Establishing a Fetal Center in a Freestanding Pediatric Hospital.

Advances in antenatal imaging have allowed early and accurate diagnosis of many fetal anomalies. This, together with the increasing understanding of the natural history of many fetal diseases, has opened the door to the possibility of offering timely fetal interventions in progressive or life-threatening conditions with the intention of improving perinatal outcomes. These interventions can occur at an adult hospital with obstetrical services (with or without pediatric care) or at a freestanding pediatric hospital. In this article, we provide an overview of the approach to develop a comprehensive fetal care center in a freestanding pediatric hospital. Services included prenatal consultation, advanced diagnostics, innovative fetal therapy, research, and special delivery services. We also review the importance of continuous improvement in achieving this goal.

Perinatal outcomes of two consecutive strategies for the management of fetal growth restriction: a before-after study.

PURPOSE: We aim to compare the perinatal outcomes of two consecutive management strategies for fetal growth restriction (FGR), with or without the inclusion of additional Doppler parameters. METHODS: A quasi-experimental before/after study was conducted in which we compared a composite perinatal outcome, prematurity rate, and neonatal complications between two management strategies in small fetuses. In the strategy 1 (S1), the management was based on fetal biometry and umbilical artery Doppler. The second strategy (S2) added the assessment of uterine and middle cerebral artery Doppler. We also compared outcomes between strategies according to early (≤ 32 weeks) and late (> 32 weeks) diagnosis subgroups. RESULTS: We included 396 patients, 163 in S1 and 233 in S2. There were no significant differences in the perinatal composite outcome (p 0.98), prematurity (p 0.19), or in the subgroup analysis. We found a significant reduction in respiratory distress syndrome (RDS) rate with S2 both globally (OR 0.50, p 0.02), and in the early diagnosis subgroup (OR 0.45, p 0.01). In addition, we observed a significant reduction in the incidence of sepsis with S2 both globally (OR 0.30, p 0.04) and in the early diagnosis subgroup (OR 0.25, p 0.02). We did not observe significant differences in necrotizing enterocolitis (p 0.41) and intraventricular hemorrhage (p 1.00). CONCLUSION: The expanded strategy for the management of FGR did not show significant differences in the primary composite outcome or prematurity. However, it was associated with a lower incidence of RDS and neonatal sepsis.

Risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic: Results of a web-based multinational cross-sectional study.

OBJECTIVE: To assess risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic using Mind-COVID, a prospective cross-sectional study that compares outcomes in middle-income economies and high-income economies. METHODS: A total of 7102 pregnant women from 12 high-income economies and nine middle-income economies were included. The web-based survey used two standardized instruments, General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). RESULT: Pregnant women in high-income economies reported higher PHQ-9 (0.18 standard deviation [SD], P < 0.001) and GAD-7 (0.08 SD, P = 0.005) scores than those living in middle-income economies. Multivariate regression analysis showed that increasing PHQ-9 and GAD-7 scales were associated with mental health problems during pregnancy and the need for psychiatric treatment before pregnancy. PHQ-9 was associated with a feeling of burden related to restrictions in social distancing, and access to leisure activities. GAD-7 scores were associated with a pregnancy-related complication, fear of adverse outcomes in children related to COVID-19, and feeling of burden related to finances. CONCLUSIONS: According to this study, the imposed public health measures and hospital restrictions have left pregnant women more vulnerable during these difficult times. Adequate partner and family support during pregnancy and childbirth can be one of the most important protective factors against anxiety and depression, regardless of national economic status.

Outcomes of late open fetal surgery for intrauterine spina bifida repair after 26 weeks. Should we extend the Management of Myelomeningocele Study time window?

OBJECTIVE: To evaluate maternal and perinatal outcomes of late open fetal repair for open spina bifida (OSB) between 26+0 -27+6  weeks. METHODS: A cohort of fetuses with OSB who underwent open surgery in two fetal surgery centers (Argentina and Mexico). Two groups were defined based on the gestational age (GA) at intervention: Management of Myelomeningocele Study (MOMS) time window group: GA 19+0 -25+6 , and late intervention group: GA 26+0 -27+6 . RESULTS: Intrauterine OSB repair was successfully performed in 140 cases, either before (n = 57) or after (n = 83) 26 weeks, at on average 25+0 (22+6 -25+6 ) and 26+5 (26+0 -27+6 ) weeks + days, respectively. There were no significant differences in the rate of premature rupture of membranes, chorioamnionitis, oligohydramnios, preterm delivery, perinatal death and maternal complications. The late intervention group showed a significantly lower surgical times (112.6 vs. 124.2 min, p = 0.01), lower interval between fetal surgery and delivery (7.9 vs. 9.2 weeks, p < 0.01) and similar rate of hydrocephalus requiring treatment (30.6% vs. 23.3%, p = 0.44) than the MOMS time window group. CONCLUSION: Late fetal surgery for OSB repair between 26+0 -27+6  weeks is feasible and was associated with similar outcomes than that performed before 26 weeks. These findings may allow an extension of the proposed time window for cases with late diagnosis or referral.

