Accuracy of the fetal cerebroplacental ratio for the detection of intrapartum compromise in nonsmall fetuses.

OBJECTIVE: To study the accuracy of the cerebroplacental ratio (CPR) for the detection of intrapartum fetal compromise (IFC) in fetuses growing over the 10th centile. METHODS: This was a prospective study of 569 nonsmall fetuses attending the day hospital unit of a tertiary hospital that underwent an ultrasound examination at 36-40 weeks, and were delivered within 4 weeks of examination. IFC was defined as a composite of: abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH < 7.20 requiring cesarean section, neonatal umbilical cord pH < 7.20, 5' Apgar score < 7 and postpartum admission to neonatal or pediatric intensive care units. The accuracy of CPR for the prediction of IFC was calculated alone and in combination with other perinatal parameters using univariate and multivariate logistic regression models, which alternatively included the onset of labor to evaluate the influence of induction of labor (IOL) on IFC and a brief composite adverse outcome of two parameters to prove the strength of the approach. RESULTS: The incidence of IFC was 17.9%. CPR sensitivity was 30.4% for a false positive rate (FFR) of 10 and 14.7% for a FPP of 5% (AUC = 0.62, p < 0.001). The multivariate analysis showed that only fetal gender and parity increased the predictive accuracy of CPR alone, although the improvement was poor (AUC = 0.67, p < 0.001). No differences were observed using any of the alternative models. Finally, IOL had no influence of IFC. CONCLUSION: Despite their apparent normality, a proportion of fetuses growing over the 10th centile suffer IFC. Some of them are suitable for detection by means of CPR

Progression of Doppler changes in early-onset small for gestational age fetuses. How frequent are the different progression sequences?

OBJECTIVE: To evaluate the progression of Doppler abnormalities in early-onset fetal smallness (SGA). METHODS: A total of 948 Doppler examinations of the umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV), belonging to 405 early-onset SGA fetuses, were studied, evaluating the sequences of Doppler progression, the interval examination-labor at which Doppler became abnormal and the cumulative sum of Doppler anomalies in relation with labor proximity. RESULTS: The most frequent sequences were that in which only the UA pulsatility index (PI) became abnormal (42.1%) and that in which an abnormal UA PI appeared first, followed by an abnormal MCA PI (24.2%). In general, 71.3% of the fetuses followed the classical progression sequence UA→MCA→DV, mostly in the early stages of growth restriction (84.1%). In addition, the UA PI was the first parameter to be affected (9 weeks before delivery), followed by the MCA PI and the DV PIV (1 and 0 weeks). Finally, the UA PI began to sum anomalies 5 weeks before delivery, while the MCA and DV did it at 3 and 1 weeks before the pregnancy ended. CONCLUSIONS: In early-onset SGA fetuses, Doppler progression tends to follow a predictable order, with sequential changes in the umbilical, cerebral and DV impedances

Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose

[EN] Background Despite treatment with pancreatic enzyme replacement therapy (PERT), patients with cystic fibrosis (CF) can still suffer from fat malabsorption. A cause could be low intestinal pH disabling PERT. The aim of this study was to assess the association between faecal pH (as intestinal pH surrogate) and coefficient of fat absorption (CFA). Additionally, faecal free fatty acids (FFAs) were quantified to determine the amount of digested, but unabsorbed fat. Methods In a 24-h pilot study, CF patients followed a standardised diet with fixed PERT doses, corresponding to theoretical optimal doses determined by an in vitro digestion model. Study variables were faecal pH, fat and FFA excretion, CFA and transit time. Linear mixed regression models were applied to explore associations. Results In 43 patients, median (1st, 3rd quartile) faecal pH and CFA were 6.1% (5.8, 6.4) and 90% (84, 94), and they were positively associated (p < 0.001). An inverse relationship was found between faecal pH and total fat excretion (p < 0.01), as well as total FFA (p = 0.048). Higher faecal pH was associated with longer intestinal transit time (p = 0.049) and the use of proton pump inhibitors (p = 0.009). Conclusions Although the clinical significance of faecal pH is not fully defined, its usefulness as a surrogate biomarker for intestinal pH should be further explored. Impact Faecal pH is a physiological parameter that may be related to intestinal pH and may provide important physiopathological information on CF-related pancreatic insufficiency. Faecal pH is correlated with fat absorption, and this may explain why pancreatic enzyme replacement therapy is not effective in all patients with malabsorption related to CF. Use of proton pump inhibitors is associated to higher values of faecal pH. Faecal pH could be used as a surrogate biomarker to routinely monitor the efficacy of pancreatic enzyme replacement therapy in clinical practice. Strategies to increase intestinal pH in children with cystic fibrosis should be targeted.We acknowledge the support of the MyCyFAPP Project consortium. We especially thank the participation and the effort of the patients involved in the study and their families. This work was fully funded by the European Union and the Horizon 2020 Research and Innovation Framework Programme (PHC-26-2014 call Self management of health and disease: citizen engagement and mHealth) under grant number 643806.Calvo-Lerma, J.; Roca-Llorens, M.; Boon, M.; Colombo, C.; De Koning, B.; Fornés-Ferrer, V.; Masip, E.... (2021). Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose. Pediatric Research. 89(1):205-210. https://doi.org/10.1038/s41390-020-0860-3S205210891Turck, D. et al. ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin. Nutr. 35, 557–577 (2016).Borowitz, D., Baker, R. D. & Stallings, V. Consensus report on nutrition for pediatric patients with cystic fibrosis. J. Pediatr. Gastroenterol. Nutr. 35, 246–259 (2002).Fieker., A., Philpott, J. & Armand, M. Enzyme replacement therapy for pancreatic insufficiency: present and future. Clin. Exp. Gastroenterol. 4, 55 (2011).Sitrin, M. D. Digestion and Absorption of Carbohydrates and Proteins in the Gastrointestinal System 137–158 (Springer, Dordrecht, 2014).Gelfond, D. et al. Intestinal pH and gastrointestinal transit profiles in cystic fibrosis patients measured by wireless motility capsule. Dig. Dis. Sci. 58, 2275–2281 (2013).Robinson, P. J. et al. Duodenal pH in cystic fibrosis and its relationship to fat malabsorption. Dig. Dis. Sci. 35, 1299–1304 (1990).Hunter, J. E. Studies on effects of dietary fatty acids as related to their position on triglycerides. Lipids 36, 655–668 (2001).Hernell, O., Staggers, J. E. & Carey, M. C. Physical–chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 2. Phase analysis and aggregation states of luminal lipids during duodenal fat digestionin healthy adult human beings. Biochemistry 29, 2041–2056 (1990).Calvo-Lerma, J. et al. A first approach for an evidence-based in vitro method to adjust pancreatic enzyme replacement therapy in cystic fibrosis. PLoS ONE 14, e0212459 (2019).Aburub, A. Comparison of pH and motility of the small intestine of healthy subjects and patients with symptomatic constipation using the wireless motility capsule. Int. J. Pharm. 544, 158–164 (2018).Calvo-Lerma, J. et al. Innovative approach for self-management and social welfare of children with cystic fibrosis in Europe: development, validation and implementation of an mHealth tool (MyCyFAPP). Br. Med. J. Open. 7, e014931 (2017).Calvo-Lerma, J. et al. 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Fat digestibility in meat products: influence of food structure and gastrointestinal conditions. Int. J. Food Sci. Nutr. 70, 530–539 (2019).Regan, P. T. et al. Reduced intraluminal bile acid concentrations and fat maldigestion in pancreatic insufficiency: correction by treatment. Gastroenterology 7, 285–289 (1979).Fallingborg, J. et al. pH‐profile and regional transit times of the normal gut measured by a radiotelemetry device. Aliment. Phamacol. Ther. 3, 605–614 (1989).Fallingborg, J. Intraluminal pH of the human gastrointestinal tract. Dan. Med Bull. 46, 183–196 (1999).Calvo-Lerma, J. et al. In vitro digestion models to assess lipolysis: the impact of the simulated conditions for gastrointestinal pH, bile salts and digestion fluids. Food Res. Int. 125, 108511 (2019).Kalantzi, L. Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies. Pharm. Res. 23, 165–176 (2006).Zelles, L. & Bai, Q. Y. 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Assessing gastro-intestinal related quality of life in cystic fibrosis: Validation of PedsQL GI in children and their parents

Background: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency, leading to fat malabsorption, malnutrition and abdominal discomfort. Until recently, no specific tool was available for assessing gastro-intestinal related quality of life (GI QOL) in patients with CF. As the Horizon2020 project MyCyFAPP aims to improve GI QOL by using a newly designed mobile application, a sensitive and reliable outcome measure was needed. We aimed to study the applicability of the existing child-specific Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Scales and Module (PedsQL GI) in children with CF. Methods: A multicenter, prospective observational study was performed in 6 European centers to validate the PedsQL GI in children with CF during 3 months. Results: In total, 248 children and their parents were included. Within-patient variability of PedsQL GI was low (24.11), and there was reasonable agreement between children and parents (ICC 0.681). Nine of 14 subscales were informative (no ceiling effect). The PedsQL GI and the median scores for 4 subscales were significantly lower in patients compared to healthy controls. Positive associations were found between PedsQL GI and age (OR = 1.044, p = 0.004) and between PedsQL GI and BMI z-score (OR = 1.127, p = 0.036). PedsQL GI correlated with most CFQ-R subscales (r 0.268 to 0.623) and with a Visual Analogue Scale (r = 0.20). Conclusions: PedsQL GI is a valid and applicable instrument to assess GI QOL in children with CF. Future research efforts should examine the responsiveness of the CF PedsQL GI to change in the context of clinical interventions and trials

Fetal cerebral and umbilical Doppler in pregnancies complicated by late-onset placental abruption.

OBJECTIVE: To evaluate whether changes in the cerebroplacental Doppler and birth weight (BW) suggestive of chronic fetal hypoxemia, precede the development of late-onset placental abruption (PA) after 32 weeks. METHODS: In a multicenter retrospective study, the Doppler examinations of the fetal umbilical artery (UA) and middle cerebral artery (MCA) recorded after 32 weeks were collected in pregnancies subsequently developing PA. The BW centiles were calculated and the MCA pulsatility indices (PI), and UA PI were converted into multiples of the median (MoM). Afterwards, a comparison was made with a group of fetuses, which did not develop PA. Logistic regression was used to adjust for potential confounders and evaluate the feasibility of the prediction model. RESULTS: Pregnancies complicated by late-onset PA (n = 31) presented lower MCA PI (p = 0.015) and were smaller (p < 0.001) than those who did not (n = 1294). Logistic regression analysis indicated that cerebral vasodilation was more important than umbilical flow in the explanation of PA (MCA PI OR = 0.106, p = 0.014 and UA PI OR 1.901, p = 0.32). In addition, the influence of BW exerted was residual (BW centile OR = 0.989, p = 0.15). CONCLUSIONS: Fetuses developing late-onset PA demonstrate significant cerebral vasodilation with scarce placental dysfunction, suggesting the existence of some kind of chronic hypoxemia that follows the late-onset pattern