Impacts of Respiratory Muscle Training on Respiratory Functions, Maximal Exercise Capacity, Functional Performance, and Quality of Life in School-Aged Children with Postoperative Congenital Diaphragmatic Hernia.

OBJECTIVES: Congenital diaphragmatic hernia (CDH) is a birth defect affecting the respiratory functions, functional performance, and quality of life (QOL) in school-aged children. Rarely have studies been conducted to evaluate the impacts of respiratory muscle training on school-aged children with postoperative CDH. The current study was designed to evaluate the impacts of respiratory muscle training on respiratory function, maximal exercise capacity, functional performance, and QOL in these children. METHODS: This study is a randomized control study. 40 children with CDH (age: 9-11 years) were assigned randomly into two groups. The first group conducted an incentive spirometer exercise combined with inspiratory muscle training (study group, n = 20), whereas the second group conducted only incentive spirometer exercise (control group, n = 20), thrice weekly for twelve consecutive weeks. Respiratory functions, maximal exercise capacity, functional performance, and pediatric quality of life inventory (PedsQL) were assessed before and after the treatment program. Results. Regarding the posttreatment analysis, the study group showed significant improvements in all outcome measures (FVC%, p < 0.001; FEV1%, p = 0.002; VO2max, p = 0.008; VE/VCO2 slope, p = 0.002; 6-MWT, p < 0.001; and PedsQL, p < 0.001), whereas the control group did not show significant changes (p > 0.05). CONCLUSION: Respiratory muscle training may improve respiratory functions, maximal exercise capacities, functional performance, and QOL in children with postoperative CDH. Clinical commendations have to be considered to include respiratory muscle training in pulmonary rehabilitation programs in children with a history of CDH.

Congenital diaphragmatic hernia and maternal dietary nutrient pathways and diet quality.

INTRODUCTION: We examined the association of congenital diaphragmatic hernia (CDH) with maternal dietary intake, using semi-Bayes hierarchical models and principal components analysis to consider intake of nutrients that contribute to one-carbon metabolism and oxidative stress pathways, and a diet quality index. METHODS: We included data on 825 cases and 11,108 nonmalformed controls born from 1997-2011 whose mother participated in the National Birth Defects Prevention Study (NBDPS), a multisite, population-based case-control study. Exposure data were from maternal telephone interviews, which included a food frequency questionnaire. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were generated from logistic regression models that included nutritional factors as continuous variables and were adjusted for maternal energy intake, race-ethnicity, parity, and vitamin supplement intake. RESULTS: In the semi-Bayes hierarchical model that included all nutrients and confounders, riboflavin was the only nutrient for which the 95% CI excluded 1.0; the aOR for a 1 SD increase was 0.83. The aORs were 0.79 (95% CI 0.69-0.91) for the one-carbon metabolism pathway score, 0.90 (95% CI 0.80-1.01) for oxidative stress, and 0.85 (95% CI 0.77-0.93) for diet quality (the aORs correspond to a 1 SD increase). CONCLUSIONS: The findings from this study provide some support for the hypothesis that better prepregnancy nutrition is associated with reduced risk for CDH. These results provide etiologic clues but should be interpreted with caution given the novelty of the investigation.

Inflammatory Bowel Disease and Risk of Birth Defects in Offspring.

BACKGROUND AND AIMS: The relationship between inflammatory bowel disease in pregnancy and birth defects is not understood. We evaluated whether Crohn's disease and ulcerative colitis in pregnant women were associated with the risk of birth defects in the offspring. METHODS: We undertook a retrospective cohort study of 2 184 888 pregnancies in Quebec, Canada, between 1989 and 2016. We calculated risk ratios [RR] and 95% confidence intervals [CI] for the association between inflammatory bowel disease and the risk of birth defects, using generalised estimating equations adjusted for maternal characteristics. We assessed associations in the period before 2000, when immunosuppressive biologic therapy and folic acid food fortification were not yet available, compared with the period after 2000 when these interventions were more widespread. RESULTS: This study included 13 099 women with Crohn's disease and 7798 with ulcerative colitis. Crohn's disease was associated with 1.90 times [95% CI 1.10-3.28] the risk of abdominal wall defects [gastroschisis, omphalocoele, and diaphragmatic hernia] and ulcerative colitis was associated with 1.53 times [95% CI 1.02-2.30] the risk of central nervous system defects. The association of Crohn's disease with abdominal wall defects was stronger before 2000 [RR 3.62, 95% CI 1.71-7.67] than after 2000 [RR 1.23, 95% CI 0.55-2.75]. Ulcerative colitis was associated with central nervous system defects regardless of time period. CONCLUSIONS: These findings suggest that inflammatory bowel disease is associated with the risk of abdominal wall and central nervous system defects, and that introduction of immunobiologic medications is unlikely to be associated with added risk. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

[The primary care of a patient with a history of a gastrointestinal malformation and abdominal wall or diaphragmatic defects]. / La atención primaria del paciente con el antecedente de una malformación digestiva, defectos de pared abdominal o diafragmáticos.

