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Biomedical subjects

Gorm Greisen

Publications and source records attributed to Gorm Greisen.

At least 37 records · Page 2Linked to original sources

Cerebral pressure autoregulation and vasoreactivity in the newborn rat.

Perinatal brain injury has been associated with impaired cerebral blood flow (CBF) pressure autoregulation. The brain of 3- to 5-d-old rat pups is immature and similar to that of a preterm infant, and therefore we tested cerebral vasoreactivity in that animal. CBF pressure autoregulation was tested in 20 Wistar pups during normocapnia and hypercapnia, respectively. Hypotension was induced by hemorrhage and cerebral perfusion was monitored with laser Doppler flowmetry and near-infrared spectroscopy. Systolic blood pressure was measured noninvasively from the tail. During normocapnia, the autoregulatory plateau was narrow. Resting systolic blood pressure (SBP) was 39.2 mm Hg and CBF remained constant until SBP decreased below 36.0 mm Hg (SE 0.8). Below the lower limit, CBF declined by a mean of 2.7% per mm Hg [95% confidence interval (CI), 2.4-3.0%], and hemoglobin difference (HbD) and total hemoglobin (HbT) changed proportionally to CBF. After inhalation of carbon dioxide, CBF increased significantly by a mean of 17.7% (95% CI, 13.7-22.8%). The CBF-CO2 reactivity was estimated to 13.4% per kPa (95% CI, 2-24.8%), p=0.026. Over the range of SBP (6-54 mm Hg), a linear relationship between CBF and SBP was found during hypercapnia, indicating abolished pressure autoregulation. A linear correlation between CBF and HbD was found (r=0.80). CBF pressure autoregulation and reactivity to CO2 operate in the newborn rat. This model may be useful for future investigations concerning perinatal pathophysiology in the immature brain.

Animals↗

Neurological sequelae in twins born after assisted conception: controlled national cohort study.

OBJECTIVE: To compare neurological sequelae in twins born after assisted conception with singletons after assisted conception and naturally conceived twins and to assess neurological sequelae in children conceived after in vitro fertilisation (IVF) compared with intracytoplasmic sperm injection (ICSI). DESIGN: Controlled, national register based, cohort study. PARTICIPANTS: Twins (n = 3393) and singletons (n = 5130) conceived by using assisted reproductive technologies and naturally conceived twins (n = 10 239) born in Denmark between 1995 and 2000. The children's age at time of follow up was 2-7 years. DATA SOURCES: Children were identified by cross linkage of the national medical birth registry and the national registry for in vitro fertilisation. Neurological and psychiatric diagnoses were retrieved from the national patients' registry and the Danish psychiatric central registry. MAIN OUTCOME MEASURES: Neurological sequelae, defined as cerebral palsy, mental retardation, severe mental developmental disturbances, and retarded psychomotor development. Further we made separate analyses on the specific cerebral palsy diagnosis. RESULTS: The crude prevalence rates per 1000 of neurological sequelae in twins and singletons after assisted conception and in naturally conceived twins were 8.8, 8.2, and 9.6, and of cerebral palsy 3.2, 2.5, and 4.0, respectively. In twins after assisted conception compared with control twins, the odds ratios of neurological sequelae and specifically of cerebral palsy, adjusted for child sex and year of birth, were 0.9 (95% confidence interval 0.6 to 1.4) and 0.8 (0.4 to 1.6), respectively. The corresponding odds ratios for twins after assisted conception compared with singletons after assisted conception were 1.1 (0.7 to 1.7) for neurological sequelae and 1.3 (0.6 to 2.9) for cerebral palsy. The odds ratio of neurological sequelae in children conceived by ICSI was 0.9 (0.5 to 1.7) nu children conceived by IVF. CONCLUSIONS: Twins from assisted conception have a similar risk of neurological sequelae as their naturally conceived peers and singletons from assisted conception. Children born after ICSI have the same risk of neurological sequelae as children born after IVF.

Cohort Studies↗

Managing births at the limit of viability: the Danish experience.

