Maternal alcohol and drug use during pregnancy affects the motor behaviour and general movements of infants aged 3-4 months.

BACKGROUND: Exposure of alcohol and/or other addictive drugs in pregnancy is a documented risk factor for later neurological impairment. AIMS: The aim of the study was to determine whether infants suffering from prenatal exposure to addictive drugs and alcohol develop an abnormal motor behaviour at three to four months of age. STUDY DESIGN: Controlled cohort study of infants exposed to alcohol and/or other addictive drugs in pregnancy who were recruited from a hospital follow-up programme. The control group consisted of healthy, unexposed infants. SUBJECTS: The study group of 108 infants exposed to alcohol and/or addictive drugs in pregnancy were enrolled based on referrals from primary health care. The control group included 106 infants who had not been exposed to the aforementioned substances. OUTCOME MEASURES: We assessed the general movements (Prechtl's General-Movement-Assessment, GMA), the motor repertoire (Assessment-of-Motor-Repertoire, AMR), and the Alberta-Infant Motor-Scale (AIMS) in all infants at three to four months of age. RESULTS: None of the infants in either group had absent fidgety movements (FMs). In the study group 5(5%) had exaggerated FMs and 5(5%) had sporadic FMs; and 68(63%) infants in the study group displayed an abnormal movement character, compared to 23(22%) in the control group (p<0.001). On the AIMS, 46(44%) infants in the study group scored below the 10th percentile, compared to 2(3%) controls (p< 0.001). CONCLUSION: The study describes an abnormal movement character of infants exposed to alcohol and/or addictive drugs in pregnancy when their motor repertoire was assessed at three to four months of age. The AIMS also showed negative effects on their motor behaviour.

Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight.

Very low birth weight (VLBW) children are at high risk of perinatal white matter injury, which, when subtle, may not be seen using conventional magnetic resonance imaging. The relationship between clinical findings and fractional anisotropy (FA) measurements in white matter of adolescents born prematurely with VLBW was studied in 34 subjects (age = 15 years, birth weight

Cerebral cortex thickness in 15-year-old adolescents with low birth weight measured by an automated MRI-based method.

Infants with low birth weight are at increased risk of perinatal brain injury. Disruption of normal cortical development may have consequences for later motor, behavioural and cognitive development. The aim of this study was to measure cerebral cortical thickness, area and volume with an automated MRI technique in 15-year-old adolescents who had low birth weight. Cerebral MRI for morphometric analysis was performed on 50 very low birth weight (VLBW, birth weight

Psychiatric symptoms and disorders in adolescents with low birth weight.

OBJECTIVE: To evaluate the prevalence of psychiatric symptoms and disorders associated with low birth weight.Design/study groups: A population based follow up study of 56 very low birthweight (VLBW: birth weight < or = 1500 g), 60 term small for gestational age (SGA: birth weight < 10th centile), and 83 term control (birth weight > or = 10th centile) children at 14 years of age. OUTCOME MEASURES: Schedule for affective disorders and schizophrenia for school aged children, attention deficit/hyperactivity disorder (ADHD) rating scale IV, autism spectrum screening questionnaire, and children's global assessment scale. RESULTS: VLBW adolescents had a higher prevalence of psychiatric symptoms (46%) than controls (13%) (odds ratio (OR) 5.7, 95% confidence interval (CI) 2.5 to 13.0) and more psychiatric disorders (25%) than controls (7%) (OR 4.3, 95%CI 1.5 to 12.0), especially anxiety disorders. Although 25% of the VLBW adolescents had attention problems, ADHD was diagnosed in only 7%. Four VLBW adolescents had symptoms of Asperger's disorder, and the VLBW group had a higher sum score than controls on the autism spectrum screening questionnaire. Although more SGA adolescents had psychiatric symptoms than controls (23% v 13%), the difference was not statistically significant. Results remained essentially the same when adolescents with low estimated intelligence quotient were excluded, and persisted after possible psychosocial confounders had been controlled for. CONCLUSION: VLBW, but not SGA adolescents, have a high risk of developing psychiatric symptoms and disorders by the age of 14, especially attention deficit, anxiety symptoms, and relational problems.

Motor skills in adolescents with low birth weight.

