The effects of maternal dietary docosahexaenoic acid intake on rat pup myelin and the auditory startle response.

UNLABELLED: We investigated the effects of maternal docosahexanoic acid (DHA) supplementation on pups' auditory startle responses and the composition of brain myelin. METHODS: Timed-pregnant rats were fed throughout pregnancy and lactation diets that contained 0, 0.3, 0.7 or 3% of total fatty acids as DHA. Milk was collected from culled pups' stomachs on postnatal day (PND) 3, latency of the auditory startle reflex was measured on PND 15, and pups were killed and brains collected on PND 24. RESULTS: Higher levels of DHA in maternal diet were reflected in milk and in pups' myelin. The latency of the auditory startle response was significantly longer in offspring of dams fed higher levels of DHA. There was a positive correlation between the myelin content of DHA and the latency of the startle response (p = 0.044), and a negative correlation between the myelin content of DHA and the myelin content of cholesterol (p = 0.005). CONCLUSION: High levels of maternal DHA intake alter the lipid composition of rat pup myelin, and are associated with longer latencies of the auditory startle response--a myelin-dependent electrophysiologic response.

Dietary nucleotides and intestinal blood flow velocity in term infants.

OBJECTIVES: Two previous studies have shown that the addition of nucleotides to single feedings of formula is associated with increased 90-minute postprandial superior mesenteric artery (SMA) blood flow velocity (BFV). To assess the effect of chronic feeding of nucleotide-supplemented formula, we measured pre- and postprandial SMA BFV in term infants fed formula with or without added nucleotides for 4 weeks. METHODS: At 1 week of age, healthy, term infants were randomized to receive formula with added nucleotides (NT+), or formula without added nucleotides (NT-) from age 1 to 5 weeks. When the infants were 5 weeks of age, SMA BFV was measured by Doppler ultrasound 15 minutes before the assigned feeding (baseline) and 30, 60, and 90 minutes after the start of feeding. A reference group of human milk-fed infants was studied before and after breast feeding. RESULTS: Thirty formula-fed (NT+ = 17; NT- = 13) and 10 human milk-fed infants were studied. Baseline BFV was similar among the three groups. BFV increased in each group from baseline to 30 minutes after initiation of feeding and progressively declined from 30 to 90 minutes in infants fed NT- formula or human milk. In infants fed NT+ formula, BFV decreased between 30 and 60 minutes. However, from 60 to 90 minutes, velocity was unchanged or increased. At 90 minutes, mean and peak systolic velocities were significantly greater in the NT+ group than the NT- group (P < 0.001). CONCLUSIONS: These data agree with those of previous studies showing increased 90-minute postprandial SMA BFV after a feeding with nucleotide-supplemented formula. The clinical significance of these findings is unknown.

Pontine hypoplasia in Carey-Fineman-Ziter (CFZ) syndrome.

We describe an infant with multiple congenital anomalies including cleft palate and micrognathia, Möbius sequence, developmental delay, myopathy, hydronephrosis, and bilateral clubfeet. These features are consistent with Carey-Fineman-Ziter (CFZ) syndrome (MIM 254940), which has been previously reported in six children (including two sibling pairs). Cranial magnetic resonance imaging (MRI) revealed an unusually small pons, a finding not previously described in CFZ syndrome.

The effects of dietary nucleotides on intestinal blood flow in preterm infants.

Nucleotides (NT) are reported to affect development of the immune and gastrointestinal systems, and they are currently added to most term infant formulas. In the present study, dietary NT effects on superior mesenteric artery blood flow were investigated. Formula-fed preterm infants were studied once with a 20 kcal/oz. term infant formula containing 80.6 mg/L of NT (NT+), and once with the same formula with no added NT (NT-) (n = 20, gestational age 28.0 +/- 2.2 wk). A reference group of preterm infants fed human milk was also studied (n = 20, gestational age 29.0 +/- 1.6 wk). Superior mesenteric artery blood flow velocities (BFV) were measured by Doppler ultrasound 15 min before and 30, 60, and 90 min after the start of the feed. BFV rose in all infants from baseline to 30 min after feed initiation, and progressively declined thereafter in infants fed NT- or human milk. However, NT+ feedings were associated with a minimal change in BFV between 60 and 90 min. As a result, the difference in blood flow velocities between baseline and 90 min was significantly greater with the NT+ versus the NT- feedings for the mean, peak systolic, and end diastolic velocities (p = 0.03, 0.05, and 0.03, respectively). BFV after the NT- and human milk feedings were similar. These data suggest that orally administered NT are associated with effects on the intestinal vasculature.

Maternal dietary docosahexanoic acid content affects the rat pup auditory system.

Previous studies of the effects of dietary docosahexanoic acid (DHA), 22:6n3, on neurodevelopment have focused mainly on visual-evoked potentials and indices of visual activity, measures that may be confounded by effects on the retina rather than on neural pathways. We investigated the effect of pre- and postnatal maternal dietary DHA content on auditory brainstem conduction times (ABCTs), the appearance of the auditory startle reflex (ASR), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) activity in brainstem homogenates. Timed pregnant dams were fed, beginning on day 2 of gestation and throughout lactation, a purified diet containing one of three levels of DHA (0, 1, or 3% of total fatty acids, or 0, 0.4 or 1.2% of total energy). On postnatal day (PND) 3, pups were randomly crossfostered within diet groups to minimize litter effects and culled to 10 per litter. Cerebrums and milk from culled pups stomachs were collected for lipid analysis. The timing of appearance of the ASR was determined between PND 10 through 14 and ABCTs were measured in pups on PND 24 and 31. Pups were sacrificed on PND 31 and cerebrums were removed. In each of two replicated studies, pups in the 1% DHA group weighed significantly less on PND 3 and they gained significantly less weight from PND 3 to 31 compared with pups in the 0 or 3% groups (p<0.01). The auditory studies were not conducted on the 1% DHA group since measures of auditory function are in part a function of somatic growth. The tissue fatty acid data for the 1% DHA group did not show unexpected findings. Higher dietary DHA was reflected in milk and pup cerebrums, and levels of arachidonic acid were inversely related to levels of DHA. In the pups of dams fed diets containing 3% versus 0% DHA, the ASR appeared significantly later (p<0.001) and the ABCTs were longer (p<0.05) on PND 31. CNPase activity levels were not different between the 0 and 3% DHA groups. This study demonstrated that the auditory brainstem response is sensitive for identifying effects of diet on neurodevelopment, and that diets supplemented with high levels of DHA may exert a negative influence on central nervous system development, potentially through effects on myelin. This study suggests the need for further studies of pre- and postnatal long chain polyunsaturated fatty acid dietary supplementation.