Chromosomal, gestational, and neonatal outcomes of embryos classified as a mosaic by preimplantation genetic testing for aneuploidy.

OBJECTIVE: To understand the clinical risks associated with the transfer of embryos classified as a mosaic using preimplantation genetic testing for aneuploidy. DESIGN: Analysis of data collected between 2017 and 2023. SETTING: Multicenter. PATIENTS: Patients of infertility treatment. INTERVENTION: Comparison of pregnancies resulting from embryos classified as euploid or mosaic using the 20%-80% interval in chromosomal intermediate copy numbers to define a mosaic result. MAIN OUTCOME MEASURES: Rates of spontaneous abortion, birth weight, length of gestation, incidence of birth defects, and chromosomal status during gestation. RESULTS: Implanted euploid embryos had a significantly lower risk of spontaneous abortion compared with mosaic embryos (8.9% [n = 8,672; 95% confidence interval {CI95} 8.3, 9.5] vs. 22.2% [n = 914; CI95 19.6, 25.0]). Embryos with mosaicism affecting whole chromosomes (not segmental) had the highest risk of spontaneous abortion (27.6% [n = 395; CI95 23.2, 32.3]). Infants born from euploid, mosaic, and whole chromosome mosaic embryos had average birth weights and lengths of gestation that were not statistically different (3,118 g and 267 days [n = 488; CI95 3,067, 3,169, and 266, 268], 3052 g and 265 days [n = 488; CI95 2,993, 3,112, and 264,267], 3,159 g and 268 days [n = 194; CI95 3,070, 3,249, and 266,270], respectively). Out of 488 infants from mosaic embryo transfers (ETs), one had overt gross abnormalities as defined by the Centers for Disease Control and Prevention. Most prenatal tests performed on pregnancies from mosaic ETs had normal results, and only three pregnancies produced prenatal test results reflecting the mosaicism detected at the embryonic stage (3 out of 250, 1.2%; CI95 0.25, 3.5). CONCLUSION: Although embryos classified as mosaic experience higher rates of miscarriage than euploid embryos (with a particularly high frequency shortly after implantation), infants born of mosaic ETs are similar to infants of euploid ETs. Prenatal testing indicates that mosaicism resolves during most pregnancies, although this process is not perfectly efficient. In a small percentage of cases, the mosaicism persists through gestation. These findings can serve as risk-benefit considerations for mosaic ETs in the fertility clinic.

Two clinical case reports of embryonic mosaicism identified with PGT-A persisting during pregnancy as true fetal mosaicism.

The health risks associated with transferring embryos classified as mosaic by preimplantation genetic testing for aneuploidies (PGT-A) are currently unknown. Such embryos produce PGT-A results indicating the presence of both euploid and aneuploid cells and have historically been deselected from transfer and grouped with uniformly aneuploid embryos as 'abnormal'. In recent years, numerous groups have reported the intentional transfer of mosaic embryos in the absence of uniformly euploid embryos, largely observing births of seemingly healthy babies. However, it remains to be understood whether the embryonic mosaicism invariably becomes resolved during the ensuing pregnancy, or whether the placenta and/or fetal tissues retain aneuploid cells, and if so to what potential clinical effect. Here, we report two cases of mosaicism persisting from the embryonic stage to the established pregnancy. Case 1 involved an embryonic low-level segmental mosaic loss in Chromosome (Chr) 1, which was confirmed in amniocentesis as well as in brain tissue of the products of conception. This pregnancy was terminated due to the chromosomal pathologies associated with 1p36 deletion syndrome, such as severe intellectual disability. Case 2 involved a low-level mosaic Chr 21 trisomy, which was confirmed with chorionic villus sampling and amniocentesis. The ensuing pregnancy was terminated after ultrasound identification of severe abnormalities in the placenta and fetus. Together, these two cases should be taken into account for risk-benefit assessments of prospective mosaic embryo transfers.