BACKGROUND: Minor motor problems have been reported in low birthweight children, but few studies have assessed motor skills in adolescents. OBJECTIVE: To examine the prevalence of motor problems in adolescents with low birth weight. METHOD: Fifty four very low birthweight (VLBW: birth weight < or = 1500 g), 59 term small for gestational age (SGA: birth weight < 10th centile), and 83 control (birth weight > or = 10th centile at term) children were assessed with the Movement assessment battery for children (Movement ABC) at the age of 14 in a population based study. RESULTS: One in four VLBW children (odds ratio (OR) 9.3, 95% confidence interval (CI) 2.5 to 34.5) and one in six SGA children (OR 4.7, 95%CI 1.2 to 18.4) had motor problems compared with controls (3.7%). There were no sex differences in motor problems in the VLBW group, and the increased risk was consistent across the continuum of the Movement ABC. For SGA children, the increased risk of motor problems was particularly in manual dexterity in boys. CONCLUSION: VLBW and SGA adolescents have increased risk of motor problems compared with control children.

Arterial air embolism after venous air infusion in newborn piglets.

UNLABELLED: In the newborn period, decreased right atrial pressure results in functional closure of the foramen ovale (FO). The objective of this study was to investigate whether air bubbles infused in the vena cava will pass through the FO into the arterial circulation in a newborn animal. Since air tends to rise to the highest point in a fluid, the study also investigated whether the animal's position could influence arterialization of air. Twelve 1-3-d-old piglets were anaesthetized and mechanically ventilated, and had catheters placed in the vena cava for infusion of air, in the aorta for blood gas and blood pressure measurements, and in the pulmonary artery for pressure measurements. After stabilization, 0.05 ml kg(-1) per minute of air was infused for 25 min followed by a 3 h observation period. Six piglets were placed in the left, and six in the right lateral recumbent position. Air bubbles in the left atrium or ventricle was monitored by echocardiography. Ultrasound Doppler probes were placed on both carotid arteries for detection of air embolism. Gas bubbles were detected in the left ventricle within 45 s of air infusion in 11 of 12 piglets. Eight piglets had air bubbles in the carotid arteries. Mean pulmonary arterial pressure (PAP) increased significantly after 1 min of air infusion, whereas mean systemic arterial pressure remained unchanged. When arterial air embolism occurred, PAP had not increased significantly. The time to reach maximum PAP with the animals in the left recumbent position was significantly shorter than in the right. CONCLUSION: This study shows that venous gas bubbles enter the arterial circulation through the FO in newborn piglets and that body position may influence the haemodynamic effect of these bubbles.

Effects of phenobarbital on cerebral blood flow velocity after endotracheal suctioning in premature neonates.

OBJECTIVE: To examine the effect of phenobarbital administration on anterior cerebral artery blood flow velocity before and after endotracheal suctioning in premature neonates. DESIGN: Transcutaneous PO(2) (TcPO(2)), heart rate, mean arterial blood pressure (MABP), and Doppler velocimeter blood flow of the left anterior cerebral artery were measured before and immediately after 3 consecutive endotracheal suctioning procedures in premature neonates. Intravenous phenobarbital (20 mg/kg) was administered immediately after the first procedure. SETTING: Neonatal intensive care unit. PATIENTS: Nine neonates with a mean birth weight of 807 g (range, 620-1060 g) and a mean gestational age of 27 weeks (range, 25-30 weeks) were studied at age 8 to 12 hours. RESULTS: Transcutaneous PO(2) decreased in response to endotracheal suctioning at each of the suctioning procedures before and after phenobarbital was given (P<.001). Changes in heart rate were not observed. There were increases in MABP and area under the velocity curve (AUVC) per minute in response to endotracheal suctioning before but not after phenobarbital administration (P=.046). Use of phenobarbital lowered the overall peak systolic blood flow velocity in response to endotracheal suctioning (P =.02, analysis of variance, interactions for the effect of phenobarbital therapy on the response to suctioning). Changes in end-diastolic blood flow velocity were not observed. There were decreases in the differences before and after endotracheal suctioning for MABP at 2 and 4 hours and for AUVC and peak systolic blood flow velocity 4 hours after phenobarbital was given (P =.04). CONCLUSIONS: In very low-birth-weight neonates, endotracheal suctioning is associated with decreases in TcPO(2) and increases in MABP and AUVC. Treatment with phenobarbital attenuates the increases in MABP and AUVC but not the decreases in TcPO(2) after endotracheal suctioning.

