The influence of supplemental docosahexaenoic and arachidonic acids during pregnancy and lactation on neurodevelopment at eighteen months

Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment. The effects of DHA (220 mg/day, n=41), DHA+AA (220 mg/day, n=39) or placebo (n=34) during pregnancy and lactation on neurodevelopment at 18 months, and the relations between umbilical cord DHA, AA and Mead acid and neurodevelopment were studied. An age-specific, standardized neurological assessment for the evaluation of minor neurological dysfunction (MND), and the Bayley Scales of Infant Development (BSID) were used. The intervention did not influence any of the outcomes. Umbilical venous (UV) Mead acid was negatively and n-6 fatty acids were weakly positively associated to the BSID mental developmental index. Children with simple MND had lower UV DHA compared to normally classified children. We conclude that relatively short-term maternal DHA or DHA+AA supplementation does not influence neurodevelopment at toddler age, although some parameters of brain development are related to perinatal DHA and AA status.     

Human placental 15-hydroxy-prostaglandin dehydrogenase activity is under fetal genetic control

Placental 15-hydroxy-prostaglandin dehydrogenase (PGDH type I) was measured in 33 placentae obtained from 1 trizygotic, 7 dizygotic and 8 monozygotic pregnancies. PGDH activity ranged from 0.33 to 4.62 nmol PGF_2α metabolized per mg placental protein per min, which was within the range observed in singleton pregnancies. Expressing PGDH activity per mg DNA, offered no advantage over expressing it per mg total protein. PGDH activity differed significantly between the placentae of 6 of the 9 genetically non-identical placental pairs. The placentae of genetically identical twins, on the other hand, showed no difference in PGDH activity between the pairs. The data indicate that the genetic constitution of the fetus determines placental PGDH activity. They also provide us with the first evidence that the variation in prostaglandin catabolized capacity of the human placenta is not entirely dictated by the maternal endocrine environment, but is under fetal control.     

Increase in placental 15-hydroxy-prostaglandin dehydrogenase in the first half of human pregnancy

NAD-dependent 15-hydroxy-prostaglandin dehydrogenase (PGDH) activity was measured in homogenates of 25 human placentae obtained between 7 and 17 weeks of gestation. PGDH activity, expressed in nanomoles PGF_2α metabolized per min, ranged from 0.2 to 5.4 nmoles per mg placental protein and from 1.5 to 80 nmoles per g wet weight. PGDH activity per mg protein and per g weight increased significantly in function of gestational age (p<0.001). Between 7–8 weeks' gestation and 15–16 weeks mean values increased tenfold from 0.4 to 3.0 nmoles per mg protein and from 2.7 to 36.6 nmoles per g wet weight. Per unit of weight these early placentae contained less PGDH activity than term controls, but this related mainly to their high water content. Per mg placental protein PGDH activities already equalled values found at term before the end of the first trimester. The data indicate that the development of terminal villi and the migration of trophoblast into the maternal spiral arteries is associated with a substantial increase in the placental capacity for prostaglandin metabolism.     

Not prostacyclin synthase but prostaglandin endoperoxide synthase increases with human placental development

Prostaglandin endoperoxide synthase (i.e. cyclooxygenase; PGH sythase) and prostacyclin synthase (PGI synthase were quantitated with specific immunoradimetric assays in microsomes from human placentae (n=20) obtained from 7 up to 17 weeks of gestation. Over that period, wherein trophoblastic invasion of the uterine spiral arteries occurs, the placetae showed a significant increase in concentrations of PGH synthase (r=0.73, p<0.001; n=20), but not in those of PGI synthase. While the variation between individual placentae was much larger for PGI synthase than for PGH synthase concentrations, there was no evidence for a large excess of PGI synthase over that of PGH synthase in any of these early placentae. The data indicate, first, that the developing placenta contains PGI synthase, but in amount which are relatively small and do not appear to increase with advancing gestation. Second, they seem to indicate that the capacity for bioconversion of arachidonic acid into prostaglandin endoperoxides increases markedly with placental development.     

