Metformin, metabolomics and inflammation in gestational diabetes

Gestational diabetes is a common pregnancy complication that increases the risk of adverse pregnancy outcomes and predicts long-term metabolic morbidity for the mother and the offspring. Gestational diabetes is treated with lifestyle modifications and metformin or insulin if needed. Besides hyperglycemia, gestational diabetes is associated with broad disturbances in lipid and amino acid metabolism and lowgrade inflammation. The effects of metformin on these changes compared to insulin are not fully known. In this secondary analysis of a previous randomized trial in gestational diabetes, the effects of metformin (n = 110) and insulin (n = 107) treatments were studied on the maternal metabolome, inflammatory marker profile and insulin-like growth factor-binding protein-1 phosphoisoforms. Patients (n = 126) not requiring antihyperglycemic medication were included as a reference group at the time of randomization to medical treatment groups. Umbilical cord blood samples were drawn after delivery in all three groups to study the effects of metformin on the fetal metabolome. Metformin treatment led to a greater increase in maternal serum alanine, total triglycerides, very low-density lipoprotein triglycerides and total fatty acids than insulin. In the cord serum metabolome, only alanine was significantly higher in the metformin group. Maternal lipids, very low-density lipoprotein cholesterol and the apolipoprotein B to A-1 ratio in particular, were related to an increased birth weight and these associations were stronger in the metformin group than the insulin group. In cord blood, omega-6 fatty acids were positively and omega-3 fatty acids inversely associated with birth weight. Metformin had no effects on fetal ketones or fetal lipid metabolism. In conclusion, insulin treatment of gestational diabetes may be more effective than metformin in ameliorating maternal dyslipidemia, although birth weight and other pregnancy outcomes were similar among the study groups. Our results suggest that the maternal metabolome could be helpful in identifying patients who benefit the most from metformin or insulin treatment. The long-term implications of elevated cord serum alanine merits further study.Metformiini, metabolomiikka ja inflammaatio raskausdiabeteksessa Raskausdiabetes on yleinen ongelma, joka lisää raskauden riskejä sekä ennustaa äidin ja lapsen myöhempää sairastavuutta. Raskausdiabetesta hoidetaan elintapamuutoksin sekä tarvittaessa lääkehoidolla. Korkean verensokerin lisäksi raskausdiabetekseen liittyy rasva- ja aminohappoaineenvaihdunnan sekä matalaasteisen tulehduksen häiriöitä. Toistaiseksi metformiinin vaikutuksia näihin muutoksiin insuliinihoitoon verrattuna ei kunnolla tunneta. Tässä aiemman satunnaistetun tutkimuksen jatkoanalyysissa verrattiin raskausdiabeteksen metformiini- (n = 110) ja insuliinihoitojen (n = 107) vaikutuksia äidin aineenvaihdunnan molekyyleihin (metabolomiin), tulehdusmerkkiaineisiin ja insuliinin kaltaista kasvutekijää sitovaan proteiini 1:een. Lääkehoidon aloitusvaiheen vertailuun otetiin myös potilaita (n = 126), jotka eivät tarvinneet verenglukoosia alentavaa lääkitystä. Napanuoraverinäytteet otettiin