Increased serum concentrations of soluble tumor necrosis factor receptors p55 and p75 in early onset neonatal sepsis.

Sepsis and pneumonia are major causes of morbidity and mortality in the neonatal period. The symptoms are variable and unspecific. So far, no reliable diagnostic test for neonatal infection has been found. In this study we measured serum levels of soluble tumor necrosis factor receptors (sTNFR) p55 and p75 in non-infected and infected neonates, and evaluated the diagnostic value of these mediators as tests for early detection of neonates with sepsis or pneumonia. Blood was collected on admission and after 3-4 days from 161 neonates consecutively admitted to the Neonatal Intensive Care Unit (NICU) during the first week of life. Twenty two neonates suffered from infection and 127 were classified as non-infected (controls). Samples were analyzed for p55 and p75, C-reactive protein (CRP) and white blood cell count with differential. Both preterm and term infected neonates had initially higher concentrations of p55 (both p <0.01) and p75 (p = 0.01 and p = 0.05, respectively) than controls. In non-infected neonates p55 levels decreased in the perinatal period, whereas p75 levels remained stable. Levels of both p55 and p75 decreased in neonates with infection during the perinatal period. CRP was a more specific parameter than p55 and p75 (CRP: 97%, p55: 65% and p75: 75%) whereas the sensitivity of all three parameters was at similar levels (CRP: 59%, p55: 70% and p75: 67%). We conclude that assessment of sTNFR may not improve accuracy in the diagnosis of early onset neonatal sepsis compared to the use of CRP.

Cerebral MRI of very low birth weight children at 6 years of age compared with the findings at 1 year.

BACKGROUND: We have previously reported the results of cerebral MRI examinations in an unselected year cohort of very low birth weight (VLBW) infants at one year of corrected age. Twenty-one (78 %) of 27 infants had abnormal myelination, mainly in the central occipital white matter (COWM) and in the centrum semiovale (CS), seen on T2-weighted images. Twelve infants had irregular and dilated lateral ventricles. We speculated whether these findings indicated perinatal periventricular leukomalacia (PVL). Only two infants had completely normal MRI at age 1 year. OBJECTIVE: To determine whether the abnormal myelination seen at 1 year of age, was still present, either as delayed myelination or as gliosis caused by perinatal PVL. MATERIALS AND METHODS: In the present study, we report the results of follow-up cerebral MRI in 20 of these infants at 6 years of age. RESULTS: Most of the children with MRI deviations at 1 year still had abnormalities at 6 years. Abnormal myelination in the central occipital white matter combined with abnormalities in the CS or with ventricular dilatation at age 1 year, presented as gliosis in 12 of 13 children at 6 years of age. Abnormalities solely in the COWM at age 1 year had normalised in two of five children and persisted as delayed myelination in three at age 6 years. Gliotic changes in periventricular white matter were found in 12 of 20 children (60 %). Areas most affected were the CS (11 children) and the COWM (9 children). Delayed myelination in COWM was found in six children (30 %), combined with gliosis in CS in three children. Twelve infants had ventricular dilatation both at 1 and 6 years of age. CONCLUSIONS: The MRI correlates of PVL, i. e. gliosis and ventricular dilatation, are common findings on cerebral MRI at 6 years of age in VLBW infants.

Can cerebral MRI at age 1 year predict motor and intellectual outcomes in very-low-birthweight children?

This follow-up study reports on cerebral MRI findings in 20 very-low-birthweight (VLBW) infants without disabilities at age 1 year in relation to motor, intellectual, and perceptual function at age 6 years. MRI findings, anthropometrics, and Bayley Scales of Infant Development scores at age 1 year as predictors of psychomotor status at age 6 years are also evaluated and compared. Outcome parameters were the Peabody Developmental Motor Scales and the Wechsler Preschool and Primary Scale of Intelligence. The results show that infants with myelin hyperintensities including the centrum semiovale or with occipital hyperintensities with associated ventricular dilatation at age 1 scored lower on the Peabody Gross Motor Locomotion Scale at age 6 than infants with normal myelination or with isolated occipital hyperintensities. This may indicate damage to motor fibers caused by perinatal periventricular leukomalacia. No relation was found between abnormal MRI findings at age 1 and later fine motor, intellectual, and perceptual function. Comparing different age 1-year predictors, an abnormality score defined by MRI was used as an independent predictor of gross motor locomotion function at age 6 years. However, the Bayley Mental Development Index scores and weight at age 1 were more important predictors of later motor and intellectual outcome, respectively, than MRI findings. It is recommended that cerebral MRI should not be used routinely to examine VLBW infants without disabilities at 1 year of age.

