Search

Authors suggest that high incidence of persistence pulmonary hypertension among neonates delivered by elective cesarean is related to lower levels of circulating norepinephrine in neonates after cesarean section than after vaginal delivery. [ABSTRACT FROM AUTHOR]

Introduction: Chronic Histiocytic Intervillositis (CHI) appears to be among the most severe placental diseases. Its rarity has limited our knowledge of the women in whom it occurs., Objective: To search for maternal characteristics linked to the existence of CHI, by first studying the current pregnancy included in the study, then their previous pregnancies., Material and Methods: We conducted a monocentric case-control study between 2000 and 2020. CHI cases were diagnosed by microscopic examination of the placenta. "Low-risk" controls gave birth just before each case, whatever the outcome. "High-risk" controls benefited from placental microscopy immediately after the case examinations., Results: 151 women were included in each group. CHI cases had twice as many previous pregnancies as both controls, but no more living children at home. Regarding obstetric history, fetal losses were significantly higher in CHI cases: compared to "low-risk" controls, there were more early miscarriages (20.0%, OR 2.6 [1.5;4.8]), late miscarriages (4.8%, OR 8.8 [1.1;187]) and in utero deaths (5.4%, OR 5.6 [1.7;19.8]). The risk of fetal loss does not appear to be increased in first pregnancies of CHI cases. However, differences appeared between cases and both "low-risk" and "high-risk" controls with a history of two previous miscarriages (21.7% vs 11.2%, p=0.009 or vs 9.6%, p=0.005) and the outcome of the second pregnancy (number of living children 59.7% vs 78.0%, p=0.033 or vs 63.0%, p=0.71), respectively., Conclusion: Women with CHI have a more frequent history of pregnancy failure than other women. This excess fetal loss seems to occur only after the second pregnancy or after two previous miscarriages., Competing Interests: Declaration of competing interest All authors declare that they did not use generative AI and AI-assisted technologies in the writing process. All authors have no conflicts of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Advances in haemolytic disease of the fetus and newborn have led to numerous treatment options. We report practice variations in the management and outcomes of haemolytic disease of the fetus and newborn in at-risk pregnancies., Methods: In this international, retrospective, observational cohort study, data from cases with moderate or severe haemolytic disease of the fetus and newborn were retrieved from 31 centres in 22 countries. Eligible participants had pregnancies with haemolytic disease of the fetus that led to fetal death at 16 + 0 weeks or later, those treated antenatally with intrauterine transfusion or intravenous immunoglobulins, or neonates without antenatal treatment who were treated with intensive phototherapy, exchange transfusion, or red blood cell transfusions. All patients had confirmed maternal alloantibodies and an antigen-positive fetus incompatible with the maternal alloantibody. Patients with ABO-incompatibility only were excluded. We assessed serological diagnostics and referrals, antenatal treatment and timing, complications, delivery route, and gestational age at birth. Outcomes were analysed in all eligible participants who had complete data available., Findings: 2443 pregnancies with haemolytic disease of the fetus and newborn treated between Jan 1, 2006, and July 1, 2021, were shared by the centres and analysed between Dec 1, 2021, and March 1, 2023. 23 pregnancies were excluded due to missing information and we included 2420 for further analysis. 1764 (72·9%) of 2420 pregnancies were affected by D-antibodies. 95 (3·9%) of 2420 pregnancies resulted in fetal death. Of the 2325 liveborn neonates, 1349 (58·1%) received any form of antenatal treatment and 976 (41·9%) were only treated postnatally. Median gestational age at referral was 20·4 weeks (IQR 14·9-28·0) and ranged between medians of 10·0 and 26·3 weeks between centres. Severe hydrops at first intrauterine transfusion was present in 185 (14·5%) of 1276 pregnancies, with proportions ranging between 0 and 42% between centres. A median of two intrauterine transfusions (IQR 1-4) were done per pregnancy. The fetal access sites used in intrauterine transfusions varied widely between centres. Non-lethal complications in intrauterine transfusions by transfusion site occurred at a lower rate in intrahepatic approaches (2·0%, 95% CI 1·1-3·3) than in placental insertion (6·9%, 5·8-8·0) and free loop (13·3%, 8·9-18·9). The use and indication for intravenous immunoglobulin administration varied widely. Neonates with intrauterine transfusion were born at a median gestational age of 35·6 weeks (IQR 34·0-36·7), ranging between medians of 33·2 and 37·3 weeks between centres, while neonates without antenatal treatment were born at a median gestational age of 37·3 (IQR 36·3-38·1), ranging between medians of 34·9 and 38·9 weeks between centres., Interpretation: We found considerable variation in antenatal management and outcomes in haemolytic disease of the fetus and newborn between sites in different countries. Our study shows the capacity of the field to gather valuable data on a rare disease and to optimise care., Funding: None., Competing Interests: Declaration of interests DPdW is doing a PhD programme partly funded by Momenta Pharmaceuticals, which was acquired by Johnson & Johnson, and is an investigator for a phase 2 trial (NCT03842189) of a new drug for the treatment of haemolytic disease of the fetus and newborn. EL is a sub-investigator for a phase 2 trial (NCT03842189) of a new drug for the treatment of haemolytic disease of the fetus and newborn, which is sponsored by Janssen Pharmaceuticals. RD reports paid lectures and participation in studies for Janssen Pharmaceuticals. PM received payment for a lecture from CSL Behrin. PM and J-MJ reports