SARS-CoV-2 can infect human embryos.

The spread of SARS-CoV-2 has led to a devastating pandemic, with infections resulting in a range of symptoms collectively known as COVID-19. The full repertoire of human tissues and organs susceptible to infection is an area of active investigation, and some studies have implicated the reproductive system. The effects of COVID-19 on human reproduction remain poorly understood, and particularly the impact on early embryogenesis and establishment of a pregnancy are not known. In this work, we explore the susceptibility of early human embryos to SARS-CoV-2 infection. By using RNA-seq and immunofluorescence, we note that ACE2 and TMPRSS2, two canonical cell entry factors for SARS-CoV-2, are co-expressed in cells of the trophectoderm in blastocyst-stage preimplantation embryos. For the purpose of viral entry studies, we used fluorescent reporter virions pseudotyped with Spike (S) glycoprotein from SARS-CoV-2, and we observe robust infection of trophectoderm cells. This permissiveness could be attenuated with blocking antibodies targeting S or ACE2. When exposing human blastocysts to the live, fully infectious SARS-CoV-2, we detected cases of infection that compromised embryo health. Therefore, we identify a new human target tissue for SARS-CoV-2 with potential medical implications for reproductive health during the COVID-19 pandemic and its aftermath.

Haplotype-aware inference of human chromosome abnormalities.

Extra or missing chromosomes-a phenomenon termed aneuploidy-frequently arise during human meiosis and embryonic mitosis and are the leading cause of pregnancy loss, including in the context of in vitro fertilization (IVF). While meiotic aneuploidies affect all cells and are deleterious, mitotic errors generate mosaicism, which may be compatible with healthy live birth. Large-scale abnormalities such as triploidy and haploidy also contribute to adverse pregnancy outcomes, but remain hidden from standard sequencing-based approaches to preimplantation genetic testing for aneuploidy (PGT-A). The ability to reliably distinguish meiotic and mitotic aneuploidies, as well as abnormalities in genome-wide ploidy, may thus prove valuable for enhancing IVF outcomes. Here, we describe a statistical method for distinguishing these forms of aneuploidy based on analysis of low-coverage whole-genome sequencing data, which is the current standard in the field. Our approach overcomes the sparse nature of the data by leveraging allele frequencies and linkage disequilibrium (LD) measured in a population reference panel. The method, which we term LD-informed PGT-A (LD-PGTA), retains high accuracy down to coverage as low as 0.05 × and at higher coverage can also distinguish between meiosis I and meiosis II errors based on signatures spanning the centromeres. LD-PGTA provides fundamental insight into the origins of human chromosome abnormalities, as well as a practical tool with the potential to improve genetic testing during IVF.

Let the data do the talking: the need to consider mosaicism during embryo selection.

Chromosomal mosaicism, the coexistence of cells with different chromosomal content, has been documented in human embryos for 3 decades. Early versions of preimplantation genetic testing for aneuploidy (PGT-A) did not measure mosaicism, either because typically only a single cell was assessed or because the technique could not accurately identify it. Although this led to a straightforward diagnosis (an embryo was considered either normal or abnormal), it simply avoided the issue and, in hindsight, may have led to numerous misdiagnoses with negative clinical consequences. Modern PGT-A evaluates a multicellular biopsy specimen with techniques capable of recognizing intermediate copy number signals for chromosomes or subchromosomal regions. We are, therefore, inevitably confronted with the issue of mosaicism and the challenge of managing embryos producing such results in the clinic. Here we discuss recent data showing that not only mosaicism in general, but specific features of mosaicism detected with PGT-A, are associated with variable clinical outcomes. The conclusion is evident: mosaicism should be considered for more informed and improved embryo selection in the clinic.

Using outcome data from one thousand mosaic embryo transfers to formulate an embryo ranking system for clinical use.

