Biomedical subjects

J Frederik Frøen

Publications and source records attributed to J Frederik Frøen.

12 recordsLinked to original sources

PubMed2006

Fetal brain injury in experimental intrauterine asphyxia and inflammation in Göttingen minipigs.

OBJECTIVE: To examine fetal brain injury in the Göttingen minipig following intrauterine asphyxia and infection/inflammation induced at 3/4 of gestational length. METHODS: We performed laparotomy after anesthesia in six pregnant sows. We randomized 29 fetuses to one of four groups: pretreatment with saline or endotoxin followed by 30 min of umbilical cord occlusion or no occlusion. After 48 h we performed a re-laparotomy and examined the fetal brains. RESULTS: After total asphyxia, brain stem injury was present in the group pretreated with saline (P < 0.01 vs. controls) and with endotoxin (P < 0.005 vs. controls). Microglia activation was more marked in the brain stem (P < 0.05) and posterior white matter (P < 0.05) in the asphyxia group than in controls. Two of five fetuses in the asphyxia group had white matter injury, while no white matter lesions were found in the asphyxia/inflammation or endotoxin only groups. CONCLUSIONS: In this Göttingen minipig model, a species closer to humans than animals commonly used in experimental studies of perinatal brain injuries, intrauterine asphyxia following pretreatment with saline caused brain stem and white matter injury. This model can be further developed to study the impact of other intrauterine exposures on brain injury.

Animals↗

PubMed2005

[Reduced fetal movements--clinical management, recommendations and information].

BACKGROUND: We reviewed the Norwegian guidelines and clinical routines in delivery units and investigated whether guidelines for management of reduced fetal movements and information given to pregnant women were based upon evidence-based knowledge. MATERIAL AND METHODS: All Norwegian delivery units responded to a questionnaire about their management of pregnancies with reduced fetal movements. Literature for professionals and pregnant women was found in databases, books and journals. RESULTS: Clinical management varied significantly. All delivery units used a non-stress test when available, but few included ultrasound and Doppler examinations routinely. Five of 55 units advised women that absence of fetal movements up to 24 hours may be normal. National guidelines and university curricula recommend that distinct reduction of fetal movements require investigation. Formal kick counting was regarded as either useful, recommended or to be dissuaded. Information for pregnant women emphasises the importance of vigilance towards fetal movements, but have contradictory limits for normal fetal movements. INTERPRETATION: We have documented significant variation in clinical routines, which do not correlate with information given to pregnant women, the literature, or guidelines. This can lead to uncertainty for both pregnant women and health care professionals and may put patient safety at risk. There is a need for evidence-based guidelines.

Cardiotocography↗

PubMed2005

[Clinical practice variation in reduced fetal movements].

BACKGROUND: Reduced fetal movements imply a risk pregnancy. This condition is present in a significant proportion of pregnancies, but both the quality of information and that of clinical care is variable. MATERIAL AND METHODS: All delivery units in Eastern Norway and Bergen have registered all consultations for reduced fetal movements, as part of the international collaborative project "Fetal Movement Intervention Assessment" (Femina). Out of 23,933 deliveries, 1200 pregnancies were examined. In 1043 pregnancies the mother had spontaneously presented her concern over reduced fetal movements; these were included in analyses. Results are presented with a 95% confidence interval. RESULTS: Asphyxia, death, growth restriction or preterm birth occurred in 19.6% (16.6-22.6%) of cases, ranging between units from 9.1% to 26.5%. Standard procedures varied extensively; ultrasonography was used in 39.0% to 98.6% and Doppler in 4.5% to 74.6% of cases. There was an association between outcomes and the procedures used. Women who waited 24 hours with reduced or absent movements before contacting healthcare had increased risk. Among those with absent movements, 47% (42-52%) had such risk behaviour. INTERPRETATION: There is a need for quality improvements in the information to pregnant women as well as in the clinical management of affected pregnancies. This could have large health benefits. We propose new guidelines for information and management.

Cardiotocography↗

PubMed2005

Effect of interleukin-10 on newborn piglet brain following hypoxia-ischemia and endotoxin-induced inflammation.