The issue of how to treat extremely premature infants has been debated several times in Denmark, and the option of withholding intensive care has received considerable support. Accordingly, a conservative, minimally invasive approach is used, with selective use of resuscitation in the delivery room, early nasal continuous positive airway pressure, and elective use of mechanical ventilation. Parents are actively involved, and the clinical process is gradual with the risks and benefits considered at each step. The risks include causing pain, suffering and loss of dignity in the short and long term for both the baby and the family. Few babies delivered before 25 completed weeks' gestation are considered to be alive at birth, and only a minority of those admitted for neonatal care do survive. Now, however, parents seem increasingly prepared to accept the suffering and uncertainty of intensive life support for the most immature babies when it becomes necessary.

Attitude of Health Personnel↗

Is improved survival of very-low-birthweight infants in the 1980s and 1990s associated with increasing intellectual deficit in surviving children?

To investigate whether the decrease in mean birthweight of the smallest infants surviving with a very low birthweight (VLBW) in the past two decades is associated with an increase in intellectual deficit rates, we compared the results obtained in two different follow-up studies: one included a cohort of children of VLBW (<1500g; n=102, 52% male) born in the early 1980s; the other included a cohort of children of extremely low birthweight (ELBW; <1000g; n=183, 46% male) born in the mid-1990s. Intellectual development was evaluated in both cohorts. McCarthy Scales of Children's Abilities were used in the cohort from the early 1980s; Wechsler's Preschool and Primary Scale of Intelligence--Revised was used in the cohort from the mid-1990s. The children were assessed at age 4-5 years, and a control group was included for each of the two studies. Mean scores in the measures of intelligence found at the assessment were recalculated to standard deviation scores from the two control groups. We found no difference in the standard deviation scores between the two cohorts despite the mean birthweight being 353g (p<0.001) lower in the cohort from the mid-1990s, and the overall survival rate of infants of VLBW having increased. Our results suggest that the improved survival of the smallest babies in the 1980s and 1990s has been achieved without an increase in the intellectual deficit in the surviving children.

Child↗

Surveillance for retinopathy of prematurity in a Copenhagen high-risk sample 1999-2001. Has progress reached a plateau?

PURPOSE: As part of a current quality control to evaluate ophthalmic findings in two combined central Copenhagen neonatology centers for birth years 1999-2001, and to compare the selected sample with data of the national register for childhood visual impairment. METHODS: In a prospective design to report on 372 infants mainly under regular surveillance for retinopathy of prematurity (ROP) in the stratified functional unit made up by the neonatal wards of Righospitalet (RH) and Hvidovre Hospital (HH). The median neonate under ophthalmic surveillance in the two wards (screening limits usually 32 weeks/1750 g) was given by gestational age (GA) and birthweight (BW) values of 27.3 weeks/907 g and 30.3 weeks/1420 g. respectively. Feedback regarding outcome was secured for those transferred to regional centres. RESULTS: The overall frequency of ROP was 38.5% in the RH (n=252) and 10.8% in the HH sample (n=120). From a peak share above 60% in those <26 weeks/750 g at delivery, the incidence of ROP showed a regular decrease with decreasing immaturity. The centralized retinal ablation therapy for advanced ROP was given to a total of 29, with birth year 2001 unexpectedly showing a peak of 17 cases. Seven of the 29 children treated are now in the register for visually impaired, mainly due to low vision. Fourteen of the 29 had been very small for gestational age. CONCLUSIONS: Supported also by recent regional Danish data, the apparent progress in the fight against ROP over many years seems to have come to a halt. Except for the continued increased survival of extremely preterm babies we have no obvious neonatological indication to explain the suggested 'adverse' trends.

Birth Weight↗

Neonatal outcome in a Danish national cohort of 3438 IVF/ICSI and 10,362 non-IVF/ICSI twins born between 1995 and 2000.