OBJECTIVE: To study how the attributes of mosaicism identified during preimplantation genetic testing for aneuploidy relate to clinical outcomes, in order to formulate a ranking system of mosaic embryos for intrauterine transfer. DESIGN: Compiled analysis. SETTING: Multi-center. PATIENT(S): A total of 5,561 euploid blastocysts and 1,000 mosaic blastocysts used in clinical transfers in patients undergoing fertility treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation (gestational sac), ongoing pregnancy, birth, and spontaneous abortion (miscarriage before 20 weeks of gestation). RESULT(S): The euploid group had significantly more favorable rates of implantation and ongoing pregnancy/birth (OP/B) compared with the combined mosaic group or the mosaic group affecting only whole chromosomes (implantation: 57.2% vs. 46.5% vs. 41.8%; OP/B: 52.3% vs. 37.0% vs. 31.3%), as well as lower likelihood of spontaneous abortion (8.6% vs. 20.4% vs. 25%). Whole-chromosome mosaic embryos with level (percent aneuploid cells) <50% had significantly more favorable outcomes than the ≥50% group (implantation: 44.5% vs. 30.4%; OP/B: 36.1% vs. 19.3%). Mosaic type (nature of the aneuploidy implicated in mosaicism) affected outcomes, with a significant correlation between number of affected chromosomes and unfavorable outcomes. This ranged from mosaicism involving segmental abnormalities to complex aneuploidies affecting three or more chromosomes (implantation: 51.6% vs. 30.4%; OP/B: 43.1% vs. 20.8%). Combining mosaic level, type, and embryo morphology revealed the order of subcategories regarding likelihood of positive outcome. CONCLUSION(S): This compiled analysis revealed traits of mosaicism identified with preimplantation genetic testing for aneuploidy that affected outcomes in a statistically significant manner, enabling the formulation of an evidence-based prioritization scheme for mosaic embryos in the clinic.

Estimating Demand for Germline Genome Editing: An In Vitro Fertilization Clinic Perspective.

Germline genome editing (GGE) holds the potential to mitigate or even eliminate human heritable genetic disease, but also carries genuine risks if not appropriately regulated and performed. It also raises fears in some quarters of apocalyptic scenarios of designer babies that could radically change human reproduction. Clinical need and the availability of alternatives are key considerations in the ensuing ethical debate. Writing from the perspective of a fertility clinic, we offer a realistic projection of the demand for GGE. We lay out a framework proposing that GGE, hereditary genetic disorders, and in vitro fertilization are fundamentally entwined concepts. We note that the need for GGE to cure heritable genetic disease is typically grossly overestimated, mainly due to the underappreciated role of preimplantation genetic testing. However, we might still find applications for GGE in the correction of chromosomal abnormalities in early embryos, but techniques for that purpose do not yet exist.

Births from embryos with highly elevated levels of mitochondrial DNA.

RESEARCH QUESTION: Conflicting data exist on the utility of quantification of mitochondrial DNA (mtDNA) levels as a predictor of blastocyst implantation in the IVF clinic. The current study determined whether blastocysts with highly elevated mtDNA levels could result in healthy pregnancies and births, and whether mitochondrial functional output might be a readout of cell stress in the embryo. DESIGN: mtDNA levels were determined in 109 blastocysts used in clinical transfers into 100 women, noting their clinical outcomes. In a separate set of embryos, mitochondrial function was quantified in a model of embryo stress, aneuploidy. Measurement of mtDNA levels made use of surplus material from the process of preimplantation genetic testing for aneuploidies, and followed recently proposed unifying guidelines for mtDNA quantification. RESULTS: Unusually high mtDNA levels did not preclude blastocyst implantation and healthy births. An analysis of 109 blastocysts showed no significant difference between mtDNA levels in implanted (n = 55) versus non-implanted (n = 54) blastocysts. No obvious differences in the degree of mitochondrial functional output were detected in a model of embryo stress. CONCLUSIONS: Measurement of mtDNA copy number might not provide any advantage in embryo prioritization and could lead to a deselection of blastocysts that would result in healthy pregnancies and births. Furthermore, the quantification of mitochondrial functional output in a model of cellular stress might suggest that mitochondria are not clear targets for biomarker identification as it relates to blastocyst viability. Any suggested link between mtDNA levels, mitochondria or their output with blastocyst transfer outcome requires further validation.