OBJECTIVE: Previous animal studies indicated that interleukin (IL)-10 attenuates the inflammatory response to a challenge by inflammation and hypoxia-ischemia, but the effect of IL-10 administration after onset of inflammation has not been studied. We wanted to assess (1) whether IL-10 had a beneficial effect on brain metabolism and microcirculation in newborn piglets after an inflammatory, hypoxic and ischemic challenge, and (2) whether IL-10 had any harmful effects per se. METHODS: Anesthetized piglets were randomized to control (n = 8), IL-10 (n = 10), endotoxin (ETX) (n = 10), or ETX and IL-10 (ETX/IL-10) (n = 10) groups. IL-10 was administered after pretreatment with saline in the IL-10 group or ETX in the ETX/IL-10 group. Then, cerebral hypoxia and ischemia was induced by bilateral clamping of the common carotid arteries and ventilation with 8% O(2) for 30 min, followed by 4 h of reoxygenation and reperfusion. Extracellular levels of lactate, pyruvate, and glycerol were measured with microdialysis in periventricular white matter and parasagittal subcortical tissue, and tissue oxygenation and microcirculation were measured with Doppler technique. We compared the areas under the concentration-time and flow-time curves and maximum concentrations between (1) the ETX/IL-10 and ETX groups, and (2) the control and IL-10 groups. RESULTS: We found no differences between (1) the ETX/IL-10 and ETX groups, and also no differences between (2) the control and IL-10 groups. CONCLUSION: We could not show that the treatment with IL-10 after onset of inflammation had neuroprotective effects in the newborn piglet brain. IL-10 did not attenuate metabolism in the absence of ETX-induced inflammation.

Animals↗

PubMed2005

Inflammation increases vulnerability to hypoxia in newborn piglets: effect of reoxygenation with 21% and 100% O2.

OBJECTIVE: The purpose of this study was to assess whether inflammation increases vulnerability to hypoxia, and influences the effect of 100% O(2) and 21% O 2 reoxygenation on brain. STUDY DESIGN: Newborn piglets (n = 31) were randomized to 4 interventional groups: pretreatment with saline or endotoxin. After hypoxia they were reoxygenated with 21% or 100% oxygen for 30 minutes, followed by 21% oxygen for all groups. To assess brain injury we measured extracellular brain tissue glucose, glycerol, and lactate/pyruvate by microdialysis, brain tissue oxygen tension, and laser Doppler flow. RESULTS: Administration of endotoxin reduced the time to reach base excess (BE) -20 mmol/L by median 32 minutes compared with saline ( P < .05). We found no differences in changes in biochemical markers, brain tissue microcirculation, or oxygen tension between piglets in the 4 groups. CONCLUSION: Endotoxin and hypoxia acted synergistically in inducing metabolic acidosis. In the presence of experimental inflammation, 21% oxygen seems as effective as 100% O(2) in reoxygenating piglets.

Analysis of Variance↗

PubMed2004

Restricted fetal growth in sudden intrauterine unexplained death.

BACKGROUND: Unexplained antepartum stillbirth is a common cause of perinatal death, and identifying the fetus at risk is a challenge for obstetric practice. Intrauterine growth restriction (IUGR) is associated with a variety of adverse perinatal outcomes, but reports on its impact on unexplained stillbirths by population-based birthweight standards have been varying, including both unexplained and unexplored stillbirths. AIM: We have studied IUGR, assessed by individually adjusted fetal weight standards, in antepartum deaths that remained unexplained despite thorough postmortem investigations. METHODS: Antenatal health cards from a complete population-based 10-year material of 76 validated sudden intrauterine unexplained deaths were compared to those of 582 randomly selected liveborn controls. Birthweight <10th percentile of the individualized standard adjusted for gestational age, maternal height, weight, parity, ethnicity, and fetal gender was defined as growth restriction. RESULTS: 52% of unexplained stillbirths were growth restricted, with a mean gestational age at death of 35.1 weeks. Suboptimal growth was the most important fetal determinant for sudden intrauterine unexplained death (odds ratio 7.0, 95% confidence interval 3.3-15.1). Concurrent maternal overweight or obesity, high age, and low education further increase the risk. Overweight and obesity increase the risk irrespective of fetal growth, and while high maternal age increases the risk of the normal weight fetus, it is not associated to growth restriction as a precursor of sudden intrauterine unexplained death. CONCLUSIONS: IUGR is an important risk factor of sudden intrauterine unexplained death, and this should be excluded in pregnancies with any other risk factor for sudden intrauterine unexplained death.

Adolescent↗

PubMed2004

A kick from within--fetal movement counting and the cancelled progress in antenatal care.

