Delphine Mitanchez

Prenatal prognosis in isolated congenital diaphragmatic hernia

OBJECTIVE A monocentric retrospective study of 79 neonates with isolated diaphragmatic hernia antenatally diagnosed was performed to identify prenatal parameters that may characterize the severity of the disease. STUDY DESIGN Postnatal treatment protocol included early high frequency ventilation, inhaled nitric oxide, and delayed surgery. Postnatal survival rate was 63.3%. RESULTS Age at diagnosis, polyhydramnios, and left ventricle/right ventricle index were not related with survival. None of the 9 left diaphragmatic hernias with intraabdominal stomach died. Neonatal mortality was significantly related with the side of the defect, intrathoracic position of the liver, the ratio of fetal lung area to head circumference value, and fetal lung volume ratio measured by resonance magnetic imaging. CONCLUSION No prenatal factor alone firmly predicts neonatal outcome. Clinicians should help stratify the severity of the disease and compare accurately different postnatal therapeutic strategies.

Glucose Regulation in Preterm Newborn Infants

After birth, continuous transplacental transfer of glucose is interrupted. Neonates have to provide brain and vital organs with sufficient glucose. In term newborn infants, this is accomplished through well-coordinated hormonal and metabolic adaptive changes. During the first week of life, preterm infants are at high risk of abnormal glucose homeostasis. They are at risk of hypoglycemia due to limited glycogen and fat stores that should have occurred in the third trimester. Continuous glucose infusion is always required soon after birth to maintain the glucose level. However, under such conditions, many preterm infants develop hyperglycemia. Defective islet β-cell processing of proinsulin is likely related to hyperglycemia. There is also evidence that preterm infants are partially resistant to insulin. By contrast with adults, hepatic glucose production is not suppressed during parenteral glucose infusion. Exogenous insulin infusion partially reduces endogenous glucose production in preterm newborn infants. This treatment is efficient and safe when used with caution. More research is needed to understand the specificity of glucose homeostasis in preterm infants and to evaluate the long-term consequences of metabolic and nutritional support during early life.

Pain Management in Newborns From Prevention to Treatment

All neonates in the Neonatal Intensive Care Unit (NICU) or during the first days of life undergo painful and stressful procedures. Epidemiologic studies have shown that pain induced by these procedures is not effectively prevented or is inadequately treated. Pain experienced during the neonatal period may lead to negative outcomes, especially in preterm neonates. Prevention is the first step of pain management, and practical guidelines should be used in the NICU. Assessment must be done with adequate tools that take into account the infant’s pathology and gestational age. Distinguishing between acute and prolonged pain is important for both assessment and treatment. The most common drugs that have been studied for the treatment of pain and stress are opioids, hypnosedatives, and NMDA receptor antagonists. Morphine and fentanyl are most frequently used for acute or prolonged pain in the NICU. They have potent analgesic effects and few immediate or long-term adverse effects. Midazolam is a commonly used hypnosedative, but its adverse effects limit its use. Drugs such as propofol and ketamine have been used for acute painful procedures; however, further research is needed to assess their long-term effects. Use of non-pharmacologic pain management techniques has increased in recent years. These methods are easy, inexpensive, and effective in helping newborns recover from painful procedures. Sweet solutions and non-nutritive sucking, breastfeeding, skin-to-skin mother care, swaddling, and facilitated tucking are the most commonly employed and evaluated non-pharmacologic methods. Hospitals should promote and improve parent involvement in pain management. In-service education and well organized hospital teams are crucial for successful implementation of pain protocols in newborns.

