Trond Markestad

Long-Term Medical and Social Consequences of Preterm Birth

BACKGROUND Advances in perinatal care have increased the number of premature babies who survive. There are concerns, however, about the ability of these children to cope with the demands of adulthood. METHODS We linked compulsory national registries in Norway to identify children of different gestational-age categories who were born between 1967 and 1983 and to follow them through 2003 in order to document medical disabilities and outcomes reflecting social performance. RESULTS The study included 903,402 infants who were born alive and without congenital anomalies (1822 born at 23 to 27 weeks of gestation, 2805 at 28 to 30 weeks, 7424 at 31 to 33 weeks, 32,945 at 34 to 36 weeks, and 858,406 at 37 weeks or later). The proportions of infants who survived and were followed to adult life were 17.8%, 57.3%, 85.7%, 94.6%, and 96.5%, respectively. Among the survivors, the prevalence of having cerebral palsy was 0.1% for those born at term versus 9.1% for those born at 23 to 27 weeks of gestation (relative risk for birth at 23 to 27 weeks of gestation, 78.9; 95% confidence interval [CI], 56.5 to 110.0); the prevalence of having mental retardation, 0.4% versus 4.4% (relative risk, 10.3; 95% CI, 6.2 to 17.2); and the prevalence of receiving a disability pension, 1.7% versus 10.6% (relative risk, 7.5; 95% CI, 5.5 to 10.0). Among those who did not have medical disabilities, the gestational age at birth was associated with the education level attained, income, receipt of Social Security benefits, and the establishment of a family, but not with rates of unemployment or criminal activity. CONCLUSIONS In this cohort of people in Norway who were born between 1967 and 1983, the risks of medical and social disabilities in adulthood increased with decreasing gestational age at birth.

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.

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.

First Day of Life Pulse Oximetry Screening to Detect Congenital Heart Defects

OBJECTIVE To evaluate the efficacy of first day of life pulse oximetry screening to detect congenital heart defects (CHDs). STUDY DESIGN We performed a population-based prospective multicenter study of postductal (foot) arterial oxygen saturation (SpO(2)) in apparently healthy newborns after transfer from the delivery suite to the nursery. SpO(2) < 95% led to further diagnostic evaluations. Of 57,959 live births, 50,008 (86%) were screened. In the screened population, 35 CHDs were [corrected] classified as critical (ductus dependent, cyanotic). CHDs were prospectively registered and diagnosed in 658/57,959 (1.1%) [corrected] RESULTS Of the infants screened, 324 (0.6%) failed the test. Of these, 43 (13%) had CHDs (27 critical), and 134 (41%) had pulmonary diseases or other disorders. The remaining 147 infants (45%) were healthy with transitional circulation. The median age for babies with CHDs at failing the test was 6 hours (range, 1-21 hours). For identifying critical CHDs, the pulse oximetry screening had a sensitivity rate of 77.1% (95% CI, 59.4-89.0), specificity rate of 99.4% (95% CI, 99.3-99.5), and a false-positive rate of 0.6% (95% CI, 0.5-0.7). CONCLUSIONS Early pulse oximetry screening promotes early detection of critical CHDs and other potentially severe diseases. The sensitivity rate for detecting critical CHDs is high, and the false-positive rate is low.

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.

A case-control study of smoking and sudden infant death syndrome in the Scandinavian countries, 1992 to 1995

AIM To establish whether smoking is an independent risk factor for sudden infant death syndrome (SIDS), if the effect is mainly due to prenatal or postnatal smoking, and the effect of smoking cessation. METHODS The analyses were based on data from the Nordic epidemiological SIDS study, a case-control study with 244 cases and 869 controls. Odds ratios were computed by conditional logistic regression analysis. RESULTS Smoking emerged as an independent risk factor for SIDS, and the effect was mainly mediated through maternal smoking in pregnancy (crude odds ratio 4.0 (95% confidence interval 2.9 to 5.6)). Maternal smoking showed a marked dose–response relation. There was no effect of paternal smoking if the mother did not smoke. Stopping or even reducing smoking was beneficial. SIDS cases exposed to tobacco smoke were breast fed for a shorter time than non-exposed cases, and feeding difficulties were also more common. CONCLUSIONS Smoking is an independent risk factor for SIDS and is mainly mediated through maternal smoking during pregnancy. Stopping smoking or smoking less may be beneficial in reducing the risk of SIDS.

