Prenatal MRI fetal lung volumes and percent liver herniation predict pulmonary morbidity in congenital diaphragmatic hernia (CDH)

Purpose

The purpose of this study was to determine whether prenatal imaging parameters are predictive of postnatal CDH-associated pulmonary morbidity.

Methods

The records of all neonates with CDH treated from 2004 to 2012 were reviewed. Patients requiring supplemental oxygen at 30 days of life (DOL) were classified as having chronic lung disease (CLD). Fetal MRI-measured observed/expected total fetal lung volume (O/E-TFLV) and percent liver herniation (%LH) were recorded. Receiver operating characteristic (ROC) curves and multivariate regression were applied to assess the prognostic value of O/E-TFLV and %LH for development of CLD.

Results

Of 172 neonates with CDH, 108 had fetal MRIs, and survival was 76%. 82% (89/108) were alive at DOL 30, 46 (52%) of whom had CLD. Neonates with CLD had lower mean O/E-TFLV (30vs.42%; p = 0.001) and higher %LH (21.3 ± 2.8 vs.7.1 ± 1.8%; p < 0.001) compared to neonates without CLD. Using ROC analysis, the best cutoffs in predicting CLD were an O/E-TFLV < 35% (AUC = 0.74; p < 0.001) and %LH > 20% (AUC =0.78; p < 0.001). On logistic regression, O/E-TFLV < 35% and a %LH > 20% were highly associated with indicators of long-term pulmonary sequelae. On multivariate analysis, %LH was the strongest predictor of CLD in patients with CDH (OR: 10.96, 95%CI: 2.5–48.9, p = 0.002).

Conclusion

Prenatal measurement of O/E-TFLV and %LH is predictive of CDH pulmonary morbidity and can aid in establishing parental expectations of postnatal outcomes.     

Fetal MRI lung volumes are predictive of perinatal outcomes in fetuses with congenital lung masses

Purpose

The purpose of this study was to evaluate fetal magnetic resonance imaging (MRI) as a modality for predicting perinatal outcomes and lung-related morbidity in fetuses with congenital lung masses (CLM).

Methods

The records of all patients treated for CLM from 2002 to 2012 were reviewed retrospectively. Fetal MRI-derived lung mass volume ratio (LMVR), observed/expected normal fetal lung volume (O/E-NFLV), and lesion-to-lung volume ratio (LLV) were calculated. Multivariate regression and receiver operating characteristic analyses were applied to determine the predictive accuracy of prenatal imaging.

Results

Of 128 fetuses with CLM, 93% (n = 118) survived. MRI data were available for 113 fetuses. In early gestation (< 26 weeks), MRI measurements of LMVR and LLV correlated with risk of fetal hydrops, mortality, and/or need for fetal intervention. In later gestation (> 26 weeks), LMVR, LLV, and O/E-NFLV correlated with neonatal respiratory distress, intubation, NICU admission and need for neonatal surgery. On multivariate regression, LMVR was the strongest predictor for development of fetal hydrops (OR: 6.97, 1.58–30.84; p = 0.01) and neonatal respiratory distress (OR: 12.38, 3.52–43.61; p ≤ 0.001). An LMVR > 2.0 predicted worse perinatal outcome with 83% sensitivity and 99% specificity (AUC = 0.94; p < 0.001).

Conclusion

Fetal MRI volumetric measurements of lung masses and residual normal lung are predictive of perinatal outcomes in fetuses with CLM. These data may assist in perinatal risk stratification, counseling, and resource utilization.     

Predictors of early lung function in patients with congenital diaphragmatic hernia

Purpose

Long-term pulmonary outcomes of congenital diaphragmatic hernia (CDH) have demonstrated airflow obstruction in later childhood. We examined pulmonary function data to assess what factors predict lung function in the first three years of life in children with CDH.

Methods

This was a retrospective study of patients treated for CDH who underwent infant pulmonary function testing (IPFT) between 2006 and 2012. IPFT was performed using the raised volume rapid thoracoabdominal compression technique and plethysmography.

