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.

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.

Neonatal mortality and morbidity in extremely preterm small for gestational age infants: a population based study.

AIM: To assess if growth restricted (small for gestational age, SGA) extremely preterm infants have excess neonatal mortality and morbidity. METHODS: This was a cohort study of all infants born alive at 22-27 weeks' post menstrual age in Norway during 1999-2000. Outcomes were compared between those who were SGA, defined as a birth weight less than the fifth percentile for post menstrual age, and those who had weights at or above the fifth percentile. RESULTS: Of 365 infants with a post menstrual age of <28 weeks, 31 (8%) were SGA. Among infants with a post menstrual age of <28 weeks, only chronic lung disease was associated with SGA status (OR 2.7, 95% CI 1.0 to 7.2). SGA infants with a post menstrual age of 26-27 weeks had excess neonatal mortality (OR 3.8, 95% CI 1.3 to 11), chronic lung disease and a significantly higher mean number of days (age) before tolerating full enteral nutrition. SGA infants with a post menstrual age of 22-25 weeks had an excess risk of necrotising enterocolitis. CONCLUSION: Extremely preterm SGA infants had excess neonatal mortality and morbidity in terms of necrotising enterocolitis and chronic lung disease.

Stimulation of sucking and swallowing to promote oral feeding in premature infants.

AIM: To study the effect of stimulation of sucking and swallowing on weaning from nasogastric (NG) feeding and length of hospital stay in premature infants. METHOD: Randomized controlled trial with blinded evaluation. Premature infants on NG feeds and post-menstrual age (PMA) less than 36 weeks who had poor ability to suck were randomized to receive one daily session of stimulation according to Vojta or no intervention other than standard nursing care. RESULTS: Of 36 infants, 18 received stimulation and 18 were observed without intervention. Mean gestational age at birth was 32.2 weeks (SD 2.4) versus 31.4 (2.3) weeks, p = 0.27, and PMA at study entry 35.1 weeks (0.8) versus 34.4 (0.9) weeks, p = 0.01, respectively. NG feeding was discontinued at 36.8 weeks (0.9) versus 36.3 (0.9) weeks' PMA, p = 0.25, and they were discharged at 37.8 weeks (0.9) versus 37.7 (1.3) weeks, p = 0.81. CONCLUSION: The stimulation programme did not result in earlier weaning from NG feeding or earlier discharge. However, such studies may need to be large to limit the possibility of type II errors.

Circadian variations in sudden infant death syndrome: associations with maternal smoking, sleeping position and infections. The Nordic Epidemiological SIDS Study.

AIM: To study circadian variation in the sudden infant death syndrome (SIDS) and possible associations with risk factors for SIDS. METHODS: A questionnaire-based case-control study matched for place of birth, age and gender was conducted in Denmark, Norway and Sweden: The Nordic Epidemiological SIDS Study. The study comprised 244 SIDS victims and 869 control infants between September 1992 and August 1995. The main outcome was hour found dead. RESULTS: A significant circadian pattern was observed among the 242 SIDS victims with a known hour found dead, with a peak at 08.00-08.59 in the morning (n = 33). Of the SIDS victims, 12% were found dead at 00.00-05.59, 58% at 06.00-11.59, 21% at 12.00-17.59 and 9.0% at 18.00-23.59. When comparing night/morning SIDS and day/evening SIDS (found dead 00.00-11.59 and 12.00-23.59, respectively), the proportion of night/morning SIDS was high among infants of smoking mothers (81% vs 53%, p < 0.001), infants with a reported cold (82% vs 64%, p = 0.007) and infants sleeping side/supine (81% vs 60%, p < 0.001). No associations were observed between hour found dead and other sociodemographic risk factors for SIDS. Risk (odds ratio and 95% confidence interval) of night/morning SIDS and day/evening SIDS was 7.0 (4.5-10.9) and 1.5 (0.8-2.5), respectively, for maternal smoking, 2.2 (1.5-3.1) and 0.6 (0.3-1.3), respectively, if the infant had a reported cold, 3.7 (2.1-6.6) and 3.1 (1.1-8.4), respectively, if the infant was put to sleep in the side position (supine reference), and 11.0 (5.9-20.2) and 21.6 (7.6-60.8), respectively, if the infant was put to sleep in the prone position. CONCLUSION: The observed higher proportion of night/morning cases in SIDS if the mother smoked, if the infant was reported to have a cold and if the infant was sleeping side/supine may contribute to the understanding of some epidemiological characteristics of SIDS.

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.

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.

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.

Determinants of cobalamin status in newborns.