Increase in placental 15-hydroxy-prostaglandin dehydrogenase in the first half of human pregnancy

NAD-dependent 15-hydroxy-prostaglandin dehydrogenase (PGDH) activity was measured in homogenates of 25 human placentae obtained between 7 and 17 weeks of gestation. PGDH activity, expressed in nanomoles PGF2 alpha metabolized per min, ranged from 0.2 to 5.4 nmoles per mg placental protein and from 1.5 to 80 nmoles per g wet weight. PGDH activity per mg protein and per g weight increased significantly in function of gestational age (p less than 0.001). Between 7-8 weeks' gestation and 15-16 weeks mean values increased tenfold from 0.4 to 3.0 nmoles per mg protein and from 2.7 to 36.6 nmoles per g wet weight. Per unit of weight these early placentae contained less PGDH activity than term controls, but this related mainly to their high water content. Per mg placental protein PGDH activities already equalled values found at term before the end of the first trimester. The data indicate that the development of terminal villi and the migration of trophoblast into the maternal spiral arteries is associated with a substantial increase in the placental capacity for prostaglandin metabolism.     

Human placental 15-hydroxy-prostaglandin dehydrogenase activity is under fetal genetic control

Placental 15-hydroxy-prostaglandin dehydrogenase (PGDH type I) was measured in 33 placentae obtained from 1 trizygotic, 7 dizygotic and 8 monozygotic pregnancies. PGDH activity ranged from 0.33 to 4.62 nmol PGF2 alpha metabolized per mg placental protein per min, which was within the range observed in singleton pregnancies. Expressing PGDH activity per mg DNA, offered no advantage over expressing it per mg total protein. PGDH activity differed significantly between the placentae of 6 of the 9 genetically non-identical placental pairs. The placentae of genetically identical twins, on the other hand, showed no difference in PGDH activity between the pairs. The data indicate that the genetic constitution of the fetus determines placental PGDH activity. They also provide us with the first evidence that the variation in prostaglandin catabolizing capacity of the human placenta is not entirely dictated by the maternal endocrine environment, but is under fetal control.     

Mildly abnormal general movement quality in infants is associated with higher Mead acid and lower arachidonic acid and shows a U-shaped relation with the DHA/AA ratio

We showed that docosahexaenoic acid (DHA) supplementation during pregnancy and lactation was associated with more mildly abnormal (MA) general movements (GMs) in the infants. Since this finding was unexpected and inter-individual DHA intakes are highly variable, we explored the relationship between GM quality and erythrocyte DHA, arachidonic acid (AA), DHA/AA and Mead acid in 57 infants of this trial. MA GMs were inversely related to AA, associated with Mead acid, and associated with DHA/AA in a U-shaped manner. These relationships may indicate dependence of newborn AA status on synthesis from linoleic acid. This becomes restricted during the intrauterine period by abundant de novo synthesis of oleic and Mead acids from glucose, consistent with reduced insulin sensitivity during the third trimester. The descending part of the U-shaped relation between MA GMs and DHA/AA probably indicates DHA shortage next to AA shortage. The ascending part may reflect a different developmental trajectory that is not necessarily unfavorable.     

Not prostacyclin synthase but prostaglandin endoperoxide synthase increases with human placental development

Prostaglandin endoperoxide synthase (i.e. cyclooxygenase; PGH synthase) and prostacyclin synthase (PGI synthase) were quantitated with specific immunoradiometric assays in microsomes from human placentae (n = 20) obtained from 7 up to 17 weeks of gestation. Over that period, wherein trophoblastic invasion of the uterine spiral arteries occurs, the placentae showed a significant increase in concentrations of PGH synthase (r = 0.73, p less than 0.001; n = 20), but not in those of PGI synthase. While the variation between individual placentae was much larger for PGI synthase than for PGH synthase concentrations, there was no evidence for a large excess of PGI synthase over that of PGH synthase in any of these early placentae. The data indicate, first, that the developing placenta contains PGI synthase, but in amounts which are relatively small and do not appear to increase with advancing gestation. Second, they seem to indicate that the capacity for bioconversion of arachidonic acid into prostaglandin endoperoxides increases markedly with placental development.