Gut microbiota promoting propionic acid production accompanies caloric restriction-induced intentional weight loss in cats.

Rodent models and human clinical studies have shown gut microbiota-derived short-chain fatty acids (SCFAs) play roles in obesity and insulin resistance. These roles have been minimally explored in cats, where in the USA an estimated 60% of cats are overweight or obese. Overweight/obese research cats (n = 7) were transitioned from a maintenance diet to a reduced calorie diet fed ad libitum for 7 days, then calories were restricted to achieve 1-2% weight loss per week for an additional 77 days. Cats then received their original maintenance diet again for 14 days. Significant intentional weight loss was noted after calorie restriction (adjusted p < 0.0001). 16S rRNA gene amplicon sequencing and targeted SCFA metabolomics were performed on fecal samples. Fecal microbial community structure significantly differed between the four study phases (PERMANOVA p = 0.011). Fecal propionic acid was significantly higher during caloric restriction-induced weight loss (adjusted p < 0.05). Repeated measures correlation revealed the relative abundances of Prevotella 9 copri (correlation coefficient = 0.532, 95% CI (0.275, 0.717), p = 0.0002) significantly correlated with propionic acid composition. Like humans, obese cats experienced an altered microbial community structure and function, favoring propionic acid production, during caloric restriction-induced weight loss.

Gut microbiota promoting propionic acid production accompanies diet-induced intentional weight loss in cats.

Rodent models and human clinical studies have shown gut microbiota-derived short-chain fatty acids (SCFAs) play roles in obesity and insulin resistance. These roles have been minimally explored in cats, where in the USA an estimated 60% of cats are overweight or obese. Overweight/obese research cats (n = 7) were transitioned from a maintenance diet to a reduced calorie diet fed ad libitum for seven days, then calories were restricted to achieve 1-2% weight loss per week for an additional 77 days. Cats then received their original maintenance diet again for 14 days. Significant intentional weight loss was noted after calorie restriction (adjusted p < 0.0001). 16S rRNA gene amplicon sequencing and targeted SCFA metabolomics were performed on fecal samples. Fecal microbial community structure significantly differed between the four study phases (PERMANOVA p = 0.011). Fecal propionic acid was significantly higher during diet-induced weight loss (adjusted p < 0.05). Spearman correlation revealed the relative abundances of Prevotella 9 copri (ρ = 0.6385, p = 0.0006) and Blautia caecimuris (ρ = 0.5269, p = 0.0068) were significantly correlated with propionic acid composition. Like humans, obese cats experienced an altered microbial community structure and function, favoring propionic acid production, during diet-induced weight loss.

Pre-discharge outcomes of 22-27 weeks gestational age infants born at tertiary care centers in Connecticut implications for perinatal management.

There is a lack of regional data on survival and morbidity of extremely premature infants born and resuscitated at tertiary care centers. This study analyzes such data from three tertiary care perinatal centers in Connecticut and provides a paradigm for its use in developing guidelines for evidence-based ethical considerations in infants at the threshold of viability. Outcomes of inborn infants 22 to 27 weeks gestation (based on obstetric estimates) who were actively resuscitated at three regional perinatal tertiary-care centers (representing 80% of such infants from Connecticut) were studied retrospectively. Survival and cumulative major morbidities at discharge, stratified by gestational age, were analyzed. Of the 405 infants studied, 278 (69%) survived to discharge. There were no survivors beyond three days at 22 weeks gestational age. Unfavorable outcome defined as death or major morbidity (> or = grade 2 intraventricular hemorrhage, periventricular leukomalacia, > or = Stage 3 retinopathy of prematurity, necrotizing enterocolitis > or = Stage 2, and severe bronchopulmonary dysplasia at 36 weeks postmenstrual age.) was seen in > 85% of 23 and 24 weeks gestation infants. At 25 weeks approximately equal to 30% of infants were discharged without an unfavorable outcome. At 26 and 27 weeks gestation 43% and 61% respectively escaped unfavorable outcomes with > 85% rates of survival. Current regional data such as these would help in developing guidelines for the perinatal management of premature infants at the threshold of viability.

Serum content of the C-propeptide of the cartilage molecule type II collagen in children.