participation in an advisory board for haemolytic disease of the fetus and newborn of Janssen Pharmaceuticals in December, 2023, and both report participation in a phase 3 trial (NCT05912517) of a new drug for the treatment of haemolytic disease of the fetus and newborn, which is sponsored by Janssen Pharmaceuticals. ET is the principal investigator for Janssen-sponsored trials Unity and Clarity in Sweden and an advisory Board Member and Steering Committee member for Janssen Pharmaceutical on haemolytic disease of the fetus and newborn and FNAIT programmes. TPS is a member of the board of the International Society of The Fetus as a Patient and member of the expert committee for Gynaecology and Obstetrics at Ministry of Health, Republic of Slovenia. EJTV is the principal investigator for a phase 2 trial (NCT03842189) and phase 3 trial (NCT05912517) of a new drug for the treatment of haemolytic disease of the fetus and newborn, which is sponsored by Janssen Pharmaceuticals. All other authors report no competing interests or financial disclosures., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: To assess the frequency of fetal therapy for fetuses with congenital pulmonary malformations (CPMs) and to investigate their short-term outcomes., Method: The study population included 435 singleton fetuses diagnosed with CPMs from a national population-based cohort study in France in 2015-2018. Information was obtained from medical records on CPM volume ratio (CVR), signs of compression, fetal therapy and perinatal outcomes. The characteristics and outcomes of fetuses with and without fetal therapy were compared using a univariate test., Results: Twenty six fetuses (6.0%, 95% CI: 4.1-8.6) received at least one fetal therapy including thoracoamniotic shunts only (n = 3), antenatal steroids only (n = 12), and a combination of several therapies including thoracentesis and amniodrainage, in addition to shunts and steroids (n = 11). Compared with fetuses without fetal therapy, those who did have higher CVR (1.6 ± 0.3 vs. 0.7 ± 0.04, p < 0.001) and more severe signs of compression (73.1% vs. 12.8%, p < 0.001). The proportion of live births after fetal therapy was 84.6% versus 98.5% (p < 0.001) for those without fetal therapy and the hospital mortality rate was 13.6% versus 1.0% (p = 0.004), respectively., Conclusion: A small minority of fetuses with CPMs underwent fetal therapy. These patients had a lower survival compared with those who did not receive fetal therapy., Trial Registration: NCT02352207., (© 2024 The Author(s). Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Objective: To assess and compare the value of antenatally determined observed-to-expected (O/E) lung-area-to-head-circumference ratio (LHR) on ultrasound examination vs O/E total fetal lung volume (TFLV) on magnetic resonance imaging (MRI) examination to predict postnatal survival of fetuses with isolated, expectantly managed left-sided congenital diaphragmatic hernia (CDH)., Methods: This was a multicenter retrospective study including all consecutive fetuses with isolated CDH that were managed expectantly in Mannheim, Germany, and in five other European centers, that underwent at least one ultrasound examination for measurement of O/E-LHR and one MRI scan for measurement of O/E-TFLV during pregnancy. All MRI data were centralized, and lung volumes were measured by two experienced operators blinded to the pre- and postnatal data. Multiple logistic regression analyses were performed to examine the effect on survival at hospital discharge of various perinatal variables, including the center of management. In left-sided CDH with intrathoracic herniation of the liver, receiver-operating-characteristics (ROC) curves were constructed separately for cases from Mannheim and the other five European centers and were used to compare O/E-TFLV and O/E-LHR in the prediction of postnatal survival., Results: From Mannheim, 309 patients were included with a median gestational age (GA) at ultrasound examination of 29.6 (range, 19.7-39.1) weeks and median GA at MRI examination of 31.1 (range, 18.0-39.9) weeks. From the other five European centers, 116 patients were included with a median GA at ultrasound examination of 26.7 (range, 20.6-37.6) weeks and median GA at MRI examination of 27.7 (range, 21.3-37.9) weeks. Regression analysis demonstrated that the survival rates at discharge were lower in left-sided CDH (odds ratio (OR), 0.349 (95% CI, 0.133-0.918), P = 0.033) and those with intrathoracic liver (OR, 0.297 (95% CI, 0.141-0.628), P = 0.001), and higher with increasing O/E-TFLV (OR, 1.123 (95% CI, 1.079-1.170), P < 0.001), advanced GA at birth (OR, 1.294 (95% CI, 1.055-1.588), P = 0.013) and when birth occurred in Mannheim (OR, 7.560 (95% CI, 3.368-16.967), P < 0.001). Given the difference in survival rate between Mannheim and the five other European centers, ROC curve comparisons between the two imaging modalities were presented separately. For cases of left-sided CDH with intrathoracic herniation of the liver, pairwise comparison showed no significant difference between the area under the ROC curves for the prediction of postnatal survival between O/E-TFLV and O/E-LHR in Mannheim (mean difference = 0.025, P = 0.610, standard error = 0.050), whereas there was a significant difference in the other European centers studied (mean difference = 0.056, P = 0.033, standard error = 0.056)., Conclusions: In fetuses with left-sided CDH and intrathoracic herniation of the liver, the predictive value for postnatal survival of O/E-TFLV on MRI examination and O/E-LHR on ultrasound examination was similar in one center (Mannheim), but O/E-TFLV had better predictive value compared to O/E-LHR in the five other European centers. Hence, in these five European centers, MRI should be included in the diagnostic process for left-sided CDH. © 2024 International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 International Society of Ultrasound in Obstetrics and Gynecology.)