Survival of patients with congenital malformation has improved over the last decades. Primary care paediatricians must be aware of the most common problems that this group of patients suffers. More importantly, paediatricians can offer a holistic view that is often lost in specialised consultation. This article is focused on common congenital malformation, such as oesophageal atresia, abdominal wall defects, anorectal malformation and Hirschsprung disease, and congenital diaphragmatic hernia. The main problems are shown, with special emphasis on long-term complications and all the dimensions of the individual.

Maternal dietary intake of vitamin A during pregnancy was inversely associated with congenital diaphragmatic hernia: the Japan Environment and Children's Study.

The pathogenesis of congenital diaphragmatic hernia (CDH) is largely unknown; however, vitamin A seems to play a role in diaphragmatic development. Previous case-control studies reported that maternal dietary vitamin A intake was inversely associated with the risk of CDH. To our knowledge, however, there is no prospective evidence regarding this association. Our aim was to examine whether maternal intake of vitamin A was associated with CDH occurrence. Baseline data, from the Japan nationwide birth cohort study (2011-2014) of 89 658 mothers (mean age at delivery = 31·2 years) who delivered singleton live births, were analysed. We assessed dietary habits using an FFQ focused on the first trimester and estimated the daily intake of total vitamin A (retinol activity equivalents), retinol, provitamin A carotenoids and vegetables. The occurrence of CDH was ascertained from medical records. A total of forty cases of CDH were documented. The adjusted OR of CDH occurrence for the high total vitamin A intake category (median = 468 µg/d) was 0·6 (95 % CI 0·3, 1·2) with reference to the low intake category (230 µg/d). When we restricted to mothers with a prepregnancy BMI of 18·5-24·9 kg/m2, vitamin A intake was inversely associated with the risk of their children being born with CDH (OR 0·5, 95 % CI 0·2, 1·0). Even given the limited number of cases in the study, our findings provide additional evidence to link vitamin A with CDH.

Impact of nutrition in the treatment of congenital diaphragmatic hernia.

BACKGROUND: The optimum enteral (EN) and parenteral nutrition (PN) regimens during acute management of congenital diaphragmatic hernia (CDH) remain unclear. We examined the effects of EN and PN on weight gain in CDH patients. METHODS: A multicenter retrospective cohort study of neonates with CDH (born 2006-2010; n = 105) who survived to discharge was conducted. Patients were divided as receiving PN ≥ or <50 kcal/kg/day at 1 week of age, and EN ≥ or <60 kcal/kg/day at 2 weeks of age. Changes in bodyweight at 30, 60, and 90 days of age were compared. RESULTS: The higher EN group (n = 39) had greater mean weight gain than the lower EN group (n = 66; 90 days: 2,501 g, 95% CI: 2,294-2,710 g vs 1,706 g, 95% CI: 1,553-1,861 g; P <0.001). When patients received lower EN, the higher PN group (n = 24) had greater mean weight gain than the lower PN group (n = 42; 90 days: 1,768 g, 95% CI: 1,574-1,961 g vs 1,411 g, 95% CI: 1,264-1,558 g; P = 0.004). CONCLUSION: The amount of EN in the acute phase of CDH management is essential for weight gain during infancy. When patients are intolerant to adequate EN, supportive PN is also essential.

