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Biomedical subjects

H Fahnenstich

Publications and source records attributed to H Fahnenstich.

At least 19 recordsLinked to original sources

Longitudinal data for intrauterine levels of fetal IGF-I and IGF-II.

OBJECTIVE: An increasing body of evidence supports a major role for the insulin-like growth factors (IGFs) in the control of human fetal growth. Individual data at various times of pregnancy suggest that IGF-I and IGF-II levels remain stable up to the 33rd week of pregnancy. Thereafter, both increase to reach values 2-3 times higher at term. In order to provide an accurate reflection of fetal IGFs in utero, we sampled fetal blood from the umbilical cord by cordocentesis. METHODS: We measured IGF-I and IGF-II in 12 fetuses longitudinally for up to 5 times between the 21st week of gestation and delivery. RESULTS: All patients showed a progressive increase in IGF-I and IGF-II levels. Data determined during different time intervals (before 29th, 29th to 32nd, after 32nd week) were compared and the main increase was found after the 32nd week. The median for IGF-I before the 29th week was 33.5 ng/ml (range 19-40.5) and increased to 41 ng/ml (32-59) between the 29th to 32nd and further to 54.1 ng/ml (range 17-70) thereafter. During the same time interval, the median for IGF-II increased from 217 ng/ml (86-326) to 349 ng/ml (227-467). In 7 patients, cord blood after delivery was available. For IGF-II a further increase was consistently found after birth (from 282 ng/ml (175-511) to 393 ng/ml (297-513)), whereas only 2 fetuses showed an increase in IGF-I. CONCLUSION: We conclude that in human fetuses, IGF-I and IGF-II levels increase longitudinally throughout pregnancy. Therefore, they may become important markers of healthy fetal development.

Cordocentesis↗

Neurodevelopmental risks in twin-to-twin transfusion syndrome: preliminary findings.

The purpose of this study was to determine the neurodevelopmental risks in patients with twin-to-twin transfusion syndrome, a rare but serious complication of monochorionic twin gestations. From a total sample of 94 twins with twin-to-twin transfusion syndrome, admitted during 1989 and 1993, 49 patients survived and 40 patients were followed to a mean age of 24 months. Neurological status and psychomotor development (Denver and Griffiths Developmental Tests) were determined. Parameters of the neonatal period were evaluated for their potential prediction. Of the 40 tested patients 18 showed a normal psychomotor development. Thirteen patients exibited a specific delay in language development and/or showed minor neurological dysfunctions. Nine twins had severe psychomotor retardation in combination with cerebral palsy. Major neurological sequelae were found, more common in recipients than in donors (6/19 vs 3/21). Correspondingly, neonatal ultrasound showed more pathological results (especially periventricular leucomalacia) in recipients. Neither anaemia nor polycythaemia at birth can predict developmental outcome. Apart from a high prenatal mortality rate, both twins, donators as well as recipients, are highly at risk for brain damage of different aetiology, associated with abnormal neonatal cerebral ultrasound.

Birth Weight↗

Concentrations of thrombopoietin and interleukin-11 in the umbilical cord blood of patients with fetal alloimmune thrombocytopenia.

The objective of this study is to determine whether the fetus compensates for fetal alloimmune thrombocytopenia (FAITP) by increasing serum concentrations of thrombopoietin (TPO) and interleukin-11 (IL-11). TPO and IL-11 concentrations were measured in cord blood sera of 12 neonates with FAITP, and 35 preterm and 25 term controls. TPO concentrations in the 12 patients (median 129 pg/mL, range 73 to 325 pg/mL) were similar to those of 35 healthy preterm neonates (median 183 pg/mL, range 71 to 290 pg/mL) and the 25 term controls (median 180 pg/mL, range 93 to 302 pg/mL), although the platelet counts were significantly lower in FAITP. TPO concentrations did not correlate with the platelet counts, platelet nadir after birth, or time to recovery of normal platelet count. IL-11 reached detectable concentrations only in four patients with FAITP (median 54 pg/mL). After birth, these patients had a more rapid recovery of the platelet count. Cord blood serum concentrations of TPO are not significantly elevated in FAITP and do not predict the severity of the thrombocytopenia. Elevated IL-11 may signal a more rapid platelet recovery in FAITP.

Fetal Blood↗

Cholesterol dynamics in the foetal and neonatal brain as reflected by circulatory levels of 24S-hydroxycholesterol.