One hundred mosaic embryos transferred prospectively in a single clinic: exploring when and why they result in healthy pregnancies.

OBJECTIVE: To investigate the parameters of mosaicism and the biological mechanisms leading to healthy pregnancies from mosaic embryo transfers. DESIGN: Prospective study. SETTING: IVF center and associated research laboratory. PATIENT(S): Fifty-nine patients. INTERVENTION(S): Embryos underwent blastocyst-stage preimplantation genetic testing for aneuploidy by next-generation sequencing. Trophectoderm biopsies containing 20%-80% abnormal cells were deemed mosaic, and corresponding blastocysts were transferred. Mosaic embryos donated to research were examined for karyotype concordance in multiple biopsies and assessed for cell proliferation and death by immunofluorescence and computational quantitation. MAIN OUTCOME MEASURE(S): Chemical start of pregnancy, implantation, fetal heartbeat, and birth. RESULT(S): Globally, mosaic embryos showed inferior clinical outcomes compared with euploid embryos. Aneuploid cell percentage in trophectoderm biopsies did not correlate with outcomes, but type of mosaicism did, as embryos with single mosaic segmental aneuploidies fared better than all other types. Mosaic blastocysts generated from oocytes retrieved at young maternal ages (≤34 years) showed better outcomes than those retrieved at older maternal ages. Mosaic embryos displayed low rates of karyotype concordance between multiple biopsies and showed significant elevation of cell proliferation and death compared with euploid embryos. CONCLUSION(S): After euploid embryos, mosaic embryos can be considered for transfer, prioritizing those of the single segmental mosaic type. If a patient has mosaic embryos available that were generated at different ages, preference should be given to those made at younger ages. Intrablastocyst karyotype discordance and differential cell proliferation and death might be reasons that embryos classified as mosaic can result in healthy pregnancies and babies.

Assessment of aneuploidy concordance between clinical trophectoderm biopsy and blastocyst.