OBJECTIVE: The C-propeptide of cartilage type II procollagen, together with the N-propeptide, are removed from newly synthesized procollagen during collagen fibril assembly in cartilage matrix. The presence and content of the C-propeptide reflect the synthesis of this molecule. Recently, we showed that serum levels of the C-propeptide are increased in adults with rheumatoid arthritis, pointing to increased synthesis of this molecule. In this study we examined its content in the sera of children to determine whether it changes during development. METHODS: Sera were obtained from 44 premature infants (cord blood), 75 children (0-18 years), 14 young adults (18-22 years) and 47 adults (35-60 years). The concentration of serum C-propeptide of type II procollagen was determined by a solution phase competitive inhibition radioimmunoassay which uses a polyclonal antiserum specific for the bovine and human C-propeptide. RESULTS: Compared with adults, concentrations of the C-propeptide of type II procollagen were significantly elevated in children of ages 0-14 years. Concentrations were constant until 10 years of age (premature infants: 14.5 +/- 1.4 ng/ml, mean +/- SE; 0-10 years: 13.6 +/- 1 ng/ml). In children of ages 10-14 years, during which the pubertal growth spurt is ordinarily observed, the mean concentration increased (10-14 years: 21.6 +/- 0.7 ng/ml) although not significantly due to the variation between individuals. Concentrations at all ages younger than 14 were significantly greater than those in older adolescents ages 14-18 (6.3 +/- 0.7 ng/ml), young adults (8.4 +/- 2.0 ng/ml) and adults (5.7 +/- 0.4 ng/ml). Serum concentrations did not show significant differences with respect to sex, but varied from child to child at any given age. CONCLUSIONS: The measurement of this circulating C-propeptide may be of use in studying the biochemical and physiological bases of changes in cartilage turnover in children, and abnormalities thereof.

Fetal myocardial calcification associated with maternal cocaine use.

Two cases of fetal myocardial calcification confirmed postnatally are reported. In contrast to other reports, both infants survived with resolution of calcification by 6 and 12 months. Diagnostic investigations failed to confirm the presence of congenital infection. Both pregnancies were complicated by early cocaine use leading to the speculation that myocardial necrosis with subsequent calcification related to the toxic and/or vascular effects of cocaine was responsible. The finding of fetal myocardial calcification on prenatal ultrasound should prompt a search for causes, which may include cocaine exposure.

Distortion-product and click-evoked otoacoustic emissions of preterm and full-term infants.

Full-term and preterm infants were evaluated with click-evoked and distortion-product otoacoustic emissions (CEOEs and DPOEs). The CEOEs and DPOEs recorded from each individual ear were analyzed by calculating the root-mean-square levels within half-octave bands. The fail criterion of the OE tests was that the half-octave RMS DPOE or CEOE levels of an ear under test were below the 10th percentile of full-term newborns in two or more bands. The DPOE data were collected from 118 ears of 61 premature babies; 80 (68%) ears passed the DPOE test, 30 (25%) ears without middle ear effusions failed the test, and 8 (7%) ears with effusions also failed. The CEOE data were collected from 128 ears of 65 premature babies; 102 (80%) ears passed the CEOE test, 18 (14%) ears without middle ear effusions failed the test, and 8 (6%) ears with effusions also failed. In 23 of 80 ears (29%) that passed the DPOE test and in 23 of 102 ears (23%) that passed the CEOE test, RMS OE levels of preterm infants were above the 90th percentile of full-term newborns. The analyses of the combined DPOE and CEOE data obtained from a group of 25 ears of full-term newborns and from a group of 72 ears of preterm babies showed statistically significant correlations between the DPOE and CEOE root-mean-square levels in each of the half-octave bands in the 1.4 to 4 kHz region. For 42 preterm infants tested with auditory brain stem response (ABR), specificity was 86% for CEOE and 74% for DPOE. All infants who failed the ABR also failed OE tests. To the best of our knowledge, this study is the first using combined DPOEs, CEOEs, and ABRs for preterm babies. It showed the feasibility of DPOEs and CEOEs for this population.

Nephrocalcinosis.

The pathogenesis of NC in VLBW infants appears to be multifactorial. The vulnerability of extreme immaturity and the underdevelopment of renal function may be the most important variables. In some ways, we view this problem as similar to that of retinopathy of prematurity. (Clearly the exposure of the retina to high partial pressures of oxygen contributes to the development of retinopathy of prematurity but other variables--some known, such as an immature retina, and others not yet defined--must be present.) Hypercalciuria is common in the VLBW infant, yet not all develop NC. Decreased glomerular filtration rate, low citrate excretion, and frequently an alkaline urine are in part due to the immaturity of renal function of these infants. The need for prolonged hyperalimentation resulting in increased oxalate excretion and the development of BPD frequently requiring diuretics that may cause phosphaturia and magnesium depletion and that may increase calcium excretion are more common in the smallest and sickest of premature infants. Even transient insults to the kidneys, such as hypoxia or hypotension or the use of nephrotoxic drugs that provoke tubular injury and cell death with the probability of crystal formation and growth by way of heterogeneous nucleation, are likely to occur more frequently in this vulnerable population.

