J. Kennard Fraley

Effect of dietary linoleic/alpha-linolenic acid ratio on growth and visual function of term infants

OBJECTIVES To determine the effect of alpha-linolenic acid (ALA) intake (or the dietary linoleic acid [LA]/ALA ratio) on the growth and visual function of term infants. STUDY DESIGN Normal term infants were assigned randomly and in masked fashion at birth to receive formulas with approximately 16% of total fatty acids as LA and 0.4%, 1.0%, 1.7%, or 3.2% of fatty acids as ALA (LA/ALA ratios of 44, 18.2, 9.7, and 4.8) for the first 4 months of life. The fatty acid pattern of plasma phospholipids was determined shortly after birth and at approximately 21, 60, and 120 days of age. Anthropometric data were obtained at the same times and also at approximately 240 days of age. Transient visual evoked responses (VERs) were measured at approximately 120 and 240 days of age. For comparisons, anthropometric and VER data also were obtained in infants who were exclusively breast-fed for the first 4 months of life. RESULTS Infants who received the formula with 3.2% ALA (LA/ALA ratio, 4.8) had higher plasma concentrations of phospholipid docosahexaenoic acid (DHA) but lower concentrations of arachidonic acid at 21, 60, and 120 days of age. Mean weight of this group at 120 days of age was 760 gm less (p < 0.05) than the mean weight of the group that received the formula with 0.4% ALA (LA/ALA ratio, 44). Despite differences in plasma phospholipid DHA contents among groups, neither VER latency nor amplitude differed significantly among formula groups or between any formula group and age-matched, breast-fed infants. CONCLUSIONS The highest versus the lowest ALA intake (or the lowest vs the highest LA/ALA ratio) resulted in higher plasma phospholipid DHA content from 21 to 120 days of age but was not associated with improved visual function as assessed by transient VER. Moreover, mean body weight of infants who received the highest versus lowest ALA intake was less at 120 days (p < 0.05). These data suggest that the lower LA/ALA ratios currently recommended for infant formulas should not be adopted until the effect of such ratios on growth are evaluated more completely.

Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial

BACKGROUND Isoflavones are naturally occurring plant estrogens that are abundant in soy. Although purported to protect against bone loss, the efficacy of soy isoflavone supplementation in the prevention of osteoporosis in postmenopausal women remains controversial. OBJECTIVE Our aim was to test the effect of soy isoflavone supplementation on bone health. DESIGN A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg of soy hypocotyl aglycone isoflavones plus calcium and vitamin D on bone changes in 403 postmenopausal women. Study subjects were tested annually and changes in whole-body and regional bone mineral density (BMD), bone mineral content (BMC), and T scores were assessed. Changes in serum biochemical markers of bone metabolism were also assessed. RESULTS After study site, soy intake, and pretreatment values were controlled for, subjects receiving a daily supplement with 120 mg soy isoflavones had a statistically significant smaller reduction in whole-body BMD than did the placebo group both at 1 y (P < 0.03) and at 2 y (P < 0.05) of treatment. Smaller decreases in whole-body BMD T score were observed among this group of women at 1 y (P < 0.03) but not at 2 y of treatment. When compared with the placebo, soy isoflavone supplementation had no effect on changes in regional BMD, BMC, T scores, or biochemical markers of bone metabolism. CONCLUSION Daily supplementation with 120 mg soy hypocotyl isoflavones reduces whole-body bone loss but does not slow bone loss at common fracture sites in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.

Effects of Early Maternal Docosahexaenoic Acid Intake on Neuropsychological Status and Visual Acuity at Five Years of Age of Breast-Fed Term Infants

