Fatty Liver in Pregnancy Linked to Higher Risk of Preterm Birth

Pregnant Women with MASLD Face Elevated Risk of Premature Birth Independent of Obesity, New Study Finds

A groundbreaking study from researchers at Karolinska Institutet has unveiled that pregnant women diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD) are at a significantly heightened risk of delivering their babies prematurely. Crucially, this association persists beyond the influence of maternal obesity, suggesting that MASLD itself may exert adverse effects on pregnancy outcomes. Published recently in the esteemed journal eClinicalMedicine, this research offers new insights into the complex interplay between maternal liver health and fetal development, with potentially wide-reaching implications for obstetric care and disease management during pregnancy.

MASLD, formerly known as non-alcoholic fatty liver disease (NAFLD), is a rapidly emerging chronic liver condition characterized by excessive fat accumulation in liver cells, in the absence of significant alcohol consumption. It is increasingly recognized as a metabolic disorder intricately linked with systemic conditions such as type 2 diabetes, insulin resistance, and obesity. Epidemiological data estimate that nearly 20% of the Swedish population and up to 30% globally have MASLD. As the prevalence of metabolic disorders rises worldwide, MASLD incidence among women of childbearing age is also escalating, warranting urgent investigation into its effects on pregnancy and neonatal health.

The recently reported investigation analyzed nationwide Swedish registry data, including a cohort of 240 births from women with biopsy-confirmed MASLD and 1140 matched births from the general population without MASLD. Utilizing comprehensive clinical and demographic data, the research team meticulously adjusted for potential confounders, such as maternal body mass index (BMI) and comorbidities, to isolate the impact of MASLD on birth outcomes. The findings were striking: women with MASLD had a more than threefold increased risk of preterm birth compared to their counterparts, an association that persisted even when compared against overweight or obese women without MASLD.

This pronounced elevation in risk highlights a critical insight—the deleterious effects observed are not merely a consequence of excess body weight or obesity-related complications but are likely driven directly by the pathological processes of MASLD. MASLD is known to induce systemic inflammation, oxidative stress, and alterations in lipid metabolism, all of which may jeopardize placental function and fetal development. Inflammatory cytokines and metabolic dysregulation linked to MASLD may impair uteroplacental blood flow or trigger premature activation of labor pathways, thereby increasing the likelihood of early delivery.

Interestingly, the study revealed that the degree of MASLD severity, as assessed by biopsy, did not correlate with a progressive increase in premature birth risk. This suggests that even early or moderate forms of MASLD may confer significant obstetric risks, underscoring the need for vigilant clinical assessment irrespective of disease stage. Lead author Dr. Carole A. Marxer, a postdoctoral researcher at Karolinska’s Department of Medical Epidemiology and Biostatistics, emphasized, “Our data challenge the conventional wisdom that obesity alone explains adverse pregnancy outcomes in MASLD patients. The liver pathology itself appears to play an independent and critical role.”

Beyond prematurity, the researchers observed a 63% higher incidence of cesarean section deliveries among women with MASLD compared to the general population. However, after stratifying for BMI, this increased cesarean rate aligned with that seen in overweight or obese women without fatty liver disease, suggesting that elevated BMI rather than MASLD per se drives the risk of surgical delivery. This nuanced finding reinforces the complex interrelationships between metabolic health, liver disease, and obstetric decisions.

Reassuringly, the study did not find increased risks of congenital malformations or neonatal mortality among offspring of women with MASLD, indicating that while prematurity risk is elevated, gross fetal maldevelopment or birth-related mortality does not appear directly linked to maternal liver disease. Senior author Professor Jonas F. Ludvigsson noted that these outcomes provide some assurance regarding the immediate neonatal prognosis but cautioned that longer-term follow-up studies are needed to assess developmental and metabolic sequelae in children born to MASLD-affected mothers.

Methodologically, the study leveraged the strength of Sweden’s comprehensive national health registries, enabling near-complete ascertainment of maternal BMI, comorbidities, and birth outcomes. The use of biopsy-proven MASLD diagnosis enhanced diagnostic precision, mitigating misclassification biases commonly encountered in studies relying solely on biochemical or imaging criteria. Despite adjustments for numerous confounders, the authors acknowledge that residual confounding from unmeasured factors cannot be entirely excluded.

The implications of this work are wide-ranging. First, it underscores the imperative to integrate liver health assessment into prenatal care for women at risk of MASLD, particularly given the silent progression of fatty liver disease and the frequent underdiagnosis before pregnancy. Furthermore, it advocates for the development of clinical guidelines tailored to pregnant women with MASLD, emphasizing close monitoring and potential interventions aimed at mitigating preterm birth risk. Potential therapeutic avenues may include targeting metabolic derangements, inflammation, or placental function, although clinical trials will be essential to evaluate efficacy and safety.

With maternal metabolic health emerging as a critical determinant of pregnancy success, this research also highlights the pressing need for public health strategies addressing the rising tide of metabolic syndrome and fatty liver disease, especially among young women. Lifestyle interventions promoting healthy weight, glycemic control, and liver function could confer benefits extending beyond maternal health to improve neonatal outcomes and long-term child wellbeing.

The study was funded by an array of prestigious organizations, including the Swiss National Science Foundation, the European Crohn’s and Colitis Organisation, the Swedish Society for Medical Research, and Karolinska Institutet. The international collaboration among hepatologists, epidemiologists, and obstetricians marks a significant stride forward in unraveling the complex interactions between liver pathology and reproductive health.

As the global prevalence of MASLD continues to surge, its implications for pregnancy and offspring health are becoming increasingly apparent. This research provides compelling evidence that MASLD is more than a silent spectator during pregnancy—it may actively shape perinatal outcomes. Healthcare providers and researchers must now mobilize to translate these findings into clinical practice, ensuring that women with MASLD receive tailored surveillance and care to optimize both maternal and neonatal health.

In conclusion, the identification of MASLD as an independent risk factor for premature birth represents a paradigm shift in our understanding of liver disease in pregnancy. This study raises important questions about the pathophysiological mechanisms linking hepatic steatosis to adverse obstetric events, beckoning further investigation into molecular pathways, immune responses, and placental biology. The future of maternal-fetal medicine will increasingly intertwine with metabolic and liver disease research, fostering integrated approaches to combat the burden of MASLD and improve pregnancy outcomes worldwide.

Subject of Research: People

Article Title: Adverse pregnancy and birth outcomes in women with biopsy-proven MASLD: A nationwide cohort study

News Publication Date: 9-May-2025

Web References:
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00170-1/fulltext
http://dx.doi.org/10.1016/j.eclinm.2025.103238

References:
Marxer, C. A., Ebrahimi, F., Bergman, D., Sun, J., Hagström, H., Thuresson, M., Stephansson, O., Ludvigsson, J. F. (2025). Adverse pregnancy and birth outcomes in women with biopsy-proven MASLD: A nationwide cohort study. eClinicalMedicine. https://doi.org/10.1016/j.eclinm.2025.103238

Keywords:
MASLD, fatty liver disease, metabolic dysfunction, pregnancy outcomes, premature birth, cesarean section, metabolic disorders, obstetrics, neonatal health, liver disease, maternal health, perinatal epidemiology

Tags: chronic liver conditions in pregnancyfatty liver disease in pregnancyfetal development and liver healthMASLD and preterm birth riskmaternal health and neonatal risksmaternal liver health impactsmetabolic disorders and pregnancy outcomesmetabolic dysfunction during pregnancynon-alcoholic fatty liver disease effectsobstetric care for MASLD patientspremature birth and obesityrising prevalence of MASLD in women