Hens A. A. Brouwers

Noninvasive measurement of fecal calprotectin and serum amyloid A combined with intestinal fatty acid–binding protein in necrotizing enterocolitis

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.

Non-invasive serum amyloid A (SAA) measurement and plasma platelets for accurate prediction of surgical intervention in severe necrotizing enterocolitis (NEC).

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.

Surfactant replacement therapy: A new risk factor in developing retinopathy of prematurity?

We documented the prevalence of retinopathy of prematurity (ROP) in a group of 46 infants suffering from a moderate or severe respiratory distress syndrome and treated with surfactant replacement therapy (SRT) and 61 controls admitted in the year prior to the institution of SRT. Mortality in the treatment group was lower than in the control group (15.5% versus 23.8;P=0.29). The ROP prevalence in the treatment group was 47.8% and in the control group was 47.8% and in the control group 27.9%. To analyse the contribution of SRT alone to the prevalence of ROP, multivariate analysis using logistic regression technique was used. The odds ratio for SRT was 5.2 with a 95% confidence interval of 1.3–20.7,P=0.02. The prevalence of severe ROP in the surfactant treated group was not increased compared to the control group. From our data we conclude that SRT increases the risk of developing ROP but is not associated with more severe forms of ROP.

Noninvasive measurement of intestinal epithelial damage at time of refeeding can predict clinical outcome after necrotizing enterocolitis

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 < 0.01). A clinically significant cutoff value of 963 pg/ml was found to discriminate between infants with poor outcome and those with good outcome (sensitivity 80%, specificity 94%).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.

National perinatal audit, a feasible initiative for the Netherlands!? A validation study

Objective. To explore the feasibility of a national perinatal audit organization. Design. Validation study. Setting. Three regions in the Netherlands. Population. 228 cases of perinatal mortality. Methods. Narratives of perinatal mortality cases were assessed by a panel of representatives of all perinatal care provider groups. 123 cases were assessed twice. Consensus was defined as 75% agreement. For the chance corrected agreement Cohens kappa statistic was used. Main outcome measures. Consensus and the chance corrected agreement on three cause of death classifications. The presence or absence of substandard factors (SSF) with the care provider, the organization of care and the relation of the SSF with perinatal death. Results. Consensus rates and chance corrected agreement for three cause of death classifications ranged from 92 to 96% and κ 0.87 to κ 0.93 (very good agreement), with comparable confidence intervals and similar values in the validation subset of 123 cases. On the presence of SSF at the level of the care provider consensus and chance corrected agreement was 68% and κ 0.53 (moderate), with comparable values in the subset of 123 cases. Consensus for the relation between SSF at the level of the care provider and perinatal death was 81.4% and κ 0.68 (good). Conclusion. Perinatal audit on a national level with relatively large audit groups with many different care providers is feasible.

Cerebrospinal fluid leakage, an uncommon complication of fetal blood sampling: a case report and review of the literature.

In a recently published randomized clinical trial on intrapartum fetal monitoring, fetal blood samples were obtained in 879 women. One serious complication of fetal blood sampling (FBS) was reported, a case in which physical examination of the neonate after delivery revealed clear fluid loss from the incision site. Four layers of the scalp appeared to be incised. The subarachnoid space was closed with 2 sutures, and antibiotics were started due to the risk of meningitis. The patient was discharged in good clinical condition. In this article, the case is presented and the literature reviewed. We found 12 articles reporting 37 cases of a complication due to FBS, none concerning leakage of cerebrospinal fluid. In conclusion, complications of FBS are rare but can be serious. Excessive fetal bleeding is most frequently reported and often associated with an underlying coagulopathy in the neonate. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this educational activity, the obstetrician/gynecologist should be better able to assess the chance of possible complications due to fetal blood sampling; select fetuses at risk for complications due to fetal blood sampling; and evaluate certain technical precautions when performing this procedure.

Correction factors for oxygen and flow-rate effects on neonatal Fleisch and Lilly pneumotachometers

Objective 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.

Substandard care in delivery‐related asphyxia among term infants: prospective cohort study

Objective. To assess substandard care factors in the case of delivery‐related asphyxia. Design. Prospective cohort study. Setting. Catchment area of the Neonatal Intensive Care Unit (NICU) of the University Medical Center Utrecht; a region in the middle of the Netherlands covering 13% of the Dutch population. Population. Term infants, without congenital malformations, who died intrapartum or were admitted to the Neonatal Intensive Care Unit due to asphyxia. Methods. During a two‐year period, cases were prospectively collected and audited by an expert panel. Main outcome measures. Substandard care factors. Results. 37 735 term infants without congenital malformations were born. There were 19 intrapartum deaths, and 89 NICU admissions of which 12 neonates died. In 63 (58%) cases a substandard care factor was identified that was possibly (n= 47, 43%) or probably (n= 16, 15%) related to perinatal death or NICU admission. In primary care, substandard care factors were mainly the low frequency of examination during labor and delay in referral to secondary care. In secondary care, misinterpretation of cardiotocography and failure to respond adequately to clinical signs of fetal distress were the most common substandard care factors. Conclusions. Substandard care is present in a substantial number of cases with delivery‐related asphyxia resulting in perinatal death or NICU admission. Improving the organization of obstetric care in the Netherlands as well as training of obstetric caregivers might reduce adverse outcomes.

RESPIRATORY STATUS, TOTAL ENERGY EXPENDITURE, AND GROWTH IN INFANTS WITH BRONCHOPULMONARY DYSPLASIA 1967

Growth failure was studied in infants with BPD by relating their nutritional balance and growth to past and current clinical status. Total daily energy expenditure (TEE) was measured with doubly labeled water in 9 preterm infants with BPD receiving supplemental oxygen (all male, age 61±13 days) and 9 matched controls (5 male, age 36 ±21 days) during a 6 day period. Energy and protein balance, and growth were assessed as well. TEE was higher in the BPD infants compared to controls (73 ±9 vs. 63 ±8 kcal/kg/day, P < 0.05), but faecal energy loss in BPD infants 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 significantly associated with energy expenditure (r2 = 0.82, P < 0.001). The fitted equation was TEE[kcal/kg/day] = 26.3 + 0.71*RR [min-1]. We conclude that total energy expenditure in BPD infants is elevated, and is strongly associated with their respiratory status. These findings support the use of high-energy feeding for the nutritional management in infants with severe BPD.