Hernia diafragmatica en pediatria / Diaphragmatic hernia in pediatrics

Resumen La hernia diafragmática (HD) consiste en un trastorno en el desarrollo del músculo diafragmático, produciéndose el paso de contenido abdominal a la cavidad torácica. Las principales son hernia de Bochdalek, Morgagni y Hiatal.1 Malformación congénita que afecta a 1 de cada 2 200 recién nacidos. Está asociada a elevada morbimortalidad, principalmente por hipoplasia pulmonar e hipertensión.2 La ecografía prenatal determina el diagnóstico, pronóstico y terapia. La cirugía consiste en cerrar el defecto, siendo el objetivo del tratamiento mantener un adecuado intercambio gaseoso, evitar o minimizar la hipoplasia y la hipertensión pulmonar.1 Las hernias diafragmáticas presentes en el momento del nacimiento se diagnostican fácilmente. En contraste, el diagnóstico de las hernias después del periodo neonatal es muy variable, puede conducir a evaluaciones clínicas y radiológicas erróneas.3

Abstract The diaphragmatic hernia is a disorder in the development of the diaphragm, causing the passage of the abdominal contents into the thoracic cavity. The main ones are Bochdalek, Hiatal and Morgagni hernias1. Congenital malformation that affects 1 in 2 200 newborns. It is associated to high morbidity and mortality mainly due to lung hypoplasia and hypertension.2 Prenatal ultrasound determines the diagnosis, prognosis and therapy. The surgical procedure consists ofthe closure of the defect. The goal of the treatment is to maintain adequate gas exchange, to prevent or minimize hypoplasia and pulmonary hypertension.1 Congenital diaphragmatic hernias present at birth are readily recognized. In contrast, the diagnosis of diaphragmatic hernia after the neonatal period varies considerably owing to misleading clinical and radiologic features.3

Robotic repair of a right-sided Bochdalek hernia: a case report and literature review.

BACKGROUND: Bochdalek hernias (BHs) are usually diagnosed in the neonatal period, occurring in 1/2200-1/12,500 live births. There are few reported cases of BHs in adults. Robotic repair has not been described in current literature as opposed to the laparoscopic approach. Here we present a case of an adult with clinical signs of bowel obstruction secondary to a BH which was repaired using a robotic approach. CASE REPORT: A 74-year-old gentleman with past medical history of benign prostatic hyperplasia presented to the emergency department with a 1-week history of nausea, vomiting, diarrhea, and decline in appetite. Computed tomography (CT) imaging of the chest and abdomen revealed elevation of the right hemidiaphragm and evidence of small bowel obstruction. The patient was managed conservatively with nasogastric tube placement and bowel rest. He underwent colonoscopy which could not be completed secondary to a transverse colon stricture which was confirmed by barium enema. Upon repeat CT imaging, the patient was found to have herniated colon through a right-sided diaphragmatic hernia which caused colonic narrowing. The patient's intestinal obstruction improved clinically with continued conservative management and he underwent robotic repair of a right posterior diaphragmatic hernia. The hernia defect was closed with interrupted figure of eight Ethibond sutures. A right-sided chest tube was placed. Intraoperatively, the herniated proximal transverse colon was noted to be ischemic and a right hemicolectomy was performed. He recovered well and was discharged home on postoperative day 5. CONCLUSION: Congenital diaphragmatic hernias usually present in the neonatal period and are rare in adults. Operative repair is recommended and laparoscopic repair has been described. Based on the existing literature regarding laparoscopic repair and the current case report, robotic repair also appears to be a viable and safe option.

[Late presentation of congenital diaphragmatic hernia]. / Late symptomen van congenitale hernia diafragmatica.

Congenital diaphragmatic hernia (CDH) is a rare congenital defect. Most cases are currently diagnosed either prenatally by ultrasound or shortly after birth. Late presentation of CDH is uncommon, and symptoms vary greatly. Here we describe two cases. The first concerns a 9-year-old boy with abdominal pain. The symptoms were interpreted as constipation and he was admitted for a high enema. After a few hours he developed severe respiratory distress; chest X-ray revealed a tension gastrothorax, and thoracostomy resulted in immediate respiratory improvement. In the second case, a 6-month-old girl presented with haematemesis and electrolyte imbalance. She was admitted for rehydration and correction of the electrolyte balance. A chest X-ray was performed because of persistent vomiting, and this showed an intrathoracal stomach. Late presentation of CDH is often misdiagnosed, with the risk of serious morbidity and mortality. Tension gastrothorax is a rare, life-threatening complication which should be treated by emergency gastric decompression..

Technical standardization of laparoscopic repair of Morgagni diaphragmatic hernia in children: results of a multicentric survey on 43 patients.