Effect of calcium/phosphorus ratio on mineral retention in parenterally fed premature infants.

We hypothesized that retention of parenterally delivered calcium (Ca) and phosphorus (P) is affected by the ratio of the delivered minerals and that a 1.7:1 ratio would be optimal since this is the ratio of retention of these minerals by the fetus. Forty-one very low birth weight (VLBW) infants were randomly assigned to one of three total parenteral nutrition (TPN) solutions that were different only in their Ca:P ratios: 2:1 (76 mg/kg/day Ca and 38 mg/kg/day of P), and 1.3:1 (58 mg/kg/day Ca and 45 mg/kg/day P), and 1.3:1 (58 mg/kg/day of Ca and 45 mg/kg/day of P). Serum levels of calcium, phosphorus, and alkaline phosphatase, retentions of calcium and phosphorus and urinary cyclic AMP levels were measured after 48 h on the assigned Ca to P ratio. Calcium retentions were higher with the 2:1 and 1.7:1 ratios and phosphorus retentions were higher with the 1.3:1 and 1.7:1 ratios. The 1.7:1 ratio allowed for the highest absolute retention of both minerals and was the closest to published in utero accretion of calcium and phosphorus. The serum and urine studies demonstrated no abnormalities on any of the three ratios. Cyclic AMPs were not different among groups and were not elevated compared to previous reports suggesting that none resulted in parathyroid hormone (PTH) stimulation. We conclude that the 1.7:1 ratio is better than higher or lower ratios for delivery of calcium and phosphorus in TPN solutions at the quantities studied.

Effect of high calcium and phosphorus intake on mineral retention in very low birth weight infants chronically treated with furosemide.

The treatment of premature infants with the diuretic furosemide appears to be a contributory factor in the development of metabolic bone disease presumably because of furosemide-induced hypercalciuria. In this study, we measured calcium and phosphorus balance in furosemide-treated very low birth weight infants (VLBW) infants with bronchopulmonary dysplasia (BPD) who were fed a specialized premature formula containing increased amounts of calcium and phosphorus. Furosemide-treated infants received 166 +/- 37 mg/kg/day and retained 80 +/- 34 mg/kg/day of calcium, and 87 +/- 19 mg/kg/day and retained 52 +/- 14 mg/kg/day of phosphorus. The amounts retained were approximately 65% of the calcium and 72% of the phosphorus requirements for in utero mineral accretion. Compared to a group of similarly fed VLBW infants without BPD and not treated with the diuretic, the furosemide-treated infants excreted a larger percent of the calcium intake in the urine but had similar total urinary calcium and phosphorus losses (mg/kg/day) and serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone (PTH) levels. From the latter two findings, we suggest that the extra mineral content of the formula may have promoted bone mineralization and prevented the occurrence of secondary hyperparathyroidism.

Simultaneous infusion of calcium and phosphorus in parenteral nutrition for premature infants: use of physiologic calcium/phosphorus ratio.

We hypothesized that parenteral delivery of calcium and phosphorus in a ratio of 1.7:1 would promote retention of these minerals and decrease urinary phosphorus excretion, and that delivery of increased amounts of this ratio would result in higher retentions. Serum levels and retention of calcium and phosphorus were measured as calcium intake was increased from 36 to 76 mg/kg/day in 10 mg increments and as phosphorus intake was adjusted to maintain the 1.7:1 ratio. Five different infants were studied at each of the five levels. The amounts of calcium and phosphorus retained increased steadily and at level 5 were 71.8 +/- 1.2 mg/kg/day and 40.9 +/- 1.7 mg/kg/day, respectively. Over the five levels the average percent calcium retention was 91.4 +/- 4.2 and the average percent phosphorus retention was 89.1 +/- 7.7. The provision of parenteral calcium and phosphorus in a 1.7:1 ratio resulted in a balanced retention of both minerals over the range studied. The use of this calcium/phosphorus ratio appears to be appropriate for the preterm infant receiving total parenteral nutrition.

Infants at risk for sudden infant death syndrome (SIDS): differential prediction for three siblings of SIDS infants.

