Major Cardiac Malformations Research Articles

Risks of congenital malformations and neonatal intensive care unit admissions with gabapentin use in pregnancy: A cohort study and scoping review with meta-analysis.

The increasing and prevalent use of gabapentin among pregnant people highlights the necessity to assess its neonatal safety. This study aimed to investigate the foetal safety of gabapentin during pregnancy using a cohort study and scoping review with a meta-analysis of published evidence. We conducted a population-based cohort study using the Manitoba health databases between 1995 and 2019. We examined the association between gabapentin use during pregnancy and the prevalence of major congenital malformations, cardiac and orofacial malformations, and neonatal intensive care unit (NICU) admissions using multivariate regression models. We searched the literature in MEDLINE and EMBASE databases from inception to October 2022 to identify relevant observational studies and conducted a meta-analysis using random-effects models, including our cohort study results. Of the 289,227 included pregnancies, 870 pregnant people were exposed to gabapentin. Gabapentin exposure during the First trimester was not associated with an increased risk of any malformations (adjusted relative risk [aRR]) 1.16 (95%confidence interval [CI] 0.92, 1.46), cardiac malformations (aRR 1.29, 95% CI 0.72, 2.29), orofacial malformations (aRR 1.37, 95% CI 0.50, 3.75), and major congenital malformations (aRR 1.00, 95% CI 0.73, 1.36). whereas exposure during any trimester was associated with an increased NICU admission risk (aRR, 1.99, 95% CI 1.70, 2.32). The meta-analysis of unadjusted results revealed an increased risk of major congenital malformations (RR 1.44, 95% CI 1.28, 1.61, I2 = 0%), cardiac malformations (RR1.66, 95% CI 1.11, 2.47, I2 = 68%), and NICU admissions (RR 3.15, 95% CI 2.90, 3.41, I2 = 10%), and increased trend of orofacial malformations (RR 1.98, 95%CI 0.79, 5.00, I2 = 0%). Gabapentin use was associated with an increased risk of NICU admissions in the cohort study and pooled meta-analysis. Clinicians should prescribe gabapentin with caution during pregnancy and further studies are warranted.

Exposure of Pregnancy to Pregestational Diabetes, Gestational Diabetes, and Antidiabetic Medications With Especial Focus on Major Congenital and Cardiac Malformations in Offspring.

The global prevalence of type 2 diabetes mellitus (T2DM) is increasing. T2DM is more common in patients with psychiatric disorders and those who take certain psychotropic drugs. T2DM occurs in 2%-7% of women of reproductive age. The prevalence of pregestational diabetes is 0.5%-2.4%, and that of gestational diabetes is 7%-28%, depending on geographical region. About 20%-50% of pregnancies, across the world, are unplanned; this figure is higher, at about 65%, in women with psychiatric disorders. As a result, many women of reproductive age who have diabetes, including women who do not know that they have diabetes, may unintentionally become pregnant, thus unknowingly exposing their pregnancy to diabetes and its treatment. Exposure of pregnancy to pregestational and gestational diabetes is associated with risks to the mother as well as risks to the child. Risks to the mother include obesity, hypertension, and preeclampsia. Risks to the child include spontaneous abortion, fetal death, macrosomia, major congenital malformations (MCMs), preterm delivery, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal respiratory distress syndrome. A recent large retrospective cohort study with data from 6 countries in Europe, Asia, and North America found that, in about 51,000 women with pregestational T2DM, neither MCMs nor cardiac malformations were more prevalent in offspring of children periconceptionally exposed to second-line antidiabetic treatments relative to exposure to insulin. These findings are reassuring but have limitations that are discussed. A reasonable conclusion from a reading of the reviewed literature is that pregestational and gestational diabetes are best treated during pregnancy, that insulin is a first-line treatment, that metformin is an increasingly accepted alternative, and that safety data on second-line antidiabetic treatments are, so far, reassuring.

Esophageal Atresia Associated with Congenital Duodenal Obstruction: Turkish Esophageal Atresia Registry (TEAR) Evaluation.

