Major Anomalies Research Articles

Clinico-epidemiological and genomic profile of first Zika Virus outbreak in India at Jaipur city of Rajasthan state

BackgroundFirst Zika virus (ZIKV) positive case from North India was detected on routine surveillance of Dengue-Like Illness in an 85-year old female. Objective of the study was to conduct an investigation for epidemiological, clinical and genomic analysis of first ZIKV outbreak in Rajasthan, North India and enhance routine ZIKV surveillance. MethodOutbreak investigation was performed in 3 Km radius of the index case among patient contacts, febrile cases, and pregnant women. Routine surveillance was enhanced to include samples from various districts of Rajasthan. Presence of ZIKV in serum and urine samples was detected by real time PCR test and CDC trioplex kit. Few ZIKV positive samples were sequenced using the next-generation sequencing method for genomic analysis. ResultOn outbreak investigation 153/2043 (7.48%) cases were found positive: 1/153 (0.65%) among contacts, 90/153 (58.8%) in fever cases, 62/153(40.5%) in pregnant females. In routine surveillance, 6/4722 (0.12%) serum samples were ZIKV positive.Majority of patients had mild signs and symptoms, no case of microcephaly and Guillain- Barre Syndrome was seen, 25 (40.3%) pregnant females delivered healthy babies, four (6.4%) reported abortion and three (4.8%) had intrauterine death, one (1.6%) child had colorectal malformation and died after few days of birth. ZIKV was found to belong to Asian lineage, mutation related to enhanced neuro-virulence and transmission in animal models was not found. ConclusionZIKV was endogenous to India belonging to Asian Lineage. Disease profile of the ZIKV was asymptomatic to mild. No major anomaly was observed in infants born to ZIKV positive mothers; however, long term follow up of these children is required. There is need to scale up surveillance in the virology lab network of India for early detection and control. Summary lineZika virus infection was endogenous due to Asian Lineage with mild disease, no case of microcephaly or Guillain- Barre Syndrome was seen but children need to be followed for anomalies and surveillance of ZIKV needs to be enhanced in the country.

Dandy-Walker Malformation

Dandy-Walker Malformation

Intracranial Hemorrhage

Intracranial Hemorrhage

A Matter of Time: Does Gestational Age Affect the Duration of the Fetal Anatomic Survey?

To assess the average duration of detailed fetal anatomic surveys in pregnancy in relation to gestational age (GA) and the maternal body mass index (BMI) to determine optimal timing of the examination. This was a retrospective cohort study of gravidae presenting for detailed fetal anatomic examinations between January 1, 2010, and June 30, 2017. After excluding examinations expected to have longer duration (ie, multifetal, major fetal anomalies), there were a total of 6522 examinations performed between GAs of 18 weeks 0 days and 22 weeks 0 days. Women were grouped by BMI, and results were analyzed by logistic regression. Gravidae of normal weight (BMI, 18.5-24.9 kg/m2 ) had a decrease of 47.47 seconds of the examination time with each increasing week of gestation (P=.036). Overweight (BMI, 25-29.9 kg/m2 ) gravidae similarly had a decrease of 66.31 seconds of the examination time with each additional week of gestation (P=.017). Underweight (BMI, 8.5 kg/m2 ) and obese (BMI, ≥30 kg/m2 ) gravidae did not have differences in the examination time with increasing GA. Increases in suboptimal examinations were noted with an increasing BMI (P < .001). There was a decreased frequency of suboptimal examinations in obese gravidae with a BMI of 40 kg/m2 or higher with increasing GA (P=.037). The duration of detailed fetal anatomic examinations decreased with increasing GA in normal-weight and overweight gravidae but not in obese gravidae. Performing the anatomy scan earlier in class I and II obese gravidae (BMI, 30-40 kg/m2 ) may enable improved pregnancy management options without increasing the examination duration or likelihood of a suboptimal evaluation.

