RESUMO
OBJECTIVE: To evaluate whether white matter injury (WMI) volumes and spatial distribution, which are important predictors of neurodevelopmental outcomes in preterm infants, have changed over a period of 15 years. STUDY DESIGN: Five hundred and twenty-eight infants born <32 weeks' gestational age from 2 sequential prospective cohorts (cohort 1: 2006 through 2012; cohort 2: 2014 through 2019) underwent early-life (median 32.7 weeks postmenstrual age) and/or term-equivalent-age MRI (median 40.7 weeks postmenstrual age). WMI were manually segmented for quantification of volumes. There were 152 infants with WMI with 74 infants in cohort 1 and 78 in cohort 2. Multivariable linear regression models examined change in WMI volume across cohorts while adjusting for clinical confounders. Lesion maps assessed change in WMI location across cohorts. RESULTS: There was a decrease in WMI volume in cohort 2 compared with cohort 1 (ß = -0.6, 95% CI [-0.8, -0.3], P < .001) with a shift from more central to posterior location of WMI. There was a decrease in clinical illness severity of infants across cohorts. CONCLUSIONS: We found a decrease in WMI volume and shift to more posterior location in very preterm infants over a period of 15 years. This may potentially reflect more advanced maturation of white matter at the time of injury which may be related to changes in clinical practice over time.
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Recém-Nascido Prematuro , Imageamento por Ressonância Magnética , Substância Branca , Humanos , Recém-Nascido , Feminino , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/lesões , Estudos Prospectivos , Idade Gestacional , Doenças do Prematuro , LactenteRESUMO
OBJECTIVE: To evaluate maternal and perinatal outcomes following fetal intervention in the context of maternal "mirror" syndrome. STUDY DESIGN: A multicenter retrospective study of all cases of fetal hydrops complicated by maternal "mirror" syndrome and treated by any form of fetal therapy between 1995 and 2022. Medical records and ultrasound images of all cases were reviewed. "Mirror" syndrome was defined as fetal hydrops and/or placentomegaly associated with the maternal development of pronounced edema, with or without pre-eclampsia. Fetal hydrops was defined as the presence of abnormal fluid collections in ≥2 body cavities. RESULTS: Twenty-one pregnancies met the inclusion criteria. Causes of fetal hydrops and/or placentomegaly included fetal lung lesions (n = 9), twin-twin transfusion syndrome (n = 6), severe fetal anemia (n = 4), and others (n = 2). Mean gestational age at "mirror" presentation was 27.0 ± 3.8 weeks. Maternal "mirror" syndrome was identified following fetal therapeutic intervention in 14 cases (66.6%). "Mirror" symptoms resolved or significantly improved before delivery in 8 (38.1%) cases with a mean interval from fetal intervention to maternal recovery of 13.1 days (range 4-35). Three women needed to be delivered because of worsening "mirror" syndrome. Of the 21 pregnancies treated (27 fetuses), there were 15 (55.5%) livebirths, 7 (25.9%) neonatal deaths and 5 (18.5%) intra-uterine deaths. CONCLUSION: Following successful treatment and resolution of fetal hydrops, maternal "mirror" syndrome can improve or sometimes completely resolve before delivery. Furthermore, the recognition that "mirror" syndrome may arise only after fetal intervention necessitates hightened patient maternal surveillance in cases of fetal hydrops.
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Terapias Fetais , Hidropisia Fetal , Humanos , Feminino , Gravidez , Hidropisia Fetal/terapia , Hidropisia Fetal/diagnóstico , Hidropisia Fetal/etiologia , Hidropisia Fetal/diagnóstico por imagem , Estudos Retrospectivos , Adulto , Terapias Fetais/métodos , Síndrome , Doenças Placentárias/terapia , Doenças Placentárias/diagnóstico , Ultrassonografia Pré-Natal , Pré-Eclâmpsia/terapia , Pré-Eclâmpsia/diagnóstico , Resultado da Gravidez/epidemiologia , Transfusão Feto-Fetal/terapia , Transfusão Feto-Fetal/complicações , Transfusão Feto-Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/diagnósticoRESUMO
Our objective was to assess the effect of maternal intravenous immunoglobulin (IVIG) administration for severe red blood cell (RBC) alloimmunisation on fetal outcomes. This is a case-control study. Women with a history of severe early onset alloimmunisation resulting in fetal loss in a previous pregnancy and high anti-D or anti-K antibody titres received IVIG in a subsequent pregnancy. We assessed gestational age at first transfusion and fetal outcomes in the subsequent pregnancy and compared these with the outcomes in the previous pregnancy. The most responsible antibody was anti-D in 17 women and anti-K in two others, whilst seven had more than one antibody. In all, 19 women received IVIG in 22 pregnancies, two of which did not even need an intrauterine transfusion (IUT). For previous early losses despite transfusion, IVIG was associated with a relative increase in fetal haemoglobin between treated and untreated pregnancies of 36.5 g/L (95% confidence interval 19.8-53.2, p = 0.0013) and improved perinatal survival (eight of eight vs. none of six, p = 0.001). For previous losses at <20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 weeks (mean 23.2 weeks). Overall, IVIG decreases the severity of haemolytic disease of the fetus and newborn and allows deferral of the first IUT to a safer gestation in severe early-onset RBC alloimmunisation and rarely may even avoid the need for IUT entirely.
