Mark Schluchter

Poor predictive validity of the Bayley Scales of Infant Development for cognitive function of extremely low birth weight children at school age.

Objective. The Bayley Scales of Infant Development, Second Edition (BSID II) are commonly used to assess outcomes of extremely low birth weight (ELBW) infants. We sought to assess the predictive validity of the BSID II Mental Developmental Index (MDI) for cognitive function at school age. Design/Methods. Of 330 ELBW infants admitted in 1992–1995, 238 (72%) survived to the age of 8 years, of whom 200 (84%) were tested at both 20 months’ corrected age (CA) and 8 years. Mean birth weight was 811 g, mean gestational age was 26.4 weeks, 41% were boys, and 60% were black. Measures included the BSID II at 20 months’ CA and the Kaufman Assessment Battery for Children (KABC) Mental Processing Composite (MPC) at 8 years’ postnatal age. BSID II MDI and MPC scores were compared and the predictive validity calculated for all 200 ELBW children and for the 154 ELBW neurosensory-intact subgroup. Predictors of stability or change in cognitive scores were examined via logistic regression adjusting for gender and sociodemographic status. Results. For all ELBW children, the mean MDI was 75.6 ± 16 versus a mean KABC of 87.8 ± 19. For the neurosensory-intact subgroup, the mean MDI was 79.3 ± 16 and the mean KABC was 92.3 ± 15. Rates of cognitive impairment, defined as an MDI or KABC of <70, dropped from 39% at 20 months’ CA to 16% at 8 years for the total ELBW population and from 29% to 7% for the neurosensory-intact subgroup. The positive predictive value of having an MPC of <70 given an MDI of <70 was 0.37 (95% confidence interval [CI]: 0.27, 0.49) for all ELBW infants, 0.20 (95% CI: 0.10, 0.35) for the neurosensory-intact subgroup, and 0.61 (95% CI: 0.42, 0.77) for the neurosensory-impaired subgroup. The negative predictive values were 0.98, 0.99, and 0.85 for the 3 groups, respectively. Neurosensory impairment at 20 months’ CA predicted lack of improvement of cognitive function (odds ratio: 6.9; 95% CI: 2.4, 20.2). Children whose cognitive scores improved between 20 months and 8 years had significantly better school performance than those whose scores stayed at <70, but they did less well than those whose scores were persistently >70. Conclusions. The predictive validity of a subnormal MDI for cognitive function at school age is poor but better for ELBW children who have neurosensory impairments. We are concerned that decisions to provide intensive care for ELBW infants in the delivery room might be biased by reported high rates of cognitive impairments based on the use and presumptive validity of the BSID II MDI.

Behavioral outcomes and evidence of psychopathology among very low birth weight infants at age 20 years.

Objective. Information on the mental health of very low birth weight (VLBW; <1500 g) children in young adulthood is sparse. We thus sought to examine gender-specific behavioral outcomes and evidence of psychopathology in a cohort of VLBW young adults at 20 years of age. Methods. We compared a cohort of 241 survivors among VLBW infants who were born between 1977 and 1979 (mean birth weight: 1180 g; mean gestational age at birth: 29.7 weeks), 116 of whom were men and 125 of whom were women, with 233 control subjects from the same population in Cleveland who had normal birth weights (108 men and 124 women). Young adult behavior was assessed at 20 years of age with the Achenbach Young Adult Self-Report and the Young Adult Behavior Checklist for parents. In addition, the young adults and parents completed the ADHD Rating Scale for Adults. Gender-specific outcomes were adjusted for sociodemographic status. Results. VLBW men reported having significantly fewer delinquent behaviors than normal birth weight (NBW) control subjects, but there were no differences on the Internalizing, Externalizing, or Total Problem Behavior scales. Parents of VLBW men reported significantly more thought problems for their sons than did parents of control subjects. VLBW women reported significantly more withdrawn behaviors and fewer delinquent behavior problems than control subjects. Their rates of internalizing behaviors (which includes anxious/depressed and withdrawn behaviors) above the borderline clinical cutoff were 30% versus 16% (odds ratio: 2.2; 95% confidence interval [CI]: 1.2-4.1). Parents of VLBW women reported significantly higher scores for their daughters on the anxious/depressed, withdrawn, and attention problem subscales compared with control parents. The odds ratios for parent-reported rates above the borderline-clinical cutoff among women for the anxious/depressed subscale was 4.4 (95% CI: 1.4-13.5), for thought problems was 3.7 (95% CI: 1.2-11.6), and for attention problems was 2.4 (95% CI: 1.0-5.5). There were no differences in the young adult self-report of attention-deficit/hyperactivity disorder (ADHD). Parents of VLBW men reported higher mean scores on the attention subtype of ADHD but not higher rates of ADHD. Conclusion. The increase in psychopathology among VLBW survivors in young adulthood indicates a need for anticipatory guidance and early intervention that might help to prevent or ameliorate potential psychopathology.

