How Accurate is the Multiplier Method in Predicting the Timing of Angular Correction After Hemiepiphysiodesis?

PURPOSE: The purpose of the study was to validate the accuracy of the Multiplier Method (MM) in predicting the timing of angular correction after hemiepiphysiodesis and to determine the role of using skeletal age when calculating those predictions. METHODS: This retrospective study included 131 physes in 77 patients treated with hemiepiphysiodesis to gradually correct a coronal plane deformity before skeletal maturity. To compare the MM's predictions to the actual treatment duration, the "desired angular correction" was considered the actual achieved angular correction determined from the "endpoint x-ray" (last x-ray before implant removal). We measured the bone length and width of the growth plate from the preoperative x-ray and calculated the MM's prediction of the duration of treatment based on the MM formula. We compared the predicted duration to the observed duration of treatment for each case. The difference was calculated by subtracting the observed duration from the predicted duration. The result was the "absolute difference," which is the number of months over or under predicted by the MM. RESULTS: The mean absolute difference between the MM's predicted duration and the observed duration was 2.31 months, which was highly significant (P≤0.001). The MM's prediction agreed with the observed duration of treatment (ie, zero absolute difference) in 15% of the predictions, 69% were under predicted, and 16% were over predicted. Sixty-eight percent of the absolute differences were within 3 months regardless of the direction of error. The mean difference was relatively less in genu varum cases and was statistically significant (P=0.047). Comparing the mean difference using chronological age and skeletal age in the formula showed no statistically significant difference. CONCLUSIONS: The MM has a tendency to under predict. Therefore, doing a guided growth right before skeletal maturity should be started 2 to 4 months earlier than suggested by the MM. Moreover, our data did not show that the bone age gave more accurate predictions than chronological age. LEVEL OF EVIDENCE: Level IV.

Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study.

CONTEXT: Deficits in bone acquisition during growth may increase fracture risk. Assessment of bone health during childhood requires appropriate reference values relative to age, sex, and population ancestry to identify bone deficits. OBJECTIVE: The objective of this study was to provide revised and extended reference curves for bone mineral content (BMC) and areal bone mineral density (aBMD) in children. DESIGN: The Bone Mineral Density in Childhood Study was a multicenter longitudinal study with annual assessments for up to 7 yr. SETTING: The study was conducted at five clinical centers in the United States. PARTICIPANTS: Two thousand fourteen healthy children (992 males, 22% African-Americans) aged 5-23 yr participated in the study. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURES: Reference percentiles for BMC and aBMD of the total body, lumbar spine, hip, and forearm were obtained using dual-energy x-ray absorptiometry for Black and non-Black children. Adjustment factors for height status were also calculated. RESULTS: Extended reference curves for BMC and aBMD of the total body, total body less head, lumbar spine, total hip, femoral neck, and forearm for ages 5-20 yr were constructed relative to sex and age for Black and non-Black children. Curves are similar to those previously published for 7-17 year olds. BMC and aBMD values were greater for Black vs. non-Black children at all measurement sites. CONCLUSIONS: We provide here dual-energy x-ray absorptiometry reference data on a well-characterized cohort of 2012 children and adolescents. These reference curves provide the most robust reference values for the assessment and monitoring of bone health in children and adolescents in the literature to date.

Tracking of bone mass and density during childhood and adolescence.

CONTEXT: Whether a child with low bone mineral density (BMD) at one point in time will continue to have low BMD, despite continued growth and maturation, is important clinically. The stability of a characteristic during growth is referred to as "tracking." OBJECTIVE: We examined the degree of tracking in bone mineral content (BMC) and BMD during childhood and adolescence and investigated whether tracking varied according to age, sexual maturation, and changes in growth status. DESIGN: We conducted a longitudinal study with measurements at baseline and annually for 3 yr. SETTING: The Bone Mineral Density in Childhood Study was conducted at five clinical centers in the United States. STUDY PARTICIPANTS: A total of 1554 girls and boys, ages 6-16 yr at baseline, participated in the study. MAIN OUTCOME MEASURES: Whole body, spine, hip, and forearm BMC and BMD were measured by dual-energy x-ray absorptiometry, and age-, sex-, and race-specific Z-scores were calculated. Deviation from tracking was calculated as the Z-score at yr 3 minus baseline. RESULTS: Correlations between Z-scores at baseline and yr 3 ranged from 0.76-0.88. Among children with a Z-score below -1.5 at baseline, 72-87% still had a Z-score below -1 after 3 yr. Age, sexual maturation, and deviations in growth status (P < 0.01) were associated with deviation from tracking; however, tracking was strongly evident even after adjusting for the effects of age, maturation, and growth. CONCLUSIONS: Bone density showed a high degree of tracking over 3 yr in children and adolescents. Healthy children with low bone density will likely continue to have low bone density unless effective interventions are instituted.

Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children.

CONTEXT: In children, bone mineral content (BMC) and bone mineral density (BMD) measurements by dual-energy x-ray absorptiometry (DXA) are affected by height status. No consensus exists on how to adjust BMC or BMD (BMC/BMD) measurements for short or tall stature. OBJECTIVE: The aim of this study was to compare various methods to adjust BMC/BMD for height in healthy children. DESIGN: Data from the Bone Mineral Density in Childhood Study (BMDCS) were used to develop adjustment methods that were validated using an independent cross-sectional sample of healthy children from the Reference Data Project (RDP). SETTING: We conducted the study in five clinical centers in the United States. PARTICIPANTS: We included 1546 BMDCS and 650 RDP participants (7 to 17 yr of age, 50% female). INTERVENTION: No interventions were used. MAIN OUTCOME MEASURES: We measured spine and whole body (WB) BMC and BMD Z-scores for age (BMC/BMD(age)), height age (BMC/BMD(height age)), height (BMC(height)), bone mineral apparent density (BMAD(age)), and height-for-age Z-score (HAZ) (BMC/BMD(haz)). RESULTS: Spine and WB BMC/BMD(age)Z and BMAD(age)Z were positively (P < 0.005; r = 0.11 to 0.64) associated with HAZ. Spine BMD(haz) and BMC(haz)Z were not associated with HAZ; WB BMC(haz)Z was modestly associated with HAZ (r = 0.14; P = 0.0003). All other adjustment methods were negatively associated with HAZ (P < 0.005; r = -0.20 to -0.34). The deviation between adjusted and BMC/BMD(age) Z-scores was associated with age for most measures (P < 0.005) except for BMC/BMD(haz). CONCLUSIONS: Most methods to adjust BMC/BMD Z-scores for height were biased by age and/or HAZ. Adjustments using HAZ were least biased relative to HAZ and age and can be used to evaluate the effect of short or tall stature on BMC/BMD Z-scores.

The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race.

CONTEXT: Low bone mass may increase risk of fracture. Several chronic medical conditions, medications, and lifestyle factors affect bone mineral accrual. Appropriate reference values are essential for identification of children with bone deficits. OBJECTIVE: Our objective was to establish reference curves for bone mineral content (BMC) and density (BMD) in children. DESIGN AND SETTING: The Bone Mineral Density in Childhood Study is an ongoing longitudinal study in which measurements are obtained annually at five clinical centers in the United States. PARTICIPANTS: Participants included 1554 healthy children (761 male, 793 female), ages 6-16 yr, of all ethnicities. MAIN OUTCOME MEASURES: Scans of the whole body, lumbar spine, hip, and forearm were obtained using dual-energy x-ray absorptiometry. Percentile curves based on three annual measurements were generated using the LMS statistical procedure. RESULTS: BMC of the whole body and lumbar spine and BMD of the whole body, lumbar spine, total hip, femoral neck, and forearm are given for specific percentiles by sex, age, and race (Black vs. non-Black). BMC and BMD were higher for Blacks at all skeletal sites (P < 0.0001). BMC and BMD increased with age, and a plateau was not evident by age 16 (girls) or age 17 (boys). The variation in BMC and BMD also increased with age. CONCLUSIONS: Age-, race-, and sex-specific reference curves can be used to help identify children with bone deficits and for monitoring changes in bone in response to chronic diseases or therapies.

Bleeding patterns after misoprostol vs surgical treatment of early pregnancy failure: results from a randomized trial.

OBJECTIVE: The purpose of this study was to describe bleeding patterns after misoprostol or curettage for early pregnancy failure (EPF). STUDY DESIGN: This was a randomized trial that included women (n = 652) with EPF. Participants were assigned to vaginal misoprostol (800 microg) or curettage in a 3:1 ratio. Participants completed a bleeding diary. We measured hemoglobin levels at baseline and 2 weeks after the treatment. RESULTS: Decreases in hemoglobin levels were greater after misoprostol (-0.7 g/dL; SD, 1.2) than curettage (-0.2 g/dL; SD, 0.9; P < .001). Large changes in hemoglobin levels (at least 2 g/dL) or low nadir hemoglobin levels (< 10 g/dL) were more frequent after misoprostol (55/428 women; 12.8%) than after curettage (6/135 women; 4.4%; P = .02). More participants in the misoprostol group reported "any bleeding" or "heavy bleeding" every study day. Four women who were treated with misoprostol required blood transfusion. CONCLUSION: Bleeding is heavier and more prolonged after medical treatment with misoprostol than with curettage for EPF; however, bleeding rarely requires intervention.

Endocrine abnormalities and impaired growth in human immunodeficiency virus-infected children.