BACKGROUND: In Denmark, one-third of twin pregnancies are the result of IVF/ICSI treatment. Limited data on neonatal outcome in IVF/ICSI twins are available in the literature. METHODS: A register study was conducted on neonatal morbidity and mortality in a complete national twin cohort including all 3438 (3393 live-born) IVF/ICSI and 10,362 (10,239 live-born) non-IVF/ICSI twins born between 1995 and 2000. Twins were identified in the National Medical Birth Registry and dichotomized into IVF/ICSI and non-IVF/ICSI by cross-reference with the Danish IVF Registry. Data on neonatal morbidity and mortality were retrieved from the Danish Patient Registry and the Danish Registry of Causes of Deaths. In order to exclude monozygotic twins, sub-analyses on unlike-sex twins were conducted. RESULTS: A birth weight discordance of >20% was observed in 20.6% of IVF/ICSI versus 15.7% of control twin pairs (P < 0.001). The risk of discordant birth weight >20% was OR 1.29 (95% CI 1.04-1.58) in unlike-sex IVF/ICSI twins versus control twins. The risk of delivery at <37 completed weeks and birth weight <2500 g was similar in the two cohorts; however, in unlike-sex IVF/ICSI versus control twins the risk of delivery at <37 weeks and birth weight <2500 g was OR 1.22 (95% CI 1.09-1.38) and OR 1.25 (1.11-1.40) respectively. After stratification for maternal age and parity, these risks disappeared. IVF/ICSI twins carried a higher risk of admittance to a neonatal intensive care unit (NICU) than control twins (OR 1.18, 95% CI 1.09-1.27), and this was even more pronounced in unlike-sex twins [OR 1.34 (95% CI 1.19-1.51)]. No differences were observed in malformation or mortality rates between the two cohorts. CONCLUSIONS: Despite higher birth weight discordance and more NICU admissions among IVF/ICSI twins, neonatal outcome in IVF/ICSI twins seems to be comparable with that of non-IVF/ICSI twins, when only dizygotic twins were considered in the comparisons.

Birth Weight↗

Gastric emptying and small intestinal transit time in preterm infants: a scintigraphic method.

OBJECTIVES: Practical methods to determine gastric emptying (GE) and small intestinal transit time in preterm infants are required. The aim of this study was to develop a scintigraphic method to determine GE and small intestinal transit time in preterm infants which produce minimal radiation exposure and physical disturbance in these infants. METHODS: Ten premature infants were studied. Median (and range) for gestational age was 28.9 (26-33) weeks, postnatal age was 19 (6-37) days, birth weight was 1194 (687-2300) grams and feeding volume was 173 (6-205) mL/kg/day. Nine of the patients were on nasal continuous positive airway pressure; one patient was on mechanical ventilation. A dose (0.2-0.4 MBq) of 99mTc-DTPA (0.5 mL) was given at the end of a meal administered by naso-gastric tube. Static images were obtained with a mobile gamma camera during the next 9 to 12 hours. The radiation dose was at most 0.30 mSv. Regions of interest (ROIs) were drawn around the stomach and the cecum. Time-activity curves were generated. Gastric emptying half-time (T(1/2)GE) was calculated. Residual gastric activity after 1 hour (R(1h)) and after 2 hours (R(2h)) was determined. Orocecal transit time was defined as the time until significant increase in activity was detected in the cecal ROI. RESULTS: Images showed gastric emptying in all cases. Median (range) half time was 1.0 (0.5-3.0) h. R(1h) was 37.5% (19% to 100%), R(2h) was 23% (6% to 61%). In one patient the tracer did not reach the cecum within 12 hours. In the remaining nine patients orocecal transit time was 3.1 (1.3-6.1) h. CONCLUSIONS: We present a new scintigraphic method to determine GE and orocecal transit time. It appears safe and practicable as a research tool in preterm infants.

Female↗

Assessment of parental sensitivity towards pre-school children born with very low birth weight.

The article introduces the Parental Sensitivity Assessment Scale (PSAS) and examines the influence of the PSAS score and other factors on the general cognitive level in pre-school children born with very low birth weight (VLBW). McCarthy general cognitive index (GCI) was obtained for 102 VLBW and 92 normal birth weight (NBW) control children in Denmark in the mid-1980s. The mean ages of the two groups were 52.4 vs. 53.1 months. Parental sensitivity was assessed using PSAS. There was no significant difference in the mean PSAS score between the two birth weight groups (p > 0.3). Birth weight group (p < 0.001) and mother's schooling (p= 0.026) significantly correlated with GCI in the children. The PSAS score was highly significantly correlated to the variance of the GCI (p < 0.001), which was not explained by VLBW and mother's schooling. We found no interactional effect between parental sensitivity and birth weight group (p > 0.5) - the prematurely born children were not more affected by low parental sensitivity than were the control children.

