Lauren A. Tomlinson

Review of cervical spine anomalies in genetic syndromes.

Study Design. Focused review of the literature. Objective. Assist spine specialists in diagnosis and treatment of cervical spine anomalies found in selected genetic syndromes. Summary of Background Data. Cervical spine instability and/or stenosis are potentially debilitating problems in many genetic syndromes. These problems can be overlooked among the other systemic issues more familiar to clinicians and radiologists evaluating these syndromes. It is imperative that spine specialists understand the relevant issues associated with these particular syndromes. Methods. The literature was reviewed for cervical spine issues in 10 specific syndromes. The information is presented in the following order: First, the identification and treatment of midcervical kyphosis in Larsen syndrome and diastrophic dysplasia (DD). Next, the upper cervical abnormalities seen in Down syndrome, 22q11.2 Deletion syndrome, pseudoachondroplasia, Morquio syndrome, Goldenhar syndrome, spondyloepiphyseal dysplasia congenita, and Kniest dysplasia. Finally, the chin-on-chest deformity of fibrodysplasia ossificans progressiva. Results. Midcervical kyphosis in patients with Larsen syndrome and DD needs to be evaluated and imaged often to track deformity progression. Upper cervical spine instability in Down syndrome is most commonly caused by ligamentous laxity at C1 to C2 and occiput–C1 levels. Nearly 100% of patients with 22q11.2 deletion syndrome have cervical spine abnormalities, but few are symptomatic. Patients with pseudoachondroplasia and Morquio syndrome have C1 to C2 instability related to odontoid dysplasia (hypoplasia and os odontoideum). Morquio patients also have soft tissue glycosaminoglycan deposits, which cause stenosis and lead to myelopathy. Severely affected patients with spondyloepiphyseal dysplasia congenita are at high risk of myelopathy because of atlantoaxial instability in addition to underlying stenosis. Kniest syndrome is associated with atlantoaxial instability. Cervical spine anomalies in Goldenhar syndrome are varied and can be severe. Fibrodysplasia ossificans progressiva features severe, deforming heterotopic ossification that can become life-threatening. Conclusion. It is important to be vigilant in the diagnosis and treatment of cervical spine anomalies in patients with genetic syndromes.

Growing-Rod Graduates: Lessons Learned from Ninety-nine Patients Who Completed Lengthening

BACKGROUND Growing-rod spinal instrumentation systems are a valuable tool for managing severe early-onset scoliosis. There is little information about the end point of treatment. METHODS A multicenter early-onset-scoliosis database was searched to identify patients who had undergone treatment with growing rods and either had had a final operative procedure or were still being treated with the growing rods after reaching skeletal maturity (defined as fourteen years of age or older). Clinical, radiographic, and operative data were analyzed. RESULTS Ninety-nine patients met the inclusion criteria, and ninety-two (93%) of them had had a final operative procedure. The remaining seven patients (7%) were older than fourteen years but had not undergone a final procedure. Of the ninety-two patients who had a final procedure, seventy-nine (86%) had an instrumented fusion, nine (10%) had growing-rod exchanges and fusion in situ, three (3%) had the growing rods left in place and fusion in situ, and one (1%) had only growing-rod removal. The mean age (and standard deviation) at the final fusion was 12.4 ± 1.9 years. In forty-four (55%) of eighty patients for whom the information was available, the number of vertebral levels fused was the same as the number of vertebral levels spanned by the growing rods. The percent correction of the curve after final fusion was none or minimal (≤ 20 %) in eleven (18%) of the sixty-two patients for whom sufficient-quality radiographs were available, moderate (21% to 50%) in thirty (48%), and substantial (≥ 51 %) in nine (15%); the curve had worsened in twelve patients (19%). The mean duration of growing-rod treatment was 5.0 ± 2.6 years. Of fifty-eight operative reports made at final fusion that contained comments on spinal flexibility, eleven (19%) described the spine as being mobile, eleven (19%) described decreased flexibility, and thirty-six (62%) described the spine as being completely stiff. At final fusion, twenty-two patients (24%) had osteotomies and seven patients (8%) had a thoracoplasty. CONCLUSIONS Most patients underwent growing-rod removal and final instrumented fusion. The final fusion often included the same levels spanned by the growing rods and usually achieved <50% additional correction of the deformity remaining at the end of the growing-rod management. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Postnatal Growth and Retinopathy of Prematurity Study: Rationale, Design, and Subject Characteristics

