A Survey on Screening and Diagnostic Criteria of Auditory Processing Disorders in India.

The current study aimed to determine the criteria used for screening and diagnosing cases with central auditory processing disorders (CAPD) in India. A cross-sectional questionnaire-based survey design was used in the present study. A questionnaire was developed to determine the criteria used for screening and diagnosing CAPD across clinics in India. Responses were obtained from 83 participants from all over India. Results indicated that 78% of respondents were currently doing CAPD evaluation. In that, the majority of respondents (63%) had a predetermined minimum battery that was relatively adaptable depending on the case history and age of the patient. In screening, most respondents used a screening questionnaire (SCAP, 75%) and a screening test (STAP, 60%). In the diagnostic protocol, the most used tests by the respondents were masking level difference (MLD), repetition of words (RW), gap detection test (GDT), pitch pattern test (PPT), speech perception in noise (SPIN), digit span test (DST), dichotic digit test (DDT), binaural fusion test (BFT), auditory brainstem response (ABR), dichotic CV test (DCVT), and duration pattern test (DPT). The current study's result will help professionals choose the minimum test battery for diagnosing CAPD.

Effect of Age on Speech Perception in Noise Abilities Across Different Stimulus.

Various factors influence speech perception in noise (SPIN): age, hearing loss, cognition, background noise, stimulus redundancy, type of stimulus used, and signal-to-noise ratio. The effect of age on SPIN with different stimuli is yet to be validated in the literature. This study aims to study the effect of age on SPIN results across different stimuli. The study is a cross-sectional study with ninety participants with normal hearing ability. All participants in the study were equally divided into three groups: the children's group aged 8 to 12 years, the adult group aged 18 to 30, and the older adult group aged 55 to 72 years. Speech perception in the background of Kannada speech babble was assessed across three stimuli: monosyllables (CV), phonemically balanced Kannada words, and Kannada sentences. The stimulus was presented at 60 dBSPL binaurally through a calibrated headphone at 0 dB SNR. The result indicated a significant main effect of age on SPIN across syllables, words, and sentences. Further, Mann-Whitney test results revealed a statistically significant difference between the SPIN scores of children and adults for syllables, words, and sentences. Also, a statistical difference was noted in SPIN scores between adults and older adults for syllables, words, and sentences. However, statistical differences between children and older adults were seen only for syllables. The trend showed that the SPIN scores for syllables, words, and sentences improve from childhood to adulthood, while scores deteriorate from the adult to older adult group. A similar trend was seen for all three stimulus types. However, the reduction in the SPIN score using syllables in the older adult group was more noticeable than words and sentences. It can be concluded that there is an effect of age on SPIN abilities across different stimuli. It highlights the importance of age-appropriate SPIN normative for various stimuli.

Comparison of a Free-Field and a Closed-Field Sound Source Identification Paradigms in Assessing Spatial Acuity in Adults With Normal Hearing Sensitivity.

BACKGROUND AND OBJECTIVES: Traditional sound field localization setups in a free-field environment closely represent real-world situations. However, they are costly and sophisticated, and it is difficult to replicate similar setups in every clinic. Hence, a cost-effective, portable, and less sophisticated virtual setup will be more feasible for assessing spatial acuity in the clinical setting. The virtual auditory space identification (VASI) test was developed to assess spatial acuity using virtual sources in a closed field. The present study compares the legitimacy of these two methods. SUBJECTS AND METHODS: Fifty-five individuals with normal hearing (mean age±SD: 21± 3.26 years) underwent spatial acuity assessment using two paradigms: 1) the sound field paradigm (localization test) and 2) the virtual paradigm (VASI test). Location-specific and overall accuracy scores and error rates were calculated using confusion matrices for each participant in both paradigms. RESULTS: The results of Wilcoxon signed-rank tests showed that the locationspecific and overall accuracy scores for both paradigms were not significantly different. Further, both paradigms did not yield significantly different localization error rates like right and left intra-hemifield errors, inter-hemifield errors, and front-back errors. Spearman's correlation analysis showed that all the measures of the two paradigms had mild to moderate correlation. CONCLUSIONS: These results demonstrate that both VASI and the sound field paradigm localization test performed equally well in assessing spatial acuity.

Test-Retest Reliability of Virtual Acoustic Space Identification Test in School-Going Children.

