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Objective To determine whether complex gastroschisis (ie, intestinal atresia, perforation, necrosis, or volvulus) can prenatally be distinguished from simple gastroschisis by fetal stomach volume and stomach‐bladder distance, using three‐dimensional (3D) ultrasound. Methods This multicenter prospective cohort study was conducted in the Netherlands between 2010 and 2015. Of seven university medical centers, we included the four centers that performed longitudinal 3D ultrasound measurements at a regular basis. We calculated stomach volumes (n = 223) using Sonography‐based Automated Volume Count. The shortest stomach‐bladder distance (n = 241) was determined using multiplanar visualization of the volume datasets. We used linear mixed modelling to evaluate the effect of gestational age and type of gastroschisis (simple or complex) on fetal stomach volume and stomach‐bladder distance. Results We included 79 affected fetuses. Sixty‐six (84%) had been assessed with 3D ultrasound at least once; 64 of these 66 were liveborn, nine (14%) had complex gastroschisis. With advancing gestational age, stomach volume significantly increased, and stomach‐bladder distance decreased (both P, What's already known about this topic? Infants with complex gastroschisis have a higher risk of morbidity than those with simple gastroschisis.Many attempts have been made to prenatally predict complex gastroschisis, using two‐dimensional ultrasound parameters. What does this study add? This longitudinal prospective multicenter study is the first to evaluate the possible benefit of the use of three‐dimensional ultrasound in fetuses with gastroschisis.Fetal stomach volume and stomach‐bladder distance, measured during pregnancy using three‐dimensional ultrasound, cannot predict complex gastroschisis.

Objective: We aimed to evaluate the relationship between chorionicity, placental abnormalities and necrotizing enterocolitis in multiple pregnancies. We hypothesized that unbalanced interfetal transfusion through vascular anastomoses in monochorionic placentation causes hypoperfusion of the intestinal mucosa, increasing the risk of developing necrotizing enterocolitis. Material and methods: All women with multiple pregnancies who delivered at the University Medical Center Utrecht between January 1995 and December 2015 were retrospectively selected. We compared baseline characteristics and neonatal and maternal outcomes. Secondly, we analyzed ultrasound and placental pathology findings of monochorionic multiples with and without necrotizing enterocolitis. Finally, we compared illness characteristics of necrotizing enterocolitis in monochorionic multiples with necrotizing enterocolitis in dichorionic multiples. Results: We included 2859 dichorionic and 817 monochorionic neonates. Necrotizing enterocolitis occurred significantly more often in monochorionic as compared to dichorionic neonates (3.3% and 1.6% respectively), also after correction for birthweight, gestational age and nulliparity (OR 1.7, 95% CI 1.0 - 2.8). Ultrasound abnormalities were not associated with necrotizing enterocolitis. Histopathology showed that necrotizing enterocolitis was significantly associated with the presence of unbalanced interfetal transfusion (76.9% of monochorionic with necrotizing enterocolitis versus 31.4% of cases without necrotizing enterocolitis, P = 0.001). Conclusion: Necrotizing enterocolitis is more common in monochorionic multiples as compared to dichorionic multiples, at least in part due to the presence of and related to the presence of unbalanced interfetal transfusion through arterial-venous anastomoses in the placenta. Possibly, subtle ischemic damage caused by intra-uterine fetal hypotension or anemia plays a key role in the development of necrotizing enterocolitis in monochorionic twins.

BACKGROUND: Reintroduction of enteral nutrition in neonates with necrotizing enterocolitis (NEC) should take place when the gut is ready for its normal function. Too early a start of oral feeding might lead to disease relapse, whereas prolonged discontinuation of enteral nutrition is associated with impaired gut function and parenteral nutrition-related complications. This study evaluated whether noninvasive urinary measurement of intestinal fatty acid binding protein (I-FABP) at the time of refeeding can predict clinical outcome in neonates with NEC.METHODS: Urinary I-FABP concentrations were measured in 21 infants with NEC just before reintroducing enteral nutrition. Poor outcome was defined as unsuccessful reintroduction of enteral feeding (EF), (re)operation for NEC, or death related to NEC after reintroduction of EF.RESULTS: Median urinary I-FABP levels in neonates with poor outcome (n = 5) were significantly higher as compared with I-FABP levels in neonates with good outcome (n = 16) (P CONCLUSION: Noninvasive urinary I-FABP measurement at time of refeeding differentiates neonates with poor outcome from neonates with good outcome in NEC. Urinary I-FABP measurement may therefore be helpful in the timing of EF in neonates with NEC.