Results

Twenty-nine neonates with CDH had IPFTs in the first 3 years of life. Their mean predicted survival using the CDH Study Group equation was 63% ± 4%. Fourteen infants (48%) required extracorporeal membrane oxygenation (ECMO). The mean age at IPFT was 85.1 ± 5 weeks. Airflow obstruction was the most common abnormality, seen in 14 subjects. 12 subjects had air trapping, and 9 demonstrated restrictive disease. ECMO (p = 0.002), days on the ventilator (p = 0.028), and days on oxygen (p = 0.023) were associated with restrictive lung disease.

Conclusion

Despite following a group of patients with severe CDH, lung function revealed mild deficits in the first three years of life. Clinical markers of increased severity (ECMO, ventilator days, and prolonged oxygen use) are correlated with reduced lung function.     

Fetal lung-head ratio is not related to outcome for antenatal diagnosed congenital diaphragmatic hernia

We asked if fetal lung-to-head ratio (LHR) of 1.0 or lower or liver herniation had a statistical effect on survival or need for extracorporeal membrane oxygenation (ECMO), compared with LHR above 1.0 in patients with congenital diaphragmatic hernia (CDH).

Methods

Antenatal records of all patients diagnosed with CDH from January of 2002 to June of 2005 were examined. Inclusion criteria were isolated left-sided CDH and absence of significant cardiac or other anomalies/syndromes, treated solely at this institution. Lung-to-head ratio values were compared based on the value currently proposed for fetal intervention: LHR of 1.0 or lower vs LHR above 1.0. Outcome was assessed as survival (discharge to home) or need for ECMO.

Results

Twenty-eight patients met inclusion criteria. Overall survival was 86% (24/28). Postnatal survival in fetuses with LHR of 1.0 or lower (8/11) was not statistically different from LHR above 1.0 (16/17) (73% vs 94%, P = .114). The need for ECMO in the group with LHR of 1.0 or lower (3/11) was not significantly different from those with LHR above 1.0 (1/17) (27% vs 6%, P = .114). Herniation of the fetal liver into the chest did not affect survival or need for ECMO (P = .228).

Conclusion

Neither LHR of 1.0 or lower nor liver herniation identified a risk factor significant enough to warrant fetal intervention. Multicenter studies may be more appropriate to investigate this clinical problem.     

Sensorineural hearing loss in congenital diaphragmatic hernia survivors is associated with postnatal management and not defect size

Background/Purpose

We determined the incidence of sensorineural hearing loss (SNHL; > 20 dB at any frequency) in a contemporary cohort of congenital diaphragmatic hernia (CDH) survivors at a single tertiary care center and identified potential risk factors for SNHL.

Methods

From 2000 through 2011, clinical and audiologic data were collected on 122 surgically-repaired Bochdalek CDH patients. CDH defect size, duration of ventilation, and cumulative aminoglycoside treatment were used for multivariate logistic regression.

Results

Incidence of SNHL was 7.4% (9/122). We identified one significant independent predictor of SNHL: cumulative length of aminoglycoside treatment (P < .001; OR 1.44, 95% CI: 1.13–1.83).

Conclusions

Over the last decade, the incidence of SNHL in our CDH patients is low compared to previous reports in the literature (7.4%) and is not associated with CDH defect size or the need for extracorporeal membrane oxygenation. Prolonged duration of aminoglycoside treatment increases the risk of SNHL independent of defect size and duration of ventilation.     

Antenatal maternally-administered phosphodiesterase type 5 inhibitors normalize eNOS expression in the fetal lamb model of congenital diaphragmatic hernia

Purpose

Pulmonary hypertension (pHTN), a main determinant of survival in congenital diaphragmatic hernia (CDH), results from in utero vascular remodeling. Phosphodiesterase type 5 (PDE5) inhibitors have never been used antenatally to treat pHTN. The purpose of this study is to determine if antenatal PDE5 inhibitors can prevent pHTN in the fetal lamb model of CDH.

Methods

CDH was created in pregnant ewes. Postoperatively, pregnant ewes received oral placebo or tadalafil, a PDE5 inhibitor, until delivery. Near term gestation, lambs underwent resuscitations, and lung tissue was snap frozen for protein analysis.