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Eritroblastose Fetal , Isoimunização Rh , Gravidez , Recém-Nascido , Humanos , Feminino , Imunoglobulinas Intravenosas/uso terapêutico , Estudos de Casos e Controles , Eritrócitos , Anticorpos , Transfusão de Sangue Intrauterina/métodos , Eritroblastose Fetal/terapiaRESUMO
BACKGROUND: We assessed variability of analgesic use across three tertiary neonatal intensive care units (NICUs) accounting for early-life pain, quantified as number of invasive procedures. We also determined whether analgesia exposure modifies associations between early-life pain and neurodevelopment. METHODS: Multicenter prospective study of 276 very preterm infants (born <24-32 weeks' gestational age [GA]). Detailed data of number of invasive procedures and duration of analgesia exposure were collected in initial weeks after birth. Eighteen-month neurodevelopmental assessments were completed in 215 children with Bayley Scales for Infant Development-Third edition. RESULTS: Multivariable linear regressions revealed significant differences in morphine use across sites, for a given exposure to early-life pain (interaction p < 0.001). Associations between early-life pain and motor scores differed by duration of morphine exposure (interaction p = 0.01); greater early-life pain was associated with poorer motor scores in infants with no or long (>7 days) exposure, but not short exposure (≤7 days). CONCLUSIONS: Striking cross-site differences in morphine exposure in very preterm infants are observed even when accounting for early-life pain. Negative associations between greater early-life pain and adverse motor outcomes were attenuated in infants with short morphine exposure. These findings emphasize the need for further studies of optimal analgesic approaches in preterm infants. IMPACT: In very preterm neonates, both early-life exposure to pain and analgesia are associated with adverse neurodevelopment and altered brain maturation, with no clear guidelines for neonatal pain management in this population. We found significant cross-site variability in morphine use across three tertiary neonatal intensive care units in Canada. Morphine use modified associations between early-life pain and motor outcomes. In infants with no or long durations of morphine exposure, greater early-life pain was associated with lower motor scores, this relationship was attenuated in those with short morphine exposure. Further trials of optimal treatment approaches with morphine in preterm infants are warranted.
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Analgesia , Recém-Nascido Prematuro , Lactente , Criança , Humanos , Recém-Nascido , Manejo da Dor , Estudos Prospectivos , Dor/tratamento farmacológico , Morfina/efeitos adversos , Analgésicos , Idade GestacionalRESUMO
OBJECTIVE: Ongoing health care challenges, low breast milk intake, and the need for rehospitalization are common during the first year of life after hospital discharge for very low birth weight (VLBW) infants. This retrospective cohort study examined breast milk intake, growth, emergency department (ED) visits, and non-surgical rehospitalizations for VLBW infants who received specialized post-discharge follow-up in western Canada, compared to VLBW infants who received standard follow-up in central Canada. DESIGN: Data were collected from two neonatal follow-up programs for VLBW babies (n = 150 specialized-care; n = 205 standard-care). Logistic regression was used to examine odds of breast milk intake and generalized estimating equations were used for odds of growth, ED visits and non-surgical rehospitalization by site. RESULTS: Specialized-care was associated with enhanced breast milk intake duration; the odds of receiving breastmilk at 4 months in the specialized-care cohort was 6 times that in the standard-care cohort. The specialized-care cohort had significantly more ED visits and rehospitalizations. However, for infants with oxygen use beyond 36 weeks compared to those with no oxygen use, the standard-care cohort had over 7 times the odds of rehospitalization where as the specialized-care cohort with no increased odds of rehospitalization. CONCLUSION: Specialized neonatal nursing follow-up was associated with continued breastmilk intake beyond discharge. Infants in the specialized-care cohort used the ED and were hospitalized more often than the standard-care cohort with the exception of infants with long term oxygen needs.
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Aleitamento Materno , Alta do Paciente , Recém-Nascido , Lactente , Feminino , Humanos , Estudos Retrospectivos , Assistência ao Convalescente , Unidades de Terapia Intensiva Neonatal , Recém-Nascido de muito Baixo Peso , Leite HumanoRESUMO
Red blood cell (RBC) alloimmunisation with anti-D and anti-K comprise the majority of cases of fetal haemolytic disease requiring intrauterine red cell transfusion (IUT). Few studies have investigated which haematological parameters can predict adverse fetal or neonatal outcomes. The aim of the present study was to identify predictors of adverse outcome, including preterm birth, intrauterine fetal demise (IUFD), neonatal death (NND) and/or neonatal transfusion. We reviewed the records of all pregnancies alloimmunised with anti-K and anti-D, requiring IUT over 27 years at a quaternary fetal centre. We reviewed data for 128 pregnancies in 116 women undergoing 425 IUTs. The median gestational age (GA) at first IUT was significantly earlier for anti-K than for anti-D (24·3 vs. 28·7 weeks, P = 0·004). Women with anti-K required more IUTs than women with anti-D (3·84 vs. 3·12 mean IUTs, P = 0·036) and the fetal haemoglobin (Hb) at first IUT was significantly lower (51.0 vs. 70.5 g/l, P = 0·001). The mean estimated daily decrease in Hb did not differ between the two groups. A greater number of IUTs and a slower daily decrease in Hb (g/l/day) between first and second IUTs were predictive of a longer period in utero. Earlier GA at first IUT and a shorter interval from the first IUT until delivery predicted IUFD/NND. Earlier GA and lower Hb at first IUT significantly predicted need for phototherapy and/or blood product use in the neonate. In the anti-K group, a greater number of IUTs was required in women with a higher titre. Furthermore, the higher the titre, the earlier the GA at which an IUT was required in both groups. The rate of fall in fetal Hb between IUTs decreased, as the number of transfusions increased. Our present study identified pregnancies at considerable risk of an unfavourable outcome with anti-D and anti-K RBC alloimmunisation. Identifying such patients can guide pregnancy management, facilitates patient counselling, and can optimise resource use. Prospective studies can also incorporate these characteristics, in addition to laboratory markers, to further identify and improve the outcomes of these pregnancies.