In Utero Stem Cell Transplantation in Patients with Alpha Thalassemia Major: Interim Results of a Phase 1 Clinical Trial

Introduction: In utero hematopoietic cell transplantation (IUHCT) has the potential to treat patients with blood disorders by taking advantage of bidirectional maternal-fetal tolerance during pregnancy. Although engraftment has only been seen in immunodeficient patients in the past, recent preclinical studies indicate that a higher dose of maternal cells should be given intravascularly to maximize engraftment in other settings. We hypothesized that: 1) fetuses will tolerate a maternal IUHCT without conditioning and develop low engraftment with sustained tolerance to maternal alloantigens; and 2) tolerant patients could receive a postnatal booster maternal transplant with minimal immunoablative conditioning and thereby achieve a cure. To test the first of these hypotheses in a controlled setting, we have initiated a phase 1 clinical trial of IUHCT in fetuses with alpha thalassemia major (ATM), who already require a fetal intervention (in utero transfusions (IUT)) to survive the pregnancy. We present interim results from the first two patients. Methods: After obtaining IND approval, we initiated the clinical trial in 2017 (NCT02986698). Fetuses with ATM between 18-26 weeks' gestation without other major anomalies were included. To date, we have evaluated 19 patients for possible inclusion: 15 patients terminated the pregnancy, 2 patients were outside the inclusion window and underwent IUT alone, and 2 have been transplanted and completed the 1 year follow up. For IUHCT, 300 ml of maternal bone marrow was harvested, CD34+ cells were selected and transplanted fresh into the fetus via the umbilical vein, along with a standard IUT. IUTs were repeated every 3 weeks until delivery. Maternal cell chimerism was detected using qRT-PCR for non-inherited maternal HLA-DR alleles on sorted cell populations in cord blood and after birth. Mixed lymphocyte reactions (MLRs) were performed by culturing CFSE-labeled host CD4 and CD8 responder cells with maternal (or third-party) derived antigen presenting cells (APC; direct pathway) or self APC/maternal lysate (indirect pathway). Results: Both fetuses were diagnosed with severe hydrops on ultrasound and received an initial IUT prior to the IUHCT. Patient 1 was transplanted at 23 weeks with 1x 108CD34+ cells/kg + 1 x 107T cells/kg and Patient 2 was transplanted at 25 weeks with 5x 107CD34+ cells/kg + 5 x 106T cells/kg; both received 4 more IUTs until birth. Prenatal hydrops resolved in both and neonatal hospitalizations were 16 and 13 days, respectively. Maternal chimerism was detected in both patients, but levels were higher and persisted throughout the year only in patient 1 (Fig 1A). We detected 70-fold higher levels of erythrocyte precursors (Fig 1B) but normal levels of CD34+ cells in the cord blood of patients compared to healthy controls, highlighting a potential barrier to engraftment in a disease with prenatal hypoxia. Patient 1 demonstrated sustained tolerance to maternal antigens by MLR throughout the year, whereas patient 2 showed reactivity against maternal antigens (Fig 1C). HLA antibodies were negative in both. Based on the finding of donor-specific tolerance in patient 1, we offered a booster transplant with maternal cells but the parents declined. Both patients are undergoing monthly transfusions and have had normal development and Bayley neurologic testing at 1 year. There were no unanticipated safety events in either mother/child pair. Conclusions: These results demonstrate the safety of IUHCT in fetuses with ATM and the potential of fetal transplantation in the second trimester to sustain tolerance to maternal cells after birth. Low engraftment levels are predicted in the setting of host hyperproliferation and lack of space-making conditioning, confirming the need for a two-step strategy (IUHCT and postnatal booster transplant) for a definitive cure. The earlier transplantation in patient 1 enabled a higher dose of cells and may explain the improved outcome observed. Implementation of earlier screening in at-risk patient groups could allow earlier diagnosis and enrollment in the future. Although parents of fetuses with ATM are commonly counseled for pregnancy termination due to concern for poor outcomes, our results indicate that fetal therapy with IUTs can result in survival to term and excellent quality of life. This strategy of maternal IUHCT could be employed to treat fetuses with other hematologic disorders in the future. Figure 1 Disclosures MacKenzie: Acrigen: Membership on an entity's Board of Directors or advisory committees; Ultragenyx: Research Funding. Vichinsky:Global Blood Therapeutics: Consultancy; Agios: Research Funding; Pfizer: Research Funding.

Comparison of outcomes of infants with giant omphaloceles over two decades.