Coexistent congenital duodenal obstruction and esophageal atresia (EA) is known to have significant morbidity and mortality. Management strategies are not well-defined for this association. The data from the Turkish EA registry is evaluated. A database search was done for the years 2015 to 2022. Among 857 EA patients, 31 (3.6%) had congenital duodenal obstruction. The mean birth weight was 2,104 (± 457) g with 6 babies weighing less than 1,500 g. Twenty-six (84%) had type C EA. The duodenal obstruction was complete in 15 patients and partial in 16. Other anomalies were detected in 27 (87%) patients. VACTERL-H was present in 15 (48%), anorectal malformation in 10 (32%), a major cardiac malformation in 6 (19%), and trisomy-21 in 3 (10%). Duodenal obstruction diagnosis was delayed in 10 (32%) babies for a median of 7.5 (1-109) days. Diagnosis for esophageal pathologies was delayed in 2. Among 19 babies with a simultaneous diagnosis, 1 died without surgery, 6 underwent triple repair for tracheoesophageal fistula (TEF), EA, and duodenal obstruction, and 3 for TEF and duodenal obstruction in the same session. A staged repair was planned in the remaining 9 patients. In total, 15 (48%) patients received a gastrostomy, the indication was long-gap EA in 8. Twenty-five (77%) patients survived. The cause of mortality was sepsis (n = 3) and major cardiac malformations (n = 3). Congenital duodenal obstruction associated with EA is a complex problem. Delayed diagnosis is common. Management strategies regarding single-stage repairs or gastrostomy insertions vary notably depending on the patient characteristics and institutional preferences.

ISUOG Practice Guidelines (updated): fetal cardiac screening.

ISUOG Practice Guidelines (updated): fetal cardiac screening.

Age-dependent changes in arterial blood pressure in neonates during the first week of life: reference values and development of a model

BackgroundArterial pressure measurements are important to monitor vital function in neonates, and values are known to be dependent of gestational and postnatal age. Current reference ranges for mean arterial pressure in neonates have been derived from small samples and combined data of noninvasive and invasive measurements. We aimed to define reference values for noninvasive mean, systolic, and diastolic blood pressure during the first week of life in otherwise healthy preterm and term neonates defined by gestational and postnatal age. MethodsIn this retrospective cohort study in a neonatal intensive care unit (NICU) in a Dutch tertiary paediatric hospital, we included the noninvasive blood pressures of neonates admitted between 2016 and 2018, with exclusion of those with severe comorbidities (major cardiac malformations, intracerebral haemorrhage, and tracheal intubation >6 h). We defined the median (P50) with −2 standard deviations (sd) (P0.23), −1 sd (P16), +1 sd (P84), and +2 sd (P97.7) for gestational age and postnatal age using quantile regression, percentiles provided online (http://bloodpressure-neonate.com/). ResultsA total of 607 neonates, with 5885 measurements, fulfilled the inclusion criteria. The P50 values of mean noninvasive arterial blood pressure in extreme preterm infants steeply increased during the first day after birth and gradually increased within a week from 27 to 49 mm Hg at 24 h of gestational age, and from 49 to 61 mm Hg at 41 weeks of gestational age. ConclusionsThese reference values for noninvasive blood pressure in neonates in the NICU for various gestational age groups provide guidance for clinical decision-making in healthy and diseased neonates during anaesthesia and sedation.

Isolated aortic arch anomalies are associated with defect severity and outcome in patients with congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) patients often have suspected isolated aortic arch anomalies (IAAA) on imaging. The purpose of this work was to describe the incidence and outcomes of CDH + IAAA patients. Cardiovascular data were collected for infants from the CDH Study Group born between 2007 and 2019. IAAA were defined as coarctation of aorta, hypoplastic aortic arch, interrupted aortic arch, and aortic aneurysmal disease on early, postnatal echocardiography. Patients with major cardiac malformations and/or chromosomal abnormalities were excluded. Primary outcomes included the rate of aortic intervention, rates of extracorporeal life support (ECLS) utilization, and mortality. Of 6357 CDH infants, 432 (7%) were diagnosed with a thoracic aortic anomaly. Of these, 165 were diagnosed with IAAA, most commonly coarctation of the aorta (n = 106; 64%) or hypoplastic aortic arch (n = 58; 35%). CDH + IAAA patients had lower birthweights (3kg vs. 2.9kg) and Apgar scores (7 vs. 6) than patients without IAAA (both χ2 p < 0.001). CDH + IAAA were less likely to undergo diaphragm repair (72 vs. 87%, p < 0.001), and overall mortality was higher for CDH + IAAA infants (58 vs. 24%, p < 0.001). When controlling for defect size, birth weight, and Apgar, IAAA were significantly associated with mortality (OR 3.3, 95% CI 2.2-5.0; p < 0.01) but not associated with ECLS (OR 0.98, 95% CI 0.65-1.50; p = 0.90). Only17% (n = 28) of CDH + IAAA patients underwent aortic intervention. IAAA in CDH are associated with increased mortality. This often simply reflects severity of the defect and thoracic anatomic derangement, as opposed to unique aortic pathology, givenfew CDH + IAAA patients undergo aortic intervention.

