Regional lymph node evaluation in pediatric conventional melanoma subtype: a single-center 10-year review.

PURPOSE: To assess the prognostic and therapeutic significance of sentinel lymph node biopsy (SLNB) and completion lymph node dissection (CLND) in pediatric conventional melanoma (CM), while evaluating potential predictive factors for outcomes. METHODS: We conducted a retrospective analysis of medical records spanning 2009-2020, focusing on patients aged 18 or younger with localized cutaneous conventional melanoma. RESULTS: Among the 33 patients, SLNB detected metastasis in 57.6% of cases, with 52.6% undergoing CLND. Positive SLN patients had higher relapse risk (HR 5.92; 95% CI 1.27-27.7; P = 0.024) but similar overall survival (HR 3.19; 95% CI 0.31-33.1, P = 0.33). No significant differences in disease-free survival (DFS) and OS were found between patients who underwent CLND and those who did not (HR 1.91; 95% CI 0.49-7.43, P = 0.35, and HR 0.52; 95% CI 0.03-8.32, P = 0.64, respectively). Univariate analysis showed age at diagnosis (P = 0.02) correlated with higher recurrence risk, with a 21% hazard increase per additional year of age. CONCLUSIONS: Positive SLN status and age at diagnosis were associated with worse DFS in CM patients. Our study did not find any prognostic or therapeutic value in CLND for pediatric melanoma. Further multicenter trials are needed to confirm our single-institution experience. LEVEL OF EVIDENCE: Level IV.

Adenoid cystic carcinoma of the parotid and submandibular glands in children and young adults: A population-based study.

OBJECTIVES: This study aims to analyze the behavior and treatment of adenoid cystic carcinoma (AdCC) in the pediatric and young adult population and to identify factors affecting overall survival (OS). MATERIALS AND METHODS: The study analyzed salivary gland malignancies in patients aged 0-21 with AdCC histology using the National Cancer Database from 2004 to 2018. RESULTS: A total of 72 patients (59.7% parotid, 36.1% submandibular, 1.4% sublingual, 2.8% unspecified) met criteria. Median age was 18 years [range: 0-21]. High-grade dysplasia was present in 67% of cases. Therapy consisted of primary surgery for all cases, regional lymph node dissection (LND) (74%), radiotherapy (71%), chemotherapy (8%), and chemoradiation (7%). The 5-year OS rate was 93.2% [95% confidence interval (CI): 86.9%-99.9%], respectively. Patients who underwent associated LND had improved OS (p = .0083, log-rank test) with a 5-year OS at 82.4% [95% CI: 66.1%-100%] versus 97.6% [95% CI: 93.0%-100%]. A significant difference in OS was found with unfavorable outcomes after positive marginal status: 5-year OS 84.1% [95% CI: 71.0%-99.7%] versus 100% [95% CI: 100%]; p < .001. Adjuvant therapy did not seem to impact the outcome. CONCLUSION: This study confirms that AdCC in children and young adults has an overall good prognosis despite frequent high grade. It suggests that cervical LND may be of importance, but the value of systematic adjuvant therapy is not confirmed. These findings emphasize the importance and relevance of population-based studies in shaping clinical practice and informing the design of future prospective investigations.

3q29 duplications: A cohort of 46 patients and a literature review.

Duplications of the 3q29 cytoband are rare chromosomal copy number variations (CNVs) (overlapping or recurrent ~1.6 Mb 3q29 duplications). They have been associated with highly variable neurodevelopmental disorders (NDDs) with various associated features or reported as a susceptibility factor to the development of learning disabilities and neuropsychiatric disorders. The smallest region of overlap and the phenotype of 3q29 duplications remain uncertain. We here report a French cohort of 31 families with a 3q29 duplication identified by chromosomal microarray analysis (CMA), including 14 recurrent 1.6 Mb duplications, eight overlapping duplications (>1 Mb), and nine small duplications (<1 Mb). Additional genetic findings that may be involved in the phenotype were identified in 11 patients. Focusing on apparently isolated 3q29 duplications, patients present mainly mild NDD as suggested by a high rate of learning disabilities in contrast to a low proportion of patients with intellectual disabilities. Although some are de novo, most of the 3q29 duplications are inherited from a parent with a similar mild phenotype. Besides, the study of small 3q29 duplications does not provide evidence for any critical region. Our data suggest that the overlapping and recurrent 3q29 duplications seem to lead to mild NDD and that a severe or syndromic clinical presentation should warrant further genetic analyses.