Contains fulltext : 168757.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To determine outcome of children born with isolated gastroschisis (no extra-gastrointestinal congenital abnormalities). STUDY DESIGN: International cohort study and meta-analysis. PRIMARY OUTCOME: time to full enteral feeding (TFEF); secondary outcomes: Duration of mechanical ventilation, length of stay (LOS), mortality and differences in outcome between simple and complex gastroschisis (complex; born with bowel atresia, volvulus, perforation or necrosis). To compare the cohort study results with literature three databases were searched. Studies were eligible for inclusion if cases were born in developed countries with isolated gastroschisis after 1990, number of cases >20 and TFEF was reported. RESULTS: The cohort study included 204 liveborn cases of isolated gastroschisis. The TFEF, median duration of ventilation and LOS was, 26days (range 6-515), 2days (range 0-90) and 33days (range 11-515), respectively. Overall mortality was 10.8%. TFEF and LOS were significantly longer (P

OBJECTIVE: To evaluate the value of biomarkers to detect severe NEC. SUMMARY BACKGROUND DATA: The time point of surgery in necrotizing enterocolitis (NEC) is critical. Therefore, there is a need for markers that detect severe NEC, because clinical signs of severe NEC often develop late. This study evaluated the value of biomarkers reflecting intestinal cell damage and inflammation to detect severe NEC. METHODS: 29 neonates with NEC were included. Two definitions of moderate versus severe NEC were analyzed: medical NEC (n = 12) versus surgical or fatal NEC (n = 17); and Bell stage II NEC (n = 13) versus stage III NEC (n = 16). Urinary intestinal fatty acid binding protein (I-FABP), serum amyloid A (SAA), C3a and C5a, and fecal calprotectin were measured. C-reactive protein (CRP), white blood cell count (WBC) and platelet count data were measured in blood. RESULTS: In both definitions of moderate versus severe NEC, urinary SAA levels were significantly higher in severe NEC. A cut-off value of 34.4 ng/ml was found in surgical NEC versus medical NEC (sensitivity, 83%; specificity, 83%; LR+, 4.88 (95% CI, 1.37-17.0); LR-, 0.20 (95% CI, 0.07-0.60)) at diagnosis of NEC and at one day prior to surgery in neonates who were operated later on. Combination of urinary SAA and platelet count increased the accuracy, with a sensitivity, 94%; specificity, 83%; LR+, 5.53 (95% CI, 1.57-20.0); and LR-, 0.07 (95% CI, 0.01-0.48). CONCLUSION: Urinary SAA is an accurate marker in differentiating severe NEC from moderate NEC; particularly if combined with serum platelet count.

ObjectiveTo assess the implementation and first results of a term perinatal internal audit by a standardised method.DesignPopulation-based cohort study.SettingAll 90 Dutch hospitals with obstetric/paediatric departments linked to community practices of midwives, general practitioners in their attachment areas, organised in perinatal cooperation groups (PCG).PopulationThe population consisted of 943 registered term perinatal deaths occurring in 2010–2012 with detailed information, including 707 cases with completed audit results.Main outcome measuresParticipation in the audit, perinatal death classification, identification of substandard factors (SSF), SSF in relation to death, conclusive recommendations for quality improvement in perinatal care and antepartum risk selection at the start of labour.ResultsAfter the introduction of the perinatal audit in 2010, all PCGs participated. They organised 645 audit sessions, with an average of 31 healthcare professionals per session. Of all 1102 term perinatal deaths (2.3/1000) data were registered for 86% (943) and standardised anonymised audit results for 64% (707). In 53% of the cases at least one SSF was identified. Non-compliance to guidelines (35%) and deviation from usual professional care (41%) were the most frequent SSF. There was a (very) probable relation between the SSF and perinatal death for 8% of all cases. This declined over the years: from 10% (n=23) in 2010 to 5% (n=10) in 2012 (p=0.060). Simultaneously term perinatal mortality decreased from 2.3 to 2.0/1000 births (pConclusionsThe perinatal audit is implemented nationwide in all obstetrical units in the Netherlands in a short time period. It is possible that the audit contributed to the decrease in term perinatal mortality.