BACKGROUND: This study aimed to standardize the surgical correction technique of congenital Morgagni diaphragmatic hernia (CMDH), analyzing the results of an international multicentric survey. METHODS: The medical records of 43 patients (29 boys, 14 girls) who underwent laparoscopic repair of CMDH in 8 pediatric surgery units in a 5-year period were retrospectively reviewed. Their average age was 3.3 years. Ten patients (23.2%) presented associated malformations: 9 Down syndrome (20.9%) and 1 palate cleft (2.3%). Thirty-five patients (81.4%) were asymptomatic, whereas 8 patients (18.6%) presented symptoms such as respiratory distress, cough or abdominal pain. As for preoperative work-up, all patients received a chest X-ray (100%), 15/43 (34.8%) a CT scan, 8/43 (18.6%) a barium enema and 4/43 (9.3%) a US. RESULTS: No conversion to open surgery was reported. Average operative time was 61.2 min (range 45-110 min). In 38/43 (88.3%) patients, a trans-parietal stitch was positioned in order to reduce the tension during the repair. In 14/43 cases (32.5%), the sac was resected; in only 1/43 case (2.3%) a dual mesh of goretex was adopted to reinforce the closure. Average hospital stay was 2.8 days. The average follow-up was 4.2 years, and it consisted in annual clinical controls and chest X-ray. We recorded 2 complications (4.6%): one small pleural opening that required no drain and one recurrence (2.3%), re-operated in laparoscopy, with no further recurrence. CONCLUSIONS: To the best of our knowledge, this is the largest series published in the literature on this topic. Laparoscopic CMDH repair is well standardized: The full-thickness anterior abdominal wall repair using non-resorbable suture with interrupted stitches is the technique of choice. Postoperative outcome was excellent. Recurrence rate was very low, about 2% in our series. We believe that children with CMDH should be always treated in laparoscopy following the technical details reported in this paper.

Neonatal bowel strangulation: Rare presentation of congenital diaphragmatic hernia.

We report a case of congenital diaphragmatic hernia (CDH) with perinatal bowel strangulation requiring intestinal resection. Ten hours after birth, the newborn started to be lethargic and developed bilious emesis. X-ray documented distended loops of bowel with air fluid levels in the abdomen and a gasless, non-homogeneous opacity of the left hemithorax, a right mediastinal shift and loss of the sharp left hemidiaphram line. On gastrographin enema the left colon was above the adjacent left diaphragm. Emergency surgery was performed at 16 h of age. The entire small bowel appeared reddish and compromised. After 24 h, second-look laparotomy was performed and only 25 cm of small bowel were viable. The postoperative period was uneventful. Neonatal bowel strangulation in CDH should be taken into account when estimating postnatal morbidity and mortality and, even if CDH treatment is not an emergency procedure, if gastrointestinal symptoms prevail over respiratory symptoms, surgery should be carried out without delay.

Clinically relevant timing of antenatal sildenafil treatment reduces pulmonary vascular remodeling in congenital diaphragmatic hernia.

Patients with congenital diaphragmatic hernia (CDH) suffer from severe pulmonary hypertension attributable to altered development of the pulmonary vasculature, which is often resistant to vasodilator therapy. Present treatment starts postnatally even though significant differences in the pulmonary vasculature are already present early during pregnancy. We examined the effects of prenatal treatment with the phosphodiesterase-5 inhibitor sildenafil on pulmonary vascular development in experimental CDH starting at a clinically relevant time. The well-established, nitrofen-induced CDH rodent model was treated daily with 100 mg/kg sildenafil from day 17.5 until day 20.5 of gestation (E17.5-20.5). Importantly, this timing perfectly corresponds to the developmental stage of the lung at 20 wk of human gestation, when CDH is detectable by 2D-ultrasonography and/or MRI. At E21.5 pups were delivered by caesarean section and euthanized by lethal injection of pentobarbital. The lungs were isolated and subsequently analyzed using immunostaining, real-time PCR, and volume measurements. Prenatal treatment with sildenafil improved lung morphology and attenuated vascular remodeling with reduced muscularization of the smaller vessels. Pulmonary vascular volume was not affected by sildenafil treatment. We show that prenatal treatment with sildenafil within a clinically relevant period improves pulmonary vascular development in an experimental CDH model. This may have important implications for the management of this disease and related pulmonary vascular diseases in human.

Congenital retrosternal hernias of Morgagni: Manifestation and treatment in children.