A Systematic Review of Cochlear Implant-Related Magnetic Resonance Imaging Artifact: Implications for Clinical Imaging.

OBJECTIVE: To conduct a systematic review of the existing literature with the aim of evaluating and consolidating the present understanding of strategies for mitigating magnetic resonance imaging (MRI) artifacts related to cochlear implants in adult and pediatric patients, covering both in-vivo and ex-vivo investigations. DATA SOURCES: A systematic review of MEDLINE-Ovid, Embase, Google Scholar, The Cochrane Library, and Scopus was performed from inception through April 2022. The protocol was registered with PROSPERO before commencement of data collection (CRD CRD42022319651). REVIEW METHODS: The data were screened and collected by two authors independently, and eligibility was assessed according to Cochrane Handbook and Preferred Reporting Items for Systematic Review and Meta-Analysis recommendations, whereas the quality of the articles was evaluated using the NIH Study Quality Assessment. RESULTS: The search yielded 2,354 potentially relevant articles, of which 27 studies were included in the final review. Twelve studies looked at 1.5-T MRI, four studies looked at 3-T MRI, eight studies looked at both 1.5 and 3 T, one study looked at 0.2 and 1.5 T, and one study looked at 3- and 7.0-T MRI. Nineteen studies focused on MRI sequences as a means of artifact reduction, nine studies focused on implant magnet positioning, two studies focused on head positioning, and one study focused on both magnet and head positioning. In terms of MRI sequences, diffusion-weighted imaging produced larger artifacts compared with other sequences, whereas fast spin echo/turbo spin echo sequences and fat suppression techniques produced smaller artifacts. The position of the magnet was also found to be important, with a magnet position more than 6.5 cm posterior to the external auditory canal producing the best images with the least distortion. The angle at which the magnet is placed also affects visibility of different brain structures. CONCLUSION: Proper head positioning, magnet placement at a distance of over 6.5 cm from the external auditory canal, use of spin echo sequences, and fat suppression techniques reduce the size and shape of MRI artifacts.

Feasibility of Optical Genome Mapping from Placental and Umbilical Cord Sampled after Spontaneous or Therapeutic Pregnancy Termination.

Optical genome mapping (OGM) is an alternative to classical cytogenetic techniques to improve the detection rate of clinically significant genomic abnormalities. The isolation of high-molecular-weight (HMW) DNA is critical for a successful OGM analysis. HMW DNA quality depends on tissue type, sample size, and storage conditions. We assessed the feasibility of OGM analysis of DNA from nine umbilical cord (UC) and six chorionic villus (CV) samples collected after the spontaneous or therapeutic termination of pregnancy. We analyzed quality control metrics provided by the Saphyr system (Bionano Genomics) and assessed the length of extracted DNA molecules using pulsed-field capillary electrophoresis. OMG data were successfully analyzed for all six CV samples. Five of the UC samples did not meet the Saphyr quality criteria, mainly due to poor DNA quality. In this regard, we found that DNA quality assessment with pulsed-field capillary electrophoresis can predict a successful OGM analysis. OGM data were fully concordant with the results of standard cytogenetic methods. Moreover, OGM detected an average of 14 additional structural variants involving OMIM genes per sample. On the basis of our results, we established the optimal conditions for sample storage and preparation required for a successful OGM analysis. We recommend checking DNA quality before analysis with pulsed-field capillary electrophoresis if the storage conditions were not ideal or if the quality of the sample is poor. OGM can therefore be performed on fetal tissue harvested after the termination of pregnancy, which opens up the perspective for improved diagnostic yield.

Optical genome mapping for prenatal diagnosis: A prospective study.

