Risk Of Cerebral Palsy In Children Research Articles

Association between gestational levels of toxic metals and essential elements and cerebral palsy in children.

Cerebral palsy (CP) is the most common motor disability in childhood, but its causes are only partly known. Early-life exposure to toxic metals and inadequate or excess amounts of essential elements can adversely affect brain and nervous system development. However, little is still known about these as perinatal risk factors for CP. This study aims to investigate the associations between second trimester maternal blood levels of toxic metals, essential elements, and mixtures thereof, with CP diagnoses in children. In a large, population-based prospective birth cohort (The Norwegian Mother, Father, and Child Cohort Study), children with CP diagnoses were identified through The Norwegian Patient Registry and Cerebral Palsy Registry of Norway. One hundred forty-four children with CP and 1,082 controls were included. The relationship between maternal blood concentrations of five toxic metals and six essential elements and CP diagnoses were investigated using mixture approaches: elastic net with stability selection to identify important metals/elements in the mixture in relation to CP; then logistic regressions of the selected metals/elements to estimate odds ratio (OR) of CP and two-way interactions among metals/elements and with child sex and maternal education. Finally, the joint effects of the mixtures on CP diagnoses were estimated using quantile-based g-computation analyses. The essential elements manganese and copper, as well as the toxic metal Hg, were the most important in relation to CP. Elevated maternal levels of copper (OR = 1.40) and manganese (OR = 1.20) were associated with increased risk of CP, while Hg levels were, counterintuitively, inversely related to CP. Metal/element interactions that were associated with CP were observed, and that sex and maternal education influenced the relationships between metals/elements and CP. In the joint mixture approach no significant association between the mixture of metals/elements and CP (OR = 1.00, 95% CI = [0.67, 1.50]) was identified. Using mixture approaches, elevated levels of copper and manganese measured in maternal blood during the second trimester could be related to increased risk of CP in children. The inverse associations between maternal Hg and CP could reflect Hg as a marker of maternal fish intake and thus nutrients beneficial for foetal brain development.

Maternal obesity and risk of cerebral palsy in children: a systematic review and meta‐analysis

Several studies have examined the links between maternal obesity and the risk of cerebral palsy (CP) in children, with inconsistent results. The aim of our study was to investigate whether maternal obesity is associated with increased risk of CP in offspring by using meta-analysis. PubMed and Web of Science were searched until August 2017. Observational studies relevant to the maternal obesity and risk of CP in children were extracted and compiled. Meta-analyses were performed for different obesity levels and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were reported. A total of five cohort studies involving 12324 cases and 7919288 participants were included in our meta-analysis. The pooled crude and adjusted ORs (95% CIs) were 1.65 (1.38-1.98) and 1.51 (1.24-1.84) respectively. Additionally, the pooled OR (95% CI) for CP in offspring in relation to maternal obesity class I (body mass index [BMI] 30.0-34.9), class II (BMI 35.0-39.9), and class III (BMI≥40.0) compared with normal weight during prepregnancy or pregnancy was 1.31 (1.15-1.50), 1.65 (1.34-2.02), and 2.37 (1.91-2.94) respectively. This meta-analysis demonstrated that increasing grades of maternal obesity are associated with a higher risk of CP in offspring. Meta-analysis demonstrates a significant positive association between maternal obesity and the risk of cerebral palsy (CP) in children. Subgroup analysis indicates that higher grades of maternal obesity are associated with increasing risk of CP.

Cerebral palsy among children of immigrants in Denmark and the role of socioeconomic status

Introduction The proportion of births by immigrants has been increasing rapidly in Denmark during the last decades. Children of immigrants have higher risk of being born preterm and with low birth weight, which are strong determinants for cerebral palsy (CP), compared with children born to Danish women. Objective To investigate differences in risk of CP between children of Danish-born mothers and children of immigrants and to explore to what degree socioeconomic status mediates the potential association between maternal immigrant status and CP. Method We conducted a register-based study including 1,274,653 children born in Denmark between 1981 and 2007 of whom 2807 had CP (2.2 per 1000). Mothers’ country of origin derived from nationwide registers was used to determine the mothers’ immigrant status. Children with CP were identified by linkage with the Danish National Cerebral Palsy Registry that includes all pre- and perinatal acquired CP cases that have been validated by neuro-pediatricians at age one to six years. Odds ratios (OR) of CP according to maternal immigrant status were estimated by using multiple logistic regression. We studied whether a potential association was explained by maternal educational level or household income by performing mediation analysis applying a counterfactual approach. Results In this study, 141,540 (11.1%) were immigrants; 3.5% from Western and 7.6% Non-Western countries. Children of immigrants from Western and Non-Western countries had lower risk of unilateral spastic CP than children of Danish mothers; OR = 0.6 (95% VI: 0.4–0.9) and OR = 0.8 (95% CI: 0.6–1.0), respectively. Children of Non-Western immigrants had higher risk of bilateral spastic CP compared with children of Danish mothers; OR = 1.3 (95% CI: 1.1–1.5), and it was the Turkish (OR = 1.7 (95%CI: 1.2–2.4) and Pakistani (OR = 1.7 (95% CI: 1.0–2.9) immigrants that accounted for the increased risk. Results from mediation analysis indicated that the association between maternal immigrant status and bilateral spastic CP was not mediated by socioeconomic status. Due to insufficient statistical power, the mediation analysis was not applicable for unilateral spastic CP. Conclusion Our results show that the risk of CP in children born in Denmark between 1981 and 2007 differed according to maternal country of origin. The higher risk of bilateral spastic CP in children of Non-Western immigrants, in particular Turkish and Pakistani, does not seem to be explained by inequality in education or household income. Future research should investigate whether the increased risk is caused by consanguineous parenthood, lifestyle factors, or suboptimal prenatal and obstetric care for immigrants.