Background: Labor induction of women with a history of uterine scarring is an increasingly frequent situation and one for which there are currently no clear professional recommendations favoring one method over another. The objectives of this study were to determine the success rate of balloon catheter induction in women with a history of caesarean section and to evaluate the main factors associated with vaginal delivery., Materials and Methods: This single-center retrospective study was conducted between January 1, 2014, and December 31, 2018, in Lille, France, and included all women with one previous caesarean section who were induced by first-line balloon catheter induction. Multivariate analysis was performed to identify the factors associated with the primary outcome (vaginal delivery)., Results: Of the 310 women in the sample, 192 delivered vaginally (62 %). After adjustment, factors associated with successful induction (vaginal delivery) were the number of previous vaginal deliveries (odds ratio [OR] 1.37; 95 % confidence interval [CI] 1.04-1.81), evolution of the Bishop score after balloon removal (OR 1.24; 95 % CI 1.10-1.41), and the initial Bishop score (OR 1.17; 95 % CI 1.00-1.37). Uterine rupture was observed in three women (1 %)., Conclusion: The vaginal delivery rate after balloon catheter induction in women with a previous caesarean section was 62 %. Prognostic factors for vaginal delivery include previous vaginal delivery, the initial Bishop score, and evolution of the Bishop score after balloon catheter induction., Competing Interests: Declaration of competing interest None declared, (Copyright © 2024. Published by Elsevier Masson SAS.)

Introduction: Fetal infection during labor with fetal inflammatory response syndrome (FIRS) is associated with neurodevelopmental disabilities, cerebral palsy, neonatal sepsis, and mortality. Current methods to diagnose FIRS are inadequate. Thus, the study aim was to explore whether fetal heart rate variability (HRV) analysis can be used to detect FIRS., Material and Methods: In chronically instrumented near-term fetal sheep, lipopolysaccharide (LPS) was injected intravenously to model FIRS. A control group received saline solution injection. Hemodynamic, blood gas analysis, interleukin-6 (IL-6), and 14 HRV indices were recorded for 6 h. In both groups, comparisons were made between the stability phase and the 6 h following injection (H1-H6, respectively) and between LPS and control groups., Results: Fifteen lambs were instrumented. In the LPS group (n = 8), IL-6 increased significantly after LPS injection (p < 0.001), confirming the FIRS model. Fetal heart rate increased significantly after H5 (p < 0.01). In our FIRS model without shock or cardiovascular decompensation, five HRV measures changed significantly after H2 until H4 in comparison to baseline. Moreover, significant differences between LPS and control groups were observed in HRV measures between H2 and H4. These changes appear to be mediated by an increase of global variability and a loss of signal complexity., Conclusion: As significant HRV changes were detected before FHR increase, these indices may be valuable for early detection of acute FIRS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chevalier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although delayed cord clamping has well-known benefits for preterm and term neonates, it has been inadequately assessed in alloimmunized neonates., Objective: This study aimed to evaluate the benefits and risks of delayed cord clamping in alloimmunized neonates., Study Design: This was a retrospective comparative pre-post cohort study conducted from 2003 to 2018 in a tertiary care center in France. All living singleton neonates whose mothers were followed up for red blood cell alloimmunization during gestation and confirmed at birth (N=224) were included. Neonates were either exposed to immediate (n=125) or delayed cord clamping (n=99). Our main outcome was the time from birth to first exchange transfusions and/or transfusions. Secondary outcomes were hemoglobin level at birth, rate of exchange transfusion, number of postnatal transfusions, maximum bilirubin level, and number of phototherapy hours., Results: Hemoglobin at birth was significantly higher in case of delayed cord clamping (mean difference, 1.7 g/dL; 95% confidence interval, 0.7-2.8). Among infants treated with exchange transfusion or transfusion, the time to initial treatment was higher in case of delayed cord clamping (median difference, 8 days; rate ratio, 1.51; 95% confidence interval, 1.09-2.10). There were no significant differences in the need for exchange transfusion, the number of transfusions, the maximum total bilirubin level, nor the number of phototherapy hours. In the subgroup analysis of neonates needing intrauterine transfusion during pregnancy (ie, severe alloimmunization), neonates had a lower rate of exchange transfusion in case of delayed cord clamping (odds ratio, 0.36; 95% confidence interval, 0.15-0.82)., Conclusion: Our results indicate a benefit of delayed cord clamping in alloimmunization, regardless of pathology severity, without increased risk of jaundice., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: To define a threshold of maternal antibodies at risk of severe fetal anemia in patients followed for anti-RH1 alloimmunization (AI)., Study, Design, and Methods: We conducted a retrospective study of patients followed for anti-RH1 AI at the Lille University Hospital. The first group, severe anemia, included patients who received one or more in utero transfusions (IUT) or who were induced before 37 weeks of pregnancy for suspected severe fetal anemia. The second group, absence of severe anemia, corresponded to patients without intervention during pregnancy related to AI. Sensitivities, specificities, and positive and negative predictive values for screening for severe fetal anemia were calculated for the antibody thresholds of 3.5 and 5 IU/ml for the quantification., Results: Between 2000 and 2018, 207 patients were included 135 in the severe anemia group and 72 in the no severe anemia group. No severe anemia was observed for an antibody titer below 16. For an antibody threshold of 3.5 IU/ml, the sensitivity was 98.2%, with 30.2% false positives. All severe anemias were detected in the second trimester; two cases of severe anemia were not detected in the third trimester. For an antibody threshold of 5 IU/ml, the sensitivity was lower at 95.6%, with five cases of severe anemia not detected., Conclusion: The antibody threshold of 3.5 IU/ml for the quantification and 16 for the titration allow targeting patients requiring close monitoring by an experienced team in case of anti-RH1 AI., (© 2023 AABB.)