PURPOSE: Cytogenetic analysis provides important information for prenatal decision-making and genetic counseling. Optical genome mapping (OGM) has demonstrated its performances in retrospective studies. In our prospective study, we assessed the quality of DNA obtained from cultures of amniotic fluid (AF) and chorionic villi (CV) and evaluated the ability of OGM to detect all clinically relevant aberrations identified by standard methods. METHODS: A total of 37 prenatal samples from pregnancies with a fetal anomaly on ultrasound were analyzed prospectively by OGM between January 1, 2021 and June 31, 2022. OGM results were interpreted blindly and compared to the results obtained by standard techniques. RESULTS: OGM results were interpretable in 92% of samples. We observed 100% concordance between OGM and karyotype and/or chromosomal microarray results. In addition, OGM identified a median of 30 small (<100 kb) structural variations per case with the involvement of 12 OMIM genes, of which 3 were OMIM morbid genes. CONCLUSION: This prospective study showed OGM performed well in detecting genomic alterations in cell cultures from prenatal samples. The place of OGM in relation to CMA or exome sequencing remains to be defined in order to optimize the prenatal diagnostic procedure.

Exploring the Epidemiology and Survival Trends in Pediatric Major Salivary Gland Malignancies: Insights from the National Cancer Database.

OBJECTIVE: To investigate the clinicopathological, therapeutic, and survival data on pediatric major salivary gland cancers. MATERIALS AND METHODS: National Cancer Database (NCDB) query from 2004 to 2018. RESULTS: In total, 967 cases of individuals under the age of 21 were identified. Most cancers affected the parotid gland (86%). Mucoepidermoid carcinoma (41.3%) and acinic cell adenocarcinoma (33.6%) were the most common. Tumors occurred more often from age 11 to 21, and females were more affected. Histology varied by age, gender, and race. In the 0-5 age group, mucoepidermoid carcinoma and myoepithelial carcinoma/sarcoma/rhabdomyosarcoma were the most common pathologies. In patients over 5 years old, mucoepidermoid carcinoma was the most frequent tumor in boys, while acinic cell adenocarcinoma was more common in girls. African American patients had a higher incidence of mucoepidermoid carcinoma, while White patients in the 0-5 age group had a higher incidence of myoepithelial carcinoma/sarcoma/rhabdomyosarcoma tumors. Low-grade tumors were commonly diagnosed at stage I, but the 0-5 age group had a high frequency of stage IV tumors. The overall 5-year survival rate was 94.9%, with 90% for the 0-5 years age group and 96% for the 11-15 years age group. Negative margins were associated with higher 5-year survival rates in high-stage tumors (93%) compared to positive margins (80%). Submandibular malignancies had worse 5-year survival rates across all age groups. CONCLUSIONS: Major salivary gland malignancies in pediatric patients exhibit variations in histopathologic characteristics by age, gender, and race. Negative margins impact 5-year survival rates, especially in high-stage tumors.

Outer Membrane Integrity-Dependent Fluorescence of the Japanese Eel UnaG Protein in Live Escherichia coli Cells.

Reporter genes are important tools in many biological disciplines. The discovery of novel reporter genes is relatively rare. However, known reporter genes are constantly applied to novel applications. This study reports the performance of the bilirubin-dependent fluorescent protein UnaG from the Japanese eel Anguilla japonicas in live Escherichia coli cells in response to the disruption of outer membrane (OM) integrity at low bilirubin (BR) concentrations. Using the E. coli wild-type strain MC4100, its isogenic OM-deficient mutant strain NR698, and different OM-active compounds, we show that BR uptake and UnaG fluorescence depend on a leaky OM at concentrations of 10 µM BR and below, while fluorescence is mostly OM integrity-independent at concentrations above 50 µM BR. We suggest that these properties of the UnaG-BR couple might be applied as a biosensor as an alternative to the OM integrity assays currently in use.

1p36 deletion syndrome: Review and mapping with further characterization of the phenotype, a new cohort of 86 patients.

Chromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminal deletion syndromes (incidence between 1/5000 and 1/10,000 live births in the American population), due to a heterozygous deletion of part of the short arm of chromosome 1. The 1p36DS is characterized by typical craniofacial features, developmental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenital heart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature. The aim of our study was to (1) evaluate the incidence of the 1p36DS in the French population compared to 22q11.2 deletion syndrome and trisomy 21; (2) review the postnatal phenotype related to microarray data, compared to previously publish prenatal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiens de Langue Française), we have collected data of 86 patients constituting, to the best of our knowledge, the second-largest cohort of 1p36DS patients in the literature. We estimated an average of at least 10 cases per year in France. 1p36DS seems to be much less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients presented mainly dysmorphism, microcephaly, developmental delay/intellectual disability, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy, or cardiovascular malformations and, pre and/or postnatal growth retardation. Cardiac abnormalities, brain malformations, and epilepsy were more frequent in distal deletions, whereas microcephaly was more common in proximal deletions. Mapping and genotype-phenotype correlation allowed us to identify four critical regions responsible for intellectual disability. This study highlights some phenotypic variability, according to the deletion position, and helps to refine the phenotype of 1p36DS, allowing improved management and follow-up of patients.

Familial transmission of chromoanagenesis leads to unpredictable unbalanced rearrangements through meiotic recombination.

Chromoanagenesis is a cellular mechanism that leads to complex chromosomal rearrangements (CCR) during a single catastrophic event. It may result in loss and/or gain of genetic material and may be responsible for various phenotypes. These rearrangements are usually sporadic. However, some familial cases have been reported. Here, we studied six families in whom an asymptomatic or paucisymptomatic parent transmitted a CCR to its offspring in an unbalanced manner. The rearrangements were characterized by karyotyping, fluorescent in situ hybridization, chromosomal microarray (CMA) and/or whole genome sequencing (WGS) in the carrier parents and offspring. We then hypothesized meiosis-pairing figures between normal and abnormal parental chromosomes that may have led to the formation of new unbalanced rearrangements through meiotic recombination. Our work indicates that chromoanagenesis might be associated with a normal phenotype and normal fertility, even in males, and that WGS may be the only way to identify these events when there is no imbalance. Subsequently, the CCR can be transmitted to the next generation in an unbalanced and unpredictable manner following meiotic recombination. Thereby, prenatal diagnosis using CMA should be proposed to these families to detect any pathogenic imbalances in the offspring.

Indocyanine green near infrared-guided surgery in children, adolescents, and young adults with otolaryngologic malignancies.

OBJECTIVE: Head and neck cancers represent critical challenges due to the restricted anatomical space in children and the proximity of critical neurovascular structures which can compromise complete tumor resection. Applications of Indocyanine green (ICG) near infrared (NIR) fluorescent image-guided surgery (FGS) have recently expanded into the pediatric population, emphasizing its relevance for tumor delineation and evaluation of tissue perfusion. The objectives of the present study are twofold. First, we aim to assess the role of ICG NIR imagery in identifying neoplastic disease and second, to evaluate its role as an adjunct to identify metastatic deposits in cervical lymph node in children, adolescents, and young adults with head and neck cancers. METHODS: Eight patients with head and neck malignancies underwent ICG NIR FGS, between January 2019 and November 2021. ICG NIR findings were compared with preoperative cross-sectional imaging and results of operative tissue pathology analyses. RESULTS: All primary tumors were identified on preoperative imaging and intraoperatively with ICG NIR; however, for one case, extension of tumor was revealed with ICG NIR and confirmed by histopathological examination but was not otherwise visible on preoperative imaging or with naked eye visual and tactile assessment. ICG NIR assisted the decision process in a difficult case for which curative resection, without significant functional morbidity and potential mortality, was unrealistic. Although ICG NIR evaluation of the surgical bed did not display residual tumor, margins were found positive in two cases. ICG NIR evaluation for local metastases changed the surgical strategy in one patient by prompting conversion to bilateral neck dissections. The sensitivity of preoperative multimodality imaging to identify cervical levels of invasion was 75% with a specificity of 70%, a PPV of 33%, a NPV of 78% and an accuracy of 72%. The ICG NIR sensitivity was 83%, its specificity was 88% with a PPV of 91%, a NPV of 80% and an accuracy of 86%. The combination of preoperative multimodality imaging with ICG NIR findings led to a sensitivity of 83%, specificity of 88% and accuracy of 86%. CONCLUSION: This case series provides a proof of concept of the feasibility of ICG NIR, as an adjunct in tumor and local metastases identification in young patients with head and neck tumors. It revealed to be feasible and safe for intra-operative tumor identification, thus guiding and facilitating resection. However, it showed some limitations in precise tumor margin assessment. The combination of preoperative multimodality imaging with ICG NIR findings improved local metastases localization.