Lung function after preterm birth: development from mid-childhood to adulthood

Background As a result of advances in perinatal care, more small preterm infants survive. There are concerns that preterm birth and its treatments may harm pulmonary development and thereby lead to chronic airway obstruction in adulthood. Objective To assess the development of spirometric lung function variables from mid-childhood to adulthood after extreme preterm birth. Methods Two population-based cohorts born at gestational age ≤28 weeks or with birth weight ≤1000 g performed lung function tests at 10 and 18 and at 18 and 25 years of age, respectively, together with matched term-born controls. The results are presented as z scores, normalised for age, sex and height. Longitudinal development was compared for groups born at term and preterm, split by a history of absence (n=20), mild (n=38) or moderate/severe (n=25) neonatal bronchopulmonary dysplasia (BPD). Results The preterm-born cohorts, particularly those with neonatal BPD, had significantly lower forced expiratory volume in 1 s and mid-expiratory flow than those born at term at all assessments (z scores in the range −0.40 to −1.84). Within each of the subgroups the mean z scores obtained over the study period were largely similar, coefficients of determination ranging from 0.64 to 0.82. The pattern of development for the BPD subgroups did not differ from each other or from the groups born at term (tests of interaction). Conclusions Airway obstruction was present from mid-childhood to adulthood after extreme preterm birth, most evident after neonatal BPD. Lung function indices were tracking similarly in the preterm and term-born groups.

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.

Sleeping position and sudden infant death syndrome (SIDS): effect of an intervention programme to avoid prone sleeping.

The proportion of prone sleeping among sudden infant death syndrome (SIDS) victims and infants in general, and the rate of SIDS were prospectively studied in the county of Hordaland, Norway, three years before (1987–89) and three years after (1990–92) a campaign to discourage prone sleeping. Before the campaign, 64% of random reference infants were put prone versus 8% after (p < 0.0001). Concurrently, the rate of SIDS decreased from 3.5 to 1.6 per 1000 live births (63 infants before and 30 after the campaign,p= 0.0002). Prone sleeping was not considered a statistically significant risk factor for SIDS before (OR 2.0,95% CI 0.8–4.5), but was highly significant (OR 11.3,95% CI 3.6–36.5) after the campaign. Prone sleeping is an important risk factor for SIDS, but the association may be missed in epidemiological studies if prone is the predominant sleeping position. Behaviour with regard to sleeping position may be changed rapidly by means of a simple campaign.

Cognitive development of term small for gestational age children at five years of age

AIM To assess the relative significance for cognitive development of small for gestational age, parental demographic factors, and factors related to the child rearing environment. METHODS IQ of a population based cohort of 338 term infants who were small for gestational age (SGA) and without major handicap, and a random control sample of 335 appropriate for gestational age (AGA) infants were compared at 5 years of age. RESULTS The mean non-verbal IQ was four points lower, while the mean verbal IQ was three points lower for the children in the SGA group. The results were not confounded by parental demographic or child rearing factors. However, parental factors, including maternal non-verbal problem solving abilities, and child rearing style, accounted for 20% of the variance in non-verbal IQ, while SGA versus AGA status accounted for only 2%. The comparable numbers for verbal IQ were 30 and 1%. Furthermore, we found no evidence that the cognitive development of SGA children was more sensitive to a non-optimal child rearing environment than that of AGA children. Maternal smoking at conception was associated with a reduction in mean IQ comparable to that found for SGA status, and this effect was the same for SGA and AGA children. The cognitive function of asymmetric SGA was comparable to that of symmetric SGA children. CONCLUSIONS Our findings indicate that child cognitive development is strongly associated with parental factors, but only marginally associated with intrauterine growth retardation.