The purpose of this study was to compare the outcomes of infants with giant omphalocele (GO) born in two different epochs over two decades at a single institution. Specifically, it examined whether the utilization of selective pulmonary vasodilators and extracorporeal membrane oxygenator (ECMO) in the management of pulmonary hypertension in the second epoch were associated with improved outcomes. The medical records of all patients diagnosed with GO at a large children's hospital from January 1, 1996 to December 31, 2016 were reviewed and divided into two epochs. Patients were classified as having an isolated GO or GO with minor or major associated anomalies. GO was defined as a defect more than or equal to 5 cm in size and/or liver in the sac. During the study period, 59 infants with GO were identified. The duration of invasive mechanical ventilation was significantly shorter among the survivors from the second epoch (p = 0.03), with none greater than seven days. There were no significant differences in the outcomes of survival to NICU discharge and length of stay (LOS) between infants in the two epochs. Infants with GO who required invasive mechanical ventilation for more than seven days did not survive in the second epoch. Survival did not improve with use of selective pulmonary vasodilators and ECMO. This information could be shared with families during prenatal and postnatal counselling to facilitate informed decision making regarding goals of care.

A STUDY ON SPECTRUM OF CONGENITALANOMALIES DELIVERED IN A TERTIARY CARE CENTER

INTRODUCTION: Congenital anomaliesaccount for 9% of neonatal deaths in India. Prevalence of birth anomalies in India is 6-7%. AIMS AND OBJECTIVES: The objective was to determine proportion and clinical spectrum of congenital anomalies and maternal and perinatal risk factors associated with congenital anomalies in live newborns in our area. MATERIALS AND METHODS: Neonates born in ALLURI SITARAMA RAJU ACADEMY OF MEDICAL SCIENCES hospital during study period with documented congenital anomalies are included. All still-borns and gestational age &lt;22wks &amp; birth weight &lt;400gm were excluded. Retrospective hospital-based study, conducted between January 2019 to December 2019 in ASRAM Hospital. RESULTS: The total number of births is 1132 during this one year of which, 106 newborns had congenital anomalies. In this study we found that major anomalies (80.2%) , Minor anomalies (19.8%).In this study we found that most of the anomalies were major and mostly involved cardiovascular system. In minor anomalies the most common defect was sacral dimple. CONCLUSION: Congenital anomalies can be reduced with in-utero surgeries, and necessary preventive measures which are becoming feasible.

Biliary-Atresia-Associated Mannosidase-1-Alpha-2 Gene Regulates Biliary and Ciliary Morphogenesis and Laterality.

Background/AimsInfectious and genetic factors are invoked, respectively in isolated biliary atresia (BA), or syndromic BA, with major extrahepatic anomalies. However, isolated BA is also associated with minor extrahepatic gut and cardiovascular anomalies and multiple susceptibility genes, suggesting common origins.MethodsWe investigated novel susceptibility genes with genome-wide association, targeted sequencing and tissue staining in BA requiring liver transplantation, independent of BA subtype. Candidate gene effects on morphogenesis, developmental pathways, and ciliogenesis, which regulates left-right patterning were investigated with zebrafish knockdown and mouse knockout models, mouse airway cell cultures, and liver transcriptome analysis.ResultsSingle nucleotide polymorphisms in Mannosidase-1-α-2 (MAN1A2) were significantly associated with BA and with other polymorphisms known to affect MAN1A2 expression but were not differentially enriched in either BA subtype. In zebrafish embryos, man1a2 knockdown caused poor biliary network formation, ciliary dysgenesis in Kupffer’s vesicle, cardiac and liver heterotaxy, and dysregulated egfra and other developmental genes. Suboptimal man1a2 knockdown synergized with suboptimal EGFR signaling or suboptimal knockdown of the EGFR pathway gene, adenosine-ribosylation-factor-6, which had minimal effects individually, to reproduce biliary defects but not heterotaxy. In cultured mouse airway epithelium, Man1a2 knockdown arrested ciliary development and motility. Man1a2–/– mice, which experience respiratory failure, also demonstrated portal and bile ductular inflammation. Human BA liver and Man1a2–/– liver exhibited reduced Man1a2 expression and dysregulated ciliary genes, known to cause multisystem human laterality defects.ConclusionBA requiring transplantation associates with sequence variants in MAN1A2. man1a2 regulates laterality, in addition to hepatobiliary morphogenesis, by regulating ciliogenesis in zebrafish and mice, providing a novel developmental basis for multisystem defects in BA.

Urinary tract infections in very low birthweight infants: A two-center analysis of microbiology, imaging and heart rate characteristics.

