Use of buprenorphine or methadone to treat opioid use disorder is recommended in pregnancy; however, their teratogenic potential is largely unknown.
To compare the risk of congenital malformations ...following in utero exposure to buprenorphine vs methadone.
This population-based cohort study used health care utilization data from publicly insured Medicaid beneficiaries in the US from 2000 to 2018. A total of 13 360 pregnancies with enrollment from 90 days prior to pregnancy start through 1 month after delivery and first trimester use of buprenorphine or methadone were included and linked to infants. Data were analyzed from July to December 2022.
A pharmacy dispensing of buprenorphine or a code for administration of methadone in the first trimester.
Primary outcomes included major malformations overall and malformations previously associated with opioids (any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, clubfoot, and oral clefts). Secondary outcomes included other organ system-specific malformations. Risk differences and risk ratios (RRs) were estimated comparing buprenorphine with methadone, adjusting for confounders with propensity score overlap weights.
The cohort included 9514 pregnancies with first-trimester buprenorphine exposure (mean SD maternal age, 28.4 4.6 years) and 3846 with methadone exposure (mean SD maternal age, 28.8 4.7 years). The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone. After confounding adjustment, buprenorphine was associated with a lower risk of malformations compared with methadone (RR, 0.82; 95% CI, 0.69-0.97). Risk was lower with buprenorphine for cardiac malformations (RR, 0.63; 95% CI, 0.47-0.85), including both ventricular septal defect (RR, 0.62; 95% CI, 0.39-0.98) and secundum atrial septal defect/nonprematurity-related patent foramen ovale (RR, 0.54; 95% CI, 0.30-0.97), oral clefts (RR, 0.65; 95% CI, 0.35-1.19), and clubfoot (RR, 0.55; 95% CI, 0.32-0.94). Results for neural tube defects were uncertain given low event counts. In secondary analyses, buprenorphine was associated with a decreased risk of central nervous system, urinary, and limb malformations but a greater risk of gastrointestinal malformations compared with methadone. These findings were consistent in sensitivity and bias analyses.
In this cohort study, the risk of most malformations previously associated with opioid exposure was lower in buprenorphine-exposed infants compared with methadone-exposed infants, independent of measured confounders. Malformation risk is one factor that informs the individualized patient decision regarding medications for opioid use disorder in pregnancy.
The exact incidence and risk factors for reoperation in partial and transitional atrioventricular septal defects are unclear. The goal of this study was to assess risk factors for left ...atrioventricular valve and left ventricular outflow tract reoperation in partial and transitional atrioventricular septal defects.
All patients undergoing partial and transitional atrioventricular septal defects repair between 1995 and 2017 were reviewed. Patients were classified as infants (<1 year), toddlers (1-3 years), children (3-17 years), and adults (≥18 years). Survival and reoperation were assessed using log-rank test and Cox models for univariate and multivariable analyses, respectively.
Overall, 265 patients underwent partial and transitional atrioventricular septal defects repair (partial: 177 67%). Median age was 2 years. The cohort included 73 infants (28%), 85 toddlers (32%), 94 children (35%), and 13 adults (5%). Trisomy 21 was present in 76 patients (29%), and in 216 patients (83%), the zone of apposition was completely closed. Perioperative mortality was 0.8%. Complete heart block did not develop in any patients. Ten-year survival and freedom from reoperation were 98% and 81%, respectively. On multivariable analysis, trisomy 21 (hazard ratio HR, 0.16) and older age compared with infants (toddlers: HR, 0.35; children: HR, 0.25) were protective for any reoperation, whereas heterotaxy (HR, 3.43) was a risk factor. For left atrioventricular valve reoperation, toddlers (HR, 0.35), children (HR, 0.25), and trisomy 21 (HR, 0.16) remained protective, whereas left atrioventricular valve anomaly was a risk factor (HR, 2.61). Likewise, for left ventricular outflow tract reoperation, toddlers (HR, 0.24) and children (HR, 0.06) were protective.
Mortality after partial and transitional atrioventricular septal defects repair is minimal, yet reoperation for left atrioventricular valve disease and left ventricular outflow tract obstruction remains significant. Patients requiring repair during infancy are at higher risk of reoperation.
Birth defects are a leading cause of neonatal mortality. Natural gas development (NGD) emits several potential teratogens, and U.S. production of natural gas is expanding.
We examined associations ...between maternal residential proximity to NGD and birth outcomes in a retrospective cohort study of 124,842 births between 1996 and 2009 in rural Colorado.