UNLABELLED: Oxysterols, particularly those hydroxylated in the steroid side-chain, are formed from cholesterol by specific cytochrome P450 enzymes and may facilitate elimination of cholesterol from extrahepatic sources. In humans, the greatest portion of circulating 24S-hydroxycholesterol (24S-OH-Chol) is derived from the brain and the absolute concentration depends on age. In the present study, concentrations of 24S-OH-Chol and for comparison 27-OH-Chol were determined by a highly sensitive isotope dilution method using gas chromatography-mass spectrometry in serum samples from normal preterm and term neonates and those with Rhesus haemolytic disease, taken serially for diagnostic purposes. Serum concentrations of cholesterol, 24S-OH-Chol and 27-OH-Chol were similar in venous versus arterial cord blood of 6 term neonates. Serum concentrations of 24S-OH-Chol and 27-OH-Chol in 12 small for gestational age (SGA) preterm neonates were significantly lower than those in 12 appropriate for gestational age (AGA) preterm neonates (p < 0.001), and also lower than those in 12 SGA (0 < 0.001) and 12 AGA term neonates (p < 0.05). Serum cholesterol was significantly higher in preterm than in term neonates (p < 0.001). 24S-OH-Chol serially determined in 8 infants with Rhesus haemolytic disease increased 5-6-fold during the first 3 mo after birth (from 42 +/- 20 ng ml(-1) to 227 +/- 71 ng ml(-1)). 27-OH-Chol increased simultaneously from 30 +/- 14 ng ml(-1) to 100 +/- 39 ng ml(-1). CONCLUSION: Serum concentrations of 24S-OH-Chol increased 5-6-fold after birth. This could be an indication of normal cholesterol metabolism in the developing neonatal brain.

Brain↗

Randomized, multicenter trial of two different formulas for very early enteral feeding advancement in extremely-low-birth-weight infants.

BACKGROUND: In extremely-low-birth-weight (ELBW) infants, formula feeding is required if human milk is not available. The tolerance of a new 'high' lactose (55 g/L), low protein, low phosphate, hydrolyzed protein formula (HLF) for early enteral feeding advancement of ELBW infants was compared with that of a low lactose (1 g/L) hydrolyzed protein formula (LLF). METHODS: In a randomized multicenter trial, 99 ELBW infants were fed according to a standardized protocol beginning at 48 hours of age with 12 ml/kg daily increments. Primary outcome was the cumulative milk feeding volume (CFV) from days 3 to 14. The authors hypothesized that feeding HLF as a supplement to human milk would increase the CFV at least by 20% in at least 60% of matched pairs compared with LLF. A secondary issue was to investigate whether human milk would increase the CFV compared with formula. RESULTS: The CFV was 720 mL/kg (range, 0-962 mL/kg) with HLF and 613 mL/kg (range, 3-1,283 mL/kg) with LLF feeding. There was no 20% difference. On day 14, the median feeding volume was 103 mL/kg. The CFV was 533 mL/kg (range, 0-962 mL/kg) in infants who received less than 10% of human milk and 832 mL/kg (range, 74-1,283 mL/kg) in infants who received more than 10%. Necrotizing enterocolitis (Bell stage > or =2) occurred only with LLF feeding (n = 5; P < 0.05). CONCLUSIONS: The study failed to find the hypothesized 20% advantage of the new HLF. The observed advantage of human milk supports the hypothesis that it should be the first diet in ELBW infants; however, this hypothesis still must be confirmed in a controlled, randomized trial.

Enteral Nutrition↗

Erythropoietin gene expression in different areas of the developing human central nervous system.

UNLABELLED: Evidence from cell culture and animal experiments suggests a neuroprotective and neurotrophic function of erythropoietin (EPO). We have quantitated the distribution of EPO mRNA expression in the developing human central nervous system (CNS). PATIENTS AND METHODS: Up to seven biopsies from different areas of the CNS of four preterm fetuses (gestational age 23-37 weeks) were obtained at routine postmortem examinations. EPO mRNA was quantitated by competitive PCR in samples from the CNS, the kidneys, and the liver where the EPO gene is predominantly expressed at this gestational age. RESULTS: EPO mRNA was most abundant in one sample from the cerebellum (0.29 amol/microg total RNA [amol=10(-18)mol]) and two from the pituitary gland (0.23 amol/microg total RNA), but levels varied considerably. EPO mRNA in the cortex cerebri (median 0.12 amol/microg total RNA; n=4) dominated over the expression in the corpora amygdala (median 0.05 amol/microg total RNA; n=4), the hippocampus (median 0.03 amol/microg total RNA; n=4), or the basal ganglia (median 0.01 amol/microg total RNA; n=3). Only little EPO mRNA (<0.01 and 0.06 amol/microg total RNA) was found in the spinal cord. EPO mRNA levels in the cerebellum, pituitary gland, or the cerebral cortex were within the same range as in the liver (0.03-1.67 amol/microg total RNA; n=4), or the kidneys (0.06-0.79 amol/microg total RNA; n=4). CONCLUSION: We found the EPO gene expressed throughout the fetal human CNS. Our data provide the basis to discuss a function for EPO in the brain of humans as well.

