vs FGR ND 7.81 (6.14-9.29) vs FGR AD 6.56 (4.22-7.99), K=45.06; p<0.0001) and CF ( control 9.27 (6.70-11.45) vs SGA 8.23 (5.67-10.65) vs FGR ND 7.68 (5.22-9.41) vs FGR AD 6.26 (4.48-7.19) K=46.14; p<0.0001) when compared to AGA controls with a progressive reduction across groups. When neurosonographic variables were corrected for fetal HC values, significant difference in the length of CC, SF, POF and CF but CV were observed only in FGR fetuses with abnormal Doppler when compared to AGA controls. CONCLUSIONS: Late onset small fetuses showed shorter CC length and a delayed cortical development when compared to control. After controlling for HC size these differences remain significant only in FGR fetuses with abnormal Dopplers. These findings support the existence of a link between brain development and impaired placental function. This article is protected by copyright. All rights reserved.

Uterine artery Doppler in early labor and perinatal outcome in low-risk term pregnancy: prospective multicenter study.

OBJECTIVE: The prediction of adverse perinatal outcomes in low-risk pregnancies is poor, mainly owing to the lack of reliable biomarkers. Uterine artery (UtA) Doppler is closely associated with placental function and may facilitate the peripartum detection of subclinical placental insufficiency. The objective of this study was to evaluate the association of mean UtA pulsatility index (PI) measured in early labor with obstetric intervention for suspected intrapartum fetal compromise and adverse perinatal outcome in uncomplicated singleton term pregnancies. METHODS: This was a prospective multicenter observational study conducted across four tertiary maternity units. Low-risk term pregnancies with spontaneous onset of labor were included. The mean UtA-PI was recorded between uterine contractions in women admitted for early labor and converted into multiples of the median (MoM). The primary outcome of the study was the occurrence of obstetric intervention, i.e. Cesarean section or instrumental delivery, for suspected intrapartum fetal compromise. Secondary outcomes were the occurrence of adverse perinatal outcomes, including 5-min Apgar score < 7, low cord arterial pH, raised cord arterial base excess, admission to the neonatal intensive care unit (NICU) and postnatal diagnosis of small-for-gestational-age fetus. Composite adverse perinatal outcome was defined as the occurrence of at least one of the following: acidemia in the umbilical artery, defined as pH < 7.10 and/or base excess > 12 mmol/L, 5-min Apgar score < 7 or admission to the NICU. RESULTS: Overall, 804 women were included, of whom 40 (5.0%) had abnormal mean UtA-PI MoM. Women who had an obstetric intervention for suspected intrapartum fetal compromise were more frequently nulliparous (72.2% vs 53.6%; P = 0.008), had a higher frequency of increased mean UtA-PI MoM (13.0% vs 4.4%; P = 0.005) and had a longer duration of labor (456 ± 221 vs 371 ± 192 min; P = 0.01). On logistic regression analysis, only increased mean UtA-PI MoM (adjusted odds ratio (aOR), 3.48 (95% CI, 1.43-8.47); P = 0.006) and parity (aOR, 0.45 (95% CI, 0.24-0.86); P = 0.015) were independently associated with obstetric intervention for suspected intrapartum fetal compromise. Increased mean UtA-PI MoM was associated with a sensitivity of 0.13 (95% CI, 0.05-0.25), specificity of 0.96 (95% CI, 0.94-0.97), positive predictive value of 0.18 (95% CI, 0.07-0.33), negative predictive value of 0.94 (95% CI, 0.92-0.95), positive likelihood ratio of 2.95 (95% CI, 1.37-6.35) and negative likelihood ratio of 0.91 (95% CI, 0.82-1.01) for obstetric intervention for suspected intrapartum fetal compromise. Pregnancies with increased mean UtA-PI MoM also showed a higher incidence of birth weight < 10th percentile (20.0% vs 6.7%; P = 0.002), NICU admission (7.5% vs 1.2%; P = 0.001) and composite adverse perinatal outcome (15.0% vs 5.1%; P = 0.008). CONCLUSION: Our study, conducted in a cohort of low-risk term pregnancies enrolled in early spontaneous labor, showed an independent association between increased mean UtA-PI and obstetric intervention for suspected intrapartum fetal compromise, albeit with moderate capacity to rule in, and poor capacity to rule out, this condition. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Role of fetal head-circumference-to-maternal-height ratio in predicting Cesarean section for labor dystocia: prospective multicenter study.

