Survey response rates in health sciences education research: A 10-year meta-analysis.

Growth in the online survey market may be increasing response burden and possibly jeopardizing higher response rates. This meta-analysis evaluated survey trends over one decade (2011-2020) to determine: (1) changes in survey publication rates over time, (2) changes in response rates over time, (3) typical response rates within health sciences education research, (4) the factors influencing survey completion levels, and (5) common gaps in survey methods and outcomes reporting. Study I estimated survey publication trends between 2011 and 2020 using articles published in the top three health sciences education research journals. Study II searched the anatomical sciences education literature across six databases and extracted study/survey features and survey response rates. Time plots and a proportional meta-analysis were performed. Per 2926 research articles, the annual estimated proportion of studies with survey methodologies has remained constant, with no linear trend (p > 0.050) over time (Study I). Study II reported a pooled absolute response rate of 67% (95% CI = 63.9-69.0) across 360 studies (k), totaling 115,526 distributed surveys. Despite response rate oscillations over time, no significant linear trend (p = 0.995) was detected. Neither survey length, incentives, sponsorship, nor population type affected absolute response rates (p ≥ 0.070). Only 35% (120 of 339) of studies utilizing a Likert scale reported evidence of survey validity. Survey response rates and the prevalence of studies with survey methodologies have remained stable with no linear trends over time. We recommend researchers strive for a typical absolute response rate of 67% or higher and clearly document evidence of survey validity for empirical studies.

An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges.

Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph-based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly "Question-of-the-Month (QotM) Challenge" series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.

Conjunctival epitheliopathy induced by topical exposure to bacterial peptidoglycan, muramyl dipeptide.

Noninfectious exudative conjunctivitis can be experimentally produced in rabbits by application of the apoptogenic bacterial cell wall peptidoglycan, muramyl dipeptide (MDP) to the ocular surface. The purpose of this study was to investigate the acute conjunctival cytopathology induced by unilateral ocular surface exposure to MDP. Hematoxylin and eosin staining assessed bilateral tear cytopathology and conjunctival histopathology. The caspases levels in conjunctival tissue and tears were measured in standard assays utilizing p-nitroanaline tagged caspase-specific substrates. Immunofluorescent antibody identified intracellular caspase-3, nuclear factor-κß (NF-κß), and oxidative DNA damage (8-OHdG; 8-oxo-2'-deoxyguanosine) in tear and conjunctiva cells. DNA extracted from conjunctival tissues and pooled tear fluids were visualized by ethydium bromide agarose gel electrophoresis. Onset of ipsilateral conjunctivitis was due to an epitheliopathy characterized by loss of conjunctival epithelial cell adherence, exuviation of conjunctival epithelial cells, and neutrophil infiltration. Caspase-3 levels were significantly higher in exuviated cells in ipsilateral than contralateral tear (p's ≤ 0.001) collected at 3-5 h post MDP. Significantly higher caspase-2, -3, -6, -8 and -9 (p's ≤ 0.03) levels were detected in ipsilateral than contralateral conjunctival tissue at 5 h. Polymeric DNA was detected in ipsilateral but not contralateral conjunctival tissue and tears. Caspase-3, NF-κß, and 8-OHdG positive neutrophils were detected in bilateral conjunctiva and tear. The caspase-3/NF-κß epithelial cells and polymeric DNA in conjunctival tissue and shedding of caspase positive cells and polymeric DNA into ipsilateral tears support MDP induction of acute programmed cell death in vivo. The results suggest that ipsilateral exudative conjunctivitis is due to acute caspase-mediated conjunctival epitheliopathy induced by topical exposure to the bacterial peptidoglycan MDP.

The precision medicine process for treating rare disease using the artificial intelligence tool mediKanren.

There are over 6,000 different rare diseases estimated to impact 300 million people worldwide. As genetic testing becomes more common practice in the clinical setting, the number of rare disease diagnoses will continue to increase, resulting in the need for novel treatment options. Identifying treatments for these disorders is challenging due to a limited understanding of disease mechanisms, small cohort sizes, interindividual symptom variability, and little commercial incentive to develop new treatments. A promising avenue for treatment is drug repurposing, where FDA-approved drugs are repositioned as novel treatments. However, linking disease mechanisms to drug action can be extraordinarily difficult and requires a depth of knowledge across multiple fields, which is complicated by the rapid pace of biomedical knowledge discovery. To address these challenges, The Hugh Kaul Precision Medicine Institute developed an artificial intelligence tool, mediKanren, that leverages the mechanistic insight of genetic disorders to identify therapeutic options. Using knowledge graphs, mediKanren enables an efficient way to link all relevant literature and databases. This tool has allowed for a scalable process that has been used to help over 500 rare disease families. Here, we provide a description of our process, the advantages of mediKanren, and its impact on rare disease patients.

