Long-term Outcomes, Including Fetal and Neonatal Prognosis, of Renal Oligohydramnios: A Retrospective Study over 22 Years.

OBJECTIVE: To assess the long-term outcome of renal oligohydramnios and risk factors for fetal, neonatal, and postneonatal death. STUDY DESIGN: This retrospective cohort study included fetuses with prenatally detected renal oligohydramnios between 2002 and 2023. Patients who were lost to follow-up were excluded. Fetal, neonatal, and long-term outcomes were evaluated, and their risk factors were analyzed. RESULTS: Of 131 fetuses with renal oligohydramnios, 46 (35%) underwent a termination of pregnancy, 11 (8%) had an intrauterine fetal death, 26 (20%) had a neonatal death, nine (7%) had a postneonatal death, and 39 (30%) survived. Logistic regression analyses showed that an earlier gestational age at onset (odds ratio 1.16, 95% confidence interval (CI) 1.01-1.37) was significantly associated with intrauterine fetal death; anhydramnios (odds ratio 12.7, 95% CI 1.52-106.7) was significantly associated with neonatal death as a prenatal factor. Although neonatal survival rates for bilateral renal agenesis, bilateral multicystic dysplastic kidney (MCDK), and unilateral MCDK with contralateral renal agenesis were lower than for other kidney diseases, one case of bilateral renal agenesis and two of bilateral MCDK survived with fetal intervention. Kaplan-Meier overall survival rates were 57%, 55%, and 51% for 1, 3, and 5 years, respectively. In the Cox proportional hazards model, birth weight <2000 g (hazard ratio 7.33, 95% CI 1.48-36.1) and gastrointestinal comorbidity (hazard ratio 4.37, 95% CI 1.03-18.5) were significant risk factors for postneonatal death. CONCLUSION: Long-term survival following renal oligohydramnios is a feasible goal and its appropriate risk assessment is important.

Pre-pregnancy body mass index and low birthweight: Secondary data analysis using health insurance claims data in Japan.

AIM: For women, being underweight increases their susceptibility to osteoporosis, anemia, and other conditions and affects the weight of their infants and the well-being of future generations. This study examined the association between low pre-pregnancy body mass index (BMI) and low birthweight using health insurance claims data and health checkup data, including weight measurements. METHODS: We used health insurance claims data and health checkup data (JMDC, Tokyo, Japan) of women and their newborns in Japan between 2006 and 2020. We used checkup data, which included more accurate weight measurements and blood test-based diagnoses of anemia and hyperlipidemia compared to self-reported data. Maternal pre-pregnancy BMI was compared across three groups: underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), and overweight (BMI ≥25.0 kg/m2). The primary outcome was low birthweight (<2500 g), and secondary outcome was preterm childbirth. Logistic regression analyses were conducted to compare outcomes in the three groups by BMI. The underweight BMI group was considered as the reference group. A subgroup analysis was performed by maternal age. RESULTS: In total, 16 363 mothers (underweight, 3418 [21%], normal weight, 11 493 [70%], and overweight, 1452 [8.9%]) were included. The risk of primary outcome (low birthweight) was significantly lower in the normal weight group than in the underweight group (4.6% vs. 5.7%; adjusted odds ratio 0.78 [95% confidence interval: 0.65-0.96]). In the subgroup analyses, no significant differences were noted in the incidences of low birthweight and preterm childbirth between maternal age groups. CONCLUSIONS: Pre-pregnancy BMI was associated with an increased risk of delivering low-birthweight infant. Awareness about the importance of women's pre-pregnancy health and appropriate BMI may reduce the incidence of low birthweight.

Genome Analysis in Sick Neonates and Infants: High-yield Phenotypes and Contribution of Small Copy Number Variations.

