Neurodevelopmental outcome in full-term newborns with refractory neonatal seizures.

AIM: This retrospective study describes the prognosis of full-term newborns with refractory neonatal seizures, comparing the need for treatment with two versus three or more antiepileptic drugs. METHODS: We reviewed our database (January 2002-December 2007) to include newborns with refractory neonatal seizures and abnormal electroencephalogram. Group A consisted of 17 newborns with two antiepileptic drugs. Group B consisted of 29 newborns with three or more antiepileptic drugs. Outcome was determined at 2 years of age using the Dutch Bayley Scales of Infant Development or a neurodevelopmental classification scheme. RESULTS: Group A and group B were comparable regarding to a variety of demographic and aetiologic factors. Thirteen newborns died before 2 years of age and one was lost to follow-up. Normal development at 2 years of age was found in 50% and 5% for group A and B, respectively. Severe neurodevelopmental delay at 2 years of age was found in 30% and 68% for group A and B, respectively. CONCLUSION: The number of antiepileptic drugs probably reflects increased seizure burden and is--in that way--related to poor outcome. This may be useful information for early prediction of adverse neurological outcome in the first days of life.

Prognostic models for stillbirth and neonatal death in very preterm birth: a validation study.

OBJECTIVES: To validate externally 2 prognostic models for stillbirth and neonatal death in very preterm infants who are either known to be alive at the onset of labor or admitted for neonatal intensive care. PATIENTS AND METHODS: All infants, with gestational age 22 to 32 weeks, of European ethnicity, known to be alive at the onset of labor (n = 17 582) and admitted for neonatal intensive care (n = 11 578), who were born in the Netherlands between January 1, 2000, and December 31, 2007. The main outcome measures were stillbirth or death within 28 days for infants known to be alive at the onset of labor and death before discharge from the NICU for infants admitted for intensive care. Model performance was studied with calibration plots and c statistic. RESULTS: Of the infants known to be alive at the onset of labor, 16.7% (n = 2939) died during labor or within 28 days of birth, and 7.8% (n = 908) of the infants admitted for neonatal intensive care died before discharge from intensive care. The prognostic model for infants known to be alive at the onset of labor showed good calibration and excellent discrimination (c statistic 0.92). The prognostic model for infants admitted for neonatal intensive care showed good calibration and good discrimination (c statistic 0.82). CONCLUSIONS: The 2 prognostic models for stillbirth and neonatal death in very preterm Dutch infants showed good performance, suggesting their use in clinical practice in the Netherlands and possibly other Western countries.

Long-term neurodevelopmental outcome of monochorionic and matched dichorionic twins.

BACKGROUND: Monochorionic (MC) twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS) or intrauterine co-twin death) or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC) twins at the age of two years. METHODS: This was a prospective cohort study. Cerebral palsy (CP) was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (un)alikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner. FINDINGS: Four out of 182 MC infants had CP (2.2%) - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death) and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5-38.2) of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffith's test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7%) had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0-1.4). Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its larger co-twin. CONCLUSIONS: There were no significant differences in occurrence of cerebral palsy as well as neurodevelopmental outcome between MC and DC twins. Outcome of MC twins seems favourable in the absence of TTTS or co-twin death.

Functioning at school age of moderately preterm children born at 32 to 36 weeks' gestational age.

OBJECTIVE: To study outcome of low-risk moderately preterm birth between 32 and 36/7 weeks' gestation. METHODS: 377 Moderately preterm children (M: 34.7, SD: 1.2 complete weeks), without need for neonatal intensive care and without dysmaturity or congenital malformations, were compared with 182 term children and assessed at eight years (M: 8.9, SD: 0.54). School situation, IQ, sustained attention, behavior problems, and attention-deficit/hyperactivity characteristics were studied. RESULTS: Special education was attended by 7.7% of the moderately preterm children, more than twice the rate of 2.8% in the general Dutch population of this age. Additional exploration for two preterm subgroups of 32 to 33 versus 34 to 36 weeks' gestation showed a need for special education in 9.7% versus 7.3% and a significant difference in grade retention for 30% versus 17%, respectively. Of the children attending mainstream primary schools, grade retention was found in 19% of the preterm versus 8% of the comparison children. Adjusting for maternal education, a group difference of 3 points was found in IQ. The preterm children needed more time for the sustained attention task. The preterm children had more behavior problems (specifically internalizing problems with 27% scoring above the borderline cut-off), as well as more attention-deficit/hyperactivity disorder characteristics (specifically attention deficits). CONCLUSIONS: Cognitive and emotional regulation difficulties affect functioning of moderately preterm children, as school problems, a slightly lower IQ, attention and behavioral problems are found when they are compared with term-born children. Identification and monitoring of precursors of these problems at younger age is needed in view of prevention purposes.

Functional outcomes and participation in young adulthood for very preterm and very low birth weight infants: the Dutch Project on Preterm and Small for Gestational Age Infants at 19 years of age.