One-Year Neurodevelopmental Outcomes After Neonatal Opioid Withdrawal Syndrome: A Prospective Cohort Study.

Purpose: The aims of this study were, in a cohort of children with neonatal opioid withdrawal syndrome (NOWS), (a) to report 1-year neurodevelopmental outcomes and specifically characterize speech, language, and hearing outcomes and (b) to report the prevalence of cleft lip and/or cleft palate. Method: This prospective observational cohort study includes newborns with confirmed in utero opioid exposure who received pharmacological treatment for NOWS. During 1-year-old developmental visits, we administered standardized assessments (Bayley Scales of Infant and Toddler Development-Third Edition [Bayley-III] or Developmental Assessment of Young Children-Second Edition [DAYC-2]-due to COVID-19 restrictions). We compared Bayley-III scores to standardized population means using one-sample z tests. We report estimates, 95% confidence intervals, and two-sided p values. Results: We enrolled 202 infants (October 2018 to March 2020). Follow-up at 1-year was 80%. Infants with NOWS had lower Bayley-III scores at 1 year compared to published norms for cognitive, language, and motor domains. One infant with NOWS was diagnosed with isolated cleft palate and Pierre Robin sequence. All infants passed the newborn hearing screen, and 7.5% had a formal hearing evaluation after neonatal intensive care unit discharge, with 40% having abnormal or inconclusive results; middle ear effusion was the leading cause of abnormal hearing (66.7%). Ten percent of children received a speech-language pathology referral prior to 2 years of age. Infants born to mothers with mental health conditions were more likely to have Bayley-III or DAYC-2 scores below 95 in language or motor domains. Conclusions: Infants with pharmacologically treated NOWS have significantly lower cognitive, language, and motor scores on standardized developmental testing compared to population means at 1 year of age. Early speech-language pathology referral is frequently necessary to promote optimal development in this population. Supplemental Material: https://doi.org/10.23641/asha.20044403.

Is an association of acro-osteolysis, bone fragility, and enchondromatosis a newfound disease caused by an amplification of PTHLH? A case report.

BACKGROUND: Acro-osteolysis (AO) refers to resorption of the distal finger and toe phalanges. It displays two patterns: (i) diffuse AO and (ii) transverse or bandlike AO. AO can be a sign of local distress (e.g. of toxic origin), but is very often a sign of a constitutional or systemic acquired disorder. CASE PRESENTATION: A 15-year-old girl was referred to a paediatric rheumatologist for recurrent pain in her fingertips. She presented a particular cross-sectional AO associated with the presence of intraosseous cysts and bone fragility with atypical fractures. Initial laboratory tests and radiological examination did not allow an etiological diagnosis. Genetic studies revealed a 12p11.22-p11.23 microduplication of 900 kb including the PTHLH (parathyroid hormone-like hormone) gene, which encodes for a hormone involved in the regulation of endochondral ossification and differentiation of chondrocytes, via its PTHLH receptor. CONCLUSIONS: To date, 12p11.22-p11.23 duplications have been reported in five families with skeletal abnormalities, and in particular AO and enchondromatosis associated with bone fragility. This new observation, added to the other reported cases, suggests a close relationship between the presence of this microduplication and the skeletal abnormalities found in the patient. We suggest the descriptive name ABES (acro-osteolysis, bone fragility and enchondromatosis syndrome) to designate this disorder.

Type IA Oromandibular-Limb Hypogenesis Syndrome: A Case Report and A Case Update.