Introduction: The objective of our study was to compare the effectiveness of induction in cephalic presentations to that of breech presentations as well as the characteristics of the latter and the maternal-fetal morbidity and mortality., Material and Methods: This was a single-center retrospective study carried out at the Lille University Hospital in the Jeanne de Flandre Maternity Hospital including all patients with a breech fetus for whom an induction was indicated beyond 37 weeks of gestation between January 2014 and December 2020. A matching was performed to include 2 cephalic presentations for one breech presentation. The primary outcome was successful induction defined by two things: passage into the active phase (cervical dilatation > 5 cm) and vaginal delivery., Results: 101 inductions of breech presentations were included and matched to 202 cephalic presentations. After adjustment by BISHOP score, there was no significant difference in the caesarean section rate between the two groups (25.7% in cephalic vs 33.7% in breech, OR 0.67 [CI95% 0.38-1.18]) or in the rate of transition to active phase (80.7% in cephalic vs 82.2% in breech, OR 1.26 [CI95% 0.65-2.44]). Post-partum blood loss was not significantly different between the two groups (14.4% in cephalic vs 12.9% in breech, OR 1.22 [CI95% 0.57-2.57]). Moderate neonatal acidosis was more frequent in the breech group (6,4% in cephalic vs 15,8% in breech, OR 3.04 [CI95% 1.38-6.71])., Conclusion: Induction of breech births beyond 37 weeks of gestation appeared to be as effective as induction of cephalic presentations. There was no difference in the rate of caesarean section and transition to active labor. Maternal morbidity was not increased., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: In the most recent recommendations of the International Federation of Gynecology and Obstetrics (FIGO), a chapter was dedicated to the physiological approach and to the description of fetal mechanisms developed to respond to hypoxia. Our objective was to classify the type of hypoxia in the case of metabolic acidemia and to describe the order of appearance of fetal heart rate abnormalities in cases of gradually evolving hypoxia., Material and Methods: 132 neonates born between 2018 and 2020 with acidemia were included. We excluded preterm birth, fetuses with congenital anomaly and twin pregnancies. Intrapartum cardiotocography traces were assigned to one of these four types of labor hypoxia: acute, subacute, gradually evolving and chronic hypoxia. For gradually evolving hypoxia, fetal heart rate abnormalities were described according to the FIGO classification., Results: 36 cardiotocography traces (27.3%) were classified as acute hypoxia, 14 (10.6%) as subacute hypoxia, and 3 (3.2%) as chronic hypoxia; gradually evolving hypoxia occurred in 62 cases (47%). In 77.4% of cases of gradually evolving hypoxia, deceleration was the first anomaly to appear, with loss of variability and bradycardia appearing later. Increased fetal heart rate was observed immediately after late deceleration in 46.8% of cases and was followed by a loss of variability or saltatory rhythm in 37.1% of cases., Conclusions: In cases of metabolic acidemia at term, the most frequent situation observed was gradually evolving hypoxia, with an initial occurrence of decelerations. The sequence of fetal heart rate modifications was variable., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: In comparison to eutrophic fetuses, intra uterine growth restriction fetuses (IUGR) have a higher risk of perinatal morbi-mortality. There are no guidelines on the labor induction of labor (IOL) method to be performed in IUGR. The main objective was to determine fetal and maternal predictive factors of successful induction in IUGR fetuses from 36 weeks. Study design We conducted a retrospective cohort single-center study including 320 women with a cephalic fetal presentation. Labour was induced after 36 weeks for suspected IUGR between January 2013 and December 2019., Results: Among the 320 patients, 246 were delivered vaginally (76.9 %) and 74 had a cesarean (23.1 %). Prognostic factors for successful IUGR induction were nonscarring uterus (OR 8.41; 95 %CI [2.92-24.21]), absence of preeclampsia (OR 7.14; 95 %CI [2.42-21.03]), multiparity (OR 4.32; 95 %CI [1.83-10.18]), normal fetal heart rate before IOL (OR 2.99; 95 %CI [1.24-7.22]) and BMI < 30 (OR 3.54; 95 %CI [1.62-7.72]). Doppler abnormalities, method and number of line of IOL, cervical evaluation were not significant in our study., Conclusion: The prognostic factors for successful IUGR induction are essentially maternal. Thus, a low BMI, multiparity, nonscarring uterus, absence of preeclampsia, and a normal FHR are good prognostic factors in IUGR