Interest for maternal fetal movement counting as a method of screening for fetal well-being boomed during the 1970's and 1980's. Several reports demonstrated that the introduction of counting charts significantly reduced stillbirth rates. However, in 1989, a large study appeared in The Lancet that annihilated research in this field by deeming charts ineffective. In retrospect, it seems evidence was lacking. This review revisits the subject of the significance of fetal movement counting in predicting outcome and reducing stillbirth rates. A structured search was performed to identify studies relating to pregnancy outcome and its association with maternal perception of fetal movements. Suspected preliminary or redundant material was excluded. Only publications from Western countries dating from after 1970 were included. Twenty-four studies were identified. Available data demonstrate that reduced fetal movements are associated with adverse pregnancy outcome, both in high and low risk pregnancies. Increased vigilance towards maternal perception of movements (e.g. by performing movement counting studies) reduces stillbirth rates, in particular stillbirths deemed avoidable. While screening for fetal well-being by maternal fetal movement counting can reduce fetal mortality rates, a resurrection in research activity is urgently needed to optimize its benefits.

Female↗

PubMed2003

Cause and risk of stillbirth in twin pregnancies: a retrospective audit.

BACKGROUND: The epidemiology of twin pregnancies complicated by stillbirth of one or both fetuses is a scarcely examined area. The risk of perinatal death in twin pregnancies is increased 2-5 times compared to singletons, and the identification of preventable risk factors becomes increasingly important as the number of multiple pregnancies is rising. We report the causes of death in twin pregnancies and their respective risk factors. METHODS: Twin pregnancies (n = 54) complicated by antepartum or intrapartum stillbirth of one or both twins (n = 68) and twin pregnancies with normal outcome (n = 103) in the counties of Oslo and Akershus, Norway, from 1986 to 1995 were included. The cases were classified and compared to the controls in multiple logistic regression analyses with regard to risk factors. RESULTS: The risk of stillbirth increased with monochorionicity, non-Western origin and assisted reproduction techniques (ART). The cases could be divided into eight different groups according to the primary diagnosis. The groups did not fit any of the existing cause-of-death classifications used on singleton stillbirths. CONCLUSIONS: The identification of monochorionic gestation should be made early in pregnancy to designate the level of risk. Assisted reproduction techniques leading to a high incidence of twins should be avoided. Health care professionals in the immigrant population should address the detrimental effects of consanguinity on reproductive outcome. We emphasize the need of a new cause-of-death classification for twin stillbirths.

Case-Control Studies↗

PubMed2002

Interleukin-10 reverses acute detrimental effects of endotoxin-induced inflammation on perinatal cerebral hypoxia-ischemia.

UNLABELLED: Perinatal brain injuries and the subsequent development of cerebral palsy are closely associated with intrauterine infections and inflammatory response. Antibiotics have proven futile in reducing perinatal brain injuries. We tested whether treatment with the anti-inflammatory cytokine IL-10 could have beneficial effects during a concomitant endotoxin and cerebral hypoxic-ischemic challenge. Thirty-three newborn piglets were randomized to pretreatment with: CONTROLS: placebo, Endotoxin: 2 kU/kg bolus and infusion of 1 kU/kg per h of endotoxin, or Endotoxin+IL-10: endotoxin in addition to 50 microg/kg of porcine recombinant IL-10. We induced cerebral hypoxia-ischemia by bilateral clamping of the common carotid arteries and ventilation with 8% oxygen for 20 min followed by 3 h of reoxygenation/reperfusion. Extracellular lactate, pyruvate, glycerol and glutamate, microcirculation and tissue oxygenation were monitored in the striatum by microdialysis, laser Doppler flow and oxygen tension probe, respectively. During and/or after cerebral hypoxia-ischemia, Endotoxin caused marked deterioration of the cerebral metabolic situation with higher lactate/pyruvate ratio (P=0.003), compared to CONTROLS and Endotoxin+IL-10. This was caused mainly by very low levels of pyruvate (P=0.001). During the following reoxygenation, Endotoxin compromised cerebral microcirculation (P=0.038) and tissue oxygenation (P=0.012) compared to CONTROLS and Endotoxin+IL-10. After a period of remission, a secondary energy failure and a new rise in the lactate/pyruvate ratio was seen in Endotoxin (P=0.002), but not in CONTROLS or Endotoxin+IL-10. At the end of observation, only the Endotoxin+IL-10 group had regained their baseline values in all variables. Thus IL-10 counteracts acute effects of endotoxin on cerebral metabolism, microcirculation and oxygen tension during hypoxia-ischemia in the perinatal brain.

Animals↗

PubMed2002

Prolonged apneas and hypoxia mediated by nicotine and endotoxin in piglets.