ABSTRACT Purpose: Postnatal-growth-based predictive models demonstrate strong potential for improving the low specificity of retinopathy of prematurity (ROP) screening. Prior studies are limited by inadequate sample size. We sought to study a sufficiently large cohort of at-risk infants to enable development of a model with highly precise estimates of sensitivity for severe ROP. Methods: The Postnatal Growth and ROP (G-ROP) Study was a multicenter retrospective cohort study of infants at 30 North American hospitals during 2006–2012. A total of 65 G-ROP-certified abstractors submitted data to a secure, web-based database. Data included ROP examination findings, treatments, complications, daily weight measurements, daily oxygen supplementation, maternal/infant demographics, medical comorbidities, surgical events, and weekly nutrition. Data quality was monitored with system validation rules, data audits, and discrepancy algorithms. Results: Of 11,261 screened infants, 8334 were enrolled, and 2927 had insufficient data due to transfer, discharge, or death. Of the enrolled infants, 90% (7483) had a known ROP outcome and were included in the study. Median birth weight was 1070 g (range 310–3000g) and mean gestational age 28 weeks (range 22–35 weeks). Severe ROP (Early Treatment of Retinopathy type 1 or 2) developed in 931 infants (12.5%). Conclusion: Successful incorporation of a predictive model into ROP screening requires confidence that it will capture cases of severe ROP. This dataset provides power to estimate sensitivity with half-confidence interval width of less than 0.5%, determined by the high number of severe ROP cases. The G-ROP Study represents a large, diverse cohort of at-risk infants undergoing ROP screening. It will facilitate evaluation of growth-based algorithms to improve efficiency of ROP screening.

Validation of the Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) Model.

Importance The Childrens Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) model uses birth weight (BW), gestational age at birth (GA), and weight gain rate to predict the risk of severe retinopathy of prematurity (ROP). In a model development study, it predicted all infants requiring treatment, while greatly reducing the number of examinations compared with current screening guidelines. Objective To validate the CHOP ROP model in a multicenter cohort that is large enough to obtain a precise estimate of the model’s sensitivity for treatment-requiring ROP. Design, Setting, and Participants This investigation was a secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study. The setting was 30 hospitals in the United States and Canada between January 1, 2006, and June 30, 2012. The dates of analysis were September 28 to October 5, 2015. Participants were premature infants at risk for ROP with a known ROP outcome. Main Outcomes and Measures Sensitivity for Early Treatment of Retinopathy of Prematurity type 1 ROP and potential reduction in the number of infants requiring examinations. In the primary analysis, the CHOP ROP model was applied weekly to predict the risk of ROP. If the risk was above a cut-point level (high risk), examinations were indicated, while low-risk infants received no examinations. In a secondary analysis, low-risk infants received fewer examinations rather than no examinations. Results Participants included 7483 premature infants at risk for ROP with a known ROP outcome. Their median BW was 1070 g (range, 310-3000 g), and their median GA was 28 weeks (range, 22-35 weeks). Among them, 3575 (47.8%) were female, and their race/ethnicity was 3615 white (48.3%), 2310 black (30.9%), 233 Asian (3.1%), 93 Pacific Islander (1.2%), and 40 American Indian/Alaskan native (0.5%). The original CHOP ROP model correctly predicted 452 of 459 infants who developed type 1 ROP (sensitivity, 98.5%; 95% CI, 96.9%-99.3%), reducing the number of infants requiring examinations by 34.3% if only high-risk infants received examinations. Lowering the cut point to capture all type 1 ROP cases (sensitivity, 100%; 95% CI, 99.2%-100%) resulted in only 6.8% of infants not requiring examinations. However, if low-risk infants were examined at 37 weeks’ postmenstrual age and followed up only if ROP was present at that examination, all type 1 ROP cases would be captured, and the number of examinations performed among infants with GA exceeding 27 weeks would be reduced by 28.4%. Conclusion and Relevance The CHOP ROP model demonstrated high but not 100% sensitivity and may be better used to reduce examination frequency. The model might be used reliably to guide a modified ROP screening schedule and decrease the number of examinations performed.

