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

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.

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.

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.

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.

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.

Congenital diaphragmatic hernia: determination of the optimal time for operation by echocardiographic monitoring of the pulmonary arterial pressure.

Preoperative stabilization and delayed operation rather than emergency repair of congenital diaphragmatic hernia (CDH) may improve survival, but there are no clear criteria for how long operation should be delayed. Because increased pulmonary vascular resistance (PVR) may be an important risk factor, we used Doppler echocardiography to study patients with CDH presenting with respiratory distress immediately after birth. During the study period 10 patients were admitted, but 2 were moribund on admission and died shortly thereafter. In the remaining patients the pulmonary arterial pressure (PAP) and direction of ductal shunt were estimated by Doppler echocardiography. Initial PAPs were in the range of 45 to 90 mm Hg, with bidirectional or right-to-left shunt through the ductus arteriosus. Reduction of pressure to 25 to 55 mm Hg, or reversal of shunt to left-to-right, reflecting decreased PVR, occurred after ventilation for 3 to 20 days (mean, 8 days). Patients underwent operation after there was evidence of reduced PVR. None developed persistent fetal circulation, and all 8 patients survived. We conclude that postponing operation until PVR has decreased seems to improve survival in patients with CDH presenting within hours of birth.

New findings in a patient with I-cell disease.

A case of I-cell disease showing some previously undescribed features is reported. The diagnosis was confirmed on the basis of lysosomal enzyme activity. The radiogram showed metaphyseal radiolucent bands not yet described and extensive epiphyseal stippling. The electronmicroscopical findings clearly demonstrated the presence of abnormal inclusion bodies in absorptive cells and in cells of the lamina propria of the small intestine. Immunological investigation revealed and increased absolute number of both B and T lymphocytes. The B cells, unlike the T cells, showed cytoplasmic vacuoles on phase contrast microscopy. The immune response to antigenic challenge was impaired, as assessed by specific antibody production and in vitro lymphocyte transformation testing.

[Growth and development in infants with a birthweight of less than 1501 grams]. / Vekst og utvikling hos barn med fødselsvekt under 1,501 gram.

37 children with a birthweight below 1.501 grams were studied between the ages of one and two years. The children were all admitted to the neonatal intensive care unit at the Regional Hospital in Trondheim in 1985 or 1986. Morbidity, development, growth and major handicaps in the study group were registered and compared with a control group of children born at term during the same period. The preterm children showed a significantly higher incidence of lower respiratory tract infections and hospital readmissions than did the children in the control group. The incidence of cerebral palsy in the study group was 10.8% among the survivors (7.3% among live births). None of the children in the control group had a major handicap. Neurological development as judged by the Gesell scale was normal in the study group. However, the control group reached a higher score than expected for their age. A striking finding was the lack of catch-up growth in the prematurely born children. This finding should receive further attention in future.

Prolonged hypercarbia in the awake newborn piglet: effect on brain blood flow and cardiac output.

In adults, exposure to prolonged hypercarbia results in a normalization of the extravascular brain pH associated with a reduction in brain blood flow (BBF). Following prolonged hypercarbia, sudden normalization of the arterial PCO2 also produces a change in the extravascular brain pH to an alkaline state, resulting in a marked decrease in BBF. We examined these physiologic phenomena in newborn subjects by exposing seven awake, spontaneously breathing newborn piglets to 4 h of sustained hypercarbia (PaCO2: 60-70 mm Hg) followed by a 45-min normocarbic period. Total and regional BBF, cardiac output (radionuclide-labeled microsphere method), arterial blood pressure, plasma catecholamine and lactate concentrations, blood gases, oxygen contents, and hematocrits were measured during a baseline period, at 1/2, 2, and 4 h of sustained hypercarbia and 1/4 and 3/4 h following an abrupt onset of normocarbia. The initial 2.5-fold increase in total BBF during hypercarbia persisted for 2 h and at 4 h decreased significantly below the level of the 30-min hypercarbic measurement, although the values still remained 2-fold above the baseline values. Brain tissue pH was reduced at the onset of hypercarbia, remaining unchanged throughout the hypercarbic period. Both total BBF and brain tissue pH returned to baseline values following the return to normocarbia. Changes in regional BBF were similar to that of total BBF with the exception of the boundary zone (periventricular area in the frontoparietal region of the cerebrum, adjacent to the caudate nucleus) and the parietal area (site of the brain tissue pH electrode), where a significant decrease from the peak hyperemia was not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Mortality and functional disabilities among children with birth weight lower than 1500 g. Changes during 1983-88 at the neonatal unit of the Trondheim regional hospital]. / Mortalitet og funksjonshemning blant barn med fødselsvekt less than or equal to 1,500 g. Endringer i perioden 1983-88 ved neonatalenheten, Regionsykehuset i Trondheim.

