Saccharomyces boulardii improves the behaviour and emotions of spastic cerebral palsy rats through the gut-brain axis pathway.

BACKGROUND: Cerebral palsy (CP) is a kind of disability that influences motion, and children with CP also exhibit depression-like behaviour. Inflammation has been recognized as a contributor to CP and depression, and some studies suggest that the gut-brain axis may be a contributing factor. Our team observed that Saccharomyces boulardii (S. boulardii) could reduce the inflammatory level of rats with hyperbilirubinemia and improve abnormal behaviour. Both CP and depression are related to inflammation, and probiotics can improve depression by reducing inflammation. Therefore, we hypothesize that S. boulardii may improve the behaviour and emotions of spastic CP rats through the gut-brain axis pathway. METHODS: Our new rat model was produced by resecting the cortex and subcortical white matter. Seventeen-day-old CP rats were exposed to S. boulardii or vehicle control by gastric gavage for 9 days, and different behavioural domains and general conditions were tested. Inflammation was assessed by measuring the inflammatory markers IL-6 and TNF-α. Hypothalamic-pituitary-adrenal (HPA) axis activity was assessed by measuring adrenocorticotropic hormone and corticosterone in the serum. Changes in the gut microbiome were detected by 16S rRNA. RESULTS: The hemiplegic spastic CP rats we made with typical spastic paralysis exhibited depression-like behaviour. S. boulardii treatment of hemiplegic spastic CP rats improves behaviour and general conditions and significantly reduces the level of inflammation, decreases HPA axis activity, and increases gut microbiota diversity. CONCLUSIONS: The model developed in this study mimics a hemiplegic spastic cerebral palsy. Damage to the cortex and subcortical white matter of 17-day-old Sprague-Dawley (SD) rats led to spastic CP-like behaviour, and the rats exhibited symptoms of depression-like behaviour. Our results indicate that S. boulardii might have potential in treating hemiplegic spastic CP rat models or as an add-on therapy via the gut-brain axis pathway.

The effect of different dietary structure on gastrointestinal dysfunction in children with cerebral palsy and epilepsy based on gut microbiota.

BACKGROUND: Gastrointestinal (GI) difficulties are very common among children with cerebral palsy (CP) and comorbid epilepsy. GI function is influenced by dietary structure on gut microbiota. The aim of this study was to compare gut microbiota differences in two dietary groups of this population and examine whether such differences are related to GI dysfunction. METHODS: Forty children with CP and epilepsy were recruited from a social welfare center, including 23 consuming a fluid diet (liquid diet group) and 17 consuming a normal diet (general diet group). Bacterial DNA was extracted from feces, the V3-V4 region of the 16S rRNA gene was amplified from the DNA, and high-throughput sequencing of the amplified sequences was performed. Microbe prevalence levels were compared on multiple phylogenic levels. RESULTS: Gut microbial populations differed substantially between the liquid diet group and general diet group. The only two phyla that differed significantly between the two groups were Bacteroidetes (p = 0.034) and Actinobacteria (p = 0.013). Regarding representation of genera, Prevotella species were selectively predominant in the general diet group (25.849% vs. 3.612% in the liquid diet group, p < 0.001), while Bifidobacterium species were selectively predominant in the liquid diet group (24.929% vs. 12.947% in the general diet group, p = 0.013). The gut microbiota of children in the general diet group contained more butyric acid-producing microbiota which was also common in healthy people (e.g. Lachnoclostridium, Dorea, Ruminococcus, Faecalibacterium, Roseburia, and Coprococcus). The gut microbiota of children in liquid diet group however, were rich in symbiotic pathogenic bacteria (e.g. Collinsella, Alistipes, and Eggerthella). CONCLUSION: The gut microbiota of children with CP and epilepsy consuming a liquid diet had elevated levels of symbiotic pathogens and diminished intestinal barrier protection bacteria, relative to a general diet group. These differences in bacterial microbiota were associated with GI dysfunction symptoms.

Lactobacillus reuteri DSM 17938 and Agave Inulin in Children with Cerebral Palsy and Chronic Constipation: A Double-Blind Randomized Placebo Controlled Clinical Trial.

