RESUMO
OBJECTIVE: To determine the impact of damaging genetic variation in proangiogenic pathways on placental function, complications of pregnancy, fetal growth, and clinical outcomes in pregnancies with fetal congenital heart defect. STUDY DESIGN: Families delivering a baby with a congenital heart defect requiring surgical repair in infancy were recruited. The placenta and neonate were weighed and measured. Hemodynamic variables were recorded from a third trimester (36.4 ± 1.7 weeks) fetal echocardiogram. Exome sequencing was performed on the probands (N = 133) and consented parents (114 parent-child trios, and 15 parent-child duos) and the GeneVetter analysis tool used to identify damaging coding sequence variants in 163 genes associated with the positive regulation of angiogenesis (PRA) (GO:0045766). RESULTS: In total, 117 damaging variants were identified in PRA genes in 133 congenital heart defect probands with 73 subjects having at least 1 variant. Presence of a damaging PRA variant was associated with increased umbilical artery pulsatility index (mean 1.11 with variant vs 1.00 without; P = .01). The presence of a damaging PRA variant was also associated with lower neonatal length and head circumference for age z score at birth (mean -0.44 and -0.47 with variant vs 0.23 and -0.05 without; P = .01 and .04, respectively). During median 3.1 years (IQR 2.0-4.1 years) of follow-up, deaths occurred in 2 of 60 (3.3%) subjects with no PRA variant and in 9 of 73 (12.3%) subjects with 1 or more PRA variants (P = .06). CONCLUSIONS: Damaging variants in proangiogenic genes may impact placental function and are associated with impaired fetal growth in pregnancies involving a fetus with congenital heart defect.
Assuntos
Proteínas Angiogênicas/genética , Desenvolvimento Fetal/genética , Variação Genética/genética , Cardiopatias Congênitas/genética , Complicações na Gravidez/etiologia , Estudos de Casos e Controles , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/cirurgia , Humanos , Recém-Nascido , Masculino , GravidezRESUMO
BACKGROUND: Since the results of the Management of Myelomeningocele Study were published, maternal-fetal surgery for the in utero treatment of spina bifida has become accepted as a standard of care alternative. Despite promise with fetal management of myelomeningocele repair, there are significant complications to consider. Chorioamniotic membrane separation and preterm premature rupture of membranes are known complications of invasive fetal procedures. Despite their relative frequency associated with fetal procedures, few data exist regarding risk factors that may be attributed to their occurrence or the natural history of pregnancies that are affected with chorionic membrane separation or preterm premature rupture of membranes related to the procedure. OBJECTIVE: The objective of this study was to review chorioamniotic membrane separation and preterm premature rupture of membranes in a cohort of patients undergoing fetal management of myelomeningocele repair including identification of risk factors and outcomes. STUDY DESIGN: This was a retrospective review of patients undergoing fetal management of myelomeningocele repair and subsequent delivery from January 2011 through December 2013 at 1 institution. Patients were identified through the institutional fetal management of myelomeningocele repair database and chart review was performed. Perioperative factors and outcomes among patients with chorioamniotic membrane separation and preterm premature rupture of membranes were compared to those without. Risk factors associated with the development of chorioamniotic membrane separation and preterm premature rupture of membranes were determined. RESULTS: A total of 88 patients underwent fetal management of myelomeningocele repair and subsequently delivered during the study period. In all, 21 patients (23.9%) were diagnosed with chorioamniotic membrane separation by ultrasound and preterm premature rupture of membranes occurred in 27 (30.7%). Among the chorioamniotic membrane separation patients, 10 (47.6%) were diagnosed with global chorioamniotic membrane separation and 11 (52.4%) with local chorioamniotic membrane separation. Earlier gestational age at the time of fetal surgery was a significant risk factor for the development of chorioamniotic membrane separation (P = .01) and preterm premature rupture of membranes (P < 0.0001). Chorioamniotic membrane separation was significantly associated with preterm premature rupture of membranes (59.1% vs 21.2%, P = .008) and earlier gestational age at delivery (32.1 ± 4.2 vs 34.4 ± 3.5 weeks, P = .01). The average number of days from chorioamniotic membrane separation to preterm premature rupture of membranes was 11.0 ± 10.1 and from chorioamniotic membrane separation to delivery was 31.0 ± 22.5. The mean time interval between fetal management of myelomeningocele repair and preterm premature rupture of membranes was 47.9 days. Mean latency period from preterm premature rupture of membranes to delivery was 25 days. Gestational age at delivery was significantly lower in patients with preterm premature rupture of membranes (31.6 ± 3.4 vs 34.9 ± 3.5 weeks, P = .0001). Using logistic regression analysis, nulliparity, gestational age at fetal management of myelomeningocele repair, and membrane separation remained significant risk factors for preterm premature rupture of membranes. CONCLUSION: Chorioamniotic membrane separation after fetal management of myelomeningocele repair is a significant risk factor for subsequent development of preterm premature rupture of membranes and preterm delivery. Fetal management of myelomeningocele repair <23 weeks is associated with higher rates of preterm premature rupture of membranes and chorioamniotic membrane separation. Therefore fetal management of myelomeningocele repair should be deferred until ≥23 weeks to mitigate these complications. Nulliparity also appears to increase the risk for preterm premature rupture of membranes.
