Foetal Doppler abnormality is associated with increased risk of sepsis and necrotising enterocolitis in preterm infants.

AIM: Fetoplacental Doppler abnormalities have been associated with increased neonatal mortality and morbidity. This study evaluated the associations between prenatal Doppler assessments and neonatal mortality and morbidity in premature infants born small for gestational age or after pre-eclampsia. METHODS: This was a population-based study of infants born alive at 22(0) -33(6) weeks of gestation, a birthweight <10th percentile for gestational age and/or maternal pre-eclampsia. Doppler assessments of the umbilical artery, middle cerebral artery and ductus venosus were evaluated in 127, 125 and 95 cases, respectively. Circulatory compromise was defined as absent or reversed end-diastolic velocity in the umbilical artery (AREDF), middle cerebral artery pulsatility index <2.5 percentile for gestational age and ductus venosus pulsatility index for veins >97.5 percentile. RESULTS: AREDF was present in 28% of the infants. This was associated with increased frequencies of neonatal sepsis and necrotising enterocolitis after adjusting for gestational age. Abnormal ductus venosus pulsatility index for veins was associated with increased risk of neonatal sepsis, but only in combination with AREDF. These associations were only present when gestational age was <28 weeks. CONCLUSION: AREDF was associated with increased neonatal morbidity in premature infants born small for gestational age or after pre-eclampsia.

Bronchopulmonary dysplasia - prevalence, severity and predictive factors in a national cohort of extremely premature infants.

AIM: To study prevalence and predictive factors of bronchopulmonary dysplasia (BPD) in a cohort of preterm infants with a high incidence of prenatal steroid and surfactant treatment. METHODS: BPD was analysed in a national cohort of infants with gestational age (GA) of 22-27 completed weeks (wks) or birth weight (BW) of 500-999 g. Of 464 infants who were transferred to a NICU, 377 infants with GA ≤ 30 wks and survived beyond 28 days were included in the study. RESULTS: Moderate or severe BPD was strongly related to GA. Of infants with GA 22-25 wks, 67.3% developed BPD compared to 36.6% at GA 26-30 wks. Overall, moderate and severe BPD was significantly more common in boys (63.3%) than in girls (36.6%) (p = 0.0004), but female gender was not a protective factor in infants with GA 22-25 wks. In multivariate analyses, BPD was significantly associated with gender, surfactant treatment and treatment for PDA. CONCLUSIONS: BPD remains a severe complication of extreme prematurity in spite of prenatal steroids and surfactant treatment. Whether associations with surfactant and PDA treatment simply reflect severity of early lung disease or have causal relationships should probably be studied in randomized controlled trials.

Faecal calprotectin concentrations in children with functional gastrointestinal disorders diagnosed according to the Pediatric Rome III criteria.

OBJECTIVE: To determine if faecal calprotectin concentrations vary with different entities of functional gastrointestinal disorders (FGID) in children. METHODS: Children (4-15 years) who were consecutively referred by general practitioners to four general paediatric outpatient clinics for the evaluation of recurrent abdominal pain were assessed according to a research protocol which included clinical examination, a minimum set of blood, urine and stool tests, and clinical reassessment after 6-9 months. The diagnoses of FGID were based on the parent version of the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III. RESULTS: Of the 152 patients included, 142 children were diagnosed with FGID. Of these, 126 (89%) provided a stool specimen for quantification of calprotectin. The median calprotectin concentrations were at or lower than 16 mg/kg which was at the lower detection limit and there were no differences between the FGID subgroups. Nine children (7%) had slightly raised values. CONCLUSION: The faecal calprotectin concentration is within normal limits in FGID and does not vary with different FGID entities suggesting that bowel inflammation is not a significant part of the pathogenesis in FGID.

Early severe weight loss in newborns after discharge from regular nurseries.