Intake of Caffeinated Soft Drinks before and during Pregnancy, but Not Total Caffeine Intake, Is Associated with Increased Cerebral Palsy Risk in the Norwegian Mother and Child Cohort Study

Background: Postnatal administration of caffeine may reduce the risk of cerebral palsy (CP) in vulnerable low-birth-weight neonates. The effect of antenatal caffeine exposure remains unknown.Objective: We investigated the association of intake of caffeine by pregnant women and risk of CP in their children.Methods: The study was based on The Norwegian Mother and Child Cohort Study, comprising >100,000 live-born children, of whom 222 were subsequently diagnosed with CP. Mothers reported their caffeine consumption in questionnaires completed around pregnancy week 17 (102,986 mother–child pairs), week 22 (87,987 mother–child pairs), and week 30 (94,372 mother–child pairs). At week 17, participants were asked about present and prepregnancy consumption. We used Cox regression models to estimate associations between exposure [daily servings (1 serving = 125 mL) of caffeinated coffee, tea, and soft drinks and total caffeine consumption] and CP in children, with nonconsumers as the reference group. Models included adjustment for maternal age and education, medically assisted reproduction, and smoking, and for each source of caffeine, adjustments were made for the other sources.Results: Total daily caffeine intake before and during pregnancy was not associated with CP risk. High consumption (≥6 servings/d) of caffeinated soft drinks before pregnancy was associated with an increased CP risk (HR: 1.9; 95% CI: 1.2, 3.1), and children of women consuming 3–5 daily servings of caffeinated soft drinks during pregnancy weeks 13–30 also had an increased CP risk (HR: 1.7; 95% CI: 1.1, 2.8). A mean daily consumption of 51–100 mg caffeine from soft drinks during the first half of pregnancy was associated with a 1.9-fold increased risk of CP in children (HR: 1.9; 95% CI: 1.1, 3.6).Conclusions: Maternal total daily caffeine consumption before and during pregnancy was not associated with CP risk in children. The observed increased risk with caffeinated soft drinks warrants further investigation.

Assessing the Risk of Cerebral Palsy in Children Born after Assisted Conception – The Role of Multiple Pregnancy and Preterm Delivery / Procena rizika od cerebralne paralize kod dece začete vantelesnim oplođenjem – uloga višestruke trudnoće i prevremenog rođenja

SUMMARY For more than three decades, assisted reproductive techniques (ART) have been used as effective treatments to overcome infertility. Since then, numerous studies have been focused on different aspects of long-term health and development of children born after assisted conception. The aim of this paper is to summarize new data on multiple pregnancy and preterm delivery as one of the risk factors which might increase the risk of developing cerebral palsy (CP) in children born after assisted conception. A comprehensive search of eight databases retrieved 108 papers, 10 of which met inclusion criteria and were relevant for this review. Despite the dissimilarities in methodological and analytic approaches in the selected studies, in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are generally considered safe, still there is an ongoing discussion whether multiple pregnancy and preterm delivery increase or do not increase the risk of CP in children born after assisted conception. All information about possible adverse maternal and/or infant outcomes should be made available to the couples seeking ART treatment

Parental infertility and cerebral palsy in children

Children born after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have been reported to have a higher risk of cerebral palsy (CP), perhaps due to the higher frequency of preterm birth, multiple births or vanishing embryo in the pregnancies. However, it has been suggested that the underlying infertility may be part of the pathway. In this study, we examined whether untreated subfecundity (measured by time to pregnancy) or infertility treatment was associated with an increased risk of CP in the offspring. Using the Danish National Birth Cohort (1997-2003), we compared children born after 0-2 months of waiting time to pregnancy (n = 35 848) with those born after a time to pregnancy of 3-5 months (n = 15 361), 6-12 months (n = 11 528) and >12 months (n = 7387), as well as those born after IVF/ICSI (n = 3617), ovulation induction with or without intrauterine insemination (n = 3000), and unplanned pregnancies (n = 13 462). CP cases were identified through the Danish CP Register. In total, 165 (0.18%) children were diagnosed with CP in the entire cohort. We found no significant association between time to pregnancy and the risk of CP in children conceived spontaneously. Children born after IVF/ICSI had an increased risk of CP, even after adjustment for preterm birth and multiplicity (hazard ratio 2.30, 95% confidence interval 1.12-4.73). Subfecundity per se did not appear to be associated with the risk of CP in children, whereas being born after IVF/ICSI conferred an increased risk.