Central Nervous System↗

Fentanyl-induced chest wall rigidity and laryngospasm in preterm and term infants.

OBJECTIVE: To assess the occurrence of muscle rigidity after fentanyl administration in premature and term neonates. DESIGN: Prospective case series, observational study. SETTING: A university hospital neonatal intensive care unit. PATIENTS: 8/89 preterm and term infants (25-40 wks gestational age) who received fentanyl for perioperative analgesia and sedation or intensive care procedures. INTERVENTIONS: Mechanical or bag mask ventilation and antagonization with naloxone. MEASUREMENTS AND MAIN RESULTS: We observed chest wall rigidity in 8 patients after low dosage of fentanyl (3-5 microg/kg body weight). All patients presented with respiratory distress, hypercapnia, and hypoxemia leading to bradycardia. In two patients, laryngospasm was noted and associated with muscle rigidity, thus making intubation impossible. Naloxone (20-40 microg/kg body weight) reversed the laryngospasm and muscle rigidity immediately, allowing restitution within 1 min. In our patient population, we found fentanyl-induced chest wall rigidity in 4% of neonates after fentanyl administration. CONCLUSION: Even low doses of fentanyl can lead to thoracic rigidity in neonates. Additionally, we observed laryngospasm in two patients and speculate that it might be a variant of muscle rigidity.

Fentanyl↗

Good prognosis for psychomotor development in survivors with nonimmune hydrops fetalis.

We examined the psychomotor development of 33 of 61 surviving children, from a series of 107 consecutive live-born cases with nonimmune hydrops fetalis. The majority had a normal outcome. Three had a (simultaneous) serious underlying disease (e.g. fetal herpes infection) and had either severe psychomotor retardation or blindness. Two showed clumsiness and were considered to have minor neurological dysfunction. We conclude that survivors, especially those with transient benign intrauterine conditions, such as lymphatic aetiology have no additional risk to their psychomotor development.

Child↗

Expression of the thrombopoietin gene in human fetal and neonatal tissues.

Thrombopoietin (TPO) regulates megakaryopoiesis and platelet production. In the adult, TPO is mainly produced by the liver and the kidneys. This study focuses on fetal and neonatal TPO mRNA expression. In 26 human fetuses and preterm neonates, samples from liver, kidney, spleen, lung, and bone marrow were extracted for total RNA. We measured platelet counts, TPO serum concentrations by enzyme-linked immunosorbent assay, and TPO mRNA contents by reverse transcription/competitive polymerase chain reaction. TPO mRNA concentrations per microgram total RNA were similar in liver, spleen, and bone marrow, slightly lower in kidney, and significantly lower in lung. When related to gram tissue, TPO mRNA levels were highest in the liver. Considering the total amount of TPO mRNA produced in liver, kidney, and spleen, the liver accounted for 95.3%. No correlations between TPO mRNA expression and serum TPO concentration, blood platelet count, or gestational age were observed. In conclusion, the liver is the primary site of TPO gene expression in human fetuses and neonates. The spleen may contribute to TPO production during fetal life. Like in the adult, TPO mRNA is expressed in fetal bone marrow.

Adult↗

Congenital hydrocephalus internus and aqueduct stenosis: aetiology and implications for genetic counselling.

UNLABELLED: Genetic counselling in families with congenital hydrocephalus internus (CHI) in combination with aqueduct stenosis (AS) is often difficult due to an uncertain aetiology. We present a series of 35 patients with CHI and AS focusing on the aetiology and presumed recurrence risk for siblings. In 13 patients (37.1%) a genetic aetiology was identified with an increased recurrence risk for siblings. The relative frequency of patients with X-linked hydrocephalus in our sample was in accordance with the literature (2/35), but was more frequent in other diseases with Mendelian inheritance. CONCLUSION: In addition to the well-known X-linked and autosomal recessive forms of aqueduct stenosis with hydrocephalus, this malformation can occur in other diseases with Mendelian inheritance. This finding is of considerable importance for genetic counselling and prognosis.