synnytyksen jälkeen kaikissa kolmessa ryhmässä metformiinin vaikutusten tutkimiseksi. Metformiinihoidetuilla äideillä seerumin alaniinin, triglyseridien kokonaismäärän, erittäin matalatiheyksisten lipoproteiinien triglyseridien sekä rasvahappojen kokonaismäärän pitoisuudet nousivat enemmän kuin insuliinihoidetuilla. Napaveren metabolomissa ainoastaan alaniini oli merkitsevästi korkeampi metformiiniryhmässä. Äidin verenkierrossa erityisesti erittäin matalatiheyksisen lipoproteiinin kolesteroli sekä apolipoproteiini B:n ja A-1:n suhde olivat yhteydessä korkeampaan syntymäpainoon ja nämä yhteydet olivat vahvempia metformiiniryhmässä. Napaveressä omega-6-rasvahapot liittyivät korkeampaan ja omega-3-rasvahapot matalampaan syntymäpainoon. Metformiinilla ei ollut vaikutuksia sikiön ketoneihin tai rasva-aineenvaihduntaan. Raskausdiabeteksen insuliinihoito metformiiniin verrattuna saattaa olla tehokkaampi äidin rasva-aineenvaihdunnan muutosten lieventämisessä, vaikka syntymäpainoissa tai raskauskomplikaatioissa ei ollut eroja ryhmien välillä. Tulokset viittaavat siihen, että tulevaisuudessa äidin metabolomista voisi olla apua niiden potilaiden tunnistamisessa, jotka hyötyvät ensisijaisesti joko metformiini- tai insuliinihoidosta. Kohonneen napaveren alaniinin mahdolliset vaikutukset lasten myöhempään terveyteen vaativat lisätutkimuksia

Effect of Labor Epidural Analgesia With Hydromorphone on Neonatal Neurobehavior and Breastfeeding Behavior in the First 24 Hours of Life

Epidural opioids and local anesthetics may depress the neonatal reflexes necessary for breastfeeding success. Literature review yielded no data for hydromorphone and conflicting results for fentanyl. This study investigated whether breastfeeding effectiveness would be less in infants whose mothers received epidural analgesia with hydromorphone compared with those whose mothers received no analgesia, and whether the total amount of drugs given or the presence of multiple stressful events or interventions would be related to the effectiveness of breastfeeding. Breastfeeding behaviors were studied in 51 infants whose mothers chose epidural analgesia compared with 51 infants whose mothers chose to have no analgesia. Women with epidural analgesia received 1.5% lidocaine with 1:200,000 epinephrine as a test dose and/or 0.25% bupivacaine with 1:200,000 epinephrine as a bolus, and 100 µg hydromorphone followed by continuous infusion of 0.05% bupivacaine with 3 µg/mL hydromorphone at 14 mL/hour. The hospital setting strongly supported breastfeeding. Effectiveness of breastfeeding was measured with the LATCH Breastfeeding Assessment Tool at 3, 12, and 24 hours after birth. LATCH scores did not differ significantly between groups at any time point and were not related to total amount of drugs administered. The presence of multiple stressful events and interventions, e.g., long duration of labor, large amount of IV fluids, oxytocin administration, induction of labor, and meconium staining/suctioning of the baby, did not significantly affect breastfeeding behavior in the overall study population (n=102), altogether contributing not more than 8% of the variability of LATCH scores in the regression model. The group receiving epidural