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Anemia Hemolítica Autoimune/terapia , Transfusão de Sangue Intrauterina/métodos , Eritrócitos/imunologia , Isoimunização Rh/fisiopatologia , Imunoglobulina rho(D)/metabolismo , Adulto , Feminino , Feto , Humanos , Gravidez , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The aim of this retrospective cohort study was to study the clinical burden associated with cardio-pulmonary critical decompensations (CPCDs) in preterm neonates and factors associated with mortality. Through the Canadian Neonatal Network (30 tertiary NICUs, 2010-2017), we identified infants < 32-week gestational age with CPCDs, defined by "significant exposure" to cardiotropes and/or inhaled nitric oxide (iNO): (1) either therapy for ≥ 3 consecutive days, (2) both for ≥ 2 consecutive days, or (3) any exposure within 2 days of death. Early CPCDs (≤ 3 days of age) and late CPCDs (> 3 days) were examined separately. Outcomes included CPCD-incidence, mortality, and inter-site variability using standardized ratios (observed/adjusted expected rate) and network funnel plots. Mixed-effects analysis was used to quantify unit-level variability in mortality. Overall, 10% of admissions experienced CPCDs (n = 2915). Late CPCDs decreased by ~ 5%/year, while early CPCDs were unchanged during the study period. Incidence and CPCD-associated mortality varied between sites, for both early (0.6-7.5% and 0-100%, respectively) and late CPCDs (2.5-15% and 14-83%, respectively), all p < 0.01. Units' late-CPCD incidence and mortality demonstrated an inverse relationship (slope = -2.5, p < 0.01). Mixed-effects analysis demonstrated clustering effect, with 6.4% and 8.6% of variability in mortality after early and late CPCDs respectively being site-related, unexplained by available patient-level characteristics or unit volume. Mortality was higher with combined exposure than with only-cardiotropes or only-iNO (41.3%, 24.8%, 21.5%, respectively; p < 0.01). CONCLUSIONS: Clustering effects exist in CPCD-associated mortality among Canadian NICUs, with higher incidence units showing lower mortality. These data may aid network-level benchmarking, patient-level risk stratification, parental counseling, and further research and quality improvement work. WHAT IS KNOWN: ⢠Preterm neonates remain at high risk of acute and chronic complications; the most critically unwell require therapies such as cardiotropic drugs and inhaled nitric oxide. ⢠Infants requiring these therapies are known to be at high risk for adverse neonatal outcomes and for mortality. WHAT IS NEW: ⢠This study helps illuminate the national burden of acute cardio-pulmonary critical decompensation (CPCD), defined as the need for cardiotropic drugs or inhaled nitric oxide, and highlights the high risk of morbidity and mortality associated with this disease state. ⢠Significant nationwide variability exists in both CPCD incidence and associated mortality; a clustering effect was observed with higher incidence sites showing lower CPCD-associated mortality.
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Unidades de Terapia Intensiva Neonatal , Óxido Nítrico , Administração por Inalação , Canadá/epidemiologia , Humanos , Lactente , Recém-Nascido , Óxido Nítrico/uso terapêutico , Estudos RetrospectivosRESUMO
OBJECTIVE: Fetal myelomeningocele closure results in better infant outcomes than postnatal closure at the cost of potential prematurity and maternal morbidity. Our aim is to describe the setup of a fetal myelomeningocele closure program in Canada and document its outcomes. METHODS: We conducted a retrospective review of all open fetal myelomeningocele closure surgeries performed at the Ontario Fetal Centre in its first 3 years of operation (2017-2020). Maternal and fetal baseline characteristics, surgical details, pregnancy outcomes, and infant follow-up until 1 year of age were recorded. RESULTS: Twenty-seven women underwent fetal myelomeningocele closure surgery, 10 of whom (37%) resided outside of Ontario. Mean gestational age at surgery was 25.0 ± 0.7 weeks. All surgeries were technically uncomplicated and no fetal deaths occurred. There was a significant negative correlation between increasing experience and skin-to-skin surgical time (R²â¯=â¯0.36; Pâ¯=â¯0.001). Of the 26 patients who have delivered, 4 (15.4%) experienced preterm prelabour rupture of membranes. Mean gestational age at delivery was 34.9±3.0 weeks. All but 1 patient delivered by cesarean. Maternal complications occurred in 9 women (34.6%). There were no maternal deaths, but 3 (11.5%) infant deaths. Of the 14 surviving infants who have reached at least 1 year of age, 5 (35.7%) underwent ventriculo-peritoneal shunting. Of the 9 infants who have not yet reached 1 year of age, 3 (33.3%) underwent endoscopic third ventriculostomy and none underwent shunting. CONCLUSION: Fetal open spina bifida closure can be performed in Canada, with results similar to those reported by other international expert centres. Long-term follow-up is ongoing.