Cerebral Aqueduct↗

Perinatal management of fetal hemolytic disease due to Rh incompatibility combined with fetal alloimmune thrombocytopenia due to HPA-5b incompatibility.

We report out experience in the perinatal management of a complex case of fetal hemolytic disease primarily due to Rhesus incompatibility combined with fetal alloimmune thrombocytopenia. The lowest fetal hemoglobin and platelet levels were 2.6 g/dl and 13,000/microliter, respectively. Intrauterine treatment consisted of six transfusions of packed red cells into the umbilical vein and one transfusion of platelets. The neonate required four transfusions of packed red cells to correct her hyporegenerative erythropoiesis. Postnatal management also included one platelet transfusion, intravenous immunoglobulins and erythropoietin. Although some degree of fetal thrombocytopenia may invariably be found in fetal red cell incompatibility, other rare causes need to be excluded.

Adult↗

Neonatal screening for hearing disorders in infants at risk: incidence, risk factors, and follow-up.

OBJECTIVE: To determine the incidence and risk factors for hearing disorders in a selected group of neonates and the feasibility of selective hearing screening. SETTINGS: Multicenter prospective trial at five centers in Germany. METHODS: Enrollment criteria: in addition to previously defined risk factors by the Joint Committee on Infant Hearing (family history of hearing loss, in utero infections, craniofacial anomalies, birth weight <1500 g, critical hyperbilirubinemia, ototoxic medications, bacterial meningitis, postnatal asphyxia, mechanical ventilation >5 days, stigmata, or syndromes associated with hearing loss), the impact of maternal drug abuse, birth weight <10th percentile, persistent pulmonary hypertension, and intracranial hemorrhage more than or equal to grade III or periventricular leukomalacia on infant hearing were evaluated. The screening procedure was performed by automated auditory brainstem response (A-ABR; ALGO 1-plus; Natus Med Inc, San Carlos, CA). STATISTICS: univariate analyses of risk factors versus A-ABR results and a multivariate regression analysis were used; additionally, the total test time was recorded. RESULTS: Seven hundred seventy recordings from 777 infants enrolled consecutively constitute the basis of this analysis. Mean gestational age was 33.8 +/- 4.3 weeks, birth weight 2141 +/- 968 g; 431 infants being male and 339 female; 41 (5.3%) infants exhibited pathologic A-ABR results (16 bilateral and 25 unilateral). Meningitis or sepsis, craniofacial malformations, and familial hearing loss were independent significant risk factors. Median total test time was 25 minutes. Follow-up examinations in 31 infants revealed persistent hearing loss in 18 infants (13 infants sensorineural, 5 from mixed disorders), 7 requiring amplification. CONCLUSION: Hearing screening in high-risk neonates revealed a total of 5% of infants with pathologic A-ABR (bilateral 2%). Significant risk factors were familial hearing loss, bacterial infections, and craniofacial abnormalities. Other perinatal complications did not significantly influence screening results indicating improved perinatal handling in a neonatal population at risk for hearing disorders.

Analysis of Variance↗

Erythropoietin mRNA expression in human fetal and neonatal tissue.

Based on animal experiments, a switch of the erythropoietin (EPO) production site from the liver in the fetus to the kidneys in the adult has been postulated. To study the switch in humans, we have quantitated EPO mRNA expression in liver, kidney, spleen, and bone marrow of human fetuses and neonates by means of a competitive polymerase chain reaction (PCR). Tissue samples from 66 routine postmortem examinations were obtained. EPO mRNA was expressed in 97% of the tissue specimen derived from the liver (n = 66) and in 93% of those from the kidneys (17 weeks of gestation until 18 months after birth; n = 59). For the first time the EPO gene was found expressed in vivo in human spleen (96% of 64 samples) and in fetal and neonatal bone marrow (81% of 21 samples). EPO mRNA expression in the kidneys increased significantly beyond 30 weeks of gestation (P < .05). Although there was a slight decrease in EPO mRNA content per g liver tissue towards birth, the liver accounted for about 80% of the total body EPO mRNA. The contribution of the spleen and bone marrow were minor compared with liver and kidneys. Our results indicate that in humans the liver is the primary site of EPO gene expression not only in fetal, but also in neonatal life. A significant increase of renal EPO mRNA expression after 30 weeks of gestation might indicate the beginning switch.

