Maturation of feedback control of thyrotropin in premature infants

Serum thyrotropin (TSH), free T4 and free T3 concentrations were measured longitudinally in 26 preterm infants for 14 weeks after birth, using highly sensitive immunoradiometric assays. Serum TSH values on days 4-5 were positively correlated with gestational age and birth weight. In the premature infants of 25 weeks mean gestation, the mean TSH concentrations increased from a very low value of 0.84 microU/ml at 5 days to a peak value of 6.1 microU/ml by 5 weeks of age, then slightly decreased and remained stable. Serum free T4 and free T3 concentrations increased in parallel and free T3 level reached the range of term infants by 6 weeks. Serum free T4/TSH and free T3/TSH ratios began to increase at the 6th week of age. The results suggest that: (i) the thyroid hormone feedback control of pituitary TSH release in the extremely premature infants begins to mature after 6 weeks of postnatal age, (ii) the maturation pattern of the hypothalamic-pituitary-thyroid system in premature infants is similar to that of the intrauterine fetus.     

Molybdenum supply of very low-birth-weight premature infants during the first months of life

This explorative study was performed to assess basic data on the Mo metabolism of premature infants. Premature (n=18, gestational age ≤32 wk, birth weight ≤1500 g) and healthy formula-fed term infants (n=14) were nourished and corrected for gestational age, identically. Plasma was collected at 3, 16, and 52 wk and 72 h balances were performed at 3 wk of age. In the premature infants, these investigations were preceded by two balance studies and an initial plasma collection. Increased Mo intake and low relative urinary excretion resulted in a retention of 4.4 (0.99–7.77) μg Mo/kg initially in premature infants (median, range). Parallel plasma concentrations were 5.5 (2.5–7.3) μg Mo/L, declining to 2.36 (0.73–3.87) μg Mo/L at 4 wk. Term infants rendered 1.49 (0.29–1.7) μg Mo/L (p<0.05), with no significant differences later. It was concluded that the supplementation of formulas for premature infants with Mo should be recinded until there is evidence for its necessity.     

Effects of parenteral lipid infusion on DNA damage in very low birth weight infants

Very low birth weight (VLBW) infants are known to have poorly developed antioxidant system and may be at increased risk for radical damage. Previous studies have reported higher levels of lipid peroxide products in lipid emulsion used for parenteral nutrition. To examine the direct effects of parenteral lipid infusion on DNA damage in VLBW infants, we measured urinary 8-hydroxydeoxyguanosine (8-OHdG) levels in VLBW infants before, during, and after the parenteral lipid infusion. In both the lipid-infused and lipid-free groups, urinary 8-OHdG excretion levels at 14 days old were significantly (p < 0.01) lower than those at 2 and 7 days old. However, there were no significant differences in urinary 8-OHdG excretion levels between the lipid-infused and lipid-free groups at 2, 7, and 14 days old. Our results suggest that parenteral lipid infusion does not cause oxidative DNA damage, but irrespective of the infusion DNA damage during the first week of life is enhanced when compared with 14 days after birth in VLBW infants.     

Effects of Parenteral Lipid Infusion on DNA Damage in Very Low Birth Weight Infants

Very low birth weight (VLBW) infants are known to have poorly developed antioxidant system and may be at increased risk for radical damage. Previous studies have reported higher levels of lipid peroxide products in lipid emulsion used for parenteral nutrition. To examine the direct effects of parenteral lipid infusion on DNA damage in VLBW infants, we measured urinary 8-hydroxydeoxyguanosine (8-OHdG) levels in VLBW infants before, during, and after the parenteral lipid infusion. In both the lipid-infused and lipid-free groups, urinary 8-OHdG excretion levels at 14 days old were significantly ( p <0.01) lower than those at 2 and 7 days old. However, there were no significant differences in urinary 8-OHdG excretion levels between the lipid-infused and lipid-free groups at 2, 7, and 14 days old. Our results suggest that parenteral lipid infusion does not cause oxidative DNA damage, but irrespective of the infusion DNA damage during the first week of life is enhanced when compared with 14 days after birth in VLBW infants.     

Hormone synthesis and storage in the thyroid of human preterm and term newborns: effect of thyroxine treatment.