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Fetoscopia/métodos , Feto/anormalidades , Feto/cirurgia , Meningomielocele/cirurgia , Espinha Bífida Cística/cirurgia , Adulto , Feminino , Fetoscopia/efeitos adversos , Idade Gestacional , Humanos , Recém-Nascido , Laparotomia , Masculino , Ontário/epidemiologia , Gravidez , Estudos Retrospectivos , Espinha Bífida Cística/diagnóstico , Resultado do TratamentoRESUMO
OBJECTIVE: Fetal thoraco-amniotic shunts (TASs) can dislodge in utero, migrating internally into the fetal thorax or externally into the amniotic cavity. Our objective was to evaluate the perinatal and long-term outcome of fetuses with TAS dislodgement and conduct a review of the literature. METHODS: This is a retrospective review of all TAS inserted for primary pleural effusions and macrocystic congenital pulmonary airway malformations (CPAMs) in a tertiary fetal medicine center (1991-2020). Antenatal history, procedural factors, and perinatal and long-term outcomes were reviewed in all fetuses with dislodged shunts and compared to fetuses with shunts that did not dislodge. RESULTS: Of 211 TAS inserted at a mean gestational age of 27.8 weeks ± 5.47 (17.4-38.1 weeks), 187 (89%) were inserted for pleural effusions and 24 (11%) for macrocystic CPAMs. Shunts dislodged in 18 fetuses (8.5%), 17 (94%) of which were for pleural effusions. Shunts migrated into the chest wall/amniotic cavity or into the thorax among 7/18 (39%) and 11/18 (61%) fetuses, respectively. Eleven (61%) fetuses were initially hydropic, which resolved in 8 (72%) cases. Effusions were bilateral in 9 (50%), amnioreduction was required in 6 (33%), and fetal rotation in 8 cases (44%). Four (22%) fetuses underwent repeat shunting, 12 (67%) neonates required ventilatory support, and 2 (11%) neonates required chest tubes. There was no significant difference in technical factors or outcomes between infants with shunts that dislodged and those that did not. Among 11 intrathoracic shunts, 2 (18%) were removed postnatally and the remainder are in situ without any shunt-related or respiratory complications over a follow-up period of 9 months to 22 years. CONCLUSION: TAS dislodged antenatally in 8.5% of fetuses, with 2/3 of shunts migrating into the thorax, and nearly 25% requiring re-shunting. Retained intrathoracic shunts were well tolerated and may not necessarily require surgical removal after birth.
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Malformação Adenomatoide Cística Congênita do Pulmão , Doenças Fetais , Derrame Pleural , Âmnio , Malformação Adenomatoide Cística Congênita do Pulmão/diagnóstico por imagem , Malformação Adenomatoide Cística Congênita do Pulmão/cirurgia , Feminino , Feto , Humanos , Lactente , Recém-Nascido , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/etiologia , Derrame Pleural/cirurgia , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVES: To examine the association between mortality or neurodevelopmental impairment at 18-24 months of corrected age and the Transport Risk Index of Physiologic Stability (TRIPS) score on admission to the neonatal intensive care unit (NICU) in extremely premature infants. STUDY DESIGN: Retrospective cohort study of extremely premature infants (inborn and outborn) born at 22-28 weeks of gestational age and admitted to NICUs in the Canadian Neonatal Network between April 2009 and September 2011. TRIPS scores and clinical data were collected from the Canadian Neonatal Network database. Follow-up data at 18-24 months of corrected age were retrieved from the Canadian Neonatal Follow-Up Network database. Neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development, Edition III. The primary outcome was death or significant neurodevelopmental impairment at 18-24 months of corrected age. The secondary outcomes were individual components of the Bayley Scales of Infant and Toddler Development, Edition III assessment. RESULTS: A total of 1686 eligible infants were included. A TRIPS score of ≥20 on admission to the NICU was significantly associated with mortality (aOR 2.71 [95% CI, 2.02-3.62]) and mortality or significant neurodevelopmental impairment (aOR 1.91 [95% CI, 1.52-2.41]) at 18-24 months of corrected age across all gestational age groups of extremely premature infants. CONCLUSION: The TRIPS score on admission to the NICU can be used as an adjunctive, objective tool for counselling the parents of extremely premature infants early after their admission to the NICU.