induction., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: This study evaluated the association between fetal heart rate variability (HRV) and the occurrence of hypoxic-ischemic encephalopathy in a fetal sheep model., Material and Methods: The experimental protocol created a hypoxic condition with repeated cord occlusions in three phases (A, B, C) to achieve acidosis to pH <7.00. Hemodynamic, gasometric and HRV parameters were analyzed during the protocol, and the fetal brain, brainstem and spinal cord were assessed histopathologically 48 h later. Associations between the various parameters and neural injury were compared between phases A, B and C using Spearman's rho test., Results: Acute anoxic-ischemic brain lesions in all regions was present in 7/9 fetuses, and specific neural injury was observed in 3/9 fetuses. The number of brainstem lesions correlated significantly and inversely with the HRV fetal stress index (r = -0.784; p = 0.021) in phase C and with HRV long-term variability (r = -0.677; p = 0.045) and short-term variability (r = -0.837; p = 0.005) in phase B. The number of neurological lesions did not correlate significantly with other markers of HRV., Conclusions: Neural injury caused by severe hypoxia was associated with HRV changes; in particular, brainstem damage was associated with changes in fetal-specific HRV markers., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Aim: Maternal immune thrombocytopenia (ITP) may induce neonatal thrombocytopenia (nTP), which carries a risk of neonatal haemorrhagic complications. Some risk factors for nTP have reached consensus such as maternal splenectomy and previous severe nTP, while others such as maternal platelet count have not., Methods: We conducted a retrospective cohort study in a university hospital, including 145 neonates of mothers with ITP. We assessed the risk of severe nTP and bleeding complications., Results: Severe nTP in the first 24 h after birth was more common in case of maternal splenectomy (OR = 4.4) and a previous severe nTP (OR = 46.9). Severe nTP at nadir (lowest platelet count during the initial postnatal days) was more frequent in cases of a previous neonate with severe nTP (OR = 42), maternal treatment during pregnancy (OR = 2.4) and a low maternal platelet count during pregnancy or at delivery. These risk factors were not significantly associated with an increased risk of neonatal haemorrhagic complications., Conclusion: In our population, we confirm the risk of severe nTP in case of maternal splenectomy or previous nTP. By monitoring the platelet count to its nadir, we identified three additional risk factors: maternal treatment during pregnancy and low maternal platelet count during pregnancy or low maternal platelet count at delivery., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: With advances in neonatal care, management of prolonged pain in newborns is a daily concern. In addition to ethical considerations, pain in early life would have long-term effects and consequences. However, its treatment remains inadequate. It was therefore important to develop an experimental model of long-lasting analgesia for neonatal research. Materials and Methods: Experiments were performed in six groups of rats with transdermal fentanyl 0, 3, 12, 50, 100, or 200 μg/kg/h from second postnatal day (P2) until weaning. Assessment of analgesia was carried out at P21, with behavioral scores (ranging from 0 to 3) using a 4% formalin test. Plasma levels of fentanyl were determined by UPLC/TQD at P22. Growth rate was investigated. Results: Fentanyl 100 and 200 μg/kg/h reduced scores of formalin-evoked behavioral pain. They increased time spent in pain score 0 (8 min 55 s and 6 min 34 s versus 23 s in controls) as in low pain scores 1 and 2, and decreased time in the most severe pain score 3 (19 min 56 s and 17 min 39 s versus 44 min 15 s). Fentanylemia increased in a dose-dependent manner from 50 μg/kg/h (2.36 ± 0.64 ng/ml) to 200 μg/kg/h (8.66 ± 1.80 ng/ml). Concerning growth, no difference was observed except weaker growth from P17 to P22 with 200 μg/kg/h. Clinically, we noticed no visible side effect from 3 to 100 μg/kg/h. Concomitantly, 200 μg/kg/h was responsible for ophthalmological side effects with appearance of corneal bilateral clouding in 90% pups. No difference was observed between male and female rats. Conclusion: Altogether, results indicate that transdermal fentanyl 100 μg/kg/h is an efficient therapeutic for long-lasting analgesia in lactating pups. This new model provides a useful tool for protection and welfare, and future opportunity for studying long-term health consequences of sustainable neonatal analgesia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dutriez-Casteloot, Emmanuelli, Wiart, Tavernier, Besengez, Storme and Houfflin-Debarge.)

