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Biomedical subjects

B Weissman

Publications and source records attributed to B Weissman.

At least 19 recordsLinked to original sources

Rejection of tumors of the B cell lineage by idiotype-vaccinated mice.

Idiotypic determinants of immunoglobulins of malignant B lymphocytes and plasma cells are tumor-specific antigens and have been used extensively in immunotherapy studies. The mechanisms involved in resistance to tumor challenge following idiotype vaccination are poorly understood. Although a predominant role has been attributed to anti-idiotype antibodies, both humoral and cellular immune responses are probably involved. Cell-mediated responses may be particularly effective against tumor cell variants that do not express the idiotype on the cell surface and are therefore resistant to anti-idiotype antibodies but continue to produce one of the original immunoglobulin polypeptides that may be processed and presented to T cells. In this report we describe two experimental models of idiotype vaccination in which antibodies are unlikely to play a role, and hence tumor immunity is attributed to cell-mediated responses. One model consists of the murine B lymphocyte tumor 38C-13 and its idiotype-negative variant DB2, which has lost the idiotypic specificity of the parental 38C-13 cell line through the production of a different light chain but expresses the original heavy chain. Vaccination of mice with the purified IgM of 38C-13 induced resistance to 38C-13 tumor cells as well as to the variant cells. Although immunized mice produced high levels of anti-idiotype antibodies that bound to 38C-13 cells, no binding of antibodies to DB2 cells occurred. The finding that idiotype-vaccinated mice were resistant to idiotype-negative DB2 cells suggested that cellular mechanisms are involved in mediating resistance. The second model consists of the two plasma cell line JLmu s and JLmu m, which produce IgM with an identical specificity. Whereas one of them (JLmu s) secretes the IgM, the other one (JLmu m) can neither secrete nor deposit it on the cell surface. Immunization against JLmu s IgM followed by tumor challenge resulted in prolonged survival of both JLmu s- and JLmu m-challenged mice. Although sera of immunized mice contained high levels of anti-idiotype antibodies, they did not react with the plasmacytoma cells. Similarly to the results obtained in the 38C-13 experimental model, these results suggest that a non-antibody-mediated mechanism was involved in the resistance of mice to tumor growth.

Adjuvants, Immunologic↗

Level of physical activity and the risk of radiographic and symptomatic knee osteoarthritis in the elderly: the Framingham study.

PURPOSE: Because osteoarthritis may be caused by "wear and tear," we examined the association between level of physical activity and risk of knee osteoarthritis in the elderly. SUBJECTS AND METHODS: Eligible subjects were participants in the Framingham Heart Study cohort who had radiographically normal knees at biennial exam 18 (1983-1985) and who also completed a physical activity questionnaire at exam 20 (1988-1989). Follow-up knee radiographs were obtained at biennial exam 22 (1992-1993). The study outcomes were the development of incident radiographic or symptomatic knee osteoarthritis between the baseline and follow-up exams. RESULTS: The number of hours per day of heavy physical activity was associated with the risk of incident radiographic knee osteoarthritis (odds ratio = 1.3 per hour, 95% confidence limits 1.1-1.6, P for trend = 0.006). Adjustment for age, sex, body mass index, weight loss, knee injury, health status, total calorie intake, and smoking strengthened this association (eg, odds ratio for > or = 4 hours heavy physical activity/day compared with no heavy physical activity = 7.0, 95% confidence limits 2.4-20, P for trend = 0.0002). Risk was greatest among individuals in the upper tertile of body mass index (odds ratio for > or = 3 hours/day of heavy physical activity = 13.0, 95% confidence limits 3.3-51). For incident symptomatic knee osteoarthritis, the results were similar, although the number of cases was small. No effects on these outcomes were observed from moderate and light physical activity, number of blocks walked, or number of flights of stairs climbed daily. CONCLUSIONS: Heavy physical activity is an important risk factor for the development of knee osteoarthritis in the elderly, especially among obese individuals. Light and moderate activities do not appear to increase risk.

Aged↗

Risk factors for incident radiographic knee osteoarthritis in the elderly: the Framingham Study.