Progress toward a universal biomedical data translator.

Clinical, biomedical, and translational science has reached an inflection point in the breadth and diversity of available data and the potential impact of such data to improve human health and well-being. However, the data are often siloed, disorganized, and not broadly accessible due to discipline-specific differences in terminology and representation. To address these challenges, the Biomedical Data Translator Consortium has developed and tested a pilot knowledge graph-based "Translator" system capable of integrating existing biomedical data sets and "translating" those data into insights intended to augment human reasoning and accelerate translational science. Having demonstrated feasibility of the Translator system, the Translator program has since moved into development, and the Translator Consortium has made significant progress in the research, design, and implementation of an operational system. Herein, we describe the current system's architecture, performance, and quality of results. We apply Translator to several real-world use cases developed in collaboration with subject-matter experts. Finally, we discuss the scientific and technical features of Translator and compare those features to other state-of-the-art, biomedical graph-based question-answering systems.

Bilateral ptosis/blepharitis due to lepromatous leprosy.

PURPOSE: To underscore the importance of histopathological evaluation in cases presenting with a constellation of unusual ocular inflammation and physical findings. OBSERVATION: A 51-year-old male, presented with a chief complaint of worsening visual field loss due to droopy eyelids two months post excision of a right upper eyelid squamous cell carcinoma. His past medical history included chronic edematous facial features, chronic sinusitis, unexplained peripheral neuropathy, and worsening fatigue. Pre-blepharoplasty work-up revealed mechanical ptosis from lid edema, madarosis, a concave nasal bridge, pancytopenia, and numerous burn marks due to inadvertent injuries. Bilateral blepharoplasty was performed, and the excised tissue submitted for histopathological evaluation that revealed non-caseating granulomatous perineural inflammation with numerous acid-fast bacilli in dermal layers and nerves. These findings prompted a diagnosis of lepromatous leprosy with suspected bone marrow involvement. The source of the infection was unknown. The blepharoplasty restored his visual fields and multi-drug therapy (MDT) improved his general health and wellbeing with concomitant reductions of pancytopenia, fatigue, and facial edema. CONCLUSIONS AND IMPORTANCE: Biopsy histopathology, in patients with longstanding ocular adnexal inflammation, can facilitate diagnosis and treatment. To the authors' knowledge, this is an unusual ocular leprosy presentation and represents the first leprosy case diagnosed via blepharoplasty.

Application of MCAT questions as a testing tool and evaluation metric for knowledge graph-based reasoning systems.

"Knowledge graphs" (KGs) have become a common approach for representing biomedical knowledge. In a KG, multiple biomedical data sets can be linked together as a graph representation, with nodes representing entities, such as "chemical substance" or "genes," and edges representing predicates, such as "causes" or "treats." Reasoning and inference algorithms can then be applied to the KG and used to generate new knowledge. We developed three KG-based question-answering systems as part of the Biomedical Data Translator program. These systems are typically tested and evaluated using traditional software engineering tools and approaches. In this study, we explored a team-based approach to test and evaluate the prototype "Translator Reasoners" through the application of Medical College Admission Test (MCAT) questions. Specifically, we describe three "hackathons," in which the developers of each of the three systems worked together with a moderator to determine whether the applications could be used to solve MCAT questions. The results demonstrate progressive improvement in system performance, with 0% (0/5) correct answers during the first hackathon, 75% (3/4) correct during the second hackathon, and 100% (5/5) correct during the final hackathon. We discuss the technical and sociologic lessons learned and conclude that MCAT questions can be applied successfully in the context of moderated hackathons to test and evaluate prototype KG-based question-answering systems, identify gaps in current capabilities, and improve performance. Finally, we highlight several published clinical and translational science applications of the Translator Reasoners.

The effects of phylogeny, body size, and locomotor behavior on the three-dimensional shape of the pelvis in extant carnivorans.