STUDY QUESTION: Is a clinical trophectoderm (TE) biopsy a suitable predictor of chromosomal aneuploidy in blastocysts? SUMMARY ANSWER: In the analyzed group of blastocysts, a clinical TE biopsy was an excellent representative of blastocyst karyotype in cases of whole chromosome aneuploidy, but in cases of only segmental (sub-chromosomal) aneuploidy, a TE biopsy was a poor representative of blastocyst karyotype. WHAT IS KNOWN ALREADY: Due to the phenomenon of chromosomal mosaicism, concern has been expressed about the possibility of discarding blastocysts classified as aneuploid by preimplantation genetic testing for aneuploidy (PGT-A) that in fact contain a euploid inner cell mass (ICM). Previously published studies investigating karyotype concordance between TE and ICM have examined small sample sizes and/or have utilized chromosomal analysis technologies superseded by Next Generation Sequencing (NGS). It is also known that blastocysts classified as mosaic by PGT-A can result in healthy births. TE re-biopsy of embryos classified as aneuploid can potentially uncover new instances of mosaicism, but the frequency of such blastocysts is currently unknown. STUDY DESIGN, SIZE, DURATION: For this study, 45 patients donated 100 blastocysts classified as uniform aneuploids (non-mosaic) using PGT-A by NGS (n = 93 whole chromosome aneuploids, n = 7 segmental aneuploids). In addition to the original clinical TE biopsy used for PGT-A, each blastocyst was subjected to an ICM biopsy as well as a second TE biopsy. All biopsies were processed for chromosomal analysis by NGS, and karyotypes were compared to the original TE biopsy. PARTICIPANTS/MATERIALS, SETTING, METHODS: The setting for this study was a single IVF center with an in-house PGT-A program and associated research laboratory. MAIN RESULTS AND THE ROLE OF CHANCE: When one or more whole chromosomes were aneuploid in the clinical TE biopsy, the corresponding ICM was aneuploid in 90 out of 93 blastocysts (96.8%). When the clinical TE biopsy contained only segmental (sub-chromosomal) aneuploidies, the ICM was aneuploid in three out of seven cases (42.9%). Blastocysts showing aneuploidy concordance between clinical TE biopsy and ICM were also aneuploid in a second TE biopsy in 86 out of 88 cases (97.7%). In blastocysts displaying clinical TE-ICM discordance, a second TE biopsy was aneuploid in only two out of six cases (33.3%). LIMITATIONS, REASONS FOR CAUTION: All embryos in this study had an initial classification of 'aneuploid' and not 'euploid' or 'mosaic'. Therefore, the findings of this study refer specifically to a TE biopsy predicting aneuploidy in the remaining blastocyst, and cannot be extrapolated to deduce the ability of a TE biopsy to predict euploidy in the blastocyst. No conclusions should be drawn from this study about the ability of a mosaic TE biopsy to predict the karyotype of the corresponding blastocyst. Caution should be exercised in generalizing the findings of the sample group of this study to the general IVF blastocyst population. The segmental aneuploidy group only contained seven samples. WIDER IMPLICATIONS OF THE FINDINGS: The high rate of intra-blastocyst concordance observed in this study concerning whole chromosome aneuploidy contributes experimental evidence to the validation of PGT-A at the blastocyst stage. Concomitantly, the results suggest potential clinical value in reassessing blastocysts deemed aneuploid by TE re-biopsy in select cases, particularly in instances of segmental aneuploidies. This could impact infertility treatment for patients who only have blastocysts classified as aneuploid by PGT-A available. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Zouves Foundation for Reproductive Medicine and Zouves Fertility Center. The authors have no competing interest to disclose. TRIAL REGISTRATION NUMBER: Not applicable.

Is mitochondrial DNA quantitation in blastocyst trophectoderm cells predictive of developmental competence and outcome in clinical IVF?

Behind every successful IVF embryo transfer, there is a great game of chance. Methods seeking to tilt the balance and increase the likelihood of implantation have been proposed and implemented with varying results, including embryo morphology, FISH-PGS, comprehensive chromosomal screening (CCS), morphokinetics, endometrial receptivity testing. It has been suggested that mitochondrial DNA (mtDNA) copy number could serve as a biomarker for embryo viability, but this concept was recently challenged. The world of IVF is left with unanswered questions: Why are there discrepancies in the reports? Should mtDNA copy number be considered to rank embryos for transfer? And in a broader sense, how well must a technique be validated before its implementation in the IVF clinic? Here, we explore these questions attempting to piece together the published data and suggest future directions to help unravel the subject matter.

Accurate quantitation of mitochondrial DNA reveals uniform levels in human blastocysts irrespective of ploidy, age, or implantation potential.