Increased understanding of characteristics of urinary tract infection (UTI) among very low birthweight infants (VLBW) might lead to improvement in detection and treatment. Continuous monitoring for abnormal heart rate characteristics (HRC) could provide early warning of UTIs. Describe the characteristics of UTI, including HRC, in VLBW infants. We reviewed records of VLBW infants admitted from 2005-2010 at two academic centers participating in a randomized clinical trial of HRC monitoring. Results of all urine cultures, renal ultrasounds (RUS), and voiding cystourethrograms (VCUG) were assessed. Change in the HRC index was analyzed before and after UTI. Of 823 VLBW infants (27.7±2.9 weeks GA, 53% male), 378 had > / = 1 urine culture obtained. A UTI (≥10,000 CFU and >five days of antibiotics) was diagnosed in 80 infants, (10% prevalence, mean GA 25.8±2.0 weeks, 76% male). Prophylactic antibiotics were administered to 29 (36%) infants after UTI, of whom four (14%) had another UTI. Recurrent UTI also occurred in 7/51 (14%) of infants not on uroprophylaxis after their first UTI. RUS was performed after UTI in 78%, and hydronephrosis and other major anomalies were found in 19%. A VCUG was performed in 48% of infants and 18% demonstrated vesicoureteral reflux (VUR). The mean HRC rose and fell significantly in the two days before and after diagnosis of UTI. UTI was diagnosed in 10% of VLBW infants, and the HRC index increased prior to diagnosis, suggesting that continuous HRC monitoring in the NICU might allow earlier diagnosis and treatment of UTI.

A Methodology for Estimation of Hourly‐Monthly Stochastic Trend Characteristics of Midlatitude Ionosphere

AbstractSpatiotemporal variability of ionosphere poses a major challenge in characterization of observable parameters, critical frequency of F2 layer (foF2), maximum ionization height (hmF2), total electron content (TEC), and slab thickness. The nature of the multiscale space‐time variability of ionosphere can be modeled as a random field. In this study, as a first step in random field modeling of the trend, hourly‐monthly parametric probability density functions (PPDF) of foF2, hmF2, slab thickness, and TEC are obtained using IONOLAB‐PDF method for three midlatitude stations (namely, Juliusruh, Pruhonice, and Rome) for low, moderate, and high solar activity years of 2009, 2012, and 2014, respectively. foF2 and hmF2 are obtained from ionosondes. TEC is estimated from dual‐frequency Global Positioning System (GPS) receivers. It is observed that hourly‐monthly PPDFs of all ionospheric parameters at the three midlatitude stations can best be represented by lognormal and Weibull distributions. The estimates of mean and standard deviations of hourly‐monthly PPDFs indicate that the spatiotemporal stochastic trend variation of the midlatitude ionosphere differs in terms of foF2 and GPS‐TEC. The hourly‐monthly PPDF of foF2 represents all major anomalies as well as seasonal and hourly trends, whereas those of GPS‐TEC is highly dependent on solar activity level and latitude. The general statistical trend of hmF2 is anticorrelated with foF2 as expected. The mean of hourly‐monthly PPDF of slab thickness is around 400 km in 2012 and 2014 for all stations between 0200 UT and 1600 UT.

Stillbirth and fetal anomalies: secondary analysis of a case-control study.

Approximately 10% of stillbirths are attributed to fetal anomalies, but anomalies are also common in live births. We aimed to assess the relationship between anomalies, by system and stillbirth. Secondary analysis of a prospective, case-control study. Multicentre, 59 hospitals in five regional catchment areas in the USA. All stillbirths and representative live birth controls. Standardised postmortem examinations performed in stillbirths, medical record abstraction for stillbirths and live births. Incidence of major anomalies, by type, compared between stillbirths and live births with univariable and multivariable analyses using weighted analysis to account for study design and differential consent. Of 465 singleton stillbirths included, 23.4% had one or more major anomalies compared with 4.3% of 1871 live births. Having an anomaly increased the odds of stillbirth; an increasing number of anomalies was more highly associated with stillbirth. Regardless of organ system affected, the presence of an anomaly increased the odds of stillbirth. These relationships remained significant if stillbirths with known genetic abnormalities were excluded. After multivariable analyses, the adjusted odds ratio (aOR) of stillbirth for any anomaly was 4.33 (95% CI 2.80-6.70) and the systems most strongly associated with stillbirth were cystic hygroma (aOR 29.97, 95% CI 5.85-153.57), and thoracic (aOR16.18, 95% CI 4.30-60.94) and craniofacial (aOR 35.25, 95% CI 9.22-134.68) systems. In pregnancies affected by anomalies, the odds of stillbirth are higher with increasing numbers of anomalies. Anomalies of nearly any organ system increased the odds of stillbirth even when adjusting for gestational age and maternal race. Stillbirth risk increases with anomalies of nearly any organ system and with number of anomalies seen.