OBJECTIVE: Cobalamin deficiency accompanied by bone marrow dysfunction and impaired central nervous system development has been reported in infants who were born to mothers with low cobalamin intake. We investigated the relation between cobalamin status in newborns and in their healthy mothers who consumed an omnivorous diet. METHODS: Serum cobalamin and the functional markers plasma methylmalonic acid (MMA) and total homocysteine (tHcy) were determined in 173 newborns and their mothers. Forty-five children and mothers were reinvestigated after 6 weeks. RESULTS: At birth, median (interquartile range) serum cobalamin levels were 245 (175-323) pmol/L in the mothers and 314 (238-468) pmol/L in the newborns. In the neonates, serum cobalamin, but not folate, was inversely associated with MMA and tHcy. Among maternal factors, low serum cobalamin was the strongest predictor of impaired cobalamin function (defined as low cobalamin, high tHcy, or high MMA levels) in the newborns. After 6 weeks, the maternal cobalamin levels had increased (to 421 [271-502] pmol/L), whereas the newborn levels had declined (to 230 [158-287] pmol/L). In the same interval, the infants had a marked increase in plasma MMA (from 0.29 [0.24-0.38] to 0.81 [0.37-1.68] micromol/L). At 6 weeks, parity was a strong predictor of cobalamin status in the infant. CONCLUSION: The cobalamin status in the neonatal period is strongly associated with maternal cobalamin status and parity. A reduction in serum cobalamin and an increase in metabolite levels are consistent with impaired cobalamin function in a significant portion of the infants who were born to healthy, nonvegetarian mothers.

Neonatal mortality rates in communities with small maternity units compared with those having larger maternity units.

OBJECTIVE: To compare neonatal mortality in geographical areas where most deliveries occur in large hospitals with areas where a larger proportion of deliveries occur in small maternity units. DESIGN: Population-based study using data from The Norwegian Medical Birth Registry. SETTING: Records on all deliveries in Norway from 1967 to 1996, a total of 1.7 million births, were equipped with data on the size of the maternity units used by delivering women in that particular area. MAIN OUTCOME MEASURE: Risk of neonatal death. RESULTS: Women living in areas where the most frequently used delivery unit had less than 2000 annual deliveries had 1.2 fold the risk of experiencing neonatal death of their newborn (95% CI 1.1-1.3). The relative risk of neonatal death in geographical areas where more than 75% of deliveries occurred in units with more than 3000 annual births was 0.8 (95% CI 0.7-0.9) compared with areas where none delivered in such large units. The relative risk of neonatal death in areas where the most frequently used delivery units had less than 100 annual births was 1.4 (95% CI 1.1-1.7) compared with areas where units of more than 3000 annual births were the most frequently used. Differences in outcome could not be explained by differences in travelling distance to an urban centre where most referral delivery units are located, differences between rural and urban municipalities, or by differences in biological or socio-economic risk factors between municipalities. CONCLUSIONS: We observed a small but significantly decreased neonatal mortality in areas where the great majority of births occurred in large hospitals.

Therapeutic electrical stimulation in cerebral palsy: a randomized, controlled, crossover trial.

The aim of this study was to evaluate the effect of therapeutic electrical stimulation (TES) applied to antagonists of spastic leg muscles on gross motor function in children with spastic diplegic cerebral palsy. Twelve children between 5 and 12 years of age completed a 24-month crossover study in which six were randomly assigned to receive TES for the first 12 months and the remaining six for the last 12 months. Physiotherapy and a home training program were not altered. All were evaluated blindly in terms of tests of motor function and video recordings at the start and at 12 and 24 months. At the end of the study parents/carers gave a subjective assessment of the effect of TES. No significant effect of TES on motor or ambulatory function was found on the blinded evaluation, but parents of 11 of the 12 children stated that TES had a significant effect. We conclude that it is unlikely that TES has a significant effect on motor and ambulatory function in spastic diplegia.

The association of Apgar score with subsequent death and cerebral palsy: A population-based study in term infants.

OBJECTIVE: To estimate the risk of adverse outcomes for newborns with a low Apgar score. STUDY DESIGN: Population-based cohort study. All 235,165 children born between 1983 and 1987 in Norway with a birth weight of at least 2500 g and no registered birth defects were followed up from birth to age 8 to 12 years by linkage of 3 national registries. Outcomes were death and cerebral palsy (CP). RESULTS: Five-minute Apgar scores of 0 to 3 were recorded for 0.1%, and scores of 4 to 6 were recorded for 0.6% of the children. Compared with children who had 5-minute Apgar scores of 7 to 10, children who had scores of 0 to 3 had a 386-fold increased risk for neonatal death (95% CI: 270-552) and an 81-fold (48-138) increased risk for CP. If Apgar scores at both 1 and 5 minutes were 0 to 3, the risks for neonatal death and CP were increased 642-fold (442-934) and 145-fold (85-248), respectively, compared with scores of 7 to 10. CONCLUSION: The strong association of low Apgar scores with death and CP in this population with a low occurrence of low scores shows that the Apgar score remains important for the early identification of infants at increased risk for serious and fatal conditions.

[Treatment of extremely premature infants--which limits and what problems?]. / Behandling av ekstremt premature born--kva grenser og kva problem?