OBJECTIVE: To evaluate the relationship between the fetal head-circumference-to-maternal-height (HC/MH) ratio measured shortly before delivery and the occurrence of Cesarean section (CS) for labor dystocia. METHODS: This was a multicenter prospective cohort study involving four tertiary maternity hospitals. An unselected cohort of women with a singleton fetus in cephalic presentation, at a gestational age beyond 36 + 0 weeks and without any contraindication for vaginal delivery, was enrolled between September 2020 and November 2021. The MH and fetal HC were measured on admission of the patient to the labor ward. The primary outcome of the study was the performance of the HC/MH ratio in the prediction of CS for labor dystocia. Women who underwent CS for any indication other than failed labor progression, including fetal distress, were excluded from the final analysis. RESULTS: A total of 783 women were included in the study. Vaginal delivery occurred in 744 (95.0%) women and CS for labor dystocia in 39 (5.0%). CS for labor dystocia was associated with shorter MH (mean ± SD, 160.4 ± 6.6 vs 164.5 ± 6.3 cm; P < 0.001), larger fetal HC (339.6 ± 9.5 vs 330.7 ± 13.0 mm; P < 0.001) and a higher HC/MH ratio (2.12 ± 0.11 vs 2.01 ± 0.10; P < 0.001) compared with vaginal delivery. Multivariate logistic regression analysis showed that the HC/MH ratio was associated independently with CS for labor dystocia (adjusted odds ratio, 2.65 (95% CI, 1.85-3.79); P < 0.001). The HC/MH ratio had an area under the receiver-operating-characteristics curve of 0.77 and an optimal cut-off value for discriminating between vaginal delivery and CS for labor dystocia of 2.09, which was associated with a sensitivity of 0.62 (95% CI, 0.45-0.77), specificity of 0.79 (95% CI, 0.76-0.82), positive predictive value of 0.13 (95% CI, 0.09-0.19) and negative predictive value of 0.98 (95% CI, 0.96-0.99). CONCLUSIONS: In a large cohort of unselected pregnancies, the HC/MH ratio performed better than did fetal HC and MH alone in identifying those cases that will undergo CS for labor dystocia, albeit with moderate predictive value. The HC/MH ratio could assist in the evaluation of women at risk for CS for labor dystocia. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Novel artificial intelligence approach for automatic differentiation of fetal occiput anterior and non-occiput anterior positions during labor.

OBJECTIVES: To describe a newly developed machine-learning (ML) algorithm for the automatic recognition of fetal head position using transperineal ultrasound (TPU) during the second stage of labor and to describe its performance in differentiating between occiput anterior (OA) and non-OA positions. METHODS: This was a prospective cohort study including singleton term (> 37 weeks of gestation) pregnancies in the second stage of labor, with a non-anomalous fetus in cephalic presentation. Transabdominal ultrasound was performed to determine whether the fetal head position was OA or non-OA. For each case, one sonographic image of the fetal head was then acquired in an axial plane using TPU and saved for later offline analysis. Using the transabdominal sonographic diagnosis as the gold standard, a ML algorithm based on a pattern-recognition feed-forward neural network was trained on the TPU images to discriminate between OA and non-OA positions. In the training phase, the model tuned its parameters to approximate the training data (i.e. the training dataset) such that it would identify correctly the fetal head position, by exploiting geometric, morphological and intensity-based features of the images. In the testing phase, the algorithm was blinded to the occiput position as determined by transabdominal ultrasound. Using the test dataset, the ability of the ML algorithm to differentiate OA from non-OA fetal positions was assessed in terms of diagnostic accuracy. The F1 -score and precision-recall area under the curve (PR-AUC) were calculated to assess the algorithm's performance. Cohen's kappa (κ) was calculated to evaluate the agreement between the algorithm and the gold standard. RESULTS: Over a period of 24 months (February 2018 to January 2020), at 15 maternity hospitals affiliated to the International Study group on Labor ANd Delivery Sonography (ISLANDS), we enrolled into the study 1219 women in the second stage of labor. On the basis of transabdominal ultrasound, they were classified as OA (n = 801 (65.7%)) or non-OA (n = 418 (34.3%)). From the entire cohort (OA and non-OA), approximately 70% (n = 824) of the patients were assigned randomly to the training dataset and the rest (n = 395) were used as the test dataset. The ML-based algorithm correctly classified the fetal occiput position in 90.4% (357/395) of the test dataset, including 224/246 with OA (91.1%) and 133/149 with non-OA (89.3%) fetal head position. Evaluation of the algorithm's performance gave an F1 -score of 88.7% and a PR-AUC of 85.4%. The algorithm showed a balanced performance in the recognition of both OA and non-OA positions. The robustness of the algorithm was confirmed by high agreement with the gold standard (κ = 0.81; P < 0.0001). CONCLUSIONS: This newly developed ML-based algorithm for the automatic assessment of fetal head position using TPU can differentiate accurately, in most cases, between OA and non-OA positions in the second stage of labor. This algorithm has the potential to support not only obstetricians but also midwives and accoucheurs in the clinical use of TPU to determine fetal occiput position in the labor ward. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Role of Doppler ultrasound at time of diagnosis of late-onset fetal growth restriction in predicting adverse perinatal outcome: prospective cohort study.