A Tiered Approach to Retinopathy of Prematurity Screening (TARP) Using a Weight Gain Predictive Model and a Telemedicine System

Importance The Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study telemedicine system of remote fundus image grading and The Children’s Hospital of Philadelphia Retinopathy of Prematurity (CHOP-ROP) postnatal weight gain predictive model are 2 approaches for improving ROP screening efficiency. Current screening has low specificity for severe ROP. Objective To describe a tiered approach to ROP screening (TARP) for identifying children who develop severe ROP using telemedicine and a predictive model synergistically. Design, Setting, and Participants This investigation was a post hoc analysis of a cohort in the e-ROP Study (a multicenter prospective telemedicine study) and the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study (a multicenter retrospective cohort study). The setting was neonatal intensive care units at The Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania. Participants in the e-ROP Study were premature infants with a birth weight less than 1251 g and a known ROP outcome enrolled between May 25, 2011, and October 31, 2013. The G-ROP Study enrolled all infants undergoing ROP examinations with a known ROP outcome who were born between January 1, 2006, and December 31, 2011. Main Outcomes and Measures The mean outcomes were the sensitivity for type 1 ROP, reductions in infants requiring imaging or examinations, numbers of imaging sessions and examinations, and total clinical encounters (imaging sessions and examinations combined). The following 4 screening approaches were evaluated: ROUTINE (only diagnostic examinations by an ophthalmologist), CHOP-ROP (birth weight and gestational age, with weekly weight gain initiating examinations when the risk cut point is surpassed), e-ROP IMAGING (trained reader grading of type 1 or 2 ROP initiates diagnostic examinations), and TARP (CHOP-ROP alarm initiates imaging, and imaging finding of severe ROP initiates diagnostic examinations). Results A total of 242 infants were included in the study, with a median birth weight of 858 g (range, 690-1035 g). The median gestational age was 27 weeks (range, 25-29 weeks). Fifty-one percent (124 of 242) were female, and 49% (118 of 242) were male. The race/ethnicity was 27.3% (66 of 242) white, 56.2% (136 of 242) black, 2.1% (5 of 242) Native American, 1.7% (4 of 242) Asian, and 12.8% (31 of 242) other. The sensitivity for detecting type 1 ROP (32 infants) was 100% (95% CI, 89.3%-100%) with each approach. With ROUTINE, 242 infants had 877 examinations; with CHOP-ROP, 184 infants had 730 examinations; with e-ROP IMAGING, 242 infants had 532 imaging sessions, and 94 infants had 345 examinations (877 patient encounters); and with TARP, 182 infants had 412 imaging sessions, and 87 infants had 322 examinations (734 patient encounters). Conclusions and Relevance The tiered approach to ROP screening was associated with a reduced number of examinations and imaging sessions compared with the other approaches. Applying a postnatal growth model and telemedicine system in a tiered approach may reduce the number of clinical ROP interventions more than either approach alone.

Validation of the Colorado Retinopathy of Prematurity Screening Model

Importance The Colorado Retinopathy of Prematurity (CO-ROP) model uses birth weight, gestational age, and weight gain at the first month of life (WG-28) to predict risk of severe retinopathy of prematurity (ROP). In previous validation studies, the model performed very well, predicting virtually all cases of severe ROP and potentially reducing the number of infants who need ROP examinations, warranting validation in a larger, more diverse population. Objective To validate the performance of the CO-ROP model in a large multicenter cohort. Design, Setting, Participants This study is a secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study, a retrospective multicenter cohort study conducted in 29 hospitals in the United States and Canada between January 2006 and June 2012 of 6351 premature infants who received ROP examinations. Main Outcomes and Measures Sensitivity and specificity for severe (early treatment of ROP [ETROP] type 1 or 2) ROP, and reduction in infants receiving examinations. The CO-ROP model was applied to the infants in the G-ROP data set with all 3 data points (infants would have received examinations if they met all 3 criteria: birth weight, <1501 g; gestational age, <30 weeks; and WG-28, <650 g). Infants missing WG-28 information were included in a secondary analysis in which WG-28 was considered fewer than 650 g. Results Of 7438 infants in the G-ROP study, 3575 (48.1%) were girls, and maternal race/ethnicity was 2310 (31.1%) African American, 3615 (48.6%) white, 233 (3.1%) Asian, 40 (0.52%) American Indian/Alaskan Native, and 93 (1.3%) Pacific Islander. In the study cohort, 747 infants (11.8%) had type 1 or 2 ROP, 2068 (32.6%) had lower-grade ROP, and 3536 (55.6%) had no ROP. The CO-ROP model had a sensitivity of 96.9% (95% CI, 95.4%-97.9%) and a specificity of 40.9% (95% CI, 39.3%-42.5%). It missed 23 (3.1%) infants who developed severe ROP. The CO-ROP model would have reduced the number of infants who received examinations by 26.1% (95% CI, 25.0%-27.2%). Conclusions and Relevance The CO-ROP model demonstrated high but not 100% sensitivity for severe ROP and missed infants who might require treatment in this large validation cohort. The model requires all 3 criteria to be met to signal a need for examinations, but some infants with a birth weight or gestational age above the thresholds developed severe ROP. Most of these infants who were not detected by the CO-ROP model had obvious deviation in expected weight trajectories or nonphysiologic weight gain. These findings suggest that the CO-ROP model needs to be revised before considering implementation into clinical practice.