analgesia (n=51) had significantly longer duration of labor, higher rates of oxytocin administration and induction of labor, and larger amounts of IV fluid administration. These factors contributed approximately 30% of the variability of LATCH scores at 3 and 24 hours. However, this finding was not significant. Although the study was limited by its nonrandomized nature, these data indicate that, by itself, epidural analgesia with hydromorphone does not decrease effectiveness of breastfeeding behaviors. Epidural analgesia increases risk of multiple stressful events or interventions, which may contribute to breastfeeding difficulties and necessitate intensive help from the nurse to achieve success in breastfeeding

Selected Lectures of the 14th International Workshop on Neonatology; Cagliari (Italy); October 24th-27th, 2018

Selected Lectures of the 14th International Workshop on Neonatology; Cagliari (Italy); October 24th-27th, 2018 • THE REVOLUTION OF MICROBIOMICS • NUTRITION, BACTERIA AND PROBIOTICS IN PERINATAL AND PEDIATRIC HEALTH LECT 1. PERINATAL PROGRAMMING: FROM THE WOMB TO THE ADULT. THE FIGO LIFE CYCLE APPROACH • M. Hod LECT 2. SINS IN PREGNANCY, SINS, AND PREGNANCY • G.C. Di Renzo LECT 3. THE HUMAN MILK AS A MODEL OF PREVENTION • G. Corsello, M. Carta LECT 4. LESS INVASIVE SURFACTANT ADMINISTRA­TION (LISA): WHERE ARE WE NOW? • E. Herting LECT 5. DRUGS AND NEUROPROTECTION • S. Perrone, E. Laschi, G. Nanni, G. Buonocore LECT 6. CRANIOFACIAL DEFORMATIONS BETWEEN ART AND SCIENCE • F. Velardi LECT 7. NON-NUTRITIVE SUCTION AND BREATHING IN PRETERM INFANTS • S. Ossola, V. Trivellin, M. Ragazzo, F. Riccaboni, L. Montericcio, L. Nosetti, S. Salvatore, L. Levrini, M. Agosti LECT 8. PARENTERAL NUTRITION IN VERY LOW BIRTH WEIGHT INFANTS: TO STANDARDIZE OR NOT TO STANDARDIZE? • S. Iacobelli, F. Bonsante LECT 9. PULMONARY HYPERTENSION: ANY NEWS? • M. Sánchez Luna LECT 10. PERSISTENT DUCTUS ARTERIOSUS: TO CLOSE OR NOT TO CLOSE? • C. Dani LECT 11. MONITORING CARDIOVASCULAR PA­RAME­TERS IN NICU • D. Doni, P.E. Tagliabue LECT 12. DO NOT ATTEMPT RESUSCITATION (DNAR) ORDERS, WITHDRAWING/WITHHOLDING CARE IN THE NICU • P. Biban, S. Lauriola, M. Ventola, C. Forcellini, B. Ficial, F. Bissolo, E. Bonafiglia, L. Chini, L. Pecoraro, I. Sibona, R. Frassoldati, R. Beghini LECT 13. VITAMINS IN THE NEWBORN • C. Romagnoli LECT 14. ANEMIA OF PREMATURITY: WHAT METABO­LOMICS CAN ADD • V. Fanos, R. Pintus, F.S. Corbu, G. Ledda, E. Coni, A. Dessì, M. Puddu, F. Cesare Marincola LECT 15. IRON STATUS AND LATE PRETERM INFANTS • R. Luciano LECT 16. NEONATAL TRANSFUSION PRACTICE • C. Franco, F. Petrillo, K. Del Vecchio, G. D’Amato, A. Del Vecchio LECT 17. INDIVIDUALIZED DEVELOPMENTAL CARE STABILIZING SLEEP, MOVEMENT, POSTURE AND CARDIORESPIRATORY CONTROL PRO­TECTS THE BRAIN IN THE NICU • F. Ferrari, N. Bertoncelli, E. Garetti, E. Della Casa, M.F. Roversi, L. Ori, L. Lucaccioni LECT 18. POINT OF CARE TESTING (POCT) INNOVATION, CONNECTED HEALTH AND BEYOND – HOW DIGITAL TECHNOLOGY IS TRANSFORMING LABMED, HEALTH, AND SOCIAL CARE? • S. Bernardini LECT 19. MICROBIOME IN FORENSIC SCIENCE • B. Benedetti, P. Roberti, E. d’Aloja LECT 20. MICROBIOME AND PROBIOTICS IN THE PERINATAL ARENA • N. Giovannini LECT 21. MICROBIOTA, PROBIOTICS