OBJECTIVE: Pregnancies complicated by late-onset fetal growth restriction (FGR) are at increased risk of short- and long-term morbidities. Despite this, identification of cases at higher risk of adverse perinatal outcome, at the time of FGR diagnosis, is challenging. The aims of this study were to elucidate the strength of association between fetoplacental Doppler indices at the time of diagnosis of late-onset FGR and adverse perinatal outcome, and to determine their predictive accuracy. METHODS: This was a prospective study of consecutive singleton pregnancies complicated by late-onset FGR. Late-onset FGR was defined as estimated fetal weight (EFW) or abdominal circumference (AC) < 3rd centile, or EFW or AC < 10th centile and umbilical artery (UA) pulsatility index (PI) > 95th centile or cerebroplacental ratio (CPR) < 5th centile, diagnosed after 32 weeks. EFW, uterine artery PI, UA-PI, fetal middle cerebral artery (MCA) PI, CPR and umbilical vein blood flow normalized for fetal abdominal circumference (UVBF/AC) were recorded at the time of the diagnosis of FGR. Doppler variables were expressed as Z-scores for gestational age. Composite adverse perinatal outcome was defined as the occurrence of at least one of emergency Cesarean section for fetal distress, 5-min Apgar score < 7, umbilical artery pH < 7.10 and neonatal admission to the special care unit. Logistic regression analysis was used to elucidate the strength of association between different ultrasound parameters and composite adverse perinatal outcome, and receiver-operating-characteristics (ROC)-curve analysis was used to determine their predictive accuracy. RESULTS: In total, 243 consecutive singleton pregnancies complicated by late-onset FGR were included. Composite adverse perinatal outcome occurred in 32.5% (95% CI, 26.7-38.8%) of cases. In pregnancies with composite adverse perinatal outcome, compared with those without, mean uterine artery PI Z-score (2.23 ± 1.34 vs 1.88 ± 0.89, P = 0.02) was higher, while Z-scores of UVBF/AC (-1.93 ± 0.88 vs -0.89 ± 0.94, P ≤ 0.0001), MCA-PI (-1.56 ± 0.93 vs -1.22 ± 0.84, P = 0.004) and CPR (-1.89 ± 1.12 vs -1.44 ± 1.02, P = 0.002) were lower. On multivariable logistic regression analysis, Z-scores of mean uterine artery PI (P = 0.04), CPR (P = 0.002) and UVBF/AC (P = 0.001) were associated independently with composite adverse perinatal outcome. UVBF/AC Z-score had an area under the ROC curve (AUC) of 0.723 (95% CI, 0.64-0.80) for composite adverse perinatal outcome, demonstrating better accuracy than that of mean uterine artery PI Z-score (AUC, 0.593; 95% CI, 0.50-0.69) and CPR Z-score (AUC, 0.615; 95% CI, 0.52-0.71). A multiparametric prediction model including Z-scores of MCA-PI, uterine artery PI and UVBF/AC had an AUC of 0.745 (95% CI, 0.66-0.83) for the prediction of composite adverse perinatal outcome. CONCLUSION: While CPR and uterine artery PI assessed at the time of diagnosis are associated independently with composite adverse perinatal outcome in pregnancies complicated by late-onset FGR, their diagnostic performance for composite adverse perinatal outcome is low. UVBF/AC showed better accuracy for prediction of composite adverse perinatal outcome, although its usefulness in clinical practice as a standalone predictor of adverse pregnancy outcome requires further research. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Papel de la ecografía Doppler en el momento del diagnóstico de la restricción del crecimiento fetal de aparición tardía para la predicción de resultados perinatales adversos: estudio prospectivo de cohortes OBJETIVO: Los embarazos complicados por la restricción del crecimiento fetal (RCF) de aparición tardía tienen un mayor riesgo de morbilidad a corto y largo plazo. A pesar de ello, es difícil identificar los casos con mayor riesgo de resultados perinatales adversos en el momento del diagnóstico de RCF. Los objetivos de este estudio fueron dilucidar la fortaleza de la asociación entre los índices Doppler fetoplacentarios en el momento del diagnóstico de la RCF de aparición tardía y el resultado perinatal adverso, y determinar su precisión predictiva. MÉTODOS: Este fue un estudio prospectivo de embarazos consecutivos con feto único complicados por una RCF de aparición tardía. La aparición tardía de la RCF se definió como peso estimado del feto (PEF) o circunferencia abdominal (CA) <3er percentil, o PEF o CA <10o percentil junto con índice de pulsatilidad (IP) de la arteria umbilical (AU) >95o percentil, o una relación cerebroplacentaria (RCP) <5o percentil, diagnosticado después de las 32 semanas. El PEF, el IP de la arteria uterina (IP-AU), el IP de la arteria cerebral media fetal (ACM), la RCP y el flujo sanguíneo de la vena umbilical normalizado para la circunferencia abdominal fetal (UVBF/AC, por sus siglas en inglés) se registraron en el momento del diagnóstico de RCF. Las variables Doppler se expresaron como puntuaciones Z para la edad gestacional. El resultado perinatal adverso compuesto se definió como la ocurrencia de al menos una cesárea de emergencia por sufrimiento fetal, test de Apgar a los 5 minutos <7, pH de la arteria umbilical <7,10 y el ingreso a la unidad de cuidados especiales de recién nacidos. Se utilizó el análisis de regresión logística para dilucidar la fortaleza de la asociación entre los diferentes parámetros de la ecografía y el resultado perinatal adverso compuesto, y se empleó el análisis de la curva de características operativas del receptor (ROC, por sus siglas en inglés) para determinar su precisión predictiva. RESULTADOS: En total, se incluyeron 243 embarazos con feto único consecutivos complicados por RCF de aparición tardía. El resultado perinatal adverso compuesto se produjo en el 32,5% (IC 95%, 26,7-38,8%) de los casos. En los embarazos con resultados perinatales adversos compuestos, en comparación con los que no los tuvieron, la puntuación Z del IP de la arteria uterina media (2,23±1,34 vs 1,88±0,89, P=0,02) fue mayor, mientras que las puntuaciones Z de UVBF/AC (-1,93±0,88 vs -0,89±0,94, P≤0,0001), IP-ACM (-1,56±0,93 vs -1,22±0,84, P=0,004) y RCP (-1,89±1,12 vs -1,44±1,02, P=0,002) fueron más bajas. En el análisis de regresión logística multivariable, las puntuaciones Z del IP de la arteria uterina media (P=0,04), RCP (P=0,002) y UVBF/AC (P=0,001) estuvieron asociadas de forma independiente con el resultado perinatal adverso compuesto. La puntuación Z del UVBF/AC tuvo un área bajo la curva (ABC) ROC de 0,723 (IC 95%, 0,64-0,80) para el resultado perinatal adverso compuesto, demostrando una mejor precisión que la de la puntuación Z del IP de la arteria uterina media (ABC, 0,593; IC 95%, 0,50-0,69) y la de la puntuación Z de la RCP (ABC, 0,615; IC 95%, 0,52-0,71). Un modelo de predicción multiparamétrico que incluía las puntuaciones Z del IP-ACM, el IP de la arteria uterina y el UVBF/AC resultó en un ABC de 0,745 (IC 95%, 0,66-0,83) para la predicción de un resultado perinatal adverso compuesto. CONCLUSIÓN: Aunque la RCP y el IP de la arteria uterina evaluados en el momento del diagnóstico están asociados de forma independiente con un resultado perinatal adverso compuesto en embarazos complicados por una RCF de aparición tardía, la eficacia del diagnóstico para el resultado perinatal adverso compuesto es baja. El UVBF/AC mostró una mayor precisión para la predicción de un resultado perinatal adverso compuesto, aunque su utilidad en la práctica clínica como parámetro indicativo independiente del resultado adverso del embarazo requiere más investigación. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Role of first-trimester umbilical vein blood flow in predicting large-for-gestational age at birth.