Results

Mean cGMP levels were 0.53 ± 0.11 in placebo-treated fetal lambs and 1.73 ± 0.21 in tadalafil-treated fetal lambs (p = 0.002). Normalized expression of eNOS was 82% ± 12% in Normal-Placebo, 61% ± 5% in CDH-Placebo, 116% ± 6% in Normal-Tadalafil, and 86% ± 8% in CDH-Tadalafil lambs. Normalized expression of β-sGC was 105% ± 15% in Normal-Placebo, 82% ± 3% in CDH-Placebo, 158% ± 16% in Normal-Tadalafil, and 86% ± 8% in CDH-Tadalafil lambs. Endothelial NOS and β-sGC were significantly decreased in CDH (p = 0.0007 and 0.01 for eNOS and β-sGC, respectively), and tadalafil significantly increased eNOS expression (p = 0.0002).

Conclusions

PDE5 inhibitors can cross the placental barrier. β-sGC and eNOS are downregulated in fetal lambs with CDH. Antenatal PDE5 inhibitors normalize eNOS and may prevent in utero vascular remodeling in CDH.     

Maternal medical and behavioral risk factors for congenital diaphragmatic hernia

Purpose

Maternal factors contributing to the etiology of congenital diaphragmatic hernia (CDH) remain unclear. We hypothesized that specific maternal medical conditions (pregestational diabetes, hypertension), and behaviors (alcohol, tobacco) would be associated with CDH.

Methods

We conducted a population-based case–control study using Washington State birth certificates linked to hospital discharge records (1987–2009). We identified all infants with CDH (n = 492). Controls were randomly selected among non-CDH infants. Maternal data were extracted from the birth record. Logistic regression was used to adjust for covariates.

Results

Cases and controls were generally similar regarding demographics, although CDH infants were more likely to be male than controls (58.5% vs. 52.5%). Isolated and complex (multiple-anomaly) CDH had similar characteristics. Each of the exposures of interest was more common among case mothers than among control mothers. In univariate analysis, alcohol use, hypertension, and pregestational diabetes were each significantly associated with the outcome. After multivariate adjustment, only alcohol use (OR = 3.65, p = 0.01) and pregestational diabetes (OR = 12.53, p = 0.003) maintained significance. Results were similar for both isolated and complex CDH.

Conclusions

Maternal pregestational diabetes and alcohol use are significantly associated with occurrence of CDH in infants. These are important modifiable risk factors to consider with regard to efforts seeking to impact the incidence of CDH.     

Pulmonary hypertension in congenital diaphragmatic hernia patients: Prognostic markers and long-term outcomes

Prenatal observed/expected lung–to-head ratio (O/E LHR) by ultrasound correlates with postnatal mortality for congenital diaphragmatic hernia (CDH) patients. The aim of this study is to determine if O/E LHR correlates with pulmonary hypertension (PH) outcomes for CDH patients.

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 12 months 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 12 months. 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 12 months 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.     

Influence of Preoperative and Postoperative Pelvic Floor Muscle Training (PFMT) Compared with Postoperative PFMT on Urinary Incontinence After Radical Prostatectomy: A Randomized Controlled Trial

Background

The efficacy of preoperative pelvic floor muscle training (PFMT) for urinary incontinence (UI) after open radical prostatectomy (ORP) and robot-assisted laparoscopic radical prostatectomy (RARP) is still unclear.

Objective

To determine whether patients with additional preoperative PFMT regain urinary continence earlier than patients with only postoperative PFMT after ORP and RARP.

Design, setting, and participants

A randomized controlled trial enrolled 180 men who planned to undergo ORP/RARP.

Intervention

The experimental group (E, n = 91) started PFMT 3 wk before surgery and continued after surgery. The control group (C, n = 89) started PFMT after catheter removal.

Outcome measurements and statistical analysis

The primary end point was time to continence. Patients measured urine loss daily (24-h pad test) until total continence (three consecutive days of 0 g of urine loss) was achieved. Secondary end points were 1-h pad test, visual analog scale (VAS), International Prostate Symptom Score (IPSS), and quality of life (King's Health Questionnaire [KHQ]). Kaplan-Meier analysis and Cox regression with correction for two strata (age and type of surgery) compared time and continence. The Fisher exact test was applied for the 1-h pad test and VAS; the Mann-Whitney U test was applied for IPSS and KHQ.