Abdominal circumference discordance for prediction of small for gestational age at birth in twin pregnancies

Objective To evaluate whether single sonographic abdominal circumference (AC) discordancy estimation can predict small for gestational age (SGA) at birth in twin gestations. Methods A retrospective analysis of prospectively collected data. Cohort included all twin gestations delivered at one university-affiliated medical center between 2010 and 2018, with available sonographic evaluation from 22 gestational weeks to term. Pregnancies complicated by fetal chromosomal abnormalities, major anomalies or twin to twin transfusion syndrome were excluded. One sonographic evaluation per pregnancy was selected randomly. AC discordance was calculated as (large twin AC – small twin AC)/large twin AC*100. Prediction of SGA at birth for at least one newborn (<10% percentile for gestational age by gender-specific local curves for multiples) was evaluated using ROC statistics with calculation of Youden index to establish best AC discordance cutoff. AC discordance prediction performance was compared to estimated fetal weight discordance performance. Results were adjusted for confounders using logistic regression analysis. Results After exclusion, 236 twin gestations entered analysis. Of them, 200/236 (84.7%) were dichorionic-diamniotic twins. Mean gestational age at ultrasound evaluation and at delivery were 30.9 ± 4.4 and 35.9 ± 2.4 weeks, respectively. In 28/236 (11.8%) pregnancies, at least one neonate was born SGA. AC discordance predicted SGA at birth as good as sonographic estimated fetal weight (sEFW) discordance: ROC-AUC 0.76, 95% CI 0.67–0.85 vs. 0.77 95% CI 0.66–0.87, p < .001 for all. Best AC discordance cutoff for prediction of SGA at birth was 7.1% (57% sensitivity, 87% specificity), ROC-AUC 0.72 (95% CI 0.61–0.84, p < .001). Results remained significant after adjustment for maternal age, nulliparity, chorionicity and ultrasound to delivery interval (aOR 1.21 95% CI 1.1–1.32, p < .001). Conclusion According to our results, AC discordance at single sonographic evaluation can predict SGA at birth in twin gestations as good as sEFW discordance. Best cutoff for SGA prediction was 7.1%.

VP18.07: Mid‐trimester left ventricular modified myocardial performance index of selective intrauterine growth restriction in monochorionic pregnancies

To evaluate the left ventricular modified myocardial performance index (LV mod-MPI) of early-onset selective intrauterine growth restriction (sIUGR) in monochorionic diamniotic (MCDA) twins. This retrospective study consisted of MCDA twins diagnosed at Asan Medical Center between 2014 and 2019. Isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and ejection time (ET) were measured between 16.0 and 24.6 weeks of gestational age. MPI was calculated as (ICT + IRT)/ET. Cases with Twin–twin transfusion syndrome and major anomalies were excluded. sIUGR was defined as an intertwin weight discordancy of >25% and weight of the smaller fetus of less than the 10th percentile. The LV mod-MPI and its components were compared using the Mann-Whitney U test. During the study period, 38 uncomplicated MCDA twins and 26 twins with sIUGR were included. Although the LV mod-MPI and IRT were slightly higher in the larger twins in those with sIUGR than in those among twins without complications (0.44 vs. 0.50, and 41 vs. 45, respectively), differences were within the normal ranges. The ICT and ET of the larger twins did not show significant differences between twins without complications and those with sIUGR. There were no significant differences in LV mod-MPI and its components in the smaller twins between the two groups. Mid-trimester LV mod-MPI and its components may not be significantly different between twins with uncomplicated MCDA and those with sIUGR.

