***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: Summary Background Pre- and postnatal tissue accretion of long-chain polyunsaturated fatty acids ( LCPUFA ) has been related to visual and cognitive development in healthy children in several studies . Children with phenylketonuria ( PKU ) consume diets with very low contents of preformed LCPUFA . We studied prospect ively the LCPUFA status in infants with PKU without or with LCPUFA supplementation during the first year of life . Subjects and methods Infants with PKU were enrolled at diagnosis ( < 4 weeks of age ) and r and omized double blind to phenylalanine-free amino acid supplements without LCPUFA ( n=11 ) or with both arachidonic ( AA , 0.46 wt% ) and docosahexaenoic acids ( DHA , 0.27 wt% ) ( n=10 ) . At enrolment and again at 1 , 2 , 3 , 4 , 6 , 9 and 12 months , plasma phospholipid fatty acids were measured and dietary intakes were calculated from dietary protocol s. Results Unsupplemented patients showed a marked LCPUFA depletion to levels clearly below those observed in healthy breast-fed infants . In contrast , supplemented infants had stable and higher LCPUFA levels than unsupplemented infants , reaching significant differences for AA values at 3 , 4 and 6 months , and for DHA values at 1 , 3 , 4 , 6 , 9 and 12 months . Plasma phospholipid levels correlated closely with estimated dietary intakes of preformed LCPUFA . Conclusion Low LCPUFA intakes with PKU diets induce marked depletion of AA and particularly of DHA in the first year of life . Thus endogenous synthesis of LCPUFA from precursors supplied by diet seems unable to compensate for low LCPUFA intakes . LCPUFA supplementation of PKU diets during the first year of life effectively enhances LCPUFA status to levels comparable to those of healthy breast-fed infants OBJECTIVE The maternal phenylketonuria ( PKU ) syndrome is caused by high blood phenylalanine ( Phe ) levels during pregnancy , leading to a host of birth defects , especially microcephaly and congenital heart disease ( CHD ) . For finding whether the maternal PKU syndrome could be prevented , an international collaborative study was organized to evaluate treatment with a Phe-restricted diet .  Blood Phe levels , maternal weight gain , and nutrient intakes during pregnancy were evaluated as to their effect on the rate of microcephaly and CHD in the offspring . METHODS The study was a prospect i ve , longitudinal effort aim ed at lowering blood Phe during pregnancy . Women were enrolled at time of referral for pregnancy .  Nutrient intake analysis , which serves as the basis for this report , was available from 251 pregnancies . Subjects were stratified by blood Phe control of < or = 600 micromol/L by 8 weeks gestation or > 600 micromol/L by 8 weeks gestation . Outcome of these pregnancies was correlated to blood Phe levels , weight gain , and nutrient intake . RESULTS The study goal was to attain blood Phe levels of 120 to 360 micromol/L 3 months preconception ; however , this goal was achieved by only a limited number of patients . Therefore , the data presented were based on blood Phe control < or = 600 micromol/L or > 600 micromol/L by 8 weeks of gestation . Blood Phe control of < or = 600 micromol/L by 8 weeks of gestation was attained by 86 ( 34.3 % ) of the 251 women in this study , whereas the other 165 women had blood Phe control > 600 micromol/L by 8 weeks of gestation . Of the 251 offspring , 166 were born with normal head circumference and 85 were born with microcephaly ( < 2 st and ard deviations below normal ) . Women with blood Phe > 600 micromol/L at 8 weeks of gestation included 78 ( 92 % ) of the 85 infants with microcephaly compared with 8 % in the group of women who had blood Phe levels < or = 600 micromol/L. Weight gain during pregnancy was related to the rate of microcephaly . The highest occurrence of microcephaly ( 58 % ) was found in the pregnant women who gained < 70 % of recommended weight gain . Stepwise logistic regression analysis was used to determine factors associated with microcephaly . Significant factors included higher blood Phe levels when off diet , higher average Phe exposure during the pregnancy , low prepregnancy weight , poor weight gain during the pregnancy , and lower intake of protein and higher iron intake during the pregnancy . Infants with CHD were found only in the group of women who had blood Phe levels > 600 micromol/L by 8 weeks of gestation . There was a higher rate of CHD in the offspring who were born to women who consumed < 50 % of the recommended