The mammalian pelvis is thought to exhibit adaptations to the functional demands of locomotor behaviors. Previous work in primates has identified form-function relationships between pelvic shape and locomotor behavior; few studies have documented such relationships in carnivorans, instead focusing on long bones. Most work on the functional morphology of the carnivoran pelvis, in particular, has used univariate measures, with only a few previous studies incorporating a three-dimensional (3D) analysis. Here we test the hypothesis that carnivoran taxa that are characterized by different locomotor modes also differ in 3D shape of the os coxae. Using 3D geometric morphometrics and phylogenetic comparative methods, we evaluate the phylogenetic, functional, and size-related effects on 3D pelvis shape in a sample of 33 species of carnivorans. Using surface models derived from laser scans, we collected a suite of landmarks (N = 24) and curve semilandmarks (N = 147). Principal component analysis on Procrustes coordinates demonstrates patterns of shape change in the ischiopubis and ilium likely related to allometry. Phylogenetic generalized least squares analysis on principal component scores demonstrates that phylogeny and body size have greater effects on pelvic shape than locomotor function. Our results corroborate recent research finding little evidence of locomotor specialization in the pelvis of carnivorans. More research on pelvic morphological integration and evolvability is necessary to understand the factors driving pelvic evolution in carnivorans.

Donning Gloves Before Surgical Gown Eliminates Sleeve Contamination.

BACKGROUND: There are numerous studies in the literature that have recognized the importance of the glove-gown interface as a potential source of intraoperative bacterial contamination. It has been demonstrated that the methods with which one dons their surgical gown and gloves can alter the level of gown contamination. We hypothesize that donning undergloves before the surgical gown will decrease if not eliminate sleeve contamination. METHODS: We performed a comparative study to assess the differences in gown contamination between three different gown and glove donning techniques. Participants ranged in experience level from intern to attending. Each participant covered their hands with ultraviolet light disclosing lotion and then donned surgical gown and gloves with their preferred technique and with the proposed technique in a randomly assigned order. The gowns were then removed and analyzed under ultraviolet light for distance and quantity of sleeve contamination. RESULTS: The gloves-first technique demonstrated zero contamination in all samples. This is significantly less than both closed and open staff-assisted techniques (P < .0001). All samples of closed and open techniques demonstrated some level of contamination. The distance of contamination on the right sleeve is significantly greater than the left sleeve (P < .0001). DISCUSSION: The gloves-first technique demonstrates zero sleeve contamination throughout all samples, regardless of the experience level. We strongly recommend considering the use of this glove and gown donning technique as opposed to the currently accepted closed and open techniques in an effort to reduce gown contamination.

Trigeminal hypertrophic interstitial neuropathy presenting as unilateral proptosis, ptosis, tearing, and facial neuralgia.

PURPOSE: To show the utility of MRI and histology in diagnosing rare cases of trigeminal hypertrophic interstitial neuropathy (HIN). OBSERVATIONS: A 57-year-old African-American woman presented with a 4-year history of right eye proptosis with tearing, headaches, and worsening right-sided trigeminal neuralgia symptoms and jaw pain. HIV and diabetes tests were negative and thyroid function was normal. MRI identified abnormal thickening of all trigeminal nerve divisions and proptosis secondary to right trigeminal nerve V1 division enlargement. The excised tissue contained S-100 positive Schwann cells in an onion-bulb pattern. Headaches resolved, but proptosis and mild trigeminal neuralgia remained 1 year post-surgery. CONCLUSIONS AND IMPORTANCE: Trigeminal HIN is very rare, but presents as chronic progressive ocular symptoms with trigeminal neuralgia. Trigeminal nerve hypertrophy is identified by MRI and confirmed histopathologically by detection of Schwann cells in an onion bulb formation.

A Review of FOXI3 Regulation of Development and Possible Roles in Cancer Progression and Metastasis.