OBJECTIVE We previously reported better psychomotor development at 30 months of age in infants whose mothers received a docosahexaenoic acid (DHA) (22:6n-3) supplement for the first 4 months of lactation. We now assess neuropsychological and visual function of the same children at 5 years of age. STUDY DESIGN Breastfeeding women were assigned to receive identical capsules containing either a high-DHA algal oil (∼200 mg/d of DHA) or a vegetable oil (containing no DHA) from delivery until 4 months postpartum. Primary outcome variables at 5 years of age were measures of gross and fine motor function, perceptual/visual-motor function, attention, executive function, verbal skills, and visual function of the recipient children at 5 years of age. RESULTS There were no differences in visual function as assessed by the Bailey-Lovie acuity chart, transient visual evoked potential or sweep visual evoked potential testing between children whose mothers received DHA versus placebo. Children whose mothers received DHA versus placebo performed significantly better on the Sustained Attention Subscale of the Leiter International Performance Scale (46.5 ± 8.9 vs 41.9 ± 9.3, P < .008) but there were no statistically significant differences between groups on other neuropsychological domains. CONCLUSIONS Five-year-old children whose mothers received modest DHA supplementation versus placebo for the first 4 months of breastfeeding performed better on a test of sustained attention. This, along with the previously reported better performance of the children of DHA-supplemented mothers on a test of psychomotor development at 30 months of age, suggests that DHA intake during early infancy confers long-term benefits on specific aspects of neurodevelopment.

Biochemical effects of dietary linoleic/α-linolenic acid ratio in term infants

Recent statements concerning linoleic (LA) and α-linolenic acid (LNA) intakes for infants include a desirable range of LA/LNA ratios. To evaluate several dietary LA/LNA ratios, the fatty acid patterns of plasma and erythrocyte phospholipid fractions, as well as plasma total lipid fractions, were determined shortly after birth and at 21, 60, and 120 d of age in term infants fed formula with 16% of fat as LA and either 0.4, 0.95, 1.7, or 3.2% as LNA (LA/LNA ratios of approximately 44, 18, 10, and 5). The content of all n-3 fatty acids in both plasma fractions was higher at all times in infants who received the highest LNA intake; however, the docosahexaenoic acid (DHA) content was only half that shortly after birth or reported in breast-fed infants of comparable ages. The LA content of plasma lipids of all groups was higher at all times than shortly after birth but did not differ among groups. The arachidonic acid (AA) content was higher in infants who received the lowest LNA intake, but only half that at birth or reported in breast-fed infants. In contrast, the DHA content of the erythrocyte phospholipid fraction did not differ among groups until 120 d of age when it was higher in those who received the highest LNA intake and the AA content of this fraction did not differ among groups at any time. These data demonstrate that dietary LA/LNA ratios between 5 and 44 do not result in plasma or erythrocyte lipid levels of DHA or plasma lipid levels of AA similar to those at birth or reported by others in breast-fed infants. However, the data indicate that the LA/LNA ratio of the formula is an important determinant of the amounts of DHA and AA required to achieve plasma and erythrocyte levels of these fatty acids similar to those of breast-fed infants.

Refinements in the implantation of pulmonary arterial stents: impact on morbidity and mortality of the procedure over the last two decades.

INTRODUCTION There is limited data on medium to long-term outcome, and the morbidity and mortality associated with the implantation, of pulmonary arterial stents. PURPOSE To assess changes in morbidity and mortality over the last two decades. METHODS Retrospective analysis of all patients stented between September, 1989 and July, 2001. RESULTS We implanted 664 Palmaz stents in 338 patients. The overall number included 229 patients who had undergone repair of tetralogy of Fallot, in whom 468 stents were implanted, 61 patients with congenital stenosis of the branches of the pulmonary trunk, in whom we placed 115 stents, 16 patients after an arterial switch operation who had 38 stents, and 32 patients after the Fontan operation who had 43 stents implanted. The mean age was 12.2 years, and the mean weight was 38 kg. The mean systolic pressure gradient decreased from 41 to 8.7 mmHg, the mean diameter of the stented vessel increased from 5.4 to 11.2 mm, and the ratio of right ventricular to femoral arterial pressure decreased from 0.66 to 0.45, each of these being significant at the level of p being less than 0.01. At a mean follow-up of 5.6 years, the mean gradient was 20 mmHg, the mean ratio of pressure between right ventricle and femoral artery was 0.5, and mean luminal diameter was 9.3 mm. Complications included migration of the stent in 8 patients, and pulmonary edema, hemoptysis and death in 5 patients each. There has been no mortality or morbidity since July of 1997. Technical changes include conservative serial dilations in congenital pulmonary arterial stenosis, avoidance of over-dilation, and simultaneous implantation of stents in the right and left pulmonary arteries in those with systemic pulmonary arterial pressure. Technological advances included shorter stents, improved balloon profiles, and central inflation of the stents. CONCLUSIONS Modification of stenting practices, and increased experience of the operators over the last two decades, has virtually abolished any morbidity or mortality associated with the implantation of stents for congenital or postoperative pulmonary arterial stenoses.

Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women

BACKGROUND Soy isoflavones are naturally occurring phytochemicals with weak estrogenic cellular effects. Despite numerous clinical trials of short-term isoflavone supplementation, there is a paucity of data regarding longer-term outcomes and safety. OBJECTIVE Our aim was to evaluate the clinical outcomes of soy hypocotyl isoflavone supplementation in healthy menopausal women as a secondary outcome of a trial on bone health. DESIGN A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg aglycone equivalent soy hypocotyl isoflavones plus calcium and vitamin D on the health of 403 postmenopausal women. At baseline and after 1 and 2 y, clinical blood chemistry values were measured and a well-woman examination was conducted, which included a mammogram and a Papanicolaou test. A cohort also underwent transvaginal ultrasound measurements to assess endometrial thickness and fibroids. RESULTS The baseline characteristics of the groups were similar. After 2 y of daily isoflavone exposure, all clinical chemistry values remained within the normal range. The only variable that changed significantly was blood urea nitrogen, which increased significantly after 2 y (P = 0.048) but not after 1 y (P = 0.343) in the supplementation groups. Isoflavone supplementation did not affect blood lymphocyte or serum free thyroxine concentrations. No significant differences in endometrial thickness or fibroids were observed between the groups. Two serious adverse events were detected (one case of breast cancer and one case of estrogen receptor-negative endometrial cancer), which was less than the expected population rate for these cancers. CONCLUSION Daily supplementation for 2 y with 80-120 mg soy hypocotyl isoflavones has minimal risk in healthy menopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.

Concurrent and Predictive Validity of the Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) and the Mental Developmental Index of the Bayley Scales of Infant Development

The Cognitive Adaptive Test/ Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was designed for use by primary pediatric health care providers to identify children with developmental delays. This study assesses the concurrent and predictive validity of CAT/CLAMS developmental quotient (DQ) scores and the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development in healthy children without risk factors for developmental delay. Overall CAT/CLAMS DQ scores correlated significantly with Bayley MDI scores at both 12 (r=0.393; p=0.008) and 30 months (r=0.742; p=0.0001) of age. Overall CAT/CLAMS DQ scores at 12 months of age also correlated modestly with Bayley MDI scores at 30 months of age (r=0.181; p=0.036). Despite its modest predictive validity at 12 months, its satisfactory concurrent validity plus its ease and speed of administration make the CAT/CLAMS a reasonable choice for assessment of early development by primary pediatric health care providers.

Evaluation of methods for assessing visual function of infants

Purpose: Commonly used behavioral and electrical testing methods for estimation of visual acuity and visual function in infants yield different estimates and may not accurately predict visual acuity and visual function in later life. Moreover, neither test-retest variability nor side-by-side comparisons of the various methods have been thoroughly evaluated in the same infant population. The purpose of this study was to provide such an evaluation. Method: The test-retest variability of visual acuity and visual function was evaluated for the Teller Acuity Card (TAC) procedure, sweep visual evoked potential (VEP), as well as latency and amplitude measured by transient pattern VEP. Groups of approximately 20 infants contributed test-retest data. Visual function estimated by the various methods in a larger group of infants (n = 118) was compared. Correlations between methods and the validity of the various methods to detect maturational changes between 4 and 8 months of age were also assessed. Administration of these tests was according to standard and usual procedures. Results: The average percent difference between test and retest estimates of acuity as well as the SD was lowest for transient VEP latency (3%, 7% SD). The other methods were markedly more variable: sweep VEP (2%, 22% SD), TAC procedure (8%, 20% SD), and transient VEP amplitude (7.5%, 39% SD). Average coefficients of variation showed a similar trend: transient VEP latency, 8%; sweep VEP, 15%; TACs, 30%; and transient amplitude, 53%. Correlations among estimates by the methods were poor, but expected changes in visual maturation from 4 to 8 months of age were detected with all methods. Conclusions: All methods evaluated provide valid and reliable test-retest data for a group, but are less valid for estimating visual acuity and visual function of an individual subject. The poor correlations between any 2 of the testing methods suggest that each test assesses a different aspect of vision. Nonetheless, expected maturational changes between 4 and 8 months of age were readily detectable by all methods evaluated. (J AAPOS 1999;3:275-82)

