Bone mineral content in term and preterm appropriate-for-gestational-age infants.

Photon absorptiometry adapted for use in small infants was utilized to measure bone mineral content in 42 term and 30 perterm appropriate-for-gestational-age infants. BMC at birth correlated significantly with gestational age and birth weight. Sequential measurements of BMC in premature infants during the first three months showed that the postnatal increase in BMC was significantly less than the BMC expected in utero. We speculate that decreased intake of calcium and phosphate effects postnatal bone mineralization in premature infants.     

Bone mineral content of appropriate and light for gestational age preterm and term newborn infants

Bone mineral content was measured by single photon absorptiometry at the right mid humerus of 122 appropriate and 35 light for gestational age newborn infants born after 26 to 42 weeks of gestation. Bone mineral content was 2.4 times greater at the mid humerus than at the distal radius. Even in extremely low birth weight infants reproducible measurements were possible at the mid humerus. Light for gestational age infants showed a lower bone mineral content than appropriate for gestational age infants when bone mineral content was related to gestational age. When related to birthweight (g) bone mineral content showed a similar linear relationship in light for gestational age (mg/cm = 44.2 + 0.037 weight) and appropriate for gestational age (mg/cm = 39.4 + 0.040 weight) infants. For all 177 infants the relationship was mg/cm = 32.3 + 0.045 weight (r = 0.91). It is concluded that in growing preterm infants bone mineral content should be assessed in relation to weight rather than to age.     

Bone mineral content and body size 65 to 100 weeks' postconception in preterm and full term infants.

A total of 36 preterm and 22 full term infants were weighed and measured at 65 to 100 weeks'' postconception. It was found that the preterm infants were on average significantly lighter by 1008 g and shorter by 3.8 cm than those born at full term. Despite the smaller size of preterm infants, mean values of bone mineral content in the mid-forearm were not significantly different between the two groups. In contrast, near 40 weeks'' postconception the mean bone mineral content observed in 35 of the preterm infants was significantly smaller than that observed in eight of the full term infants. Our results suggest that there is a phase of rapid mineral accretion between 40 and 60 weeks'' postconception. This ''catch up'' in mineral accretion reduces the perinatal mineralisation deficit that might otherwise persist into childhood.     

Bone mineral content in children 1 to 6 years of age. Detectable sex differences after 4 years of age

Age- and sex-specific bone mineral measures have not been available for healthy preschool children. We determined bone mineral content (BMC) and bone width in 89 children 1 to 6 years of age using direct photon absorptiometry at the one-third distal radius site. The BMC increased significantly with age, and bone width increased slightly with age. After stratification by age, male and female children had similar BMC from 1 to 4 years of age, but female children had significantly lower BMC at 5 to 6 years of age.     

Bone turnover in preterm infants

Total parenteral nutrition is associated with osteopenia in preterm infants. Insufficient calcium and phosphate are likely causes: aluminum contamination is another possible contributing factor as this adversely affects bone formation and mineralization. The study was designed to evaluate changes in biochemical markers of bone turnover in 22 preterm infants receiving total parenteral nutrition in comparison with 19 term infants. We collected urine and serum samples from 22 preterm infants, mean gestational age 29 wk, within 48 h and again at 3 wk of life. We also collected urine samples from 19 term infants, mean gestational age 39 wk, during the first day of life. Bone resorption was assessed by the measurement of urinary pyridinium cross-links by HPLC and ELISA and the N-telopeptide of type I collagen by ELISA. Bone formation was assessed in premature infants by the measurement of serum osteocalcin. The N-telopeptide of type I collagen was higher in the preterm infants compared with term at baseline (p < 0.01). There was no difference between the pyridinium cross-links in the preterm and term infants. All the biochemical markers of bone turnover increased significantly in the preterm infants during the first 3 wk of life, e.g. N-telopeptide was a 153% change from baseline (p < 0.001). Aluminum in the total parenteral nutrition solutions did not cause a decrease in bone formation at the level administered (3-6 microg, 0.1-0.2 micromol x kg(-1) x d(-1)).     

Bone mineralization in preterm infants fed human milk with and without mineral supplementation