In Norway about 300 babies with a birthweight of 500-999 grams and 200 with a gestational age of 24-27 weeks are born annually. This gives a total of 320-330 babies who come under the definition of extreme prematurity. Obstetric care is important in order to avoid premature birth, or, when premature birth is unavoidable, to find the optimal time and place for delivery. There is ongoing discussion of what constitutes reasonable lower limits for offering life support. The survival rate for babies born before 24 gestational weeks is low and the risk of serious neurological damage high. The risk of severe lung disease is reduced with pre- and postnatal treatment with corticosteroids and postnatal treatment with surfactant, but excessive corticosteroid treatment may possibly increase the risk of neurological damage. Despite major recent progress in the treatment of the preterm baby, significant understanding of why disabilities occur is lacking.

[Approaching the acutely ill child]. / Tilnaerming til det akutt syke barnet.

The proper evaluation of the acutely ill infant and child requires a systematic approach, and knowledge of normal and pathological clinical findings according to age. In this paper guidelines are suggested on how the child may be evaluated clinically and by judicious use of supplementary investigations which are readily available.

Randomised controlled trial of infantile colic treated with chiropractic spinal manipulation.

AIMS: To investigate the efficacy of chiropractic spinal manipulation in the management of infantile colic. METHODS: One hundred infants with typical colicky pain were recruited to a randomised, blinded, placebo controlled clinical trial. RESULTS: Nine infants were excluded because inclusion criteria were not met, and five dropped out, leaving 86 who completed the study. There was no significant effect of chiropractic spinal manipulation. Thirty two of 46 infants in the treatment group (69.9%), and 24 of 40 in the control group (60.0%), showed some degree of improvement. CONCLUSION: Chiropractic spinal manipulation is no more effective than placebo in the treatment of infantile colic. This study emphasises the need for placebo controlled and blinded studies when investigating alternative methods to treat unpredictable conditions such as infantile colic.

Assessing quality of obstetric care for low-risk deliveries; methodological problems in the use of population based mortality data.

BACKGROUND: Studies evaluating safety of different birth settings for low-risk deliveries are often difficult to interpret because of great methodological problems. OBJECTIVE: To assess potential bias in comparisons of mortality between maternity institutions with different size and level of care, particularly when using various definitions of low-risk delivery and when studying stillbirth rates. DESIGN: Population-based study. POPULATION: The population of 1.74 million births in Norway from 1967 to 1996 recorded in The Medical Birth Registry of Norway. METHODS: First we explored the problems of properly identifying low-risk deliveries from population-based data and calculated adjusted perinatal mortality rates in sub-populations by excluding different risk factors. Then we measured the difference in apparent low-risk deliveries between institutions of different size and level of care. Finally we explored bias by using stillbirths and discuss the loss of statistical power by studying only livebirths. RESULTS: The occurrence of a whole spectrum of risk factors differed between small and large institutions, even after adjustment for birthweight. Although the majority of births were from low-risk deliveries, only 1/10th of all perinatal deaths occurred in this group after admission to a maternity unit. There was a systematic difference in the reporting of time of death for stillbirths between types of institutions; the rate of stillbirths occurring during delivery was higher among small institutions, while large institutions were more often uncertain in classifying time of death for stillbirths. CONCLUSIONS: Adjustments for a large number of different risk factors, large sample-sizes and caution in including stillbirth as outcome measure are needed when comparisons of safety between different sizes of delivery units are made for low-risk pregnancies.

Maternal smoking and birthweight: effect modification of period, maternal age and paternal smoking.

OBJECTIVE: To study the effect on birthweight of maternal smoking, and its modification by study period, maternal age and paternal smoking. DESIGN: A retrospective questionnaire based national survey comprising a random sample (n=34,799) of all mothers giving birth in Norway 1970-91. Variables studied were parental smoking during pregnancy, birthweight, maternal age and infant's year of birth. RESULTS: The overall difference in mean birthweight between non-smoking and smoking mothers was 197 g. The difference in birthweight between non-smoking and smoking mothers increased with maternal age from 182 g (<20 years of age) to 232 g (35+ years of age). There was no significant effect of paternal smoking on birthweight when the mother was a non-smoker. When the mother was a smoker and the father was a non-smoker, the birthweight, adjusted for maternal age, was reduced by 153 g (p<0.005). However, when both parents smoked, the birthweight, adjusted for maternal age, was reduced by 201 g (p<0.0005). Even though the prevalence of paternal smoking decreased by 38% during the study period, there was no significant increase in overall mean birthweight. IMPLICATION AND RELEVANCE OF RESULTS: The negative effect of maternal smoking on birthweight appears to increase with maternal age. For a non-smoking pregnant woman to live with a smoking partner has little, if any, effect on birthweight. The negative effect of paternal smoking was only observed when the mother was smoking and might reflect two possible mechanisms: (1) that a smoking mother has a greater cigarette consumption when the partner also smokes, and (2) that a smoking mother is less concerned about passive smoking than a non-smoking mother.