OBJECTIVES: To describe umbilical vein (UV) hemodynamics at 11 + 0 to 13 + 6 weeks of gestation in pregnancies delivering a large-for-gestational-age (LGA) neonate, and to build a multiparametric model, including pregnancy and ultrasound characteristics in the first trimester, that is able to predict LGA at birth. METHODS: This was a matched case-control study, of singleton pregnancies that underwent ultrasound examination at 11 + 0 to 13 + 6 weeks for aneuploidy screening, at a single center over a 4-year period. Cases were women who delivered a neonate with birth weight (BW) > 90th centile for gestational age and sex, according to local birth-weight standards, while controls were those who delivered a neonate with BW ranging between the 10th and 90th centiles, matched for maternal and gestational age, at a ratio of 1:3. Each included case underwent Doppler assessment of the uterine arteries and UV, including measurement of its diameter, time-averaged maximum velocity (TAMXV) and UV blood flow (UVBF). UVBF and its components were expressed as Z-scores. Fisher's exact test and Mann-Whitney U-test were used to compare differences in maternal biomarkers and ultrasound characteristics between pregnancies complicated by LGA and controls. Logistic regression and receiver-operating-characteristics (ROC) curve analyses were carried out to identify independent predictors of LGA and to build a multiparametric prediction model integrating different maternal, pregnancy and ultrasound characteristics. Subgroup analysis was also performed, considering women who delivered a neonate with BW > 4000 g. RESULTS: In total, 964 pregnancies (241 with LGA at birth and 723 without) were included in the study. In LGA pregnancies compared with controls, UV-TAMXV Z-score (0.8 (interquartile range (IQR), 0.4-1.5) vs 0.0 (IQR, -0.3 to 0.5); P ≤ 0.001) and UVBF Z-score (1.3 (IQR, 0.8-1.9) vs 0.1 (IQR, -0.4 to 0.4); P ≤ 0.001) were higher, while there was no difference in median UV diameter Z-score (P = 0.56). Median uterine artery pulsatility index multiples of the median (MoM; 0.94 (IQR, 0.78-1.12) vs 1.02 (IQR, 0.84-1.19); P = 0.04) was significantly lower in LGA pregnancies. On multivariate logistic regression analysis, maternal body mass index (BMI; adjusted odds ratio (aOR), 1.2 (95% CI, 1.1-1.7); P < 0.001), parity (aOR, 1.4 (95% CI, 1.2-1.6); P < 0.001), pregnancy-associated plasma protein-A (PAPP-A) MoM (aOR, 1.1 (95% CI, 1.0-1.6); P = 0.04) and UVBF Z-score (aOR, 1.6 (95% CI, 1.1-1.9); P < 0.001) were associated independently with LGA. A multiparametric model integrating parity, BMI and PAPP-A MoM provided an area under the ROC curve (AUC) of 0.72 (95% CI, 0.67-0.76) for the prediction of LGA. The addition of UVBF Z-score to this model significantly improved the prediction of LGA provided by maternal and biochemical factors, with an AUC of 0.79 (95% CI, 0.75-0.83; P = 0.03). Similarly, the model incorporating UVBF Z-score predicted BW > 4000 g with an AUC of 0.83 (95% CI, 0.75-0.93). CONCLUSIONS: UVBF measured at the time of the 11-14-week scan is associated independently with, and is predictive of, LGA and BW > 4000 g. Adding measurement of UVBF to a multiparametric model that includes maternal (parity and BMI) and biochemical (PAPP-A) parameters improves the diagnostic accuracy of prenatal screening for LGA at birth. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

