Evidence of brain injury in fetuses of mothers with preterm labor with intact membranes and preterm premature rupture of membranes - 24/12/24
Abstract |
Background |
Brain injury and poor neurodevelopment have been consistently reported in infants and adults born before term. These changes occur, at least in part, prenatally and are associated with intra-amniotic inflammation. The pattern of brain changes has been partially documented by magnetic resonance imaging but not by neurosonography along with amniotic fluid brain injury biomarkers.
Objective |
This study aimed to evaluate the prenatal features of brain remodeling and injury in fetuses from patients with preterm labor with intact membranes or preterm premature rupture of membranes and to investigate the potential influence of intra-amniotic inflammation as a risk mediator.
Study Design |
In this prospective cohort study, fetal brain remodeling and injury were evaluated using neurosonography and amniocentesis in singleton pregnant patients with preterm labor with intact membranes or preterm premature rupture of membranes between 24.0 and 34.0 weeks of gestation, with (n=41) and without (n=54) intra-amniotic inflammation. The controls for neurosonography were outpatient pregnant patients without preterm labor or preterm premature rupture of membranes matched 2:1 by gestational age at ultrasound. Amniotic fluid controls were patients with an amniocentesis performed for indications other than preterm labor or preterm premature rupture of membranes without brain or genetic defects whose amniotic fluid was collected in our biobank for research purposes matched by gestational age at amniocentesis. The group with intra-amniotic inflammation included those with intra-amniotic infection (microbial invasion of the amniotic cavity and intra-amniotic inflammation) and those with sterile inflammation. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture and/or positive 16S ribosomal RNA gene. Inflammation was defined by amniotic fluid interleukin 6 concentrations of >13.4 ng/mL in preterm labor and >1.43 ng/mL in preterm premature rupture of membranes. Neurosonography included the evaluation of brain structure biometric parameters and cortical development. Neuron-specific enolase, protein S100B, and glial fibrillary acidic protein were selected as amniotic fluid brain injury biomarkers. Data were adjusted for cephalic biometrics, fetal growth percentile, fetal sex, noncephalic presentation, and preterm premature rupture of membranes at admission.
Results |
Fetuses from mothers with preterm labor with intact membranes or preterm premature rupture of membranes showed signs of brain remodeling and injury. First, they had a smaller cerebellum. Thus, in the intra-amniotic inflammation, non–intra-amniotic inflammation, and control groups, the transcerebellar diameter measurements were 32.7 mm (interquartile range, 29.8–37.6), 35.3 mm (interquartile range, 31.2–39.6), and 35.0 mm (interquartile range, 31.3–38.3), respectively (P=.019), and the vermian height measurements were 16.9 mm (interquartile range, 15.5–19.6), 17.2 mm (interquartile range, 16.0–18.9), and 17.1 mm (interquartile range, 15.7–19.0), respectively (P=.041). Second, they presented a lower corpus callosum area (0.72 mm2 [interquartile range, 0.59–0.81], 0.71 mm2 [interquartile range, 0.63–0.82], and 0.78 mm2 [interquartile range, 0.71–0.91], respectively; P=.006). Third, they showed delayed cortical maturation (the Sylvian fissure depth–to–biparietal diameter ratios were 0.14 [interquartile range, 0.12–0.16], 0.14 [interquartile range, 0.13–0.16], and 0.16 [interquartile range, 0.15–0.17], respectively [P<.001], and the right parieto-occipital sulci depth ratios were 0.09 [interquartile range, 0.07–0.12], 0.11 [interquartile range, 0.09–0.14], and 0.11 [interquartile range, 0.09–0.14], respectively [P=.012]). Finally, regarding amniotic fluid brain injury biomarkers, fetuses from mothers with preterm labor with intact membranes or preterm premature rupture of membranes had higher concentrations of neuron-specific enolase (11,804.6 pg/mL [interquartile range, 6213.4–21,098.8], 8397.7 pg/mL [interquartile range, 3682.1–17,398.3], and 2393.7 pg/mL [interquartile range, 1717.1–3209.3], respectively; P<.001), protein S100B (2030.6 pg/mL [interquartile range, 993.0–4883.5], 1070.3 pg/mL [interquartile range, 365.1–1463.2], and 74.8 pg/mL [interquartile range, 44.7–93.7], respectively; P<.001), and glial fibrillary acidic protein (1.01 ng/mL [interquartile range, 0.54–3.88], 0.965 ng/mL [interquartile range, 0.59–2.07], and 0.24 mg/mL [interquartile range, 0.20–0.28], respectively; P=.002).
Conclusion |
Fetuses with preterm labor with intact membranes or preterm premature rupture of membranes had prenatal signs of brain remodeling and injury at the time of clinical presentation. These changes were more pronounced in fetuses with intra-amniotic inflammation.
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Key words : amniocentesis, biomarkers, cerebellum, corpus callosum, cortical maturation, fetal brain, glial fibrillary acidic protein, intra-amniotic inflammation, microbial invasion of the amniotic cavity, neuron-specific enolase, neurosonography, preterm labor with intact membranes, preterm premature rupture of membranes, protein S100B, spontaneous preterm delivery
Plan
E.E., M.P., and T.C. contributed equally as last authors of the article. |
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The authors report no conflict of interest. |
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This study is funded by the competitive grant “Ajut a la recerca Josep Font” from the Hospital Clínic de Barcelona. C.M. was employed by the same grant “Ajut a la recerca Josep Font” for 3 years to conduct this project. Amniotic fluid analysis and costs for publication were also funded by the Institute of Health Carlos III (proyectos de investigación en salud: PI19/00580 and PI22/00663). E.E. was partially supported by Convocatòria Intensificació Interna per als Professionals de l’Hospital Clínic de Barcelona 2023, granted by the Hospital Clínic de Barcelona. |
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The findings of this article were presented in the following meetings: the 19th World Congress in Fetal Medicine, Fetal Medicine Foundation, Crete, Greece, June 26–30, 2022; the 32nd World Congress 2022 on Ultrasound in Obstetrics and Gynecology, the International Society of Ultrasound in Obstetrics and Gynecology, London, United Kingdom, September 16–18, 2023; the Society for Maternal-Fetal Medicine (SMFM) 43rd Annual Pregnancy Meeting, SMFM, San Francisco, CA, February 6–11, 2023; and the 20th World Congress in Fetal Medicine, Fetal Medicine Foundation, Valencia, Spain, June 25–29, 2023. |
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Cite this article as: Murillo C, Eixarch E, Rueda C, et al. Evidence of brain injury in fetuses of mothers with preterm labor with intact membranes and preterm premature rupture of membranes. Am J Obstet Gynecol 2025;232:114.e1-24. |
Vol 232 - N° 1
P. 114.e1-114.e24 - janvier 2025 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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