Fetal endoscopic tracheal occlusion reduces pulmonary hypertension in severe congenital diaphragmatic hernia.

OBJECTIVE: Fetal endoscopic tracheal occlusion (FETO) is associated with increased perinatal survival and reduced need for extracorporeal membrane oxygenation (ECMO) in fetuses with severe congenital diaphragmatic hernia (CDH). This study evaluates the impact of FETO on the resolution of pulmonary hypertension (PH) in fetuses with isolated CDH. METHODS: We reviewed retrospectively the medical records of all fetuses evaluated for CDH between January 2004 and July 2017 at a single institution. Fetuses with additional major structural or chromosomal abnormalities were excluded. CDH cases were classified retrospectively into mild, moderate and severe groups based on prenatal magnetic resonance imaging indices (observed-to-expected total fetal lung volume and percentage of intrathoracic liver herniation). Presence of PH was determined based on postnatal echocardiograms. Logistic regression analyses were performed to evaluate the relationship between FETO and resolution of PH by 1 year of age while controlling for side of the CDH, use of ECMO, gestational age at diagnosis, gestational age at delivery, fetal gender, sildenafil use at discharge and CDH severity. Resolution of PH by 1 year of age was compared between a cohort of fetuses with severe CDH that underwent FETO and a cohort that did not have the procedure (non-FETO). A subanalysis was performed restricting the analysis to isolated left CDH. Parametric and non-parametric tests were used for comparisons. RESULTS: Of 257 CDH cases evaluated, 72% (n = 184) had no major structural or chromosomal anomalies of which 58% (n = 107) met the study inclusion criteria. The FETO cohort consisted of 19 CDH cases and the non-FETO cohort (n = 88) consisted of 31 (35%) mild, 32 (36%) moderate and 25 (28%) severe CDH cases. All infants with severe CDH, regardless of whether they underwent FETO, had evidence of neonatal PH. FETO (OR, 3.57; 95% CI, 1.05-12.10; P = 0.041) and ECMO (OR, 5.01; 95% CI, 2.10-11.96; P < 0.001) were independent predictors of resolution of PH by 1 year of age. A higher proportion of infants with severe CDH that underwent FETO had resolution of PH by 1 year after birth compared with infants with severe CDH in the non-FETO cohort (69% (11/16) vs 28% (7/25); P = 0.017). Similar results were observed when the analysis was restricted to cases with left-sided CDH (PH resolution in 69% (11/16) vs 28% (5/18); P = 0.032). CONCLUSION: In infants with severe CDH, FETO and ECMO are independently associated with increased resolution of PH by 1 year of age. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Fetal lower urinary tract obstruction: proposal for standardized multidisciplinary prenatal management based on disease severity.

OBJECTIVE: To present a single center experience of a standardized prenatal multidisciplinary management protocol for fetal lower urinary tract obstruction (LUTO) and to propose a classification of fetal LUTO based on disease severity. METHODS: This was a retrospective cohort study of 25 consecutive fetal patients with prenatal diagnosis of primary LUTO. Fetal intervention was offered after evaluation by a multidisciplinary team. Analyses were conducted using Bayesian methodology to determine predictors of survival at 6 months postpartum. Odds ratios (ORs) with 95% credibility intervals are reported. RESULTS: Fifteen (60.0%) of the 25 patients referred for assessment survived to postnatal evaluation. Fetal vesicoamniotic shunt was placed in 14 (56.0%) patients with 12 survivors. Multivariable analysis suggested that fetal intervention (OR, 6.97 (0.88-70.16), Pr(OR > 1) = 96.7%), anhydramnios (OR, 0.12 (0.04-0.35), Pr(OR < 1) = 99.9%), favorable fetal urine analysis (OR, 3.98 (0.63-25.15), Pr(OR > 1) = 92.7%) and absence of renal cortical cysts (OR, 3.9 (0.66-24.2), Pr(OR > 1) = 93.3%) were predictors of survival. CONCLUSIONS: Fetal intervention and fetal renal function were independently associated with postnatal survival of fetuses with LUTO. A classification based on the severity of disease is proposed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

High performance liquid chromatography-tandem mass spectrometric assay of dexmedetomidine in plasma, urine and amniotic fluid samples for pregnant ewe model.

Dexmedetomidine (DEX; Precedex(®)), approved by the Food and Drug Administration (FDA) in 1999 as a sedative for use in the intensive care unit, is a potent and highly selective α2-adrenoceptor agonist with significant sedative, analgesic and anxiolytic effects. However, the research of DEX use during pregnancy is limited and the impact of DEX on the fetal development is unclear. This article describes a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay suitable for various biomatrices of plasma, urine and amniotic fluid, as a prerequisite for pharmacokinetic characterization of DEX in the pregnant ewe model. DEX and testosterone (internal standard; IS) were extracted from 200µL of plasma, urine or amniotic fluid with ethyl acetate. The HPLC resolution was achieved on an Agilent ZORBAX SB-CN column with a gradient elution at a flow rate of 0.5mL/min using a mobile phase of 5-100% of acetonitrile with 0.5% formic acid (mobile phase B) in water (mobile phase A). The detection was performed by a triple quadrupole tandem mass spectrometer with positive electrospray ionization. The precursor/product transitions (m/z) in the positive ion mode [M+H](+) were m/z 201.5→95.4 for DEX and m/z 289.2→109.1 for IS. The method was validated in the concentration range of 25 (lower limit of quantification; LLOQ)-5000pg/mL for both maternal and fetal plasma, and of 50 (LLOQ)-5000pg/mL for urine and amniotic fluid, respectively. The intra- and inter-day precision and accuracy were within ±9%. The overall recoveries of DEX were 82.9-87.2%, 85.7-88.4%, 86.2-89.7% and 83.7-88.1% for maternal plasma, urine, fetal plasma and amniotic fluid, respectively. The percentage matrix factors in different biomatrices were less than 120%. Stability studies demonstrated that DEX was stable after three freeze/thaw cycles, in the autosampler tray at 20°C for 24h and during the 3h sample preparation at room temperature. The validated HPLC-MS/MS method has been successfully employed for pharmacokinetic evaluation of DEX in pregnant ewes and fetuses.