Cytomegalovirus Infection and HIV-1 Disease Progression in Infants Born to HIV-1–Infected Women

Background and Methods Cytomegalovirus (CMV) has been implicated as a cofactor in the progression of human immunodeficiency virus type 1 (HIV-1) disease. We assessed 440 infants (75 of whom were HIV-1–infected and 365 of whom were not) whose CMV status was known, who were born to HIV-1–infected women, and who were followed prospectively. HIV-1 disease progression was defined as the presence of class C symptoms (according to the criteria of the Centers for Disease Control and Prevention [CDC]) or CD4 counts of less than 750 cells per cubic millimeter by 1 year of age and less than 500 cells per cubic millimeter by 18 months of age.

Behavioral Outcomes of Extremely Low Birth Weight Children at Age 8 Years

Objective: To describe the prevalence of behavioral problems and symptomatology suggestive of Autism and Aspergers disorders at age 8 years among extremely low birth weight (ELBW, <1 kg) children, born 1992 through 1995. Method: Parent reports of the behavior of 219 ELBW (mean birth weight, 810 g; gestational age 26 weeks) were compared with 176 normal birth weight children of similar maternal sociodemographic status, sex, and age. Behavior was assessed via the Child Symptom Inventory that includes both Symptom Severity Scores and scores meeting DSM-IV criteria for disorders. Results: ELBW compared with normal birth weight children had significantly higher mean Symptom Severity Scores for the inattentive, hyperactive, and combined types of attention-deficit hyperactivity disorder (all p < .001) as well as higher scores for Generalized Anxiety (p < .01) and Autistic (p < .001) and Aspergers (p < .01) disorders. When DSM-IV criteria were considered, ELBW children also had significantly higher rates of attention-deficit hyperactivity disorder of the inattentive (10% vs 3%, p < .01) and combined (5% vs 0.6%, p < .05) types. Conclusions: Attention-deficit hyperactivity disorder, mainly the inattentive type is prevalent among ELBW children. Our findings of an increase in symptoms pertaining to Autistic and Aspergers disorders at school age agree with recent reports of others during early childhood. Early identification and intervention for these problems might improve child functioning and ameliorate parent and child distress.

Reduction in asthma morbidity in children as a result of home remediation aimed at moisture sources.

Objective Home dampness and the presence of mold and allergens have been associated with asthma morbidity. We examined changes in asthma morbidity in children as a result of home remediation aimed at moisture sources. Design In this prospective, randomized controlled trial, symptomatic, asthmatic children (n = 62), 2–17 years of age, living in a home with indoor mold, received an asthma intervention including an action plan, education, and individualized problem solving. The remediation group also received household repairs, including reduction of water infiltration, removal of water-damaged building materials, and heating/ventilation/air-conditioning alterations. The control group received only home cleaning information. We measured children’s total and allergen-specific serum immuno-globulin E, peripheral blood eosinophil counts, and urinary cotinine. Environmental dust samples were analyzed for dust mite, cockroach, rodent urinary protein, endotoxin, and fungi. The follow-up period was 1 year. Results Children in both groups showed improvement in asthma symptomatic days during the preremediation portion of the study. The remediation group had a significant decrease in symptom days (p = 0.003, as randomized; p = 0.004, intent to treat) after remodeling, whereas these parameters in the control group did not significantly change. In the postremediation period, the remediation group had a lower rate of exacerbations compared with control asthmatics (as treated: 1 of 29 vs. 11 of 33, respectively, p = 0. 003; intent to treat: 28.1% and 10.0%, respectively, p = 0.11). Conclusion Construction remediation aimed at the root cause of moisture sources and combined with a medical/behavioral intervention significantly reduces symptom days and health care use for asthmatic children who live in homes with a documented mold problem.

Prevalence and Predictors of Interval Colorectal Cancers in Medicare Beneficiaries

After a colonoscopy that is negative for cancer, a subset of patients may be diagnosed with colorectal cancer, also termed interval cancer. The frequency and predictors have not been well studied in a population‐based US cohort.

A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity.