VP32.03: Aberrant right subclavian artery as only finding in a mosaic Turner syndrome

Aberrant right subclavian artery (ARSA) is the most common congenital abnormality of the aortic arch and occurs in about 0.5−2% of the normal population. Usually, when isolated, ARSA is considered a normal variant rather than a true defect. However, there is an important association with chromosomal abnormalities, cardiac defects and genetic anomalies. The most frequent genetic abnormalities associated with ARSA are chromosomal aberrations, especially Trisomy 21 and Trisomy 18. We report a case of a mosaic Turner Syndrome detected by karyotype analysis performed due to ARSA as an isolated sonographic finding. A 28year-old woman, primigravida, started pregnancy surveillance only at 22 weeks. The first ultrasound, at 23 weeks, revealed an ARSA, without other changes. After genetic counselling, the parents opted for karyotype analysis and FISH for 22q11 deletion that revealed a mosaic 45XO/46XX, with about 19% of the cells in monosomy. At 36th week of gestation, the estimated fetal weight was in the 4th percentile with abnormal Doppler blood flow in middle cerebral artery and umbilical artery. An induction of labour was decided a week later and an 2225gr female infant with Apgar score of 9/10 was delivered by vaginal delivery. Postnatal examination and echocardiography confirmed that ARSA was the only finding in the fetus. Turner's syndrome is a relatively common chromosomal disorder occurring in approximately 1 in 2000 live births. The syndrome is caused by complete or partial absence of the second X chromosome, with or without cell line mosaicism. The most serious clinical aspect of this syndrome is due to congenital cardiovascular anomalies, in particular elongation of the transverse arch and aort coarctation. Mosaic monosomy X has been associated with a significant lower incidence of major cardiovascular anomalies. The performance of a fetal karyotype test when ARSA is an isolated finding is still a debatable issue, however it should be discussed with the parents.

Clinical Significance of Hyperechogenic Bowel in Second-Trimester Ultrasound Scan

Background: This study aimed to report the incidence of bowel obstruction, chromosomal abnormality, congenital infection, fetal growth restriction (FGR), and otheranomalies in fetuses with hyperechogenic bowel (HEB) diagnosed during the second-trimester fetal ultrasound scan.Methods: In total, 350 fetuses with a diagnosis of HEB in our maternal-fetal medicine referral center were evaluated with a detailed fetal ultrasound examination by an experienced perinatologist. If no associated anomalies were observed, women were counseled about the risk of potential fetal disorders and offered appropriate testing, including detailed fetal sonography, karyotype, maternal cytomegalovirus (CMV), and toxoplasmosis serology,as well as serial fetal biometry and bowel diameter follow up.Results: Altogether there were 18(5.1%) fetuses with associated problems, including major anomalies, chromosomal abnormalities, and CMV infection. Moreover, 32(9.1%) fetuses developed FGR during follow-up.Conclusion: An overall rate of adverse conditions of 14.2% with prenatally detected HEB serves to inform obstetricians and emphasizes the importance of careful screening fetal ultrasound studies and timely referral for an additional assessment about associated findings.It should be noted that isolated HEB has good outcomes.

Asset pricing implications of money: New evidence

We provide new evidence on the role of real money balances in terms of explaining equity risk premia by using a rich cross-section of average stock returns (associated with 11 major CAPM anomalies). By estimating Euler equations associated with a cash-in-advance (CIA) model, we find that such model produces substantially smaller pricing errors than the baseline consumption model, while still generating lower estimates of the risk aversion coefficient. The estimates of the parameter governing the share of cash goods are highly significant and plausible in economic terms. A transaction-costs model and a money-in-the-utility model perform considerably worse than the CIA model, both in terms of statistical fit and in terms of the plausibility of the structural parameter estimates. Moreover, a linear version of the CIA model also largely underperforms the corresponding non-linear model.

Unprecedented health costs of smoke-related PM2.5 from the 2019–20 Australian megafires

In flammable landscapes around the globe, longer fire seasons with larger, more severely burnt areas are causing social and economic impacts that are unsustainable. The Australian 2019–20 fire season is emblematic of this trend, burning over 8 million ha of predominately Eucalyptus forests over a six-month period. We calculated the wildfire-smoke-related health burden and costs in Australia for the most recent 20 fire seasons and found that the 2019–20 season was a major anomaly in the recent record, with smoke-related health costs of AU$1.95 billion. These were driven largely by an estimated 429 smoke-related premature deaths in addition to 3,230 hospital admissions for cardiovascular and respiratory disorders and 1,523 emergency attendances for asthma. The total cost was well above the next highest estimate of AU$566 million in 2002–03 and more than nine times the median annual wildfire associated costs for the previous 19 years of AU$211 million. There are substantial economic costs attributable to wildfire smoke and the potential for dramatic increases in this burden as the frequency and intensity of wildfires increase with a hotter climate. Worldwide, longer fire seasons are causing unsustainable impacts. This study finds that the 2019–20 Australia fire season caused health-related costs of AU$1.95 billion, nine times the median for the previous 19 years.