OBJECTIVE: Knee osteoarthritis (OA) is highly prevalent, especially in the elderly. Preventive strategies require a knowledge of risk factors that precede disease onset. The present study was conducted to determine the longitudinal risk factors for knee OA in an elderly population. METHODS: A longitudinal study of knee OA involving members of the Framingham Study cohort was performed. Weight-bearing knee radiographs were obtained in 1983-1985 (baseline) and again in 1992-1993. Incident disease was defined as the occurrence of new radiographic OA (Kellgren and Lawrence grade > or = 2 on a 0-4 scale) in those without radiographic OA at baseline. Risk factors assessed at baseline and in the interim were tested in univariate and multivariate equations to evaluate their association with incident knee OA. RESULTS: Of 598 patients without knee OA at baseline (mean age 70.5 years, 63.7% women), 93 (15.6%) developed OA. After adjustment for multiple risk factors, women had a higher risk of OA than did men (adjusted odds ratio [OR] = 1.8, 95% confidence interval [95% CI] 1.1-3.1). Higher baseline body mass index increased the risk of OA (OR = 1.6 per 5-unit increase, 95% CI 1.2-2.2), and weight change was directly correlated with the risk of OA (OR = 1.4 per 10-lb change in weight, 95% CI 1.1-1.8). Physical activity increased the risk of OA (for those in the highest quartile, OR = 3.3, 95% CI 1.4-7.5). Smokers had a lower risk than did nonsmokers (for those who smoked an average of > or = 10 cigarettes/day, OR = 0.4, 95% CI 0.2-0.8). Factors not associated with the risk of OA included chondrocalcinosis and a history of hand OA. Weight-related factors affected the risk of OA only in women. CONCLUSION: Elderly persons at high risk of developing radiographic knee OA included obese persons, nonsmokers, and those who were physically active. The direction of weight change correlated directly with the risk of developing OA.

Aged↗

Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham Study.

BACKGROUND: Evidence suggests that pathophysiologic processes in bone are important determinants of outcome in osteoarthritis of the knee. Low intake and low serum levels of vitamin D may compromise favorable responses of bone to osteoarthritis, predisposing patients to progression. OBJECTIVE: To determine whether dietary intake and serum levels of vitamin D would predict the incidence and progression of osteoarthritis of the knee in participants of the Framingham Study. DESIGN: Prospective observational study. SETTING: The Framingham Study. PARTICIPANTS: Participants in the Framingham Heart Study who had knee radiography at examinations 18 (done between 1983 and 1985) and 22 (done between 1992 and 1993) and received interim assessments of vitamin D intake and serum levels. MEASUREMENTS: Intake of vitamin D and serum levels of 25-hydroxyvitamin D, calculated on the basis of dietary habits and supplement use as reported on a questionnaire, were evaluated at examination 20 (1988 to 1989). Knee radiographs were given scores for global severity of osteoarthritis, using a modification of the scale of Kellgren and Lawrence (range, 0 to 4), and for the presence of osteophytes and joint-space narrowing (range, 0 to 3). Covariates measured at examinations 18 and 20 were age, sex, body mass index, weight change, injury, physical activity, health status, bone mineral density, and energy intake. RESULTS: 556 participants (mean age at baseline +/- SD, 70.3 +/- 4.5 years) had complete assessments. Incident osteoarthritis occurred in 75 knees; progressive osteoarthritis occurred in 62 knees. Serum levels of vitamin D were modestly correlated with vitamin D intake (r = 0.24). Risk for progression increased threefold in participants in the middle and lower tertiles for both vitamin D intake (odds ratio for the lower compared with the upper tertile, 4.0 [95% Cl, 1.4 to 11.6]) and serum levels of vitamin D (odds ratio for the lower compared with the upper tertile, 2.9[Cl, 1.0 to 8.2]). Low serum levels of vitamin D also predicted loss of cartilage, as assessed by loss of joint space (odds ratio, 2.3 [Cl, 0.9 to 5.5]) and osteophyte growth (odds ratio, 3.1 [Cl, 1.3 to 7.5]). Incident osteoarthritis of the knee occurring after baseline was not consistently related to either intake or serum levels of vitamin D. CONCLUSIONS: Low intake and low serum levels of vitamin D each appear to be associated with an increased risk for progression of osteoarthritis of the knee.

Cartilage, Articular↗

Catch-up growth during childhood among very low-birth-weight children.

