Association of surfactant protein A polymorphisms with otitis media in infants at risk for asthma

BACKGROUND: Otitis media is one of the most common infections of early childhood. Surfactant protein A functions as part of the innate immune response, which plays an important role in preventing infections early in life. This prospective study utilized a candidate gene approach to evaluate the association between polymorphisms in loci encoding SP-A and risk of otitis media during the first year of life among a cohort of infants at risk for developing asthma. METHODS: Between September 1996 and December 1998, women were invited to participate if they had at least one other child with physician-diagnosed asthma. Each mother was given a standardized questionnaire within 4 months of her infant's birth. Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Genotyping was done on 355 infants for whom whole blood and complete otitis media data were available. RESULTS: Polymorphisms at codons 19, 62, and 133 in SP-A1, and 223 in SP-A2 were associated with race/ethnicity. In logistic regression models incorporating estimates of uncertainty in haplotype assignment, the 6A(4)/1A(5)haplotype was protective for otitis media among white infants in our study population (OR 0.23; 95% CI 0.07,0.73). CONCLUSION: These results indicate that polymorphisms within SP-A loci may be associated with otitis media in white infants. Larger confirmatory studies in all ethnic groups are warranted

Respiratory symptoms among infants at risk for asthma: association with surfactant protein A haplotypes

BACKGROUND: We examined the association between single nucleotide polymorphisms (SNPs) in loci encoding surfactant protein A (SFTPA) and risk of wheeze and persistent cough during the first year of life among a cohort of infants at risk for developing asthma. METHODS: Between September 1996 and December 1998, mothers of newborn infants were invited to participate if they had an older child with clinician-diagnosed asthma. Each mother was given a standardized questionnaire within 4 months of her infant's birth. Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Due to the association of SFTPA polymorphisms and race/ethnicity, analyses were restricted to 221 white infants for whom whole blood and respiratory data were available. Ordered logistic regression models were used to examine the association between respiratory symptom frequency and SFTPA haplotypes. RESULTS: The 6A allele haplotype of SFTPA1, with an estimated frequency of 6% among our study infants, was associated with an increased risk of persistent cough (OR 3.69, 95% CI 1.71, 7.98) and wheeze (OR 4.72, 95% CI 2.20, 10.11). The 6A/1A haplotype of SFTPA, found among approximately 5% of the infants, was associated with an increased risk of persistent cough (OR 3.20, 95% CI 1.39, 7.36) and wheeze (OR 3.25, 95% CI 1.43, 7.37). CONCLUSION: Polymorphisms within SFTPA loci may be associated with wheeze and persistent cough in white infants at risk for asthma. These associations require replication and exploration in other ethnic/racial groups

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Maternal pregnancy outcomes in women with cardiomyopathy: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to systematically assess the impact of cardiomyopathy on maternal pregnancy outcomes. DATA SOURCES: PubMed, Ovid Embase, Ovid MEDLINE, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to April 24, 2022. STUDY ELIGIBILITY CRITERIA: Observational cohort, case-control, and case-cohort studies in human populations were included if they reported predefined maternal outcomes for pregnant women with cardiomyopathy (any subtype) and for an appropriate control population (pregnant women with no known heart disease or pregnant women with noncardiomyopathy heart disease). METHODS: Two reviewers independently assessed the articles for eligibility and risk of bias, and conflicts were resolved by a third reviewer. Data were extracted and synthesized according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analyses of Observational Studies in Epidemiology guidelines. RESULTS: A total of 14 studies (n=57,539,306 pregnancies) were eligible for inclusion. Women with cardiomyopathy were more likely to deliver by cesarean delivery than women with no heart disease (odds ratio, 2.96; 95% confidence interval, 2.47-3.55; I2=95%; P≤.00001) or women with noncardiomyopathy heart disease (odds ratio, 1.90; 95% confidence interval, 1.62-2.22; I2=91%; P<.00001). Having cardiomyopathy conferred a greater risk for experiencing severe maternal adverse cardiovascular events during pregnancy when compared with not having any heart disease (odds ratio, 206.64; 95% confidence interval, 192.09-222.28; I2=73%; P<.0001) or having noncardiomyopathy heart disease (odds ratio, 7.09; 95% confidence interval; 6.08-8.27; I2=88%; P<.00001). In-hospital mortality was significantly higher among women with cardiomyopathy than among women with no heart disease (odds ratio, 126.67; 95% confidence interval, 43.01-373.07; I2=87%; P<.00001) or among women with noncardiomyopathy heart disease (odds ratio, 4.30; 95% confidence interval, 3.42-5.40; I2=0%; P<.00001). CONCLUSION: Pregnant women with cardiomyopathy have increased risks for adverse maternal outcomes, including maternal death, when compared with both women with no heart disease and women with noncardiomyopathy heart disease. Our results highlight the importance of preconception risk assessments to allow for informed decision-making before pregnancy. Pregnancies affected by cardiomyopathy are high risk and should be managed by expert, multidisciplinary obstetrical and cardiology teams