Iodine and thyroglobulin concentrations, as well as iodine, T3, T4 and sialic acid contents of thyroglobulin, were measured in thyroid glands collected postmortem from 42 human premature or term newborns and infants. Three groups were considered: very preterm newborns (24-32 postmenstrual weeks, < 5 days postnatal life), preterm and term newborns (34-41 postmenstrual weeks, < 5 days postnatal life) and infants (born at term, postnatal age 1-8 months). Five very preterm and seven preterm newborns received a daily dose of 10 microg/kg L-T4 for at least 3 days. Thyroid weight and sialic acid content of thyroglobulin progressed with maturation. Intrathyroidal concentrations of iodine and thyroglobulin did not increase significantly before the 42nd week of postmenstrual age. The level of thyroglobulin iodination increased during the postnatal life, except in the very preterm neonates. T4 and T3 content of thyroglobulin was directly proportional to its degree of iodination and positively related to its sialic acid content. L-T4 treatment of preterm newborns increased thyroglobulin iodination and T4-T3 content, without increasing thyroglobulin concentration in the thyroid. It was concluded that the storage of thyroglobulin and iodine in the thyroid develops around term birth. This, associated with the resulting rapid theoretical turnover of the intrathyroidal pool of T4 in Tg, could be an important factor of increased risk of neonatal hypothyroxinemia in the premature infants. The L-T4 treatment of preterm newborns does not accelerate the maturational process of the thyroid gland.     

Premature labor and indomethacin.

Administration of indomethacin to 29 women in the 26th--37th week of gestation with premature labor contractions was followed in 26 by a significant decrease of uterine activity. The effect of therapy was monitored by serial external tocometry recordings and by plasma concentrations of estriol, h.P.L., alpha-fetoprotein, and estriol/creatinine ratio in urine. The labor was monitored by cardiotocography; the new born infants were examined by the pediatrician. Following oral indomethacin treatment (25 mg every 6 Hours for 5 days) no untoward effects was observed on maternal and fetal wellbeing during pregnancy and labor. Four out 29 newborn infants, all appropriate for gestational age of 36--40 weeks, had one-minute Apgar scores less than 7, cyanosis, tachypnea, hypoxemia and serious oxygen dependency for several days. All the infant survived. These abnormalities may be due to short-term exposure to indomethacin and consequent inhibition of cyclo-oxygenase, impairement of prostaglandin-dependent physiological regulation of vessel tone during fetal life and circulatory disorders at birth.     

Premature labor and indomethacin

Administration of indomethacin to 29 women in the 26th–37th week of gestation with premature labor contractions was followed in 26 by a significant decrease of uterine activity. The effect of therapy was monitored by serial external tocometry recordings and by plasma concentrations of estriol, h.P.L., alpha-fetoprotein, and estriol/creatinine ratio in urine. The labor was monitored by cardiotocography; the newborn infants were examined by the pediatrician. Following oral indomethacin treatment (25 mg every 6 Hours for 5 days) no untoward effects was observed on maternal and fetal wellbeing during pregnancy and labor. Four out 29 newborn infants, all appropriate for gestational age of 36–40 weeks, had one-minute Apgar scores less than 7, cyanosis, tachypnea, hypoxemia and serious oxygen dependency for several days. All the infant survived. These abnormalities may be due to short-term exposure to indomethacin and consequent inhibition of cyclo-oxygenase, impairement of prostaglandin-dependent physiological regulation of vessel tone during fetal life and circulatory disorders at birth.     

Oxidative stress in erythrocytes from premature and full-term infants during their first 72 h of life