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Deficiências do Desenvolvimento/etiologia , Doenças do Prematuro/mortalidade , Medição de Risco , Bases de Dados Factuais , Deficiências do Desenvolvimento/mortalidade , Feminino , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Doenças do Prematuro/etiologia , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Masculino , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To describe the sonographic characteristics of periventricular hemorrhagic infarction (PVHI) and their association with mortality and neurodevelopmental disability in very preterm infants born in 2008-2013. STUDY DESIGN: Retrospective multicenter observational cohort study. Diagonal PVHI size was measured and severity score assessed. PVHI characteristics were scored and temporal trends were assessed. Neurodevelopmental outcome at 2 years of corrected age was assessed using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales. Multigroup analyses were applied as appropriate. RESULTS: We enrolled 160 infants with median gestational age of 26.6 weeks. PVHI was mostly unilateral (90%), associated with an ipsilateral grade III intraventricular hemorrhage (84%), and located in the parietal lobe (51%). Sixty-four (40%) infants with PVHI died in the neonatal period. Of the survivors assessed at 2 years of corrected age, 65% had normal cognitive and 69% had normal motor outcomes. The cerebral palsy rate was 42%. The composite outcome of death or severe neurodevelopmental disability was observed in 58%, with no trends over the study period (P = .6). Increasing PVHI severity score was associated with death (P < .001). Increasing PVHI size and severity score were negatively associated with gross motor scores (P = .01 and .03, respectively). Trigone involvement was associated with cerebral palsy (41% vs 14%; P = .004). Associated posthemorrhagic ventricular dilation (36%) was an independent risk factor for poorer cognitive and motor outcomes (P < .001 for both). CONCLUSIONS: Increasing PVHI size and severity score were predictive of less optimal gross motor outcome and death in very preterm infants.
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Hemorragia Cerebral/diagnóstico por imagem , Infarto Cerebral/diagnóstico por imagem , Ventrículos Cerebrais/diagnóstico por imagem , Doenças do Prematuro/diagnóstico por imagem , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/patologia , Infarto Cerebral/mortalidade , Infarto Cerebral/patologia , Paralisia Cerebral/complicações , Ventrículos Cerebrais/patologia , Pré-Escolar , Deficiências do Desenvolvimento/complicações , Deficiências do Desenvolvimento/diagnóstico por imagem , Feminino , Idade Gestacional , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/mortalidade , Doenças do Prematuro/patologia , Masculino , Estudos Retrospectivos , UltrassonografiaRESUMO
OBJECTIVES: To assess the natural evolution of the size of the fetal lateral ventricles throughout pregnancy in fetuses with callosal anomalies. METHODS: Cases of fetal callosal anomalies were retrospectively classified as isolated or complex based on the presence of other structural or genetic anomalies. Longitudinal ultrasound studies were reviewed, and postnatal outcomes were retrieved for isolated cases. RESULTS: In 135 fetuses, those who first presented after 24 weeks' gestation were more likely to have ventriculomegaly (n = 58 of 68 [85%]) than those who presented before 24 weeks (n = 39 of 67 [58%]; P < .001). In 79 cases that had longitudinal follow-up, the mean increase in ventricular width was 0.6 mm/wk, without a significant difference between isolated and complex cases (mean ± SD, 0.6 ± 1.5 versus 0.6 ± 1.1 mm; P = .45). CONCLUSIONS: Callosal anomalies are associated with progressive ventriculomegaly on prenatal ultrasound imaging, without a difference between isolated and complex anomalies. This feature should be considered part of the disease spectrum. The consequence of progressive ventriculomegaly on the long-term neurodevelopmental outcome is still unknown, and further studies should be aimed at obtaining long-term follow-up of these cases.
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Agenesia do Corpo Caloso/complicações , Agenesia do Corpo Caloso/diagnóstico por imagem , Hidrocefalia/complicações , Hidrocefalia/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Adolescente , Adulto , Agenesia do Corpo Caloso/embriologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/embriologia , Progressão da Doença , Feminino , Humanos , Hidrocefalia/embriologia , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVES: To determine the outcomes and resource usage of infants born at ≤ 25 weeks gestational age (GA). METHODS: Retrospective study of infants born between April 2009 and September 2011 at ≤ 25 weeks' GA in all neonatal intensive care units in Canada with follow-up in the neonatal follow-up clinics. Short-term morbidities, neurodevelopmental impairment, significant neurodevelopmental impairment, and resource utilization of infants born at ≤ 24 weeks were compared with neonates born at 25 weeks. RESULTS: Of 803 neonates discharged alive, 636 (80.4%) infants born at ≤ 25 weeks' GA were assessed at 18 to 24 months. Caesarean delivery, lower birth weight, and less antenatal steroid exposure were more common in infants born ≤ 24 weeks as compared with 25 weeks. They had significantly higher incidences of ductus arteriosus ligation, severe intracranial hemorrhage, retinopathy of prematurity as well as longer length of stay, central line days, days on respiratory support, days on total parenteral nutrition, days on antibiotics, and need for postnatal steroids. Neurodevelopmental impairment rates were 68.9, 64.5, and 55.6% (P=0.01) and significant neurodevelopmental impairment rates were 39.3, 29.6, and 20.9% (P<0.01) for infants ≤ 23, 24, and 25 weeks GA, respectively. Postdischarge service referrals were higher for those ≤ 23 weeks. Nonsurviving infants born at 25 weeks GA had higher resource utilization during admission than infants born less than 25 weeks. CONCLUSIONS: Adverse outcomes and resource usage were significantly higher among infants born ≤ 24 weeks GA as compared with 25 weeks GA.