The outcome for three siblings of SIDS (SSIDS) infants was predicted, using as a risk model the sleep and respiratory characteristics of a SIDS victim studied extensively during the neonatal period. The SIDS infant had shown unstable state organization and deviant respiration patterns, including a deficit of brief apneic pauses. Like the SIDS infant, the SSIDS infants and a group of 16 normal infants were observed in the home for 7-hr periods when they were 2, 3, 4, and 5 weeks old. Two of the infants showed normal sleep and respiratory characteristics, and they were predicted to develop without respiratory dysfunction. In contrast, the third infant showed a pattern of deviancies similar to the SIDS infant; and at 4 months, she had prolonged apneic episodes, requiring resuscitation on two occasions. The findings are consistent with the notion of subtle central nervous system (CNS) dysfunction in SIDS risk infants from the time of birth.

Longitudinal development of specific and functional antibody in very low birth weight premature infants.

We evaluated the formation of specific and functional antibody in preterm infants born weighing less than 1500 g (mean 1088 g) and less than 32 wk gestational age (mean 28.8 wk). Plasma IgG antibody against tetanus and diphtheria toxoids were measured by an enzyme-linked immunosorbent assay. Opsonic activity of heat-inactivated plasma was measured using radiolabeled bacteria, adult polymorphonuclear leukocytes and exogenous human complement. In the presence of complement, the strain of coagulase negative staphylococcus used was opsonized by IgG antibody, and the strain of Escherichia coli by IgM. Geometric mean plasma levels of tetanus and diphtheria IgG antibody fell from birth to 4 months chronological age, but rose significantly by 9 months (approximately 2 months after the third dose of diphtheria, tetanus, pertussis vaccine). However, at 9 months they remained lower than the respective geometric mean levels in 9-month-old term infants (tetanus: p less than 0.001; diphtheria: p = 0.02). The preterm infants' mean plasma IgG staphylococcal opsonic activity fell from birth to 2.5 months, but by 9 months was comparable to that of term infants of the same age. Mean IgM opsonic activity for E. coli was very low at birth in both preterm and term infants. It rose with chronological age, correlating with the rise in total IgM (r = 0.48, p less than 0.001) and by 9 months the mean preterm and term infants' levels of IgM opsonic activity for E. coli were comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Alternate day infusion of calcium and phosphate in very low birth weight infants: wasting of the infused mineral.

Very low birth weight infants require greater intakes of calcium and phosphate than can be supplied simultaneously in parenteral nutrition. We investigated the biochemical effects and retention of calcium and phosphate when each was administered for 24 h on an alternate day schedule as part of total parenteral nutrition. Serum and urine were collected during a 24 h basal period and during randomly ordered 24 h infusions of either calcium or phosphate in 14 infants during the first week of life. In general, the urinary excretion of the infused mineral (calcium or phosphorus) increased during the 24 h period of its infusion. The serum phosphorus level fluctuated widely from day to day while the serum calcium level did not change. During the 24 h infusion of phosphate, phosphate retention was 67.9 +/- 7.4% and, during the 24 h infusion of calcium, calcium retention was 72.5 +/- 4.3%. However, ongoing excretion of each mineral on the day it was not infused meant that 48.3% of the 48 h phosphate intake and 42.2% of the 48 h calcium intake were lost in the urine. We conclude that excessive amounts of the administered mineral were excreted and that alternate day infusion of calcium and phosphate is an unsatisfactory method for providing these minerals. Attainment of sufficient retentions of calcium and phosphate will require development of novel methods of simultaneous administration which provide calcium and phosphate in high concentrations.

Phosphorus deficiency syndrome in very low birth weight infants.

Inadequate dietary phosphorus intake is a contributing factor to the occurrence of metabolic bone disease in very low birth weight infants. This article reviews the clinical presentation and the pathophysiology of the phosphorus deficiency syndrome in premature infants. Recommendations for therapy and prevention of phosphorus deficiency are presented.

Growth and phosphorus metabolism in premature infants fed human milk, fortified human milk, or special premature formula. Use of serum procollagen as a marker of growth.

Human milk promotes less than optimal growth and is associated with phosphorus deficiency and decreased bone mineralization in very-low-birth-weight (VLBW) infants. In this study, the effects of feeding premature infants either human milk (HM), fortified human milk (FHM), or special premature formula (Similac Special Care [SSC]) on growth, phosphorus metabolism, and serum type I procollagen (pColl-I-C) were evaluated. Infants fed FHM exhibited a rate of weight gain and an increase in head circumference comparable with infants fed SSC and significantly greater than infants fed HM, despite the fact that both the FHM group and the HM group demonstrated biochemical evidence of phosphorus deficiency. The pColl-I-C concentrations in VLBW infants were tenfold to 20-fold greater than concentrations in normal children older than 2 years of age. The pColl-I-C levels correlated positively with weight gain and were significantly greater in the FHM and SSC groups than in the HM group. By contrast, serum alkaline phosphatase levels did not correlate with weight gain and were significantly lower in the rapidly growing SSC group than in either of the two groups with phosphorus deficiency and presumed poor bone mineralization. We conclude that the serum pColl-I-C concentration is a biochemical marker of growth in VLBW infants and may prove useful as a predictor of growth responses to various nutritional and therapeutic interventions.