Prenatal Diagnosis, Associated Findings, and Postnatal Outcome in Fetuses with Double Inlet Ventricle (DIV).

To assess the spectrum of associated cardiac anomalies, the intrauterine course, and postnatal outcome of fetuses with double inlet ventricle (DIV). Retrospective analysis of prenatal ultrasound of 35 patients with DIV diagnosed between 2003 and 2021 in two tertiary referral centers in Germany. All fetuses underwent fetal echocardiography and a detailed anomaly scan. Postnatal outcome and follow-up data were retrieved from pediatric reports. 33 cases of DIV were correctly diagnosed prenatally. 24 fetuses (72.7%) had a double inlet ventricle with dominant left (DILV), 7 (21.2%) with dominant right ventricular morphology (DIRV), and 2 cases (6%) with indeterminate morphology (DIIV). 4 (16.6%) were Holmes hearts. 5 of the 7 fetuses (71.4%) with DIRV had a double outlet right ventricle (DORV). Malposition of the great arteries was present in 84.8%. Chromosomal abnormalities were absent. Termination of pregnancy was performed in 8 cases (24.2%). 24 fetuses (72.7%) were live-born. 5 (20.8%) were female and 19 (79.2%) were male. The median gestational age at birth was 38+2.5 weeks. All but one child received univentricular palliation. The median follow-up time was 5.83 years with an adjusted survival rate of 91.6% (22 of 24 live-born children). There was one case of Fontan failure at 15.7 years. DIV remains a major cardiac malformation although both prenatal diagnostics and cardiac surgery have improved over the years. The course of pregnancy is commonly uneventful. All children need univentricular palliation. The children are slightly physically limited, develop a normal intellect, and attend school regularly.

Hospital Survival After Surgical Repair of Truncus Arteriosus with Interrupted Aortic Arch: Results from a Multi-institutional Database.

Truncus arteriosus (TA) is a major congenital cardiac malformation that requires surgical repair in the first few weeks of life. Interrupted aortic arch (IAA) is an associated malformation that significantly impacts the complexity of the TA operation. The aim of this study was to (1) define the comorbid conditions associated with TA and (2) determine the hospital survival and morbidity of patients with TA with and without an IAA. Data was collected from the Vizient Clinical Database/Resource Manager, formerly University HealthSystem Consortium, which encompasses more than 160 academic medical centers in the United States. The database was queried for patients admitted from 2002 to 2016 who were ≤ 4months of age at initial admission, diagnosed with TA, and underwent complete surgical repair during that hospitalization. Of the 645 patients with TA who underwent surgery, 98 (15%) had TA with an interrupted aortic arch (TA-IAA). Both TA and TA-IAA were associated with a high prevalence of comorbidities, including DiGeorge syndrome, prematurity, and other congenital malformations. There was no difference in mortality between TA and TA-IAA (13.7-18.4%, p value = 0.227). No comorbid conditions were associated with an increased mortality in either group. However, patients with TA-IAA had a longer post-operative length of stay (LOS) compared to those without IAA (30 versus 40.3days, p value = 0.001) and this effect was additive with each additional comorbid condition. In conclusion, the addition of IAA to TA is associated with an increased post-operative LOS, but does not increase in-hospital mortality.

Prenatal Antidepressant Use and Risk of Adverse Neonatal Outcomes.