Perinatal outcomes in pregnancies complicated by maternal cardiomyopathy: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to systematically assess perinatal outcomes of pregnancies complicated by maternal cardiomyopathy. DATA SOURCES: PubMed, Ovid Embase, Ovid MEDLINE, the Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to August 25, 2022. STUDY ELIGIBILITY CRITERIA: Observational cohort, case-control, and case-cohort studies in human populations were included if they reported predefined perinatal outcomes in pregnant women with cardiomyopathy (any subtype) and an appropriate control population (either pregnant women with no known cardiac disease or pregnant women with noncardiomyopathy cardiac disease). METHODS: Of note, 2 reviewers independently assessed the articles for eligibility and risk of bias, and conflicts were resolved by a third reviewer. Data were extracted and synthesized according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines. RESULTS: Here, 13 studies (representing 2,291,024 pregnancies) were eligible for inclusion. Perinatal death was more likely in neonates born to women with cardiomyopathy than in (1) neonates born to women with no cardiac disease (stillbirth: odds ratio, 20.82; 95% confidence interval, 6.68-64.95; I2 = not available; P<.00001; neonatal mortality: odds ratio, 6.75; 95% confidence interval, 3.54-12.89; I2=0%; P<.00001) and (2) neonates born to women with other forms of cardiac disease (stillbirth: odds ratio, 3.75; 95% confidence interval, 1.86-7.59; I2=0%; P=.0002; neonatal mortality: odds ratio, 2.42; 95% confidence interval, 1.39-4.21; I2=0%; P=.002). Pregnancies affected by maternal cardiomyopathy were significantly more likely to result in preterm birth (odds ratio, 2.21; 95% confidence interval, 1.31-3.73; I2=77%; P=.003) and small-for-gestational-age neonates (odds ratio, 2.97; 95% confidence interval, 2.38-3.70; I2=47%; P<.00001), both major causes of short- and long-term morbidities, than pregnancies affected by other forms of cardiac disease. CONCLUSION: There was an increased likelihood of adverse perinatal outcomes in pregnancies affected by maternal cardiomyopathy compared with both pregnancies affected by noncardiomyopathy cardiac disease and pregnancies without cardiac disease. Women with cardiomyopathy who plan to get pregnant should receive detailed counseling regarding these risks and have their pregnancies managed by experienced multidisciplinary teams that can provide close fetal monitoring and neonatology expertise.Funding: CEA is supported by a Medical Research Council New Investigator Grant (MR/T016701/1) and the NIHR Cambridge Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funders had no role in in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication

Cardiomyopathy confers increased risks of maternal adverse outcomes.

We are grateful to Dr Sun and colleagues for their interest in our study “Maternal pregnancy outcomes in women with cardiomyopathy: A systematic review and meta-analysis”1, and very pleased to have an opportunity to underline the robustness of our findings.CEA is supported by a Medical Research Council New Investigator Grant (MR/T016701/1) and the NIHR Cambridge Biomedical Research Centre

Maternal left ventricular function and adverse neonatal outcomes in women with cardiac disease