Achievement of in utero retention of calcium and phosphorus accompanied by high calcium excretion in very low birth weight infants fed a fortified formula.

Calcium and phosphorus retention was evaluated in 13 very low birth weight infants who were fed an experimental formula designed to deliver quantities of calcium and phosphorus sufficient to meet the intrauterine accretion rates for these minerals. Retention of calcium and phosphorus in slight excess of these rates was achieved without any apparent difficulties for the infants. Biochemical measurements demonstrated normal serum calcium (9.8 +/- 8 mg/dL) and alkaline phosphatase (242 +/- 51.6 IU) values. However, there was evidence of high tubular reabsorption of phosphate (98.1% +/- 3.3%), hypercalciuria (7.2 +/- 3.8 mg/kg/d), and a relatively low serum phosphorus concentration (5.7 +/- 0.6 mg/dL). This biochemical picture is similar to that seen in phosphorus deficiency except for the low alkaline phosphatase activity. The latter finding, in concert with the high retention of calcium and phosphorus in these balance studies, makes such a diagnosis unlikely. We speculate that this biochemical picture is the result of an inappropriately high calcium/phosphorus ratio.

Peripheral blood T-cell subpopulations in the very low birth weight (less than 1,500-g) infant.

The development of monoclonal antibodies to cell-surface antigens has provided method for characterizing distinct subpopulations of T-cells. In the present study we have quantified peripheral blood T-cell subpopulations in premature infants born weighing less than 1,500 g (1123 +/- 223 g) and ranging in gestational age from 25 to 32 weeks. The relative proportion of T4 cells in the very low birth weight (VLBW) infants was markedly higher at 1 week and 1 month of age (mean +/- SEM; 67.5 +/- 4.1 and 59.2 +/- 1.6) than in adult controls (47.2 +/- 1.5). The percentage of T4 cells remained elevated until 6 months of age, when it decreased to a level comparable to that in adults. In contrast, the proportion of T8 cells was significantly lower than the adult level at 1 week and 1 month of age. The T4/T8 ratio in the VLBW infants was higher at 1 week (4.3 +/- 0.5) and 1 month (3.5 +/- 0.2) than in adult controls (2.0 +/- 0.1). Thereafter, the T4/T8 ratio decreased but was still significantly higher than that in adult controls at 6 months of age (2.6 +/- 0.2). The absolute numbers of total T-cells (T3) and T8 and T4 cells were significantly higher in VLBW infants. The numbers of T8 cells were significantly lower in the first month of life than at 3-6 months of age. These alterations in the T-cell subsets in the first 6 months of life suggest that postnatal T-cell phenotypic changes in VLBW infants may parallel the T-cell ontogenetic process which occurs during the last trimester of pregnancy in full-term infants.

Development of the immune system in very low birth weight (less than 1500 g) premature infants: concentrations of plasma immunoglobulins and patterns of infections.

Plasma immunoglobulin concentrations of premature infants of birth weight less than 1500 g were measured longitudinally from birth to 10 months chronological age. Infants were divided into two groups based on gestational age (group I: 25-28 wk; group II: 29-32 wk). In the 1st wk of life, plasma IgG levels correlated with gestational age (r = 0.5, p less than 0.001). At 3 months chronological age, the geometric mean plasma IgG levels were 60 mg/dl in group I and 104 mg/dl in group II infants. Most infants remained hypogammaglobulinemic at 6 months with seven of 11 infants in group I and 13 of 21 infants in group II having plasma IgG levels below 200 mg/dl. In the 1st wk of life, plasma IgM concentrations were 7.6 and 9.1 mg/dl in groups I and II, respectively. They rose to 41.8 and 34.7 by 8 to 10 months of life. Plasma IgA concentrations were comparable for groups I and II in the 1st wk of life (1.2 and 0.6 mg/dl, respectively), but at 1 month of age group I infants had a transient increase in IgA which was not seen in the group II infants (4.5 versus 1.9 mg/dl, respectively, p less than 0.02). This transient elevation in IgA did not correlate with type or route of feeding or amounts of transfused blood. Group I and group II infants had comparable rates of infections prior to discharge from the nursery (p = 0.27). After discharge, the 43 preterm infants followed until 10 months chronological age had a significantly higher incidence of infections than 41 term infants (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)