Increasing prevalence of cerebral palsy in children born very preterm in Denmark.

AIM: To analyse the rising prevalence of cerebral palsy (CP) in children born preterm in Denmark. METHOD: We included all live-born children born preterm in Denmark from 1997 to 2013. The prevalence of CP in children born preterm was categorized by gestational age and correlated with neonatal mortality and changes in clinical factors. RESULTS: Among 70 876 children, 824 (1.2%) had CP. The overall CP prevalence in children born preterm decreased substantially until 2001, from when it increased annually by 2.8% (95% confidence interval 0.6-5.0). When categorized, the prevalence only increased significantly in children born very preterm (gestational weeks 28-31). Neonatal mortality rates decreased steadily at all gestational ages during the entire study period. Clinical factors that changed during the study period were increasing numbers of high-risk pregnancies, maternal obesity, emergency caesarean sections, neonatal admissions, and usage of assisted ventilation. INTERPRETATION: The increasing prevalence of CP in children born preterm was driven by the subgroup born very preterm and matched their decrease in neonatal mortality. In similar population studies, decreased mortality was not followed by increased CP prevalence. An increase in clinical risk factors was unlikely to explain our findings, but more active neonatal life support may have played a role.

Impact of a National Follow-Up Program on the Age at Diagnosis for Cerebral Palsy.

BACKGROUND: The Danish National Cerebral Palsy Follow-up Program (CPOP) is a nationwide program offering standardized treatment to all children with cerebral palsy (CP) since 2004. We aimed to establish if its implementation had a positive impact on the diagnostic age of CP. METHODS: Children with validated CP diagnoses were identified from the Danish Cerebral Palsy Registry and the CPOP. We then compared the age at diagnosis and the clinical features of children with CP born in 2000 to 2003 with those born in 2010 to 2013. Differences in time to diagnosis were compared using log-rank test. RESULTS: The age at diagnosis was not different in the two periods (P = 0.23), with identical overall median diagnostic ages at 13.0 months. The number of children with severe motor disability decreased markedly from 47.5% in 2000 to 2003 to 32.0% in 2010 to 2013 (P < 0.001). There was increased usage of cerebral magnetic resonance imaging; however, this was not associated with lower diagnostic age. CONCLUSIONS: The diagnostic age of CP did not change after the implementation of a nationwide follow-up program, offering standardized and early assessments. However, central clinical aspects also changed significantly between the periods compared, which possibly affected the diagnostic age.

The magnitude rather than the rate of decline in fetal growth is a stronger risk factor for perinatal mortality in term infants.

BACKGROUND: Prenatal diagnosis of an infant suspected of having fetal growth restriction is important because of its strong association with perinatal mortality and morbidity. The current Delphi consensus criteria include a decline of >50th percentiles in fetal growth when diagnosing late fetal growth restriction; however, the evidence underpinning this criterion is limited. OBJECTIVE: This study aimed to analyze the relationships among the magnitude of decline in fetal growth and stillbirth, perinatal mortality, and adverse neonatal outcomes. STUDY DESIGN: This cohort study of 15,861 pregnancies was conducted at the Mater Mother's Hospital in Brisbane, Australia. The decline in fetal growth was calculated as a drop in either estimated fetal weight or abdominal circumference percentiles between 2 ultrasound scans performed after 18 weeks of gestation. Relationships between declining fetal growth and the outcomes were, firstly, analyzed as a continuous variable and, if significant, further assessed with the rate of decline and different magnitudes of decline, compared to the referent category (change in growth of ±10 percentiles between scans). The 3 categories of growth decline were >10th to <25th percentiles, ≤25th to <50th percentiles, and ≥50th percentiles. Associations were analyzed by logistic regressions. The primary study outcomes were stillbirth and perinatal mortality (composite of stillbirth and neonatal death). The secondary outcomes were birth of a small-for-gestational-age infant (birthweight of <10th percentile for gestation), emergency cesarean delivery for nonreassuring fetal status, and composite severe neonatal morbidity. RESULTS: The risks of stillbirth and perinatal mortality increased significantly by 2.6% (0.4%-4.6%) and 2.8% (1.0%-4.5%), respectively, per 1 percentile decline in fetal growth. In addition, the odds of stillbirth (adjusted odds ratio, 3.68 (1.32-10.24) and perinatal mortality (4.44) (1.82-10.84)) compared to the referent group were significantly increased only when the decline was ≥50th percentiles, regardless of birthweight. Furthermore, none of the primary outcomes were significantly associated with the rate of growth decline. The risk of a small-for-gestational-age infant increased by 2.4% (2.2%-2.7%) for every percentile decline. Conversely, reduced fetal growth was not associated with emergency cesarean delivery for nonreassuring fetal status or severe neonatal morbidity. CONCLUSION: Our results supported the use of a ≥50th percentile decline in fetal growth as a criterion for identifying infants at risk of late fetal growth restriction. This cutoff also identified fetuses at high risk of perinatal mortality, regardless of birthweight and rate of growth decline. Our findings may guide obstetrical practice by alerting clinicians to the importance of incorporating the magnitude of fetal growth decline into antenatal counseling and decisions regarding the timing of birth.