OBJECTIVES: To examine growth attainment and correlates of catch-up growth at 8 years of age in a cohort of very low-birth-weight (VLBW) children (< 1500 g), including appropriate and small-for-gestational-age children, and to compare their growth with normal-birth-weight (NBW) children. DESIGN: Eight-year longitudinal follow-up of a cohort of VLBW children. A geographically based, randomly selected sample of NBW children was recruited at 8 years of age. SETTING: Tertiary perinatal center. PARTICIPANTS: Two hundred forty-nine VLBW children born between January 1, 1977, and December 31, 1979 (78% of survivors), of whom 199 were born appropriate for gestational age and 50 were small for gestational age (< -2 SD). The NBW population included 363 children. MAIN OUTCOME MEASURES: For the VLBW population, rates of subnormal weight (below the third percentile) and height were obtained at birth, at 40 weeks (term), and at 8 and 20 months. For the VLBW and NBW populations, mean weight, height, and percentile distribution at 8 years were derived from the National Center for Health Statistics standards. RESULTS: Catch-up growth to above the third percentile occurred between 40 weeks and 8 months, 8 and 20 months, and up to 8 years of age among the VLBW children. At 40 weeks, 54% were subnormal in weight and 60% were subnormal in height; at 8 months, 33% and 22%, respectively, and at 8 years, 8% were subnormal in weight and height. Small-for-gestational-age children had lower rates of catch-up growth. Multivariate analyses disclosed maternal height, race, birth weight, and neurologic abnormality to predict percentile distribution of height; and maternal height, small for gestational age, and neurologic abnormality to predict subnormal height. CONCLUSIONS: Catch-up growth occurs during childhood among VLBW children. These results have implications when counseling parents about the potential growth attainment of their children.

Child↗

Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis?

OBJECTIVE: Cumulative damage to tissues, mediated by reactive oxygen species, has been implicated as a pathway that leads to many of the degenerative changes associated with aging. We hypothesized that increased intake of antioxidant micronutrients might be associated with decreased rates of osteoarthritis (OA) in the knees, a common age-related disorder. METHODS: Participants in the Framingham Osteoarthritis Cohort Study underwent knee evaluations by radiography at examinations 18 (1983-1985) and 22 (1992-1993). Usual dietary intake was assessed using the Food Frequency Questionnaire, administered at examination 20 (1988-1989). Knees without OA at baseline (Kellgren and Lawrence [K&L] grade < or = 1) were classified as having incident OA if they had a K&L grade > or = 2 at followup. Knees with OA at baseline were classified as having progressive OA if their score increased by > or = 1 at followup. Knees were also classified as having cartilage loss or osteophyte growth if their maximal joint space narrowing or osteophyte growth score increased by > or = 1 (range 0-3). The association of vitamin C, beta carotene, and vitamin E intake, ranked in sex-specific tertiles, with incidence and progression of OA was compared with that of a panel of nonantioxidant vitamins, Bl, B6, niacin, and folate, using logistic regression and generalized estimation equations to adjust for correlation between fellow knees. The lowest tertile for each dietary exposure was used as the referent category. Odds ratios (OR) were adjusted for age, sex, body mass index, weight change, knee injury, physical activity, energy intake, and health status. RESULTS: Six hundred forty participants received complete assessments. Incident and progressive OA occurred in 81 and 68 knees, respectively. We found no significant association of incident OA with any nutrient. A 3-fold reduction in risk of OA progression was found for both the middle tertile (adjusted OR = 0.3, 95% confidence interval [95% CI] 0.1-0.8) and highest tertile (adjusted OR = 0.3, 95% CI 0.1-0.6) of vitamin C intake. This related predominantly to a reduced risk of cartilage loss (adjusted OR = 0.3, 95% CI 0.1-0.8). Those with high vitamin C intake also had a reduced risk of developing knee pain (adjusted OR = 0.3, 95% CI 0.1-0.8). A reduction in risk of OA progression was seen for beta carotene (adjusted OR = 0.4, 95% CI 0.2-0.9) and vitamin E intake (adjusted OR = 0.7, 95% CI 0.3-1.6), but was less consistent. No significant associations were observed for the nonantioxidant nutrients. CONCLUSION: High intake of antioxidant micronutrients, especially vitamin C, may reduce the risk of cartilage loss and disease progression in people with OA. We found no effect of antioxidant nutrients on incident OA. These preliminary findings warrant confirmation.

Aged↗

Tendon shift in hallux valgus: observations at MR imaging.