Development and cancer share a variety of functional traits such as EMT, cell migration, angiogenesis, and tissue remodeling. In addition, many cellular signaling pathways are noted to coordinate developmental processes and facilitate aspects of tumor progression. The Forkhead box superfamily of transcription factors consists of a highly conserved DNA binding domain, which binds to specific DNA sequences and play significant roles during adult tissue homoeostasis and embryogenesis including development, differentiation, metabolism, proliferation, apoptosis, migration, and invasion. Interestingly, various studies have implicated the role of key Fox family members such as FOXP, FOXO, and FOXA during cancer initiation and metastases. FOXI3, a member of the Forkhead family affects embryogenesis, development, and bone remodeling; however, no studies have reported a role in cancer. In this review, we summarize the role of FOXI3 in embryogenesis and bone development and discuss its potential involvement in cancer progression with a focus on the bone metastasis. Moreover, we hypothesize possible mechanisms underlying the role of FOXI3 in the development of solid tumor bone metastasis.

The James A. Rand Young Investigator's Award: Battling the Opioid Epidemic with Prospective Pain Threshold Measurement.

BACKGROUND: Responsible analgesic prescribing is paramount in the opioid epidemic era, yet no standardized protocol exists. We aim to (1) quantify and correlate outpatient opioid need after total knee and hip arthroplasties (TKA and THA) with preoperative objective pain pressure thresholds (PPTs) and subjective pain measures and (2) report incidence of nonsurgical opioid prescriptions 6 weeks postoperatively. METHODS: Prospectively, PPTs were measured using an algometer with a maximum force of 20 pounds in 160 consecutive patients (90 TKA and 70 THA). Two locations were tested: operative joint (medial epicondyle TKA and lateral iliac crest THA) and ipsilateral olecranon for systemic control. Visual Analog Score, Pain Severity Score, Pain Interference Score, and subjective pain threshold were obtained. Six-week outpatient narcotic consumption morphine equivalents recorded and prescriptions crosschecked with the state Controlled Substance Reporting System. Multivariate analysis was performed to evaluate local and/or systemic PPT and subjective measures with narcotic consumption. RESULTS: Average operative site and systemic PPT was 6.91 and 7.72 pounds force, respectively. Subjective averages: Visual Analog Score 7.14, Pain Severity Score 5.05, Pain Interference Score 5.16, and perceived threshold 6.77. Six-week average outpatient narcotic consumption was 314.9 morphine equivalents or 125 five milligram oxycodones. Twenty percent received opioids from outside providers. Linear regression revealed a negative correlation between operative site PPT (-0.26; P = .047) and systemic PPT (-0.31; P = .021). Subjective pain metrics failed to meet significance. CONCLUSION: This novel study demonstrated a statistically significant negative correlation between preoperative pain threshold and outpatient narcotic consumption. Twenty percent of patients received opioid prescriptions outside orthopedic providers in the 6 weeks after surgery highlighting the importance of interdisciplinary communication.

Influence of Trainee Experience on Choice of Orthopaedic Subspecialty Fellowship.

INTRODUCTION: Most orthopaedic surgery residents elect to pursue additional subspecialty training; however, factors influencing the choice of subspecialty and the ways that these factors change during training are not well understood. The aim of this investigation was to determine, on the basis of a trainee's postgraduate year (PGY), whether variability exists in factors valued when choosing a specific subspecialty. METHODS: We emailed an online survey (intended for distribution to current trainees) to a list of orthopaedic surgery residency program coordinators in the United States. The survey queried demographic information, PGY level, and the importance of 14 discrete factors in the selection of fellowship specialty according to a Likert scale rating from 1 to 4. RESULTS: There were 359 respondents representing an even distribution of PGY levels. Junior trainees assigned greater relative value to geographic location, on-call responsibilities, financial compensation, and the tradition of the residency program, whereas senior trainees assigned greater relative value to variety of cases and intellectual stimulation (all P < 0.05). DISCUSSION: The differences seen in factors valued based on trainee experience may highlight the relative importance of greater exposure to the breadth of orthopaedic surgical practice during training and increasing awareness of clinical competencies and responsibilities. CONCLUSIONS: When deciding on orthopaedic subspecialty choice, junior trainees value lifestyle factors relatively more than do senior trainees, whereas senior trainees value case variety and stimulation relatively more than junior trainees do.

Factors Influencing Orthopedic Surgery Residents' Choice of Subspecialty Fellowship.