OBJECTIVE: Young adults who were born very preterm or with a very low birth weight remain at risk for physical and neurodevelopmental problems and lower academic achievement scores. Data, however, are scarce, hospital based, mostly done in small populations, and need additional confirmation. METHODS: Infants who were born at < 32 weeks of gestation and/or with a birth weight of < 1500 g in The Netherlands in 1983 (Project on Preterm and Small for Gestational Age Infants) were reexamined at age 19. Outcomes were adjusted for nonrespondents using multiple imputation and categorized into none, mild, moderate, or severe problems. RESULTS: Of 959 surviving young adults, 74% were assessed and/or completed the questionnaires. Moderate or severe problems were present in 4.3% for cognition, 1.8% for hearing, 1.9% for vision, and 8.1% for neuromotor functioning. Using the Health Utility Index and the London Handicap Scale, we found 2.0% and 4.5%, respectively, of the young adults to have > or = 3 affected areas in activities and participation. Special education or lesser level was completed by 24%, and 7.6% neither had a paid job nor followed any education. Overall, 31.7% had > or = 1 moderate or severe problems in the assessed areas. CONCLUSIONS: A total of 12.6% of young adults who were born very preterm and/or with a very low birth weight had moderate or severe problems in cognitive or neurosensory functioning. Compared with the general Dutch population, twice as many young adults who were born very preterm and/or with a very low birth weight were poorly educated, and 3 times as many were neither employed nor in school at age 19.

Lower mortality but higher neonatal morbidity over a decade in very preterm infants.

Better perinatal care has led to better survival of very preterm children, but may or may not have increased the number of children with cerebral and pulmonary morbidity. We therefore investigated the relationship between changes in perinatal care during one decade, and short-term outcome in very preterm infants. Perinatal risk factors and their effects on 28-day and in-hospital mortality, and on intraventricular haemorrhage and bronchopulmonary dysplasia (BPD) in survivors, were compared in two surveys of very preterm singleton infants in the Netherlands. Between 1983 and 1993, 28-day mortality decreased from 52.1% to 31.8% in infants of 25-27 weeks' gestation and from 15.2% to 11.3% in infants of 28-31 weeks' gestation. The incidence of intraventricular haemorrhage in survivors did not change (44.4% and 43.3% in infants of 25-27 weeks' gestation, and 29.0% and 24.0% in infants of 28-31 weeks' gestation). The incidence of BPD in survivors increased from 40.3% to 60.0% in infants of 25-27 weeks' gestation and remained similar in infants of 28-31 weeks' gestation (8.5% and 9.8% respectively). In multivariable analysis, higher mortality was associated with congenital malformation, low gestational age, low birthweight, no administration of steroids before birth, low Apgar scores and intraventricular haemorrhage, in 1983 as well in 1993, and with male gender in 1993. The effect of maternal age on mortality diminished significantly between 1983 and 1993. Intraventricular haemorrhage in surviving children was associated with low gestational age and artificial ventilation, both in 1983 and in 1993. The effect of artificial ventilation on the incidence of intraventricular haemorrhage diminished significantly between 1983 and 1993. BPD was associated with low gestational age and artificial ventilation, both in 1983 and in 1993, and with low birthweight and caesarean section in 1993. We conclude that the better survival of very preterm infants, especially of those of 25-27 weeks' gestation, has been accompanied by a similar incidence (and thus with an increased absolute number) of children with intraventricular haemorrhage and by an increased incidence of children with BPD.

Outcome of perinatal care for very preterm infants at 5 years of age: a comparison between 1983 and 1993.

Perinatal mortality in very preterm infants has decreased by up to 50% during the last decades. Studies of changes of long-term outcome are inconclusive. We studied the visual, auditory, neuromotor, cognitive and behavioural development of two geographically defined populations of very preterm, singleton infants, born in 1983 and in 1993, and analysed the relationship between perinatal risk factors and outcomes. The incidence of disabling cerebral palsy increased from 6.0% to 11.1% (OR 2.45 [95% CI 1.11, 5.38]). Impaired vision and strabismus decreased significantly, presumably by continuous monitoring of pO(2). Hearing problems, the need for special education and the incidence of behavioural problems did not change over time. The proportion of children who showed optimal performance in every developmental domain increased from 29.5% in 1983 to 43.2% in 1993. Cerebral palsy was associated with male gender in 1983, with low Apgar score and intraventricular haemorrhage in 1993, and with seizures both in 1983 and in 1993. The intensiveness of neonatal treatment has increased, leading to the survival of many more healthy infants, but at the cost of more infants with cerebral damage. Modern perinatal care is no longer limited by the devastating effects of pulmonary problems as it was in the past, but fails to safeguard cerebral integrity in very preterm infants.

Is paediatric assessment of motor development of very preterm and low-birthweight children appropriate?

AIM: To determine whether paediatricians that examine, in regular clinical practice, very preterm and very-low-birthweight children at 5 y of age detect neurological impairments and functional motor problems in these children. METHODS: We compared a paediatric judgement, a standardized neurological examination (Touwen examination) and a screening of motor development (Denver Developmental Screening Test; DDST) with the Movement ABC in 396 5-y-old very preterm and low-birthweight children. RESULTS: The Movement ABC detected clinically important motor disorders in 20.5% and borderline disturbances in 22.5% of the children. Compared to the Movement ABC, the sensitivity of the paediatric judgement was 0.19, Touwen examination 0.62 and DDST 0.52; the negative predictive values were 0.61, 0.74 and 0.69, respectively. CONCLUSION: Paediatric assessment of motor development in 5-y-old very preterm and low-birthweight children generally is not sensitive enough to detect functional motor problems. The Movement ABC should be added to the assessment of the motor development of very preterm and low-birthweight children at 5 y of age.