OBJECTIVE: This study was undertaken to demonstrate a shift in tendon alignment at the first metatarsophalangeal joint in patients with hallux valgus by means of magnetic resonance imaging. DESIGN: Ten normal feet and 20 feet with the hallux valgus deformity conforming to conventional clinical and radiographic criteria were prospectively studied using magnetic resonance imaging. Correlation was made between tendon position at the first metatarsophalangeal joint and the severity of the hallux valgus deformity. RESULTS: There is a significant shift in tendon position at the first metatarsophalangeal joint of patients with hallux valgus. The insertion of the abductor hallucis tendon is markedly plantarward and the flexor and extensor tendons bowstring at the first metatarsophalangeal joint compared with patients without the deformity. The severity of the tendon shift correlates with the hallux valgus angle and clinical severity of the hallux valgus deformity in each case. CONCLUSION: Patients with hallux valgus have a significant tendon shift at the first metatarsophalangeal joint which appears to contribute to development of the deformity.

Case-Control Studies↗

Are risk factors for patellofemoral and tibiofemoral knee osteoarthritis different?

OBJECTIVE: To determine whether patellofemoral (PF), tibiofemoral (TF), and combined patterns of knee osteoarthritis (OA) differ in their strengths of associations with any of the known risk factors for knee OA, and especially to evaluate whether body mass index (BMI) correlates with all 3 patterns, or only with tibiofemoral disease, as previously suggested. METHODS: We obtained anteroposterior and lateral knee radiographs on 608 participants at the 22nd biennial examination of the Framingham cohort study (1992-3). The presence or absence of OA in the TF and PF compartments of each knee was scored, and subjects were classified on the basis of the pattern of compartmental involvement in their 2 knees. The strength of association of age, sex, BMI, chondrocalcinosis, and knee injury was computed for PF, TF, and combined pattern of knee OA using multiple logistic regression. RESULTS: The mean age and BMI of the sample were 80.7 yrs (SD 5.0) and 25.4.kg-2 (SD 3.7), respectively. PF, TF, and combined patterns of knee OA were present in 5.3, 23.0 and 19.7%, respectively. Elevated BMI was a risk factor for all 3 patterns of disease (adjusted OR for highest vs lowest tertile of BMI 3.7, 1.9, and 7.0 for PF, TF, and combined pattern, respectively). Risk factor profiles were broadly similar for TF and PF OA, with the possible exception of knee injury in men (adjusted OR = 2.0 for PF, 3.7 for TF OA). Risk factors were generally more strongly associated with the combined pattern of OA. CONCLUSION: Obesity is an important risk factor for PF, TF, and combined patterns of knee OA. The relationships of these patterns with the risk factors investigated here appear similar and are strongest for the combined pattern.

Aged↗

Genetic heterogeneity of heart-hand syndromes.

BACKGROUND: Heart-hand syndromes compose a class of combined congenital cardiac and limb deformities. The proto-typical heart-hand disorder is Holt-Oram syndrome, which is characterized by cardiac septation defects and radial ray limb deformity. We have recently mapped the Holt-Oram syndrome gene defect to the long arm of human chromosome 12 in two families. The role of this disease locus in the pathogenesis of related conditions such as heart-hand syndrome type III (cardiac conduction disease accompanied by skeletal malformations) or familial atrial septal defects is unknown. METHODS AND RESULTS: Clinical evaluations and genetic linkage analyses were performed in five additional kindreds with Holt-Oram syndrome and also in one kindred with heart-hand syndrome type III and one kindred with familial atrial septal defect and conduction disease. Holt-Oram syndrome in all five kindreds mapped to chromosome 12q2. These studies and previous data provide odds of greater than 10(25):1 that the Holt-Oram syndrome disease gene is at chromosome 12q2. In contrast, neither the phenotypically similar disorder heart-hand syndrome type III nor the locus responsible for a familial atrial septal defect with atrioventricular block maps to chromosome 12q2. CONCLUSIONS: We demonstrate that heart-hand syndromes are genetically heterogeneous. Conditions that clinically appear to be partial phenocopies of Holt-Oram syndrome arise from distinct disease genes.