OBJECTIVE Retinopathy of prematurity (ROP), a vasoproliferative disorder of the retina in preterm infants, is associated with multiple factors, including oxygenation level. We explored whether the common intermittent hypoxemic events in preterm infants are associated with the development of ROP. STUDY DESIGN Oxygen desaturation events were quantified in 79 preterm infants (gestational age, 24 to 27-6/7 weeks) during the first 8 weeks of life. Infants were classified as requiring laser treatment for ROP versus having less severe or no ROP. A linear mixed model was used to study the association between the incidence of intermittent hypoxia and laser treatment of ROP, controlling for gestational age, sex, race, multiple births, and initial severity of illness. RESULTS For all infants, hypoxemic events increased with postnatal age (P<.001). Controlling for all covariates, a higher incidence of oxygen desaturation events was found in the infants undergoing laser therapy for ROP (P<.001), males (P<.02), and infants of younger gestational age (P<.003). CONCLUSIONS The incidence of hypoxemic events was higher in infants with ROP requiring laser therapy. Therapeutic strategies to optimize oxygenation in preterm infants should include minimization of desaturation episodes, which may in turn decrease serious morbidity in this high-risk population.

Consequences and risks of <1000-g birth weight for neuropsychological skills, achievement, and adaptive functioning.

A cohort of 219 children with extremely low birth weight (<1000 g, extremely low birth weight [ELBW]) born from 1992 to 1995 was followed to mean age 8 years to evaluate outcomes and identify risk factors. We compared 204 of these children with 176 term-born normal birth weight (NBW) controls on neuropsychological skills, academic achievement, and adaptive behavior. The ELBW group had worse outcomes than the NBW on all measures. Within the ELBW group, lower scores on NEPSY tests of executive function and memory were related to <750 g birth weight, B (SE) = −0.93 (0.36), p =.010; cranial ultrasound abnormality, B = −1.03 (0.22), p =.002; postnatal steroid therapy, B = −1.00 (0.33), p =.003; and necrotizing enterocolitis, B = −2.26 (0.75), p =.008. A lower score on the Test of Motor Proficiency was related to chronic lung disease, B = −7.33 (1.98), p <.001. Neuropsychological skills mediated the effects of neonatal risk on achievement and adaptive functioning. The findings document the neuropsychological consequences of ELBW at school age in a recently born cohort and identify risks for adverse outcomes.

The losartan renal protection study — rationale, study design and baseline characteristics of RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan)

The RENAAL Study is a double-blind, placebo-controlled trial to evaluate the renal protective effects of losartan in Type 2 diabetic patients with nephropathy. The study has enrolled 1513 patients and is expected to continue for 3.5 years after the last patient has been entered. Eligible patients must have a urinary albumin:creatinine ratio of at least 300 mg/g and serum creatinine between 1.3 to 3.0 mg/dL. Eligible hypertensive or normotensive patients are randomised to receive either losartan or placebo, in addition to their existing antihypertensive therapy. Medications that block angiotensin production or action, are excluded. The primary endpoint is a composite of the time to first event of doubling of serum creatinine, end-stage renal disease, or death; secondary endpoints include cardiovascular events, progression of renal disease, and changes in proteinuria; tertiary endpoints include quality of life, healthcare resource utilisation, and amputations. Patients include Caucasians (48.6%), Blacks (15.2%), Asians (16.7%), and Hispanics (18.2%). Baseline urinary albumin:creatinine ratio and serum creatinine levels average 1867 mg/g and 1.9 mg/dL, respectively. Mean systolic and diastolic blood pressures are 153 and 82 mmHg, respectively. RENAAL will document whether blockade of the AII receptor with losartan produces clinical benefits in patients with Type 2 diabetes and nephropathy.

Blood Pressure Among Very Low Birth Weight (<1.5 kg) Young Adults

Our objective was to compare the blood pressure of 20-y-old very low birth weight (VLBW; <1.5 kg) individuals with that of normal birth weight (NBW) control individuals. The population included 195 VLBW (92 female and 103 male) and 208 NBW (107 female and 101 male) individuals who were born between 1977 and 1979. Independent effects of birth weight status (VLBW versus NBW) and within the VLBW cohort of intrauterine growth (birth weight z score) were examined via multiple regression analyses. VLBW individuals had a higher mean systolic blood pressure (SBP) than NBW control individuals (114 ± 11 versus 112 ± 13 mm Hg). SBP for VLBW female infants was 110 ± 9 versus NBW 107 ± 12 and for VLBW male individuals was 118 ± 11 versus NBW 117 ± 11 mm Hg. After adjustment for gender, race, and maternal education, the difference in SBP between VLBW and NBW individuals was 1.9 mm Hg but was 3.5 mm after also adjustment for later size (20-y weight and height z scores), which reflects catch-up growth. For female individuals, the difference in SBP between VLBW and NBW individuals was significant both unadjusted and adjusted for later size, whereas for male individuals, the difference was significant only after adjustment for later size. Intrauterine growth did not have a significant effect on SBP within the VLBW group, even after adjustment for later size. VLBW individuals, specifically female individuals, have a higher SBP than NBW control individuals. This is not explained by intrauterine growth failure.