Results and limitations

Patients with additional preoperative PFMT had no shorter duration of postoperative UI compared with patients with only postoperative PFMT (p = 0.878). Median time to continence was 30 and 31 d, and median amount of first-day incontinence was 108 g and 124 g for groups E and C, respectively. Cox regression did not indicate a significant difference between groups E and C (p = 0.773; hazard ratio: 1.047 [0.768–1.425]). The 1-h pad test, VAS, and IPSS were comparable between both groups. However, “incontinence impact” (KHQ) was in favor of group E at 3 mo and 6 mo after surgery.

Conclusions

Three preoperative sessions of PFMT did not improve postoperative duration of incontinence.

Trial registration

Netherlands Trial Register No. NTR 1953.     

Incidence and factors associated with sensorineural and conductive hearing loss among survivors of congenital diaphragmatic hernia

Purpose

The reported incidence of sensorineural hearing loss (SNHL) in long-term survivors of congenital diaphragmatic hernia varies widely in the literature. Conductive hearing loss (CHL) is also known to occur in CDH patients, but has been less widely studied. We sought to characterize the incidence and risk factors associated with SNHL and CHL in a large cohort of CDH patients who underwent standardized treatment and follow-up at a single institution.

Methods

We retrospectively reviewed charts of all CDH patients in our pulmonary hypoplasia program from January 2004 through December 2012. Categorical variables were analyzed by Fisher’s exact test and continuous variables by Mann–Whitney t-test (p ≤ 0.05).

Results

A total of 112 patients met study inclusion criteria, with 3 (2.7%) patients diagnosed with SNHL and 38 (34.0%) diagnosed with CHL. SNHL was significantly associated with requirement for ECMO (p = 0.0130), prolonged course of hospitalization (p = 0.0011), duration of mechanical ventilation (p = 0.0046), requirement for tracheostomy (p = 0.0013), and duration of loop diuretic (p = 0.0005) and aminoglycoside therapy (p = 0.0003).

Conclusions

We have identified hearing anomalies in over 30% of long-term CDH survivors. These findings illustrate the need for routine serial audiologic evaluations throughout childhood for all survivors of CDH and stress the importance of targeted interventions to optimize long-term developmental outcomes pertaining to speech and language.     

Antithrombin III administration in neonates with congenital diaphragmatic hernia during the first three days of extracorporeal membrane oxygenation

Purpose

To evaluate the effect of Antithrombin III (ATIII) on blood product requirement in neonates receiving extracorporeal membrane oxygenation (ECMO).

Methods

A retrospective case control study of neonates presenting with or without congenital diaphragmatic hernia (CDH) requiring ECMO between 2006 and 2010 was performed. Patient demographics, laboratory data, and information on blood products administered were compared in patients treated before (n = 37) and after (n = 38) a protocol for antithrombin-III (ATIII) administration was implemented.

Results

During the first three days on ECMO patients with CDH received less fresh frozen plasma (FFP) and platelets after ATIII administration was introduced (78.1 ± 19.2 ml/kg vs. 27.8 ± 6.2 ml/kg, p < 0.007 and 67.8 ± 8.6 ml/kg vs. 47.8 ± 8.4 ml/kg, p = 0.05 respectively), while FFP and platelet administration in patients without CDH was not different between the two periods. Patients both with and without CDH received less packed red blood cell (PRBC) transfusions after the ATIII protocol was introduced (230 ± 51.5 ml/kg vs. 73.8 ± 9.7 ml/kg, p < 0.002 and 173.2 ± 22.2 ml/kg vs. 66.0 ± 6.6 ml/kg, p < 0.001, respectively). Finally, cryoprecipitate administered was not different in patients with and without CDH between the two periods (13 ± 2.9 ml/kg vs. 15.9 ± 7.2 ml/kg, p = NS and 6.1 ± 1.8 ml/kg vs. 3.4 ± 0.6 ml/kg, p = NS, respectively).