Chromosomes, Human, Pair 12↗

The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome)

BACKGROUND: The Holt-Oram syndrome is an autosomal dominant condition characterized by skeletal abnormalities that are frequently accompanied by congenital cardiac defects. The cause of these disparate clinical features is unknown. To identify the chromosomal location of the Holt-Oram syndrome gene, we performed clinical and genetic studies. METHODS: Two large families with the Holt-Oram syndrome were evaluated by radiography of the hands, electrocardiography, and transthoracic echocardiography. Genetic-linkage analyses were performed with polymorphic DNA loci dispersed throughout the genome to identify a locus that was inherited with the Holt-Oram syndrome in family members. RESULTS: A total of 19 members of Family A had Holt-Oram syndrome with mild-to-moderate skeletal deformities, including triphalangeal thumbs and carpal-bone dysmorphism. All affected members of Family A had moderate-to-severe congenital cardiac abnormalities, such as ventricular or atrial septal defects or atrioventricular-canal defects. Eighteen members of a second kindred (Family B) had Holt-Oram syndrome with moderate-to-severe skeletal deformities, including phocomelia. Twelve of the affected members had no cardiac defects; six had only atrial septal defects. Genetic analyses demonstrated linkage of the disease in each family to polymorphic loci on the long arm of chromosome 12 (combined multipoint lod score, 16.8). These data suggest odds greater than 10(16):1 that the genetic defect for Holt-Oram syndrome is present on the long arm of chromosome 12 (12q2). CONCLUSIONS: Mutations in a gene on chromosome 12q2 can produce a wide range of disease phenotypes characteristic of the Holt-Oram syndrome. This gene has an important role in both skeletal and cardiac development.

Adolescent↗

Corneal abrasion associated with contact lens correction of keratoconus--a retrospective study.

BACKGROUND: Corneal abrasion is a frequently encountered complication of contact lens wear, but we are not aware of any previous study of relative frequency comparing keratoconic to nonkeratoconic patients. METHODS: We retrospectively studied the incidence of corneal abrasion during 2 months of contact lens practice. RESULTS: 784 contact lens-related patient visits (494 total patients); patients were assessed by 3 optometrists and 13 abrasions (11 patients) were diagnosed. Only the total number of individual patients and the first abrasion for each patient were statistically considered; the overall frequency of abrasion was therefore 11/494 (2.3%)/2 months. The frequency of abrasion was 5/68 (7.4%)/2 months for keratoconic patients and 6/426 (1.4%)/2 months for nonkeratoconic patients and this difference was significant (chi 2 test: p < 0.01). Among nonkeratoconic patients, the frequency of abrasion was 2/246 (0.8%)/2 months with hydrogel contact lens wear and 4/178 (2.2%)/2 months with rigid gas permeable (RGP) contact lens wear, but this difference did not achieve significance (chi 2 test: p = 0.10). IDENTIFIED RISK FACTORS INCLUDED: Contact lens wear; a torn lens and chemical keratitis for hydrogel lens wearers; an adherent "bound" lens and keratoconus for rigid lens wearers. CONCLUSION: Keratoconus appears to be a statistically significant risk factor for corneal abrasion among contact lens wearers.

Adolescent↗

Health of very low birth weight children during their first eight years.

To determine the impact of very low birth weight (VLBW) on medical outcomes during childhood, we compared the health of 249 VLBW children born from 1977 through 1979 with that of 363 normal birth weight (NBW) control children at 8 years of age. Measures included the rates of specific illnesses, surgical procedures and accidents, growth, and other physical findings. The number of medical conditions and surgical procedures was significantly greater in the VLBW children than in the NBW control children. Eighteen percent of VLBW versus 5% of NBW children had had respiratory conditions (p < 0.001), mainly before 3 years of age. Surgical procedures were more common both before and after 3 years of age, but accidents occurred with similar frequency. The VLBW children had significantly lower weight, height, and head circumference and more minor physical stigmata. Thus medical illness, surgical interventions, and poor growth attainment are part of the ongoing morbidity of VLBW children during childhood.

Accidents↗

The effect of very low birth weight and social risk on neurocognitive abilities at school age.