Prediction of neonatal survival according to lung-to-head ratio in fetuses with right congenital diaphragmatic hernia (CDH): A multicentre study from the Latin American CDH Study Group registry.

OBJECTIVE: To evaluate survival outcomes of fetuses with right sided congenital diaphragmatic hernia (CDH) treated in Latin American centres and to assess the utility of left lung area to predict neonatal survival. METHODS: A retrospective cohort including isolated right sided CDH cases managed expectantly during pregnancy in six tertiary centers from five Latin American countries. The utility of the observed/expected lung-to-head ratio (O/E-LHR) in predicting neonatal survival was assessed, and the best cut-off to predict prognosis was automatically selected by decision tree analysis. RESULTS: A total of 99 right sided CDH cases were recruited, 58 isolated fetuses were selected at a median gestational age of 26.2 weeks, showing an overall survival rate of 26.2%. A linear trend was observed between survival and the O/E-LHR, showing that at higher O/E-LHR, the greater probability of survival (r = 0.56, p < 0.001). O/E-LHR discriminates two groups with different survival outcomes: fetuses with an O/E-LHR ≥65% showed a significantly higher survival rate than those with an O/E-LHR <65% (81.8% vs. 15.6%, p < 0.01). CONCLUSIONS: Overall survival rate in right sided CDH is lower in Latin American countries. The severity category of pulmonary hypoplasia should be classified according to lung area and the survival rate in such population.

Attitudes of Argentinean Neonatologists toward Resuscitation of Infants with Trisomies 21, 18, and 13: A Multicenter Survey.

OBJECTIVE: This study was aimed to explore the attitude of Argentinean neonatologists in the delivery room on resuscitating infants with trisomies. STUDY DESIGN: An anonymous questionnaire was completed by neonatologists staffing level-III neonatal intensive care units (NICUs) on resuscitation of children with trisomies 21, 18, and 13. Potential sociocultural factors influencing the decision to resuscitate were included. RESULTS: Overall, 314 neonatologists in 34 units in the Buenos Aires region participated (response rate of 54%). The position of neonatologists regarding the resuscitation in the delivery room was that 98% would resuscitate newborns with trisomy 21, and 47% with trisomy 18 or trisomy 13. Resuscitation of newborns with trisomy 18 or trisomy 13 by neonatologists was significantly associated with working in the public sector, religious beliefs, and legal framework. CONCLUSION: With improvement in the management and treatment of infants with trisomies 18 and 13, Argentinean neonatologists showed a favorable attitude toward resuscitating them in the delivery room. KEY POINTS: · We explored the attitudes of Argentinean neonatologists on resuscitation of children with trisomies.. · Half of neonatologists would resuscitate newborns with trisomies18 and 13.. · These results suggest an ongoing paradigm shift of the most severe trisomies..

Impact of emerging virus pandemics on cause-specific maternal mortality time series: a population-based natural experiment using national vital statistics, Argentina 1980-2017.

Background: Emerging pandemic viruses may have multiple deleterious effects on maternal health. This study examines the effects of a pandemic influenza virus on cause-specific maternal mortality time series, using Argentinian vital statistics. Methods: We conducted a population-based natural experiment from national vital records of maternal deaths between 1980 and 2017. Joinpoint regression models were used to model time series of the maternal mortality ratio (MMR). The sensitivity of the registry to detect the effects of the pandemic H1N1 2009 influenza virus on cause-specific MMR was analysed using a panel of parallel interrupted time series (ITS). Findings: Over this 38-year study, the MMR decreased by 58·6% (69·5 to 28·8 deaths/100,000 live births), transitioning from direct obstetric causes (67·0 to 21·1/100,000 live births; 68·4% decrease) to indirect causes (2·6 to 7·7/100,000 live births; 196·2% increase). The regression analysis showed an average reduction of -2·2%/year (95% CI: -2·9 to -1·4) with 2 join points in the total trend (1998 and 2009). Parallel ITS analyses revealed the pandemic H1N1 virus had an increasing effect on mortality from the respiratory system- and sepsis-related complications (level change 4·7 and 1·6/100,000 live births respectively), reversing after the outbreak. No effect was found on MMR from hypertensive disorders, haemorrhage, abortive outcomes, other direct obstetric causes, and indirect non-respiratory comorbidities. Interpretation: The Argentinian maternal death registry appears sensitive to detect different effects of emerging infectious epidemics on maternal health. In a population-based natural experiment, pandemic H1N1 virus impacted maternal mortality almost exclusively from the respiratory system- and sepsis-related complications. Funding: Supported by FISAR www.fisarchile.org.

