Per Ivar Kaaresen

Early Death, Morbidity, and Need of Treatment Among Extremely Premature Infants

Objective. To determine outcomes, in terms of perinatal and early death, need for treatment, and morbidity at the time of discharge home, among extremely preterm infants. Design. A prospective observational study of all infants with a gestational age (GA) of 22 to 27 completed weeks or a birth weight of 500 to 999 g who were born in Norway in 1999 and 2000. Results. Of 636 births, 174 infants (27%) were stillborn or died in the delivery room, 86 (14%) died in the NICU, and 376 (59%) were discharged from the hospital. The risk of being registered as stillborn or not being resuscitated increased with decreasing GA below 25 weeks. The survival rates for all births and for infants admitted to a NICU were, respectively, 0% for <23 weeks, 16% and 39% for 23 weeks, 44% and 60% for 24 weeks, 66% and 80% for 25 weeks, 72% and 84% for 26 weeks, 82% and 93% for 27 weeks, and 69% and 90% for >27 weeks. For the survivors, days of mechanical ventilation decreased from a median of 37 days to 3 days and the proportion in need of oxygen at 36 weeks’ postconceptional age decreased from 67% to 26% at 23 and 27 weeks’ GA, respectively. At 40 weeks’ postconceptional age, the respective figures were 11% and 6%. The proportion with retinopathy of prematurity (ROP) requiring treatment decreased from 33% for GA of 23 weeks to 0% for >25 weeks. Periventricular hemorrhage of more than grade 2 occurred for 6% of the survivors and significant periventricular leukomalacia occurred for 5%, with no significant association with GA. The proportion of survivors without severe neurosensory or pulmonary morbidity increased from 44% for 23 weeks’ to 86% for 27 weeks’ GA. Apart from ROP, the morbidity rate was not associated with GA. Conclusions. The survival rate was high and the morbidity rate at discharge home was low in the present study, compared with previous population-based studies. With the exception of ROP, the morbidity rates among the survivors were not higher at the lowest GAs, possibly because withholding treatment was considered more acceptable for the most immature infants. The need for intensive care increased markedly for survivors with the lowest GAs.

A Randomized, Controlled Trial of the Effectiveness of an Early-Intervention Program in Reducing Parenting Stress After Preterm Birth

BACKGROUND. Preterm birth has been associated with increased parenting stress in early infancy, and some reports have found this to be a risk factor for later behavioral problems. There are, however, few studies and conflicting results. Information about the fathers is scarce. OBJECTIVES. Our goal was to study the effects of an early-intervention program on parenting stress after a preterm birth until 1 year corrected age. METHODS. A randomized, controlled trial was conducted including infants with a birth weight <2000 g treated at the University Hospital of North Norway Trust, which serves the 2 northern-most counties in Norway, to examine the effects of a modified version of the Mother-Infant Transaction Program on parenting stress measured by the Parenting Stress Index. A term control group was also recruited. The Parenting Stress Index was administered to the mothers at 6 and 12 months’ corrected age and to the fathers at 12 months’ corrected age. The intervention consisted of 8 sessions shortly before discharge and 4 home visits by specially trained nurses focusing on the infant’s unique characteristics, temperament, and developmental potential and the interaction between the infant and the parents. RESULTS. Seventy-one infants were included in the preterm intervention group, and 69 were included in the preterm control group. The preterm groups were well balanced. Seventy-four infants were included in the term control group. Compared with the preterm controls, both the mothers and fathers in the preterm intervention group reported significant lower scores in child domain, parent domain, and total stress on all occasions except the mother-reported child domain at 12 months. These differences were not related to birth weight or gestational age. The level of stress among the preterm intervention group was comparable to their term peers. Both parents in the intervention group reported consistently lower scores within the distractibility/hyperactivity, reinforces parents, competence, and attachment subscales compared with the preterm control group. There were no differences in mean summary stress scores between the mothers and fathers in the 2 preterm groups at 12 months, but the intraclass correlation coefficient was higher in the intervention group. CONCLUSIONS. This early-intervention program reduces parenting stress among both mothers and fathers of preterm infants to a level comparable to their term peers. We are now studying whether this will result in long-term beneficial effects.

Late-Onset Septicemia in a Norwegian National Cohort of Extremely Premature Infants Receiving Very Early Full Human Milk Feeding