We tested the hypothesis that very low birth weight (VLBW < 1.5 kg) children would have significantly poorer neurocognitive abilities at school age than would normal birth weight full-term age mates, that differences would persist after control for neurologic impairment and social risk, and that VLBW would interact with social risk. Two hundred forty-nine VLBW children and a randomly selected sample of 363 normal birth weight age mates born 1977 through 1979 were tested at 8 years. A neurologic examination and tests of intelligence, language, speech, reading, mathematics, spelling, visual and fine motor abilities, and behavior were performed. Twenty-four (10%) VLBW had a major neurologic abnormality compared with none of the controls. VLBW had significantly poorer scores on all tests, with the exception of speech and the total behavior score. These differences persisted among VLBW children without major neurologic abnormality, with the exception of social competence, reading, and spelling. Even normal IQ, neurologically normal VLBW had significantly poorer scores than did controls in expressive language, memory, visuomotor, and fine motor function, and measures of hyperactivity. When social risk was controlled in multiple regression analyses, VLBW still had an adverse effect on all outcome measures with the exception of speech. Social risk was, however, the major determinant of outcome. We found an interaction between VLBW and social risk only in verbal IQ and in the opposite direction than hypothesized.

Brain Damage, Chronic↗

Complex expression of the genes coding for plasminogen activators and their inhibitors in HeLa-smooth muscle cell hybrids.

As cells progress through the multistep process of neoplastic transformation, they eventually acquire the property of invasive behavior. Although both plasminogen activators (PA) and their inhibitors (PAI) contribute to this process, their regulation in normal and transformed cells remains poorly defined. Because somatic cell hybrids provide useful tools for examining the transformation pathway, tumorigenic and invasive HeLa cells were fused with human normal vascular smooth muscle cells and tested for invasion-related parameters, including the expression of PA and PAI genes, and matrix degradation. Both parental cell lines produced large amounts of PAI activities with no detectable PA in either cellular or secreted form. Opposite findings were obtained with the hybrid cell lines, which demonstrated the presence of receptor-bound and secreted PA but absence of enzymatically measurable PAI activities. Both urokinase-type and tissue-type PA were found in cell-associated and secreted form in the hybrid cells. In addition, expression of the urokinase-type PA receptor gene was found in the three hybrid cells and the vascular smooth muscle cells but not in the HeLa cells. Expression of active, receptor-bound and secreted PA provided the nontumorigenic hybrid cells with the enzymatic tools to degrade extracellular proteins in a plasminogen-dependent manner. Thus, the hybrid cells lost tumorigenicity while retaining the tissue-degrading capability of HeLa cells. These hybrid cell lines should prove to be important reagents for investigating the complex regulatory control of PA and PAI gene expression.

Extracellular Matrix↗

Effect of very low birth weight and subnormal head size on cognitive abilities at school age.

BACKGROUND: We tested the hypothesis that very-low-birth-weight (less than 1.5 kg) infants with perinatal growth failure whose head size is not normal by eight months of age (corrected for prematurity) have significantly poorer growth and neurocognitive abilities at school age than very-low-birth-weight children with a normal head size at eight months. We also hypothesized that these differences would persist even after control for major neurologic impairment and perinatal and sociodemographic risk factors. METHODS: We have followed a cohort of very-low-birth-weight children since their birth during the period 1977 to 1979. At eight to nine years of age 249 children were evaluated with a neurologic examination and tests of intelligence; receptive and expressive language skills; speech, reading, mathematics, and spelling aptitude; visual and fine motor abilities; and behavior. Ages were corrected for premature birth. RESULTS: Among these 249 very-low-birth-weight children, head size was subnormal (less than the mean -2 SD for age) at birth in 30 (12 percent), at term in 57 (23 percent), and at eight months in 33 (13 percent). As compared with the 216 children with normal head sizes, the 33 children with subnormal head sizes at the age of eight months had significantly lower mean birth weights (1.1 vs. 1.2 kg) and higher neonatal risk scores (71 vs. 53) and at the age of eight years had a higher incidence of neurologic impairment (21 percent vs. 8 percent) and lower IQ scores (mean verbal, 84 vs. 98). Even among the children without neurologic abnormalities, a subnormal head size at eight months of age was predictive of poorer verbal and performance IQ scores at eight years of age; lower scores for receptive language, speech, reading, mathematics, and spelling; and a higher incidence of hyperactivity. In multiple regression analyses to control for socioeconomic and neonatal risk factors, intrauterine growth failure, birth weight, and neurologic impairment, a subnormal head size at eight months of age had an independently adverse effect on IQ and on scores for receptive language, speech, reading, and spelling. CONCLUSIONS: In very-low-birth-weight infants, perinatal growth failure, as evidenced by a subnormal head circumference at eight months of age, is associated with poor cognitive function, academic achievement, and behavior at eight years of age.

Cephalometry↗