A Metabolomic Profiling of Intra-Uterine Growth Restriction in Placenta and Cord Blood Points to an Impairment of Lipid and Energetic Metabolism.

(1) Background: Intrauterine growth restriction (IUGR) involves metabolic changes that may be responsible for an increased risk of metabolic and cardiovascular diseases in adulthood. Several metabolomic profiles have been reported in maternal blood and urine, amniotic fluid, cord blood and newborn urine, but the placenta has been poorly studied so far. (2) Methods: To decipher the origin of this metabolic reprogramming, we conducted a targeted metabolomics study replicated in two cohorts of placenta and one cohort of cord blood by measuring 188 metabolites by mass spectrometry. (3) Results: OPLS-DA multivariate analyses enabled clear discriminations between IUGR and controls, with good predictive capabilities and low overfitting in the two placental cohorts and in cord blood. A signature of 25 discriminating metabolites shared by both placental cohorts was identified. This signature points to sharp impairment of lipid and mitochondrial metabolism with an increased reliance on the creatine-phosphocreatine system by IUGR placentas. Increased placental insulin resistance and significant alteration of fatty acids oxidation, together with relatively higher phospholipase activity in IUGR placentas, were also highlighted. (4) Conclusions: Our results show a deep lipid and energetic remodeling in IUGR placentas that may have a lasting effect on the fetal metabolism.

The use of biofeedback for children with fecal incontinence secondary to retentive constipation: Experience of a French Pediatric Center.

BACKGROUND: Fecal incontinence (FI) secondary to chronic retentive constipation is a frequent demand in pediatric gastroenterology clinics. The management of constipation in children includes laxatives (polyethylene glycol, PEG), enhanced toilet training, and dietary advice. Biofeedback is a possible treatment for children above the age of 7 years with resistant FI. AIM: To analyze any changes in volume to trigger defecation (VTD) and envy score over the course of biofeedback sessions according to clinical response. METHODS: In this retrospective study, we reviewed the medical records of 23 children diagnosed with FI according to the Rome IV criteria and treated with biofeedback. For each biofeedback session, a mean VTD by subject was measured. At the end, therapy was considered a success if soiling disappeared and a failure if any persisted. The need to defecate expressed by the child was described as an envy score. A 0-10 visual analog scale was used to express the intensity of this sensation. Follow-up involved calling the parents 12 months after the biofeedback sessions had ended to assess symptoms remotely. RESULTS: The study included 19 boys and 4 girls with a median age of 10 years. Patients' ages ranged between 7 and 17 years. None of them had any associated neurological disorders. All children had FI for >1 year. The median number of soiling episodes per week was 7. The average number of biofeedback sessions was 3 (range 1-5). At the end of the rehabilitation sessions, 12 children (52%) were in the "success" group. In the latter, median VTD decreased from 97 ml to 70 ml between the first and last session. In the "failure" group, VTD decreased from 120 ml to 100 ml. The between-group difference in the median VTD at the first session was not statistically significant. The last observation carried forward (LOCF) VTD was significantly lower in the "success" group compared to the "failure" group (70 ml versus 100 ml, p = 0.03). Median envy scores decreased during the biofeedback sessions with no statistical difference between the groups at the last session. Follow-up of children in the "success" group one year after the last biofeedback session revealed that 10 patients had no relapse (83%) and 2 were lost to follow-up. CONCLUSIONS: Biofeedback might be an effective tool for the management of FI resistant to medical treatment in children.

Study of mitochondrial function in placental insufficiency.

INTRODUCTION: It has been suggested that mitochondria play a crucial role in sustaining pregnancy and foetal growth. The aim of the study was to assess the influence of mitochondrial functions and genetics on placental insufficiency diseases. METHODS: A total of 115 patients were recruited, subdivided into 74 placenta samples and 41 maternal blood samples: placental insufficiency diseases including intra uterine growth restriction (IUGR) (n = 35), preeclampsia (PE) (n = 13), IUGR associated to PE (PER) (n = 25); and controls (n = 42). Haplogroups were determined for all patients. Eighty-six placenta samples were studied for quantitative and qualitative analyses of mtDNA: IUGR (n = 25), PE (n = 1), PER (n = 18) and controls (n = 42). Sixteen placenta samples were selected for functional analysis: IUGR (n = 6), PER (n = 2) and controls (n = 8). RESULTS: Mitochondrial DNA copy numbers and rearrangements and haplogroup distribution were not significantly altered in the patient group. Enzyme activity and expression of respiratory chain complexes were also comparable between both groups. DISCUSSION: Our results do not argue in favour of a mitochondrial involvement in placental insufficiency, suggesting that the glycolytic pathway may represent a key energetic source in placental insufficiency diseases.