AIMS: To study incidence and risk factors of early neonatal dehydration in a Norwegian population based cohort. METHODS: Term neonates admitted to a paediatric department during 2002-2008 with a weight loss > or = 12% within three weeks of age were identified retrospectively through review of medical records. For each patient a sex-matched control group of two full-term infants was selected to assess risk factors for dehydration. RESULTS: A total of 38 of 37 321 infants (1.0 per thousand) were admitted at a median age of 6 (interquartile range 5-12) days, and the admission rate increased during the study period (p for trend = 0.008). Simultaneously, mean nursery stay decreased from 3.5 to 2.7 days (p = 0.022). Mean weight loss was 15.0% of birth weight and 17 of 29 (58.6%) had serum sodium above 145 mmol/L. The only significant difference between patients and controls was that mothers of patients were older (32.3 +/- 5.0 vs. 29.4 +/- 5.4 years, p = 0.005). CONCLUSION: Short nursery stay may be a risk factor for dehydration in newborn infants.

Mid-childhood outcomes after pre-viable preterm premature rupture of membranes.

OBJECTIVES: Investigate cardiorespiratory outcomes in children surviving previable preterm premature rupture of membranes (PV-PPROM) before 22 weeks' gestational age (GA) with minimum 2 weeks latency. STUDY DESIGN: Single institution, follow-up of retrospectively identified children who were born after PV-PPROM during 2000-2004, and individually matched preterm-born controls. RESULTS: Eleven PV-PPROM and matched control children were included at mean age of 10.5 and 10.7 years. Rupture of membranes occurred at mean GA 182 and 276 weeks and birth at 283 and 286 weeks, respectively. Compared to controls, the PV-PPROM group had significantly poorer lung function, findings on echocardiography indicating mild pulmonary hypertension, and lower peak oxygen consumption. Chart reviews suggested more motor difficulties and a tendency towards more problems with learning and attention. CONCLUSION: The findings highlight a preterm-born sub-group in need of targeted long-term monitoring and possibly interventions regarding future cardiorespiratory and neurodevelopmental function.

Plasma concentrations of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, and 25,26-dihydroxyvitamin D in the first year of life.

Plasma concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D], 24,25-dihydroxyvitamin D [24,25-(OH)2D], and 25,26-dihydroxyvitamin D [25,26-(OH)2D] were determined in 80 healthy infants of 4 days, 6 weeks, 6 months, and 12 months of age. The 4-day-old babies received breast milk, while the 6-week-old infants were either exclusively breast or formula fed. The older infants were on mixed diets and received daily vitamin D supplements. The levels were analyzed with regard to age and the concentrations of 25-hydroxyvitamin D (25OHD), calcium, phosphate, magnesium, and alkaline phosphatase and were compared with adult levels of vitamin D metabolites. The median 1,25-(OH)2D concentration was highest at 4 days of age and lowest at 6 weeks, but, except for the 6-week-old group, all had higher levels than the adults (6 weeks, P less than 0.1; others, P less than 0.01). 1,25-(OH)2D and 25OHD levels showed significant correlation only at 4 days (r = 0.74; P less than 0.0005), and there were no consistent relationships between 1,25-(OH)2D and the other variables. The median concentration of 24,25-(OH)2D was lower (P less than 0.01), while the 25,26-(OH)2D value was similar to that in the adults. Both were, however, positively related to the 25OHD level [24,25-(OH)2D, r = 0.82; 25,26-(OH)2D, r = 0.65; P less than 0.0005], as in the adults. The ratio of 24,25-(OH)2D to 25OHD was lower beyond 4 days of life than in the adults (medians, 3.4% vs. 5.1%; P less than 0.02). The data suggest that 1,25-(OH)2D synthesis has relative priority over 24,25-(OH)2D production during infancy compared with that in adulthood.

Effect of estrogen on vitamin D metabolism in tall girls.

To determine the effect of estrogen on vitamin D metabolism in pubertal girls, we studied 16 tall girls treated with a daily dose of 4-8 mg estradiol valerate to curtail excessive adult height. In all but one girl the plasma concentration of 1,25-dihydroxyvitamin D (1,25-(OH)2D) increased to values significantly higher than the corresponding pretreatment value (P less than 0.0005). The ratio of 24,25-dihydroxyvitamin D (24,25-(OH)2D) to 25-hydroxyvitamin D decreased in all girls (P less than 0.0005). The vitamin D binding protein (DBP) also increased significantly after estrogen (P less than 0.025), and there was a significant positive correlation between the plasma concentration of 1,25-(OH)2D and DBP (r = 0.66; P less than 0.0005). The free fraction of 1,25-(OH)2D remained unchanged after estrogen. It appears that estrogen treatment increases the plasma concentration of 1,25-(OH)2D. The effect might be explained by the concomitant increase in DBP and/or by estrogen stimulation of renal 1 alpha-hydroxylase.