OBJECTIVE: The aim of this study was to evaluate the extent of lipid peroxidation and the response of the enzymatic and non-enzymatic antioxidant defence system in erythrocytes from full-term and premature infants at birth, after 3 and after 72 h of life. STUDY DESIGN: Twenty infants were selected and divided in two groups according to their gestational age. Blood samples were taken at birth, at 3 and at 72 h of life, erythrocytes were isolated and the following parameters were measured: fatty-acid profile, coenzyme Q, alpha-tocopherol, hydroperoxides and the activity of the antioxidant enzymes catalase, superoxide dismutase (SOD) and cytosolic glutathione peroxidase (cGPx). RESULTS: For the three studied periods, several differences between full-term and premature infants were found. Premature children showed a higher concentration of hydroperoxides, a lower level of alpha-tocopherol and lower SOD and cGPx activity (except for cGPx at birth). Moreover, n-3 polyunsaturated fatty-acids percentages (essential for good neonatal development) were higher in full term children throughout all the study. CONCLUSION: Results suggest a strong imbalance between oxidants and antioxidants in premature infants during their first 72 h of life, a situation which could lead to several pathologies. Therefore, further research is needed, including possible nutritional intervention (with antioxidant therapy, supplementation of essential fatty acids and other dietary constituents) before and after birth.     

Oxidative Stress in Erythrocytes from Premature and Full-term Infants During their First 72 h of Life

Objective : The aim of this study was to evaluate the extent of lipid peroxidation and the response of the enzymatic and non-enzymatic antioxidant defence system in erythrocytes from full-term and premature infants at birth, after 3 and after 72 h of life. Study design: Twenty infants were selected and divided in two groups according to their gestational age. Blood samples were taken at birth, at 3 and at 72 h of life, erythrocytes were isolated and the following parameters were measured: fatty-acid profile, coenzyme Q, &#102 -tocopherol, hydroperoxides and the activity of the antioxidant enzymes catalase, superoxide dismutase (SOD) and cytosolic glutathione peroxidase (cGPx). Results: For the three studied periods, several differences between full-term and premature infants were found. Premature children showed a higher concentration of hydroperoxides, a lower level of &#102 -tocopherol and lower SOD and cGPx activity (except for cGPx at birth). Moreover, n-3 polyunsaturated fatty-acids percentages (essential for good neonatal development) were higher in full term children throughout all the study. Conclusion: Results suggest a strong imbalance between oxidants and antioxidants in premature infants during their first 72 h of life, a situation which could lead to several pathologies. Therefore, further research is needed, including possible nutritional intervention (with antioxidant therapy, supplementation of essential fatty acids and other dietary constituents) before and after birth.     

Concentrations of Homovanillic Acid and 5-Hydroxyindoleacetic Acid in Cerebrospinal Fluid from Human Infants in the Perinatal Period

To assess maturation of central serotonin and catecholamine pathways at birth, we measured lumbar CSF homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), stable acid metabolites of dopamine and serotonin, using HPLC with electrochemical detection. CSFs from 57 neonates (38 premature and 19 at term) and 13 infants 1-6 months old were studied. HVA levels increased with maturity (p less than 0.05; ANOVA), whereas 5-HIAA levels were similar in all these subjects. HVA/5-HIAA ratios increased markedly from 1 +/- 0.12 in the most premature neonates to 1.98 +/- 0.17 in the older infants (p less than 0.01; t test). There were no sex differences for these values.     

Plasma protease inhibitors in premature infants: influence of gestational age, postnatal age, and health status

In newborn infants, the influence of gestational age (GA), postnatal age (PA), and health status on the plasma protease inhibitors alpha 2-macroglobulin (alpha 2-M), alpha 1-antitrypsin (alpha 1-AT), C1 esterase inhibitor (C1E-INH), alpha 2-antiplasmin (alpha 2-AP), and antithrombin III (AT-III) was investigated. Inhibitor levels were measured by radial-immunodiffusion and expressed as a percentage of pooled plasma from adults (mean +/- SEM). In total, 54 premature infants (28-36 weeks gestation) were classified at birth as healthy (N = 22) (IV fluids, antibiotics only) or sick (N = 32) (all other support, but excluding infants with disseminated intravascular coagulation (DIC] and studied on Days 1 and/or 7 of life. Healthy term infants (N = 18) and infants with DIC (N = 10) were studied on Day 1 only. All inhibitors except C1E-INH increased with increasing gestational age (P less than 0.01). In healthy premature infants all inhibitor levels reached the normal adult range by 1 week of age. In contrast, at 1 week of age, sick infants had lower levels of alpha 2-M and alpha 2-AP, and higher levels of alpha 1-AT compared to healthy infants (P less than 0.01). The presence of DIC depressed all of the inhibitors on Day 1 except alpha 1-AT when compared to healthy controls (P less than 0.01). Thus, gestational age, postnatal age, and health status all significantly influenced the levels of these plasma protease inhibitors.     