Open intrauterine repair of spina bifida aperta: Historical aspects, current availability, and clinical outcomes from the Latin American Spina Bifida Consortium.

OBJECTIVE: To determine the historical aspects, current availability, and clinical outcomes of open intrauterine repair of spina bifida aperta (IRSBA) in Spanish-speaking Latin American countries. METHODS: Cases were collected from centers with at least 2 years of experience and a minimum of 10 open IRSBA interventions by December 2020. Clinical variables were compared to the results of the Management of Myelomeningocele Study (MOMS) trial. RESULTS: Clinical experience with 314 cases from seven centers was reviewed. Most cases (n = 189, 60.2%) were performed between 24 and 25.9 weeks' gestation. Delivery at less than 30 weeks' gestation occurred in 36 cases (11.5%) and the overall perinatal mortality rate was 5.4% (17 of 314). The rate of maternal complications was low, including the need for blood transfusion (n = 3, 0.9%) and dehiscence or a thin uterine scar (n = 4, 1.3%). No cases of maternal death were recorded. Fifteen neonates required additional surgical repair of the spinal defect (4.8%) and 63 of 167 infants (37.7%) required a cerebrospinal fluid diversion procedure. Only two of the seven centers reported preliminary experience with fetoscopic IRSBA. CONCLUSIONS: Clinical experience and outcomes were within the expected results reported by the MOMS trial. There is still very limited experience with fetoscopic IRSBA in this part of the world.

Prenatal genetic considerations in congenital ventriculomegaly and hydrocephalus.

BACKGROUND: Fetal ventriculomegaly (VM) is a frequent finding in prenatal ultrasound. Rather than a proper diagnosis, VM is a sonographic sign, making prenatal counseling a complex and challenging undertaking. VM can range from severe pathologic processes leading to severe neurodevelopmental delay to normal variants. DISCUSSION: A growing number of genetic conditions with different pathophysiological mechanisms, inheritance patterns, and long-term prognosis have been associated both to isolated and complex fetal VM. These include chromosomal abnormalities, copy number variants, and several single gene diseases. In this review, we describe some of the most common genetic conditions associated with fetal VM and provide a simplified diagnostic workflow for the clinician.

A multicentre study to predict neonatal survival according to lung-to-head ratio and liver herniation in fetuses with left congenital diaphragmatic hernia (CDH): Hidden mortality from the Latin American CDH Study Group Registry.

OBJECTIVE: To evaluate natural history of fetuses congenital diaphragmatic hernia (CDH) prenatally diagnosed in countries where termination of pregnancy is not legally allowed and to predict neonatal survival according to lung area and liver herniation. METHODS: Prospective study including antenatally diagnosed CDH cases managed expectantly during pregnancy in six tertiary Latin American centres. The contribution of the observed/expected lung-to-head ratio (O/E-LHR) and liver herniation in predicting neonatal survival was assessed. RESULTS: From the total population of 380 CDH cases, 144 isolated fetuses were selected showing an overall survival rate of 31.9% (46/144). Survivors showed significantly higher O/E-LHR (56.5% vs 34.9%; P < .001), lower proportion of liver herniation (34.8% vs 80.6%, P < .001), and higher gestational age at birth (37.8 vs 36.2 weeks, P < 0.01) than nonsurvivors. Fetuses with an O/E-LHR less than 35% showed a 3.4% of survival; those with an O/E-LHR between 35% and 45% showed 28% of survival with liver up and 50% with liver down; those with an O/E-LHR greater than 45% showed 50% of survival rate with liver up and 76.9% with liver down. CONCLUSIONS: Neonatal mortality in CDH is higher in Latin American countries. The category of lung hypoplasia should be classified according to the survival rates in our Latin American CDH registry.