Neonatal outcome of gastroschisis is mainly influenced by nutritional management

Objective: The aim of the study was to evaluate early minimal enteral feeding (MEF) and gradual enteral nutrition increment on neonatal outcome of gastroschisis. Patients and Methods: An intervention group was prospectively assessed and compared with an observational historical control group. The prospective study relied on a new protocol of enteral nutrition. According to the new protocol, MEF was initiated 5 days after bowel reintegration and milk amounts were increased 12 mL/kg/day. In the control group, enteral nutrition was delayed until resolution of postoperative ileus, and increment of feeding was not systematized. Results: Twenty-two patients were included in the MEF group and compared with 51 control patients. Infants in the control group had lower gestational age (36 vs 35 gestational weeks [GW], P = 0.03) and birth weight (2465 vs 2200 g, P = 0.05). Time to first enteral nutrition (5 vs 11.5 days, P = 0.0005) was significantly shorter in the MEF group. All patients in this group were fully enteral fed at day 60, though 30.4% of patients in the control group still needed parenteral nutrition at day 60 (P = 0.004). Incidence of nosocomial infection was reduced (9% of patients vs 40%, P = 0.016) and hospital stay tended to be shorter in the MEF group (40 vs 54.5 days, P = 0.08). In the univariate analysis, factors influencing the length of parenteral nutrition during the 2 periods were the severity of perivisceritis and new nutritional protocol. In the multivariate analysis, only nutritional protocol was significantly associated with the length of parenteral nutrition (P = 0.038). Conclusions: Early MEF and controlled increase of nutritional elements after bowel reintegration significantly improved outcome of gastroschisis in newborns.

Complications fœtales et néonatales du diagnostic gestationnel: mortalité périnatale, malformations congénitales, macrosomie, dystocie des épaules, traumatisme obstétrical, complications néonatales

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 39 - N° 8S2 - p. 189-199

Neonatal care in patients with giant ompholocele: arduous management but favorable outcomes.

OBJECTIVES The objectives of the study were to provide a review of patients with giant omphalocele managed in a single institution (2001-2006), focusing on medical management in the neonatal period, and to evaluate short-term outcomes. METHODS Data from 14 neonates with giant ompholocele (abdominal wall defect >5 cm and/or containing liver) and the absence of malformation and chromosomal anomalies during fetal screening were retrospectively reviewed. All were intubated and sedated before surgical treatment. Initial management consisted of progressive reduction of the herniated organs by gentle compression. After sequential reduction, abdominal wall closure was attempted at the skin and fascia level and, when necessary, with a Gore-Tex patch. RESULTS Median gestational age was 39 weeks (38-40), and median birth weight was 3100 g (2470-3700). Median age at closure was 6 days (0-20). A central Gore-Tex patch was inserted in 10 cases. Median ventilation length was 26 days (2-78). Full enteral diet was achieved after an average of 33 days (8-82), and median time until discharge from the intensive care unit was 24.5 days (11-85). Nine patients developed sepsis in the postoperative course. In 10 patients, at least 1 associated malformation was diagnosed in the postnatal course, among which cardiac and diaphragmatic defects were the most common. Survival rate was 85.7%. CONCLUSION Mortality rate of giant omphalocele without chromosomal anomaly or major malformations is low when treated by gradual reduction of the contents. Parents should be informed of the long hospitalization in the intensive care unit at birth, the potential nonthreatening associated malformations to be diagnosed after birth, and the high risk of sepsis.

Risk factors for developing transient neonatal cholestasis.

Objectives: To describe the incidence and the characteristics of neonatal cholestasis in a cohort of patients with known risk factors and to investigate additional risk factors. Methods: A prospective observational study conducted between April 2008 and 2009 involved all neonates admitted in the neonatal ward. They were divided into high- and low-risk groups for cholestasis. The high-risk group included preterm birth <34 weeks of gestation, small for gestational age (SGA), parenteral nutrition (PN) >7 days, abdomino-pelvic or thoracic surgery. Bilirubinemia was weekly measured in the high-risk group. Results: Of the 460 newborns studied, 234 were included in the high-risk group and 226 in the low-risk group. Cholestasis developed in 32 patients (13.7%) in the high-risk group at mean (SD) age of 14.7 (12.9) days; all were receiving PN. None of the patients in the low-risk group developed cholestasis. An analysis was carried out in the 207 patients in the high-risk group who received PN. The odds ratio (OR) for developing cholestasis was 2.3 [1.1–5.0] and 5.6 [2.5–12.5] for SGA or surgical patients, respectively. Cholestasis was associated with neonatal severe conditions, longer PN duration, and more intravenous macronutrients’ intakes. In multivariate analysis, SGA and neonatal surgery were strong independent risk factors for cholestasis, with OR (95% confidence interval [95% CI]) of 4.4 [1.6–12.5] and 4.6 [1.7–12.3], respectively. Conclusions: Transient neonatal cholestasis is a complication of PN. SGA and neonatal surgery are additional risk factors. There is no evidence to limit intravenous protein intakes in preterm.