BACKGROUND: Due to scarcity of congenital diaphragmatic hearnias of Morgagni (CDHM), non-specific clinical presentation in the pediatric age group, we aimed to investigate the incidence, clinical manifestations, anatomical characteristics, and develop diagnostic algorithm and treatment of CDHM in children. MATERIALS AND METHODS: The patients' records of children with CDHM treated in our hospital during past 20 years were retrospectively reviewed for the age at diagnosis, gender, clinical findings, anatomical features, operative details and outcome. RESULTS: Since 1995 to 2014 we observed 6 (3 boys, 3 girls) patients with CDHM, that comprise 3.2% of all congenital diaphragmatic hernia cases (n = 185). Age at diagnosis varied from 3 mo. to 10y.o. Failure to thrive was main symptom in 4 patients, followed by recurrent respiratory infections (n = 3), dyspnea (n = 3), and gastrointestinal manifestations: constipation (n = 2), abdominal pain (n = 1). Work-up consisted of plain X-ray for all (n = 6), upper GI (n = 3), barium enema (n = 2), sonography (n = 6) and CT (n = 2). Abdominal approach used in 5 patients, and thoracotomy in one. Herniated contents were: liver lobes (n = 4), transverse colon (n = 3) and greater omentum (n = 1). 5 had right-sided lesion, 1- left-sided. Defect repaired using local tissues. Post-operative course was uneventful; all patients appeared well during follow-up. CONCLUSION: CDHM is very uncommon anomaly, very occasionally diagnosed at the early age. Failure to thrive and recurrent respiratory infections are most frequent clinical manifestations. In suspected CDHM we advocate the following work-up: plain chest and abdominal X-ray, contrast study (upper GI series or barium enema), ultrasonographic screen and CT scan. Surgical repair via abdominal approach, using local tissues and hernia sac removal is preferred.

Antenatal Saireito (TJ-114) Can Improve Pulmonary Hypoplasia and Pulmonary Vascular Remodeling in Nitrofen-Induced Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia (CDH) can induce lung hypoplasia and pulmonary hypertension and is associated with high mortality. The purpose of this study is to examine the efficacy and safety of antenatal Saireito (TJ-114), a traditional Japanese herbal medicine, in a rat CDH model. Sprague-Dawley rats were exposed to an herbicide (nitrofen, 100 mg) on embryonic day 9 (E9) to induce CDH, and antenatal Saireito (2000 mg/kg/day) was orally administered from E10 to E20. On E21, fetuses were delivered. Antenatal Saireito significantly decreased the incidence of CDH (p < 0.01), increased lung volume (p < 0.01), improved alveolarization and pulmonary artery remodeling using histological analysis, and improved respiratory function using gasometric analysis (pH; p < 0.05, and PCO2 ; p < 0.01). In addition, antenatal Saireito significantly decreased endothelin-1 and endothelin receptor A expression in the pulmonary arteries. Taken together, our results demonstrated that antenatal Saireito can improve fetal pulmonary hypoplasia and pulmonary vascular remodeling and, as a result, can improve respiratory function in a rat CDH model. Copyright © 2016 John Wiley & Sons, Ltd.

Antenatal BAY 41-2272 reduces pulmonary hypertension in the rabbit model of congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (CDH) fail to adapt at birth because of persistent pulmonary hypertension (PH), a condition characterized by excessive muscularization and abnormal vasoreactivity of pulmonary vessels. Activation of soluble guanylate cyclase by BAY 41-2272 prevents pulmonary vascular remodeling in neonatal rats with hypoxia-induced PH. By analogy, we hypothesized that prenatal administration of BAY 41-2272 would improve features of PH in the rabbit CDH model. Rabbit fetuses with surgically induced CDH at day 23 of gestation were randomized at day 28 for an intratracheal injection of BAY 41-2272 or vehicle. After term delivery (day 31), lung mechanics, right ventricular pressure, and serum NH2-terminal-pro-brain natriuretic peptide (NT-proBNP) levels were measured. After euthanasia, lungs were processed for biological or histological analyses. Compared with untouched fetuses, the surgical creation of CDH reduced the lung-to-body weight ratio, increased mean terminal bronchial density, and impaired lung mechanics. Typical characteristics of PH were found in the hypoplastic lungs, including increased right ventricular pressure, higher serum NT-proBNP levels, thickened adventitial and medial layers of pulmonary arteries, reduced capillary density, and lower levels of endothelial nitric oxide synthase. A single antenatal instillation of BAY 41-2272 reduced mean right ventricular pressure and medial thickness of small resistive arteries in CDH fetuses. Capillary density, endothelial cell proliferation, and transcripts of endothelial nitric oxide synthase increased, whereas airway morphometry, lung growth, and mechanics remained unchanged. These results suggest that pharmacological activation of soluble guanylate cyclase may provide a new approach to the prenatal treatment of PH associated with CDH.