We calculated inverse distance weighted natural gas well counts within a 10-mile radius of maternal residence to estimate maternal exposure to NGD. Logistic regression, adjusted for maternal and infant covariates, was used to estimate associations with exposure tertiles for congenital heart defects (CHDs), neural tube defects (NTDs), oral clefts, preterm birth, and term low birth weight. The association with term birth weight was investigated using multiple linear regression.
Prevalence of CHDs increased with exposure tertile, with an odds ratio (OR) of 1.3 for the highest tertile (95% CI: 1.2, 1.5); NTD prevalence was associated with the highest tertile of exposure (OR = 2.0; 95% CI: 1.0, 3.9, based on 59 cases), compared with the absence of any gas wells within a 10-mile radius. Exposure was negatively associated with preterm birth and positively associated with fetal growth, although the magnitude of association was small. No association was found between exposure and oral clefts.
In this large cohort, we observed an association between density and proximity of natural gas wells within a 10-mile radius of maternal residence and prevalence of CHDs and possibly NTDs. Greater specificity in exposure estimates is needed to further explore these associations.
Folic acid (FA), as a synthetic form of folate, has been widely used for dietary supplementation in pregnant women. The preventive effect of FA supplementation on the occurrence and recurrence of ...fetal neural tube defects (NTD) has been confirmed. Incidence of congenital heart diseases (CHD), however, has been parallelly increasing worldwide. The present study aimed to evaluate whether FA supplementation is associated with a decreased risk of CHD.
We searched the literature using PubMed, Web of Science and Google Scholar, for the peer-reviewed studies which reported CHD and FA and followed with a meta-analysis. The study-specific relative risks were used as summary statistics for the association between maternal FA supplementation and CHD risk. Cochran's Q and I
statistics were used to test for the heterogeneity.
Maternal FA supplementation was found to be associated with a decreased risk of CHD (OR = 0.82, 95% CI: 0.72-0.94). However, the heterogeneity of the association was high (P < 0.001, I
= 92.7%). FA supplementation within 1 month before and after pregnancy correlated positively with CHD (OR 1.10, 95%CI 0.99-1.23), and high-dose FA intake is positively associated with atrial septal defect (OR 1.23, 95%CI 0.64-2.34). Pregnant women with irrational FA use may be at increased risk for CHD.
Data from the present study indicate that the heterogeneity of the association between maternal FA supplementation and CHD is high and suggest that the real relationship between maternal FA supplementation and CHD may need to be further investigated with well-designed clinical studies and biological experiments.
Scalp defects may occur due to various causes, such as head trauma. For reconstruction of the defect, a primary closure process, skin grafting, or local flap use are the foremost choices when the ...defect area is not wide. However, repair is difficult when the wound condition further deteriorates due to chronic inflammation. In this condition, free tissue transfer or a pedicled flap is required to restore normal blood supply. The sternocleidomastoid (SCM) flap is conventionally raised as a superiorly or inferiorly based pedicled flap, easily harvested to rectify a nearby scalp defect; additionally, it may either be muscular or myocutaneous. This report describes a case of successful use of the SCM flap for scalp reconstruction, raised as a superiorly based myocutaneous flap.
Single layers and combined layer systems with Cu(In,Ga)(S,Se) sub(2), ZnS-nanodot (nd) and In sub(2)S sub(3) layers were investigated by surface photovoltage spectroscopy in the Kelvin-probe ...arrangement and compared with the open-circuit voltage (V sub(OC)) of solar cells. The In sub(2)S sub(3) and ZnS-nd layers were prepared by the spray ion layer gas reaction (ILGAR) technique from Indium chloride (InCl sub(3)), Indium acetylacetonate (In(acac) sub(3)) and Zinc acetylacetonate, respectively. The surface photovoltage signals of Cu(In,Ga)(S,Se) sub(2) were larger for the Cu(In,Ga)(S,Se) sub(2)/ZnS-nd/In sub(2)S sub(3) than for the Cu(In,Ga)(S,Se) sub(2)/In sub(2)S sub(3) layer system showing that a ZnS-nd layer additionally passivated the Cu(In,Ga)(S,Se) sub(2) surface. ILGAR In sub(2)S sub(3) deposition from InCl sub(3) precursor solution led to a modification of surface defects of ZnS-nd and to generation of defect states below the band gap of Cu(In,Ga)(S,Se) sub(2), which has not been observed for deposition from Indium acetylacetonate precursor. Defect generation during ILGAR In sub(2)S sub(3) deposition with InCl sub(3) precursor resulted in a lower V sub(OC) of Cu(In,Ga)(S,Se) sub(2)/ZnS-nd/In sub(2)S sub(3)/ZnO:Al solar cells. Copyright copyright 2012 John Wiley & Sons, Ltd. ZnS nanodots deposited on Cu(In,Ga)(S,Se) sub(2) absorber and surface photovoltage (SPV) spectra of Mo / ZnS-nd / In sub(2)S sub(3) for In sub(2)S sub(3) deposited by spray ILGAR from chloride and acetylacetonate solutions demonstrating the decreased (increased) SPV signal related to defects below (absorption above) the bandgap of ZnS-nd / In super(2)S super(3) (acac).