Hypoglossia is a rare congenital anomaly resulting in a small rudimentary tongue. It is classified under the oromandibular-limb hypogenesis syndrome and can be found in isolation (Type IA) but is more often associated with other congenital disorders, such as limb defects. Isolated hypoglossia cases are rare, and while feeding disorders are common, in some cases, neonatal airway obstruction is the most problematic. In the present report, we discuss two cases of newborns presenting with hypoglossia without limb deformities or visceral anomalies: one new case and a 10-year update of a previously reported case. These two cases highlight the variability in presenting symptoms and the challenges in diagnosis and management of a rare clinical entity. We focus on the discussion of early diagnosis, multidisciplinary management, and shared decision-making, with emphasis on the current therapeutic strategies available to the clinician and their limitations during the neonatal period. Early surgical multivector mandibular distraction osteogenesis can be proposed with minimal short- and long-term morbidity, pending a consistent follow-up. This clinical entity will require multidisciplinary team care into adult years.

Special Considerations for Tympanoplasty Type I in the Oncological Pediatric Population: A Case-Control Study.

Introduction: Although cutting-edges antineoplastic therapies increase survival in children with malignancies, the optimal surgical strategy to address associated comorbidities such as chronic tympanic membrane perforation is still poorly documented. The aim of this study is to evaluate the outcomes of type I tympanoplasty in pediatric cancer survivors who received chemo and/or radiotherapy to the skull and to identify potential associated risk factors. Methods: This case-control study included medical records review of oncologic patients (age <21) treated at the same Academic medical oncologic center between March 2015 and July 2021 and referred for conductive hearing loss and chronic tympanic membrane perforation. Patients and middle ear status-related variables were analyzed, and outcomes were compared with matched peers without any history of malignancies. Results: A total of seven pediatric cancer survivors and seven paired children without any history of malignancies were included in this report. The mean age at tympanoplasty type I surgery was 10.2 years (range = 4.3-19.9; median = 7.9 years) for the pediatric cancer survivors' group and 10.1 years (range = 5.5-19.2; median = 7.9 years) in the control group. Three pediatric cancer patients had received chemotherapy alone, one patient had radiotherapy to the skull base, and three patients had received chemoradiotherapy. On average, surgery was performed 3.9 years after chemo and/or radiotherapy termination, except for 1 patient for whom the tympanoplasty was performed during chemotherapy treatment. A retroauricular approach was used for one of the pediatric cancer patients, a transcanal approach was performed in one other and five patients benefited from an otoendoscopic approach. Tragal perichondrium with cartilage was used in most of the pediatric cancer survivor cases (four out seven cases) while xenograft (Biodesign) and Temporalis fascia without cartilage graft were used in five out of the seven control cases. Rate of tympanic membrane perforation recurrence was similar between groups (28.6%). Mean functional gain for air conduction Pure Tone Average (AC PTA) was 2.6 and 7.7 dB HL for the oncologic and control group, respectively. Mean postoperative air-bone gap (ABG) was 10.7 dB HL [median = 8.7; inter-quartile range (IQR) = 13.8] for the oncologic cohort and 10.1 dB HL (median = 10.7; IQR = 9.6) for the control group. Discussion: Chemo- and chemoradiotherapy to the skull are associated with damages to the inner and middle ear structures with secondary eustachian tube dysfunction and chronic middle ear effusion. Although healing abilities and immunological defenses are compromised as part of the expected effects of antineoplastic therapies, type I tympanoplasty can be safe and effective in this population. While different approaches may be considered, otoendoscopy showed excellent results with less morbidity in this vulnerable population.

Reduced telomere length in amniocytes: an early biomarker of abnormal fetal development?

Telomeres protect chromosome ends and control cell division and senescence. During organogenesis, telomeres need to be long enough to ensure the cell proliferation necessary at this stage of development. Previous studies have shown that telomere shortening is associated with growth retardation and congenital malformations. However, these studies were performed in newborns or postnatally, and data on telomere length (TL) during the prenatal period are still very limited. We measured TL using quantitative PCR in amniotic fluid (AF) and chorionic villi (CV) samples from 69 control fetuses with normal ultrasound (52 AF and 17 CV) and 213 fetuses (165 AF and 48 CV) with intrauterine growth retardation (IUGR) or congenital malformations diagnosed by ultrasound. The samples were collected by amniocentesis at the gestational age (GA) of 25.0 ± 5.4 weeks and by CV biopsy at 18.1 ± 6.3 weeks. In neither sample type was TL influenced by GA or fetal sex. In AF, a comparison of abnormal versus normal fetuses showed a significant telomere shortening in cases of IUGR (reduction of 34%, P < 10-6), single (29%, P < 10-6) and multiple (44%, P < 10-6) malformations. Similar TL shortening was also observed in CV from abnormal fetuses but to a lesser extent (25%, P = 0.0002; 18%, P = 0.016; 20%, P = 0.004, respectively). Telomere shortening was more pronounced in cases of multiple congenital anomalies than in fetuses with a single malformation, suggesting a correlation between TL and the severity of fetal phenotype. Thus, TL measurement in fetal samples during pregnancy could provide a novel predictive marker of pathological development.

