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OBJECTIVE: To investigate whether maternal paracetamol use in early pregnancy is associated with cerebral palsy (CP) in offspring. STUDY DESIGN: We conducted a registry and biobank-based case-control study with mother-child pairs. We identified CP cases (n = 322) born between 1995 and 2014 from a nationwide CP-registry. Randomly selected controls (n = 343) and extra preterm controls (n = 258) were obtained from a birth registry. For each mother, a single serum sample from early pregnancy (gestation weeks 10-14) was retrieved from a biobank and analyzed for serum concentrations of paracetamol, categorized into unexposed (<1 ng/ml), mildly exposed (1-100 ng/ml), and highly exposed (>100 ng/ml), and in quartiles. Analyses were performed using logistic regression and adjusted for potential confounders. Separate analyses were conducted including only those children born preterm and only those born term. RESULTS: Of the 923 participants, 36.8% were unexposed, 53.2% mildly exposed, and 10% highly exposed to paracetamol. Overall, prenatal exposure to paracetamol was not associated with CP. Sensitivity and subgroup analyses showed no clear associations between paracetamol and CP across strata of term/preterm birth as well as subtypes of CP. CONCLUSIONS: The present study does not support an association between intrauterine exposure to paracetamol in early pregnancy and the risk of CP. However, it is important to stress that the exposure estimate is based on a single serum sample.

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OBJECTIVE: To survey the incidence of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) by gestational age and to report the impact on mortality and neurodevelopmental outcome in very preterm/very low birthweight infants. STUDY DESIGN: This was a population-based cohort study of 1927 very preterm/very low birthweight infants born in 2014-2016 and admitted to Flemish neonatal intensive care units. Infants underwent standard follow-up assessment until 2 years corrected age with the Bayley Scales of Infant and Toddler Development and neurological assessments. RESULTS: No brain lesion was present in 31% of infants born at <26 weeks of gestation and 75.8% in infants born at 29-32 weeks of gestation. The prevalence of low-grade IVH/PVL (grades I and II) was 16.8% and 12.7%, respectively. Low-grade IVH/PVL was not related significantly to an increased likelihood of mortality, motor delay, or cognitive delay, except for PVL grade II, which was associated with a 4-fold increase in developing cerebral palsy (OR, 4.1; 95% CI, 1.2-14.6). High-grade lesions (III-IV) were present in 22.0% of the infants born at <26 weeks of gestational and 3.1% at 29-32 weeks of gestation, and the odds of death were ≥14.0 (IVH: OR, 14.0; 95% CI, 9.0-21.9; PVL: OR, 14.1; 95% CI, 6.6-29.9). PVL grades III-IV showed an increased odds of 17.2 for motor delay and 12.3 for cerebral palsy, but were not found to be associated significantly with cognitive delay (OR, 2.9; 95% CI, 0.5-17.5; P = .24). CONCLUSIONS: Both the prevalence and severity of IVH/PVL decreased significantly with advancing gestational age. More than 75% of all infants with low grades of IVH/PVL showed normal motor and cognitive outcome at 2 years corrected age. High-grade PVL/IVH has become less common and is associated with adverse outcomes.

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OBJECTIVE: To investigate the associations between maternal or paternal age at the time of delivery and offspring's risk for cerebral palsy (CP) in California. STUDY DESIGN: We conducted a population-based, case-control study that included 8736 singleton CP cases and 90 250 singleton controls, matched by sex and birth year, selected from California birth certificate records from 1994 to 2010. We estimated OR and 95% CIs for CP diagnosis according to maternal and paternal age recorded on the birth certificates. Causal mediation analysis was performed to estimate direct and indirect effects of parental ages on CP with preterm delivery as a potential mediator. RESULTS: Children born to younger mothers (≤19 years) or older mothers (35-39 years; ≥40 years) had a greater risk of CP compared with children of mothers aged 25-29 years (ORs ranging from 1.13 to 1.59). Compared with paternal age 25-29 years, older paternal age (40-44 years; ≥45 years) also was associated with an increased risk for CP independent of maternal age. When analyzing jointly using both parents of ages 20-34 years as the reference, the greatest risk was estimated for older parents (≥35 years). Preterm birth was estimated to mediate 19%-34% of the total effects between maternal or paternal age and offspring CP risk. CONCLUSIONS: Young maternal age and an older age in either or both parents were associated with a greater risk of CP in their children. Although preterm birth was a mediator, additional factors related to parental age need further exploration to explain risk of CP.