AND PREBIOTICS • F. Indrio, V. Dargenio LECT 22. URINARY MICROBIOTA: IS THERE ANY DIFFERENCE IN CHILDREN WITH URINARY TRACT DISEASE? • G. Masnata, M. Limone, V. Manca LECT 23. METABOLOME AND MICROBIOME IN AUTISM: THE LAST DATA • M. Mussap, V. Fanos LECT 24. MODE OF CHILDBIRTH AND EFFECT ON NEONATAL AND MATERNAL HEALTH AND DISEASES • A. Ragusa, S. Rugolotto, A. Svelato, C. Incarnato LECT 25. PRETERM LABOR FROM THE SOCIETY FOR MATERNAL-FETAL MEDICINE (SMFM) POINT OF VIEW: AN UPDATE • T. Frusca LECT 26. BIG DATA, ULTRASOUND, AND NEONATAL RESPIRATORY DISTRESS: ANYTHING IN COMMON? • F. Raimondi LECT 27. GESTATIONAL DIABETES • F. Mecacci LECT 28. GESTATIONAL DIABETES FROM A PEDIATRIC VIEWPOINT • R. Antonucci, C. Locci LECT 29. EXCESSIVE GESTATIONAL WEIGHT GAIN: INTERVENTIONS AIMED TO REDUCE THE EFFECTS ON MATERNAL AND OFFSPRING HEALTH • L. Di Cerbo, D. Menichini, F. Facchinetti LECT 30. “TOO MUCH” AND “NOT ENOUGH” WEIGHT IN PREGNANCY • A. Dessì, M. Puddu, V. Fanos LECT 31. UNRAVELING THE COMPLEX GENETICS OF CHILDHOOD AND ADOLESCENT PSYCHO­PATHOLOGY, INCLUDING AGGRES­SION, THROUGH INTERNATIONAL COL­LABORA­TIONS: AN UPDATE ON THE CAPICE AND ACTION PROJECTS • M. Manchia, V. Fanos LECT 32. THE ROLE OF BIG DATA IN NEUROPSYCHIA­TRIC DISORDERS: A FOCUS ON METABOLO­MICS • H.S.R. Rajula, M. Manchia, V. Fanos LECT 33. SHARING RESEARCH: COMMUNICATION CAN HELP • M. Mauri, V. Fanos LECT 34. ENDOCRINE DISRUPTORS AND NEURO­DEVELOPMENT • M.E. Street, F. Cirillo, C. Catellani, P. Palanza, G.C. Panzica, E. Grossi, P. Lazzeroni, C. Sartori LECT 35. MATERNAL-INFANT HEALTH CARE: QUES­TIONS AND ISSUES ON AN INTEGRATED PRACTICE • G. Perricone LECT 36. URINARY GC-MS METABOLOMICS COM­PARISON BETWEEN TWO COHORTS OF TODDLER AND ADOLESCENT SUBJECTS AF­FECTED BY AUTISM SPECTRUM DISORDER • A. Noto, C. Fattuoni, M. Mussap, L. Barberini, M. Siracusano, L. Mazzone, R. Francavilla, P. Curatolo, V. Fanos LECT 37. LUNG MICROBIOTA • U. Pelosi, R. Pintus LECT 38. THE EXCEPTION CONFIRMING THE RULE • G. Ottonello, F. Bardanzellu, M.E. Trudu, G.Z. Trapletti, G. Masnata LECT 39. DIARRHEA, GASTROENTERITIS, AND IN­FLAM­MATORY BOWEL DISEASE: THE RATIONALE OF PROBIOTICS • M. Corpino LECT 40. IRON AND GASTROINTESTINAL DISEASES • M.G. Clemente LECT 41. HOW TO FEED THE GUT MICROBIOTA • G. Biasucci LECT 42. HUMAN MILK, BACTERIA, AND ALLERGIC OUTCOMES • D. Peroni, M.E. Di Cicco, P. Comberiati LECT 43. INFANT EXPOSURE – HISTORICAL AND AN­THROPOLOGICAL NOTES • L. Cataldi, M.G. Gregorio LECT 44. THE BABY HATCH OF THE THIRD MILLENNIUM • P. Paolillo, F. Di Palma, S. Picone LECT 45. NON-INVASIVE TEST FOR PRENATAL DIAG­NOSIS OF CONGENITAL DISEASES AND PREG­NANCY TUMORS • G. Floris LECT 46. LUNG PATHOLOGY IN THE NEWBORN: A NEW CT SCAN-BASED SAMPLING METHOD ALLOWS A BETTER ANALYSIS OF THE IMMATURE LUNG IN RESPIRATORY DISTRESS SYNDROME • G. Faa, C. Gerosa, R. Garau, V. Marinelli, C. Moretti, F. Cau, C. Loddo, V. Fanos LECT 47. STAINED AMNIOTIC FLUID: WHAT’S NEW? • A.M. Fulghesu, E. Canu, L. Barberini, C. Fattuoni, V. Fanos LECT 48. MYSTERIES OF THE PERINATAL HEARTH • A. Faa, E. Podda, G. Faa, V. Fanos LECT 49. THE KIDNEY: A FASCINATING AND MYS­TE­RIOUS ORGAN • C. Gerosa, D. Fanni, V. Fanos, G. Faa LECT 50. SECRETS OF THE BRAIN • M. Vendemmia LECT 51. FOCUS