OBJECTIVE: To delineate the diagnostic efficacy of medical exome, whole exome, and whole genome sequencing according to primary symptoms, the contribution of small copy number variations, and the impact of molecular diagnosis on clinical management. STUDY DESIGN: This was a prospective study of 17 tertiary care centers in Japan, conducted between April 2019 and March 2021. Critically ill neonates and infants less than 6 months of age were recruited in neonatal intensive care units and in outpatient clinics. The patients underwent medical exome, whole exome, or whole genome sequencing as the first tier of testing. Patients with negative results after medical exome or whole exome sequencing subsequently underwent whole genome sequencing. The impact of molecular diagnosis on clinical management was evaluated through contacting primary care physicians. RESULTS: Of the 85 patients, 41 (48%) had positive results. Based on the primary symptoms, patients with metabolic phenotypes had the highest diagnostic yield (67%, 4/6 patients), followed by renal (60%, 3/5 patients), and neurologic phenotypes (58%, 14/24 patients). Among them, 4 patients had pathogenic small copy number variations identified using whole genome sequencing. In the 41 patients with a molecular diagnosis, 20 (49%) had changes in clinical management. CONCLUSIONS: Genome analysis for critically ill neonates and infants had a high diagnostic yield for metabolic, renal, and neurologic phenotypes. Small copy number variations detected using whole genome sequencing contributed to the overall molecular diagnosis in 5% of all the patients. The resulting molecular diagnoses had a significant impact on clinical management.

A fetus with large mediastinal cystic lymphatic malformation managed with prenatal serial thoracocentesis and postnatal sclerotherapy.

We report a very rare case of large fetal mediastinal cystic lymphatic malformation (cLM), formerly called lymphangioma, that was managed with prenatal serial thoracocentesis and postnatal sclerotherapy. A fetal pericardial effusion-like lesion gradually increased the size until it occupied more than half of the thoracic cavity. Thoracocentesis was performed three times, namely at 31 and 35 weeks of gestation, and also just before the delivery for decompression. The characteristic shape changes of the lesion were observed after thoracocentesis. A boy delivered by planned cesarian section at term required respiratory support after birth. Postnatal magnetic resonance imaging (MRI), which showed a large cystic lesion with septa and hemorrhage without solid components, led to the diagnosis of cLM. The fluid from the cyst continued to be drained. Neonatal sclerotherapy using OK-432 was effective and the infant recovered well. Fetal thoracocentesis may be useful for the diagnosis and management of a large mediastinal cLM.

Long-term neurodevelopmental outcomes of the pump twin in twin reversed arterial perfusion sequence treated by radiofrequency ablation.

OBJECTIVES: To assess long-term neurodevelopmental outcomes in children after radiofrequency ablation (RFA) for twin reversed arterial perfusion (TRAP) sequence. METHODS: This cross-sectional study included children who underwent RFA for the TRAP sequence between 2012 and 2018. We assessed neurodevelopment in children using the Kinder Infant Development Scale, a validated questionnaire. The developmental quotient (DQ) assessed in nine subscales was calculated as the developmental age divided by the chronological age. Neurodevelopmental delay (NDD) was defined as a DQ of <70 points. RESULTS: In total, 38 children from 37 pregnancies underwent RFA for the TRAP sequence during the study period; 6 fetuses died in utero. We sent the questionnaire to the parents of the 32 surviving children and obtained answers for 27 (84%). The median age at the assessment was 2 years and 5 months old. The median total DQ was 111 (80-150). Most median DQs in the nine subscales were above 70. The incidence of NDD was 0% (0/27). There were no marked differences in DQ by chorionicity. CONCLUSIONS: Children who survived after RFA for TRAP sequence showed favorable long-term neurodevelopmental outcomes. Radiofrequency ablation seems to rarely affect fetal neurodevelopment. Pregnant women with TRAP sequence are encouraged to be treated by RFA.

Risk Profiling of the Solomon Technique versus Selective Technique of Fetoscopic Laser Surgery for Twin-Twin Transfusion Syndrome.

We evaluated the outcomes and adverse events after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) using the Solomon technique in comparison to the selective technique. A retrospective analysis of a single-center consecutive cohort of FLS-treated TTTS using the selective (January 2010 to July 2014) and Solomon (August 2014 to December 2017) techniques was performed. Among 395 cases, 227 underwent selective coagulation and 168 underwent the Solomon technique. The incidence rates of recurrent TTTS (Solomon vs. selective: 0% vs. .9%, p = .510) and twin anemia-polycythemia sequence (.6% vs. .4%, p = .670) were very low in both groups. The incidence rates of placental abruption (Solomon vs. selective: 10.7% vs. 3.5%, p = .007) and preterm premature rupture of the membranes (pPROM) with subsequent delivery before 32 weeks (20.2% vs. 7.1%, p < .001) were higher in the Solomon group. The median birth recipient weight was significantly smaller in the Solomon group (1790 g vs. 1933 g, p = .049). The rate of survival of at least one twin was significantly higher in the Solomon group (98.2% vs. 93.8%, p = .046). The Solomon technique and total laser energy were significant risk factors for pPROM (odds ratio: 2.64, 1.07, 95% CI [1.32, 5.28], [1.01, 1.13], p = .006, p = .014, respectively). These findings suggest that the Solomon technique led to superior survival outcomes but increased risks of placental abruption, pPROM and fetal growth impairment. Total laser energy was associated with the occurrence of pPROM. Close attention to adverse events is required for perinatal management after FLS to treat TTTS using the Solomon technique.