Objectives. To investigate the occurrence of and risk factors for late-onset septicemia (LOS) in a national cohort of extremely premature infants who received very early full human milk feeding. Methods. A prospective study of all infants born in Norway in 1999 and 2000 with gestational age of <28 weeks or birth weight of <1000 g was performed. Extensive clinical information, including data on feeding practices and episodes of septicemia, was collected on predefined forms. LOS was defined as growth of bacteria or fungi in blood cultures in conjunction with clinical symptoms consistent with systemic infection occurring after day 6 of life. Cox regression models, including models allowing for time-dependent covariates, were applied in the analysis of LOS. Results. Of 464 eligible infants, 462 (99.6%) were enrolled and 405 (87.7%) survived until day 7. LOS was diagnosed for 80 (19.7%). The predominant pathogens were coagulase-negative staphylococci, followed by Candida spp. Case fatality rates associated with septicemia were 10% in general and 43% for Candida spp septicemia. Necrotizing enterocolitis or bowel perforation was diagnosed for 19 infants (4%). Enteral feeding with human milk was initiated within the third day for 98% of patients, and 92% were receiving full enteral feeding (FEF) with human milk within the third week. Both high Clinical Risk Index for Babies scores and an umbilical venous catheter in situ at 7 days of age significantly predicted LOS. However, the overall most influential risk factor for LOS was the number of days without establishment of FEF with human milk, with an adjusted relative risk of 3.7 (2.0–6.9) for LOS if FEF was not established within the second week of life. Conclusions. The incidence and case fatality rate of septicemia for this cohort of extremely preterm infants were lower than values in comparable studies. The main difference, compared with other studies, was the feeding practice, and the data suggest that very early FEF with human milk significantly reduces the risk of LOS among extremely premature infants.

Early Intervention Improves Behavioral Outcomes for Preterm Infants: Randomized Controlled Trial

Objective: The aim of this study was to examine the effectiveness of an early intervention program on behavioral outcomes at corrected age of 5 years for children with birth weights (BWs) of <2000 g. Methods: A randomized controlled trial of a modified version of the Mother-Infant Transaction Program was performed. Outcomes were measured by the Child Behavior Check List report (parents) and Strengths and Difficulties Questionnaire at 5 years (parents and preschool teachers). Results: A total of 146 infants were assigned randomly (intervention group: 72 infants; reference group: 74 infants). A term group was recruited (75 infants). The mean BWs were 1396 ± 429 g for the intervention group, 1381 ± 436 g for the control group, and 3619 ± 490 g for the term reference group. Parents in the intervention group reported significantly fewer behavioral problems measured by both instruments at 5 years. There were no differences in behavior problems reported by preschool teachers. Significantly more children in the preterm control group scored within the clinical area of both instruments. Conclusions: This modified version of the Mother-Infant Transaction Program led to fewer behavioral problems reported by parents at corrected age of 5 years for children with BWs of <2000 g.

Prediction of Neurodevelopmental and Sensory Outcome at 5 Years in Norwegian Children Born Extremely Preterm

OBJECTIVE: To examine the prevalence of neurodevelopmental disability and the predictive value of pre-, peri-, and postnatal data on neurologic, sensory, cognitive, and motor function in children born extremely preterm. METHODS: This was a prospective observational study of all infants born in Norway between 1999 and 2000 with gestational ages between 22 and 27 weeks or birth weights between 500 and 999 g. Cognitive function was assessed with the Wechsler Preschool and Primary Scale of Intelligence–Revised, motor function with the Movement Assessment Battery for Children, and severity of cerebral palsy with the Gross Motor Function Classification for Cerebral Palsy. Disabilities were described as mild, moderate, or severe. RESULTS: Of 371 eligible children, 306 (82%) were examined at a mean (SD) age of 5 years and 10 (4) months. For gestational age less than 28 weeks (n = 239), 26 (11%) children had cerebral palsy alone (n = 21) or in combination with blindness (n = 3) or deafness (n = 2); 1 was blind and 1 was deaf. Of the remaining children, the mean full-scale IQ was 94 ± 15, and significant predictors were (values given as the difference in IQ points [95% confidence intervals]) high maternal education (9.6 [5.7–13.4]), preeclampsia (−7.7 [−12.7 to −2.7]), and retinopathy of prematurity higher than grade 2 (−17.5 [−27.1 to −8.0]). Movement Assessment Battery for Children scores were positively associated with gestational age and prenatal steroids and negatively associated with being small for gestational age, male gender, and having retinopathy of prematurity. Moderate to severe neurodevelopmental disability was more common for gestational ages 25 weeks or less (28 of 87 children) than for 26 to 27 weeks (12 of 152 children; P < .001) and 28 weeks or more (7 of 67 children; P = .001). CONCLUSIONS: The outcome was poorer for children with gestational ages of 25 weeks or less compared with those with gestational ages between 26 and 27 weeks. For those without cerebral palsy, blindness, or deafness, however, gestational age had a limited association with cognitive and motor function.

Septicemia in the first week of life in a Norwegian national cohort of extremely premature infants.