The main objective was to assess the efficacy of a probiotic (Lactobacillus reuteri DSM 17938), a prebiotic (agave inulin), and a synbiotic on the stool characteristics in children with cerebral palsy and chronic constipation. Thirty-seven children with cerebral palsy and chronic constipation were included. The probiotic group received 1 × 108 colony forming unit (cfu) of L. reuteri DSM 17938 plus placebo, the prebiotic group received 4 g of agave inulin plus placebo, the synbiotic group received L. reuteri DSM 17938 plus agave inulin, and the placebo group received two placebos for 28 days. The probiotic group showed a significant decrease in stool pH (p = 0.014). Stool consistency improved in the prebiotic group (p = 0.008). The probiotic, prebiotic, and synbiotic groups showed a significant improvement in the history of excessive stool retention, the presence of fecal mass in the rectum, and the history of painful defecation. L. reuteri concentration in feces was higher in the probiotic group than in the placebo group (p = 0.001) and showed an inverse correlation with stool pH in the probiotic group (r = -0.762, p = 0.028). This study showed that the use of L. reuteri DSM 17938 and/or agave inulin improved the stool characteristics such as the history of painful defecation and the presence of fecal mass in the rectum against placebo in children with cerebral palsy and chronic constipation.

Empyema necessitatis due to Pseudomonas aeruginosa in a child with cerebral palsy.

Empyema necessitatis (EN) is a rare complication of empyema in which the pleural infection spreads outside the pleural space. Lower airway infections are common among children with cerebral palsy (CP). Although harmless to healthy individuals, Pseudomonas aeruginosa can cause invasive infections, including CP, in immunocompromised hosts. Mycobacterium tuberculosis and Actinomyces spp. have been reported as common causative organisms of EN. However, EN caused by P. aeruginosa has never been reported. We report the case of an 8-year-old girl with CP without tracheotomy who was admitted to our hospital with complaints of fever and increased epileptic seizures. First, she was diagnosed with pneumonia and treated with antibiotics. However, seven days after admission, a palpable mobile mass overlying the lower part of the shoulder blade was noticed. Enhanced magnetic resonance imaging revealed broad high signal area on T2-weighted and diffusion-weighted images, indicating empyema of the left lower lung that had penetrated the pleural wall and spread to the subcutaneous area of the left back. Thus, she was diagnosed with EN. Twelve days after admission, P. aeruginosa was detected from the pus culture. Patients with CP who have chronic lung diseases, such as pneumonia, atelectasis, or empyema, may need careful follow up.

Cerebral palsy and perinatal infection in children born at term.

OBJECTIVE: To investigate the link between infection-related risk factors for cerebral palsy subtypes in children born at term. METHODS: A case-control study was performed in a population-based series of children with cerebral palsy born at term (n=309) matched with a control group (n=618). The cases were divided into cerebral palsy subtypes: spastic hemiplegia, spastic diplegia, spastic tetraplegia, and dyskinetic cerebral palsy. All forms of spastic cerebral palsy were also analyzed together. All records were examined for maternal and neonatal signs of infection. Univariate and adjusted analyses were performed. RESULTS: Infection-related risk factors were shown to be independent risk factors for spastic cerebral palsy in the adjusted analyses. This was especially pronounced in the subgroup with spastic hemiplegia in which bacterial growth in urine during pregnancy (n=11 [7.5%], odds ratio [OR] 4.7, 95% confidence interval [CI] 1.5-15.2), any infectious disease during pregnancy (n=57 [39.0%], OR 2.9, 95% CI 1.7-4.8), severe infection during pregnancy (n=12 [8.2%], OR 15.4, 95% CI 3.0-78.1), antibiotic therapy once during pregnancy (n=33 [22.6%], OR 6.3, 95% CI 3.0-15.2) as well as several times during pregnancy (n=9 [6.2%], OR 15.6, 95% CI 1.8-134.2) constituted strong independent risk factors. However, only neonatal infection (n=11 [9.1%], OR 14.7, 95% CI 1.7-126.5) was independently significantly associated with an increased risk of spastic diplegia and tetraplegia. CONCLUSIONS: Infection-related factors are strong independent risk factors for the subgroup with spastic hemiplegia in children with cerebral palsy born at term. The finding is less pronounced in the subgroups with spastic diplegia or tetraplegia. LEVEL OF EVIDENCE: II.

Microbiologic and histologic characteristics of the extremely preterm infant's placenta predict white matter damage and later cerebral palsy. the ELGAN study.