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BACKGROUND: Little information on gross motor function of congenital Zika syndrome (CZS) children is available. OBJECTIVES: To evaluate gross motor function in CZS children aged up to 3 years, and its associated factors and changes in a minimum interval of 6 months. METHODS: One hundred children with CZS and cerebral palsy (36 with confirmed and 64 with presumed CZS) were evaluated with the Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure (GMFM-88/GMFM-66). Forty-six were reevaluated. Wilcoxon tests, Wilcoxon tests for paired samples, percentile scores, and score changes were performed. RESULTS: Clinical and socioeconomic characteristics (except maternal age), GMFM scores and GMFCS classification of confirmed and probable cases, which were analyzed together, were similar. The mean age was 25.6 months (±5.5); the median GMFM-88 score was 8.0 (5.4-10.8); and the median GMFM-66 score was 20.5 (14.8-23.1); 89% were classified as GMFCS level V. Low economic class, microcephaly at birth, epilepsy, and brain parenchymal volume loss were associated with low GMFM-66 scores. The median GMFM-66 percentile score was 40 (20-55). On the second assessment, the GMFM-66 scores in two GMFCS level I children and one GMFCS level IV child improved significantly. In one GMFCS level III child, one GMFCS level IV child, and the group of GMFCS level V children, no significant changes were observed. CONCLUSIONS: Almost all CZS children had severe cerebral palsy; in the third year of life, most presented no improvement in gross motor function and were likely approaching their maximal gross motor function potential.

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AIM: To evaluate the occurrence of developmental defects of enamel (DDE) in children and adolescents with Cerebral Palsy (CP) and to analyze the effect of common factors in the etiology of CP on the occurrence of DDE. METHODS: A case-control study was carried out using the modified DDE index to classify enamel defects. The study group (SG) consisted of 45 participants with CP aged between three and 14 years. The control group (CG) consisted of 88 normotypical schoolchildren, paired by gender and age group. Caregivers answered a questionnaire on their socioeconomic status and medical history. The Chi-square tests, bivariate and multivariate analysis were performed (level significance < 0.05). RESULTS: The occurrence of DDE in SG and CG was 60% and 64.8%, respectively (p value = 0.726). The most frequent defect observed in SG was diffuse opacity (44.4%), followed by demarcated opacity (26.7%) and enamel hypoplasia (2.2%). No difference was observed in the defect's distribution among both groups (p value = 0.083). For SG, the bivariate analysis revealed a statically significant association between the presence of DDE and age group 7-14 years old and maternal schooling below 11 years. After adjusting for confounding variables, age, family income and maternal schooling were not associated with DDE. CONCLUSION: In conclusion, the occurrence of DDE was high and similar in both groups. The pre, peri or post-natal factors associated with CP were not significant for the presence of DDE.

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OBJECTIVE: To assess whether chorioamnionitis is associated with cerebral palsy (CP) or death at 2 years' corrected age in infants born before 32 weeks of gestation after spontaneous birth. STUDY DESIGN: EPIPAGE-2 is a national, prospective, population-based cohort study of children born preterm in France in 2011; recruitment periods varied by gestational age. This analysis includes infants born alive after preterm labor or preterm premature rupture of membranes from 240/7 to 316/7 weeks of gestation. We compared the outcomes of CP, death at 2 years' corrected age, and "CP or death at age 2" according to the presence of either clinical chorioamnionitis or histologic chorioamnionitis. All percentages were weighted by the duration of the recruitment period. RESULTS: Among 2252 infants born alive spontaneously before 32 weeks of gestation, 116 (5.2%) were exposed to clinical chorioamnionitis. Among 1470 with placental examination data available, 639 (43.5%) had histologic chorioamnionitis. In total, 346 infants died before 2 years and 1586 (83.2% of the survivors) were evaluated for CP at age 2 years. CP rates were 11.1% with and 5.0% without clinical chorioamnionitis (P = .03) and 6.1% with and 5.3% without histologic chorioamnionitis (P = .49). After adjustment for confounding factors, CP risk rose with clinical chorioamnionitis (aOR 2.13, 95% CI 1.12-4.05) but not histologic chorioamnionitis (aOR 1.21, 95% 0.75-1.93). Neither form was associated with the composite outcome "CP or death at age 2." CONCLUSIONS: Among infants very preterm born spontaneously, the risk of CP at a corrected age of 2 years was associated with exposure to clinical chorioamnionitis but not histologic chorioamnionitis.