Assuntos
Âmnio/diagnóstico por imagem , Córion/diagnóstico por imagem , Ruptura Prematura de Membranas Fetais/etiologia , Feto/cirurgia , Meningomielocele/cirurgia , Complicações Pós-Operatórias , Adulto , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Modelos Logísticos , Paridade , Gravidez , Complicações na Gravidez , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: Hydrops and pulmonary hypoplasia are associated with significant morbidity and mortality in the setting of a congenital lung lesion or pleural effusion (PE). We reviewed our experience using in utero thoracoamniotic shunts (TA) to manage fetuses with these diagnoses. METHODS: A retrospective review of fetuses diagnosed with a congenital lung lesion or pleural effusion who underwent TA shunt placement from 1998-2013 was performed. RESULTS: Ninety-seven shunts were placed in 75 fetuses. Average gestational age (±SD) at shunt placement and birth was 25±3 and 34±5 weeks. Shunt placement resulted in a 55±21% decrease in macrocystic lung lesion volume and complete or partial drainage of the PE in 29% and 71% of fetuses. 69% of fetuses presented with hydrops, which resolved following shunt placement in 83%. Survival was 68%, which correlated with GA at birth, % reduction in lesion size, unilateral pleural effusions, and hydrops resolution. Surviving infants had prolonged NICU courses and often required either surgical resection or tube thoracostomy in the perinatal period. CONCLUSION: TA shunts provide a therapeutic option for select fetuses with large macrocystic lung lesions or PEs at risk for hydrops and/or pulmonary hypoplasia. Survival following shunting depends on GA at birth, reduction in mass size, and hydrops resolution.
Assuntos
Âmnio/cirurgia , Drenagem/métodos , Doenças Fetais/cirurgia , Feto/cirurgia , Pneumopatias/congênito , Derrame Pleural/cirurgia , Ducto Torácico/cirurgia , Feminino , Idade Gestacional , Humanos , Lactente , Mortalidade Infantil/tendências , Recém-Nascido , Pneumopatias/complicações , Pneumopatias/cirurgia , Masculino , Pennsylvania/epidemiologia , Derrame Pleural/etiologia , Derrame Pleural/mortalidade , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: To determine whether the mode of delivery of infants prenatally diagnosed with hypoplastic left heart syndrome (HLHS) affects markers of perinatal hemodynamics. STUDY DESIGN: A retrospective review of patients diagnosed prenatally with HLHS and delivered within our institution was undertaken. Arterial blood gases, echocardiographic data, and markers of end organ function were compared based on route of delivery. RESULTS: A total of 79 infants with HLHS were enrolled between January 2002 and December 2008. The infants delivered by elective cesarian delivery (CD) had younger gestational age compared with those delivered by vaginal delivery (VD) or by urgent CD/operative VD. Those delivered by elective CD had lower pH and higher partial pressure of CO(2) on arterial cord blood gas analysis. There were no differences in partial pressure of O(2) and base deficit among the 3 study groups. One-minute and 5-minute Apgar scores, markers of end organ function, echocardiographic parameters, length of hospitalization, and survival to discharge were similar among the groups. CONCLUSIONS: Overall, newborns with a prenatal diagnosis of HLHS transitioned well to extrauterine life without significant acidosis regardless of the mode of delivery. Delivery of newborns with HLHS by elective CD did not demonstrate any hemodynamic advantage over VD in our cohort of patients.
Assuntos
Cesárea , Parto Obstétrico , Síndrome do Coração Esquerdo Hipoplásico/sangue , Síndrome do Coração Esquerdo Hipoplásico/fisiopatologia , Índice de Apgar , Biomarcadores , Gasometria , Glicemia/análise , Soluções Tampão , Dióxido de Carbono/sangue , Creatinina/sangue , Estudos Transversais , Ecocardiografia , Feminino , Sangue Fetal/química , Idade Gestacional , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Ácido Láctico/sangue , Pressão Parcial , Gravidez , Diagnóstico Pré-Natal , Respiração Artificial , Estudos Retrospectivos , Bicarbonato de Sódio/uso terapêutico , Trometamina/uso terapêuticoRESUMO
OBJECTIVE: We sought to assess outcome in patients with CDH and HD to determine if LHR is also predictive of outcome in this subset of patients. STUDY DESIGN: We carried out a retrospective review (April 1996-October 2000) of patients with isolated CDH (n = 143, 82.2%) and patients with HD (n = 31, 17.8%) to determine the incidence of additional anomalies, survival to term, CDH repair, cardiac repair, and survival to discharge. Survival based on LHR was analyzed in a subset of fetuses. RESULTS: The risk of death from birth to last follow-up was 2.9 times higher for patients with CDH plus HD than for patients with CDH alone (P <.0001). Of 11 patients with CDH plus HD who had CDH repair (5 of whom also had HD repair), 5 survived. All 10 patients with an LHR <1.2 died; 3 of 6 with an LHR >1.2 survived (Fisher exact test, P =.04). CONCLUSION: Heart disease remains a significant risk factor for death in infants with CDH. The LHR helps predict survival in this high-risk group of patients.