OBJECTIVE: To accurately determine mitochondrial DNA (mtDNA) levels in human blastocysts. DESIGN: Retrospective analysis. SETTING: IVF clinic. PATIENT(S): A total of 1,396 embryos derived from 259 patients. INTERVENTION(S): Blastocyst-derived trophectoderm biopsies were tested by next-generation sequencing (NGS) and quantitative real-time polymerase chain reaction (qPCR). MAIN OUTCOME MEASURE(S): For each sample the mtDNA value was divided by the nuclear DNA value, and the result was further subjected to mathematical analysis tailored to the genetic makeup of the source embryo. RESULT(S): On average the mathematical correction factor changed the conventionally determined mtDNA score of a given blastocyst via NGS by 1.43% ± 1.59% (n = 1,396), with maximal adjustments of 17.42%, and via qPCR by 1.33% ± 8.08% (n = 150), with maximal adjustments of 50.00%. Levels of mtDNA in euploid and aneuploid embryos showed a statistically insignificant difference by NGS (euploids n = 775, aneuploids n = 621) and by qPCR (euploids n = 100, aneuploids n = 50). Blastocysts derived from younger or older patients had comparable mtDNA levels by NGS ("young" age group n = 874, "advanced" age group n = 514) and by qPCR ("young" age group n = 92, "advanced" age group n = 58). Viable blastocysts did not contain significantly different mtDNA levels compared with unviable blastocysts when analyzed by NGS (implanted n = 101, nonimplanted n = 140) and by qPCR (implanted n = 49, nonimplanted n = 51). CONCLUSION(S): We recommend implementation of the correction factor calculation to laboratories evaluating mtDNA levels in embryos by NGS or qPCR. When applied to our in-house data, the calculation reveals that overall levels of mtDNA are largely equal between blastocysts stratified by ploidy, age, or implantation potential.

School-Based Interventions for Anxious Children: Long-Term Follow-Up.

This study examined the long-term outcomes of a nonclinical sample of anxious children (N = 61) who were randomized by school to 9 weeks of group cognitive-behavioral therapy (CBT) for children, group CBT for children plus parent training, or no-treatment control. Parents and children completed measures of anxiety symptoms at baseline, posttreatment, and at 3-, 6-, 12-month, 2-, and 3-year posttreatment follow-ups. Piecewise longitudinal growth curve analyses were applied to the data. When the two CBT groups were combined and compared with control, the combined treatment group showed significantly greater reduction in children's anxiety severity based on the parent ratings in the first longitudinal phase. However, on the parent Clinician Severity Rating, gains were maintained to 3 years. Child report revealed no significant differences between groups on anxiety reduction. This study maintained a small no-treatment control group during the entire follow-up period. From parental perspective only, school-based group CBT appeared to be beneficial in decreasing severity of anxiety symptoms and maintaining gains over time.

Comparison of clinical characteristics of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and childhood obsessive-compulsive disorder.

OBJECTIVE: The objectives of this study were to identify unique clinical characteristics of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) compared with a control group of children with non-PANDAS obsessive-compulsive disorder (OCD) with respect to ancillary symptoms, types of obsessions and compulsions, symptom severity, and co-morbid DSM-IV diagnoses. METHOD: Classification of PANDAS was based on review of pediatric and psychiatric records using the criteria developed by Swedo and colleagues. Children aged 6-14 with PANDAS (n = 21) and non-PANDAS OCD (n = 18) were assessed by blind independent evaluators using the PANDAS Questionnaire, Children's Yale-Brown Obsessive Compulsive Scale, Yale Global Tic Severity Scale, and Anxiety Disorders Interview Schedule for DSM-IV. RESULTS: PANDAS children were significantly more likely to present with separation anxiety, urinary urgency, hyperactivity, impulsivity, deterioration in handwriting, and decline in school performance during their initial episode of neuropsychiatric illness compared with children with OCD. Total tics and vocal tics were more severe in PANDAS children. Separation anxiety disorder and social phobia were more prevalent in non-PANDAS OCD children. Children with non-PANDAS OCD were significantly more likely to include others in their rituals. There were no significant differences between groups on demographics or severity of OCD. CONCLUSIONS: Distinguishing clinical characteristics in PANDAS, which included urinary urgency, hyperactivity, impulsivity, and deterioration in handwriting, are linked to basal ganglia functions. These clinical characteristics will aid in the differentiation of PANDAS children for research and clinical purposes and ultimately advance our understanding and treatment of this disorder.

Videoconferencing at psychology internships: interns' perceptions of interactive television experiences and prospects.

