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Histologic chorioamnionitis in preterm infants: correlation with brain magnetic resonance imaging at term equivalent age.

ABSTRACT: To explore the associations between histologic chorioamnionitis with brain injury, maturation and size on magnetic resonance imaging (MRI) of preterm infants at term equivalent age.Preterm infants (23-36 weeks' gestational age) were recruited into two longitudinal cohort studies. Presence or absence of chorioamnionitis was obtained from placental histology and clinical data were recorded. MRI at term-equivalent age was assessed for brain injury (intraventricular haemorrhage, cysts, signal abnormalities), maturation (degree of myelination, gyral maturation) and size of cerebral structures (metrics and brain segmentation). Histologic chorioamnionitis was assessed as a predictor of MRI variables using linear and logistic regression, with adjustment for confounding perinatal variables.Two hundred and twelve infants were included in this study, 47 (22%) of whom had histologic chorioamnionitis. Histologic chorioamnionitis was associated with higher odds of intraventricular haemorrhage (odds ratio [OR] (95% confidence interval [CI])?=?7.4 (2.4, 23.1)), less mature gyral maturation (OR (95% CI)?=?2.0 (1.0, 3.8)) and larger brain volume (mean difference in cubic centimeter (95% CI) of 14.1 (1.9, 26.2)); but all relationships disappeared following adjustment for perinatal variables.Histologic chorioamnionitis was not independently associated with IVH, less mature gyral maturation or brain volume at term-equivalent age in preterm infants.

SUBMITTER: Granger C

PROVIDER: S-EPMC5815189 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Histologic chorioamnionitis in preterm infants: correlation with brain magnetic resonance imaging at term equivalent age.

Granger Claire C Spittle Alicia J AJ Walsh Jennifer J Pyman Jan J Anderson Peter J PJ Thompson Deanne K DK Lee Katherine J KJ Coleman Lee L Dagia Charuta C Doyle Lex W LW Cheong Jeanie J

BMC pediatrics 20180215 1

<h4>Background</h4>To explore the associations between histologic chorioamnionitis with brain injury, maturation and size on magnetic resonance imaging (MRI) of preterm infants at term equivalent age.<h4>Methods</h4>Preterm infants (23-36 weeks' gestational age) were recruited into two longitudinal cohort studies. Presence or absence of chorioamnionitis was obtained from placental histology and clinical data were recorded. MRI at term-equivalent age was assessed for brain injury (intraventricula ...[more]

PMID: 29448926

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Project description:IntroductionPreterm infants are at increased risk of exposure to histologic chorioamnionitis (HCA) when compared to term-born controls, and this is associated with several neonatal morbidities involving brain, lungs and gut. Preterm infants could benefit from immunomodulatory therapies in the perinatal period, but development of rational treatment strategies requires improved characterization of the perinatal response to HCA. We had two objectives: The first, to characterize the umbilical cord blood immune profile in preterm infants compared to term-born controls; the second, to investigate the postnatal immune response in preterm infants exposed to HCA versus those who were not.PopulationFor objective one 59 term infants [mean gestational age (GA) 39+4 (37+3 to 42+0)] and 55 preterm infants [mean GA29+0(23+3 to 32+0)] with umbilical cord samples available were included; for objective two we studied 96 preterm infants [mean GA29+1(23+2 to 32+0)] for whom placental histology and postnatal blood samples were available.MethodsPlacental histopathology was used to identify reaction patterns indicative of HCA, and a customized immunoassay of 24 inflammatory markers and trophic proteins selected to reflect the perinatal immune response was performed on umbilical cord blood in term and preterm participants and postnatal day 5 blood in the preterm group.ResultsThe umbilical cord blood immune profile classified gestational age category with 86% accuracy (95% CI 0.78-0.92), p-value=1.242x10-14. Pro-inflammatory proteins IL-6, MCP-1 and CRP were elevated in the cord blood of preterm infants whilst BDNF, C3, C9, IL-18, MMP-9 and RANTES were decreased, compared to infants born at term. In preterm infants, exposure to HCA was associated with elevations in 8 immune proteins on postnatal day 5 (BDNF, C3, C5a, C9, IL-8, MCP-1, MIP-1β and MMP-9) when compared to preterm infants who were not exposed.ConclusionPreterm birth is associated with a distinct immune profile in umbilical cord blood and preterm infants exposed to HCA with evidence of a fetal inflammatory response have specific alterations in immune function that are apparent on day 5 of postnatal life.