Adult↗

Transient hyperoxia and residual cerebrovascular effects in the newborn rat.

Unrestricted use of oxygen in the delivery room after preterm birth has been associated with reduced cerebral blood flow (CBF) 2 h later. To further investigate residual cerebrovascular effects of transient hyperoxia, we developed a newborn rat model in which laser-Doppler flowmetry (LDF) and near-infrared spectroscopy (NIRS) were used to monitor changes in cerebral perfusion. The hypothesis to be tested was that hyperoxic exposure limits cerebral vasodilation in response to increase in carbon dioxide tension (Pco(2)). Twenty-four 3- to 5-d-old rats were kept on spontaneous breathing with doxapram under light isoflurane anesthesia, randomized into two groups, and exposed to either room air or 100% oxygen for 30 min. Then, after 15 min of stabilization in normoxia, 8% CO(2) was given for 5 min. No significant differences in CO(2) responses were observed between the two groups: mean CBF-CO(2) reactivity as measured by NIRS was 13.3 +/- 3.9 %/kPa in the normoxia-group versus 8.8 +/- 4.1 %/kPa in the hyperoxia group (NS). The oxygenation index [(HbO(2) - Hb)/2] increased by 0.67 +/- 0.17 micromol/L/kPa in the normoxia group compared with 1.18 +/- 0.19 micromol/L/kPa in the hyperoxia group (NS). Cortical perfusion, monitored by LDF, increased by 7.3 +/- 1.5 %/kPa versus 6.8 +/- 1.8 %/kPa in the normoxia and hyperoxia groups, respectively (NS). We conclude that in newborn rats the CBF-CO(2) reactivity remains intact after 30 min of oxygen exposure.

Animals↗

A newborn rat model for the study of cerebral hemodynamics by near-infrared spectroscopy and laser-Doppler flowmetry in the immature brain.

An animal model for the study of cerebrovascular physiology in the immature brain was developed. Twelve 3- to 5-day-old rat pups were maintained on spontaneous breathing under light anesthesia for either 1 or 2 h. Transcutaneous carbon dioxide tension and arterial oxygen saturation were monitored. Continuous infusion of doxapram limited respiratory acidosis. Cerebral blood flow (CBF) and volume (CBV) could be monitored by near-infrared spectroscopy (NIRS) and laser-Doppler flowmetry (LDF) in spite of some movement artifacts. CBV and CBF were 6.0 +/- 0.3 SE ml/100 g and 36.3 +/- 3.1 SE ml/100 g/min, respectively, and remained stable during the study. Cerebrovascular responses, as monitored by LDF and NIRS, to hypoxic and hypercapnic gas mixtures were consistent.

Acid-Base Equilibrium↗

[Late sequelae after severe intracranial hemorrhage in 23 premature children. Parental perspectives].

INTRODUCTION: Cerebral hemorrhage in very premature infants results in high mortality and increases the risk of handicap. The aim of the study was to evaluate: 1) the parental opinion of the child's motor function, 2) their opinion of the child's development compared to their expectations, and 3) how they experienced the information given by nurses and doctors at the time of the diagnosis. MATERIAL AND METHODS: Parents of 23 of 24 premature infants answered a questionnaire. During the neonatal period all infants had suffered from a major cerebral hemorrhage. The children had reached an age between two and seven years. RESULTS: Half of the children had motor deficits (48%), and 22% of the children had severe motor problems. Future development and motor function were reliably estimated by the doctors during the neonatal period. Most of the parents (79%), however, estimated that their child's development was better than expected. The majority of the parents were satisfied with the information that had been given at the time of diagnosis, and they had received adequate support. DISCUSSION: Cerebral hemorrhage in premature infants is still a major problem. Our results, however, do not suggest major change of clinical practice.

Cerebral Hemorrhage↗

Improving blood gas control in mechanically ventilated, premature infants through monitoring and evaluation of clinical practice.