Purpose: To evaluate the relationship between maternal left ventricular systolic function, utero-placental circulation, and risk of adverse neonatal outcomes in women with cardiac disease. Methods: 119 women managed in the pregnancy heart clinic (2019–2021) were identified. Women were classified by their primary cardiac condition. Adverse neonatal outcomes were: low birth weight ( 20 weeks’ gestation). Parameters of left ventricular systolic function (global longitudinal strain, radial strain, ejection fraction, average S’, and cardiac output) were calculated and pulsatility index was recorded from last growth scan. Results: Adverse neonatal outcomes occurred in 28 neonates (24%); most frequently in valvular heart disease (n = 8) and cardiomyopathy (n = 7). Small-for-gestational-age neonates were most common in women with cardiomyopathy (p = 0.016). Early pregnancy average S’ (p = 0.03), late pregnancy average S’ (p = 0.02), and late pregnancy cardiac output (p = 0.008) were significantly lower in women with adverse neonatal outcomes than in those with healthy neonates. There was a significant association between neonatal birth-weight centile and global longitudinal strain (p = 0.04) and cardiac output (p = 0.0002) in late pregnancy. Pulsatility index was highest in women with cardiomyopathy (p = 0.007), and correlated with average S’ (p < 0.0001) and global longitudinal strain (p = 0.03) in late pregnancy. Conclusion: Women with cardiac disease may not tolerate cardiovascular adaptations required during pregnancy to support fetal growth. Adverse neonatal outcomes were associated with reduced left ventricular systolic function and higher pulsatility index. The association between impaired systolic function and reduced fetal growth is supported by insufficient utero-placental circulation

Maternal left ventricular function and adverse neonatal outcomes in women with cardiac disease.

PURPOSE: To evaluate the relationship between maternal left ventricular systolic function, utero-placental circulation, and risk of adverse neonatal outcomes in women with cardiac disease. METHODS: 119 women managed in the pregnancy heart clinic (2019-2021) were identified. Women were classified by their primary cardiac condition. Adverse neonatal outcomes were: low birth weight ( 20 weeks' gestation). Parameters of left ventricular systolic function (global longitudinal strain, radial strain, ejection fraction, average S', and cardiac output) were calculated and pulsatility index was recorded from last growth scan. RESULTS: Adverse neonatal outcomes occurred in 28 neonates (24%); most frequently in valvular heart disease (n = 8) and cardiomyopathy (n = 7). Small-for-gestational-age neonates were most common in women with cardiomyopathy (p = 0.016). Early pregnancy average S' (p = 0.03), late pregnancy average S' (p = 0.02), and late pregnancy cardiac output (p = 0.008) were significantly lower in women with adverse neonatal outcomes than in those with healthy neonates. There was a significant association between neonatal birth-weight centile and global longitudinal strain (p = 0.04) and cardiac output (p = 0.0002) in late pregnancy. Pulsatility index was highest in women with cardiomyopathy (p = 0.007), and correlated with average S' (p < 0.0001) and global longitudinal strain (p = 0.03) in late pregnancy. CONCLUSION: Women with cardiac disease may not tolerate cardiovascular adaptations required during pregnancy to support fetal growth. Adverse neonatal outcomes were associated with reduced left ventricular systolic function and higher pulsatility index. The association between impaired systolic function and reduced fetal growth is supported by insufficient utero-placental circulation.CEA is supported by a Medical Research Council New Investigator Grant (MR/T016701/1) and the NIHR Cambridge Biomedical Research Centr

Perceived benefits of patient support groups and their format for people with an implantable cardioverter defibrillator

Background: Support groups for people with Implantable Cardioverter Defibrillators (ICDs) are widely used, however, it is not clear what people with ICDs gain from a support group or what format they should take. Objectives: The aim of the present study is to define the perceived benefit of ICD support groups and develop practical recommendations for group format. Methods: 14 individuals with ICDs were interviewed using a semi-structured interview guide. Reflexive thematic analysis methods were utilised to code and analyse the transcripts before generating themes. Results: Four themes were defined: confronting mortality, coping through sharing, coping through learning, and providing space. Making connections with other people with ICDs, reassurance, access to information, and advice from health care professionals were important perceived benefits of the support group. Conclusion: People with ICDs may have to confront their own mortality and adapt to considerable life changes after implant. The findings from the present study have improved understanding of how support groups are perceived and how ICD indication and group format influence the experience. A blended format of in-person community meetings, online forums, HCP-led education and space for person-person interaction is recommended. Importantly, provision of support should not be time-limited to allow people to access it when it most likely to be of benefit to them