The bone mineral status of healthy preterm infants fed maternal milk was compared with that of similar infants fed maternal milk with mineral supplementation. Fifty infants with birth weight less than 1600 g were fed human milk for 1 week until reaching an intake of 120 kcal/kg/d. Thereafter, infants were assigned randomly to one of three diets: (1) continued unsupplemented human milk, providing an intake of 40 to 50 mg/kg/d calcium and 23 to 30 mg/kg/d phosphorus; (2) human milk mixed with a high mineral containing formula, providing total intakes of 130 mg/kg/d calcium and 68 mg/kg/d phosphorus; or (3) human milk alone for 1 additional week, followed by human milk mixed with a powdered fortifier, providing total intakes of 160 mg/kg/d calcium and 90 mg/kg/d phosphorus. Infants fed human milk with formula supplementation, but not those fed human milk with fortifier, had significantly higher serum phosphorus concentrations and significantly lower serum alkaline phosphatase concentrations than did those fed unsupplemented human milk (P less than 0.01). Bone mineral content of the humerus, determined by photon absorptiometry, however, was similar in all three groups; values averaged 0.104 g/cm at the beginning of the study, and remained unchanged irrespective of mineral supplementation. Shortly before hospital discharge, study diets were discontinued and infants were fed standard proprietary formula or were nursed by their mothers. At 44 weeks postconceptional age (7 to 10 weeks after change in diet), infants were reexamined. Serum phosphorus concentrations increased, serum alkaline phosphatase concentrations decreased, and bone mineral content more than doubled to values comparable with those in term infants. Results at follow-up were comparable for all three initial diet groups and for infants who were formula-fed or breast-fed after hospital discharge. The lack of any significant effect of early maternal milk supplementation on bone mineralization by 44 weeks postconceptional age suggests that these methods of supplementation of maternal milk may not be warranted for healthy preterm infants.     

Neurological examination of preterm infants at term equivalent age

BACKGROUNDS: We previously reported the neurological findings of the Dubowitz neonatal examination in a cohort of 157 low-risk preterms born between 25 and 33 weeks gestational age (GA) and examined at term equivalent age (TEA). Median and range of scores were wider than those found in term-born infants and preterms showed a different neurological behaviour in specific items. However, the cohort number was too small to draw any definitive conclusion about the distribution of findings. AIMS: We provide normative data from a low-risk cohort of 380 preterm infants; we also assess the findings and their relationship to motor outcome in preterms with major cranial ultrasound (US) abnormality. STUDY DESIGN: We assessed, at TEA, 380 low-risk preterms born <35 weeks gestation (range 25-34.9, median 29) with normal 2 year motor outcome and 85 preterm infants with major US abnormality. RESULTS: At TEA low-risk preterms had less flexor limb tone, poorer head control but better visual following than term-born infants. For 28/34 of the neurological items the range and median scores were similar across gestational ages. In infants with major US lesions the range and median scores differed from low-risk preterms in 20/34 items; 40% of infants developing a diplegia and 80% developing a tetraplegia had >7 items outside the 90th centile; all infants with >12 items outside the 90th centile developed a tetraplegia. CONCLUSIONS: We provide reference values for the neurological examination of low-risk preterms at TEA. In infants with major US abnormality the number of items outside the 90th centile was an indicator of outcome severity.     

Body water content of extremely preterm infants at birth

BACKGROUND: Preterm birth is often associated with impaired growth. Small for gestational age status confers additional risk. AIM: To determine the body water content of appropriately grown (AGA) and small for gestational age (SGA) preterm infants in order to provide a baseline for longitudinal studies of growth after preterm birth. METHODS: All infants born at the Hammersmith and Queen Charlotte's Hospitals between 25 and 30 weeks gestational age were eligible for entry into the study. Informed parental consent was obtained as soon after delivery as possible, after which the extracellular fluid content was determined by bromide dilution and total body water by H(2)(18)O dilution. RESULTS: Forty two preterm infants were studied. SGA infants had a significantly higher body water content than AGA infants (906 (833-954) and 844 (637-958) ml/kg respectively; median (range); p = 0.019). There were no differences in extracellular and intracellular fluid volumes, nor in the ratio of extracellular to intracellular fluid. Estimates of relative adiposity suggest a body fat content of about 7% in AGA infants, assuming negligible fat content in SGA infants and lean body tissue hydration to be equivalent in the two groups. CONCLUSIONS: Novel values for the body water composition of the SGA preterm infant at 25-30 weeks gestation are presented. The data do not support the view that SGA infants have extracellular dehydration, nor is their regulation of body water impaired.     

Diet and bone mineral content at term in premature infants

Premature infants are at risk of developing metabolic bone disease mainly because of low calcium and phosphorus intake. We have examined the effect of different mineral supplements on bone mineral content at term in 127 premature infants with gestational age <32 wk in a double-blinded randomized trial. We used either phosphate supplementation of human milk as recommended by the European Society of Pediatric Gastroenterology and Nutrition or fortified supplementation with protein, calcium, and phosphorus or preterm formula as recommended by the American Academy of Pediatrics. The intervention period was from 1 week old until 36 wk of gestational age, and the infants were fed approximately 200 mL x kg(-1) x d(-1). Bone mineral content was measured at term by dual-energy x-ray absorptiometry scan. Surprisingly, neither phosphate, fortifier, nor preterm formula supplementation had any significant effect on bone mineral content at term compared with infants fed their own mother's milk only. There was a tendency to higher total bone mineral content in infants fed preterm formula compared with infants fed their own mother's milk only (p = 0.05), but when the bone mineral content was corrected for the size of the infant, there was no difference (p = 0.68). Infants fed preterm formula had a significantly higher weight at term compared with infants fed their own mother's milk only (p = 0.02), but did not differ significantly in length or head circumference. In a regression analysis, the amount of supplemented phosphorus was significantly associated with weight at term (p = 0.008). We conclude that when feeding 200 mL x kg(-1) x d(-1), mineral supplementation of human milk or use of preterm formula does not significantly improve bone mineralization outcome at term.     

