Effect Of Perinatal Iron Deficiency On Brainstem Auditory Evoked Potential And Psychomotor Development In Infancy

Iron is a ubiquitous element that is required for many basic biochemical functions. Iron deficiency is the most common single nutrient deficiency disorder in the world which especially affects pregnant women,infants and children,owing to the high demand for iron but low iron in diet.Iron deficiency is known to effect of more than 1.2 billion people worldwide.The most well described effect of iron deficiency is anemia, but the effect of all other organ systems should not be underestimated.Iron deficiency anemia in infancy is associated with delayed brain development such as cognition, behavior,social-emotion,neurophysiology et al.This poor development during infancy persists in most cases after iron therapy has corrected the iron status.Studies on animal models have documented that iron is one of the largest amount of trace elements in brain except zinc.Iron plays a significant role in neurodevelopment because of iron-containing enzymes involved in brain-energy metabolism,neurotransmitter synthesis and myelination.Animal studies have shown that plausible biological mechanisms of iron deficiency effects on brain are hypomyelination,reduction in the density and affinity of dopamine D₂ receptor,alteration of tissue oxygenation and energy metabolism in the brain.Considerable researches on iron deficiency in the human infants have involved into 6 to 24 month old healthy babies born at term with normal birth weights and without perinatal problems.In contrast to the literature on postnatal iron deficiency,perinatal (i.e.late fetal and neonatal)iron deficiency has received little attention.Certain gestational conditions associated with decreased fetal iron delivery and/or increased fetal iron demand beyond the placental transport capacity can result in perinatal iron deficiency.Many factors have a negative effect on fetal iron status during the perinatal period such as maternal iron deficiency,maternal diabetes mellitus,maternal smoking and intrauterine growth retardation et al.Maternal iron deficiency is the most common cause of perinatal iron deficiency worldwide.Iron deficiency during the perinatal period also appears to be detrimental to the developing brain.Researches from animal models have demonstrated neurometabolic,structural,electrophysiological and behavioral alterations in developing rats subjected to perinatal iron deficiency.Few studies have assessed the role of perinatal iron deficiency on neurodevelopment in human infants. Tamura et al.have described impaired language ability,fine-motor skills and tractability at 5 years in children with cord serum ferritin concentration＜76μg/L.No literature has reported the adverse effect of perinatal iron deficiency on brainstem auditory evoked potential(BAEP)and psychomotor development in infancy.The purposes of our study were as following:First is to investigate the prevalence of anemia,iron deficiency,iron deficiency anemia in pregnant women at different gestational ages in Zhejiang province.Second is to explore the range of ferritin level in healthy full-term neonates and the correlation of the ferritin concentration of cord blood with maternal blood at different gestational ages.The third is to investigate the effect of fetal iron status on BAEP,psychomotor development in infancy.Part OneIron status in perinatal period and relation between fetal iron status and maternal iron statusObjectives1.To investigate the prevalence of anemia,iron deficiency,iron deficiency anemia in pregnant women during the perinatal period in Zhejiang province.2.To explore the normal range of umbilical cord serum ferritin in healthy full-term infants and define the cut-off value for low ferritin concentration.3.To evaluate the correlation between fetal iron status and maternal iron statusMethodsBetween September 2005 and April 2007,a total of 4262 pregnant women were included into the study,who came for antenatal care in the three local hospitals of Zhejiang province:Fuyang women and children's hospital,Yongkang women and children's hospital and Huzhou women and children's hospital.Among them,371 were in the 28～32 week GA,3891 in the 37～40 week GA.Iron status of 3550 neonates matched with the pregnant women was also determined,149 were in the 28～32 week GA,3401 in the 37～42 week GA.All pregnant women and neonates were determined for hemoglobin,ferritin,lead and neonates for high sensitivity C-reactive protein in addition.Results1.The prevalence rate of anemia,iron deficiency,iron deficiency anemia of pregnant women in 28～32 week GA was high.40%of women had anemia, 25.8%had iron deficiency anemia and 58.5%had iron deficiency.2.The prevalence rate of anemia,iron deficiency,iron deficiency anemia of pregnant women in 37～42 week GA was lower than those in 28～32 week GA (P＜0.01).28.1%of women had anemia,19.3%had iron deficiency anemia, 49.6%had iron deficiency.3.A significant positive correlation was found between the cord ferritin concentration and maternal ferritin concentration(37～40 week GA group)(r =0.095,P＜0.01),but no correlation with that of 28～32 week GA group.4.The mean value of cord ferritin of healthy,full-term neonates was 187.2±102.31μg/L,the 5^th,10^th,75^thpercentile rank were 59.8μg/L,76.2μg/L,239μ/L respectively.Conclusions1.In Zhejiang province,the prevalence rate of anemia,iron deficiency,iron deficiency anemia of women during the third trimester of pregnancy was high, especially iron deficiency.2.The mean value of cord ferritin of healthy,full-term neonates was 187.2±102.3μg/L,the 5^th,10^th,75^thpercentile rank were 59.8μg/L,76.2μg/L,239μg/L respectively.3.A significant positive correlation was found between the cord ferritin concentration and maternal ferritin concentration.Maternal iron deficiency may influence the neonatal iron status.Part TwoFetal iron status and brainstem auditory evoked potential, psychomotor development in infancyObjectives1.To investigate the alteration of BAEP in infants with low fetal iron status. 2.To evaluate the effect of fetal iron status on mental and psychomotor development in infancy.MethodsA total of 115 infants were followed,62 at 3-month old,53 at 10-month old. According to the umbilical cord serum ferritin concentration,all infants were divided to two groups:low fetal iron status group(cord ferritin concentration＜75μg/L)and normal fetal iron status(cord ferritin concentration between 75μg/L and 239μg/L). The BAEP indexes and developmental scores of BSID and PDMS-2 were obtained in infants at three months old and ten months old.The parameters or scores for evaluation are as following:1.BAEP indexes:Peak latency and amplitude of wavesâ… ,â…¢,â…¤,and interpeak latency of waveâ… -â…¢,â…¢-â…¤andâ… -â…¤.2.Bayley scales of infant development:mental development index(MDI)and psychomotor development index(PDI).3.Peabody Developmental Motor Scales 2:Percentiles and standard scores for subtests(reflexes,stationary,locomotion,grasping,visual-motor integration) and composites(gross motor scales,fine motor scales and total motor scales), gross motor quotient(GMQ),fine motor quotient(FMQ),total motor quotient (TMQ).Results1.Peak latency for waveâ…¤and interpeak latency forâ… -â…¤were significantly longer in all infants with low fetal iron status(P＜0.05).Amplitude for waveâ…¤was significantly lower in all infants with-low fetal iron status(P＜0.05)2.For 3-month old infants,no significant difference was found in scores of BSID and PDMS-2 between low fetal iron status group and normal fetal iron status group.3.For 10-month old infants,PDI,standard scores for stationary,locomotion, grasping,gross motor,total motor were significantly lower in infants with low fetal iron status(P＜0.05).GMQ and TMQ were significantly lower in infants with low fetal iron status(P＜0.05).No significant difference was found in MDI,standard scores for reflexes,visual-motor integration and FMQ between the two groups(P＞0.05).ConclusionsPoor fetal iron status is associated with the changes of peak latency and amplitude of BAEP in infancy.It may also attribute to poor psychomotor development in 10-month old infants.BAEP is more sensitive than psychomotor development test for understanding the effect of perinatal iron deficiency on brain development in infancy.