Longitudinal body composition data in exclusively breast-fed infants: a multicenter study

Reference %fat and total fat-free mass data is necessary for evaluating growth in infants. We aimed to develop longitudinal %fat and total fat-free mass data in infants from birth to 6 months of age. An observational, multicenter, prospective cohort study was conducted with assessments at birth, 1 week, 2 weeks, 1, 2, 3, 4, 5, and 6 months of age. Subjects were exclusively breast-fed and were enrolled at three centers. Whole-body composition (i.e., % fat and total fat-free mass) were assessed using air-displacement plethysmography (ADP) (PEA POD; Life Measurement, Concord, CA). Maternal prepregnancy BMI, gestational weight gain, and infant anthropometric data were collected. A total of 160 infants (boys = 84) were assessed from birth to 4 months of age. Mean birth weight was 3.46 ± 0.39 kg % fat and fat-free mass significantly increased from birth to 4 months of age (P < 0.0001). Gender-specific %fat and total fat-free mass curves for infants from birth to 4 months of age were created. This study will be beneficial to health-care professionals in evaluating normal growth and nutritional patterns in the first months of life.     

Effect of maturation on the extrathoracic airway stability of infants.

The influence of maturation on extrathoracic airway (ETA) stability during quiet sleep was determined in 13 normal preterm infants of 1.41 +/- 0.14 (SD) kg birth weight and 32 +/- 2 wk estimated gestational age. Studies began in the first week of life and were performed three times at weekly intervals. A drop in intraluminal pressure within the ETA was produced by external inspiratory flow-resistive loading (60 cmH2O.l-1 x s at 1 l/min); an increase in intrinsic resistance, indicating airway narrowing, was sought as a measure of ETA instability. Baseline total pulmonary resistance was not significantly different between weeks 1, 2, and 3 (88 +/- 35, 65 +/- 24, and 61 +/- 17 cmH2O.l-1 x s, respectively) but increased markedly above baseline with loading to 144 +/- 45 cmH2O.l-1.s during week 1 (P < 0.001), 89 +/- 28 cmH2O.l-1 x s at week 2 (P < 0.01), and 74 +/- 25 cmH2O.l-1 x s at week 3 (n = 10). The increment with loading was significantly greater during week 1 than during weeks 2 or 3 (P < 0.02). Similar studies were also done in seven full-term infants in the first week of life to evaluate the influence of gestational maturity on ETA stability. Despite a relatively greater drop in intraluminal pressure within the ETA of term vs. preterm infants with loading (P < 0.001), total pulmonary resistance failed to increase (68 +/- 21 to 71 +/- 32 cmH2O.l-1.s). These data reveal that ETA instability is present in preterm infants at birth and decreases with increasing postnatal age. Full-term neonates, by comparison, display markedly greater ETA stability in the immediate neonatal period.     

Glucose polymer supplementation of feeds for very low birthweight infants.

The feeds of 14 very low birthweight infants (birth weight less than 1500 g) were supplemented with a glucose polymer (Caloreen) at the rate of 6 g/kg body weight daily. Seven day periods of supplementation were alternated with seven day periods of normal feeding. Adding the glucose polymer significantly increased the rate of weight gain in these infants from 105 g/week to 140 g/week; growth rates in terms of length and head circumference were not affected. No adverse effects were noted. Glucose polymer is a useful energy supplement for very low birthweight infants.     

Urine screening of five-day-old newborns: metabolic profiling of neonatal galactosuria

We determined urinary galactose and 4-hydroxyphenyllactic acid (4HPLA) in 4338 of 5-day-old newborns using a newly developed GC–MS screening method. Fifty-two infants were chemically diagnosed as having transient galactosuria based upon elevated urinary galactose levels (4.78–30.53 mg/mg creatinine, control 1.10±0.89 mg/mg creatinine). These infants did not excrete galactitol or galactonic acid into the urine, which is typical of hereditary galactosemia. Nearly 40% of the transient galactosuria was associated with immature infants (low birth weight or borne before 37 gestational weeks). Immature hepatic function is one explanation for neonatal transient galactosuria, but heterozygotes or the carriers of galactose degradation enzyme deficiencies were also suspected in some of the newborns, judging from the comparisons of urinary galactose and 4HPLA excretion between neonates and patients with galactosemia.     