To estimate the risk of neonatal outcomes from patterns of prenatal antidepressant use. From the OptumLabs Data Warehouse, 226 932 singleton deliveries were identified. Antidepressant claims with coverage between the last menstrual period and 35 weeks' gestation were converted to fluoxetine equivalents, and a longitudinal cluster analysis was performed. Outcomes included major cardiac malformations (11.7 of 1000 births), preterm birth (75.7 of 1000 births), and newborn respiratory distress (54.2 of 1000 births). The lowest trajectory was the primary reference group, and depression and anxiety with no antidepressant claims served as secondary reference groups. From 15 041 (6.6%) pregnancies exposed to an antidepressant, use patterns were best described as (1) low use (∼10 mg/day) with first-trimester reduction, (2) low sustained use (∼20 mg/day), (3) moderate use (∼40 mg/day) with first-trimester reduction, (4) moderate sustained use (∼40 mg/day), and (5) high sustained use (∼75 mg/day). Moderate sustained use increased the risk of major cardiac malformations, although results included the null when compared with depression or anxiety reference groups. Moderate sustained (adjusted risk ratio [RR] 1.31; 95% confidence interval [CI] 1.16-1.49) and high sustained (adjusted RR 1.78; 95% CI 1.48-2.14) trajectories were associated with an increased risk of preterm birth. All 4 trajectories increased the risk of neonatal respiratory distress in a dose-response fashion (adjusted RRs 1.36 [95% CI 1.20-1.50] to 2.23 [95% CI 1.83-2.77]). Although findings support continuation of the lowest effective dose to treat depression or anxiety, which benefits the mother, they also highlight an increased risk for newborn respiratory distress in all groups and preterm birth at moderate to high sustained doses.

In utero exposure to antibiotics and risk of congenital malformations: a population-based study

Antibiotics are commonly prescribed during pregnancy. Although the safety of most penicillins is well established, some controversy and uncertainty are associated with the use of other commonly prescribed antibiotics. To determine the risk of congenital malformations following first-trimester in utero exposure to 10 commonly prescribed antibiotics in Denmark. This was a cohort study comprising all singleton liveborn children in Denmark between 2000 and 2015. Data on malformations were collected through 2016. Merging validated and comprehensive populationwide Danish healthcare and civic registries, we merged data on pregnancy, prescription drugs purchases during first trimester and congenital malformations. Using logistic regression, we calculated the odds ratio for congenital malformations (any), major congenital malformations, and cardiac congenital malformations for the 10 most commonly prescribed antibiotics (excluding 4 penicillins that served as control). In the primary analysis, the exposed cohort was compared to a cohort exposed to any of 4 penicillins considered safe during pregnancy (ampicillin, pivampicillin, benzylpenicillin, and phenoxymethylpenicillin). In sensitivity analysis, the exposed cohort was compared to an unexposed cohort. Covariate adjustments were made for maternal age at delivery, year of delivery, parity, pre-pregnancy body mass index, smoking, educational status, employment status, and annual personal income. We found no increased risk of congenital malformations to be related to first-trimester in utero exposure to the 10 most commonly prescribed antibiotics in Denmark compared to a cohort of pregnant women exposed to penicillins that are considered safe during pregnancy. Compared to unexposed pregnancies, small increased risks for major malformations and cardiac malformations were apparent for pivmecillinam (odds ratio, 1.13; confidence interval, 1.06-1.19; and odds ratio, 1.15; confidence interval, 1.04-1.28, respectively), sulfamethizole (odds ratio, 1.15; confidence interval, 1.07-1.24; and odds ratio, 1.22; confidence interval, 1.07-1.39, respectively), and azithromycin (odds ratio, 1.19, confidence interval, 1.03-1.38; and odds ratio, 1.29, confidence interval, 0.99-1.67, respectively). In this large populationwide cohort study, we found, with a high degree of precision, no increased risk of congenital malformations following first-trimester exposure to 10 commonly prescribed systemic antibiotics.