PURPOSE: The virtual acoustic space identification (VASI) test was designed to assess spatial-hearing acuity by simulating sound location perception in a closed field (under headphones). The utility of this tool in children can be asserted only if the test results are consistent across measurement sessions, which is evaluated in this study using test-retest reliability assessments. METHOD: The VASI test assessed the spatial abilities of 40 typically developing school-aged children aged 7-13 years (M age = 10.47 ± 1.83 years, 22 boys, 18 girls). The test consisted of eight virtual location percepts (with 45° separation) produced under headphones (Sennheiser HD 569). Each spatial percept was presented randomly 7 times at 65 dB SPL. Each participant completed the assessment in three measurement sessions (baseline, intrasession, and intersession). The accuracy scores at each location and overall accuracy scores were compared across the sessions. RESULTS: The Shapiro-Wilk test indicated that the VASI data were not normally distributed. Intraclass correlation coefficient analysis revealed excellent test-retest reliability of the overall accuracy scores and moderate-to-high reliability of location-specific scores. This was complimented by the low response variability of the overall and location-specific accuracy scores. The Bland-Altman analysis also indicated minimal bias in VASI accuracy scores across the three sessions. CONCLUSIONS: It can be concluded from the results that VASI is a reliable tool for assessing spatial-hearing acuity in school-aged children. The high test-retest reliability and ease of portability make the test highly relevant for classroom setups where early diagnosis and intervention of spatial deficits can play a critical role in determining the academic success of school-going children.

Age differences in binaural and working memory abilities in school-going children.

OBJECTIVES: Binaural hearing is the interplay of acoustic cues (interaural time differences: ITD, interaural level differences: ILD, and spectral cues) and cognitive abilities (e.g., working memory, attention). The current study investigated the effect of developmental age on auditory binaural resolution and working memory and the association between them (if any) in school-going children. METHODS: Fifty-seven normal-hearing school-going children aged 6-15 y were recruited for the study. The participants were divided into three groups: Group 1 (n=17, Mage = 7.1y ± 0.72 y), Group 2 (n = 23; Mage = 10.2y ± 0.8 y), Group 3 (n = 17; Mage: 14.1 y ±1.3 y). Group 4, with normal hearing young adults (n = 20; Mage = 21.1 y± 3.2 y), was included for comparing the maturational changes in former groups with adult values. Tests of binaural resolution (ITD and ILD thresholds) and auditory working memory (forward and backward digit span and 2n-back digit) were administered to all the participants. RESULTS: Results indicated a main effect of age on spatial resolution and working memory, with the median of lower age groups (Group 1 & Group 2) being significantly poorer (p < 0.01) than the higher age groups (Group 3 & Group 4). Groups 2, 3, and 4 performed significantly better than Group 1 (p < 0.001) on the forward span and ILD task. Groups 3 and 4 had significantly better ITD (p = 0.04), backward span (p = 0.02), and 2n-back scores than Group 2. A significant correlation between scores on working memory tasks and spatial resolution thresholds was also found. On discriminant function analysis, backward span and ITD emerged as sensitive measures for segregating older groups (Group 3 & Group 4) from younger groups (Group 1 & Group 2). CONCLUSIONS: The present study showed that the ILD thresholds and forward digit span mature by nine years. However, the backward digit span score continued to mature beyond 15 y. This finding can be attributed to the influence of auditory attention (a working memory process) on the binaural resolution, which is reported to mature till late adolescence.

Effect of Age and Hearing Loss on Auditory Processing Skills.

Background: The present study aimed to evaluate the effect of age and hearing loss on auditory processing abilities. For this purpose, auditory processing abilities were compared among young and older adults with normal hearing sensitivity and older adults with and without hearing loss. Method: The study comprised 20 normal-hearing young adults (18-25 years), 20 older adults with normal hearing sensitivity (50-70 years), and 20 older adults with mild to moderate sensorineural hearing impairment (50-70 years). All 60 participants underwent gap detection (GDT), dichotic consonant-vowe (DCV)l, speech in noise (SPIN), duration pattern (DPT), and working memory (forward and backward span) tests in a sound treated test room. Results: Results showed that young normal-hearing adults performed significantly better than normal-hearing older adults in SPIN, GDT, DCV, working memory, and DPT. Futher, normal-hearing older individuals performed better than older individuals with hearing impairment on all the auditory processing tests except on the forward span test and DPT. Conclusion: Auditory processing abilities deteriorate with age and hearing loss also has a pronounced effect on most auditory processing abilities.

Relationship Between Central Auditory Processing Abilities and Working Memory During Adolescence.