ON… MITOCHONDRIA • F. Bardanzellu, M.C. Pintus, V. Fanos, M.A. Marcialis LECT 52. THE EXTRAORDINARY REGENERATIVE POW­ER OF HUMAN ENDOMETRIUM • F. Bardanzellu, G. Faa, D. Fanni, V. Fanos, M.A. Marcialis LECT 53. PLACENTA AND METABOLOMICS • L. Barberini LECT 54. PERINATAL ENDOMETRIOSIS • S. Angioni, F. Dessolis LECT 55. PEDIATRIC FATTY LIVER DISEASE • D. Fanni, C. Gerosa, G. Faa LECT 56. THE QUESTIONS OF THE MOTHERS • A. Dessì LECT 57. DORIS AND THE OTHER CHILDREN WHO TOOK CARE OF ME… • P. Zanolla LECT 58. METABOLOME AND MICROBIOME IN PERI­NATAL MEDICINE: AN UPDATE • V. Fanos, M. Mussap LECT 59. NEONATOLOGICAL ORTHOPEDIC CASE RE­PORTS • V. Setzu, A. Dolc

Perinatal losses in beef herds in Orkney : Assessing incidence and associated pathology from general practice

There is a long history of high quality beef production in the Orkney Islands; however, perinatal losses (death of a full term calf from birth to 48 hours old) remain a major loss of potential income to producers. In an ideal situation, perinatal losses should occur in <2% of all calving cattle on British beef herds (Caldow et al., 2005). Local veterinary surgeons in Orkney perceived a high incidence of perinatal losses in beef herds which prompted further investigation of the incidence and aetiologies of these losses. A post mortem examination protocol and diagnostic algorithm were developed for the systematic investigation and categorisation of bovine perinatal losses in beef cattle, to allow the establishment of time of death, proximal cause of death and contributing factors to death. The incidence of perinatal losses and association with specified calving-related factors were described in a convenience sample of beef suckler herds in Orkney (n=11 herds, 1101 cows) (targeted herds) for the 2016 calf crop (1st February to 10th June). The proximal cause of calf death and contributing risk factors to death were determined in beef calves presented to a veterinary practice in Orkney for the 2016 calf crop from both targeted and passive herds. Targeted herds were defined as recruited herds, which were required to submit all perinatal losses. Passive herds were defined as herds submitting calves ad-hoc according to farmer motivation, with no further perinatal loss submission requirements. A total of 53 calves were submitted for gross post-mortem examination and further testing. Bovine perinatal mortality incidence varied from 1.6% to 12.4% across targeted herds, with an overall incidence of 5.1%, representing a higher incidence than the target for British beef herds. A proximal cause of death was reported for 89% of submissions. Diagnoses for perinatal losses included; anoxia, infection, congenital malformation and traumatocia. In submissions from targeted herds, death due to anoxia developing during stage two of parturition represented the largest cause of death (58%), with varying contributing factors. This was in comparison to submissions from passive herds, where death due to infection represented the largest cause of death (40%). Through application of a systematic diagnostic protocol, this study has indicated that perinatal losses in beef herds are a significant problem and require further industry attention to reduce losses