Neuroendocrine factors regulate retinoic acid receptors in normal and hypoplastic lung development.

KEY POINTS: Retinoic acid (RA) and ghrelin levels are altered in human hypoplastic lungs when compared to healthy lungs. Although considerable data have been obtained about RA, ghrelin and bombesin in the congenital diaphragmatic hernia (CDH) rat model, neuroendocrine factors have never been associated with the RA signalling pathway in this animal model. In this study, the interaction between neuroendocrine factors and RA was explored in the CDH rat model. The authors found that normal fetal lung explants treated with RA, bombesin and ghrelin showed an increase in lung growth. Hypoplastic lungs presented higher expression levels of the RA receptors α and γ. Moreover bombesin and ghrelin supplementation, in vitro, to normal lungs increased RA receptor α/γ expression whereas administration of bombesin and ghrelin antagonists to normal and hypoplastic lungs decreased it. These data reveal for the first time that there is a link between neuroendocrine factors and RA, and that neuroendocrine factors sensitise the lung to the RA action through RA receptor modulation. ABSTRACT: Congenital diaphragmatic hernia (CDH) is characterised by a spectrum of lung hypoplasia and consequent pulmonary hypertension, leading to high morbidity and mortality rates. Moreover, CDH has been associated with an increase in the levels of pulmonary neuroendocrine factors, such as bombesin and ghrelin, and a decrease in the action of retinoic acid (RA). The present study aimed to elucidate the interaction between neuroendocrine factors and RA. In vitro analyses were performed on Sprague-Dawley rat embryos. Normal lung explants were treated with bombesin, ghrelin, a bombesin antagonist, a ghrelin antagonist, dimethylsulfoxide (DMSO), RA dissolved in DMSO, bombesin plus RA and ghrelin plus RA. Hypoplastic lung explants (nitrofen model) were cultured with bombesin, ghrelin, bombesin antagonist or ghrelin antagonist. The lung explants were analysed morphometrically, and retinoic acid receptor (RAR) α, ß and γ expression levels were assessed via Western blotting. Immunohistochemistry analysis of RAR was performed in normal and hypoplastic lungs 17.5 days post-conception (dpc). Compared with the controls, hypoplastic lungs exhibited significantly higher RARα/γ expression levels. Furthermore considering hypoplastic lungs, bombesin and ghrelin antagonists decreased RARα/γ expression. Normal lung explants (13.5 dpc) treated with RA, bombesin plus RA, ghrelin plus RA, bombesin or ghrelin exhibited increased lung growth. Moreover, bombesin and ghrelin increased RARα/γ expression levels, whereas the bombesin and ghrelin antagonists decreased RARα/γ expression. This study demonstrates for the first time that neuroendocrine factors function as lung growth regulators, sensitising the lung to the action of RA through up-regulation of RARα and RARγ.

[Familial congenital diaphragmatic hernia with anencephly-exencephaly and spina bifida]. / Rodzinne wystepowanie wrodzonej przepukliny przeponowej z wada dystroficzna i bezczaszkowiem.

Congenital Diaphragmatic Hernia (CDH) occurs with an estimated incidence of 1 to 2500 live births. Even though the exact etiology is still unknown, more and more often current research points out genetic factors as the possible cause of the defect. According to the latest data and the own experience 50-60% of CDH cases are isolated. The rest forms a group of CDH complicated by an additional anatomic defect or a genetic syndrome caused by a mutation of a single gene or the whole chromosome. We have presented a case study of a 32 years-old multigravida para 3, who has been referred to the Reference Centre of Prenatal Cardiology in 30 weeks of gestation due to the diagnosis of acrania with exencephaly, spina bifida and suspicion for CDH in a fetus. Although the patient's first child died due to CDH, the patient neither before nor during the pregnancy was getting a folic acid supplementation. Moreover, she has not agreed on a further cytogenetic testing or an advanced consultation with a clinical geneticist. The child died after delivery in a local hospital. The case was described to indicate the problem that the CDH diagnostic procedure is still missing a molecular genetic analysis especially in the cases of recurrent CDH. By saying that in the cases of CDH we should always strive to complete the molecular testing having in mind that by discovering pathogenesis and genes responsible for the formation of CDH we not only might improve the therapeutic methods but also find a way to prevent its development.