First-trimester biomarkers and the risk of cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is the most common severe motor disability and a manifestation of early brain damage. AIMS: To analyze if abnormal levels of first-trimester biomarkers were associated with CP. Furthermore, to investigate their clinical applicability in early predicting of CP. STUDY DESIGN: Nationwide cohort study. SUBJECTS: We included 258.057 singleton live births, born during 2008-2013 with completed first-trimester assessments. OUTCOME MEASURES: Data on beta subunit of human chorionic gonadotropin (beta-hCG), pregnancy-associated plasma protein-A (PAPP-A), nuchal translucency thickness, and biparietal diameter (BPD) were converted to multiple of the medians (MoM). Associations were analyzed by comparing mean and extreme levels between pregnancies with and without CP. All CP diagnoses were validated by trained neuropediatricians. Logistic regression was used to create an early prediction model. RESULTS: The mean beta-hCG value was significantly lower in pregnancies with CP (0.96MoM [95% CI 0.91-1.02] vs 1.04MoM [1.04-1.04], p = 0.01) and the mean PAPP-A value tended to be lower (0.96MoM [0.91-1.01] vs 1.01MoM [1.00-1.01], p = 0.07). Moreover, fetuses that developed CP more likely had a BPD measurement below the fifth percentile (7.5% vs 5%, p = 0.045). The final prediction model had poor discrimination. CONCLUSIONS: Pregnancies with CP tend to have lower values of beta-hCG and PAPP-A in the first trimester, however, the associations are mediated differently. Nonetheless, abnormal levels of the most common first-trimester biomarkers only have weak associations with CP; resulting in inadequate predictive abilities when included in an early prediction model.

[Magnesium sulphate treatment decreases the risk of cerebral palsy after preterm birth].

Children born preterm have an increased risk of severe morbidity, e.g. cerebral palsy (CP), compared to children born at term. CP cannot be treated, which is why a prophylactic approach is essential, as argued in this review. Six randomised controlled trials (RCTs) have provided data on MgSO4 treatment as CP neuroprotection in preterm birth, including a new RCT from Denmark. Recently, an updated meta-analysis with trial sequential analysis detected a significant neuroprotective effect of MgSO4 treatment in preterm birth. There is now sufficient evidence, that MgSO4 treatment should be used as neuroprotection in preterm birth.

Continuing decline in the prevalence of cerebral palsy in Denmark for birth years 2008-2013.

AIM: To quantify and analyse the prevalence and clinical features of cerebral palsy (CP) in Denmark for birth years 2008-2013 and compare results with previous periods. METHOD: A nationwide register-based study covering all children with a confirmed diagnosis of CP born in Denmark. Information about CP subtype, aetiology and severity was collected from the Cerebral Palsy Follow-up Program and supplemented from medical files. Data from the Danish Medical Birth Register was included, and the results were compared to previous data from the Danish National Cerebral Palsy Register. Prevalence per 1000 live births and proportions were analysed using the Cochran-Armitage test for trend. RESULTS: The period covered 368,618 live births and 636 children with CP, making the overall prevalence for the period 1.73 per 1000 live births. This was significantly lower than the prevalence of 1.99 for the previous period 1999-2007 (p = 0.004). The decline in prevalence between the two periods was mainly due to a decrease in children with bilateral spastic and dyskinetic CP born after 37 gestational weeks. The decline in prevalence was accompanied by a smaller proportion of children with associated impairment. CONCLUSION: We found a decrease in prevalence and severity in CP among Danish children. The decline was most pronounced in children born after 37 gestational weeks with severe subtypes of CP. National guidelines that recommend induction of labour before the completion of week 42 and therapeutic hypothermia for term neonates with hypoxic-ischaemic encephalopathy, may have contributed to the decline.