Nitric Oxide in the Evaluation of Congenital Heart Disease with Pulmonary Hypertension: Factors Related to Nitric Oxide Response

Inhaled nitric oxide (NO) has been used in the preoperative evaluation of patients with congenital heart disease and pulmonary hypertension. The purpose of this study was to characterize responses in pulmonary vascular resistance (PVR) to oxygen and increasing doses of NO during cardiac catheterization and to determine if any related factors affect the response of the pulmonary vascular bed to NO. A prospective analysis of 42 patients (median age, 3.0 years) with congenital heart disease and pulmonary hypertension who underwent NO testing was performed. Systemic vascular resistance (SVR) and PVR were assessed in room air, 100% oxygen, and oxygen plus 20, 40, and 80 parts per million (ppm) NO. Changes in pulmonary artery pressure, PVR, and SVR were assessed. The response to NO was then correlated to individual patient’s age, gender, type of heart defect, the presence of trisomy 21, and baseline PVR/SVR. There was a greater decrease in PVR and PVR/SVR with 20 ppm NO than with oxygen alone. There was no additional decrease at 40 or 80 ppm NO. There was no correlation between age, gender, type of congenital heart disease, and baseline PVR/SVR ratio with the degree of response to NO. Patients with trisomy 21 had less of a response to NO (p = 0.017) than patients without trisomy 21. There is no difference in determining PVR response with doses of NO beyond 20 ppm during cardiac catheterization. Age, gender, and baseline PVR/SVR ratio are not associated with responsiveness to NO. Patients with trisomy 21 may be less responsive to NO.

Growth Characteristics of Children With Ectodermal Dysplasia Syndromes

Objective.Clinical observations suggested that growth abnormalities may be present in children with ectodermal dysplasia (ED) syndromes. This study characterizes the longitudinal pattern of growth in a cohort of children with the ED syndromes. We hypothesized that (1) linear and ponderal growth abnormalities are present in children with ED from infancy through adolescence, and (2) linear and ponderal growth abnormalities differ among the clinical variants of these disorders. Methods.We studied 138 children who had ED and were registered with the National Foundation for Ectodermal Dysplasias, 74% of whom had clinical features consistent with the hypohidrotic EDs (HEDs). Height (or length) and weight measurements were obtained by standardized techniques and from review of available medical records. We converted these measurements to weight-for-height (children younger than 5 years and <103 cm in length) or BMI (children ≥2 years old). Height, weight, weight-for-height, and BMI were converted to age- and gender-specific z scores. We applied linear regression, 1-sample t tests, and analysis of variance to detect linear and ponderal growth abnormalities in children with ED compared with a reference population. Results.Mean weight-for-age, weight-for-height, and BMI-for-age z scores but not height-for-age z score, were significantly lower in children with the ED syndromes than in the reference population. Mean weight-for-age and weight-for-height z scores but not BMI-for-age or height-for-age z scores increased significantly with increasing age. The mean height-for-age z score of children with the ED syndromes other than the HEDs was significantly lower than that of children with the HEDs. Conclusions.Growth abnormalities, measured as weight deficits, were present at an early age in children with the ED syndromes and persisted through adolescence. Height deficits were seen only in children with ED syndromes other than HEDs. Clinicians should evaluate carefully children with ED syndromes for growth abnormalities.