25-Hydroxyvitamin D and 1,25-dihydroxyvitamin D of D2 and D3 origin in maternal and umbilical cord serum after vitamin D2 supplementation in human pregnancy.

Serum concentrations of 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] of vitamin D2 and D3 origin were determined separately in 10 women before vitamin intake in early pregnancy, and repeated in maternal and cord serum obtained at delivery after 20 to 30 wk of vitamin D2 supplementation in a dose of 400 IU/day. Before supplementation 25-OHD2 and 1,25-(OH)D2D2 were present in just traceable or nondetectable concentrations, but the levels increased in all to a mean +/- 1 SD of 7.3 +/- 3.7 ng/ml and 37.2 +/- 18.1 pg/ml, respectively (p less than 0.0025), by the time of delivery. At delivery the total 25-OHD and 1,25-(OH)2D levels were always lower in the cord than in the maternal serum (30.7 +/- 14.2 versus 20.1 +/- 9.1 ng/ml, and 90.1 +/- 31.2 versus 37.3 +/- 11.6 pg/ml, p less than 0.0025). The paired concentrations of 25-OHD were closely related (r = 0.89, p less than 0.0005), while the association for 1,25-(OH)2D was not statistically significant (r = 0.53, p less than .01). The 25-OHD of D2 and D3 origin accounted for a similar proportion of the total 25-OHD in the maternal and cord serum (ratio of 25-OHD2 to 25-OHD3: 0.40 +/- 0.28 versus 0.45 +/- 0.29, p = NS), as did the respective 1,25-(OH)2D metabolites [ratio of 1,25-(OH)2D2 to 1,25-(OH)2D3: 0.73 +/- 0.35 versus 0.90 +/- 0.50, p = NS].(ABSTRACT TRUNCATED AT 250 WORDS)

Intermittent high-dose vitamin D prophylaxis during infancy: effect on vitamin D metabolites, calcium, and phosphorus.

In infants receiving intermittent high dose vitamin D prophylaxis (600,000 IU ergocalciferol per dose orally) every 3-5 mo, the serum concentrations of vitamin D metabolites, calcium (Ca), and phosphorus (P) were determined before and 2 wk after each dose. The 25-hydroxyvitamin D (OHD) concentrations increased to well above normal but the values returned to the normal range before each subsequent dose. The 24,25- and 25,26-dihydroxyvitamin D ([OH]2D) levels followed a pattern similar to that of 25-OHD, and both were closely related to the latter (r = 0.85, p less than 0.005, and r = 0.84, p less than 0.005, respectively). The 1,25-(OH)2D concentrations did not vary in a consistent pattern and remained largely within the normal range. All infants had normal Ca levels before the first dose but 14 infants (34%) later had one or both Ca values above the upper normal limit of 2.80 mmol/L (2.81-3.32 mmol/L), indicating that the vitamin D doses were excessive despite the lack of accumulative increases in serum vitamin D concentrations.

Effect of parathyroid hormone on cAMP and 1,25-dihydroxyvitamin D formation and renal handling of phosphate in vitamin D-dependent rickets.