Neonatal systemic juvenile Xanthogranuloma with Hydrops diagnosed by Purpura skin biopsy: a case report and literature review.

BACKGROUND: Systemic juvenile xanthogranuloma is a very rare disease typically presents as skin lesions with yellow papules or nodules and is sometimes fatal. We report a case of congenital neonatal systemic juvenile xanthogranuloma with atypical skin appearance that made the diagnosis difficult. CASE PRESENTATION: A preterm Japanese female neonate with prenatally diagnosed fetal hydrops in-utero was born with purpuric lesions involving the trunk and face. Since birth, she had hypoxemic respiratory failure, splenomegaly, anemia, thrombocytopenia, coagulopathy, and was transfusion dependent for red blood cells, fresh frozen plasma, and platelets. Multiple cystic lesions in her liver, part of them with vascular, were detected by ultrasound. A liver biopsy was inconclusive. A skin lesion on her face similar to purpura gradually changed to a firm and solid enlarged non-yellow nodule. Technically, the typical finding on skin biopsy would have been histiocytic infiltration (without Touton Giant cells) and immunohistochemistry results which then would be consistent with a diagnosis of systemic juvenile xanthogranuloma, and chemotherapy improved her general condition. CONCLUSIONS: This case report shows that skin biopsies are necessary to detect neonatal systemic juvenile xanthogranuloma when there are organ symptoms and skin eruption, even if the skin lesion does not have a typical appearance of yellow papules or nodules.

Low vancomycin trough concentration in neonates and young infants.

BACKGROUND: Vancomycin (VCM) is useful for treating methicillin-resistant Staphylococcus aureus. In infants, calibrating the initial VCM dose is difficult, and many regimens have been proposed. For instance, our center uses the VCM regimen recommended for infants in the 2012-13 Nelson's Pediatric Antimicrobial Therapy. Nonetheless, our experience has shown that the initial VCM trough concentrations were frequently off target. We therefore analyzed the data on the initial VCM trough concentration in infant patients at our center. METHODS: The study subjects were inborn infants born between July 2014 and June 2019 who were given VCM at earlier than day 60 in the neonatal intensive care unit. The primary outcome was the initial VCM trough concentration. The patients were divided into three groups by VCM trough concentration: <10, 10-15, and >15 mg/L. We also estimated VCM trough concentration by one method using Monte Carlo simulation, based on Nelson regimen dosage. RESULTS: Thirty-three patients were analyzed. The number of patients with <10, 10-15, and >15 mg/L was 24, 4, and 5, respectively. There was no significant difference in clinical characteristics between <10 versus 10-15 and 10-15 versus >15 mg/L. The numbers of patients with <10, 10-15, and >15 mg/L in the simulation were 26, 6, and 1, respectively. CONCLUSIONS: Most initial VCM trough concentrations were below the target. We could not find any significant clinical characteristics, which affected VCM trough concentration. Increasing the VCM dosage of the Nelson regimen with simulation should therefore be considered.

Neurodevelopmental impairment at 3 years of age after fetoscopic laser surgery for twin-to-twin transfusion syndrome.

BACKGROUND: Data on neurodevelopmental outcomes of children surviving after fetoscopic laser surgery (FLS) for twin-to-twin transfusion syndrome (TTTS) are scarce. METHODS: We retrospectively investigated children surviving after FLS for TTTS at 16 to 26 weeks' gestation between 2003 and 2014. Children were evaluated by standardized neurologic examinations using the Kyoto Scale 2001 at a corrected age of 3 years ± 6 months. Neurodevelopmental impairment (NDI) was defined as cerebral palsy (CP), bilateral blindness, bilateral deafness or a developmental quotient (DQ) < 70 points. Brain magnetic resonance imaging (MRI) was performed at term-equivalent age. RESULTS: A total of 188 children from 110 twin pregnancies were evaluated. NDI was detected in 16/188 (8.5%) children, including six cases of CP (3.2%). No children had bilateral blindness or deafness. An earlier gestational age at delivery was associated with a higher incidence of NDI (P < .001). Abnormal brain MRI findings were detected in 9/16 (56%) of children with NDI, including 6/6 (100%) with CP. CONCLUSION: The incidence of NDI in children following FLS at 3 years old was 8.5%. Prematurity is a strong risk factor for NDI. Brain MRI may predict the development of CP.