Objectives. To investigate the incidence, causes, predictors, and outcomes of septicemia in the first week of life in a national cohort of extremely premature infants. Methods. A prospective study of survival of all infants with gestational age of <28 weeks or birth weight of <1000 g who were born in Norway in 1999–2000 was performed. Data on the maternal prenatal history, delivery, and neonatal course, including detailed information on episodes of microbiologically verified septicemia, were collected on predefined forms. Septicemia was reported in 2 groups, ie, episodes diagnosed on the day of delivery (ie, very early-onset septicemia [VEOS]) and episodes diagnosed from day 2 to day 7 of life (ie, early-onset septicemia [EOS]). Logistic regression models were used for the selection of variables for predictor analysis in each group. Results. Of 462 included infants, VEOS occurred for 15 (32.5 per 1000 population) and EOS for 15 (35.5 per 1000 population). The most prevalent bacteria were Escherichia coli in VEOS (n = 9) and staphylococci (coagulase-negative staphylococci and Staphylococcus aureus) (n = 15) in EOS. Case fatality rates were 40% and 13%, respectively. Independent predictive factors for VEOS were clinical chorioamnionitis (odds ratio [OR]: 10.5; 95% confidence interval [CI]: 3.3-33.4) and high maternal age (OR: 1.2; 95% CI: 1.0–1.3), whereas not receiving systemic antibiotic therapy within 2 days of age (OR: 13.6; 95% CI: 3.7–50.2) and receiving nasal continuous positive airway pressure (n-CPAP) support at 24 hours of age (OR: 9.8; 95% CI: 2.5–38.4) independently predicted septicemia after the first day of life. Conclusions. Whereas vertically transmitted septicemia was dominated by Gram-negative bacteria, with predictors being exclusively of maternal origin, EOS was dominated by typically nosocomial flora, with n-CPAP treatment at 24 hours of age being a powerful predictor. Early n-CPAP treatment, as opposed to mechanical ventilation, as a powerful predictor of septicemia in the early neonatal period, even with adjustment for early systemic antibiotic treatment, is a new observation among extremely premature infants that warrants additional study.

Major congenital heart disease in Northern Norway: shortcomings of pre- and postnatal diagnosis.

Background.  Congenital heart disease (CHD) is a significant cause of perinatal mortality and morbidity worldwide. Prenatal detection rate of CHD remains low in most European countries and a substantial proportion of infants with serious heart disease are diagnosed only after discharge from hospital after birth. Earlier recognition of treatable abnormalities may improve the perinatal outcome. The purpose of this study was to evaluate the incidence, pre‐ and postnatal diagnosis and outcome of major CHD in two northern‐most counties of Norway.

Acute osteomyelitis in children: a population-based retrospective study 1965 to 1994.

OBJECTIVES To investigate changes in occurrence, clinical features, laboratory and other investigations, aetiology and use of antibiotics, and to calculate the incidence of acute hematogenous osteomyelitis (AHO) in children up to 12 y of age in the county of Troms in the northern part of Norway. METHODS Retrospective chart review of 86 children, newborn to 11 y old. with AHO between 1965 and 1994. RESULTS A constant yearly incidence (95% CI) of 0.1 (0.08-0.12) per 1000 children could be calculated (X2 for trend 0.51;p = 0.48). The female proportion (95% CI) was 0.6 (0.48-0.72). The median duration of complaints prior to admission was 4 days. Erythrocyte sedimentation rate (ESR; mean (95% CI)= 59 mm/h (52-66)) and C-reactive protein concentration (CRP; mean (95% CI)= 63 mg/l (36-90)) were elevated in 96% and 89%, respectively. Local and/or blood cultures were taken in 97%. In 55% an agent was found. Staphylococcus aureus (S. aureus) was responsible in 76%. The proportion of betalactamase-producing strains tended to increase (49%; X2 for trend 3.72; p = 0.054). In 78% the long bones of the upper or lower extremities were affected. Penicillin or ampicillin combined with cloxacillin or dicloxacillin was the preferred therapy. The median duration of antibiotic treatment was 7 weeks. The use of penicillin declined (p = 0.008), whereas that of cloxacillin/dicloxacillin increased (p < 0.001). The use of ampicillin was unchanged (p = 0.79). CONCLUSION The study confirms reports from various epochs and remote regions concerning the unchanged characteristics of AHO in children, except for the high proportion of females in the present study. An incidence for childhood AHO in a defined geographical region is given.

Patient comfort during treatment with heated humidified high flow nasal cannulae versus nasal continuous positive airway pressure: a randomised cross-over trial

Objective To compare patient comfort in preterm infants treated with heated humidified high flow nasal cannulae (HHHFNC) versus nasal continuous positive airway pressure (NCPAP). Design Randomised cross-over trial (2×24 h). Setting Single tertiary neonatal unit. Patients 20 infants less than 34 weeks postmenstrual age treated with NCPAP due to mild respiratory illness. Interventions After parental consent, infants were randomised to 24 h of treatment with NCPAP or HHHFNC followed by 24 h of the alternate therapy. Main outcome measures Primary outcome was patient comfort assessed by the EDIN (neonatal pain and discomfort) scale. Secondary outcomes were respiratory parameters (respiratory rate, FiO2, SpO2, TcPCO2), ambient noise, salivary cortisol and parental assessments of their child. Results We found no differences between HHHFNC and NCPAP in mean cumulative EDIN score (10.7 vs 11.1, p=0.25) or ambient noise (70 vs 74 dBa, p=0.18). Parents assessed HHHFNC treatment as significantly better in the three domains, 1) child satisfied, 2) parental contact and interaction and 3) possibility to take part in care. Mean respiratory rate over 24 h was lower during HHHFNC than CPAP (41 vs 46, p=0.001). Other respiratory parameters were similar. Conclusions Using EDIN scale, we found no difference in patient comfort with HHHFNC versus NCPAP. However, parents preferred HHHFNC, and during HHHFNC respiratory rate was lower than during NCPAP. ClinicalTrials.gov, number NCT01526226.

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.