Retrocolic isoperistaltic gastrojejunostomy as an alternative to Kimura's duodenoduodenostomy in low- and very low-birth-weight babies of duodenal atresia: A 5 year retrospective study

Background: Duodenal atresia is a frequent occurrence in babies requiring emergent surgical intervention. Conventionally, Kimura's diamond duodenoduodenostomy has been considered as the gold standard. However, in low-birth-weight (LBW), very LBW (VLBW), and extremely LBW (ELBW) babies, we have found it to be a procedure that is not well tolerated and resulted in mortality. In these conditions, a retrocolic isoperistaltic gastrojejunostomy is well tolerated by patients. Most of the patients that public hospitals cater to are from the lower socioeconomic strata belonging to poor families, immigrant population, and daily wagers. Aim: The aim of the study is to evaluate gastrojejunostomy as an alternative to Kimura's duodenoduodenostomy in LBW, VLBW, and ELBW neonates having duodenal atresia without major cardiac malformations. Materials and Methods: We did a retrospective analysis of all patients with birth weight

β-Blocker Use in Pregnancy and the Risk for Congenital Malformations: An International Cohort Study.

β-Blockers are a class of antihypertensive medications that are commonly used in pregnancy. To estimate the risks for major congenital malformations associated with first-trimester exposure to β-blockers. Cohort study. Health registries in the 5 Nordic countries and the U.S. Medicaid database. Pregnant women with a diagnosis of hypertension and their offspring. First-trimester exposure to β-blockers was assessed. Outcomes were any major congenital malformation, cardiac malformations, cleft lip or palate, and central nervous system (CNS) malformations. Propensity score stratification was used to control for potential confounders. Of 3577 women with hypertensive pregnancies in the Nordic cohort and 14900 in the U.S. cohort, 682 (19.1%) and 1668 (11.2%), respectively, were exposed to β-blockers in the first trimester. The pooled adjusted relative risk (RR) and risk difference per 1000 persons exposed (RD1000) associated with β-blockers were 1.07 (95% CI, 0.89 to 1.30) and 3.0 (CI, -6.6 to 12.6), respectively, for any major malformation; 1.12 (CI, 0.83 to 1.51) and 2.1 (CI, -4.3 to 8.4) for any cardiac malformation; and 1.97 (CI, 0.74 to 5.25) and 1.0 (CI, -0.9 to 3.0) for cleft lip or palate. For CNS malformations, the adjusted RR was 1.37 (CI, 0.58 to 3.25) and the RD1000 was 1.0 (CI, -2.0 to 4.0) (based on U.S. cohort data only). Analysis was restricted to live births, exposure was based on dispensed medication, and cleft lip or palate and CNS malformations had few outcomes. The results suggest that maternal use of β-blockers in the first trimester is not associated with a large increase in the risk for overall malformations or cardiac malformations, independent of measured confounders. The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Söderström König Foundation.

Maternal and infant outcomes associated with lithium use in pregnancy: an international collaborative meta-analysis of six cohort studies

Concerns about teratogenicity and maternal and offspring complications restrict the use of lithium during pregnancy for the treatment of mood disorders. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity, and congenital malformations. In this meta-analysis, primary data from pregnant women and their children from six international cohorts based in the community (Denmark, Sweden, and Ontario, Canada) and in clinics (the Netherlands, UK, and USA) were analysed. Pregnancies were eligible for analysis if the pregnancy resulted in a liveborn singleton between 1997 and 2015, if health-related information was available for both mother and infant, and if the mother had a mood disorder (bipolar disorder or major depressive disorder) or if she had been given lithium during pregnancy (at least two dispensations of lithium during pregnancy that were dispensed any time from 1 month before conception until the delivery, or a single lithium dispensation during pregnancy when there was at least one other lithium dispensation within 6 months before or after this date). Pregnancies during which the mother had been prescribed known teratogenic drugs were excluded. Pregnancies were grouped into a lithium-exposed group and a mood disorder reference group. The main outcome measures were pregnancy complications, delivery outcomes, neonatal readmission to hospital within 28 days of birth, and congenital malformations (major malformations and major cardiac malformations). Analyses were done at each site by use of a shared protocol. Adjusted odds ratios (aORs) and 95% CIs were calculated by use of logistic regression models, and site-specific prevalence rates and ORs were pooled by use of random-effects meta-analytical models. 22 124 eligible pregnancies were identified across the six cohorts, of which 727 pregnancies were eligible for inclusion in the lithium-exposed group (557 [77%] from register-based cohorts and 170 [23%] from clinical cohorts). Lithium exposure was not associated with any of the predefined pregnancy complications or delivery outcomes. An increased risk for neonatal readmission within 28 days of birth was seen in the lithium-exposed group compared with the reference group (pooled prevalence 27·5% [95% CI 15·8-39·1] vs 14·3% [10·4-18·2]; pooled aOR 1·62, 95% CI 1·12-2·33). Lithium exposure during the first trimester was associated with an increased risk of major malformations (pooled prevalence 7·4% [95% CI 4·0-10·7] vs 4·3% [3·7-4·8]; pooled aOR 1·71, 95% CI 1·07-2·72) but for major cardiac malformations the difference was not significant (2·1% [0·5-3·7] vs 1·6% [1·0-2·1]; pooled aOR 1·54, 95% CI 0·64-3·70). Considering both the effect sizes and the precision of the estimates in this meta-analysis, treatment decisions for pregnant women with mood disorders must weigh the potential for increased risks of lithium during pregnancy-in particular those associated with use of lithium during the first trimester-against its effectiveness at reducing relapse. None.