Feasibility and outcomes of fetoscopic endoluminal tracheal occlusion for severe congenital diaphragmatic hernia: A Japanese experience.

AIM: To present the feasibility, safety and outcomes of fetoscopic endoluminal tracheal occlusion (FETO) for the treatment of severe congenital diaphragmatic hernia (CDH). METHODS: This was a single-arm clinical trial of FETO for isolated left-sided CDH with liver herniation and Kitano Grade 3 stomach position (>50% stomach herniation into the right chest). FETO was performed at 27-29 weeks of gestation for cases with observed/expected lung to head ratio (o/e LHR) <25% and at 30-31 weeks for cases with o/e LHR ≥25%. RESULTS: Eleven cases were enrolled between March 2014 and March 2016, and balloon insertion was successful in all cases. The median o/e LHR at entry was 27% (range, 20-33%). The median gestational age at FETO was 30.9 (range, 27.1-31.7) weeks. There were no severe maternal adverse events. One fetus died unexpectedly at 33 weeks of gestation due to cord strangulation by the detached amniotic membrane. There were 3 cases (27%) of preterm premature rupture of membranes. In all 10 cases, balloon removal at 34-35 weeks of gestation was successful. The median gestational age at delivery was 36.5 (range, 34.2-38.3) weeks. The median duration of occlusion and the median interval between balloon insertion and delivery were 26 days (range: 17-49 days) and 43 days (range, 21-66 days), respectively. Both the survival rate at 90 days of age and the rate of survival to discharge were 45% (5/11). CONCLUSION: The FETO is feasible without maternal morbidity in Japan and could be offered to women whose fetuses show severe isolated left-sided CDH to accelerate fetal lung growth.

Utilizing Video versus Direct Laryngoscopy to Intubate Simulated Newborns while Contained within the Incubator: A Randomized Crossover Study.

OBJECTIVE: The use of video laryngoscopy for intubating neonates in ergonomically challenging settings has not been studied well. We aimed to assess the usefulness of video laryngoscopy for experienced neonatologists to intubate neonatal manikins in incubators via side hand ports or head window. STUDY DESIGN: In this randomized crossover trial at three neonatal intensive care units in Japan, 27 neonatologists were randomized into two groups, namely, those intubating neonatal simulators using video laryngoscopy and then using direct laryngoscopy, or vice versa. The intubations were performed via hand ports or head window without opening top and side walls in incubators in two manikin positions (rotated 90° or unrotated). Glottis visualization (0-100%), success rate, intubation time, and ease of laryngoscopy (from 1 [very difficult] to 10 [very easy]) were compared between video laryngoscopy and direct laryngoscopy. Generalized linear models were used for the analyses. RESULTS: This study assessed 108 intubations performed by 27 neonatologists. The use of video laryngoscopy improved the glottis visualization by 14% (95% confidence interval, 7.4-20%; p < 0.01) and easiness scores of laryngoscopy by 0.8 (0.2-1.4; p < 0.01), but did not reduce the intubation time. CONCLUSION: Video laryngoscopy is useful for experienced neonatologists for intubating neonatal manikins in incubators without opening the top or side walls.

Umbilical catheterization training: Tissue hybrid versus synthetic trainer.

BACKGROUND: This study of umbilical catheterization deliberate practice training compared skill and knowledge outcomes of umbilical catheterization using a tissue-hybrid simulator (REAL) versus a synthetic simulated umbilical cord task trainer (ART). METHODS: This was a prospective randomized control study. Pediatric residents were randomized to REAL or ART umbilical catheterization deliberate practice training. Pre-post-training changes in skill performance and knowledge scores for REAL and ART groups were compared. Fidelity of REAL and ART were compared by neonatologists. RESULTS: Twenty-seven pediatric residents completed training. Post-training mean skill scores were improved compared to pre-test scores (REAL, P < 0.001; ART, P < 0.0001). Post-training skill, knowledge, and self-efficacy scores were not different between the REAL and ART groups. Fidelity of REAL was higher than ART for neonatologists (P < 0.01). CONCLUSIONS: The face validity of REAL was superior to ART, but resident umbilical cord deliberate practice training demonstrated no difference in skill, knowledge, and self-efficacy improvements between REAL and ART. Further studies on real patients are needed to evaluate the impact of using real or simulated umbilical cords for umbilical venous catheter/umbilical arterial catheter training.