OBJECTIVE: Infections and maternal smoking are risk factors for SIDS, and toxins from common bacteria have been proposed as a causative link between infections and SIDS. Nicotine can be transferred in significant amounts postnatally to the infant through environmental tobacco smoke or maternal smoking before nursing. We investigated the acute effects of nicotine and endotoxin on repeated apnea by laryngeal reflex stimulation and the following autoresuscitation. DESIGN: Thirty-four 1-week-old (+/- 1 day) piglets were sedated and randomized to 1 of 4 pretreatment groups: (1) 1 microg endotoxin i.v./kg; (2) 5 microg nicotine i.v./kg; (3) 1 microg endotoxin i.v./kg and 5 microg nicotine i.v./kg, and (4) placebo. Apnea was induced by insufflation of 0.1 ml of acidified saline (pH 2) in the subglottic space of the trachea three times with intervals of 2 min. RESULTS: Pretreatment with endotoxin caused a significant increase in plasma TNF-alpha in the endotoxin groups (mean value +/- SEM 953 +/- 246 and 980 +/- 226 pg/ml, respectively) but no significant change in plasma IL-1 beta. Blood pressure, respiratory rate or S(a)O(2) was not significantly affected before induced apnea. Both pretreatment with nicotine and endotoxin caused prolonged apneas by 35-45%, a complete loss of normal hyperventilation during autoresuscitation, and prolonged hypoxia after apnea. CONCLUSIONS: Nicotine and endotoxin interferes with autoresuscitation after apnea. This experimental model on piglets may shed light over important mechanisms involved in the causation of SIDS.

Animals↗

PubMed2002

Detrimental effects of nicotine and endotoxin in the newborn piglet brain during severe hypoxemia.

Hypoxia-ischemia is a major cause of perinatal brain damage, but evidence shows that brain injury also is associated with intrauterine infections and maternal smoking. The mechanisms are not known, and we therefore explored the effects of experimental inflammation or nicotine on perinatal brain metabolism and injury during severe hypoxemia. Twenty-eight 1-week-old piglets were anesthetized and instrumented with microdialysis probes in the striatum and brainstem. We studied three pretreatment groups: (1) 20 microg/kg i.v. nicotine (n = 9); (2) 1 microg/kg i.v. endotoxin from Escherichia coli (n = 11), or (3) control (n = 8). The piglets were subsequently exposed to 30 min of hypoxemia (6% O(2)). In order to minimize any ischemic component and increase survival, this was abrupted for 1 min if blood pressure fell to 30 mm Hg. During hypoxemia, both the pretreatment with endotoxin and nicotine induced higher levels of extracellular lactate and peak lactate/pyruvate ratio compared with controls (54.7 +/- 9.6 (p < 0.01) and 65.2 +/- 13.1 (p < 0.02) vs. 15.9 +/- 7.4, respectively), reflecting a deterioration of the metabolic status in these groups. The two pretreated groups reached significantly higher peak levels of extracellular glycerol (30.9 +/- 4.1 vs. 77.9 +/- 12.7 and 89.4 +/- 14.2 micromol/l, respectively, p = 0.01), indicating a higher level of cellular membrane disintegration or leakage. In addition, 3 endotoxin piglets and 4 nicotine piglets died during reoxygenation, while all controls survived (p = 0.13 and p < 0.04, respectively). Mortality was associated with a rise in extracellular glutamate at the end of hypoxemia/start reoxygenation (p = 0.02). These findings contribute in explaining how nicotine and inflammatory response to bacterial toxins could act as cofactors for hypoxic-ischemic neurologic injury in the immature brain.

Animals↗

PubMed2002

Maternal health in sudden intrauterine unexplained death: do urinary tract infections protect the fetus?

OBJECTIVE: To study the impact of maternal health and obstetric complications on the risk for sudden intrauterine unexplained death. METHODS: All 76 cases of sudden intrauterine unexplained death and 165 explained stillbirths among singletons in Oslo, Norway (1986-1995) were compared with 582 controls. Information on maternal health was registered from antenatal health cards and the Medical Birth Registry of Norway. The effect of pregnancy duration was studied before logistic regression analysis corrected for pregnancy duration was performed. RESULTS: Urinary tract colonization or infection in pregnancy was associated with a reduced risk for subsequent sudden intrauterine unexplained death (odds ratio [OR] 0.29 [0.12-0.74]), whereas insufficient physiologic hemodilution during pregnancy (lowest hemoglobin greater than 13 g/mL) increased the risk for sudden intrauterine unexplained death (OR 9.50 [1.30-69.3]). However, the risk for sudden intrauterine unexplained death remained unaffected by the total number of indicators of impaired maternal health during pregnancy, in contrast to significant impact on other stillbirths. CONCLUSION: Urinary tract colonization or infection may offer protection against sudden intrauterine unexplained death. We hypothesize that the subsequent maternal immune response offers transplacental protection against lethal fetal infections by common pathogens of urinary tract infections. Other health indicators have little impact on sudden intrauterine unexplained death.

Female↗