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TOPLINE:

Higher maternal anti-human leukocyte antigen (HLA) antibody levels are associated with fetal growth restriction (FGR), with 22.0% of women with antibody levels > 1000 mean fluorescence intensity (MFI) experiencing FGR compared with 15.3% of those with lower levels. Anti-HLA antibody levels increased with the number of prior pregnancies and decreased with time since the last pregnancy, consistent with pregnancy-related alloimmunization.

METHODOLOGY:

• Researchers conducted a retrospective cohort study in collaboration between the Department of Obstetrics and Gynecology at Antoine Béclère Hospital, Assistance Publique – Hôpitaux de Paris (AP-HP), Clamart, France, and the Nouvelle-Aquitaine regional branch of the French Blood Establishment, involving 574 women who underwent routine anti-HLA antibody screening between 2010 and 2020.
• A total of 1469 pregnancies were reported in the 574 participants, with a mean of 2.5 pregnancies per participant; obstetric history was collected using a secure online questionnaire distributed over a 2-month period.
• Anti-HLA antibodies were measured at the time of blood donation using a Luminex screening assay, with MFI values providing a semi-quantitative measure of overall anti-HLA reactivity; a threshold of > 1000 MFI was used to define higher antibody levels.
• Multivariable logistic regression models were adjusted for maternal age at pregnancy, BMI, and number of pregnancies to assess the association between anti-HLA antibody levels and the occurrence of at least one obstetric complication, including FGR defined as birthweight below the 10th percentile for gestational age.
• Women with prior transfusion or organ transplantation were excluded from blood donation eligibility, ensuring pregnancy was the only identified source of HLA sensitization in the study population.

TAKEAWAY:

• Higher maternal anti-HLA antibody levels (> 1000 MFI) were independently associated with FGR after adjustment for maternal age, BMI, and number of pregnancies (adjusted odds ratio [aOR], 1.57; 95% CI, 1.02-2.41; P = .04).
• Anti-HLA antibody levels increased significantly with the number of ongoing pregnancies (aOR, 3.06; 95% CI, 1.77-5.27) and decreased with time since the last pregnancy (aOR, 0.93; 95% CI, 0.88-0.97), supporting pregnancy-related alloimmunization.
• No significant association was observed between anti-HLA antibody levels and overall obstetric complications (aOR, 1.27; 95% CI, 0.91-1.78) or complications beyond the first trimester (aOR, 1.35; 95% CI, 0.93-1.96).
• In exploratory analyses of 53 pregnancies occurring after antibody testing in women with a single prior live birth, FGR occurred predominantly in women with anti-HLA antibody levels > 1000 MFI (26.7% vs 2.6%; P = .019).

IN PRACTICE:

“Higher maternal anti-HLA antibody levels were associated with FGR, supporting the hypothesis that alloimmune mechanisms may contribute to a subset of growth-restricted pregnancies. These results are hypothesis-generating and do not support routine anti-HLA antibody testing in clinical practice at this stage,” the authors of the study wrote.

SOURCE:

The study was led by Pierre Hannoun, MD, Department of Obstetrics and Gynecology, Antoine Béclère Hospital, AP-HP, Université Paris Saclay, Clamart, France. It was published online in American Journal of Obstetrics and Gynecology.

LIMITATIONS:

The retrospective design based on self-reported obstetric histories introduces a risk for recall bias and outcome misclassification, limiting precise clinical phenotyping and precluding detailed classification of complications such as early vs late FGR or spontaneous vs medically indicated preterm birth. Anti-HLA antibody testing was performed outside of pregnancy in a blood donor population, introducing selection bias and limiting generalizability to pregnant populations. No placental histopathologic data or functional assays were available, and the absence of parental HLA typing prevented confirmation of fetus-specific antibodies involved in immune-mediated placental lesions. Subgroup analyses were limited by small sample sizes, and residual confounding cannot be excluded.

DISCLOSURES:

This study received partial funding from Ferring, Gentilly, France. The work was sponsored by AP-HP. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.