Prevalence of head deformities in preterm infants at term equivalent age

Introduction

Due to a rising number of head deformities in healthy newborns, there has been an increasing interest in nonsynostotic head deformities in children over recent years. Although preterm infants are more likely to have anomalous head shapes than term newborns, there is limited data available on early prevalence of head deformities in preterm infants.

Aims

The purposes of the present study were to acquire quantitative data on head shape of preterm infants at Term Equivalent Age (TEA), to determine the prevalence of symmetrical and asymmetrical head deformities and to identify possible risk factors.

Methods

In a cross-sectional study design, Cranial Vault Asymmetry Index (CVAI) and Cranial Index (CI) calculated from routine head-scans with a non-invasive laser shape digitizer were recorded and categorized in type and severity of deformation for three different groups of gestational age. Perinatal and postnatal patient data was tested for possible associations.

Results

Scans of 195 infants were included in the study. CVAI at TEA was higher in very preterm (4.1%) compared to term and late preterm infants. Prevalence of deformational plagiocephaly was 38% in very preterm infants. CI was lower in very (71.4%) and late (77.2%) preterm infants compared to term infants (80.0%). Compared to term babies (11%), a large number of very (73%) and late (28%) preterm infants exhibited dolichocephaly at TEA.

Discussion

Prevalence of symmetrical and asymmetrical head deformities in preterm infants is high at TEA. Interventions are required to prevent head deformities in preterm infants during the initial hospital stay.     

Neurological assessment at five years of age in infants born preterm

AIM: To evaluate the agreement between Touwen's neurological examination and a derived simplified one, created to be applied at the age of 5 y to infants born preterm. METHODS: 185 children born at a gestational age (GA) of <33 wk and/or with a birthweight <1501 g, free of cerebral palsy, underwent Touwen's neurological examination at a mean age of 5 y and 8 mo (5-6.5 y). One-hundred and seventy had a full examination and were included into the study. They were born at a mean GA of 30 wk (range 24-35 wk) with a mean birthweight of 1250 g (range 600-2690 g). A simplified examination, based on the clinical experience of two of the authors, was created a priori. The data were reviewed retrospectively and the concordance between the two forms was assessed. The reviewers were blinded to the original categorization from the long form. RESULTS: On the basis of the original Touwen's neurological examination, the 170 children were classified into 122 with a normal neurological examination, 41 with grade 1 minor neurological dysfunction (MND) and 7 with grade 2 MND, giving 28% of the cohort with MND. The concordance between the two forms was excellent, with an agreement in 169 out of 170 subjects. None of the infants with the most complex form of MND was misclassified. CONCLUSION: The simplicity of this examination could allow its diffusion and its use in follow-up programmes. It could improve the quality of routinely collected follow-up data of preterm neonates.     

Neurologic examination of preterm infants at term age: comparison with term infants

OBJECTIVES: The aim was to establish the range of neurologic findings in preterm infants reaching term age, their relation to gestational age at birth, and the possible differences with healthy term newborns tested during the first days of life. STUDY DESIGN: The Dubowitz neonatal neurologic examination was performed at term age in 157 low-risk preterm infants born between 25 and 34 weeks' gestation who had cranial ultrasonograms that were normal or showed minor abnormalities. Infants were subdivided in 3 groups according to their gestational age at birth. RESULTS: Within the preterm cohort, the range of scores for the 3 gestational age subgroups was different from each other for 21 of the 34 items, although the median scores were different only in 10 of the 34 items. The range of scores and their median in preterm infants however was wider than that found in term infants. Preterm infants examined at term were also more hyperexcitable and tended to have less flexor tone in the limbs and less extensor tone in the neck in the sitting posture. CONCLUSIONS: The distribution of scores provides useful guidelines when a preterm infant is examined at term.     

Bone Mineral Content in Preterm Infants at Age 4 to 16

Using photon absorptiometry the forearm bone mineral content (BMC) was determined in 75 children aged 4 to 16, who all had a low birth weight. Forty-five of them were born preterm AGA (27 boys, 18 girls, mean weight 1580 g; range 920-2060 g) and 30 preterm SGA (17 boys, 13 girls, mean weight 1510; range 940-2130 g). The results were compared with a control group of children of the same age, and analyses of covariance with age, height and weight as the covariant factors were performed. The BMC, weight and height did not differ between the children born AGA or SGA. Irrespective of AGA or SGA, the BMC was significantly decreased in boys but the difference was less pronounced and less significant when height and weight were used as covariant factors. Boys who had been born preterm had a less BMC than the control boys for their age but the were also somewhat shorter and lighter than expected with regard to their age.     