Contains fulltext : 89807.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To improve diagnosis of necrotizing enterocolitis (NEC) by noninvasive markers representing gut wall integrity loss (I-FABP and claudin-3) and gut wall inflammation (calprotectin). Furthermore, the usefulness of I-FABP to predict NEC severity and to screen for NEC was evaluated. METHODS: Urinary I-FABP and claudin-3 concentrations and fecal calprotectin concentrations were measured in 35 consecutive neonates suspected of NEC at the moment of NEC suspicion. To investigate I-FABP as screening tool for NEC, daily urinary levels were determined in 6 neonates who developed NEC out of 226 neonates included before clinical suspicion of NEC. RESULTS: Of 35 neonates suspected of NEC, 14 developed NEC. Median I-FABP, claudin-3, and calprotectin levels were significantly higher in neonates with NEC than in neonates with other diagnoses. Cutoff values for I-FABP (2.20 pg/nmol creatinine), claudin-3 (800.8 INT), and calprotectin (286.2 microg/g feces) showed clinically relevant positive likelihood ratios (LRs) of 9.30, 3.74, 12.29, and negative LRs of 0.08, 0.36, 0.15, respectively. At suspicion of NEC, median urinary I-FABP levels of neonates with intestinal necrosis necessitating surgery or causing death were significantly higher than urinary I-FABP levels in conservatively treated neonates. Of the 226 neonates included before clinical suspicion of NEC, 6 developed NEC. In 4 of these 6 neonates I-FABP levels were not above the cutoff level to diagnose NEC before clinical suspicion. CONCLUSIONS: Urinary I-FABP levels are not suitable as screening tool for NEC before clinical suspicion. However, urinary I-FABP and claudin-3 and fecal calprotectin are promising diagnostic markers for NEC. Furthermore, urinary I-FABP might also be used to predict disease severity. 01 juni 2010

Background Perinatal mortality is an important indicator of health. European comparisons of perinatal mortality show an unfavourable position for the Netherlands. Our objective was to study regional variation in perinatal mortality within the Netherlands and to identify possible explanatory factors for the found differences. Methods Our study population comprised of all singleton births (904,003) derived from the Netherlands Perinatal Registry for the period 2000–2004. Perinatal mortality including stillbirth from 22+0 weeks gestation and early neonatal death (0–6 days) was our main outcome measure. Differences in perinatal mortality were calculated between 4 distinct geographical regions North-East-South-West. We tried to explain regional differences by adjustment for the demographic factors maternal age, parity and ethnicity and by socio-economic status and urbanisation degree using logistic modelling. In addition, regional differences in mode of delivery and risk selection were analysed as health care factors. Finally, perinatal mortality was analysed among five distinct clinical risk groups based on the mediating risk factors gestational age and congenital anomalies. Results Overall perinatal mortality was 10.1 per 1,000 total births over the period 2000–2004. Perinatal mortality was elevated in the northern region (11.2 per 1,000 total births). Perinatal mortality in the eastern, western and southern region was 10.2, 10.1 and 9.6 per 1,000 total births respectively. Adjustment for demographic factors increased the perinatal mortality risk in the northern region (odds ratio 1.20, 95% CI 1.12–1.28, compared to reference western region), subsequent adjustment for socio-economic status and urbanisation explained a small part of the elevated risk (odds ratio 1.11, 95% CI 1.03–1.20). Risk group analysis showed that regional differences were absent among very preterm births (22+0 – 25+6 weeks gestation) and most prominent among births from 32+0 gestation weeks onwards and among children with severe congenital anomalies. Among term births (≥ 37+0 weeks) regional mortality differences were largest for births in women transferred from low to high risk during delivery. Conclusion Regional differences in perinatal mortality exist in the Netherlands. These differences could not be explained by demographic or socio-economic factors, however clinical risk group analysis showed indications for a role of health care factors.

textabstractObjective: To assess the effects of different oxygen concentrations and flow rates on the measurement errors of neonatal pneumotachometers in heated and unheated situations and to develop correction factors to correct for these effects. Design: Prospective laboratory study. Setting: Outpatient clinic with equipment in a standardized setting. Subjects: Neonatal pneumotachometers. Interventions: In standardized conditions, the tested pneumotachometer was calibrated at a flow rate of 3 L/min with 60% oxygen and was set in series with a closed spirometer system being used as a reference. Different air-flow levels (1-9 L/min) and oxygen concentrations (21-100%) were infused into the closed system with the pneumotachometer and spirometer. Measurements and Main Results: The pneumotachometers were significantly affected by changing oxygen concentrations (p < .01) and increasing flow rates (p < .01), increasing the actually measured flow rate. Correction factors, developed by multiple regression analysis, significantly reduced the overall maximum errors of the pneumotachometers from -1.1 to 0.6 L/min to -0.5 to 0.4 L/min. Conclusions: The effects of changes in oxygen concentrations and flow rates on neonatal pneumotachometers could be considerably decreased by the use of correction factors such as were calculated in this study. This will preclude frequent calibration procedures with actual flow and oxygen levels during changes in experimental settings. Copyright