This article reviews the use and perceptions of videoconferencing in psychology internship training from the perspective of interns. Videoconferencing offers a means of expanding training beyond conventional on-site models. Psychology interns completed an online survey about their experiences with videoconferencing and perspectives of its impact on training. Most participants encountered it in their didactics. Some used it for supervision or other purposes. Interns' perspectives were complex, with videoconferencing seen as supporting learning similar to conventional training in some ways, yet as less desirable overall. Direct comparisons between videoconferencing and on-site training revealed interns perceived videoconferencing as somewhat less effective, and as deleteriously affecting learning dynamics. Challenges and potential benefits of incorporating videoconferencing into psychology internship training were identified. Potential benefits include augmenting available internship training and increasing rural sites' access to training.

Anxiety disorders and posttraumatic stress disorder update.

Anxiety disorders are one of the most common categories of psychopathology in children and adolescents. This article provides an overview of several anxiety disorders that are diagnosed often during childhood and adolescence, including separation anxiety disorder, generalized anxiety disorder, social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder. Although anxiety disorders commonly show similar clinical characteristics during childhood and adulthood, this article highlights some of the differences that may present across the life span.

Generalized anxiety disorder in a nonclinical sample of children: symptom presentation and predictors of impairment.

Presentation of generalized anxiety disorder (GAD) in a nonclinical sample of children (7-11 years old) and factors that predict overall impairment were examined. Symptom presentation was compared in children with GAD (n=49) and anxious children without GAD (n=42). Children with GAD endorsed significantly more worries, greater intensity of worries, and more DSM-IV associated symptoms than anxious children without GAD. Eighty-six percent of children with GAD had a comorbid diagnosis with 4% having a depressive disorder. Number of associated symptoms was most predictive of GAD impairment based on child perspective and intensity of worry was most predictive based on clinician perspective. Overall, findings from the current study are consistent with reports based on clinical samples. The DSM-IV-TR criteria for GAD were supported, with the exception that children with GAD typically present with several associated symptoms, rather than only one.

School-based interventions for anxious children: 3-, 6-, and 12-month follow-ups.

OBJECTIVE: To follow 61 participants (7-11 years old) from a study that compared three school-based interventions for anxious children: group cognitive-behavioral therapy (CBT) for children, group CBT for children plus parent training, and no-treatment control to determine whether posttreatment benefits are sustained longitudinally. METHOD: Parent, child, and clinician report measures of child anxiety were completed at 3, 6, and 12 months posttreatment. Semistructured diagnostic interviews were administered at 6- and 12-month follow-ups. For initial analyses, the group CBT and group CBT plus parent training conditions were collapsed into one group and compared to control. When significant results were found, each active treatment group was compared to control. RESULTS: Across several measures, the collapsed CBT group sustained significant improvement in anxiety severity and impairment across a 12-month period compared to control. There were no significant differences between the three groups on remission of baseline anxiety disorders or incidence of new anxiety disorders during the follow-up. Several parent-report measures at 3 and 6 months posttreatment suggested that group CBT for children plus parent training provided additional benefit over the group CBT for children when each was compared to the control group. CONCLUSIONS: School-based CBT appears effective in decreasing anxiety symptoms up to 12 months posttreatment for anxious children.

Effects of parent and family characteristics on treatment outcome of anxious children.

This study examines relations between family functioning, parenting stress, parental psychopathology, and treatment outcome. Participants included 61 children (ages 7-11 years) with features or diagnoses of separation anxiety disorder, generalized anxiety disorder, and/or social phobia. Treatment conditions included group cognitive behavioral therapy (CBT) and no-treatment control. Higher family cohesion at baseline was associated with significantly greater decreases in child anxiety at posttreatment for participants who received CBT, while no association was found for the no-treatment control participants. Parenting stress and parental psychopathology were not associated with treatment outcome for either condition. Post hoc analyses examining relations between family cohesion, parenting stress, and parental psychopathology showed that parents from families low in cohesion reported significantly higher levels of parenting stress and psychopathology compared to parents from families high in cohesion. These results will facilitate development and implementation of effective interventions with anxious children.