OBJECTIVES: Identify endocrine differences between human immunodeficiency virus- (HIV) infected versus uninfected children and evaluate associations of growth and body composition with endocrine measures. STUDY DESIGN: Nested case-control study in 21 HIV-infected and 46 age- and sex-matched uninfected children in the Women and Infant Transmission Study. Plasma specimens from children between 2.5 to 7.0 years of age, taken during 3-4 visits, were tested for insulin-like growth factor binding protein-3 (IGFBP-3), cortisol, dehydroepiandrosterone (DHEA), growth hormone and thyroid studies. Longitudinal mixed and generalized estimating equation models compared group means and examined effects of endocrine measures on growth and body composition, respectively. RESULTS: HIV-infected children had lower IGFBP-3 than uninfected children (1.96 +/- 0.09 mg/L versus 2.34 +/- 0.06 mg/L, P < 0.001). In infected but not in uninfected children, IGFBP-3 values and DHEA:cortisol ratios were associated with weight- and body mass index-for-age z scores ([WAZ] P = 0.019, <.001 respectively, and [BMZ] P = 0.029, 0.038). DHEA concentration was associated with height-for-age z score (P = 0.049). CONCLUSIONS: In these HIV-infected children compared with their uninfected counterparts, IGFBP-3 concentration was different between groups. Infected children had multiple endocrine associations with growth and body composition not found in their uninfected peers. We hypothesize that in HIV-infected children, growth hormone resistance and shunting of precursors from adrenal androgen to cortisol production contributes to altered body composition and stunting.

A comparison of medical management with misoprostol and surgical management for early pregnancy failure.

BACKGROUND: Misoprostol is increasingly used to treat women who have a failed pregnancy in the first trimester. We assessed the efficacy, safety, and acceptability of this treatment in a large, randomized trial. METHODS: A total of 652 women with a first-trimester pregnancy failure (anembryonic gestation, embryonic or fetal death, or incomplete or inevitable spontaneous abortion) were randomly assigned to receive 800 microg of misoprostol vaginally or to undergo vacuum aspiration (standard of care) in a 3:1 ratio. The misoprostol group received treatment on day 1, a second dose on day 3 if expulsion was incomplete, and vacuum aspiration on day 8 if expulsion was still incomplete. Surgical treatment (for the misoprostol group) or repeated aspiration (for the vacuum-aspiration group) within 30 days after the initial treatment constituted treatment failure. RESULTS: Of the 491 women assigned to receive misoprostol, 71 percent had complete expulsion by day 3 and 84 percent by day 8 (95 percent confidence interval, 81 to 87 percent). Treatment failed in 16 percent of the misoprostol group and 3 percent of the surgical group (absolute difference, 12 percent; 95 percent confidence interval, 9 to 16 percent) by day 30. Hemorrhage or endometritis requiring hospitalization was rare (1 percent or less in each group), with no significant differences between the groups. In the misoprostol group, 78 percent of the women stated that they would use misoprostol again if the need arose and 83 percent stated that they would recommend it to others. CONCLUSIONS: Treatment of early pregnancy failure with 800 microg of misoprostol vaginally is a safe and acceptable approach, with a success rate of approximately 84 percent.

Quality of life in women undergoing medical treatment for early pregnancy failure.

OBJECTIVES: To examine predictors of quality of life, depression, and stress in women undergoing medical management of early pregnancy failure with misoprostal and to assess the relationship of quality of life, depression, and stress to treatment acceptability. DESIGN: Descriptive observational study of women undergoing medical management of early pregnancy failure with misoprostol conducted as part of a multicenter pilot study testing the efficacy of saline-moistened versus dry application of vaginal misoprostol. Data were collected prior to treatment through 15 days posttreatment. SETTING: Four university-based hospitals. PARTICIPANTS: Women (n = 80) < or = 1 weeks pregnant diagnosed with anembryonic gestation or fetal demise. INTERVENTION: Vaginal misoprostol for medical evacuation. MAIN OUTCOME MEASURES: Quality of life (physical role functioning, emotional role functioning, social functioning, vitality, and bodily pain), depression, stress, and treatment acceptability. RESULTS: Women who received medical evacuation demonstrated poorer quality of life than same-age published population norms, scoring 0.25 to 0.78 of a standard deviation below the population mean for four of the five subscales. CONCLUSIONS: Nurses should assist patients to minimize and manage physical symptoms during treatment for early pregnancy failure. Women with higher external demands and lower social/tangible support may need greater assistance.

Morbidity and mortality during the first two years of life among uninfected children born to human immunodeficiency virus type 1-infected women: the women and infants transmission study.