Conclusions

Introduction of routine ATIII administration was associated with decreases in FFP, platelet, and PRBC exposure in neonates with CDH and decreases in PRBC transfusions in neonates without CDH during the first three days of ECMO support.     

Gonocyte transformation to spermatogonial stem cells occurs earlier in patients with undervirilisation syndromes

Aim

Fertility post-orchidopexy is dependent on transformation of neonatal gonocytes (G) into adult dark spermatogonia at about 3 months, the same time as gonadotrophins stimulate androgen secretion. We examined how androgen blockade affects transformation of gonocytes to spermatogonial stem cells (SSC) during this period in patients with undervirilisation syndromes.

Methods

Patients with undervirilisation syndromes (n = 30, 1.5 weeks–16 years) underwent review of medical records, pathology reports, and H&E slides of testes (ethics HREC32164). Fluorescent immunohistochemistry against anti-Mullerian hormone (AMH, Sertoli cells), mouse VASA homologue (MVH, germ cells) and DAPI (nuclei) allowed the number of MVH-positive gonocytes/spermatogonial stem cells per seminiferous tubular cross-section (G/T or SSC/T) to be counted.

Results

Gonocytes (MVH-positive cells in the tubular lumen) were present in 15/16 patients under 2 years old. SSC (MVH-positive cells on the tubule basement membrane) were present in 25/30 patients. With increasing age, the mean number of SSC/T decreased from ~ 4 to 0, and G/T decreased from ~ 1.5 to 0. SSC were present in CAIS and PAIS patients at 1.5 and 3.5 weeks old, respectively.

Conclusions

Gonocytes transform into SSC earlier than expected in patients with undervirilisation syndromes. Lack of androgens may stimulate non-androgenic regulators to trigger transformation. Understanding how gonocytes transform may enable optimization of spermatogonial development to preserve fertility post-orchidopexy.     

Outcome of CDH infants following fetoscopic tracheal occlusion — influence of premature delivery

Purpose

To evaluate the mortality and morbidity of infants with congenital diaphragmatic hernia who had undergone fetal endoscopic tracheal occlusion (FETO) and whether this was influenced by premature birth.

Methods

The gestational age at delivery, lung–head ratio (LHR) pre and post FETO, neonatal outcomes, and respiratory, gastro-intestinal, neurological, surgical, and musculoskeletal problems at follow up of consecutive infants who had undergone FETO were determined. Elective reversal of FETO was planned at 34 weeks of gestation.

Results

The survival rate of the 61 FETO infants was 48%, with 84% delivered prematurely. Thirty-one delivered < 35 weeks of gestation. Their survival rate was 18%. Twenty-three of 24 infants who had emergency balloon removal were born < 35 weeks of gestation. Survival was related to gestational age at delivery (OR 0.55, 95% CI 0.420, 0.77, p < 0.001) and the duration of FETO (OR 0.73, 95% CI 0.59, 0.91, p < 0.005). Infants born prior to 35 weeks of gestation compared to those born at ≥ 35 weeks required a longer duration of ventilation (median 45 days versus 12 days, p < 0.001), and a greater proportion had surgery for gastro-oesophageal reflux (50% versus 9%, p = 0.011).

Conclusion

These results emphasize the need to reduce premature delivery following FETO.     

Prenatal retinoic acid increases lipofibroblast expression in hypoplastic rat lungs with experimental congenital diaphragmatic hernia

Background/purpose

Prenatal administration of all-trans retinoic acid (ATRA) has been shown to stimulate alveolarization in nitrofen-induced pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial lipofibroblasts (LIFs), characterized by adipocyte differentiation-related protein (ADRP), play a critical role in alveolar development by coordinating lipid homeostasis. Previous studies have demonstrated that ATRA positively affects LIF expression in developing lungs. We hypothesized that pulmonary LIF expression is increased after prenatal ATRA treatment in the nitrofen model of CDH-associated PH.