Maximization of calcium and phosphate in neonatal total parenteral nutrition.

BACKGROUND: Appropriate calcium and phosphate supplementation is essential for bone growth in preterm infants. Using Rehabix-K2™ (AY Pharmaceuticals, Tokyo, Japan) and Pleamin-P Injection™ (Fuso Pharmaceutical Industries, Osaka, Japan) as the total parenteral nutrition (TPN) and amino acid solution, respectively, we investigated ways of maximizing calcium and phosphate in the TPN solution. METHODS: Rehabix-K2, Pleamin-P, calcium gluconate, sodium phosphate, 50% glucose, and water were mixed in varying proportions to create 16 formulations. Precipitation assessment was done three times for each of the 16 formulations, and was based on the Japanese Pharmacopeia. RESULT: Precipitation was observed 24 h after mixing when the calcium and phosphate were 60 mEq/L and 30 mmol/L or 80 mEq/L and 40 mmol/L, respectively. No precipitation was observed when the calcium and phosphate were 20 mEq/L and 10 mmol/L, respectively. Precipitation was observed once out of three times, when the calcium and phosphate were 40 mEq/L and 20 mmol/L, respectively, and the amino acids were 2% and 3% (mean pH, 6.13 and 6.26, respectively). No precipitation was observed, however, when the calcium and phosphate were 40 mEq/L and 20 mmol/L, respectively, and the amino acids were 0% and 1% (mean pH, 5.88 and 6.05, respectively). CONCLUSION: Not only the concentration of calcium and phosphate, but also the pH of the TPN solution, are crucial factors for precipitation. Based on these results, a well-balanced TPN solution maximizing calcium and phosphate availability will be able to be formulated.

Congenital cytomegalovirus in Japan: More than 2 year follow up of infected newborns.

BACKGROUND: The aim of this study was to evaluate the outcome of congenital cytomegalovirus (CMV) infection identified on urine-filter screening assay at >2 years' follow up, and to observe the clinical outcomes after anti-CMV treatment. METHODS: Sixty of 72 congenital CMV patients were enrolled and clinically observed for >2 years. Forty-three were asymptomatic at birth; seven were symptomatic at birth but untreated with anti-CMV drugs; and 10 were symptomatic and treated with anti-CMV drugs. RESULTS: Of the 43 asymptomatic patients, three developed hearing loss or language disability for which association with congenital CMV has been repeatedly reported, and two had neurological sequelae of which the etiology was unclear, indicating that the rate of CMV-associated late-onset sequelae was 7-12%. All seven symptomatic infants without treatment developed sequelae, while three of the 10 treated patients were free from any sequelae. CONCLUSIONS: The rate of late-onset sequelae observed in Japan is similar to that reported in the USA and Europe. The treatment of symptomatic patients with antiviral agents results in favorable clinical outcomes. Thus, newborn urine-filter paper screening of congenital CMV infection is warranted.

The outcomes of 31 cases of trisomy 13 diagnosed in utero with various management options.

There are few reports on the prognosis of prenatally diagnosed trisomy 13 in relation to postnatal management. The aim of this study was to report on the prenatal and postnatal outcomes and postnatal management of trisomy 13 fetuses that were prenatally diagnosed at our center between 2003 and 2015. The data were retrospectively reviewed from medical records. Of the 31 cases of trisomy 13, 12 patients were diagnosed before 22 weeks of gestation, and 19 were diagnosed at or after 22 weeks of gestation. Nine families opted for termination of the pregnancy, 14 fetuses died, and 8 were born alive. Aggressive treatment was requested in two of the live births, with one patient achieving long-term survival (7 years). The other died during infancy (Day 61). One out of four who received palliative treatment is alive at two years of age with only nutrition supplementation. These three patients who achieved neonatal survival had few structural anomalies. Fetal death and early neonatal death are common in trisomy 13; however, fetuses that receive medical treatment for cases without major ultrasound abnormalities may achieve neonatal survival. Therefore, it is useful to provide comprehensive information, including precise ultrasound findings and treatment options, to parents with trisomy 13 fetuses during genetic counseling.