The aim of the present study was to evaluate whether increased resources led to a higher rate of survival among infants with a birth weight less than or equal to 1,500 g, admitted to our department during the period 1983-88. During this period both personnel and equipment were upgraded. The number of patients more than doubled from 1983-84 to 1987-88 (37 versus 89). In spite of a significant decrease in gestational age from the first to the last period (29.6 weeks versus 28.2 weeks), the total mortality rate was halved, from 40.5% in 1983-84 to 22.5% in 1987-88. There was no significant increase in disability rate among survivors. The larger increasing number of disabled children was accounted for mainly by mild spastic diplegias.

[Late mortality among small premature infants. Significance of respiratory distress and bronchopulmonary dysplasia for early and late mortality among infants with birth weights lower than 1,501 g]. / Sen mortalitet blant små premature. Betydningen av respiratorisk distress og bronkopulmonal dysplasi for tidlig og sen mortalitet blant barn med fødselsvekt less than 1,501 g.

We have studied neonatal and late mortality rates among children with a birthweight of less than 1.501 grams. The sample consisted of children admitted to the neonatal intensive care unit at the Dept. of Pediatrics in Trondheim during 1985 and 1986. 58 children were admitted, three of whom had lethal malformations (two triploids, one trisomi 18). Of the remaining 55 children, 12 died in the neonatal period. This gives a neonatal mortality rate of 21.8%, which is comparable with the results reported from other centers. However, six children died after the neonatal period, giving a late mortality rate of 10.9%. This is higher than reported in the literature. Most reports that we have been able to find are six to ten years old, and at that time the neonatal mortality rates were significantly higher. Five of the six children who died late had bronchopulmonary dysplasia. The sixth child suffered a sudden infant death. The incidence of bronchopulmonary dysplasia was 27.2%, which is comparable with the incidence reported in the literature. The present study clearly shows the importance of taking late mortality rates into consideration when evaluating neonatal care.

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.

Atropine prevents increases in brain blood flow during hypertension in newborn piglets.

Cerebral hyperperfusion associated with hypertension, may play an important role in the pathogenesis of intraventricular hemorrhage in preterm infants. To examine the effect of hypertension on changes in total and regional brain blood flow (BBF), we increased the mean arterial blood pressure (MABP) in nine awake newborn piglets by an infusion of 0.7 mg/kg of metaraminol bitartrate (Aramine) (group I) and studied cerebral circulatory changes. In order to prevent the Aramine-associated bradycardia, we pretreated nine other piglets with atropine, which produced a higher level of hypertension (group II). MABP and BBF were measured and cerebral vascular resistance (CVR) was calculated during baseline, the Aramine infusion, and twice at decreasing MABP following the discontinuation of the Aramine infusion. In group I, the significant increase in MABP from 68 +/- 3 to 100 +/- 3 mm Hg (mean +/- SEM) during the Aramine infusion resulted in a significant increase in BBF (98 +/- 9 to 118 +/- 11 ml X min-1 X 100 g-1). MABP decreased significantly (although remained significantly above baseline levels), when Aramine was discontinued; however, total BBF remained elevated. CVR increased during the Aramine infusion, but decreased significant (versus the Aramine-infused state) in the post-Aramine period. Regional BBF increased significantly to the cerebrum and cerebellar cortex, but remained unchanged to the other regions including the brain stem. In group II, the Aramine infusion resulted in a significantly greater increase in MABP, a sustained increase in vascular resistance, and no increase in total BBF. Thus, atropine prevents increased BBF during hypertension in the newborn piglet.

The effects of variations in PaCO2 on brain blood flow and cardiac output in the newborn piglet.

The acute effects of normoxemic hypocarbia and hypercarbia were examined in six newborn piglets. Brain blood flow was maintained during hypocarbia until extremely low PaCO2 (less than 15 mm Hg) levels were achieved at which time total brain and cerebral blood flow decreased significantly from baseline values. Blood flow to the thalamus, cerebellum and brain stem was unchanged from baseline conditions during hypocarbia. This suggests that the newborn brain is relatively insensitive to moderate degrees of hypocarbia. Extreme hypocarbia (PaCO2 less than 15 mm Hg) was associated with a significant increase in heart rate, accompanied by a significant decrease in mean arterial blood pressure; however, cardiac output was not significantly different from baseline determinations. Hypercarbia with normoxemia was associated with significant increases in total brain blood flow, with greater blood flow to the brain stem, cerebellum, and thalamus than to the cerebrum. The percentage of cardiac output received by the brain was also significantly increased, although total cardiac output was unchanged. This demonstrates that the newborn cerebral vasculature is sensitive to hypercarbia and that regional differences in sensitivity may account for the greater increments in blood flow to the caudal portions of the brain than that to the cerebrum.

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.