Managing fertile women under lithium treatment: the challenge of a Teratology Information Service.

The objective of the present study is to review the literature regarding the management of fertile patients under lithium treatment for bipolar disorder and to report the experience of our Teratology Information Service over the past thirteen years in managing women treated with lithium during preconception, pregnancy and breastfeeding. This research focuses on a selective review of the literature and a retrospective survey has been carried out on fertile women under lithium treatment who called our service at A. Gemelli University Hospital in Rome from May 2002 to December 2015. A total of 140 women under lithium treatment called our TIS. A complete follow-up has been performed on 34 patients: 29 called during pregnancy and 5 called during preconception. None of the patients called during breastfeeding, while half of the patients were taking concomitant drugs during pregnancy. One major cardiac malformation (hypoplastic left heart syndrome) has been reported. No minor malformations have been detected. Twenty-one patients delivered a living child, with one premature neonate. Two patients underwent voluntary interruption of pregnancy and six patients had early spontaneous abortion. In one patient, intrauterine growth retardation occurred, but with no adverse neonatal outcomes. Four neonates experienced transient respiratory distress at birth. Two children developed mild to severe language delay, but normal motor development. Lithium treatment in fertile women is a very delicate topic, where risks and benefits of discontinuing therapy when women plan to become pregnant should be accurately evaluated. Thorough peri-conceptional counselling is crucial for the outcome of pregnancy and for maternal health status during preconception, gestation and breastfeeding.

Prenatally versus postnatally diagnosed congenital diaphragmatic hernia – Side, stage, and outcome

AimTo compare outcomes between prenatally and postnatally diagnosed CDH in a large multicenter database of prospectively collected data and evaluate factors associated with poorer outcome for prenatally diagnosed CDH. Material and MethodsWe used information from the multicenter, multinational CDH Study Group database on patients born between 2007 and 2015. We compared differences between prenatally and postnatally diagnosed CDH with respect to survival, side, size, ECMO needs, associated major cardiac malformations and liver position. Results3746 cases of CDH were entered in the registry between 2007 and 2015, with an overall survival of 71%. Of those, 68% had a prenatal diagnosis. Survival rates were significantly better in the postnatally diagnosed group, 83 vs 65%. There was a higher proportion of bigger defect sizes, C and D, in the prenatally diagnosed group, but the survival rates were similar when patients were stratified by defect size. The rate of ECMO utilization was higher overall in the prenatally diagnosed group, 33 vs 22%, but it was similar within similar defect sizes. Right-sided defects are more commonly missed at prenatal screening than left-sided CDH, 53 vs 35% (p < 0.0001). ConclusionsPrenatally diagnosed CDH is associated with larger defect sizes compared to those with a postnatal diagnosis, and consequently have higher morbidity and mortality. Right-sided CDH are more often missed at prenatal ultrasound. The increasing rate of prenatal detection requires a clear understanding of accurate risk stratification, in order to counsel families and to provide appropriate perinatal management. Level of EvidenceI for a Prognosis Study – This is a high-quality, prospective cohort study with 99% of patients followed to the study end point (death or discharge).