Inflammatory phenomena seem to contribute to the occurrence of perinatal cerebral white matter damage and CP. The stimulus that initiates the inflammation remains obscure. One thousand two hundred forty-six infants born before the 28th postmenstrual week had a protocol ultrasound scan of the brain read concordantly by two independent sonologists. Eight hundred ninety-nine of the children had a neurologic examination at approximately 24-mo postterm equivalent. The placenta of each child had been biopsied under sterile conditions and later cultured. Histologic slides of the placenta were examined specifically for this study. Recovery of a single microorganism predicted an echolucent lesion, whereas polymicrobial cultures and recovery of skin flora predicted both ventriculomegaly and an echolucent lesion. Diparetic CP was predicted by recovery of a single microorganism, multiple organisms, and skin flora. Histologic inflammation predicted ventriculomegaly and diparetic CP. The risk of ventriculomegaly associated with organism recovery was heightened when accompanied by histologic inflammation, but the risk of diparetic CP was not. Low-virulence microorganisms isolated from the placenta, including common skin microflora, predict ultrasound lesions of the brain and diparetic CP in the very preterm infant. Organism recovery does not seem to be needed for placenta inflammation to predict diparetic CP.

The group B streptococcal serine-rich repeat 1 glycoprotein mediates penetration of the blood-brain barrier.

BACKGROUND: Group B Streptococcus (GBS) is the leading cause of bacterial meningitis in newborn infants. Because GBS is able to invade, survive, and cross the blood-brain barrier, we sought to identify surface-expressed virulence factors that contribute to blood-brain barrier penetration and the pathogenesis of meningitis. METHODS: Targeted deletion and insertional mutants were generated in different GBS clinical isolates. Wild-type and mutant bacteria were analyzed for their capacity to adhere to and invade human brain microvascular endothelial cells (hBMECs) and to penetrate the blood-brain barrier using our model of hematogenous meningitis. RESULTS: Analysis of a GBS (serotype V) clinical isolate revealed the presence of a surface-anchored serine-rich protein, previously designated serine-rich repeat 1 (Srr-1). GBS Srr-1 is a glycosylated protein with high molecular weight. Deletion of srr1 in NCTC 10/84 resulted in a significant decrease in adherence to and invasion of hBMECs. Additional mutants in other GBS serotypes commonly associated with meningitis showed a similar decrease in hBMEC invasion, compared with parental strains. Finally, in mice, wild-type GBS penetrated the blood-brain barrier and established meningitis more frequently than did the Deltasrr1 mutant strain. CONCLUSIONS: Our data suggest that GBS Srr glycoproteins play an important role in crossing the blood-brain barrier and in the development of streptococcal meningitis.

Antibiotic-loaded allograft decreases the rate of acute deep wound infection after spinal fusion in cerebral palsy.

STUDY DESIGN: A retrospective matched cohort study with control group. OBJECTIVE: To compare the infection rate after posterior spinal fusion with unit rod instrumentation with or without gentamicin-impregnated allograft bone in children with cerebral palsy (CP). SUMMARY OF BACKGROUND DATA: Previous studies evaluating wound infection rates after spinal fusion surgery in children with CP report an 8.7% to 10% wound infection rate. The concept of using antibiotic-loaded bone graft (AbBGF) to provide local antibiotics has been explored in high risk patients, such as those with osteomyelitis or infected joint arthroplasty. There have been no reports of using AbBGF prophylactically in spine surgery. METHODS: After IRB approval, the medical records of 220 children with CP who underwent spinal fusion with unit rod instrumentation for a primary spinal deformity between January 2000 through December 2006 at a single institution were retrospectively reviewed. We evaluated the incidence of postoperative wound infection in patients with AbBGF and those without bone graft (BGF). RESULTS: One hundred fifty-four patients received AbBGF during spinal fusion surgery and 6 patients (3.9%) developed a deep wound infection. Ten (15.2%) of the 66 patients without AbBGF developed a deep wound infection. The difference between groups was statistically different (P = 0.003). The mean age at surgery, preoperative Cobb angle, correction rate, operative time, and estimated blood loss were not statistically different between the 2 groups (P > 0.05). The length of hospital stay was decreased in the AbBGF group (P < 0.05). CONCLUSION: The incidence of deep wound infection after spinal fusion in 220 children with CP scoliosis decreased from 15% to 4% with the use of prophylactic antibiotics in the corticocancellous allograft bone.

Supracondylar femur fracture complicating epileptic insult: a specific and under diagnosed complication?