Studies were carried out to compare the effects of parathyroid extract (PTE) on the serum concentration of 1,25-dihydroxyvitamin D (1,25[OH]2D), 24,25-dihydroxyvitamin D (24,25[OH]2D), 25,26-dihydroxy vitamin D (25,26[OH]2D) and cAMP, and the urinary excretion of calcium, phosphorus, and cAMP in two normal adult subjects, and in a girl with vitamin D-dependent rickets. The concentration of 1,25[OH]2D was markedly decreased even when she was receiving a daily dose of 25,000 IU of ergocalciferol. PTE infusion resulted in a prompt and distinct increase in the serum levels and the urinary excretion of cAMP in the patient and control subjects. In the control subjects the serum concentration of 1,25[OH]2D increased after the PTE infusion, whereas there was no response in the patient with vitamin D-dependent rickets. The two other dihydroxylated metabolites of vitamin D showed no consistent response to the PTE infusion in the control subjects or the patient. The patient showed no phosphaturic response to PTE while she was receiving high-dosage ergocalciferol treatment. By contrast, when the patient was re-studied after therapy with 1 alpha-hydroxyvitamin D, PTE infusion resulted in an increase in urinary phosphate excretion. These findings might lend support for the notion that 1,25[OH]2D has an effect on tubular phosphate resorption and has a permissive role in the phosphaturic effect of parathyroid hormone. The present findings also confirm that the formation of 1,25[OH]2D is impaired in vitamin D-dependent rickets and indicate that the renal 25-hydroxyvitamin D-1 alpha-hydroxylase is unresponsive to the stimulatory effect of parathyroid hormone in this condition.

Effect of parathyroid hormone on vitamin D metabolism in osteopetrosis.

Indices of vitamin D metabolism were studied before and after infusion of bovine parathyroid hormone extract in three children with osteopetrosis. Basal serum concentrations of calcium, alkaline phosphatase, and 25-hydroxyvitamin D tended to be low. Serum immunoreactive parathyroid hormone levels were in the upper normal range in two patients. A marked increase in urinary cyclic adenosine 3':5'-monophosphate (cAMP) in all patients was solely due to an increase in the nephrogenous cAMP. The basal concentration of 1,25-dihydroxyvitamin D was clearly more than the upper limit of normal range in all three patients and increased after parathyroid extract infusion in one patient. The basal serum levels of 24,25-dihydroxyvitamin D were within normal limits and tended to decrease after parathyroid extract infusion in two of the patients. Parathyroid hormone and 1,25-dihydroxyvitamin D act in concert to increase calcium resorption from bone, and the increased serum levels of both these factors may reflect lack, or unresponsiveness, of target cells in bone.

Ultrasound screening for developmental dysplasia of the hip in the neonate: the effect on treatment rate and prevalence of late cases.

OBJECTIVE: To assess the effect of ultrasound screening on primary diagnosis, management, and prevalence of late cases of developmental dysplasia of the hip (DDH). DESIGN: A randomized, controlled trial, including 11,925 newborn infants who were allocated to receive either general, or selective or no ultrasound screening in addition to the clinical examination. In the selectivity screened group only infants with risk factors or clinical findings of DDH received an ultrasound examination. The infants were at least 27 months old at the conclusion of the study. Those with risk factors for DDH had a radiograph examination of the hips at 4.5 months of age. RESULTS: The three study groups did not differ in terms of sex distribution or positive Barlow/Ortolani tests. General ultrasound screening resulted in a higher treatment rate than in either the selective or in the no ultrasound screening groups (3.4% vs 2.0% and 1.8%, P < .0001). For infants not subjected to treatment, ultrasound screening resulted in a higher follow-up rate because of nonconclusive early findings (13%, 1.8%, 0%, respectively; P < .0001). The prevalence of late subluxation or dislocation was lower for subjects assigned to general ultrasound screening than for those subjected to selective or no ultrasound screening, but the differences were not statistically significant (0.3, 0.7, 1.3 per 1000, respectively; P = .11, test for trend). CONCLUSION: The effect of ultrasound screening in reducing the prevalence of late DDH was at best marginal despite a considerable increase in diagnostic and therapeutic efforts.

Cost-effectiveness of alternative screening strategies for developmental dysplasia of the hip.