Neurodevelopmental outcomes of infants with esophageal atresia and tracheoesophageal fistula

BackgroundEsophageal atresia with or without tracheoesophageal fistula (EA/TEF) is a complex disorder, and most outcome data are confined to mortality and feeding-related morbidities. Our objective was to examine mortality, growth and neurodevelopmental outcomes in a large recent cohort of infants with EA/TEF. MethodsSingle center study of EA/TEF infants referred from January 2000 to December 2015. Data collected included associated defects, neonatal morbidity and mortality and growth and neurodevelopmental outcomes at age 12–36months. Multiple regression analysis was used to determine variables associated with adverse outcome. ResultsOf the 253 infants identified, 102 infants (40%) were preterm. Overall mortality was 8.3%, the majority from major cardiac malformations (p<0.001) Neurodevelopmental assessments (n=182) showed that 76% were within normal, while some delay was seen in 24%, most often in expressive and receptive language. Nine infants had hearing impairment and 5 had visual impairment. Gastrostomy tubes were required in 47 patients and 15% continued to have weight growth velocities less than the 10th centile. A number of specialist interventions were required, Speech/Language being frequent. ConclusionMortality in EA/TEF is primarily related to concomitant anomalies, especially cardiac. Multidisciplinary follow up is important for early identification and intervention for growth failure and developmental delay. Type of studyRetrospective study Level of evidenceLevel II

Tracheoesophageal fistula in sibilings - A rare occurence

Introduction Esophageal atresia is one of the most common congenital malformations occurring in 1 in every 2000-4000 live births. Previously considered to be a fatal condition, it has now become an eminently treatable condition with survival limited only by the presence or absence of major cardiac malformations. For the majority of families, the condition is unique to one child which in itself is challenging. It is extremely rare to affect more than one sibling in any family. The risk of recurrence is 0.5-2% and rises to 20% if another sibling is affected. Case description We report on two siblings, born two years apart with Type C TOF who were treated at King Hamad University Hospital, Bahrain. The first sibling was born with a short gap esophageal atresia with a distal fistula and repaired shortly after birth in another institution. The second sibling was born with a more challenging long gap esophageal atresia also with a distal fistula. The fistula was ligated on the second day of life and a gastrostomy tube put in place for feeding; repair of the atresia took place 2 months later. Both patients underwent serial dilatations to overcome strictures but are both tolerating oral diets. The third sibling in the family was unaffected with TOF or any VACTREL association. Conclusion The etiology of TOF is multifactorial with genetic, environmental and unknown components. There were no known environmental factors which could have contributed to this rare occurrence, but the only factor of significance is consanguinity of the parents who are first cousins. On the other hand, genetic factors are responsible for 12% of cases, these are classified as Chromosomal mutations, Syndromic or Isolated. These siblings do not fall into any of the mentioned categories and it is therefore speculated that this occurrence is due to a sporadic mutation. Take-home message Esophageal atresia with or without fistula is a fairly common condition encountered by paediatric surgeons on a daily basis. Despite increased experience and advancements in management of complex cases, the etiology remains a mystery. Future research should focus on more in-depth genetic studies on the impact of co-sanguinity on sibling TOFs.

P27.09: Diagnostic accuracy of basic fetal heart examination at 11–13 weeks' gestation of pregnancy