PURPOSE: In epileptic patients fractures are six times more frequent than in the general population. Known predisposing factors are anticonvulsant drugs, malnutrition, lack of physical activity and sunlight exposure. METHODS: In this study we describe two patients, one with a bilateral supracondylar fracture and one with a unilateral supracondylar fracture after an epileptic seizure. The literature concerning femur fracture following an epileptic insult is reviewed. RESULTS: A review of the literature revealed several cases of femur fractures associated with epilepsy, however no cases were found involving a supracondylar femur. CONCLUSIONS: Our hypothesis is that a tonic seizure with simultaneous contraction of both agonists and antagonists can cause this type of fracture in predisposing patients.

Participation in age-related activities and influence of cultural factors--comments from youth and parents of children with postnatal post infectious hemiplegia in Stockholm, Sweden.

PURPOSE: To investigate whether children with postnatal post-infectious hemiplegic cerebral palsy, and their parents, felt that participation in activities typical for the child's age and gender was affected. To identify factors, intra- and extra-personal that influenced disability with emphasis on factors related to immigration. METHOD: Interviews with six youths and 15 caregivers regarding the child's ability to participate in age-related activities, the consequences of disability in their home country compared to Sweden, and whether immigration influenced being a parent to a disabled child. RESULTS: All reported large difficulties participating in age-related activities. Positive and negative differences in participation in different cultures were described. War, culture, eating habits, hygiene habits, and school could differ and create difficulties when in Sweden. Language skills and intra personal factors influenced information gathering and participation in parental activities. CONCLUSIONS: Surprisingly large difficulties in participation may separate those with a postnatal post-infectious aetiology from hemiplegia of other aetiologies. High degrees of additional impairments may influence participation more than the physical disability. Language skills and cultural factors influence ability to seek and gain information. A mutual process where both Swedes and immigrants know traditions of care for disabled in both places may create understanding and improved dialogue.

Perinatal infections and cerebral palsy.

Cerebral palsy (CP) is a complex disease characterized by the aberrant control of movement or posture that appears in early life and affect about 2 per 1000 live-born children. CP represents the most common physical disability in childhood. An association between clinical chorioamnionitis and cerebral palsy has been recognised. Very low-birthweight infants constitute more than 1/4 of all new cases of cerebral palsy. The use of antimicrobial treatment of pregnant women with bacterial vaginosis, a complete course of antenatal steroids and magnesium sulphate are the most important strategies to prevent cerebral palsy.

Developmental effects on neonatal mortality and subsequent cerebral palsy in infants exposed to intrauterine infection.

BACKGROUND: Intrauterine bacterial infection is important as a high risk factor associated with subsequent brain damage of the newborn. AIMS: To see if mature fetuses require both hypoxia and intrauterine infection to lead to cerebral palsy, while premature fetuses need infection alone. STUDY DESIGN: A retrospective cohort study. SUBJECTS: 230 singleton live-born infants of 22 to 32 weeks of gestation, exposed to intrauterine infection during labor and delivery, from 1995 to 2002. METHODS: Mortality and incidence of cerebral palsy at 2 years old were compared among the 3 groups; immature (n=89, 22-27 weeks), premature (n=73, 28-33 weeks) and mature (n=68, >34 weeks). The relationship between cerebral palsy and fetal pH values was examined. OUTCOME MEASURES: Mortality and cerebral palsy. RESULTS: Mortality and cerebral palsy were significantly decreased with advancing gestation. Mortality was significantly decreased after 28 weeks of gestation while cerebral palsy was significantly decreased after 34 weeks of gestation. Acidosis was associated with cerebral palsy in mature infants, but not in less mature infants. CONCLUSIONS: : Premature infants were more susceptible to intrauterine infection to cause death or cerebral palsy than mature infants. Mature infants may require exposures to both infection and hypoxia but less mature infants need infection alone to cause cerebral palsy, suggesting different pathogenesis during the developmental stage.

Perinatal infections and cerebral palsy.

Infections of the mother, the intrauterine environment, the fetus, and the neonate can cause cerebral palsy through a variety of mechanisms. Each of these processes is reviewed. The recently proposed theory of cytokine-induced white matter brain injury and the systemic inflammatory response syndrome with multiple organ dysfunction syndrome is critically evaluated.

Periodontal conditions and subgingival microflora in Down syndrome patients. A case-control study.