Project description:BACKGROUND AND PURPOSE:Currently available MRI scoring systems of cerebral maturation in term and preterm infant at term equivalent age do not include the changes of transient fetal compartments that persist to term age. We studied the visibility and the pattern of these structures in healthy term newborns compared to preterm infants at term equivalent age in order to investigate if they can be included in a new MRI score system. We hypothesized that transient fetal compartments are different in both groups, and that these differences can be characterized using the clinical T2-weighted MRIs. MATERIALS AND METHODS:Using 3T MRI T2-weighted brain sequences of 21 full-term and 41 preterm infants (< 32 weeks), scanned at term equivalent age, 3 raters independently scored the maturation level of 3 transient fetal compartments: the periventricular crossroads, von Monakow segments of the white matter, and the subplate compartment. These 3 new items were included in a scoring system along with validated parameters of brain maturation (germinal matrix, bands of migration, subarachnoid space and quality of gyrification). A cumulative maturity score was calculated separately for both groups of newborns by adding together each item. More mature were the brain structures, higher was the cumulative maturity score. RESULTS:Cumulative maturity score distinguished full-term from preterm infants (mean score 41/60 ± 1.4 versus 37/60 ± 2.5 points, p < 0.001), with an increase of 0.5 points for each supplemental gestational week at birth (r?=?0.5, 95% CI 0.5 - 0.85). While a majority of transient fetal compartments were less mature in preterm group at term equivalent age, von Monakow segments of the white matter and subplate compartment presented a more advanced maturational stage in the preterm group compared to the term group. No subject had all scored items in the most mature state. Except a slight intra-rater agreement for von Monakow segment II, inter- and intra-rater agreements were moderate to excellent indicating the potential of the developed scoring system in routine clinical practice. CONCLUSION:Brain transient fetal structures can be assessed on regular T2-weighted MRI in newborns. Their appearance differs between term and preterm babies. However our results suggest a more complex situation, with both delayed and accelerated maturation pattern in preterm infants. It remains to be determined if these differences could be biomarkers of the future neurodevelopment of preterm infants.

Project description:The link between histologic acute chorioamnionitis and infection is well established in preterm deliveries, but less well-studied in term pregnancies, where infection is much less common.We conducted a secondary analysis among 195 low-risk women with term pregnancies enrolled in a randomized trial. Histologic and microbiologic evaluation of placentas included anaerobic and aerobic cultures (including mycoplasma/ureaplasma species) as well as PCR. Infection was defined as ≥1,000 cfu of a single known pathogen or a ≥2 log difference in counts for a known pathogen versus other organisms in a mixed culture. Placental membranes were scored and categorized as: no chorioamnionitis, Grade 1 (subchorionitis and patchy acute chorioamnionitis), or Grade 2 (severe, confluent chorioamnionitis). Grade 1 or grade 2 histologic chorioamnionitis was present in 34% of placentas (67/195), but infection was present in only 4% (8/195). Histologic chorioamnionitis was strongly associated with intrapartum fever >38°C [69% (25/36) fever, 26% (42/159) afebrile, P<.0001]. Fever occurred in 18% (n = 36) of women. Most febrile women [92% (33/36)] had received epidural for pain relief, though the association with fever was present with and without epidural. The association remained significant in a logistic regression controlling for potential confounders (OR = 5.8, 95% CI = 2.2,15.0). Histologic chorioamnionitis was also associated with elevated serum levels of interleukin-8 (median = 1.3 pg/mL no histologic chorioamnionitis, 1.5 pg/mL Grade 1, 2.1 pg/mL Grade 2, P = 0.05) and interleukin-6 (median levels = 2.2 pg/mL no chorioamnionitis, 5.3 pg/mL Grade 1, 24.5 pg/mL Grade 2, P = 0.02) at admission for delivery as well as higher admission WBC counts (mean = 12,000 cells/mm(3) no chorioamnionitis, 13,400 cells/mm(3) Grade 1, 15,700 cells/mm(3) Grade 2, P = 0.0005).Our results suggest histologic chorioamnionitis at term most often results from a noninfectious inflammatory process. It was strongly associated with fever, most of which was related to epidural used for pain relief. A more 'activated' maternal immune system at admission was also associated with histologic chorioamnionitis.

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Histologic chorioamnionitis in preterm infants: correlation with brain magnetic resonance imaging at term equivalent age.

Publications

Histologic chorioamnionitis in preterm infants: correlation with brain magnetic resonance imaging at term equivalent age.

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