Purpose: Adolescence is a period of transformation in humans with changes in the neural physiology at subcortical and cortical levels. However, its significance on auditory processing skills and working memory skills and their association is yet to be well understood. Hence, the current study was designed to evaluate and establish the association between auditory processing skills and working memory abilities in adolescents. Method: A total of 125 adolescents within the age range of 10 to 15 years participated in the current study. All of them had normal hearing sensitivity and no associated obvious peripheral or central deficits. All the participants underwent auditory closure ability assessment using quick speech perception in noise test in Kannada, binaural integration ability assessment using dichotic CV test, and temporal processing assessment using gap detection test. Auditory working memory abilities were assessed using auditory digit span and digit sequencing. Results: Spearman correlation was done to assess the correlation between auditory processing skills and working memory abilities. Results revealed a significant negative correlation between most of the central auditory processing abilities and all the working memory spans. Conclusions: Findings of the current study indicate that individuals with poor working memory abilities have difficulty in auditory processing abilities.

Implementing Social Risk Screening and Referral to Resources in the NICU.

OBJECTIVE: Social risk screening is recommended by the American Academy of Pediatrics, but this practice is underutilized in NICUs. To address this gap in social care, we aimed to increase rates of: (1) systematic social risk screening and (2) connection with community resources, each to ≥50% over a 14-month period. METHODS: We conducted a quality improvement initiative from November 2020 to January 2022. We adapted a screening tool and used Plan-Do-Study-Act cycles to integrate screening and referral to resources into clinical workflow. Primary outcome measures included the percentage of (1) families screened and (2) connection with resources. We examined screening by maternal race/ethnicity and primary language. Process measures were (1) time from admission to screening and (2) percentage of referrals provided to families reporting unmet needs and requesting assistance. We used statistical process control to assess change over time and χ2 tests to compare screening by race/ethnicity and language. RESULTS: The rates of systematic screening increased from 0% to 49%. Among 103 families screened, 84% had ≥1, and 64% had ≥2 unmet needs, with a total of 221 needs reported. Education, employment, transportation, and food were the most common needs. Screening rates did not vary by race/ethnicity or language. Among families requesting assistance, 98% received referrals. The iterative improvement of a written resource guide and community partnerships led to increased rates of connection with resources from 21% to 52%. CONCLUSION: Leveraging existing staff, our social risk screening and referral intervention built the capacity to address the high burden of unmet needs among NICU families.

Selective Unilateral Inner Hair Cell Injury: A Case Report.

Sensorineural hearing loss (SNHL) is known to be associated with lesions at various sites, including outer hair cell (OHC) and inner hair cell (IHC) injury, as well as auditory dyssynchrony or vestibulocochlear nerve tumors. Therefore, it is important to establish the differential diagnosis of SNHL, which however is particularly challenging in patients with unilateral SNHL. The test battery approach is effective for accurate diagnosis in such cases. In this report, we discuss the usefulness of the test battery approach to accurately detect the site of the lesion in a patient with unilateral hearing loss. A 14-year-9-month-old adolescent who observed decreased hearing sensitivity in the left ear accompanied by difficulty with understanding speech at a distance was diagnosed with unilateral hearing loss in the left ear. In this report, we describe a rare and diagnostically challenging case of unilateral SNHL in a patient with normal OHC function and selective injury to IHCs, which was diagnosed using a test battery approach.

Effect of Use of N-95 Mask on Aided Speech Identification Scores in Older Adults with Hearing Loss.

The present study aimed to investigate the effect of use of N-95 masks on aided speech identification scores (SIS) in older adults with hearing loss. A total of 35 older adults in the age range of 60 years to 79 years (mean age of 64.97 years) participated in the present study. All the participants were diagnosed with moderate to severe sensorineural hearing loss. A prospective pre-test post-test study design was used in the present study with purposive convenient sampling method. The study was carried out in two phases. Phase 1 included the hearing aid fitting and verification. Phase 2 included measuring the speech identification scores (SIS) with and without N- 95 mask. The results of the present study showed that aided SIS scores obtained in without mask condition was significantly better than with N-95 mask condition. Thus is can be concluded that wearing of mask has detrimental effect of SIS in older adults. Hence audiologists can use this as a condition to counsel during hearing aid fitting and also to counsel about the decreased clarity issues due to wearing of mask.

Relationship Between Peripheral and Central Auditory Abilities and Iron Deficiency Anemia in Adolescent Girls.