Cirugía fetal de Mielomeningocele: evolución obstétrica y resultados perinatales a corto plazo de una cohorte de 21 casos / Fetal surgery for myelomeningocele: obstetric evolution and short-term perinatal results of a cohort of 21 cases

Objetivo: Describir la técnica quirúrgica, evolución obstétrica y resultados perinatales de una cohorte de pacientes sometidas a cirugía intrauterina para reparación de una disrafia fetal abierta (DFA). Métodos: Análisis prospectivo de 21 casos consecutivos de DFA con diagnóstico y tratamiento quirúrgico prenatal en nuestra institución entre 2015 y 2017. La técnica de la cirugía fetal (QF) fue similar a la descripta en el estudio MOMS, excepto que se utilizó histerotomía con asa bipolar. Los cuidados postoperatorios, nacimiento y cuidados neonatales se realizaron en la misma institución. Se analizaron complicaciones perioperatorias de la QF, la evolución obstétrica y los resultados perinatales. Resultados: La QF se realizó a una edad gestacional media de 25.8 semanas (24.1-27.6). La edad gestacional media al nacer fue 34.2 semanas (29.2-37.1). El tiempo quirúrgico medio fue 138 min (101-187) con tendencia descendente y el tiempo de internación medio, 7.1 días (4-32). El 52% (11/21) de las pacientes experimentó rotura prematura de membranas (RPM). Ninguna paciente requirió transfusiones postcesárea. No hubo casos de desprendimiento placentario, rotura uterina ni muertes maternas. La cicatrización de la histerorafia fue normal en 95% de las pacientes. La sobrevida perinatal fue del 95% (20/21, una muerte intrauterina secundaria a banda amniótica). La necesidad de cierre cutáneo postnatal (CCP) fue del 5%. Ninguno de los casos (20) reparados con tejidos fetales requirió CCP. El 70% (14/20) de los pacientes no requirió ningún tratamiento para hidrocefalia. Cuatro pacientes (20%) requirieron una derivación ventriculoperitoneal (DVP) y dos más fueron sometidos adicionalmente, a una tercer ventriculostomía endoscópica (ETV) (10%). El nivel funcional motor neonatal (NFN) fue mejor que el nivel anatómico prenatal (NAP) en 45% (9/20), igual en 50% (10/20) y peor en 5% (1/20). Conclusiones: El presente estudio confirma que la cirugía fetal de disrafias abiertas se asocia a un mayor riesgo de parto prematuro y rotura prematura de membranas, pero reduce significativamente la necesidad de tratamiento postnatal de hidrocefalia y mejora la función motora a corto plazo. Nuestros resultados son similares a los publicados en el ensayo aleatorizado MOMS.

Objective: To describe the surgical technique, obstetrical evolution and perinatal outcomes of a cohort of fetuses undergoing intrauterine surgery to repair open spina bifida (OSB). Methods: We performed a prospective analysis of 21 consecutive fetuses with OSB at our institution between 2015 and 2017. The surgical technique was similar to that described in the MOMS trial, except that the hysterotomy was performed using a bipolar dissector. Post-operative maternal and infant care both were provided at the same institution. There were no losses to follow-up. Surgical and obstetrical complications and perinatal outcomes were analyzed. Results: Fetal surgery was performed at a mean gestation of 25.8 weeks (24.1-27.6). The mean gestational age at birth was 34.2 weeks (29.2-37.1). The mean surgical time was 138 min (101-187), the duration of surgery trending downward over time; while the average admission length was 7.1 days (4-32). Fifty two percent (11/21) of the patients experienced pre-term premature rupture of membranes (pPROM). No patient required any post-cesarean transfusions. There were no instances of placental abruption, uterine rupture, or maternal death. Uterine scar healing was normal in 95% of the patients. All but one of the 21 fetuses (95%) survived, the one fetal death due to an amniotic band. The need for postnatal skin closure (PSC) was 5%, with one of 20 repaired prenatally with a synthetic skin patch. No case (19) repaired with fetal tissues required PSC. Seventy percent (14/20) of the infants required no further treatment for hydrocephalus over their first year of life; four patients (20%) required a ventriculoperitoneal shunt (VPS), while two others underwent an endoscopic third ventriculostomy (ETV) (10%). Neonatal motor function (NMF) was better than the prenatal anatomical level (PAL) in 45% (9/20), equal in 50% (10/20), and worse in 5% (1/20). Conclusions: Our data confirm that fetal surgery for OSB is associated with an increased risk of preterm delivery and PROM, but significantly reduces the need for postnatal treatment of hydrocephalus and improves short-term motor outcomes. Our results are similar to those published for the randomized MOMS trial.

[Fetal surgery for myelomeningocele: Obstetric evolution and short-term perinatal outcomes of a cohort of 21 cases]. / Cirugía fetal de mielomeningocele: Evolución obstétrica y resultados perinatales a corto plazo de una cohorte de 21 casos.