OBJECTIVE: To compare the cost-effectiveness of adding either a general or a selective ultrasound screening program to the routine clinical examination for developmental dysplasia of the hip (DDH) with use of the data from a large, randomized study of 11,925 newborns. METHODS: Our previous study comparing the clinical outcomes of three strategies for screening infants for DDH suggested (but results were not statistically significant) that general ultrasound screening resulted in fewer children requiring hospitalization and surgery for DDH than did a strategy based on ultrasound screening of the 11.8% of infants considered to be at increased risk of DDH or one with no ultrasound screening. General ultrasound screening led to early splinting of 3.4% of the newborns compared with 2.0% for the selectively screened group and 1.8% for the group not receiving ultrasound screening. Using these data, we decided on sequences and intervals of diagnostic and therapeutic actions considered to be sufficient for each regimen. We applied estimates of the costs of screening, treatment of DDH discovered early and late, and follow-up examinations to arrive at total program costs for each strategy. RESULTS: Total program costs were similar for each of the three screening strategies (costs varied by < 5%). However, treatment of late cases accounted for only 22% of total costs in the group undergoing general screening vs 65% in the two latter groups. The cost estimates were sensitive to several variables. Application of the data to a hypothetical ultrasound program in which all girls and only boys at increased risk for DDH underwent an ultrasound examination showed substantially reduced total program costs. CONCLUSIONS: Application of costs from other centers to our data regarding frequency of clinical outcomes may yield different comparative program costs. If the findings of our clinical study can be generalized to other centers, a strategy of screening all girls and boys with risk factors for DDH may be the most cost-effective approach.

Parental factors in cognitive outcome of non-handicapped low birthweight infants.

A population based cohort of 144 children weighing less than 2000 g who were without major handicap, and a random control sample of 163 children born at term and weighing over 3000 g were investigated. The aim was to assess the relative importance for cognitive development at 5 years of age, of birthweight, parental demographic factors, and factors related to the environment in which the child was reared. The mean non-verbal IQ was 6.1 points lower (95% CI, 2.3 to 10) for the low birthweight (LBW) group, but the difference was reduced to 4.8 points (95% CI, 1.1 to 8.5) after adjusting for confounding parental demographic and childrearing factors. The verbal IQ was similar for the two groups after such adjustment. Paternal education was the main confounding variable, and demographic factors such as parental education and family income were much stronger predictors of child IQ than birthweight or factors related to the childrearing environment. There was no evidence that the cognitive development of low birthweight children was more sensitive to a non-optimal childrearing environment than that of normal birthweight children. These findings indicate that the risk of impaired cognitive development increases with decreasing socioeconomic status, and that this risk is much larger than, and independent of, the small risk attributable to low birthweight.

Population based, controlled study of behavioural problems and psychiatric disorders in low birthweight children at 11 years of age.

OBJECTIVE: To evaluate the risk of long term behavioural problems and psychiatric disorders associated with being born with low birth weight. DESIGN/STUDY GROUPS: A population based, controlled follow up study at 11 years of age of 130 low birthweight (LBW) children weighing less than 2000 g at birth who were without major handicaps, and a random sample of 131 normal birthweight (NBW) children born at term weighing over 3000 g. MAIN OUTCOME MEASURES: Validated questionnaires addressing behaviour completed by mothers and teachers and child evaluation by child psychiatrist using a semistructured interview. RESULTS: Behavioural problems, as defined by abnormal scores on more than four of 32 measures, were found in 40% of LBW children compared with 7% of NBW children (odds ratio (OR) 8.2, 95% confidence interval (CI) 3 to 25, p = 0001). A psychiatric disorder was diagnosed in 27% of the LBW children compared with 9% of the NBW children (OR 3.1, 95% CI 1.5 to 6.5, p = 0.001). The LBW children were more often inattentive, had social problems, and low self esteem. None of the pre-, neo-, or peri-natal variables in the LBW group were statistically significant predictors of behavioural outcomes or the presence of psychiatric disorders. Behavioural problems and psychiatric disorders were as common in those with birth weight less than 1500 g as those with birth weight 1500-2000 g. CONCLUSION: An increased risk of behavioural problems and psychiatric disorders persists in LBW adolescents.

Relation between size of delivery unit and neonatal death in low risk deliveries: population based study.

AIM: To examine risk of neonatal death after low risk pregnancies in relation to size of delivery units. METHODS: A population based study of live born singleton infants in Norway with birthweights of at least 2500 g was carried out. Antenatal risk factors were adjusted for. RESULTS: From 1972 to 1995, 1.25 million births fulfilled the criteria. The neonatal death rate was lowest for maternity units with 2001-3000 annual births and steadily increased with decreasing size of the maternity unit to around twice that for units with less than 100 births a year (odds ratio 2.1; 95 % confidence interval 1.6 to 2.8). Institutions with more than 3000 deliveries a year also had a higher rate (odds ratio 1.7; 95% CI 1.4 to 2.0), but analyses suggest that this rate is overestimated. CONCLUSION: Around 2000 to 3000 annual births are needed to reduce the risk of neonatal deaths after low risk deliveries.