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BACKGROUND: There is no consensus regarding the optimal antenatal treatment of fetal/neonatal alloimmune thrombocytopenia (F/NAIT). We aimed to review the fetal blood sampling (FBS)-related risk, fetal response to maternal intravenous immunoglobulin (IVIG), and cesarean section (CS) rate in pregnancies with a history of F/NAIT. METHODS: Maternal demographics, alloantibodies, pregnancy management, fetal and neonatal outcomes, and index case characteristics were collected. Responders (R) and non-responders (NR) were defined as women treated with IVIG in whom fetal platelets (PLTs) were normal or low (< 50 × 109/L). RESULTS: An FBS-related risk occurred in 1.6% (2/119) of procedures. Maternal characteristics did not differ between responders (n = 21) and non-responders (n = 21). HPA-1a antibody was detected in all non-responders and in 72% of responders (p < 0.01). The index case had a significantly lower PLT count at birth in non-responders versus responders (median PLT count: R = 20 × 109/L [IQR 8-43] vs. NR = 9 × 109/L [IQR 4-18], p < 0.02). No differences were found in IVIG treatment duration or dosage. PLTs at birth were significantly lower in non-responders compared to responders. No intracranial hemorrhages occurred. CSs were performed for obstetric indications only in all but two cases. CONCLUSION: Maternal IVIG can elicit different fetal responses. The lack of prognostic factors to predict responders or non-responders suggests that there remains a role for FBS in F/NAIT in experienced hands.
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Antígenos de Plaquetas Humanas/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Trombocitopenia Neonatal Aloimune/terapia , Adulto , Feminino , Humanos , Recém-Nascido , Integrina beta3 , Masculino , Gravidez , Estudos Retrospectivos , Medição de Risco , Resultado do TratamentoRESUMO
BACKGROUND: The risk factors determining the frequency of intrauterine transfusions (IUTs) for severely affected red blood cell alloimmunized singleton pregnancies are not well known. OBJECTIVE: To assess factors associated with IUT frequency and adverse pregnancy outcomes in transfused pregnancies. METHODS: Retrospective cohort analysis of 246 consecutive cases between 1991 and 2014. Time-to-event survival analysis for repeated events was used to evaluate risk of subsequent IUT. Multivariable logistic regression assessed odds of a composite adverse pregnancy outcome (intrauterine fetal death, termination of pregnancy, neonatal death, preterm birth <34 weeks' gestation). RESULTS: Full information was available on232 cases (94.3%) and 716 IUTs. Fetal hydrops was associated with increased frequency (hazard ratio [HR] 1.29 [95% CIs 1.15-1.47, p < 0.001]) while higher fetal hemoglobin (Hb) pre-IUT (HR) 0.99 (95% CI 0.99-1.00, p = 0.021) and post-IUT (HR 0.99 [95% CI 0.99-1.00] p = 0.042), and higher transfused blood volume (HR 0.98 [95% CI 0.97-0.99] p < 0.001) were associated with reduced IUT frequency. Adverse pregnancy outcomes were more likely with lower gestational age (GA) at initial IUT. Antibody type was not associated with IUT frequency or adverse pregnancy outcomes. CONCLUSIONS: Hydrops is associated with increased IUT frequency while lower GA at initial IUT is associated with higher adverse pregnancy outcomes in alloimmunized pregnancies.Higher transfused blood volumes, pre- and post-IUT Hb are associated with lower IUT frequency.
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Transfusão de Sangue Intrauterina , Eritroblastose Fetal/terapia , Hemoglobina Fetal/metabolismo , Hidropisia Fetal/terapia , Isoimunização Rh , Aborto Induzido , Adulto , Transfusão de Sangue Intrauterina/efeitos adversos , Transfusão de Sangue Intrauterina/mortalidade , Eritroblastose Fetal/sangue , Eritroblastose Fetal/imunologia , Eritroblastose Fetal/mortalidade , Feminino , Morte Fetal/etiologia , Humanos , Hidropisia Fetal/sangue , Hidropisia Fetal/imunologia , Hidropisia Fetal/mortalidade , Lactente , Mortalidade Infantil , Nascido Vivo , Gravidez , Nascimento Prematuro/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
A retrospective cohort study of neonates born extremely preterm with persistent patent ductus arteriosus after unsuccessful pharmacologic closure compared outcomes between 166 surgically ligated and 142 nonligated neonates. After adjustment for confounders, ligation was not associated with the composite outcome of death or neurodevelopmental impairment, neurodevelopmental impairment alone, chronic lung disease, or retinopathy of prematurity among survivors.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Permeabilidade do Canal Arterial/cirurgia , Lactente Extremamente Prematuro , Doenças do Prematuro/cirurgia , Tratamento Conservador , Permeabilidade do Canal Arterial/complicações , Permeabilidade do Canal Arterial/tratamento farmacológico , Permeabilidade do Canal Arterial/mortalidade , Feminino , Seguimentos , Humanos , Recém-Nascido , Doenças do Prematuro/tratamento farmacológico , Doenças do Prematuro/mortalidade , Estimativa de Kaplan-Meier , Ligadura , Modelos Logísticos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Inhaled corticosteroids (ICS) offer targeted treatment for bronchopulmonary dysplasia (BPD) with minimal systemic effects compared to systemic steroids. However, dosing of ICS in the management of infants at high-risk of developing BPD is not well established. The objective of this study was to determine an effective dose of ICS for the treatment of ventilator-dependent infants to facilitate extubation or reduce fractional inspired oxygen concentration. METHODS: Forty-one infants born at < 32 weeks gestational age (GA) or < 1250 g who were ventilator-dependent at 10-28 days postnatal age were included. A non-randomized dose-ranging trial was performed using aerosolized inhaled beclomethasone with hydrofluoralkane propellant (HFA-BDP). Four dosing groups (200, 400, 600 and 800 µg twice daily for 1 week) with 11, 11, 10 and 9 infants in each group, respectively, were studied. The primary outcome was therapeutic efficacy (successful extubation or reduction in FiO2 of > 75% from baseline) in ≥60% of infants in the group. Oxygen requirements, complications and long-term neurodevelopmental outcomes were also assessed. RESULTS: The median age at enrollment was 22 (10-28) postnatal days. The primary outcome, therapeutic efficacy as defined above, was not achieved in any group. However, there was a significant reduction in post-treatment FiO2 at a dose of 800 µg bid. No obvious trends were seen in long-term neurodevelopmental outcomes. CONCLUSIONS: Therapeutic efficacy was not achieved with all studied doses of ICS. A significant reduction in oxygen requirements was noted in ventilator-dependent preterm infants at 10-28 days of age when given 800 µg of HFA-BDP bid. Larger randomized trials of ICS are required to determine efficacy for the management of infants at high-risk for development of BPD. TRIAL REGISTRATION: This clinical trial was registered retrospectively on clinicaltrials.gov. The registration number is NCT03503994 .