Cerebral magnetic resonance imaging and mental and motor function of very low birth weight children at six years of age.

In this follow-up study, 20 of a geographically based year cohort of 31 surviving non-disabled VLBW (birthweight < 1500 g) children were examined at six years of age. The aim of the study was to relate cerebral MRI findings to neuro-development in these non-disabled children at six years of age. All MRI scans were evaluated for myelination pattern, periventricular gliosis, ventricular dilation and cortical atrophy. The Peabody motor test and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) were used in the evaluation of motor, mental and perceptual function. A diagnosis of attention deficit disorder with hyperactivity was made based on the examiner's impression of the child during the examination and based on the parent's history. We found that ten (50%) of the children had periventricular gliosis, mainly in centrum semiovale (CS) (nine children) and in central occipital white matter (COW) (six children). Gliosis in CS was related to lower scores on the Peabody gross motor test for locomotion, indicating involvement of corticospinal tracts. Additional gliosis in COW was related to both fine motor and gross motor impairments. We speculate that this indicates damage to both motor and visual pathways, affecting eye-hand coordination and balance function. No relationship between MRI deviations at six years and mental function based on performance, verbal and total IQ scores was found. However, there was a significant relationship between periventricular gliosis in COW and C5 and low scores on the WPPSI performance subtests: Picture completion test and Block design test. This may indicate visual and spatial perception problems, caused by damage to posterior visual pathways and occipito-thalamic tracts dealing with visuo-motor integration.

Postnatal changes in mechanisms mediating acetylcholine-induced relaxation in piglet femoral arteries.

We studied the nitric oxide-cGMP pathway in endothelium-dependent relaxation in femoral arterial rings from piglets at different postnatal ages. Responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined in phenylephrine-precontracted rings from newborn (10-22-h) and 7 d (7-10-d)-old piglets. Relaxant responses were investigated in endothelium-denuded rings and endothelium-intact controls, and in endothelium-intact rings incubated with the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine acetate (L-NMMA), indomethacin, or the superoxide anion generator 6-anilinoquinoline-5,8-quinone (LY83583). Arterial rings from both age groups relaxed to a similar degree in response to ACh. Relaxation in rings from newborn piglets was insensitive to NOS inhibition by L-NMMA, whereas in artery rings from 7-d-old piglets, the relaxant response was significantly inhibited by L-NMMA. Incubation with LY83583 gave an inhibition of ACh-induced relaxation very similar to that of L-NMMA. Incubation with indomethacin had no significant effect on ACh-induced relaxation in either age group. Artery rings from both age groups relaxed 100% to SNP; the 7-d-old group was more sensitive than the newborn. NOS inhibition potentiated SNP-induced relaxation in both groups, but the potentiating effect was of greater magnitude in the newborn. Our results indicate a difference in the mechanism(s) underlying ACh-induced relaxation in the femoral artery from newborn and 7-d-old piglets, with an intact relaxant response in rings from the newborn despite NOS inhibition. The SNP results indicate a down-regulated soluble guanylate cyclase in the newborn, possibly related to a difference in basal NO release between the two age groups.

Relationship between intrauterine growth retardation and early postnatal superior mesenteric artery blood flow velocity.