Congenital Cytomegalovirus Infection Manifesting as Neonatal Persistent Pulmonary Hypertension: Report of Two Cases

Various neonatal symptoms can lead to a diagnosis of congenital CMV infection. We report two cases of persistent pulmonary hypertension in relation with congenital CMV infection following maternal primary infection and reinfection, respectively. Both infants had severe refractory hypoxemia, requiring high-frequency ventilation, inhaled nitric oxide and inotropic support. One of them required extracorporeal membrane oxygenation for five days. Ganciclovir therapy was attempted in the two cases on day 12 postnatal. One of the infant died on day 15 postnatal. The other survived and is developing uneventfully at 15 months of age. Conclusion: Neonatal persistent pulmonary hypertension can be the consequence of congenital CMV infection. Intensive respiratory support and IV ganciclovir are indicated in case of life-threatening condition.

Differentiating Transient Idiopathic Hyperglycaemia and Neonatal Diabetes Mellitus in Preterm Infants

Background/Aims: Transient idiopathic hyperglycaemia (TIH) is partly due to defective processing of proinsulin to insulin in preterm neonates, whereas transient neonatal diabetes mellitus (TNDM) is a rare genetic form of pancreatic β-cell dysfunction. Distinguishing these two conditions is difficult yet essential to allow personalised management and genetic testing. Here we investigated whether metabolic or therapeutic features contributed to the diagnosis in preterm neonates. Methods: We prospectively included 13 preterm neonates with TIH between 2008 and 2011, and we identified 2 patients with TNDM in the French neonatal diabetes cohort registry. All of them were born before 32 weeks of gestation. We compared clinical features, glycaemic profiles, insulin dosages, and nutritional intakes. Results: TNDM patients had higher day-1 glycaemia levels before insulin therapy [median 23.5 (20-27) vs. 13.6 (10.7-19.8) mmol/l, p = 0.025] and higher insulin requirements [median 1.2 (0.9-1.5) vs. 0.8 (0.3-0.9) IU/kg/day, p = 0.037] compared to TIH. They also required insulin therapy earlier [median 0.75 (0.5-1) vs. 2 (0.5-7) days, p = 0.036] and for a longer time [median 85 (57-113) vs. 11 (4-15) days, p = 0.036]. Conclusion: TNDM and TIH are different clinical and genetic entities with specific pathophysiological mechanisms. Metabolic and therapeutic features may help to detect TNDM in preterm neonates as soon as day-1 of hyperglycaemia.

Effect of maternal obesity on birthweight and neonatal fat mass: A prospective clinical trial

Objective To discriminate the effect of maternal obesity and gestational diabetes on birth weight and adipose tissue of the newborn. Methods Normal BMI women (group N, n = 243; 18.5≤ BMI<25 kg/m2) and obese women (group Ob, n = 253; BMI≥30 kg/m2) were recruited in a prospective study between 15 and 18 weeks of gestation. All women were submitted to a 75g oral glucose tolerance test in the second and third trimester. First trimester fasting blood glucose was also obtained from Ob women. All women with one measurement above normal values were considered positive for gestational diabetes and first treated by dietary intervention. When dietary measures were not efficient, they were treated by insulin. Neonatal anthropometrics, sum of skinfolds and cord serum hormones were measured. Results 222 N and 226 Ob mothers and their newborns were included in the analysis. Diabetes was diagnosed in 20% and 45.2% of N and Ob women, respectively. Birth weight was not statistically different between groups (boys: 3456g±433 and 3392g±463; girls: 3316g±402 and 3391g±408 for N and Ob, respectively). Multivariate analysis demonstrated that skinfold thickness and serum leptin concentrations were significantly increased in girls born to women with obesity (18.0mm±0.6 versus 19.7mm±0.5, p = 0.004 and 11.3ng/mL±1.0 versus 15.3ng/mL±1.0, p = 0.02), but not in boys (18.4mm±0.6 versus 18.5mm±0.5, p = 0.9 and 9.3ng/mL±1.0 versus 9.0ng/mL±1.0, p = 0.9). Based on data from 136 N and 124 Ob women, maternal insulin resistance at 37 weeks was also positively related to skinfold in girls, only, with a 1-point increase in HOMA-IR corresponding to a 0.33mm±0.08 increase in skinfold (p<0.0001). Conclusions Regardless of gestational diabetes, maternal obesity and insulin resistance were associated with increased adiposity in girls only. Persistence of this sexual dimorphism remains to be explored during infancy.