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Displasia Broncopulmonar/tratamento farmacológico , Glucocorticoides/administração & dosagem , Administração por Inalação , Displasia Broncopulmonar/terapia , Esquema de Medicação , Sistemas de Liberação de Medicamentos , Glucocorticoides/efeitos adversos , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Respiração Artificial , Resultado do Tratamento , Desmame do RespiradorRESUMO
BACKGROUND: Late-onset intrauterine growth restriction (IUGR) results from a failure of the placenta to supply adequate nutrients and oxygen to the rapidly growing late-gestation fetus. Limitations in current monitoring methods present the need for additional techniques for more accurate diagnosis of IUGR in utero. New magnetic resonance imaging (MRI) technology now provides a noninvasive technique for fetal hemodynamic assessment, which could provide additional information over conventional Doppler methods. OBJECTIVE: The objective of the study was to use new MRI techniques to measure hemodynamic parameters and brain growth in late-onset IUGR fetuses. STUDY DESIGN: This was a prospective observational case control study to compare the flow and T2 of blood in the major fetal vessels and brain imaging findings using MRI. Indexed fetal oxygen delivery and consumption were calculated. Middle cerebral artery and umbilical artery pulsatility indexes and cerebroplacental ratio were acquired using ultrasound. A score of ≥ 2 of the 4 following parameters defined IUGR: (1) birthweight the third centile or less or 20% or greater drop in the centile in estimated fetal weight; (2) lowest cerebroplacental ratio after 30 weeks less than the fifth centile; (3) ponderal index < 2.2; and (4) placental histology meets predefined criteria for placental underperfusion. Measurements were compared between the 2 groups (Student t test) and correlations between parameters were analyzed (Pearson's correlation). MRI measurements were compared with Doppler parameters for identifying IUGR defined by postnatal criteria (birthweight, placental histology, ponderal index) using receiver-operating characteristic curves. RESULTS: We studied 14 IUGR and 26 non-IUGR fetuses at 35 weeks' gestation. IUGR fetuses had lower umbilical vein (P = .004) and pulmonary blood flow (P = .01) and higher superior vena caval flow (P < .0001) by MRI. IUGR fetuses had asymmetric growth but smaller brains than normal fetuses (P < .0001). Newborns with IUGR also had smaller brains with otherwise essentially normal findings on MRI. Vessel T2s, oxygen delivery, oxygen consumption, middle cerebral artery pulsatility index, and cerebroplacental ratio were all significantly lower in IUGR fetuses, whereas there was no significant difference in umbilical artery pulsatility index. IUGR score correlated positively with superior vena caval flow and inversely with oxygen delivery, oxygen consumption, umbilical vein T2, and cerebroplacental ratio. Receiver-operating characteristic curves revealed equivalent performance of MRI and Doppler techniques in identifying IUGR that was defined based on postnatal parameters with superior vena caval flow area under the curve of 0.94 (95% confidence interval, 0.87-1.00) vs a cerebroplacental ratio area under the curve of 0.80 (95% confidence interval, 0.64-0.97). CONCLUSION: MRI revealed the expected circulatory redistribution in response to hypoxia in IUGR fetuses. The reduced oxygen delivery in IUGR fetuses indicated impaired placental oxygen transport, whereas reduced oxygen consumption presumably reflected metabolic adaptation to diminished substrate delivery, resulting in slower fetal growth. Despite brain sparing, placental insufficiency limits fetal brain growth. Superior vena caval flow and umbilical vein T2 by MRI may be useful new markers of late-onset IUGR.