Joint association of Apgar scores and early neonatal symptoms with minor disabilities at school age.

OBJECTIVE: To examine whether the combination of a low five minute Apgar score and symptoms of neonatal encephalopathy is associated with minor impairments at school age. DESIGN: Population based cohort study. SETTING: Norway. PARTICIPANTS: All 727 children of the cohort were born between 1983 and 1987, had normal birth weights, no congenital malformations, and no major neurological abnormalities. The cohort comprised three groups with five minute Apgar scores of 0-3, 4-6, and 7-10, and were followed from birth to 8-13 years of age by combining data from The Medical Birth Registry, questionnaires, hospital discharge summaries, and the National Insurance Scheme. MAIN OUTCOME MEASURE: Neurodevelopmental impairments such as learning, behavioural, and minor motor difficulties. RESULTS: Children with a five minute Apgar score of 3 or less and signs consistent with neonatal encephalopathy had a significantly increased risk of developing minor motor impairments (odds ratio (OR) 12.8, 95% confidence interval (CI) 2.6 to 63.2), epilepsy (OR 7.0, 95% CI 1.3 to 39.2), need of extra resources in kindergarten (OR 7.0, 95% CI 1.3 to 39.2) or at school (OR 3.4, 95% CI 1.8 to 6.3), and had reduced performance in reading (OR 4.6, 95% CI 2.3 to 9.5) and mathematics (OR 3.3, 95% CI 1.5 to 7.3), compared with children with normal Apgar scores and no neonatal symptoms. They also more often had problems related to tractability, aggressivity, passivity, anxiety, academic performance, and fine motor development. CONCLUSION: Children with low Apgar scores and subsequent signs of cerebral depression who do not develop cerebral palsy may still have an increased risk of developing a variety of neurodevelopmental impairments and learning difficulties.

Morbidity during the first year of life in small for gestational age infants.

Postneonatal morbidity during infancy was studied in 284 small for gestational age (SGA) and 359 non-SGA term infants. None of these babies had congenital malformations and they were born to para 1 and para 2 mothers. SGA infants had an increased risk (OR: 1.7, 95% confidence interval: 1.1-2.6) of being admitted to hospital compared with non-SGA infants. The principal cause was respiratory tract infections. Increased hospitalisation among SGA infants was a factor only if the mother was a smoker-that is, smoked cigarettes at the time of conception. Among subgroups of SGA babies, there was an increased risk for infants of non-repeaters (women without a previous SGA child) (OR: 2.4, 95% CI: 1.4-3.8) and for infants with symmetric (OR: 2.0, 95% CI: 1.2-3.3) body proportions compared with non-SGA infants. The results suggest that, beginning in early pregnancy, growth retardation may have long term consequences for subsequent infant morbidity, particularly if the mother is smoker.

Behavior in term, small for gestational age preschoolers.

AIMS: To evaluate whether being born small for gestational age (SGA) was associated with an increased frequency of preschool behavioral problems. STUDY DESIGN: Follow-up study at 5 years of age. SUBJECTS: A population based cohort of 318 term infants who were SGA, defined as having a birthweight less than the 15th percentile for gestational age, and without major handicap such as cerebral palsy or mental retardation, and a random control sample of 307 appropriate for gestational age (AGA) infants. OUTCOME MEASURES: The Personality Inventory for Children and the Yale Children's Inventory (completed by the mothers), and child behavior during psychometric testing. RESULTS: Behavior problems was not more common among the SGA children. The results were not confounded by a wide range of parental demographic and child rearing factors, including maternal non-verbal problem solving abilities, child rearing style, and maternal psychological distress. However, the parental factors explained 13% of the variance in a summary score of child behavior compared to 1% explained by SGA vs. AGA status. The SGA children were not more sensitive to the negative impacts of parental risk factors than AGA controls. The study does not address the outcome of severely growth-retarded SGA infants. CONCLUSION: Being born moderately SGA is not a significant risk factor for preschool behavior problems.