Objective: To evaluate various signal intensity ratios in isolated congenital diaphragmatic hernia (CDH) and to compare their potential in predicting survival with that of the observed-to-expected (O/E) ratio of total fetal lung volume (TFLV) using magnetic resonance imaging (MRI) measurements. Our second objective was to evaluate the impact of operator's experience in comparing the prediction of postnatal survival by O/E-TFLV., Methods: In 75 conservatively managed CDH fetuses and in 50 who underwent fetoscopic endoluminal tracheal occlusion (FETO), the fetal lung-to-amniotic fluid, lung-to-liver, lung-to-muscle, lung-to-spinal fluid signal intensity ratios, respectively LAFSIR, LLSIR, LMSIR, and LSFSIR, were measured, as was O/E-TFLV. Receiver operating characteristic (ROC) curves were constructed and used to compare the various signal intensity ratios with O/E-TFLV in the prediction of postnatal survival. In 72 MRI lung volumes assessed by the referring radiologists in Paris and Lille and secondarily by our expert radiologist in Brussels (M.M.C.) using the same MRI examinations, ROC curves were constructed and used to compare the value of O/E-TFLV determined by the two centers in the prediction of postnatal survival., Results: In the total cohort of CDH fetuses, O/E-TFLV and LLSIR were predictive of postnatal survival whereas in the conservatively managed group O/E-TFLV, LLSIR, and LMSIR predicted postnatal survival. O/E-TFLV predicted postnatal survival far better than the signal intensity ratios: area under the ROC curve for prediction by O/E-TFLV in the total cohort was 0.866 ( p  < .001; standard error = 0.031). The area under the ROC curve for prediction of postnatal survival using O/E-TFLV by MRI evaluated at the referral centers was 0.640 ( p  = 102; standard error = 0.085), and with O/E-TFLV reevaluated by M.M.C., it was 0.872 ( p  < .001; standard error = 0.061). Pairwise comparison showed a significant difference between the areas under the ROC curves (difference = 0.187, p  = .012; standard error = 0.075)., Conclusion: In fetuses with CDH with/without FETO, LLSIR was significantly correlated with the prediction of postnatal survival. However, measurement of O/E-TFLV was far better in predicting postnatal outcome. Operator experience in measurement of lung volumes using MRI seem to play a role in the predictive value of the technique.

Introduction: Preterm prelabor rupture of membranes (PPROM) occurs in 3% of pregnancies and is the main cause (~30%) of premature delivery. Home care seems to be a safe alternative for the management of patients with PPROM, who have a longer latency than those with PPROM managed with conventional hospitalization. We aimed to identify the risk factors associated with a shortened latency before delivery in women with PPROM managed as outpatients., Material and Methods: The design was a retrospective cohort study and the setting was a Monocentric Tertiary centre (Lille University Hospital, France) from 2009 to 2018. All consecutive patients in home care after PPROM at 24-36 weeks were included. For the main outcome measure we calculated the latency ratio for each patient as the ratio of the real latency period to the expected latency period, expressed as a percentage. The risk factors influencing this latency ratio were evaluated., Results: A total of 234 patients were managed at home after PPROM. Mean latency was 35.5 ± 20.7 days, corresponding to an 80% latency ratio. In 196 (83.8%) patients the length of home care was more than 7 days. A lower latency ratio was significantly associated with oligohydramnios (p < 0.001), gestational age at PPROM (p = 0.006), leukocyte count at PPROM more than 12 × 10 9 /L (p = 0.025), and C-reactive protein concentration more than 5 mg/L at 7 days after PPROM (p = 0.046). Cervical length was not associated with a lower latency ratio., Conclusions: Women with PPROM managed with home care are stable. The main risk factor associated with a reduced latency is oligohydramnios. Outpatients with oligohydramnios should be informed of the probability of a shortened latency period., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Introduction: Evaluation of fetal well-being during labor is based on fetal heart rate (FHR) analysis, which requires physiology expertise. The aim of the present study was to assess medical residents' fetal physiology training in terms of theoretical knowledge, FHR interpretation, and use of second-line examinations., Methods: This single-center, prospective study of obstetrics and gynecology residents (N = 34) at CHU de Lille Hospital (Lille, France) was conducted from November 2017 to November 2018. Evaluation and training were conducted in three stages. First, residents' pre-training knowledge of FHR interpretation and use of fetal scalp blood sampling (FBS) was assessed using clinical cases. Second, a didactic training session on fetal physiology was delivered. Finally, post-training knowledge was evaluated using the same cases presented during pre-training. I: Pre-training, 3%, 11.8%, and 14.7% of residents considered their training on fetal physiology, FHR analysis, and second-line examinations, respectively, to be sufficient. Training significantly improved their theoretical knowledge, which was assessed using multiple-choice questions (median [interquartile range]: 1.5 [1.0-2.0] vs. 4.0 [3.0-4.5], p<0.001), and reduced the number of FBS requested (36.3% vs. 29.5%, p = 0.002). Krippendorff's alpha coefficient for the reproducibility of residents' responses improved significantly, reflecting greater homogenization of clinical practice decisions (alpha [95% confidence interval]: 0.60 [0.55-0.65] vs. 0.72 [0.67-0.76])., Conclusion: Improved fetal physiology knowledge promotes more accurate FHR interpretation, better indications for second-line examinations, and greater homogenization of clinical practice decisions. Future studies should evaluate the impact of fetal physiology training on clinical practice., Competing Interests: Declaration of Competing Interests The authors report no conflict of interest., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: Compared with standard karyotype, chromosomal microarray analysis improves the detection of genetic anomalies and is thus recommended in many prenatal indications. However, evidence is still lacking on the clinical utility of chromosomal microarray analysis in cases of isolated fetal growth restriction., Objective: This study aimed to estimate the proportion of copy number variants detected by chromosomal microarray analysis and the incremental yield of chromosomal microarray analysis compared with karyotype in the detection of genetic abnormalities in fetuses with isolated fetal growth restriction., Study Design: This retrospective study included all singleton fetuses diagnosed with fetal growth restriction and no structural ultrasound anomalies and referred to 13 French fetal medicine centers over 1 year in 2016. Fetal growth restriction was defined as an estimated fetal weight of