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Peso ao Nascer , Encéfalo/embriologia , Retardo do Crescimento Fetal/diagnóstico , Retardo do Crescimento Fetal/fisiopatologia , Hemodinâmica , Imageamento por Ressonância Magnética , Adulto , Área Sob a Curva , Estudos de Casos e Controles , Circulação Cerebrovascular , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Humanos , Recém-Nascido , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiologia , Oxigênio/metabolismo , Consumo de Oxigênio , Placenta/irrigação sanguínea , Placenta/patologia , Circulação Placentária , Gravidez , Terceiro Trimestre da Gravidez/fisiologia , Estudos Prospectivos , Fluxo Pulsátil , Curva ROC , Fluxo Sanguíneo Regional , Ultrassonografia Doppler , Artérias Umbilicais/diagnóstico por imagem , Artérias Umbilicais/fisiologia , Veia Cava Superior/diagnóstico por imagem , Veia Cava Superior/fisiologiaRESUMO
Importance: For many very low-birth-weight (VLBW) infants, there is insufficient mother's milk, and a supplement of pasteurized donor human milk or preterm formula is required. Awareness of the benefits of mother's milk has led to an increase in use of donor milk, despite limited data evaluating its efficacy. Objective: To determine if nutrient-enriched donor milk compared with formula, as a supplement to mother's milk, reduces neonatal morbidity, supports growth, and improves neurodevelopment in VLBW infants. Design, Setting, and Participants: In this pragmatic, double-blind, randomized trial, VLBW infants were recruited from 4 neonatal units in Ontario, Canada, within 96 hours of birth between October 2010 and December 2012. Follow-up was completed in July 2015. Interventions: Infants were fed either donor milk or formula for 90 days or to discharge when mother's milk was unavailable. Main Outcomes and Measures: The primary outcome was the cognitive composite score on the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 18 months' corrected age (standardized mean, 100 [SD, 15]; minimal clinically important difference, 5 points). Secondary outcomes included Bayley-III language and motor composite scores, growth, and a dichotomous mortality and morbidity index. Results: Of 840 eligible infants, 363 (43.2%) were randomized (181 to donor milk and 182 to preterm formula); of survivors, 299 (92%) had neurodevelopment assessed. Mean birth weight and gestational age of infants was 996 (SD, 272) g and 27.7 (2.6) weeks, respectively, and 195 (53.7%) were male. No statistically significant differences in mean Bayley-III cognitive composite score (adjusted scores, 92.9 in donor milk group vs 94.5 in formula group; fully adjusted mean difference, -2.0 [95% CI, -5.8 to 1.8]), language composite score (adjusted scores, 87.3 in donor milk group vs 90.3 in formula group; fully adjusted mean difference, -3.1 [95% CI, -7.5 to 1.3]), or motor composite score (adjusted scores, 91.8 in donor milk group vs 94.0 in formula group; fully adjusted mean difference, -3.7 [95% CI, -7.4 to 0.09]) were observed between groups. There was no statistically significant difference in infants positive for the mortality and morbidity index (43% in donor milk group, 40% in formula group) or changes in growth z scores. Conclusions and Relevance: Among VLBW infants, use of supplemental donor milk compared with formula did not improve neurodevelopment at 18 months' corrected age. If donor milk is used in settings with high provision of mother's milk, this outcome should not be considered a treatment goal. Trial Registration: isrctn.org Identifier: ISRCTN35317141.
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Método Duplo-Cego , Leite Humano , Canadá , Idade Gestacional , Humanos , Lactente , Fórmulas Infantis , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo PesoRESUMO
OBJECTIVE: Fetal infection with human parvovirus B19 (hParvo-B19) has been associated mainly with fetal anemia, although data regarding other fetal hematologic effects are limited. Our aim was to assess the rate and consequences of severe fetal thrombocytopenia after fetal hParvo-B19 infection. STUDY DESIGN: We conducted a retrospective study of pregnancies that were complicated by fetal hParvo-B19 infection that underwent fetal blood sampling (FBS). The characteristics and outcomes of fetuses with severe thrombocytopenia (<50 × 10(9)/L) were compared with those of fetuses with a platelet concentration of ≥50 × 10(9)/L (control fetuses). Fetuses in whom 3 FBSs were performed (n = 4) were analyzed to assess the natural history of platelet levels after fetal hParvo-B19 infection. RESULTS: A total of 37 pregnancies that were affected by fetal hParvo-B19 infection were identified. Of the 29 cases that underwent FBS and had information regarding fetal platelets, 11 cases (38%) were complicated by severe fetal thrombocytopenia. Severely thrombocytopenic fetuses were characterized by a lower hemoglobin concentration (2.6 ± 0.9 g/dL vs 5.5 ± 3.6 g/dL; P = .01), lower reticulocyte count (9.1% ± 2.8% vs 17.3% ± 10.6%; P = .02), and lower gestational age at the time of diagnosis (21.4 ± 3.1 wk vs 23.6 ± 2.2 wk; P = .03). Both the fetal death rate within 48 hours of FBS (27.3% vs 0%; P = .02) and the risk of prematurity (100.0% vs 13.3%; P < .001) were higher in fetuses with severe thrombocytopenia. Fetal thrombocytopenia was more common during the second trimester but, in some cases, persisted into the third trimester. Intrauterine transfusion (IUT) of red blood cells resulted in a further mean decrease of 40.1% ± 31.0% in fetal platelet concentration. CONCLUSION: Severe fetal thrombocytopenia is relatively common after fetal hParvo-B19 infection, can be further worsened by IUT, and may be associated with an increased risk of procedure-related fetal loss after either FBS or IUT.