Abnormal neurological responses in young adult offspring caused by excess omega-3 fatty acid (fish oil) consumption by the mother during pregnancy and lactation

Abstract

Consuming omega-3 fatty acids (ω-3 FA) during pregnancy and lactation benefits fetal and infant brain development and might reduce the severity of preterm births by prolonging pregnancy. However, diets that are relatively rich in ω-3 FA can adversely affect fetal and infant development and the auditory brainstem response (ABR), a measure of brain development and sensory function. We previously examined the offspring of female rats fed excessive, adequate or deficient amounts of ω-3 FA during pregnancy and lactation. The 24-day-old offspring in the Excess group, compared to the Control group, had postnatal growth retardation and poor hearing acuity and prolonged neural transmission times as evidenced by the ABR. The Deficient group was intermediate. The current study followed these offspring to see if these poor outcomes persisted into young adulthood. Based on prior findings, we hypothesized that the Excess and Deficient offspring would "catch-up" to the Control offspring by young adulthood. Female Wistar rats received one of the three diet conditions from day 1 of pregnancy through lactation. The three diets were the Control ω-3 FA condition (ω-3/ ω-6 ratio ~ 0.14), the Excess ω-3 FA condition (ω-3/ω-6 ratio ~ 14.0) and Deficient ω-3 FA condition (ω-3/ω-6 ratio ~ 0% ratio). The Control diet contained 7 % soybean oil; whereas the Deficient and Excess ω-3 FA diets contained 7% safflower oil and 7% fish oil, respectively. One male and female offspring per litter were ABR-tested as young adults using tone pip stimuli of 2, 4, 8 and 16 kHz. The postnatal growth retardation and prolonged neural transmission times in the Excess and Deficient pups had dissipated by young adulthood. In contrast, the Excess group had elevated ABR thresholds (hearing loss) at all tone pip frequencies in comparison to the Control and Deficient groups. The Deficient group had worse ABR thresholds than the Control group in response to the 8 kHz tone pips only. The Excess group also had ABR amplitude-intensity profiles suggestive of hyperacusis. These results are consistent with the Barker hypothesis concerning the fetal and neonatal origins of adult diseases. Thus, consuming diets that are excessively rich or deficient in ω-3 FA during pregnancy and lactation seems inadvisable because of risks for long-lasting adverse effects on brain development and sensory function.

Repeated antenatal corticosteroid treatments adversely affect neural transmission time and auditory thresholds in laboratory rats

“…The P1 latency measures the auditory (peripheral) nerve’s transmission time and the P1- P4 IPL measures the brainstem (central) transmission time. These secondary outcome variables allowed us to determine if treatment effects on the P4 latency had peripheral and/or central origins [13,17]. …”

“…ABR thresholds were determined by the method of limits [13,17]. Here, serial ABRs were gathered to a range of stimulus intensities starting at 100dB and then descending to 80, 60, 50, 40, 35, 30, 25, 20, and 15 dB as the ABR threshold was reached and passed.…”

“…A subject with a SNHL will also have an elevated ABR threshold, however the P2 latencies will typically be normal or near normal in response to loud stimulus intensities but progressively curve upward from the normal range as the stimulus intensity decreases [13]. In rodents, one typically uses the ABR’s P2 wave to derive an animal’s latency-intensity (L-I) profile because the rodent’s P2 wave is the largest wave and usually the last wave to disappear as the sound stimulus decreases [13,17]. P2 latency was measured at this waveform’s positive peak.…”

Excess omega-3 fatty acid consumption by mothers during pregnancy and lactation caused shorter life span and abnormal ABRs in old adult offspring

“…This is known as the Barker or “Fetal Programming” Hypothesis [10]. No one has investigated the possibility that nutritional toxicity from high levels of dietary ω-3 FA or a high ω-3/ω-6 ratio can cause fetal programming of adult-onset disorders, with the exception of studies by our group which found abnormal neurological function [29] and altered body fat composition in young adult rats born to dams receiving diets rich in ω-3 FA during pregnancy and lactation [45]. Only one animal study has investigated the life-long effects of prenatal essential FA deficiency and found a faster aging brain in old age as evidenced by the ABR [12].…”

Deficits in Docosahexaenoic Acid Accrual during Adolescence Reduce Rat Forebrain White Matter Microstructural Integrity: An in vivo Diffusion Tensor Imaging Study

“…Preclinical studies further suggest that n-3 PUFAs promote oligodendrocyte maturation and myelin expression [30,31], and are protective against axonal WM injury induced by trauma [32] and inflammation [33,34]. However, other studies suggest that maternal n-3 PUFA supplementation or deficiency impair neonatal axonal conduction, which is consistent with dysmyelination [35][36][37]. While these findings suggest that there are optimal n-3 PUFA levels required for normal axonal WM maturation and resilience, the effect that altering n-3 PUFA levels has on brain WMI has not been systematically evaluated in vivo using DTI.…”