Neural tube defects (NTDs) are associated with substantial mortality, morbidity, disability, and psychological and economic costs. Many are preventable with folic acid, and access to appropriate ...services for those affected can improve survival and quality of life. We used a compartmental model to estimate global and regional birth prevalence of NTDs (live births, stillbirths, and elective terminations of pregnancy) and subsequent under‐5 mortality. Data were identified through web‐based reviews of birth defect registry databases and systematic literature reviews. Meta‐analyses were undertaken where appropriate. For 2015, our model estimated 260,100 (uncertainty interval (UI): 213,800–322,000) NTD‐affected birth outcomes worldwide (prevalence 18.6 (15.3–23.0)/10,000 live births). Approximately 50% of cases were elective terminations of pregnancy for fetal anomalies (UI: 59,300 (47,900–74,500)) or stillbirths (57,800 (UI: 35,000–88,600)). Of NTD‐affected live births, 117,900 (∼75%) (UI: 105,500–186,600) resulted in under‐5 deaths. Our systematic review showed a paucity of high‐quality data in the regions of the world with the highest burden. Despite knowledge about prevention, NTDs remain highly prevalent worldwide. Lack of surveillance and incomplete ascertainment of affected pregnancies make NTDs invisible to policy makers. Improved surveillance of all adverse outcomes is needed to improve the robustness of total NTD prevalence estimation, evaluate effectiveness of prevention through folic acid fortification, and improve outcomes through care and rehabilitation.
Because of its thickness‐dependent direct bandgap and exceptional optoelectronic properties, indium(III) selenide (In2Se3) has emerged as an important semiconductor for electronics and ...optoelectronics. However, the scalable synthesis of defect‐free In2Se3 flakes remains a significant barrier for its practical applications. Here, a facile electrochemical strategy is presented for the ultrafast delamination of bulk layered In2Se3 crystals in nonaqueous media, resulting in high‐yield (83%) production of defect‐free In2Se3 flakes with large lateral size (up to 26 µm). The intercalation of tetrahexylammonium (THA+) ions mainly creates stage‐3 intercalated compounds in which every three layers of In2Se3 are occupied by one layer of THA molecules. The subsequent exfoliation leads to a majority of trilayer In2Se3 nanosheets. As a proof of concept, solution‐processed, large‐area (400 µm × 20 µm) thin‐film photodetectors embedded with the exfoliated In2Se3 flakes reveal ultrafast response time with a rise and decay of 41 and 39 ms, respectively, and efficient responsivity (1 mA W−1). Such performance surpasses most of the state‐of‐the‐art thin‐film photodetectors based on transition metal dichalcogenides.
An ultrafast and scalable method is developed to produce defect‐free, solution‐processable In2Se3 nanosheets. According to the variation of the cathodic currents, three distinct stages, In2Se3 crystals, (THA+)xIn2Se3x− intercalation compounds, and decomposition of the tetrahexylammonium (THA+) ions, are discovered. The intercalation of THA+ ions mainly creates stage‐3 intercalated compounds, leading to a majority of trilayer In2Se3 nanosheets.
This review provides an updated summary of the state of our knowledge of the genetic contributions to the pathogenesis of congenital heart disease. Since 2007, when the initial American Heart ...Association scientific statement on the genetic basis of congenital heart disease was published, new genomic techniques have become widely available that have dramatically changed our understanding of the causes of congenital heart disease and, clinically, have allowed more accurate definition of the pathogeneses of congenital heart disease in patients of all ages and even prenatally. Information is presented on new molecular testing techniques and their application to congenital heart disease, both isolated and associated with other congenital anomalies or syndromes. Recent advances in the understanding of copy number variants, syndromes, RASopathies, and heterotaxy/ciliopathies are provided. Insights into new research with congenital heart disease models, including genetically manipulated animals such as mice, chicks, and zebrafish, as well as human induced pluripotent stem cell-based approaches are provided to allow an understanding of how future research breakthroughs for congenital heart disease are likely to happen. It is anticipated that this review will provide a large range of health care-related personnel, including pediatric cardiologists, pediatricians, adult cardiologists, thoracic surgeons, obstetricians, geneticists, genetic counselors, and other related clinicians, timely information on the genetic aspects of congenital heart disease. The objective is to provide a comprehensive basis for interdisciplinary care for those with congenital heart disease.
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