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Patterns of perinatal exposure to PUFAs and child neurodevelopment: evidence from Mendelian randomization using FADS
Aline Abou Assi1, Martine Armand2, Catherine Sarté2
1Université Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Centre for Research in Epidemiology and StatisticS, Paris, France.
Insights
Perinatal exposure to omega-3 long-chain polyunsaturated fatty acids (PUFAs) may benefit child neurodevelopment. However, exposure to linoleic acid (LA) and dihomo-gamma-linolenic acid (DGLA) might have adverse effects on cognitive development.
Area of Science:
- Nutritional Neuroscience
- Developmental Pediatrics
- Genetic Epidemiology
Background:
- The impact of perinatal polyunsaturated fatty acids (PUFAs) on child neurodevelopment is debated.
- Understanding these effects is crucial for early life health interventions.
Purpose of the Study:
- To investigate the causal relationship between perinatal PUFA exposure patterns and child neurodevelopment.
- Utilizing conventional regression and Mendelian randomization (MR) for robust inference.
Main Methods:
- Analysis of 1096 mother-child pairs from the French Etude des Déterminants Pré- et Postnatals du Développement de la Santé de L'enfant cohort.
- PUFA patterns identified from maternal, cord, and colostrum samples.
- Child intelligence quotients (IQs) assessed at ages 5-6 years.
- Maternal FADS1 and FADS3 variants used as genetic instruments for MR analysis.
Main Results:
- A pattern high in omega-3 and low in omega-6 long-chain PUFAs (LC-PUFAs) correlated with higher verbal and full-scale IQs.
- A pattern characterized by colostrum LC-PUFAs showed positive associations with all IQ measures.
- MR analysis supported a beneficial effect of the colostrum LC-PUFA pattern on performance IQ.
- The fourth pattern, involving linoleic acid (LA) and dihomo-gamma-linolenic acid (DGLA), was associated with lower performance IQ.
Conclusions:
- Perinatal exposure to LC-PUFAs appears to positively influence child neurodevelopment.
- Specific PUFA patterns, like those high in omega-3 LC-PUFAs, are linked to enhanced cognitive outcomes.
- Exposure to LA and DGLA during the perinatal period may negatively impact neurodevelopment.
Background:
The potential causal effects of perinatal exposure to polyunsaturated fatty acids (PUFAs) on child neurodevelopment remains controversial.
Objective:
To infer causation, we assessed the association of perinatal PUFA patterns and child neurodevelopment by using conventional regression analyses and 1-sample Mendelian randomization (MR).
Methods:
Among 1096 mother-child pairs from the French Etude des Déterminants Pré- et Postnatals du Développement de la Santé de L'enfant cohort, patterns of perinatal exposure to PUFAs were previously identified combining PUFA levels from maternal and cord erythrocytes, and colostrum. Child verbal, performance, and full-scale intelligence quotients (IQs) were assessed at ages 5-6 y. Among maternal fatty acid desaturase (FADS) variants genotyped, 2 candidates, rs174546 (FADS1) and rs174634 (FADS3), were selected, as instrumental variables, for the MR analysis. The association of PUFA patterns with child IQ was examined by conventional multivariable linear regression and 2-stage least-squares MR regression.
Results:
In the conventional approach, the first pattern "high omega-3 long-chain PUFAs (LC-PUFAs), low omega-6 LC-PUFAs" was positively associated with verbal IQ [β (95% confidence interval) = 1.24 (0.27, 2.21) points per 1 standard deviation (SD) increase in pattern] and full-scale IQ [1.11 (0.18, 2.05)]. This pattern was independent of FADS variants, rendering MR analysis inapplicable. The third pattern, "colostrum LC-PUFAs," was positively associated with verbal [1.11 (0.19, 2.02)], performance [1.01 (0.09, 1.93)], and full-scale IQ [1.13 (0.25, 2.01)]. The MR approach, based on genetic instruments strongly associated with the third pattern, supported the beneficial effect on performance IQ [2.93 (0.05, 5.81) points per 1 SD increase in genetically predicted pattern]. The MR also suggested a deleterious effect of the fourth pattern "linoleic acid (LA) and dihomo-gamma-linolenic acid (DGLA)" on performance IQ [-1.66 (-3.22, -0.09)].
Conclusions:
These findings supported the potential beneficial effects of perinatal exposure to LC-PUFAs on child neurodevelopment while highlighting possible adverse effects associated with exposure to LA and DGLA.
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