[Ultrasonographic and clinical methods in the management of prolonged pregnancy]. / Confronto tra metodiche cliniche e strumentali nella gestione della gravidanza protratta.

AIM: The aim of this study was to evaluate the role of Bishop score, sonographic measurements of uterine cervical length and maternal characteristics, as predictors of spontaneous onset of labor within 24 hours, as well as response to induction in prolonged pregnancies. METHODS: Pregnancies with gestational age over 280 days were followed as outpatient. Patients were included in the study if spontaneous delivery occurred between 286 and 295 days of gestation, or in pregnancies with gestational age of 291-293 days who required labor induction. Data about Bishop score, ultrasonographic cervical characteristics (length, funneling, volume) and maternal features (parity, body mass index and age) registered at the last control immediately before the delivery were retrieved from clinical charts. RESULTS: Data from 195 patients were available. Bishop score and, in particular, ultrasonographic cervical length can predict the spontaneous onset of labor with a positive predictive value (PPV) of 22% and 44%, respectively in 24 hours. On the other hands, in patients requiring labor induction, parity and ultrasonographic cervical length remained the only predictive parameters with a PPV of 39% and 42%, respectively. In term of predictive performance, the value of 30 mm was identified as the best cut-off value for the ultrasonographic cervical length (specificity 59% and sensitivity 69%). CONCLUSION: In prolonged pregnancies, Bishop score and ultrasonographic cervical length were shown to be relevant in the prediction of spontaneous onset of labor, while in patients who required labor induction, ultrasonographic cervical length represented the only clinic parameter predicting the onset of labor.

In-utero stem cell transplantation: clinical use and therapeutic potential.

Early evidence suggests that in-utero stem cell transplantation represents a new therapeutic strategy for different congenital disease. Moreover, gene therapy constitutes one of the most promising new approach to treat a wide spectrum of genetic disorders. It was shown that the fetus could represent an ideal recipient because of his immunologic early naiveté in gestation that reduces the risk of immunoreactions. Clinical experience in human fetus was performed in order to treat immunodeficiency and metabolic disorders, hemoglobinopathies and some other genetic diseases. Use of alternative source (i.e., cord blood, placenta, membrane, amniotic fluid, fetal tissue) of stem cell transplanted has been only one of the several strategies to improve donor cell advantages on host stem cell. The present review focused on the clinical use and therapeutic potential of in-utero stem cell transplantation, reporting the outcome of human cases treated and the limits of this therapy and possible future applications.

Source of cell injected is a critical factors for short and long engraftment in xeno-transplantation.

This study aims to investigate engraftment of human cord blood and foetal bone marrow stem cells after in utero transplantation via the intracoelomic route in the sheep. Here, we performed transplantation in 14 single and 1 twin sheep foetuses at 40-47 days of development, using a novel schedule for injection. (i) Single injection of CD34(+) human cord blood stem cells via the coelomic route (from 10 to 50 x 10(4)) in seven single foetuses. (ii) Single injection of CD34(+) foetal bone marrow stem cells via the intracoelomic route with further numbers of cells (20 x 10(5) and 8 x 10(5), respectively) in three single and in one twin foetuses. (iii) Double fractioned injection (20-30 x 10(6)) via the coelomic route and 20 x 10(6) postnatally, intravenously, shortly after birth of CD3-depleted cord blood stem cells in four single foetuses. In the first group, three single foetuses showed human/sheep chimaerism at 1, 8 and 14 months after birth. In the second group, the twin foetuses showed human/sheep chimaerism at 1 month after birth. In the third group, only two out of four single foetuses that underwent transplantation showed chimaerism at 1 month. While foetal bone marrow stem cells showed good short-term engraftment (1 month after birth), cord blood stem cells were able to persist longer in the ovine recipients (at 1, 8 and 14 months after birth).