intake of protein in the first trimester . The main source of protein for women with PKU is the medical food ; therefore , when protein intake was low , vitamin and mineral intakes were also inadequate . CONCLUSIONS The data indicate that blood Phe control and how soon it is attained during pregnancy with PKU is important . Normal pregnancy weight gain should be encouraged to reduce microcephaly . Adequate protein and vitamin intakes early in pregnancy may have a protective effect for the prevention of CHD , even if blood Phe is elevated . The rate of microcephaly and CHD may be reduced if nutrient intake is optimal while attempting to control blood Phe levels PURPOSE To prospect ively determine the relationship between serum phenylalanine levels and apparent diffusion coefficient ( ADC ) values in the cerebral white matter of patients with phenylketonuria ( PKU ) . MATERIAL S AND METHODS Institutional review board approval was obtained , and participants provided informed consent . Magnetic resonance ( MR ) imaging , which included T1- and T2-weighted , fluid-attenuated inversion-recovery ( FLAIR ) , and diffusion-weighted examinations , was performed in 21 patients with PKU ( nine male and 12 female patients ; age range , 3 - 44 years ; mean age , 19.4 years ) .  ADC values in deep cerebral white matter were calculated for each patient . Serum phenylalanine levels were obtained in all patients within 12 days after MR imaging . Serum phenylalanine levels were measured in 16 patients 1 year before MR imaging . ADC values in cerebral white matter and serum phenylalanine levels were compared . A total of 21 control subjects ( 12 male and nine female patients ; age range , 3 - 33 years ; mean age , 20.6 years ) underwent MR imaging .  ADC values in cerebral white matter were compared with serum phenylalanine levels by using the Pearson correlation . RESULTS Abnormal high signal intensity in white matter on T2-weighted and FLAIR MR images was noted in patients with PKU who had serum phenylalanine levels of more than 8.5 mg/dL ( 514.2 micromol/L ) . Diffusion in posterior deep cerebral white matter tended to be restricted in patients when increased serum phenylalanine levels were measured after MR imaging ( r = -0.62 ) . There was a correlation between ADC values in posterior cerebral white matter and serum phenylalanine levels measured 1 year before MR imaging ( r = -0.77 ) . ADCs of control subjects were significantly higher than ADCs of patients with PKU ( P < .005 ) . CONCLUSION Posterior deep white matter in patients with PKU and a serum phenylalanine level of more than 8.5 mg/dL showed high signal intensity in white matter on T2-weighted and FLAIR MR images and revealed decreased ADC . We suggest that to avoid brain-restricted diffusion due to hyperphenylalanemia , patients with PKU should maintain serum phenylalanine levels of less than 8.5 mg/dL ( 514.2 micromol/L ) Summary : Women with phenylketonuria ( PKU ) must follow a strict low-phenylalanine diet during pregnancy in order to protect the fetus from the deleterious effects of high maternal blood phenylalanine . The Re source Mothers Study of Maternal PKU was undertaken to determine whether a home visitation programme was effective in helping women with PKU attain blood phenylalanine control earlier during pregnancy . Re source Mothers were trained to provide social support and practical assistance to women with PKU during pregnancy . Eight metabolic clinics in the United States participated in the study . Women with PKU who were planning pregnancy or already pregnant were enrolled in the study and were treated with a low-phenylalanine diet aim ed at controlling blood phenylalanine to 120–360 µmol/L. They were r and omly assigned to receive the services of a Re source Mother ( RM group ) or to a control group . Fifty women were enrolled , and accounted for 44 pregnancies which result ed in 28 live births , and 6 spontaneous abortions . Ten women are currently pregnant and another 6 have not become pregnant . Fifty-six percent of enrolled women began the diet prior to becoming pregnant . Fifty-three percent of women in the Re source Mother group were in metabolic control by 10 weeks gestation as compared to 39 % in the control group . In addition , women who began diet after pregnancy and had a Re source Mother attained metabolic control earlier ( mean gestational age of 22.4 weeks in the RM group vs 29.8 weeks in the control group ) . There was no difference in birth measurement z-scores of offspring born to women in the RM group