Background: S100B and cardiac troponin T (c-TnT) are relevant biomarkers at birth of hypoxic-ischemic encephalopathy (HIE) and myocardial ischemia secondary to metabolic acidosis during labor, respectively. The purpose was to assess in-utero changes in S100B and c-TnT levels in an experimental model of labor-like acidosis., Methods: Repeated umbilical cord occlusions (UCOs) in ten experiments were performed in mild (phase A, 1 UCO/5 mn), moderate (phase B, 1 UCO/3 mn), and severe (phase C, 1 UCO/2 mn) period. The experiments were stopped if arterial pH reached 6.90., Results: UCOs resulted in fetal acidosis with pH dropping to 6.99 ±0.13. When compared to the baseline period fetal S100B increased between phases A and B (7% ± 4 vs 17% ± 13, p = 0.030) and between phases A and C (7% ± 4 vs 24% ± 8, p < 0.001). Fetal c-TnT serum levels increased during occlusions: 102 ng/L (58-119) in phase A, vs 119 ng/L (103-198) in phase B vs 169 ng / L (128-268) in phase C (p < 0.05, for all). When compared to the baseline control period, fetal ΔcTnT was significantly modified throughout UCO series: 5.0% (-3; 45) in phase A, 51% (4; 263) in phase B, and 77% (56.5; 269) in phase C (p < 0.05 for all)., Conclusions: S100B and c-TnT increased when fetal acidosis occurred, which reflects the potential neurological damage and fetal cardiovascular adaptation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Fetal well-being during labor is usually assessed by visual analysis of a fetal heart rate (FHR) tracing. Our primary objective was to evaluate the ability of automated heart rate variability (HRV) analysis methods, including our new fetal stress index (FSI), to predict neonatal acidosis. 552 intrapartum recordings were analyzed. The analysis occurred in the last 90 min before birth and was conducted during two 5-min intervals: (i) a stable period of FHR and (ii) the period corresponding to the maximum FSI value. For each period, we computed the mean FHR, FSI, short-term variability (STV), and long-term variability (LTV). Visual FHR interpretation was performed using the FIGO classification. The population was separated into two groups: (i) an acidotic group with an arterial pH at birth ≤ 7.10 and a control group. Prediction of a neonatal pH ≤ 7.10 was assessed by computing the receiver-operating characteristic area under the curve (AUC). FHR, FSI, STV, and LTV did not differ significantly between groups during the stable period. During the FSI max peak period, LTV and STV correlated significantly in the acidotic group (- 5.85 ± 2.19, p = 0.010 and - 0.62 ± 0.29, p = 0.037, respectively). The AUC values were 0.569 for FIGO classification, 0.595 for STV, and 0.622 for LTV. The multivariate model (FIGO, FSI, FC, STV, LTV) had the greatest accuracy for predicting acidosis (AUC = 0.719). FSI was not predictive of neonatal acidosis probably because of the low quality of the FHR signal in cardiotocography. When used separately, HRV indexes and visual FHR analysis were poor predictors of neonatal acidosis. Including all indexes in a multivariate model increased the predictive ability., (© 2020. Springer Nature B.V.)

Background: Sheep models are commonly used to study fetal cortical activity, including response to hypoxia. The standard technique consists of recording electrocorticogram (ECOG) in utero using electrodes placed on the dura mater., New Method: We propose a new method for recording the electroencephalogram (EEG) of fetal sheep, using electrodes placed above the skull bone and fixed to the cranial periosteum., Results: Twelve animals were instrumented with this new technique. The EEG signal recorded in utero was of sufficient quality for visual and quantitative analysis of the fetal cortical activity., Comparison With Existing Method: This new method is less invasive than the standard method commonly used to record cerebral activity in fetal sheep, because it avoids drilling the skull by hand. The EEG signal recorded in utero had visual and quantitative characteristics comparable to ECOG., Conclusions: We present a new method of EEG recording that appears to be an acceptable alternative to the standard ECOG recording method. Fetal sheep EEG can be used to better understand the physiological mechanisms involved in the cerebral response to hypoxia., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Delivery mode of term breech presentation is still being discussed. The aim of this study was to compare the labor management of a breech presentation to a vertex presentation during a vaginal delivery attempt., Methods: It was a single-center, comparative, descriptive retrospective study from 2014 to 2017. We studied fetal heart rate (FHR) during labor and expulsion, duration of the different stage of labor, mode of delivery and neonatal outcomes for breech and vertex presentations., Results: Two hundred and thirty-nine patients were included whom 106 (44%) breech presentation. The use of oxytocin was more common in breech group (63,2% versus 48,1%, P=0.020). Average dilatation rate was slower for breech presentation than for vertex presentation (1.9cm/h vs. 2.8cm/h; P=0.005). There was more FHR with high risk of acidosis in the breech presentations (37.2% vs 19.1%, P=0.001) and Melchior's FHR classification were comparable in both groups., Conclusions: The per-partum management of a fetus in breech presentation differs from a fetus in cephalic presentation. It must be known and anticipated for an optimal management in the delivery room., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the use of the intracervical balloon compared with locally applied prostaglandins for cervical ripening for induction in patients with preterm premature rupture of membranes., Methods: Monocentric, retrospective (from 2002 to 2017) observational cohort study of singleton pregnancies complicated by preterm premature rupture of membranes and