Methods

Timed-pregnant rats were treated with nitrofen or vehicle on E9.5, followed by injection of ATRA or placebo on E18.5, E19.5, and E20.5. Fetal lungs were dissected on E21.5 and divided into Control + Placebo, Control + ATRA, Nitrofen + Placebo, and Nitrofen + ATRA. Pulmonary gene expression levels of ADRP were analyzed by quantitative real-time polymerase chain reaction, and LIF expression was investigated by ADRP immunohistochemistry, oil-red-O-, and immunofluorescence-double-staining.

Results

Relative mRNA expression of pulmonary ADRP was significantly increased in Nitrofen + ATRA compared to Nitrofen + Placebo (0.31 ± 0.02 vs. 0.08 ± 0.01; P < 0.0001). ADRP immunoreactivity and oil-red-O-staining were markedly increased in alveolar interstitium of Nitrofen + ATRA compared to Nitrofen + Placebo. Immunofluorescence-double-staining confirmed markedly increased LIF expression in alveolar walls of Nitrofen + ATRA compared to Nitrofen + Placebo.

Conclusions

Increased LIF expression after prenatal treatment with ATRA in nitrofen-induced PH suggests that ATRA may have a therapeutic potential in attenuating CDH-associated PH by stimulating alveolar development.     

Developmental outcomes of children with congenital diaphragmatic hernia: A multicenter prospective study

Purpose

To determine developmental outcomes and associated factors in patients with congenital diaphragmatic hernia (CDH) at 2 years of age.

Methods

This is a multicenter prospective study of a CDH birth cohort. Clinical and socioeconomic data were collected. Bayley Scales of Infant Development (BSID-III) and Vineland Adaptive Behavior Scales (VABS-II) were performed at 2 years of age.

Results

BSID-III and VABS-II assessments were completed on 48 and 49 children, respectively. The BSID-III mean cognitive, language, and motor scores were significantly below the norm mean with average scores of 93 ± 15, 95 ± 16, and 95 ± 11. Ten percent (5/47) scored more than 2 standard deviations below the norm on one or more domains. VABS-II scores were similar to BSID-III scores with mean communication, daily living skills, social, motor, adaptive behavior scores of 97 ± 14, 94 ± 16, 93 ± 13, 97 ± 10, and 94 ± 14. For the BSID-III, supplemental oxygen at 28 days, a prenatal diagnosis, need for extracorporeal membrane oxygenation (ECMO) and exclusive tube feeds at time of discharge were associated with lower scores. At 2 years of age, history of hospital readmission and need for tube feeds were associated with lower scores. Lower socioeconomic status correlated with lower developmental scores when adjusted for significant health factors.

Conclusion

CDH patients on average have lower developmental scores at 2 years of age compared to the norm. A need for ECMO, oxygen at 28 days of life, ongoing health issues and lower socioeconomic status are factors associated with developmental delays.     

Extracorporeal fetal support: A new animal model with preservation of the placenta

Background

Previous models of support for premature sheep fetuses have consisted of cesarean delivery followed by catheterization of umbilical or central vessels and support with extracorporeal membrane oxygenation (ECMO). The limitations of these models have been insufficient blood flow, significant fetal edema, and hemorrhage related to anticoagulation.

Methods

We performed a gravid hysterectomy on 13 ewes between 135 and 145 days gestational age. The uterine vessels were cannulated bilaterally and circulatory support was provided via ECMO. Successful transition was defined as maintenance of fetal heart rate for 30 minutes after establishing full extracorporeal support. Circuit flow was titrated to maintain mixed venous oxygen saturation (SvO₂) of 70–75%.

Results

Seven experiments were successfully transitioned to ECMO, with an average survival time of 2 hours 9 minutes. The longest recorded time from cannulation to death was 6 hours 14 minutes. By delivering a circuit flow of up to 2120 ml/min, all but one of the transitioned uteri were maintained within the desired SvO₂ range.

Conclusion

We report a novel animal model of fetal ECMO support that preserves the placenta, mitigates the effects of heparin, and allows for increased circuit flow compared to prior techniques. This approach may provide insight into a technique for future studies of fetal physiology.     

