The FADS insertion-deletion polymorphism drives the arachidonic acid/dihomo-gamma-linolenic acid ratio in preterm infants and may contribute to patency of ductus arteriosus - a pilot study.
Herrman K, Reid D, et al. • Prostaglandins, leukotrienes, and essential fatty acids • 2026
The FADS Indel polymorphism significantly modulates the ARA/DGLA ratio in preterm infants consistent with adults, while PDA associations were nonsignificant but trends warrant study in larger cohorts.
Key Findings
Results
The FADS Indel polymorphism (rs66698963) significantly modulates the ARA/DGLA ratio in preterm infants, with I/I homozygotes showing a 33% higher ratio than D/D homozygotes.
Study enrolled 65 premature infants with a mean gestational age of 28 weeks
ARA/DGLA ratio was 33% higher in I/I than D/D infants (ANOVA p=0.029; Welch's t-test p=0.04)
The difference remained significant after gestational-age adjustment (p=0.025)
Gestational age did not differ by genotype (p=0.68), ruling out confounding by gestational age
Results
Genotype distribution in the preterm infant cohort was D/D in 40%, I/D in 48%, and I/I in 12% of infants.
D/D genotype: 26 infants (40%)
I/D genotype: 31 infants (48%)
I/I genotype: 8 infants (12%)
Blood fatty acids were analyzed by gas chromatography and genotype by PCR
Results
PDA rates showed a nonsignificant increasing trend from D/D to I/D to I/I genotype.
PDA rates were 42% in D/D, 45% in I/D, and 50% in I/I infants
Cochran-Armitage trend test p=0.70; OR=1.15, p=0.70
The association was nonsignificant in this pilot cohort of 65 infants
The authors note that trends warrant study in larger cohorts
Results
Among echo-confirmed PDA cases, spontaneous closure rates varied by genotype with differences in rates of catheter-based closure.
29 infants had echo-confirmed PDA
Spontaneous closure rates were 60% in D/D, 31% in I/D, and 50% in I/I infants
Six infants required Piccolo occlusion (catheter-based closure)
I/I infants had more catheter-based closures than D/D genotype infants
Background
In adults, homozygous I/I individuals have up to 84% higher ARA/DGLA ratios than D/D homozygotes, and this study confirms the FADS Indel modulates fatty acid desaturase activity in preterm neonates as well.
FADS1 converts dihomo-γ-linolenic acid (DGLA) to arachidonic acid (ARA)
ARA is the precursor to prostaglandin E2 (PGE2), a key mediator of ductal patency
Prior adult data showed up to 84% higher ARA/DGLA in I/I vs D/D homozygotes
Whether this relationship extended to preterm neonates was previously unknown
Methods
Genotype associations with PDA outcomes were assessed using multiple statistical approaches including Fisher's exact test, Cochran-Armitage trend test, and logistic regression.
Fatty acid comparisons used Welch's t-test and one-way ANOVA
The study was prospective in design
The study is described as a pilot study, limiting statistical power
The authors acknowledge the nonsignificant PDA associations may reflect insufficient sample size
What This Means
This research suggests that a specific genetic variant in the FADS gene (called the Indel polymorphism, rs66698963) influences how premature babies process certain fatty acids. Specifically, preterm infants who carry two copies of the 'insertion' version of this gene (I/I) had about 33% higher levels of arachidonic acid (ARA) relative to its precursor molecule (DGLA) compared to infants with two copies of the 'deletion' version (D/D). This is notable because arachidonic acid is converted in the body into a substance called prostaglandin E2, which plays a key role in keeping a blood vessel called the ductus arteriosus open after birth. Normally this vessel closes shortly after birth, but when it stays open — a condition called patent ductus arteriosus (PDA) — it can cause medical problems in premature infants.
The study also found that PDA rates appeared to increase slightly with each copy of the insertion gene variant (42% in D/D, 45% in I/D, and 50% in I/I infants), and that I/I infants tended to need more procedural interventions to close the vessel. However, these differences were not statistically significant, meaning they could have occurred by chance, particularly given the small sample size of only 65 infants.
This research suggests that genetic differences in fatty acid metabolism may help explain why some premature infants are more likely to develop PDA than others. The finding that this gene variant influences ARA/DGLA ratios in preterm infants — just as it does in adults — is a meaningful confirmation, but the clinical implications for PDA require investigation in much larger groups of infants before any conclusions can be drawn.
Herrman K, Reid D, Li Y, Park H, Mukherjee P, Brand K, et al.. (2026). The FADS insertion-deletion polymorphism drives the arachidonic acid/dihomo-gamma-linolenic acid ratio in preterm infants and may contribute to patency of ductus arteriosus - a pilot study.. Prostaglandins, leukotrienes, and essential fatty acids. https://doi.org/10.1016/j.plefa.2026.102767