Investigate the diagnostic performance of a simplified fetal heart examination in a routine setting of first trimester ultrasound screening for aneuploidies. This was a prospective observational study, in which a basic cardiac examination applying the cross-sections of the 4-chamber and/or 3-vessels views using colour Doppler was performed at the 11 to 13 weeks' gestation scan in a routine setting in single pregnancies. A total of 1850 single fetuses performed first and second trimester ultrasound scans between January 1st 2016 and January 13th 2017. Overall, 1799 cases with second trimester scan, echocardiography or autopsy findings were included. In 1177 cases (65.4%) basic heart examination was not performed during first trimester because of difficult fetal position, maternal obesity with inadequate visualisation of the heart structures or when the examiner was not comfortable with early heart examination. Patients with incomplete anatomy scan at second trimester and with unknown outcome were excluded. In 622 cases (34.5%) a basic cardiac examination applying the cross-sections of the 4-chamber and / or 3-vessels views using colour Doppler was carried out. In total, there were 16 cases with a confirmed congenital heart defect (0.89%) and 16 cases of fetuses with chromosomal abnormalities. Evaluation by the 4-chamber and/ or 3 vessels view had a sensitivity and specificity of 66.7% and 99.5% respectively, with a positive and negative predictive values of 85.7% and 99.5%, respectively. Overall, at our unit, 37.5% of the cardiac malformations were detected at first trimester scan. Major heart anomalies such as hypoplastic left heart syndrome, pulmonary hypoplasia, transposition of the great vessels and atrioventricular septal defect were depicted at the 11-13 weeks' scan by performing basic heart evaluation. Basic heart views allow for selection of 67% cases with major cardiac malformations at the 11 to 13 weeks' routine ultrasound scan, providing the option for early confirmation by echocardiography.

Isolated tracheoesophageal fistula versus esophageal atresia – Early morbidity and short-term outcome. A single institution series

PurposeWe compared the postnatal course, morbidity and early results after repair for cases of isolated or “pure” TEF with those for cases of esophageal atresia (EA) with distal tracheoesophageal fistula (TEF). MethodsTwenty-four consecutive infants were divided into two groups: isolated TEF [TEF group] (n = 5) and EA with distal TEF [EA group] (n = 19). Results. A high rate of prematurity (29%) and major cardiac and other surgically-relevant malformations (0.8 vs. 0.7 per infant) was found in both groups. The median age at surgery was 8 days for the TEF group vs. 1 day for the EA group (p < 0.01). Most infants of both cohorts had stable acid-base and respiratory parameters at admission. Generally, tracheoscopy provided valuable information regarding the position of the TEF. Surgery for isolated TEF was performed via right cervicotomy in 4 cases and via thoracotomy in one. Postoperative thoracostomy tubes were inserted in 3 cases and one emergency gastrostomy was created for acute gastric overextension (exclusively in patients with EA). The duration of postoperative mechanical ventilation (49 vs. 113 h, p = 0.045) and the median length of stay in the pediatric surgery unit (10 vs. 20.5 days, p = 0.003) were shorter for the isolated TEF group. Four EA patients experienced severe events. Total mortality was 8% (0 out of 5 with TEF vs. 2 out of 19 with EA). ConclusionDevelopmental delay and a high rate of morbidity were found in both groups. More complex surgery increased perioperative morbidity in cases of EA. With early recognition of isolated TEF, a less complicated course can be expected in comparison with esophageal atresia.

The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis.

The aim of this study was to perform an up-to-date meta-analysis on the risk of cardiac malformations associated with gestational exposure to paroxetine, taking into account indication, study design and reference category. A systematic review of studies published between 1966 and November 2015 was conducted using embase and MEDLINE. Studies reporting major malformations with first trimester exposure to paroxetine were included. Potentially relevant articles were assessed and relevant data extracted to calculate risk estimates. Outcomes included any major malformations and major cardiac malformations. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models. Twenty-three studies were included. Compared with non-exposure to paroxetine, first trimester use of paroxetine was associated with an increased risk of any major congenital malformations combined (pooled OR 1.23, 95% CI 1.10, 1.38; n=15 studies), major cardiac malformations (pooled OR 1.28, 95% CI 1.11, 1.47; n=18 studies), specifically bulbus cordis anomalies and anomalies of cardiac septal closure (pooled OR 1.42, 95% CI 1.07, 1.89; n=8 studies), atrial septal defects (pooled OR 2.38, 95% CI 1.14, 4.97; n=4 studies) and right ventricular outflow track defect (pooled OR 2.29, 95% CI 1.06, 4.93; n=4 studies). Although the estimates varied depending on the comparator group, study design and malformation detection period, a trend towards increased risk was observed. Paroxetine use during the first trimester of pregnancy is associated with an increased risk of any major congenital malformations and cardiac malformations. The increase in risk is not dependent on the study method or population.