University Children's Hospital Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.Growth failure is a well-known problem in infants with bronchopulmonary dysplasia (BPD). We studied BPD infants' total daily energy expenditure (Ee), nutritional balance, and growth in relation to their past and current clinical status. Applying the doubly labelled water technique, Ee was measured in nine preterm infants with BPD receiving supplemental oxygen (postnatal age 61 +/- 13 days) and nine matched controls (36 +/- 21 days) during a 6-day period. Energy and protein balance, past and present respiratory status, and growth were assessed as well. The results show that Ee was higher in the BPD infants compared to controls (73 +/- 9 vs 63 +/- 8 kcal/kg/day, P < 0.05), but their faecal energy loss was lower (P < 0.01). Weight gain, energy intake, energy cost of growth, protein retention, and physical activity were not different. The respiratory frequency (RR) in the BPD infants was elevated in comparison with controls (P < 0.01). Within the BPD group, RR was positively correlated with energy expenditure (regression equation: Ee [kcal/kg/day] = 26.3 + 0.71*RR [min-1]; r2 = 0.82, P < 0.001), and was the single most significant determinant of Ee. CONCLUSION: Total energy expenditure in BPD infants is elevated and is strongly associated with their respiratory status. These findings could be of practical value for the nutritional management in infants with severe BPD.

Objective To compare incidences of perinatal mortality and severe perinatal morbidity between low risk term pregnancies supervised in primary care by a midwife and high risk pregnancies supervised in secondary care by an obstetrician. Design Prospective cohort study using aggregated data from a national perinatal register. Setting Catchment area of the neonatal intensive care unit (NICU) of the University Medical Center in Utrecht, a region in the centre of the Netherlands covering 13% of the Dutch population. Participants Pregnant women at 37 weeks’ gestation or later with a singleton or twin pregnancy without congenital malformations. Main outcome measures Perinatal death (antepartum, intrapartum, and neonatal) or admission to a level 3 NICU. Results During the study period 37 735 normally formed infants were delivered at 37 weeks’ gestation or later. Sixty antepartum stillbirths (1.59 (95% confidence interval 1.19 to 1.99) per 1000 babies delivered), 22 intrapartum stillbirths (0.58 (0.34 to 0.83) per 1000 babies delivered), and 210 NICU admissions (5.58 (4.83 to 6.33) per 1000 live births) occurred, of which 17 neonates died (0.45 (0.24 to 0.67) per 1000 live births). The overall perinatal death rate was 2.62 (2.11 to 3.14) per 1000 babies delivered and was significantly higher for nulliparous women compared with multiparous women (relative risk 1.65, 95% confidence interval 1.11 to 2.45). Infants of pregnant women at low risk whose labour started in primary care under the supervision of a midwife had a significant higher risk of delivery related perinatal death than did infants of pregnant women at high risk whose labour started in secondary care under the supervision of an obstetrician (relative risk 2.33, 1.12 to 4.83). NICU admission rates did not differ between pregnancies supervised by a midwife and those supervised by an obstetrician. Infants of women who were referred by a midwife to an obstetrician during labour had a 3.66 times higher risk of delivery related perinatal death than did infants of women who started labour supervised by an obstetrician (relative risk 3.66, 1.58 to 8.46) and a 2.5-fold higher risk of NICU admission (2.51, 1.87 to 3.37). Conclusions Infants of pregnant women at low risk whose labour started in primary care under the supervision of a midwife in the Netherlands had a higher risk of delivery related perinatal death and the same risk of admission to the NICU compared with infants of pregnant women at high risk whose labour started in secondary care under the supervision of an obstetrician. An important limitation of the study is that aggregated data of a large birth registry database were used and adjustment for confounders and clustering was not possible. However, the findings are unexpected and the obstetric care system of the Netherlands needs further evaluation.

Item does not contain fulltext BACKGROUND: Diagnosis of necrotizing enterocolitis (NEC), prevalent in premature infants, remains challenging. Enterocyte damage in NEC can be assessed by intestinal fatty acid-binding protein (I-FABP), with a sensitivity of 93% and a specificity of 90%. Numerous markers of inflammation are known, such as serum amyloid A (SAA) and fecal calprotectin. PURPOSE: The aim of the present study was to evaluate which combination of noninvasive measurement of inflammatory markers and I-FABP improves the diagnostic accuracy in neonates suspected for NEC. METHODS: In 62 neonates with clinical suspicion of NEC (29 with final diagnosis of NEC), urinary I-FABP, urinary SAA, and fecal calprotectin levels were determined quantitatively. Diagnostic accuracy was calculated for the combinations I-FABP-SAA and I-FABP-fecal calprotectin, using a multivariable logistic regression model. RESULTS: The combination of SAA and I-FABP did not increase the diagnostic accuracy of I-FABP. However, the combination of fecal calprotectin and I-FABP improved accuracy significantly. The combination of urinary I-FABP and fecal calprotectin measurement produced a sensitivity of 94%, a specificity of 79%, a positive likelihood ratio of 4.48, and a negative likelihood ratio of 0.08. CONCLUSION: The combination of noninvasive measurement of I-FABP and fecal calprotectin seems promising for diagnosing NEC at an early time point. Prospective analysis is required to confirm this finding and to evaluate better treatment strategies based on noninvasive measurement of I-FABP and calprotectin. 01 september 2012