During the first week of life, we examined the changes in the systemic, intestinal and cerebral circulation, and the circulatory responses to feeding in 10 small for gestational age (SGA) infants using the ultrasound Doppler technique. From day 1 to day 3, preprandial cardiac output decreased (p < 0.01), whereas mean blood pressure (p < 0.01), superior mesenteric artery mean flow velocity (Vmean; p < 0.01) and middle cerebral artery Vmean (p < 0.01) increased. On day 1, cardiac output was higher in the SGA than in those of term and preterm appropriate for gestational age infants reported from our laboratory. Preprandial superior mesenteric artery Vmean was inversely related to the degree of growth retardation (r = 0.63, p < 0.05). However, growth retardation did not influence the postprandial increase in superior mesenteric artery Vmean and end-diastolic flow velocity, or the cerebral circulation.

Lack of evidence of permanent engraftment after in utero fetal stem cell transplantation in congenital hemoglobinopathies.

The use of fetal hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy. In one fetus with alpha-thalassemia, one with sickle cell anemia, and one with beta-thalassemia, we have transplanted fetal liver cells obtained from legal abortions in gestational weeks 6-11. The fetus with alpha-thalassemia was transplanted twice during pregnancy, in the 15th (20.4 x 10(8) cells/kg) and in the 31st weeks of gestation (1.2 x 10(8) cells/kg), and is now two years of age. One fetus with sickle cell anemia received its transplant in the 13th week of gestation (16.7 x 10(8) cells/kg), and is now one year old. The fetus with beta-thalassemia was transplanted in 18th week (8.6 x 10(8) cells/kg), and is now three months old. Engraftment was evaluated by chromosomal analysis (sex chromosomes), red cell phenotyping, HLA class I and II typing, and PCR (polymerase chain reaction) for Y chromosome-specific sequences and DNA polymorphisms in cord and peripheral blood. The children with alpha- and beta-thalassemia underwent bone marrow aspirations at 3 and 7 months of age, respectively. In neither of these cases were we able to detect convincing evidence of stem cell engraftment. Thus, the administration of fetal stem cells to fetal recipients after the 12th week of gestation did not result in permanent hematochimerism. It remains to be determined whether the engraftment process can be promoted by earlier transplantations and/or higher cell doses.

Mesenteric blood flow velocity and its relation to transitional circulatory adaptation in appropriate for gestational age preterm infants.

We investigated the early postnatal changes of the mesenteric circulation and its relation to the systemic circulation in 15 preterm infants. The infants were studied before the first feeding on d 1 and pre- and postprandially on d 3, 4, 5, and 7. Blood flow velocity was measured by ultrasound Doppler in the superior mesenteric artery, middle cerebral artery, and the aortic orifice for cardiac output calculations. Blood pressure and heart rate were monitored. From d 1 to d 3, the preprandial stroke volume decreased [1.5 +/- 0.3 to 1.3 +/- 0.2 mL/kg (mean +/- SD), p < 0.05], whereas blood pressure (36 +/- 3 to 50 +/- 7 mm Hg, p < 0.001), superior mesenteric artery mean velocity (Vmean) (0.17 +/- 0.08 to 0.30 +/- 0.11 m/s, p < 0.05), and middle cerebral artery Vmean increased (0.15 +/- 0.05 to 0.22 +/- 0.03 m/s, p < 0.001). From d 3 through d 7, the preterm infants demonstrated higher preprandial end diastolic flow velocity in the superior mesenteric artery than we previously reported in term infants (0.15 +/- 0.05 versus 0.12 +/- 0.04, p < 0.05). Like the term infants, preterm infants increased their superior mesenteric artery Vmean by 83% postprandially and maintained a stable cerebral circulation with feeding. Unlike the term infants, feeding in the preterm infants induced a blood pressure decrease (51 +/- 6 to 48 +/- 6 mm Hg, p < 0.01) and a cardiac output increase (176 +/- 30 to 188 +/- 32 mL/kg/min, p < 0.001). These findings suggest that, in contrast to term infants, healthy preterm infants require compensatory systemic hemodynamic changes in response to feeding.

Mesenteric blood flow velocity and its relation to circulatory adaptation during the first week of life in healthy term infants.