OBJECTIVE: We evaluated morbidity and mortality during the first 2 years of life among children born to human immunodeficiency virus-(HIV) type 1-infected women enrolled in the Women and Infants Transmission Study (WITS) during an 11-year period (1990-2001). DESIGN AND METHODS: As part of WITS, evaluations were performed at birth and at 1, 2, 4, 6, 9, 12, 18 and 24 months of age. Growth, hospitalization and the incidence of clinical disease were assessed regularly. RESULTS: Data regarding 1118 children born to HIV-infected women (955 HIV-uninfected children and 163 HIV-infected children) were analyzed. Fewer changes in the caretaker of the child and fewer in utero exposures to drugs, tobacco and alcohol occurred in the latter periods of the study (all P values for time trend analyses <0.01). The percentages of HIV-uninfected children with poor weight gain (44 of 767; 5.7%), short stature (32 of 703; 4.5%) and wasting (27 of 792; 3.4%) were higher than expected for the general population. Two or more changes in caretaker were associated with all growth deficiencies except wasting, and fetal exposure to tobacco was associated with height abnormalities. Anemia was common and was associated with receipt of zidovudine prophylaxis. Morbidity and mortality decreased during the study period. For the uninfected children, a decrease in class A events (Kaplan-Meier rates: group 1, 22.3%; group 2, 6.8%; group 3, 4.2%; P < 0.001) and class C events and death (Kaplan- Meier event rates: group 1, 2.0%; group 2, 1.7%; group 3, 0.2%; P = 0.062) during the first 2 years of life account for the differences in the curves over time. CONCLUSIONS: During an 11-year period, morbidity and mortality during the first 24 months of life decreased substantially for children born to HIV-infected women.

Hormone pattern after misoprostol administration for a nonviable first-trimester gestation.

OBJECTIVE: To evaluate serial hormone concentrations in subjects treated with vaginally administered misoprostol for early pregnancy failure. DESIGN: As part of a randomized clinical trial, serum was collected on treatment days 1, 3, 8, and 15. SETTING: Multicenter clinical trial. PATIENT(S): Women with a nonviable first-trimester pregnancy. INTERVENTION(S): Serum concentrations of human chorionic gonadotropin (hCG), progesterone, and sex hormone binding globulin (SHBG) were evaluated. MAIN OUTCOME MEASURE(S): A logistic regression model was constructed to assess the associations of percent and complete expulsion of the gestational sac and/or successful management. RESULT(S): The percent change from the day of treatment until the first follow-up visit was predictive for complete expulsion for progesterone (P) (P<.005) and hCG (P<.005), but not for SHBG. The actual value was not significantly associated with complete expulsion or successful management. A decrease (day 1-3) of 79% for both hCG and P was associated with a 90% probability of complete passage of the gestational sac. A 90% probability of successful management was noted if P decreased by 78% on day 3 or 59% on day 7, or hCG decreased by 74% on day 3 or 78% on day 7 compared with pretreatment values. CONCLUSION(S): Percent change, but not absolute change, in serial hormone values are strongly associated with both the complete expulsion of the gestational sac with one dose of misoprostol and ultimate success.

Persistent parvovirus B19 infection without the development of chronic anemia in HIV-infected and -uninfected children: the Women and Infants Transmission Study.

We evaluated the prevalence of persistent parvovirus B19 (B19) infection and associated anemia in human immunodeficiency virus (HIV)-infected and HIV-uninfected children. B19 persistence was defined as B19 DNA detected in specimens collected >16 weeks apart. Of 182 children, 3 HIV-infected children and two HIV-uninfected children had evidence of persistent B19 infection. Of the 5 children, none had evidence of B19-associated anemia. Our data suggest that B19 infections can persist in children without the development of symptomatic anemia.

A randomized trial of saline solution-moistened misoprostol versus dry misoprostol for first-trimester pregnancy failure.

OBJECTIVE: The purpose of this study was to estimate whether the efficacy of treatment with intravaginal misoprostol for first-trimester pregnancy failure is enhanced by the addition of saline solution. STUDY DESIGN: Eighty women with embryonic/fetal death or anembryonic pregnancy were assigned randomly to receive either 800 microg of misoprostol with saline solution (group I, 41 women) or without (group II, 39 women). Treatment was repeated on day 3 if the gestational sac remained. Curettage was performed if the gestational sac remained on day 8 or as necessary during at least 30 days of follow-up. Data were analyzed with the Student t test and the chi(2) or Fisher exact test. RESULTS: By the first follow-up visit, 73% (group I) and 64% (group II) of women passed the gestational sac (P=.38). By the second follow-up visit, expulsion rates were 83% and 87%, respectively (P=.59). Five subjects in each group underwent curettage. CONCLUSION: Misoprostol is effective for the treatment of failed first-trimester pregnancy. The expulsion rate is not improved by adding saline solution.