OBJECTIVES: The periodontal conditions and the subgingival microflora of children, adolescents and young adults (8-28 years old) with Down syndrome were investigated in the present cross-sectional study and compared with those of healthy individuals and subjects with cerebral palsy. MATERIAL AND METHODS: Seventy Down syndrome patients, 121 age-matched healthy individuals and 76 patients with cerebral palsy participated in the present study. Full-mouth recordings of clinical parameters (probing depth, probing attachment level, bleeding on probing, hygiene index) and the community periodontal index of treatment needs were assessed and subgingival plaque samples were taken from the Ramfjord teeth and analysed for 14 species using "checkerboard" DNA-DNA hybridization. RESULTS: Clinical indices of periodontal inflammation and treatment needs were statistically significant higher among Down syndrome patients compared with the other two groups (ANOVA, p=0.000). Important periodontal pathogens colonize these subjects earlier and at higher levels (chi-squared test, p=0.000). DISCUSSION: Down syndrome patients display more severe periodontal destruction earlier, and heavier colonization with periodontal pathogens compared with age-matched healthy individuals and patients with cerebral palsy.

Maturational effects of lipopolysaccharide on white-matter injury in fetal sheep.

White-matter damage has been associated with the development of cerebral palsy in children born both prematurely and at term, and it has been suggested that intrauterine infection can contribute to the brain injury. However, the relative importance of age on white-matter injury following infectious exposure in utero remains unclear. In this study, fetal sheep were exposed to systemic endotoxemia by administration of Escherichia coli lipopolysaccharide (88.7 +/- 7.7 ng/kg) at 65% or 85% of gestation. These gestational ages approximately correspond to human brain development in preterm and near-term infants respectively. White-matter injury was evaluated 3 days after lipopolysaccharide exposure with regard to microglia activation and loss of neurofilament and myelin basic protein. The expression of oligodendrocytes at different maturational stages was demonstrated in preterm and near-term fetuses with the oligodendroglial markers O4 and 2 ,3 -cyclic nucleotide 3 -phospodiesterase. Forty percent of the fetuses in the preterm group and 22% in the near-term group died within 8 hours of the endotoxin exposure. Three of six preterm and two of seven near-term surviving fetuses demonstrated pathologic changes in the brain with regard to increased microglia activation and loss of neurofilament staining. The number of activated microglia was enhanced in the subcortical white matter in both the preterm lipopolysaccharide-exposed fetuses (lipopolysaccharide: 235 +/- 64 cells/mm2; control: 72 +/- 28 cells/mm2; P = .0374) and the near-term fetuses (lipopolysaccharide: 180 +/- 40 cells/mm2; control 23 +/- 16 cells/mm2; P = .0152). There was a loss of neurofilament staining in both preterm fetuses (lipopolysaccharide: 2.20 +/- 0.77 pixel units; control: 0.20 +/- 0.10 pixel units; P = .0306) and near-term fetuses (lipopolysaccharide: 1.15 +/- 0.48 pixel units; control: 0.06 +/- 0.06 pixel units; P = .0285). O4-positive cells were detected at both gestational ages, whereas 2,3-cyclic nucleotide 3-phospodiesterase-positive cells and myelin basic protein staining were mainly detected in the near-term fetuses. In summary, we found white-matter injury in a proportion of both preterm and near-term fetuses after administration of lipopolysaccharide. These results are in agreement with clinical evidence suggesting that both preterm and term infants are at risk of periventricular leukomalacia in association with intrauterine infection.

Intrauterine infection and the development of cerebral palsy.

Cerebral palsy is a serious motor disorder that appears in early life. The expectation that improved obstetrical and neonatal care would decrease the rate of this condition has not been realised. Recent evidence indicates that white matter brain lesions, often termed periventricular leukomalacia (PVL), are the most important identifiable risk factors for the development of cerebral palsy. The hypothesis under examination is that inflammatory cytokines released during the course of intrauterine infection play a central role in the genesis of preterm parturition, fetal PVL, and cerebral palsy. We examined the relationship between umbilical cord plasma concentrations of cytokines at birth and the occurrence of PVL in preterm gestation and demonstrated that umbilical cord plasma concentrations of interleukin (IL)-6 was a significant independent predictor of PVL-associated lesions. We also demonstrated that preterm neonates born to mothers with elevated amniotic fluid concentrations of pro-inflammatory cytokines were at increased risk for the subsequent development of PVL and cerebral palsy. Histological chorioamnionitis and congenital neonatal infection-related morbidity were more common in neonates with PVL than those without PVL in this study. We have also been able to induce PVL-like brain white matter lesions in the fetal rabbit after experimental ascending intrauterine infection. In support of this hypothesis, we were able to demonstrate overexpression of tumour necrosis factor-alpha and IL-6 in histological sections of neonatal brains with PVL. Moreover, the presence of funisitis, a histological counterpart of the fetal inflammatory response syndrome, and elevated concentrations of amniotic fluid IL-6 and IL-8 were strong and independent risk factors for the subsequent development of cerebral palsy at the age of 3 years in our recent study. Therefore, clinical and experimental data provide strong support for the hypothesis. There are significant implications of our findings. First, cytokine determinations in amniotic fluid provide information about the risk of PVL and cerebral palsy before birth. Second, the process responsible for some cases of PVL and cerebral palsy begins during intrauterine life, implying that effective strategies for the prevention of cerebral palsy associated with PVL must begin in utero.