Growth in children with congenital diaphragmatic hernia during the first year of life.

PURPOSE: Infants with congenital diaphragmatic hernia (CDH) have high rates of mortality and long-term morbidity, including poor growth and failure to thrive. The aim of this study was to describe growth patterns during the first year of life in infants with congenital diaphragmatic hernia in a non-ECMO cohort. METHODS: Medical records of infants with CDH admitted to our center between January 2005 and December 2011 were reviewed. Infants with anthropometric measurements at 3, 6 and 12months were included. Anthropometric measurements were obtained for the first year of life. Logistic regression analyses were performed to find predictive associations with failure to thrive (FTT). RESULT: Of the 45 survivors, 38 were seen twice (84%) and 24 (53%) were seen on three occasions to age 12months. Poor growth was observed with weight being most affected. FTT was present in 63% during the first six months of life. Days of mechanical ventilation were the only predictor of FTT. Besides poor weight gain, height and head circumference were also reduced. However, catch-up growth occurred during the second half of infancy and at age 12months failure to thrive had reduced by two thirds to 21%. CONCLUSIONS: Poor growth is a common early finding in CDH patients, which improves during infancy. This emphasizes the importance of close follow-up and aggressive nutritional management in CDH patients.

Nitrofen increases total retinol levels in placenta during lung morphogenesis in the nitrofen model of congenital diaphragmatic hernia.

BACKGROUND: It has been shown that pulmonary retinol level is decreased during lung morphogenesis in the nitrofen-induced PH in congenital diaphragmatic hernia (CDH). Placenta has a major role in the retinol homeostasis in fetal life. Since there is no fetal retinol synthesis, maternal retinol has to cross the placenta. Placenta is the main fetal retinol store where retinol is stored in retinyl-ester formation. Trophoblasts have to produce its own retinol-binding protein (RBP) for retinol transport from placenta to fetus. Recently, we demonstrated that trophoblastic RBP expression is decreased in the nitrofen model of CDH. The aim of this study was to investigate the retinol transfer from mother to the placenta in nitrofen model of CDH. METHODS: Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal placenta harvested on D21 and divided into two groups: control (n = 11) and nitrofen with CDH (n = 11). Retinoid levels in placenta were measured using HPLC. Immunohistochemistry was performed to evaluate trophoblastic expression of main RSP genes. RESULTS: Total retinol levels in the placenta were significantly increased in CDH placenta compared to control placenta. The retinyl-ester levels were significantly increased in CDH placenta compared to control placenta. Markedly, decreased immunoreactivity of retinoid signaling pathway was observed in trophoblast cells in CDH compared to control placenta. CONCLUSIONS: Increased placental retinol levels show that retinol is transferred from mother to placenta and stored in the placenta in nitrofen model of CDH during lung morphogenesis. Nitrofen may disturb the mobilization of retinol from placenta to fetal circulation causing PH in CDH.

Increased uptake of dietary retinoids at the maternal-fetal barrier in the nitrofen model of congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: The retinol signaling pathway is disrupted in congenital diaphragmatic hernia (CDH). Since there is no fetal retinol synthesis, maternal retinol has to cross the placenta. Nitrofen interferes with the retinol-binding protein (RBP) transfer pathway in CDH. However, in RBP knockout mice, retinol has been shown to be present. In this model, increased uptake of maternal dietary retinyl ester (RE) bounded in low-dense-lipoprotein (LDL) through low-density-lipoprotein-receptor 1 (LRP1) and increased activity of RE hydrolysis by lipoprotein-lipase (LPL) have been found. The aim of this study was to investigate the RE transfer pathway in the nitrofen CDH model. METHODS: Pregnant rats were treated with nitrofen or vehicle on gestational day (D9) and sacrificed on D21. Immunohistochemistry was performed to evaluate LRP1 and LPL protein expression. Serum LDL levels were measured by ELISA. Pulmonary and serum retinoid levels were measured using HPLC. RESULTS: Markedly increased trophoblastic and pulmonary LRP1 and LPL immunoreactivity were observed in CDH compared to controls. Significantly increased serum LDL and RE levels were observed in CDH compared to controls. CONCLUSIONS: The increased uptake of dietary retinoids at the maternal-fetal barrier in the nitrofen CDH model suggests that the RE transfer pathway may be the main source of retinol in this model.