PURPOSE: This study evaluated the peripheral hearing and central auditory processing abilities in Indian adolescent girls with iron deficiency anemia (IDA). METHOD: The participants consisted of 75 adolescent girls with IDA, 50 adolescent girls without IDA, and 50 adolescent boys without IDA. Participants underwent a test battery to evaluate auditory processing and peripheral hearing assessment. In this study, central auditory processing abilities were assessed using Speech Perception in Noise test in Kannada (SPIN-K) and quick speech perception in noise tests in Kannada, dichotic consonant-vowel test, gap detection threshold (GDT), and auditory digit sequencing and auditory digit span tests. RESULTS: Results showed that the hearing thresholds at extremely low and high frequencies (250 and 8000 Hz), although within clinically normal limits, were poorer in girls with IDA than in the control groups. Also, girls with IDA performed poorly in SPIN-K of the right ear, GDT, and auditory backward digit span tests. CONCLUSION: These subtle auditory deficiencies may be attributed to the compromised blood supply to the central auditory nervous system, as observed in the current study.

The association between pre-tonsillectomy education and postoperative emergency department returns: A retrospective cohort pilot study.

INTRODUCTION: Tonsillectomy is the most common pediatric surgery in Canada. Post-tonsillectomy 30-day Emergency Department (ED) visit rates are higher than other pediatric day surgeries. To date, there have been no studies assessing whether additional preoperative education directed by Child Life Specialists impacts preventable ED visits. The primary aim of this study was to evaluate whether additional preoperative tonsillectomy education is feasible and is associated with fewer ED visits and admissions in the immediate postoperative period compared to standard care. The secondary aim of this study was to assess whether this education was associated with a lower ED visit rate for preventable causes. METHODS: This is a retrospective chart review conducted in an academic tertiary pediatric hospital. Patients undergoing tonsillectomy surgery (from 2014 to 2019) were divided into three groups: consultation with a Child Life Specialist plus educational Booklet plus traditional surgeon-led education (CLS), educational Booklet plus surgeon-led education (Booklet), and traditional surgeon-led education (Traditional). The feasibility of the CLS education was assessed and the 30-day ED visit and admission rates were compared between groups. Visits included patients who returned to ED post-tonsillectomy and were not admitted, whereas admission included those who returned to ED and were admitted. RESULTS: 2081 patients undergoing tonsillectomy were included. 329 (15.8%) presented to the ED (within a median of 5 days), and 92 (4.4%) were admitted. ED visit/admission rates by group were: 14.7%/4.4% (CLS), 15.8%/4.1% (Booklet), and 16.2%/4.7% (Traditional) (p = 0.81/p = 0.84). The most common reason for return to ED was Hemorrhage (4.9%). Patients also returned to the ED for preventable reasons such as dehydration, pain, nausea/vomitting and fevers. CONCLUSIONS: Additional preoperative tonsillectomy education is feasible but is not associated with fewer ED visits and admissions, or fewer ED visits for preventable causes. Further research is needed to identify the optimal intervention to address the high post-tonsillectomy ED visit rate.

Relationship between temporal processing and phonological awareness in children with speech sound disorders.

Temporal processing ability contributes to the identification of small phonetic elements that is important for speech perception. Difficulty in these interferes with normal speech perception and phoneme recognition. The present study aimed to assess the temporal and phonological processing abilities in children with speech sound disorders (SSD). Temporal processing and phonological skills were evaluated in 32 participants in the age range of 6-10 years, equally divided into two groups. Group I included typically developing children, and Group II included children with SSD. Gap detection test and duration pattern test were used to assess temporal processing abilities, and phonological sensitivity training kit in Kannada (PhoST-K) assessed phonological processing abilities. The results showed that there was a significant difference in temporal and phonological processing between the two groups of children. A significant correlation between gap detection ability and deletion tasks and between duration pattern ability and oddity tasks was obtained. Based on the results, it is recommended to assess the temporal process pertinent to central auditory processing in children with SSD, as a close relationship between temporal processing abilities and phonological awareness exists.

Endocervical trophoblast for interrogating the fetal genome and assessing pregnancy health at five weeks.

