What Emerging Research Reveals About Fetal Brain Development in Preterm Labor

What Emerging Research Reveals About Fetal Brain Development in Preterm Labor

February 26, 2026

By Brittany M. Woodman, Esq.

Recent research published in the American Journal of Obstetrics and Gynecology adds to a growing body of evidence suggesting that fetal neurological injury associated with preterm birth may begin before delivery, rather than solely as a consequence of postnatal complications. In a prospective cohort study, researchers evaluated fetal brain structure and biochemical markers in pregnancies complicated by preterm labor with intact membranes (“PTL”) or preterm premature rupture of membranes (“PPROM”), identifying prenatal signs of brain remodeling and injury at the time of clinical presentation. [1].

The study examined singleton pregnancies between 24 and 34 weeks’ gestation using detailed fetal neurosonography combined with amniotic fluid analysis. [1]. Fetuses exposed to PTL or PPROM demonstrated measurable differences in brain development when compared to gestational-age matched controls, including smaller cerebellar measurements, reduced corpus callosum area, and delayed cortical maturation. Id. These structural findings were accompanied by elevated concentrations of amniotic fluid biomarkers associated with neuronal and glial injury, including neuron-specific enolase (NSE), protein S100B, and glial fibrillary acidic protein (GFAP). Id.

Importantly, this study analyzed outcomes based on the presence or absence of intra-amniotic inflammation (“IAI”). Fetuses exposed to IAI exhibited more pronounced structural and biochemical changes, supporting the authors’ conclusion that inflammation acts as a significant mediator of fetal brain injury. [1]. However, the study also identified evidence of brain remodeling in fetuses without IAI, suggesting that inflammation, while influential, is not the sole mechanism underlying prenatal neurological vulnerability in preterm labor. Id.

In a subsequent Letter to the Editor, separate researchers interpreted these findings with earlier clinical literature examining neurodevelopmental outcomes following PTL and PPROM. [2]. The authors highlighted prior research demonstrating that, in cases of PPROM, gestational age at membrane rupture, rather than latency period or gestational age at delivery, was independently associated with later cerebral palsy risk. Id. They further emphasized that neurological injury may arise through different clinical and biological mechanisms in PTL as compared to PPROM, underscoring the importance of timing, inflammatory status, and the underlying condition precipitating preterm birth. [2].

While direct comparison between prenatal imaging findings and postnatal neurologic outcomes remains limited, researchers in the Letter to the Editor noted that the American Journal of Obstetrics and Gynecology’s recent publication provides important in vivo evidence supporting the hypothesis that neurological injury may originate before birth. [2]. Together, these publications suggest that fetal brain development may be altered during preterm labor itself, rather than exclusively as a downstream effect of prematurity-related neonatal complications.

These findings carry potential implications for clinical surveillance and counseling in pregnancies complicated by PTL or PPROM. The identification of prenatal brain remodeling raises questions regarding the role of targeted neurological monitoring, the interpretation of inflammatory markers, and the need for continued long-term studies linking prenatal imaging to long-term neurodevelopmental outcomes. As cautioned by the Letter to the Editor, further research is necessary to clarify causation, refine risk stratification, and determine whether antenatal interventions can mitigate adverse neurological sequelae. [2].

Taken together, the instant study and the subsequent response contribute to an evolving understanding of fetal neurodevelopment in the setting of preterm labor. By shifting attention toward the prenatal period, this work reinforces the importance of early identification, sophisticated interpretation of inflammatory processes, and continued investigation into the timing and mechanisms of fetal brain injury.

Citations: 
[1] Clara Murillo, Elisenda Eixarch, Claudia Rueda, et al., Evidence of Brain Injury in Fetuses of Mothers with Preterm Labor with Intact Membranes and Preterm Premature Rupture of Membranes, 232 Am. J. Obstet. Gynecol. 114.e1–114.e24 (2025), https://doi.org/10.1016/j.ajog.2024.04.025.

[2] Federica Fernicola, Sara Ornaghi & Anna Locatelli, Evidence of Brain Injury in Fetuses of Mothers with Preterm Labor with Intact Membranes and Preterm Premature Rupture of Membranes (Letter to the Editor), Am. J. Obstet. Gynecol. (2026), https://doi.org/10.1016/j.ajog.2026.01.025.

Disclaimer: This publication is not intended to provide legal advice but to provide general information on legal matters. Transmission is not intended to create and receipt does not establish an attorney-client relationship. Readers should seek specific legal and/or medical advice before taking any action with respect to matters mentioned in this publication. The attorney responsible for this publication is Brittany Woodman. This post constitutes a form of attorney advertising as defined by some state bar associations.