Long-term experience with the one-and-a-half ventricle repair for simple and complex congenital heart defects

The one-and-a-half ventricle repair (1.5VR) is a surgical alternative to Fontan circulation or high-risk biventricular repair in patients with complex congenital heart disease (CHD) with a hypoplastic right ventricle (RV). We report our 25 years of experience to evaluate whether the degree of anatomical complexity of the CHD can affect long-term outcomes. This is a retrospective study including patients undergoing 1.5VR between 1994 and 2018. Clinical records and operative reports were reviewed. Follow-up data were collected from all survivors at the last evaluation or by phone contact. Twenty-nine patients underwent 1.5VR [median age: 3.5 years, interquartile range (IQR) 0.8-7.8]. Fifteen patients had 'simple' (i.e. confined to right heart lesions) anatomical characteristics (48.3%); the median tricuspid valve annulus z-score was -3.5 (IQR -6.2 to +3.6). There were no operative deaths. The median hospital stay was 21 days (IQR 10-33), with postoperative complications in 21 patients (75.8%). At a median follow-up of 13.2 years (IQR 3.2-25.6 years; completeness 96.6%), there were 3 late deaths. There was no significant difference in survival and in freedom from adverse events between simple and complex anatomy groups. However, stress test findings showed a tendency towards a higher maximum oxygen uptake in the simple group (P = 0.055). The 1.5VR strategy is an effective low-risk surgical option for patients with CHD with hypoplastic RV. When it is planned from birth, late outcomes can be satisfactory. In our experience, the presence of associated major cardiac anomalies was not associated with either worse early or long-term outcomes and functional status.

First-trimester absent nasal bone: is it a predictive factor for pathogenic CNVs in the low-risk population?

To evaluate the association of first-trimester absent nasal bone (NB) and genetic abnormalities at G-banding karyotype and chromosomal microarray analysis (CMA) according to the nuchal translucency (NT) thickness. This is a retrospective cohort study of fetuses that underwent the first-trimester scan for the combined test at 11+0 to 13+6 weeks' gestation. Invasive test with G-banding karyotype and/or CMA was performed based on the result of the combined test or if fetal defects were detected or for patient's choice, after genetic counseling. All cases with absent NB in the first and second trimester underwent a detailed anomaly scan with echocardiography in the second trimester, had a longitudinal ultrasound, and postnatal follow-up up to at least 1 year. Between 2013 and 2018, 7228 women underwent the first-trimester scan at 11+0 to 13+6 weeks. Overall prevalence of absent NB was 1.3% (96/7228). Of those, in 86 pregnancies (1.2%), the absence of NB was confirmed also in the second trimester: 0.58% (40/6909) in the group with NT <95th centile; 6%(14/233) in the group with NT between 95 and 99th centile; and 37.2% (32/86) in the group with NT >99th centile, respectively. CMA pathogenic variants were found only in the group with NT >99th centile with a diagnostic yield of 9.4%. Fetuses with absent NB and NT between 95 and 99th centile had in 57% (8/14) a major chromosomal anomaly, while in the NT <95 centile group, there were 5% (2/40) of chromosomal abnormalities (one inherited from the father). In the first trimester, the risk for genetic syndromes detectable by CMA is related mainly to the NT thickness rather than to the absence of NB per se. In fetuses with absent NB and NT >99th centile, CMA should be performed after karyotype analysis, while for NT between 95 and 99th centile, a karyotype should be proposed as first-line procedure. Data provided by our study may be helpful in counseling women/couples when an absent NB is identified in the first trimester.

AIUM Practice Parameter for the Performance of Detailed Diagnostic Obstetric Ultrasound Examinations Between 12 Weeks 0 Days and 13 Weeks 6 Days.

AIUM Practice Parameter for the Performance of Detailed Diagnostic Obstetric Ultrasound Examinations Between 12 Weeks 0 Days and 13 Weeks 6 Days.