Prenatal testing for fetal genetic traits and risk of obstetrical complications is essential for maternal-fetal healthcare. The migration of extravillous trophoblast (EVT) cells from the placenta into the reproductive tract and accumulation in the cervix offers an exciting avenue for prenatal testing and monitoring placental function. These cells are obtained with a cervical cytobrush, a routine relatively safe clinical procedure during pregnancy, according to published studies and our own observations. Trophoblast retrieval and isolation from the cervix (TRIC) obtains hundreds of fetal cells with >90% purity as early as five weeks of gestation. TRIC can provide DNA for fetal genotyping by targeted next-generation sequencing with single-nucleotide resolution. Previously, we found that known protein biomarkers are dysregulated in EVT cells obtained by TRIC in the first trimester from women who miscarry or later develop intrauterine growth restriction or preeclampsia. We have now optimized methods to stabilize RNA during TRIC for subsequent isolation and analysis of trophoblast gene expression. Here, we report transcriptomics analysis demonstrating that the expression profile of TRIC-isolated trophoblast cells was distinct from that of maternal cervical cells and included genes associated with the EVT phenotype and invasion. Because EVT cells are responsible for remodeling the maternal arteries and their failure is associated with pregnancy disorders, their molecular profiles could reflect maternal risk, as well as mechanisms underlying these disorders. The use of TRIC to analyze EVT genomes, transcriptomes and proteomes during ongoing pregnancies could provide new tools for anticipating and managing both fetal genetic and maternal obstetric disorders.

Influence of subcortical auditory processing and cognitive measures on cocktail party listening in younger and older adults.

OBJECTIVE: The study aimed to investigate the influence of subcortical auditory processing and cognitive measures on cocktail party listening in younger and older adults with normal hearing sensitivity. DESIGN: Tests administered included quick speech perception in noise test to assess cocktail party listening, speech auditory brainstem response to assess subcortical auditory processing and digit span, digit sequencing and spatial selective attention test to assess cognitive processing. STUDY SAMPLE: A total of 92 participants with normal hearing sensitivity participated in the study. They were divided into two groups: 52 young adults (20-40 years) and 40 older adults (60-80 years). RESULTS: The older adults performed significantly poorer than, the younger adults on the quick speech perception in noise test and various cognitive measures. Further, cognitive measures correlated with speech perception in noise in younger and older adults. The results of this study also showed that there was a significant deterioration in brainstem encoding of speech with ageing. Further, it was also noted that the fundamental frequency of the speech auditory brainstem response correlated with speech perception in noise. CONCLUSIONS: It can be concluded from this study that subcortical auditory processing and cognitive measures play a role in cocktail party listening.

Efficacy of SGLT2 Inhibitors as the Fifth Drug in the Management of Type 2 Diabetes Mellitus in Asian Indians not Controlled with at least 4 Oral Antidiabetic Drugs.

AIM: To evaluate the efficacy of SGLT2 inhibitors as an add-on therapy along with stricter lifestyle modification in Asian Indian type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control despite receiving an optimum dose of at least 4 oral antidiabetic drugs (OADs). METHODOLOGY: A retrospective analysis of data of 808 T2DM patients being treated with an SGLT2 inhibitor (Dapagliflozin, Empagliflozin or Canagliflozin) as an add-on drug in patients with inadequate glycemic control despite receiving optimum doses of at least any four OADs(metformin, sulphonylureas, pioglitazone, DPP4 Inhibitors, alpha-Glucosidase Inhibitors) and who preferred not to initiate insulin. RESULTS: The average age of the patients included was 51.63 years (SD ± 9.88). 57.7% were males. Average weight was 81.95±16.08 kg. Mean duration of diabetes was 34.08±39.04 months. The mean baseline fasting plasma glucose was 198.21 ± 38.21 mg/dl and mean post prandial plasma glucose was 264.22 ± 45.22 mg/ dl. The baseline HbA1c was 8.92 ± 1.47 %. Total 87.4 % of the cases responded to addition of SGLT2 inhibitors during a mean follow-up period of 6 months. The fasting plasma glucose (FBS) was reduced by -63.65 ± 19.93 mg/dl to a mean FBS of 134.57 ± 33.65 mg/dl (P=0.001). The post prandial plasma glucose (PPBS) was reduced by -79.28 ± 23.57 mg/dl to a mean PPBS of 184.94 ± 38.34 mg/dl (P=0.001). The mean HbA1c reduced significantly by -1.63 ± 0.99 % (P= 0.001). The mean weight reduction at 6 months of therapy was -3.03± 01.84 kg that is 3.8 % decrease from baseline (p=0.001).The response in age group < 55 years was 90.9 %, whereas in ≥55 years, it was 82.2% (p=0.001). The males responded more (91.0%) compared to females (82.5%) (p=0.001). Those with BMI < 23.5 kg/ m2 had marginally higher but insignificant response of 93.0% as compared to 87.1% in patients with high a BMI (≥23.5 kg/m2) (p=0.253). Patients with < 5years duration of diabetes responded better (91.8%) as compared to patients with a ≥ 5 years of diabetes (85.4%). CONCLUSION: SGLT2 inhibitors are effective in achieving desired glycemic goals even when used as a fifth add-on drug along with strict lifestyle modification in patients with inadequate glycemic control despite receiving an optimum dose of at least 4 oral antidiabetic drugs (OADs). SGLT2 inhibitors can be effectively used at any stage of diabetes.