Role of admission gas exchange measurement in predicting congenital diaphragmatic hernia survival in the era of gentle ventilation

Background/Purpose

Neonates with significant congenital diaphragmatic hernia (CDH) require cardiopulmonary support. Management has been characterized by progressive abandonment of hyperventilation. Ability to prognosticate outcomes using measures of ventilation and oxygenation with gentle ventilation remains unclear. We sought to determine whether assessment of gas exchange at the time of NICU admission is predictive of survival in this current era.

Methods

Neonates with CDH admitted to a Children’s Hospital from 1995 to 2006 were evaluated for demographics, blood gas (ABG) measurements and ventilator settings for the first 48 hours, and discharge outcome.

Results

One-hundred-and-nineteen CDH patients were admitted, 88 (74%) survived. Mean admission ABG pCO₂ was higher in infants who died compared to survivors (86 ± 48 versus 49 ± 20, p ≤ 0.001); positive predictive value (PPV) for mortality of pCO₂ ≥ 80 mmHg was 0.71. Mean first hour preductal oxygen saturation (preductalO₂Sat) was lower in infants who died compared to survivors (81 ± 17 versus 97 ± 5, p < 0.001); PPV for mortality of preductalO₂Sat < 85% was 0.82. Eleven patients met both pCO₂ and preductalO₂Sat criteria, and 10 (91%) died, PPV of 0.92. Within hours of admission, pCO₂ and preductalO₂Sat differences between survivors and nonsurvivors lost significance.

Conclusion

Admission pCO₂ and preductalO₂Sat may be useful in predicting survival in neonatal CDH. The differential in gas exchange between survivors and nonsurvivors loses significance with contemporary neonatal care.     

Hypernatremia severity and the risk of death after traumatic brain injury

Purpose

To investigate the relationship between severity of hypernatremia and the risk of death for patients with traumatic brain injury (TBI) who have been admitted to the neurosurgical intensive care unit (NICU).

Methods

A total of 1044 patients with TBI were admitted to our NICU from January 2005 to January 2010. Of these patients, 881 were included in this study. Based on blood serum sodium level in the NICU the 881 patients were divided into four groups: 614 had normal serum sodium (Na < 150 mmol/L), 34 had mild hypernatremia (Na 150–<155 mmol/L), 66 had moderate hypernatremia (Na 155–160 mmol/L) and 167 had severe hypernatremia (Na ≥ 160 mmol/L).

Results

The mortality rates for the mild, moderate, and severe hypernatremia groups were 20.6%, 42.4%, and 86.8%, respectively; the mortality rate for the normal group was 2.0%. In multivariable analysis, mild, moderate, and severe hypernatremia were independent risk factors for mortality; compared with the normal group the odds ratios of mild, moderate, and severe hypernatremia were 9.50, 4.34, and 29.35, respectively.

Conclusions

Severe hypernatremia is an independent risk factor with extremely high odds ratio for death in patients with TBI who are admitted to the NICU.     

Prenatally-counseled congenital diaphragmatic hernia parents exhibit positive well-being before and after surgical repair

Background/Purpose

The purpose of this paper was to examine the effect of prenatal counseling in the Advanced Fetal Care Center (AFCC) on the well-being of parents of infants with congenital diaphragmatic hernia (CDH).

Methods

From 2008 through 2012, 26 mothers and fathers of surgically repaired CDH patients who received prenatal counseling at our institution, and 15 who received no prenatal counseling, each completed the Short-Form 36 version 1 (SF-36v1) at the appropriate time points: prenatal, two weeks, and six months post-surgery.

Results

Parents in both groups did not differ by demographic characteristics. Patients who received prenatal counseling had significantly longer ventilatory time and length of stay (LOS) in the ICU and in the hospital compared to those who did not receive prenatal counseling (all P < .01). Mothers and fathers had similar SF-36v1 mental and physical component summary (MCS, PCS) post-surgery scores when compared by counseling status. Prenatal MCS scores for mothers and fathers (47 vs. 41; P = .24) were similar to those at six months post-surgery (47 vs. 47; P = .90).

Conclusions

When hospital LOS was controlled between groups stratified by AFCC counseling status, MCS scores were comparable prenatally and were sustained at six months post-surgery for both parents. These findings may reflect the support services parents received beginning in the prenatal period.