compared to controls . All but 4 women rated themselves as feeling worse about the diet at the end of pregnancy than at the beginning , and few women in either group remained on diet after delivery OBJECTIVE To determine the effects of large neutral amino acid ( LNAA ) supplements on brain and plasma phenylalanine ( Phe ) levels and other metabolites in early treated subjects with classical phenylketonuria ( PKU ) , and to investigate the relationship between these metabolites and neuropsychological performance . METHODS This was a prospect i ve , double blind , cross over study consisting of four two-week phases with a 4 week washout period . Sixteen subjects ( 7 males ) , with classical PKU were recruited into the study and completed all 4 phases . Each phase consisted of either the LNAA supplement or placebo , and either the patient 's usual medical product or not . Subjects were instructed to follow their usual Phe restricted diet , maintain energy intake and complete a 3-day food record during each phase . At the end of each phase , brain Phe and other metabolites were measured by proton magnetic resonance spectroscopy ( MRS ) , and plasma amino acids quantified . A detailed neuropsychological assessment was performed on the same day as the MRS and plasma collection . RESULTS There was no correlation between plasma and brain Phe , but few of the plasma Phe readings were over 1200 micromol/L. Plasma Phe decreased with LNAA supplementation when patients were not taking their medical formula . LNAA supplementation had a specific impact on executive functions particularly in verbal generativity and cognitive flexibility . Measures of attention were better on medical product , with or without LNAA supplements . CONCLUSIONS LNAA supplementation was associated with a trend to a lowering of plasma Phe levels .  LNAA supplementation had a specific impact on executive functions particularly in verbal generativity and flexibility . For individuals already complying with diet and PKU medical product , additional supplementation with LNAA is of limited value . LNAA supplementation may be of benefit to those unable to comply with PKU medical product by reducing plasma Phe , perhaps by competing with Phe at the level of transport across the gut OBJECTIVE To assess cognitive and behavioral outcome in treated maternal phenylketonuria ( PKU ) offspring . METHODS In this prospect i ve , longitudinal study , 228 children who were born to mothers with treated PKU or untreated mild hyperphenylalaninemia were compared with 70 control subjects at 7 years of age . RESULTS Offspring cognitive outcome negatively correlated with the number of gestational weeks that elapsed until maternal metabolic control was achieved ( r = -0.61 ) . Behavioral outcome was similarly affected . Postnatal measurement of stimulation in the home was also related to offspring IQ . CONCLUSIONS Children who are born to mothers who have PKU and attain metabolic control before or very early in pregnancy seem to begin life with undiminished potential . Delay in attainment of maternal metabolic control is associated with declines in offspring developmental outcome . The postnatal environment also significantly affects outcome . Interventions to improve dietary compliance before and throughout pregnancy as well as interventions to improve the postnatal home environment may reduce the risks associated with maternal PKU The aims of the study were to examine the relationship between long-chain polyunsaturated fatty acid ( LCPUFA ) status at diagnosis of phenylketonuria ( PKU ) and neurodevelopment through the first 12 months of life , and to assess whether any difference exists between infants breastfed and bottlefed in the first days of life on the basis of LCPUFA status . Twenty infants with PKU were prospect ively examined through the first year of life .  Plasma fatty acids  were measured in infants at diagnosis . Plasma phenylalanine levels were determined monthly . Main outcome measures were the Bayley Mental Developmental Index ( MDI ) and Psychomotor Developmental Index ( PDI ) at 5 and 12 months of age , and the visual function at 12 months , evaluated by P100 wave latencies with visual ev 
    Output:
    
Despite the remarkable success of public health programs that have instituted newborn screening and early introduction of dietary therapy for PKU , there is a growing body of evidence that suggests that neurocognitive , psychosocial , quality of life , growth , nutrition , bone pathology and maternal PKU outcomes are suboptimal .