induced between 34 and 37 weeks. The primary outcome measure was balloon catheter efficiency evaluated by Cesarean section rate. Secondary outcomes were : interval from induction to delivery, labor duration, oxytocin use, intrauterine infection rate, maternal complications (i.e., postpartum hemorrhage and endometritis), and neonatal complications., Results: 60 patients had cervical ripening with prostaglandins alone and 58 had balloon catheter. Demographic characteristics were similar between the groups, except for induction term and neonatal weight. There was not a significant difference in occurrence of Cesarean section rate (p = 0.14). Nor were there significant differences in time from induction to birth (p = 0.32) or in intrauterine infection rate (p = 0.95). Labor duration was shorter (p = 0.006) and total oxytocin dose lower (p = 0.005) in patients induced by prostaglandins alone. Concerning neonatal outcomes, there were more transfers to intensive care (p = 0.008) and more respiratory distress (p = 0.005) among newborns induced by prostaglandins., Conclusion: Compared with locally applied prostaglandins, balloon catheter induction is not associated with an increase of Cesarean section rate in patients with preterm premature rupture of membranes., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: To determine which parameter of umbilical arterial cord gas analysis, pH, base deficit, lactate concentration, ionogram values, or glucose level index is the best predictor of neonatal morbidity at term., Design: We conducted a 15-month retrospective cohort study that included all nonanomalous, singleton, term births at a single center. The predictive ability of lactate concentration, base deficit, pH, ionogram values, and glucose level were compared using receiver-operating characteristic curves for global and neurological composite morbidity. Optimal cutoff values for lactate concentration, base deficit, and pH were estimated based on their maximum area under the curve., Results: We included 5161 newborns: 52 (1.01 %) had global composite morbidity, and 17 had (0.33 %) neurological composite morbidity. Blood levels of potassium, calcium, natremia, glucose level, and HCO 3 - did not differ significantly between groups. pH, partial pressure of CO 2 , partial pressure of O 2 , base deficit, and lactate levels differed significantly between neonates in the groups with and without global composite morbidity. Nearly similar results were found for neurological composite morbidity. The predictive ability did not differ between arterial pH and arterial lactate concentration (P = .25) and base deficit (P = .79). Optimal cutoff values to predict global composite morbidity were arterial pH 7.144, venous pH 7.236, and arterial lactate concentration 6.5 mmol/L., Conclusions: Acid-base status analysis remains the best objective indicator for predicting neonatal morbidity and can be estimated using pH, lactate, or base deficit. Ionogram cord blood composition and glucose level do not appear to be useful for this purpose., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest or financial ties to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Heart rate variability analysis is a recognized non-invasive tool that is used to assess autonomic nervous system regulation in various clinical settings and medical conditions. A wide variety of HRV analysis methods have been proposed, but they all require a certain number of cardiac beats intervals. There are many ways to record cardiac activity: electrocardiography, phonocardiography, plethysmocardiography, seismocardiography. However, the feasibility of performing HRV analysis with these technologies and particularly their ability to detect autonomic nervous system changes still has to be studied. In this study, we developed a technology allowing the simultaneous monitoring of electrocardiography, phonocardiography, seismocardiography, photoplethysmocardiography and piezoplethysmocardiography and investigated whether these sensors could be used for HRV analysis. We therefore tested the evolution of several HRV parameters computed from several sensors before, during and after a postural change. The main findings of our study is that even if most sensors were suitable for mean HR computation, some of them demonstrated limited agreement for several HRV analyses methods. We also demonstrated that piezoplethysmocardiography showed better agreement with ECG than other sensors for most HRV indexes.

Background: The autonomic nervous system has a major role in fetal adaptation to hypoxia. Its activity might be assessed using heart rate variability and heart rate deceleration analyses., Objective: To evaluate the ability of different heart rate variability and morphological deceleration analyses to predict fetal acidosis during labor in an experimental fetal sheep model., Study Design: Repeated 1-minute total umbilical cord occlusions were performed at mild (1minute every 5 min), moderate (1 min every 3 min), and severe (1 min every 2 min) umbilical cord occlusion periodicities until arterial pH reached 7.10. Hemodynamic,blood gas analysis, morphological analysis of decelerations (magnitude, slope, and area ofdecelerations), and heart rate variability parameters were recorded throughout the experiment.Heart rate variability analysis included temporal analysis (root mean square of successivedifferences between adjacent RR intervals, standard deviation of normal to normal RR intervals, short term variability), spectral analysis (low frequencies, high frequencies,normalized high frequencies), and a new index developed by our team, the Fetal Stress Index.We defined and compared three pH groups: >7.20, 7.10-7.20, and <7.10., Results: Eleven experiments were performed. Repetitive umbilical cord occlusions resulted in progressive fetal acidosis. Fetal Stress Index was correlated with pH and lactate (p < 0.05) and increased with acidosis. There were no significant correlations between pH, lactate, and other indices (spectral analysis, temporal analysis, or morphological analysis of decelerations)., Conclusion: This protocol allowed us to identify the progressive onset of fetal acidosis in an experimental model close to labor. Fetal Stress Index is a heart rate variability method that varies with acidosis and indicates an increase in parasympathetic nervous system activity in response to fetal acidosis., (Copyright © 2020 Elsevier B.V. All rights reserved.)