Multiplicity and early gestational age contribute to an increased risk of cerebral palsy from assisted conception: a population-based cohort study

This paper assesses the risk of cerebral palsy (CP) in children born after assisted conception compared with children born after natural conception (NC). This population based follow-up study included all 588,967 children born in Denmark from 1995 to 2003. Assisted conception was defined as IVF, with or without ICSI, and ovulation induction (OI), with or without subsequent insemination. There were 33 139 (5.6%) children born in Denmark from 1995 to 2003 as a result of assisted conception and through to June 2009, 1146 (0.19%) children received a CP diagnosis. Children born after assisted conception had an increased risk of a CP diagnosis, crude hazard rate ratio (HRR) 1.90 (95% CI: 1.57-2.31) compared with NC children. Divided into IVF and OI children compared with NC children, the risk was HRR 2.34 (95% CI: 1.81-3.01) and HRR 1.55 (95% CI: 1.17-2.06), respectively. When we included the intermediate factors multiplicity and gestational age in multivariate models, the risk of CP in assisted conception disappeared. In general, children with CP born after assisted conception had similar CP subtypes and co-morbidities as children with CP born after NC. The risk of CP is increased after both IVF and OI. The increased risk of CP in children born after assisted conception, and in particular IVF, is strongly associated with the high proportion of multiplicity and preterm delivery in these pregnancies. A more widespread use of single embryo transfer warrants consideration to enhance the long-term health of children born after IVF.

Maternal Infection and Cerebral Palsy in Infants of Normal Birth Weight

Context. —Exposure to maternal or placental infection is related to risk of preterm birth and, in premature infants, of brain lesions predictive of cerebral palsy (CP). Few studies have investigated whether maternal infection is associated with risk of CP in children of normal birth weight. Objective. —To investigate maternal infection during the admission for delivery as a possible risk factor for CP in infants born weighing 2500 g or more. Design. —Population-based case-control study. Setting. —All hospitals in 4 northern California counties, 1983 through 1985. Participants. —A total of 46 children with disabling spastic CP who had no recognized prenatal brain lesions and 378 randomly selected control children weighing 2500 g or more at birth and surviving to age 3 years. Main Outcome Measures. —Disabling spastic CP and signs of neonatal morbidity. Results. —Maternal fever exceeding 38°C in labor was associated with increased risk of unexplained CP (odds ratio [OR], 9.3; 95% confidence interval [CI], 2.7-31.0), as was a clinical diagnosis of chorioamnionitis. One or more indicators of maternal infection were present in 2.9% of control children, 22% of children with CP (OR, 9.3; 95% CI, 3.7-23.0), and 37% of those with the spastic quadriplegic subtype of CP (OR, 19.0; 95% CI, 6.5-56.0). Newborns exposed to maternal infection, both cases and controls, had 5-minute Apgar scores below 6 more often than those unexposed. Among children with CP, those born to infected women were more often hypotensive, needed intubation, had neonatal seizures, and received a clinical diagnosis of hypoxic-ischemic encephalopathy. Conclusion. —Intrauterine exposure to maternal infection was associated with a marked increase in risk of CP in infants of normal birth weight. Maternal infection was also linked with low Apgar scores, other evidence of hypertension and need for resuscitation, and neonatal seizures—signs commonly attributed to birth asphyxia.

Maternal Infection and Cerebral Palsy in Infants of Normal Birth Weight

Exposure to maternal or placental infection is related to risk of preterm birth and, in premature infants, of brain lesions predictive of cerebral palsy (CP). Few studies have investigated whether maternal infection is associated with risk of CP in children of normal birth weight. To investigate maternal infection during the admission for delivery as a possible risk factor for CP in infants born weighing 2500 g or more. Population-based case-control study. All hospitals in 4 northern California counties, 1983 through 1985. A total of 46 children with disabling spastic CP who had no recognized prenatal brain lesions and 378 randomly selected control children weighing 2500 g or more at birth and surviving to age 3 years. Disabling spastic CP and signs of neonatal morbidity. Maternal fever exceeding 38 degrees C in labor was associated with increased risk of unexplained CP (odds ratio [OR], 9.3; 95% confidence interval [CI], 2.7-31.0), as was a clinical diagnosis of chorioamnionitis. One or more indicators of maternal infection were present in 2.9% of control children, 22% of children with CP (OR, 9.3; 95% CI, 3.7-23.0), and 37% of those with the spastic quadriplegic subtype of CP (OR, 19.0; 95% CI, 6.5-56.0). Newborns exposed to maternal infection, both cases and controls, had 5-minute Apgar scores below 6 more often than those unexposed. Among children with CP, those born to infected women were more often hypotensive, needed intubation, had neonatal seizures, and received a clinical diagnosis of hypoxic-ischemic encephalopathy. Intrauterine exposure to maternal infection was associated with a marked increase in risk of CP in infants of normal birth weight. Maternal infection was also linked with low Apgar scores, other evidence of hypotension [corrected] and need for resuscitation, and neonatal seizures-signs commonly attributed to birth asphyxia.