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OBJECTIVE: To assess the gross motor development of children with presumed congenital Zika virus (ZIKV) infection over the first 2 years of their lives. METHODS: Seventy-seven children were assessed at the median ages of 11, 18, and 24 months, using the evaluative instrument Gross Motor Function Measure (GMFM-66). At the third assessment, the children with diagnoses of cerebral palsy (CP) were classified by severity through the Gross Motor Function Classification System (GMFCS) and stratified by topography indicating the predominantly affected limbs. With these instruments in combination and using the motor development curves as reference, the rate of development and functional ability were estimated. RESULTS: At 2 years of age, all children had the diagnosis of CP. Seventy-four (96.1%) presented gross motor skills similar to those of children aged 4 months or younger, according to the World Health Organization's standard. The GMFM-66 median score among the 73 (94.8%) children with quadriplegia and GMFCS level V showed significant change between 11 and 18 months (p < 0.001) and between 11 and 24 months (p < 0.001). No significant difference (p = 0.076) was found between 18 and 24 months. CONCLUSION: Despite showing some gross motor progress during the initial 18 months of life, these children with presumed congenital ZIKV infection and CP experienced severe motor impairment by 2 years of age. According to the motor development curves, these children with quadriplegia have probably already reached about 90% of their motor development potential.

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Preterm birth is one of the main country health indicators. It is associated with high mortality and significant morbidity in preterm newborns with cerebral palsy and potential long-term neurodevelopmental disabilities like cognitive and learning problems. The main lesions could be: a) white matter injuries, generally associated with cortical and other regions of grey matter neuronal-axonal disturbances; b) intracranial hemorrhage that includes germinal matrix, intraventricular and parenchymal, c) cerebellum injuries. The white matter lesions include cystic and non-cystic (with microscopic focal necrosis) periventricular leukomalacia and non-necrotic diffuse white matter injury. Multiple etiologic factors are associated with these injuries. Anatomical and physiological characteristics of periventricular vascular structures predispose white matter to cerebral ischemia and, interacting with infection/inflammation factors, activate microglia, generating oxidative stress (mediated by free oxygen and nitrogen radicals), pro-inflammatory cytokine and glutamate toxicity, energetic failure and vascular integrity disturbances. All these factors lead to a particular vulnerability of pre-oligodendrocytes that will affect myelination. Hypoxia-ischemia also may produce selective neuronal necrosis in different cerebral regions. Germinal matrix is a highly vascularized zone beneath ependymal or periventricular region that constitutes a capillary bed with a particular structural fragility that predispose it to hemorrhage.

Los nacimientos prematuros son uno de los principales indicadores de salud de un país. Están asociados a una alta mortalidad e importante morbilidad en niños con parálisis cerebral y otros trastornos del neurodesarrollo, incluyendo problemas cognitivos y del aprendizaje. Los principales tipos de lesión encefálica en los recién nacidos prematuros son: a) las lesiones de la sustancia blanca, generalmente asociadas a alteraciones neuronales y axonales en la corteza cerebral y otras zonas de sustancia gris; b) hemorragias intracraneanas que incluyen las de la matriz germinal, intraventriculares e intraparenquimatosas y c) del cerebelo. Las lesiones de sustancia blanca incluyen la leucomalacia periventricular quística, no quística (con focos de necrosis microscópicos) y lesiones difusas de sustancia blanca, no necróticas. Estas lesiones tienen múltiples factores etiológicos. Las características anatómicas y fisiológicas de las estructuras vasculares periventriculares predisponen a la sustancia blanca a ser muy vulnerable a las situaciones de isquemia cerebral y, en interacción con factores infecciosos/inflamatorios, activan a las microglías generando estrés oxidativo (por liberación de radicales libres del oxígeno y del nitrógeno), liberación de citoquinas proinflamatorias, liberación de glutamato, fallo energético y alteración de la integridad vascular. Todo lo anteriormente mencionado genera una particular vulnerabilidad de los pre-oligodendrocitos que termina alterando la mielinización. La hipoxia-isquemia también puede producir necrosis neuronal selectiva en diferentes regiones encefálicas. La matriz germinal es un área altamente vascularizada en la región subependimaria periventricular con una estructura capilar muy frágil que la predispone a las hemorragias.