We investigated early postnatal changes of the mesenteric circulation and its relationship to the systemic circulation in two groups of newborn infants. Group I (n = 10) was studied before the first feeding at 1 h and preprandially at 6 and 24 h. Group II (n = 10) was studied before the first feeding at 2 h of age and preprandially and postprandially at d 3, 4, and 5. Blood flow velocity was measured with ultrasound Doppler in the superior mesenteric artery (SMA), middle cerebral artery, subclavian artery, and aortic orifice for cardiac output (CO) calculations. Blood pressure and heart rate were monitored. SMA mean velocity (Vmean) decreased from 1 [0.33 +/- 0.07 m/s (mean +/- SD)] to 6 h (0.23 +/- 0.08 m/s, p < 0.005) in group I, probably due to ductal steal, returning to the 1-h value at 24 h. In contrast, middle cerebral artery Vmean remained unchanged in the first 24 h. From d 3, SMA Vmean increased 92% postprandially, with no relation to increasing amounts of food. The postprandial increase in SMA Vmean was not associated with changes in CO and blood pressure; however, a fall in relative mesenteric vascular resistance suggested regional redistribution of CO. Middle cerebral artery Vmean increased from h 2 to d 3 with a further increase on d 4 (p < 0.01). This increase was associated with an increase in blood pressure. The relative fraction of CO to middle cerebral artery increased during the first days of life, suggesting a redistribution of blood flow to the metabolically active organs in the neonatal period.

Phototherapy-associated changes in mesenteric blood flow response to feeding in term neonates.

Doppler blood flow velocity of the superior mesenteric artery was measured preprandially and postprandially in 12 term neonates during phototherapy and 4 hours after discontinuation of this therapy. The postprandial increase in blood flow velocity was significantly less during than after phototherapy. We suggest that the phototherapy-induced peripheral vasodilation may be responsible for diverting blood from the intestines and limiting the normal neonatal postprandial response.

Cerebral magnetic resonance imaging (MRI) and mental and motor function of very low birth weight infants at one year of corrected age.

Thirty-one (77.5%) of a year cohort of 40 surviving infants with birth weight < 1500 grams were seen on follow-up examination at one year of corrected age. At neurological evaluation 20 infants were normal (Group 1), seven infants were considered at risk (Group 2), and four infants had cerebral palsy (Group 3). Assessment on the Bayley Scales gave significantly lower mean scores in Group 3 compared with Group 1, both on the Mental Index (63 versus 102, p < 0.001) and on the Psychomotor Index (PDI) (60 versus 94, p < 0.005). Mean PDI score in Group 2 was significantly lower than in Group 1 (74 versus 94, p < 0.005). Cerebral MRI was performed in 27 infants. Of the 19 infants in Group 1 examined with MRI, 14 infants showed deviating changes in both myelin deposition and maturation (2). In all 14 infants the central occipital white matter was affected and in three infants also the centrum semiovale, both areas correspond to predilection sites for periventricular leukomalacia (PVL). Five infants had irregular shape of the occipital horns of the lateral ventricles. These findings may also represent the end stages of PVL (4). Only four out of seven infants were examined with MRI in Group 2. However, three infants had deviating myelination and three had irregular shape of the posterior horns. In Group 3 all infants were examined with MRI and all had deviating myelination and irregular and slightly dilated posterior horn. There was a significant correlation between abnormally dilated occipital horns seen with MRI, and cerebral palsy and low scores on the Denver and the Bayley tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Omega-3 fatty acids: essential fatty acids with important biological effects, and serum phospholipid fatty acids as markers of dietary omega 3-fatty acid intake.

Serum phospholipid eicosapentaenoic (PL-EPA) and docosahexaenoic acid (PL-DHA) concentrations are associated with the dietary intake of omega 3 fatty acids. PL-EPA and PL-DHA concentrations measured 4 y apart in 211 diabetic patients were highly correlated, with Spearman correlation coefficients of 0.49 (p = 0.0001) and 0.64 (p = 0.0001), respectively. PL-DHA was positively associated with Bayley psychomotor and mental developmental indexes (PDI and MDI, respectively) in preterm infants. Using multiple-regression analysis, 64% (R2 = 0.639; p = 0.0001) of PDI variance was explained by 1/DHA and weight at 1 y, whereas 82% (R2 = 0.816; p = 0.0001) of MDI variance was explained by weight at 1 y, Apgar score, 1/DHA, and 1/EPA. 1/DHA was negatively correlated with PDI and MDI, whereas 1/EPA was positively correlated with MDI. The results suggest that infant formulas should contain preformed DHA, and that a too-high supply of EPA in addition to DHA might be harmful in preterm infants.