Bone and collagen markers in preterm infants: relationship with growth and bone mineral content over the first 10 weeks of life.

In a longitudinal study of 25 preterm infants, we have examined the relationship of bone-specific alkaline phosphatase (ALP), C-terminal propeptide of type I collagen (PICP), N-terminal propeptide of type III procollagen (P3NP), C-terminal telopeptide of type I collagen, urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd), with rates of gain in weight, length, and lower leg length and with bone mineral content (BMC), all measured at weekly intervals over the first 10 wk of life. Concentrations of all collagen markers were 10-fold higher than in older children. Each marker showed a distinctive pattern of postnatal change, with early increases in PICP and P3NP and decreases in ICTP reflecting postnatal growth. Once markers had reached a plateau during weeks 4-10, P3NP was positively correlated, whereas Pyd and Dpd were negatively correlated with rate of weight gain (r = +0.44, -0.46, and -0.40, respectively, p < 0.05). P3NP was also positively correlated with overall linear growth (r = +0.44, p < 0.05). PICP was strongly correlated with mean BMC (r = +0.63,p < 0.01) and with total BMC attained by the end of the study period (r = +0.81, p < 0.001). Bone ALP was positively correlated with the rate of bone mineral accretion (r = +0.55, p = 0.01). We conclude that the marker of soft-tissue collagen formation, P3NP, is a good marker for overall ponderal and linear growth in preterm infants, whereas the markers of collagen breakdown, Pyd and Dpd, have inverse relationships with weight gain. The osteoblast markers, PICP and bone ALP, seem to be good surrogate markers for bone mineralization in preterm infants. Markers may provide information on whole-body turnover of bone and collagen that is complementary to traditional physical measures of growth and bone mineralization.     

Bone growth with low bone mineral content in very low birth weight premature infants

We report serial measurements of bone mineral content (BMC), bone width (BW, a measure of appositional bone growth), and the ratio of BMC:BW by photon absorptiometry of the left radius through the first 10 wk of life in 38 very low birth weight premature infants (birth weight less than 1300 g, gestational age less than 32 wk). Fifteen of 38 infants developed bronchopulmonary dysplasia (BPD) and as a group they could not be distinguished from the 23 infants without BPD, despite the high association between BPD and metabolic bone disease. As BPD occurred in the smaller patients, the BPD group had a significantly lower mean birth weight and mean gestational age as compared to controls (950 +/- 125 g versus 1119 +/- 149, and 28.0 +/- 0.8 versus 29.0 +/- 1.3 wk). For both control and BPD groups, BMCs did not differ and remained relatively unchanged throughout the first 10 wk of life, lagging significantly behind the intrauterine rate as defined by measuring BMC in 175 infants of varying gestational ages during the first few days of life. BW also did not differ during this period between groups. BW did increase significantly in both groups (from 3.2 +/- 0.3 to 3.9 +/- 0.4 mm in the controls and from 3.0 +/- 0.3 to 3.8 +/- 0.4 mm in the BPD group), but remained significantly delayed compared to the intrauterine rate. In both groups, BMC remained relatively constant despite increasing BW and thus BMC/BW decreased during the first 10 wk of life (from 11.5 +/- 1.3 to 10.2 +/- 1.9 in the controls and from 11.0 +/- 1.3 to 8.6 +/- 2.2 in the BPD group).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neurological assessment of preterm infants at term conceptional age in comparison with normal full-term infants

In a long-term prospective study 46 unselected infants born before 35 weeks of gestational age were followed up, which included repeated neurological and psychological examination. 40 of them were neurologically evaluated at term conceptional age and compared with 26 full-term newborns, all the infants being considered healthy. There was no difference in mean weight or length between the two groups, but mean head circumference was greater in the preterm group. The preterm infants had lower muscle tone as judged by spontaneous posture of arms and legs, and poor resistance to passive movements and slow arm recoil. In the traction test they had more head lag. The withdrawal and Moro reflexes were weaker, while asymmetric tonic neck reflex (ATNR) was easier to elicit. Head control in the sitting position was better. All infants were evaluated with a prenatal and perinatal optimality score, which was not however significantly correlated with the neurological findings. The preterm infants with only slightly reduced optimality score (low risk group) had approximately the same birth weight and gestational age as the other preterms. They more resembled the full-term infants with good resistance to passive movements, fast arm recoil and good responses concerning the withdrawal and Moro reflexes. However, they had a semiflexed position in supine and thus in this respect were more like the other preterms.