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Los nacimientos prematuros son uno de los principales indicadores de salud de un país. Están asociados a una alta mortalidad e importante morbilidad en niños con parálisis cerebral y otros trastornos del neurodesarrollo, incluyendo problemas cognitivos y del aprendizaje. Los principales tipos de lesión encefálica en los recién nacidos prematuros son: a) las lesiones de la sustancia blanca, generalmente asociadas a alteraciones neuronales y axonales en la corteza cerebral y otras zonas de sustancia gris; b) hemorragias intracraneanas que incluyen las de la matriz germinal, intraventriculares e intraparenquimatosas y c) del cerebelo. Las lesiones de sustancia blanca incluyen la leucomalacia periventricular quística, no quística (con focos de necrosis microscópicos) y lesiones difusas de sustancia blanca, no necróticas. Estas lesiones tienen múltiples factores etiológicos. Las características anatómicas y fisiológicas de las estructuras vasculares periventriculares predisponen a la sustancia blanca a ser muy vulnerable a las situaciones de isquemia cerebral y, en interacción con factores infecciosos/inflamatorios, activan a las microglías generando estrés oxidativo (por liberación de radicales libres del oxígeno y del nitrógeno), liberación de citoquinas proinflamatorias, liberación de glutamato, fallo energético y alteración de la integridad vascular. Todo lo anteriormente mencionado genera una particular vulnerabilidad de los pre-oligodendrocitos que termina alterando la mielinización. La hipoxia-isquemia también puede producir necrosis neuronal selectiva en diferentes regiones encefálicas. La matriz germinal es un área altamente vascularizada en la región subependimaria periventricular con una estructura capilar muy frágil que la predispone a las hemorragias.

Preterm birth is one of the main country health indicators. It is associated with high mortality and significant morbidity in preterm newborns with cerebral palsy and potential long-term neurodevelopmental disabilities like cognitive and learning problems. The main lesions could be: a) white matter injuries, generally associated with cortical and other regions of grey matter neuronal-axonal disturbances; b) intracranial hemorrhage that includes germinal matrix, intraventricular and parenchymal, c) cerebellum injuries. The white matter lesions include cystic and non-cystic (with microscopic focal necrosis) periventricular leukomalacia and non-necrotic diffuse white matter injury. Multiple etiologic factors are associated with these injuries. Anatomical and physiological characteristics of periventricular vascular structures predispose white matter to cerebral ischemia and, interacting with infection/inflammation factors, activate microglia, generating oxidative stress (mediated by free oxygen and nitrogen radicals), pro-inflammatory cytokine and glutamate toxicity, energetic failure and vascular integrity disturbances. All these factors lead to a particular vulnerability of pre-oligodendrocytes that will affect myelination. Hypoxia-ischemia also may produce selective neuronal necrosis in different cerebral regions. Germinal matrix is a highly vascularized zone beneath ependymal or periventricular region that constitutes a capillary bed with a particular structural fragility that predispose it to hemorrhage.

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ABSTRACT Introduction: Cerebral palsy involves loss or impairment of motor function attributed to non-progressive disturbances occurring in the developing fetal or infant brain. Self-inflicted oral trauma is a recurrent parafunctional habit in individuals with cerebral palsy. Objective: Describe two treatment modes for self-inflicted oral trauma in a 6-year-old male patient with cerebral palsy over a 5-year follow-up period. Case presentation: The child had been having pain due to injuries to the mouth floor and lingual frenum regions. Initially, low-level laser therapy was applied to accelerate the healing process of the wounds. Five years later, the child started to present worse oral injuries and placement of a fixed oral appliance was proposed. Intraoral examination showed that the wounds had healed completely in response to the oral appliance. Conclusions: Different therapies may be useful to control the recurrence of self-inflicted oral injuries(AU)

RESUMEN Introducción: La parálisis cerebral provoca una pérdida o deterioro de la función motora atribuida a trastornos no progresivos del desarrollo cerebral fetal o infantil. La lesión autoinfligida es un hábito parafuncional recurrente en personas con parálisis cerebral. Objetivo: Describir dos modalidades de tratamiento para las lesiones autoinfligidas en un niño de 6 años de edad con parálisis cerebral durante un periodo de seguimiento de 5 años. Presentación del caso: El niño presentaba dolor debido a lesiones en la región del suelo de la boca y el frenillo lingual. Inicialmente se aplicó terapia con láser de baja intensidad para acelerar el proceso de cicatrización de las heridas. Cinco años más tarde el niño empezó a presentar lesiones bucales más severas, por lo que se propuso la colocación de un dispositivo oral fijo. El examen intraoral mostró que las lesiones habían cicatrizado completamente en respuesta al dispositivo oral instalado. Conclusiones: Diferentes terapias pueden ser útiles para controlar la recurrencia de las lesiones orales autoinfligidas(AU)

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