Mechanical ventilation causing hypocapnia or hyperoxia carries a risk for the pre-term infant. The aim was to improve blood gas control in our unit. A guideline was written, and all personnel were motivated concerning blood gas control. Case records of all mechanically ventilated premature infants were examined during two 3-month periods, before and after intervention. The hours spent with hypocapnia (pCO2 < 4 kPa) or hyperoxia (PO2 > 12 kPa) were recorded. Case records of 31 infants were examined for a total of 1358 h of mechanical ventilation, 641 h before and 717 h after the intervention. The percentage time of hypocapnia before intervention (7.0%) was reduced significantly (P = 0.044) to less than half (2.9%) after intervention. Hyperoxia was reduced from 14.5% to 8.7% (P = 0.072). Blood gas control of mechanically ventilated premature infants could be improved with little effort, but hyperoxia is too frequent.

Blood Gas Analysis↗

Recombinant factor VIIa in preterm neonates with prolonged prothrombin time.

The purpose of the study was to estimate the effects of a minimal and a normal dose of rFVIIa on prothrombin time, and to compare it to the effect of a standard volume of fresh frozen plasma. Recombinant factor VIIa (rFVIIa) was tested in babies with gestational age less than 33 weeks and prothrombin time greater than 48 s (reference 23.7 s; i.e. inclusion at international normalized ratio 2.0) during the first 7 days of life. Firstly, 5 microg/kg rFVIIa was given to five babies. One hour after the bolus, prothrombin time had significantly shortened from a mean of 64 s (range 53-79 s) to 46 s (range 39-56 s). Next, the effect of 80 microg/kg rFVIIa was compared to the effect of 10 mL/kg fresh frozen plasma. Prothrombin time at inclusion was 68 s (range 53-92 s). One hour after treatment, prothrombin time was 33 s (range 21-42 s) in the six babies given rFVIIa, compared with 51 s (range 40-59 s) in four babies given fresh frozen plasma (P = 0.02). Prothrombin time remained lower in the rFVIIa group (P = 0.01) at 3 h than in the frozen plasma group, whereas at 6 and 12 h the differences were statistically insignificant. One baby continued to have slight bleeding from the umbilical site and one baby developed severe pulmonary haemorrhage in spite of rFVIIa treatment. In conclusion, rFVIIa partially normalized prothrombin time in preterm babies. There was no evidence of side effects. Future randomized studies are needed to evaluate the haemostatic effect.

Blood Coagulation Disorders↗

Intrauterine growth retardation and consequences for endocrine and cardiovascular diseases in adult life: does insulin-like growth factor-I play a role?

Low birth weight has been associated with an increased incidence of ischaemic heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental GH is detectable in maternal serum from the 8th to the 12th gestational week, and rises gradually during pregnancy where it replaces pituitary GH in the maternal circulation. The rise in placental GH may explain the pregnancy-induced rise in maternal serum IGF-I levels. In the fetal compartment, IGF-I levels increase significantly in normally growing fetuses from 18 to 40 weeks of gestation, but IGF-I levels are four to five times lower than those in the maternal circulation. Thus IGF-I levels in fetal as well as in maternal circulation are thought to regulate fetal growth. Circulating levels of IGF-I are thought to be genetically controlled and several IGF-I gene polymorphisms have been described. IGF-I gene polymorphisms are associated with birth weight in some studies but not in all. Likewise, IGF-I gene polymorphisms are associated with serum IGF-I in healthy adults in some studies, although some controversy exists. Serum IGF-I decreases with increasing age in healthy adults, and this decline could hypothetically be responsible for the increased risk of IHD with ageing. A recent nested case-control study found that adults without IHD, but with low circulating IGF-I levels and high IGF binding protein-3 levels, had a significantly increased risk of developing IHD during a 15-year follow-up period. In summary, the GH/IGF-I axis is involved in the regulation of fetal growth. Furthermore, it has been suggested that low IGF-I may increase the risk of IHD in otherwise healthy subjects. Hypothetically, intrauterine programming of the GH/IGF axis may influence postnatal growth, insulin resistance and consequently the risk of cardiovascular disease. Thus IGF-I may serve as a link between fetal growth and adult-onset disease.

Adult↗