Resolution of liver disease in transient abnormal myelopoiesis with fish oil emulsion.

Neonates with Down syndrome are at risk of developing transient abnormal myelopoiesis (TAM), which is characterized by transient clonal myeloproliferation of the blast cells. TAM can resolve spontaneously, but some patients die at an early age due to organ failure. Liver fibrosis in TAM is a life-threatening condition, but treatment options have not yet been established. Here, we report on the case of an infant with TAM complicated by liver disease, whose hyperbilirubinemia was successfully ameliorated with omega-3 fatty acid (ω3FA) lipid emulsion. Timely ω3FA lipid emulsion may be a feasible treatment for liver disease in TAM before serious liver damage develops.

Fetoscopic laser photocoagulation for amniotic fluid discordance bordering on twin-twin transfusion syndrome: Feasibility, perinatal and long-term outcomes.

AIM: This study investigated the feasibility and safety of fetoscopic laser photocoagulation (FLP) for amniotic fluid discordance (AFD) bordering on twin-twin transfusion syndrome (TTTS) with an absent or reverse end-diastolic velocity (AREDV) in the umbilical artery (UA), and evaluated the perinatal and long-term outcomes. METHODS: A prospective intervention study was performed between 20 + 0 and 25 + 6 weeks of gestation (UMIN000004165). AFD bordering on TTTS was defined as maximum vertical pocket (MVP) of amniotic fluid in one twin's sac ≤3 cm and amniotic fluid MVP in the other twin's sac ≥7 cm excluding TTTS. Neurodevelopmental outcome was evaluated at 6 months and at 3 years of age. RESULTS: Eleven women were treated without complications between September 2010 and July 2011. In all cases amnioinfusion was required, with a median surgical time of 70 min. There were nine cases of selective intrauterine growth restriction in which the growth discordant rate was >25%. The survival rates of the donor and recipient twins were 27.3% (3/11) and 100% (11/11), respectively. None of the surviving donor twins and two of the 11 recipient twins had hemiplegia at 6 months of age. One additional recipient twin had developmental delay at 3 years of age. CONCLUSIONS: Fetoscopic laser photocoagulation for AFD bordering on TTTS with AREDV in the UA was feasible without complications but frequently resulted in donor twin death and a high survival rate of the recipient twin, albeit with neurodevelopmental abnormalities in some cases. FLP does not seem to be a promising treatment option for AFD bordering on TTTS.

Cord blood-derived endothelial colony-forming cell function is disrupted in congenital diaphragmatic hernia.

Vascular growth is necessary for normal lung development. Although endothelial progenitor cells (EPCs) play an important role in vascularization, little is known about EPC function in congenital diaphragmatic hernia (CDH), a severe neonatal condition that is associated with pulmonary hypoplasia. We hypothesized that the function of endothelial colony-forming cells (ECFCs), a type of EPC, is impaired in CDH. Cord blood (CB) was collected from full-term CDH patients and healthy controls. We assessed CB progenitor cell populations as well as plasma vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1α (SDF1α) levels. CB ECFC clonogenicity; growth kinetics; migration; production of VEGF, SDF1α, and nitric oxide (NO); vasculogenic capacity; and mRNA expression of VEGF-A, fms-related tyrosine kinase 1 (FLT1), kinase insert domain receptor (KDR), nitric oxide synthase (NOS) 1-3, SDF1, and chemokine (C-X-C motif) receptor 4 (CXCR4) were also assessed. Compared with controls, CB ECFCs were decreased in CDH. CDH ECFCs had reduced potential for self-renewal, clonogenicity, proliferation, and migration. Their capacity for NO production was enhanced but their response to VEGF was blunted in CDH ECFCs. In vivo potential for de novo vasculogenesis was reduced in CDH ECFCs. There was no difference in CB plasma VEGF and SDF1α concentrations, VEGF and SDF1α production by ECFCs, and ECFC mRNA expression of VEGF-A, FLT1, KDR, NOS1-3, SDF1, and CXCR4 between CDH and control subjects. In conclusion, CB ECFC function is disrupted in CDH, but these changes may be caused by mechanisms other than alteration of VEGF-NO and SDF1-CXCR4 signaling.