Effect of a 0.5% chlorhexidine gel on dental plaque superinfecting microorganisms in mentally handicapped patients.

A randomized clinical trial was conducted to investigate the effect of a 0.5% chlorhexidine (CHX) gel on dental plaque superinfecting microorganisms in mentally handicapped patients. Thirty inmates from the institution "Casas André Luiz" were assigned to either test group (CHX gel, n = 15) or control group (placebo gel, n = 15). The gel was administered over a period of 8 weeks. Supragingival plaque samples were collected at baseline, after gel use (8 weeks) and 16 weeks after baseline. The presence of Gram-negative Enterobacteriaceae, Staphylococcus and yeasts was evaluated. No significant growth of any superinfecting microorganism was observed in the CHX group, when compared to the placebo group. The results indicated that the 0.5% chlorhexidine gel did not produce an undesirable shift in these bacterial populations.

Chorioamnionitis and brain injury.

The limited available evidence supports a strong association of chorioamnionitis with neonatal encephalopathy and CP in the term infant. The association of chorioamnionitis with depressed Apgar scores or neonatal seizures and with CP is equivocal in the preterm infant. Different study results may be related to differences in study populations, perhaps specifically to differences in susceptibility by stages of neurologic development as well as differences in gene frequencies associated with inflammation and thrombophilia. We require further understanding of the normal roles of cytokines in brain development, pregnancy, and inflammatory homeostasis before clinical interventions directed at cytokines, their receptors, or the inflammatory process are considered.

Perinatal infections and brain injury: current treatment options.

Antimicrobial therapy can ameliorate infection and prevent long-term morbidity caused by several pathogens that infect the fetus and neonate. Ultimately, however, preventive strategies need to be developed and incorporated into routine preconceptional care. The future of prevention lies in immunizations, and if past and current successes with smallpox, polio, rubella, and measles vaccination programs are any indication, the future is bright for the developing fetus.

The association of coagulase-negative staphylococci isolated from the chorioamnion at delivery and subsequent development of cerebral palsy.

OBJECTIVE: To find out whether there is an association between cultures positive for coagulase negative staphylococci (CONS) taken from babies in the Neonatal Intensive Care Unit (NICU) and a subsequent outcome of cerebral palsy. STUDY DESIGN: At delivery, we obtained cultures from the chorioamnion space and, when medically indicated, we obtained bacterial cultures from children in the NICU. Surviving neonates underwent final examination for cerebral palsy at age 18 months. RESULTS: Of six children in the Magnesium and Neurologic Endpoints Trial who had cerebral palsy, chorioamnion cultures had been obtained for five of six. Four of these five children (80%) had CONS-positive cultures, whereas 26 of 102 (25%) children without cerebral palsy were CONS positive (p = 0.02). In the NICU, of children with cerebral palsy, the prevalence of culture-proven CONS was 80% (4/5); for those without cerebral palsy, the prevalence was 17% (15/86) (p = 0.01). Using multivariable logistic regression to control for confounding, CONS in the chorioamnion remained significant (adjusted odds ratio [OR] 37.7, 95% confidence interval [CI] 3.0 to +infinity; p = 0.003). However, when controlled for extremely low birth weight, nonvertex presentation, and being on a ventilator > or = 20 days, the association between culture-proven CONS in the NICU and cerebral palsy became insignificant (adjusted OR 3.0, 95% CI 0.2 to +infinity; p = 0.42). CONCLUSION: CONS in the chorioamnion space are associated with cerebral palsy, but in these data, CONS in the NICU are not found to be associated with cerebral palsy.