Development of Modified Screening Criteria for Retinopathy of Prematurity: Primary Results From the Postnatal Growth and Retinopathy of Prematurity Study

Importance Current retinopathy of prematurity (ROP) guidelines, which are based on studies of high-risk infants and expert opinion, have low specificity for disease requiring treatment. Postnatal weight gain–based models improve specificity but have been limited by complexity and small development cohorts, which results in model overfitting and resultant decreased sensitivity in validation studies. Objective To develop a birth weight (BW), gestational age (GA), and weight gain (WG) prediction model using data from a broad-risk cohort of premature infants. Design, Setting, and Participants The Postnatal Growth and ROP Study was a retrospective multicenter cohort study conducted in 29 hospitals in the United States and Canada from 2006 to 2012 that included 7483 premature infants at risk for ROP with a known ROP outcome. A hybrid modeling approach was used that combined BW/GA criteria, weight comparison with expected growth from infants without ROP, multiple growth-interval assessments, consideration of nonphysiological WG, and user-friendly screening criteria. Numerous BW/GA levels, postnatal age periods, time intervals, and WG percentile thresholds were evaluated to identify the most robust parameters. Main Outcome and Measures Sensitivity for Early Treatment of ROP Study type 1 ROP and potential reduction in infants who require examinations. Results Of 7483 infants, the median (SD) BW was 1099 (359) g, the median GA was 28 weeks (range, 22-35), 3575 (47.8%) were female, 3615 (48.4%) were white, 2310 (30.9%) were black, 233 (3.1%) were Asian, 93 (1.2%) were Pacific Islander, and 40 (0.5%) were American Indian/Alaskan Native. Infants who met any of 6 criteria would undergo examinations: (1) a GA of younger than 28 weeks; (2) a BW of less than 1051 g; a WG of less than 120 g, 180 g, or 170 g during ages 10 to 19, 20 to 29, or 30 to 39 days, respectively; or hydrocephalus. These criteria predicted 459 of 459 (100%) type 1 (sensitivity, 100%; 95% CI, 99.2%-100%), 524 of 524 (100%) treated, and 466 of 472 (98.7%) type 2 cases while reducing the number of infants who required examinations by 2269 (30.3%). Conclusions and Relevance This cohort study, broadly representative of infants who are undergoing ROP examinations, provides evidence-based screening criteria. With validation, the Postnatal Growth and ROP Study criteria could be incorporated into ROP screening guidelines to reduce the number of infants who require examinations in North America.

Distraction Phenomenon After Lengthening of Spinal Growing Rods

The treatment of early-onset scoliosis remains challenging, and growing-rod instrumentation has been shown to be an option for allowing trunk and lung development while partially straightening and controlling spine deformity1-4. Initial treatment with single rods had an unacceptable risk-benefit ratio3-6, and dual rods are currently preferred, achieving corrections from 30% to 64% at the time of the final spinal fusion3,7. Unfortunately, dual-rod systems retain complication rates ranging from 19% to 58%2,3,8,9 in instrumented patients. The most common complications include wound infections, skin breakdown, proximal and distal junctional kyphosis, and implant-related complications (e.g., rod breakage, implant prominence, and hook and/or screw pullout)8,10. Spontaneous fusion rates of 89% were also reported as a potential complication associated with submuscular rod placement and surgical procedures at early ages7,11, sometimes requiring osteotomies during the final posterior fusion7. To the best of our knowledge, there is no prior report of distraction phenomenon related to the growing-rod lengthening procedure. The patient’s parents were informed that data concerning the case would be submitted for publication, and they provided consent. A two-day-old girl was urgently transferred to our hospital because of a thoracic mass that grossly resembled arachnoid tissue. Radiographs showed a right thoracic curve measuring 15° from T1 to T10, a localized kyphosis of 57° from T5 to T7, and a global kyphosis of 18° from T2 to T12. Additional image investigation revealed a congenital malformation with butterfly vertebrae from T5 to T7 and a posterior vertebral defect with incomplete laminae extending from T3 to T6. Magnetic resonance imaging showed that the mass had grown out from the spinal cord. The patient underwent neurosurgery, and the final histologic characteristics …