OBJECTIVE: The aim of this study is to describe the surgical technique, obstetrical evolution, and perinatal outcomes of a cohort of fetuses undergoing intrauterine surgery to repair open spina bifida (OSB). METHODS: We performed a prospective analysis of 21 consecutive fetuses with OSB at our institution between 2015 and 2017. The surgical technique was similar to that described in the management of myelomeningocele study (MOMS) (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00060606) trial, except that the hysterotomy was performed using a bipolar dissector. Postoperative maternal and infant care both were provided at the same institution. There were no losses to follow-up. Surgical and obstetrical complications and perinatal outcomes were analyzed. RESULTS: Fetal surgery was performed at a mean gestation of 25.8 weeks (24.1-27.6). The mean gestational age at birth was 34.2 weeks (29.2-37.1). The mean surgical time was 138 min (101-187), the duration of surgery trending downward over time; while the average admission length was 7.1 days (4-32). Fifty-two percent (11/21) of the patients experienced preterm premature rupture of membranes. No patient required any postcesarean transfusions. There were no instances of placental abruption, uterine rupture, or maternal death. Uterine scar healing was normal in 95% of the patients. All but one of the 21 fetuses (95%) survived; the one fetal death was due to an amniotic band. The need for postnatal skin closure was 5%, with one of 20 repaired prenatally with a synthetic skin patch. No case (19) repaired with fetal tissues required postnatal skin closure. Seventy percent (14/20) of the infants required no further treatment for hydrocephalus over their first year of life; four patients (20%) required a ventriculoperitoneal shunt, while two others underwent an endoscopic third ventriculostomy (10%). Neonatal motor function was better than the prenatal anatomical level in 45% (9/20), equal in 50% (10/20), and worse in 5% (1/20). CONCLUSIONS: Our data confirm that fetal surgery for OSB is associated with an increased risk of preterm delivery and premature rupture of membranes, but significantly reduces the need for postnatal treatment of hydrocephalus and improves short-term motor outcomes. Our results are similar to those published for the randomized MOMS trial.

Prenatal diagnosis of skeletal dysplasias: contribution of three-dimensional computed tomography.

OBJECTIVE: To describe the contribution of 3-dimensional computed tomography (3D-CT) in the prenatal diagnosis of skeletal dysplasias (SD) in a cohort of patients with inconclusive diagnosis by ultrasound (US). METHODS: Between May 2007 and February 2010, six pregnant women with suspected fetal SD on US examination but with no specific diagnosis were studied with 3D-CT. The images were evaluated by a multidisciplinary team who proposed a likely diagnosis. Further postnatal workup included clinical and radiological evaluation in all cases. Prenatal and postnatal diagnoses were compared. RESULTS: The use of 3D-CT provided a precise diagnosis confirmed postnatally in 5/6 patients. These included osteogenesis imperfecta type II (n = 2), osteogenesis imperfecta type III (n = 1), chondrodysplasia punctata (n = 1) and thanatophoric dysplasia type I (n = 1). A precise diagnosis could not be made in 1 case - either pre- or postnatally. CONCLUSION: Prenatal 3D-CT contributed to the diagnosis of the specific fetal SD in the majority of these cases. 3D-CT may have a complementary role to US where fetal SD is suspected, but no specific diagnosis can be made using US alone. Further studies on clinical performance and risk-benefit analysis are needed.

Maternal serum activin a at 11-13 weeks of gestation in hypertensive disorders of pregnancy.

OBJECTIVES: To investigate whether the maternal serum concentration of activin A at 11-13 weeks of gestation in pregnancies that subsequently develop hypertensive disorders is different from those with a normal outcome and to examine whether any possible differences are related to uterine artery pulsatility index (PI), serum pregnancy-associated plasma protein A (PAPP-A) and serum tumor necrosis factor-alpha receptor-1 (TNF-R1). MATERIAL AND METHODS: Serum activin A, TNF-R1, PAPP-A and uterine artery PI were determined in a case-control study of 126 cases that developed preeclampsia, 88 that developed gestational hypertension and 214 controls. RESULTS: In preeclampsia, compared to controls, uterine artery PI, serum activin A and serum TNF-R1 were higher and serum PAPP-A was lower. In gestational hypertension, compared to controls, serum activin A was higher but uterine artery PI, serum PAPP-A and serum TNF-R1 were not significantly different. There were no significant associations between serum activin A and either uterine artery PI or serum TNF-R1 in either the hypertensive groups or the controls. DISCUSSION: The data do not support the hypothesis linking activin A with impaired trophoblastic invasion of the maternal spiral arteries, placental hypoxia and the release of cytokines which in turn cause endothelial dysfunction and the development of the clinical symptoms of the disease.