In the setting of increasing student debt, a rapidly changing health care system, and growing transparency in the age of outcome reporting, residents have many factors to consider when determining which fellowship to pursue. An institutional review board-approved link to an online survey was emailed to orthopedic surgery trainees across the United States. Demographics were collected, and 14 fellowship influences were assessed using a Likert scale. A total of 360 responses were received. Of the respondents, 85.5% (n=308) were male and 14.5% (n=52) were female. Responses were received from every region of the United States and from every postgraduate year. Respondents represented the gamut of relationship status and indebtedness. Respondents were interested in all of the current major subspecialties. Pursuit of an intellectually stimulating subspecialty had the highest average Likert score (3.38), followed by variety of cases (3.26). The lowest scores were for residency program with a strong tradition of placing into a particular subspecialty (2.08) and potential to conduct research in that subspecialty (2.09). Marital status, number of children, and level of debt did not significantly affect the importance of factors in selecting a fellowship. Choice of subspecialty did influence the level of importance of various factors. Intellectual stimulation and a strong mentor were the most influential factors in the decision to pursue a given fellowship. Because fellowship is now the norm, it is important to understand the motives behind young orthopedic surgeons' career aspirations. [Orthopedics. 2017; 40(5):e820-e824.].

Development of IsoTaG, a Chemical Glycoproteomics Technique for Profiling Intact N- and O-Glycopeptides from Whole Cell Proteomes.

Protein glycosylation can have an enormous variety of biological consequences, reflecting the molecular diversity encoded in glycan structures. This same structural diversity has imposed major challenges on the development of methods to study the intact glycoproteome. We recently introduced a method termed isotope-targeted glycoproteomics (IsoTaG), which utilizes isotope recoding to characterize azidosugar-labeled glycopeptides bearing fully intact glycans. Here, we describe the broad application of the method to analyze glycoproteomes from a collection of tissue-diverse cell lines. The effort was enabled by a new high-fidelity pattern-searching and glycopeptide validation algorithm termed IsoStamp v2.0, as well as by novel stable isotope probes. Application of the IsoTaG platform to 15 cell lines metabolically labeled with Ac4GalNAz or Ac4ManNAz revealed 1375 N- and 2159 O-glycopeptides, variously modified with 74 discrete glycan structures. Glycopeptide-bound glycans observed by IsoTaG were found to be comparable to released N-glycans identified by permethylation analysis. IsoTaG is therefore positioned to enhance structural understanding of the glycoproteome.

Lenalidomide Induces Interleukin-21 Production by T Cells and Enhances IL21-Mediated Cytotoxicity in Chronic Lymphocytic Leukemia B Cells.

The immunomodulatory drug lenalidomide has demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL), despite a lack of direct cytotoxic effects in vitro The mechanism of lenalidomide efficacy in vivo is thought to occur via a combination of enhanced immune activity and an alteration of tumor cell-microenvironment interactions. We demonstrate in whole blood from patients with CLL that lenalidomide significantly depletes malignant B cells. Lenalidomide also induced production of interleukin-21 (IL21) and its mRNA in T cells from patients with CLL. In addition, lenalidomide enhanced upregulation of functional IL21 receptor (IL21R) on the cell surface and increased receptor mRNA in vitro The in vitro combination of IL21 and lenalidomide enhanced IL21-mediated cytotoxicity toward CLL cells through a variety of mechanisms. We show association of cell death with upregulation of Bid by IL21, enhanced upregulation of Bid by the combination therapy, and diminished Lck and downstream BCR signaling activation of Syk and PLCG2. Collectively, we demonstrated an immune cell-tumor cell interaction through lenalidomide-mediated induction of IL21 and IL21R, with enhanced IL21-mediated cytotoxicity, which provides justification for this combination in clinical trials for patients with CLL. Cancer Immunol Res; 4(8); 698-707. ©2016 AACR.

Biomechanical performance of a new device for medial malleolar fractures.

BACKGROUND: Displaced medial malleolus fractures require surgical repair because of the critical role the structure plays in normal joint function. Various approaches exist, but options are limited for small fragment fractures. This study compared repair with the Medial Malleolar Sled fixation system (Trimed, Inc, Valencia, CA) to lag screws in 2 modes of biomechanical loading in a cadaveric model. METHODS: A Müller type B medial malleolus fracture was simulated on matched pairs of cadaveric lower extremities and repaired with the sled or 2 cancellous lag screws. Tibial distraction (tension, n = 10) or internal rotation (torsion, n = 11) was applied. Fragment movement was measured in the sagittal (tension and torsion) and transverse (torsion-only) planes. Fragment movement at 1 mm and 2 mm (clinical malunion) of gapping during tension and at 2, 4, 6, and 8 N-m during torsion was analyzed via paired t tests. RESULTS: In tension, the load at the 2-mm gap was statistically lower for screws (P = .026). Opening angle was statistically larger for the sled at the 1-mm (P = .0004) and 2-mm (P = .008) gap. In torsion, gapping was statistically lower for the sled (ranging from P = .0013 at 4 N-m to P = .0187 at 8 N-m). No differences were detected for opening angle or transverse plane movement. CONCLUSION: The sled appeared stronger in tension and as effective as lag screws in torsion. The sled may be a viable option for fractures too small for 4.0- or 3.5-mm lag screws. CLINICAL RELEVANCE: The sled may be suitable in applications where a tension band would normally be considered and may provide stronger fixation in osteoporotic bone compared with lag screw fixation.