Epidemiology of spontaneous premature rupture of membranes: factors in pre-term births

The frequency of spontaneous premature rupture of membranes (PROM) was determined in the pregnancies of 1,848 white mothers and their singleton infants, born at the University of Kansas Medical Center between April 1975 and April 1978. The frequency of PROM increased significantly from a low of 34/707 (4.8 percent) among low-risk mothers, to 40/444 (9.0 percent) among mothers smoking one to 60 cigarettes a day, to 21/204 (10.3 percent) among mothers with multiple adverse maternal practices, and to 12/46 (26 percent) among mothers with selected complications of their pregnancies. The proportion of low birth weight (LBW) (less than 2,500 g) pre-term infants born to PROM mothers increased among the risk factor groups in a similar manner, from a low of 2/34 (6 percent) in low-risk pregnancies to 8/40 (20 percent) among mothers smoking one to 60 cigarettes a day, to 7/21 (33 percent) among mothers with multiple adverse practices, and to 7/12 (58 percent) among mothers with selected complications of pregnancy. The increased incidence of low birth weight pre-term infants born to mothers with PROM was associated with evidence of growth retardation among full-term infants in the high-risk groups. This finding was manifested by reductions in mean birth weights of full-term infants born to high-risk mothers but not observed in full-term infants born to low-risk mothers. The attained growth at birth of low birth weight pre-term infants could not be determined, because appropriate birth weight standards for pre-term infants born to mothers with low-risk pregnancies are not available. These results suggest that growth retardation in fetuses increased the probability of the mothers having PROM prior to the onset of labor, and, if PROM did occur, of having a premature delivery. We hypothesize that the tensile strength of the amnion and chorion is diminished by the same conditions that retard fetal growth, and that this reduction in strength of the fetal membranes contributes to premature rupture of membranes and pre-term delivery.     

Macaca thibetana at Mt. Emei,China: II. Birth seasonality

Birth censuses were conducted every 2 or 3 days for each of six groups of Macaca thibetana along trails at Mt. Emei in southwest China from March 7 to June 15, 1986. Based on direct observations and the timetable of forehead hair growth and behavior, each of 32 infants could be placed in one of sixteen 14-day periods of the 1986 birth season. The mean estimated birth date was March 27 (SD = 39 days); the median estimated birth date was March 14. Sex ratios in newborns and yearlings did not deviate significantly from 1:1. Seasonal birth timing was correlated with the altitude of the range (r = ?0.84, P < .05); that is, infants were born earlier in the season at higher altitudes.     

Factors associated with initiation and exclusive breastfeeding at hospital discharge: late preterm compared to 37 week gestation mother and infant cohort

Background

To investigate and examine the factors associated with initiation of, and exclusive breastfeeding at hospital discharge of, late preterm (34 ^0/7 - 36 ^6/7 weeks) compared to 37 week gestation (37 ^0/7 - 37 ^6/7 week) mother and baby pairs.

Methods

A retrospective population-based cohort study using a Perinatal National Minimum Data Set and clinical medical records review, at the Royal Hobart Hospital, Tasmania, Australia in 2006.

Results

Late preterm and 37 week gestation infants had low rates of initiation of breastfeeding within one hour of birth, 31 (21.1%) and 61 (41.5%) respectively. After multiple regression analysis, late preterm infants were less likely to initiate breastfeeding within one hour of birth (OR 0.3 95% CI 0.1, 0.7 p = 0.009) and were less likely to be discharged exclusively breastfeeding from hospital (OR 0.4 95% CI 0.1, 1.0 p = 0.04) compared to 37 week gestation infants.

Conclusion

A late preterm birth is predictive of breastfeeding failure, with late preterm infants at greater risk of not initiating breastfeeding and/or exclusively breastfeeding at hospital discharge, compared with those infants born at 37 weeks gestation. Stratifying breastfeeding outcomes by gestational age groups may help to identify those sub-populations at greatest risk of premature cessation of breastfeeding.