Acoustic Cry Characteristics of Infants as a Marker of Neurological Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: Atypical cries have been identified in infants with neurological dysfunction. The aim of this study was to conduct a systematic review and meta-analysis to appraise existing evidence for associations between acoustic cry characteristics and neurological dysfunction in infants aged 18 months or less. METHODS: PubMed/MEDLINE, PsycINFO, CINAHL, and Embase were searched for original, peer-reviewed studies published in English reporting cry variables in infants aged 18 months or less with or at risk of neurological dysfunction. Studies without a nonneurologically impaired control sample were excluded. Pooled effect sizes were estimated using standardized mean difference (SMD) and odds ratio (OR). I2 indicated study heterogeneity, and the risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: From March 2018 to February 2019, 28,294 studies were retrieved. Eight were meta-analyzed. Infants with or at risk of neurological dysfunction exhibited higher mean (SMD = 0.11 [95% confidence interval, 0.00 to 0.23]) and minimum (SMD = 0.93 [0.64 to 1.23]) fundamental frequency; higher odds of hyperphonation (OR = 13.17 [1.05 to 165.87]), biphonation (OR = 10.62 [1.53 to 73.59]), rise-fall-rise melodies (OR = 4.66 [1.16 to 18.66]), and flat melodies (OR = 4.47 [1.27 to 15.68]); and lower odds of fall-rise-fall melodies (OR = 0.21 [0.05 to 0.83]). CONCLUSIONS: Infants with underlying neuropathology have unique cries characterized by higher fundamental frequency, dysphonation, and atypical melodies, although study heterogeneity and imprecision of effect size estimates limited our interpretation. Assessment of acoustic cry characteristics offers the potential for noninvasive, rapid, point-of-care screening for neurologically high-risk infants.

Randomized Trial to Increase Speech Sound Differentiation in Infants Born Preterm.

OBJECTIVE: To test whether infant-directed foreign language active learning would specifically increase speech sound differentiation to the intervention language while not decreasing differentiation in response to English. STUDY DESIGN: Pilot randomized controlled trial of stable infants born preterm in the newborn intensive care unit with normal auditory brainstem responses, whose parents spoke only English and had no musical training or familial hearing abnormality. Assignment was to 1 of 3 groups: passive exposure to English infant-directed lullabies and readings (English-enrichment, control group) and contingent exposure by active sucking on a sensor-equipped pacifier to either infant-directed French lullabies and readings (English environment, French-contingent learning group) or infant-directed Mandarin lullabies and readings (English environment, Chinese-contingent learning group). The main outcome measures were preintervention and postintervention event-related potentials (ERPs) in response to standardized speech syllables in each language. RESULTS: Forty-one subjects completed the study, including 15 in the English-enrichment control group and 13 each in the French-contingent and Chinese-contingent groups. The median gestational age at birth was 34 weeks (IQR, 8.75 weeks); postmenstrual age at intervention ranged from 36 to 46 weeks and was similar across the 3 groups. Postintervention mean ERP amplitude to pairs of English speech sounds did not differ across the 3 groups; however, ERP amplitude in French sound differentiation was greater in the French-contingent group than in the Chinese-contingent or English-enrichment groups, and ERP amplitude greater in Chinese sound differentiation was greater in the Chinese-contingent group compared with the other 2 groups. CONCLUSION: Contingent infant-directed foreign language exposure increased speech sound differentiation specific to the intervention language and did not decrease differentiation in response to English. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03232931.