Orbital sporadic Burkitt lymphoma in an adult diabetic African American female and a review of adult orbital cases.

A case of sporadic Burkitt lymphoma (sBL) presenting with jaw and lid involvement in a diabetic adult African American female and a review of adult orbital Burkitt lymphoma cases are presented. Lid edema, visual loss, ophthalmoparesis, proptosis, and sinusitis progressed over 4 weeks despite antibiotic and steroid treatment. Upper lid biopsy histopathological evaluation and immunophenotyping revealed a homogenous mass of atypical CD10 and CD20-negative B-cells and tingible body macrophages yielding a "starry sky" appearance. Cytogenetic analysis detected a minor variant c-MYC translocation, but no Epstein-Barr virus RNA. Detection of multiple lesions prompted a diagnosis of stage IV disease that totally regressed following radiation and chemotherapy. Review results of the six adult orbital sBL cases support a poor prognosis and a heightened suspicion of variant CD10, CD20 and BCL6 positive sBL in adults presenting with jaw pain and rapidly progressive orbital symptoms, particularly in female, African American, and diabetic patients.

Orbital metastasis of keratinizing squamous cell cervical carcinoma with giant cells. A case report.

A case of orbital metastasis of cervical keratinizing squamous cell carcinoma is presented. The patient, in remission from primary cervical and ovarian cancers, presented with complaints of left eye ptosis and pain. Examination revealed the presence of a moderately tender mass along the left supra-temporal orbital rim and downward displacement of the left globe. Computed tomography revealed a poorly circumscribed mass with superior lateral wall bone loss. Excised tissue contained invasive, poorly differentiated nests of pan keratin and epithelial membrane antigen-positive squamous cells with numerous pleomorphic multinucleated giant cells. Multiple treatment regimes were unsuccessful, and the patient expired due to disease complications after 3 months.

Subclinical hypothyroidism and pregnancy outcomes.

BACKGROUND: Clinical thyroid dysfunction has been associated with pregnancy complications such as hypertension, preterm birth, low birth weight, placental abruption, and fetal death. The relationship between subclinical hypothyroidism and pregnancy outcomes has not been well studied. We undertook this prospective thyroid screening study to evaluate pregnancy outcomes in women with elevated thyrotropin (thyroid-stimulating hormone, TSH) and normal free thyroxine levels. METHODS: All women who presented to Parkland Hospital for prenatal care between November 1, 2000, and April 14, 2003, had thyroid screening using a chemiluminescent TSH assay. Women with TSH values at or above the 97.5th percentile for gestational age at screening and with free thyroxine more than 0.680 ng/dL were retrospectively identified with subclinical hypothyroidism. Pregnancy outcomes were compared with those in pregnant women with normal TSH values between the 5th and 95th percentiles. RESULTS: A total of 25,756 women underwent thyroid screening and were delivered of a singleton infant. There were 17,298 (67%) women enrolled for prenatal care at 20 weeks of gestation or less, and 404 (2.3%) of these were considered to have subclinical hypothyroidism. Pregnancies in women with subclinical hypothyroidism were 3 times more likely to be complicated by placental abruption (relative risk 3.0, 95% confidence interval 1.1-8.2). Preterm birth, defined as delivery at or before 34 weeks of gestation, was almost 2-fold higher in women with subclinical hypothyroidism (relative risk, 1.8, 95% confidence interval 1.1-2.9). CONCLUSION: We speculate that the previously reported reduction in intelligence quotient of offspring of women with subclinical hypothyroidism may be related to the effects of prematurity. LEVEL OF EVIDENCE: II-2.