Trophoblast survival signaling during human placentation requires HSP70 activation of MMP2-mediated HBEGF shedding.

Survival of trophoblast cells in the low oxygen environment of human placentation requires metalloproteinase-mediated shedding of HBEGF and downstream signaling. A matrix metalloproteinase (MMP) antibody array and quantitative RT-PCR revealed upregulation of MMP2 post-transcriptionally in human first trimester HTR-8/SVneo trophoblast cells and placental villous explants exposed to 2% O2. Specific MMP inhibitors established the requirement for MMP2 in HBEGF shedding and upregulation. Because α-amanitin inhibited the upregulation of HBEGF, differentially expressed genes were identified by next-generation sequencing of RNA from trophoblast cells cultured at 2% O2 for 0, 1, 2 and 4 h. Nine genes, all containing HIF-response elements, were upregulated at 1 h, but only HSPA6 (HSP70B') remained elevated at 2-4 h. The HSP70 chaperone inhibitor VER 155008 blocked upregulation of both MMP2 and HBEGF at 2% O2, and increased apoptosis. However, both HBEGF upregulation and apoptosis were rescued by exogenous MMP2. Proximity ligation assays demonstrated interactions between HSP70 and MMP2, and between MMP2 and HBEGF, supporting the concept that MMP2-mediated shedding of HBEGF, initiated by HSP70, contributes to trophoblast survival at the low O2 concentrations encountered during the first trimester, and is essential for successful pregnancy outcomes. Trophoblast survival during human placentation, when oxygenation is minimal, required HSP70 activity, which mediated MMP2 accumulation and the transactivation of anti-apoptotic ERBB signaling by HBEGF shedding.

Development of equally intelligible Telugu sentence-lists to test speech recognition in noise.

OBJECTIVE: To develop sentence lists in the Telugu language for the assessment of speech recognition threshold (SRT) in the presence of background noise through identification of the mean signal-to-noise ratio required to attain a 50% sentence recognition score (SRTn). DESIGN: This study was conducted in three phases. The first phase involved the selection and recording of Telugu sentences. In the second phase, 20 lists, each consisting of 10 sentences with equal intelligibility, were formulated using a numerical optimisation procedure. In the third phase, the SRTn of the developed lists was estimated using adaptive procedures on individuals with normal hearing. STUDY SAMPLE: A total of 68 native Telugu speakers with normal hearing participated in the study. Of these, 18 (including the speakers) performed on various subjective measures in first phase, 20 performed on sentence/word recognition in noise for second phase and 30 participated in the list equivalency procedures in third phase. RESULTS: In all, 15 lists of comparable difficulty were formulated as test material. The mean SRTn across these lists corresponded to -2.74 (SD = 0.21). CONCLUSIONS: The developed sentence lists provided a valid and reliable tool to measure SRTn in Telugu native speakers.

Fetal genome profiling at 5 weeks of gestation after noninvasive isolation of trophoblast cells from the endocervical canal.

Single-gene mutations account for more than 6000 diseases, 10% of all pediatric hospital admissions, and 20% of infant deaths. Down syndrome and other aneuploidies occur in more than 0.2% of births worldwide and are on the rise because of advanced reproductive age. Birth defects of genetic origin can be diagnosed in utero after invasive extraction of fetal tissues. Noninvasive testing with circulating cell-free fetal DNA is limited by a low fetal DNA fraction. Both modalities are unavailable until the end of the first trimester. We have isolated intact trophoblast cells from Papanicolaou smears collected noninvasively at 5 to 19 weeks of gestation for next-generation sequencing of fetal DNA. Consecutive matched maternal, placental, and fetal samples (n = 20) were profiled by multiplex targeted DNA sequencing of 59 short tandem repeat and 94 single-nucleotide variant sites across all 24 chromosomes. The data revealed fetal DNA fractions of 85 to 99.9%, with 100% correct fetal haplotyping. This noninvasive platform has the potential to provide comprehensive fetal genomic profiling as early as 5 weeks of gestation.