Bone Marrow↗

Color Doppler echocardiographic evaluation of tricuspid regurgitation and systolic pulmonary artery pressure in the full-term and preterm newborn.

Color Doppler echocardiography of tricuspid valve regurgitation (TR) is a valid, noninvasive method of determining systolic pulmonary artery pressure (SPAP). In a prospective study the authors examined 56 healthy full-term newborns (group I), 36 healthy preterm newborns (group II), and 10 preterm newborns with severe respiratory distress syndrome requiring surfactant replacement therapy (group III). Doppler studies were repeated until the transtricuspid gradient was < 20 mm Hg. In 83.3% of children a reproducible spectral curve was recorded at least once. The authors estimated the transtricuspid gradient delta p (RV-RA) by using the modified Bernoulli equation. Within the first twenty-four hours delta p (RV-RA) was < 20 mm Hg in 72.7%, 50%, and 25% of children with measurable TR in groups I, II, and III, respectively, increasing to 91.1%, 78.6%, and 55.6% within forty-eight hours. There was no significant correlation between SPAP and gestational age, birth weight, mode of delivery, and ductal closing time. Continuous holosystolic envelope tracing of TR was recorded in 16.6%. In these patients delta p (RV-RA) was measured markedly higher (mean of 30.1 mm Hg) than in the others (mean 17.3 mm Hg). The authors conclude that there is a high prevalence of TR in neonates, which allows estimation of SPAP in > 80% of newborns without considerable impairment. Normalization of SPAP takes place within four days in most patients, but there is a delay in preterm infants with severe respiratory distress syndrome.

Blood Pressure↗

Erythropoietin concentrations and erythropoiesis in newborns suffering from renal agenesis and congenital kidney diseases.

UNLABELLED: We studied serum concentrations of erythropoietin (EPO) in the cord blood of 31 newborns. In patients with renal agenesis (n = 6), the EPO levels were 68.2 (23-177) mU/ml (median, range). These values are clearly above EPO levels in the reference groups (median/range: < 30 weeks 11.0 (5.5-17.5) mU/ml; 30-32 weeks 18.1 (5.5-136) mU/ml; 33-34 weeks 17.7 (8.3-423) mU/ml; 35-37 weeks 17.3 (5.5-272) mU/ml; > or = 38 weeks 17.8 (8.7-40.3) mU/ml). Neonates with polycystic kidney diseases (n = 12, EPO 23.5 (9.7-491) mU/ml) and with severe bilateral hydronephrosis due to obstructive uropathy (n = 13, 18.6 (7.5-30.7) mU/ml) showed no difference to the reference groups. In all groups there were only slight differences in haemoglobin/haematocrit values. CONCLUSION: In spite of renal agenesis and severe congenital kidney diseases, erythropoiesis is sufficiently maintained during fetal life. The liver of congenitally kidney-damaged fetuses is sufficiently able to compensate the reduction in--or lack of--renal EPO production.

Erythropoiesis↗

Cerebral tissue oxygenation during hypoxia and hyperoxia using artificial placentation in lamb.

Aiming at a better understanding of the pathophysiologic basis of perinatal encephalopathy, we evaluated patterns of tissue oxygenation during hypoxia and hyperoxia. We utilized both laserspectroscopy and invasive tissue-Po2 microneed measurements synchronously in five newborn lambs (141-143 days of gestation). The model of artificial placentation provided defined changes of the blood gases, using a extracorporeal circuit with interposition of membrane lung. During hyperoxia, the Po2 at the blood outlet port of the lung was raised to > 300 mmHg for five minutes. During hypoxia, Po2 was diminished as oxygen at the gas phasis was replaced by nitrogen. After the induction of hyperoxia, a rise of tissue-Po2 was observed. The synchronously recorded data of the laserspectroscopy showed adequately rising HbO2 values in concordance (r = 0.97, p < 0.001). As a constant finding we did not observe Cyt-aa3 changes during induced hyperoxia with tissue-Po2 values of < 40 mmHg. Furthermore, no changes in blood volume occurred in this case. A different pattern of the laserspectroscopic parameters was found when the tissue-Po2 rose above a value of > 40 mmHg and Cyt-aa3 rose after a lag-time occurred. During induced hypoxia an immediate fall of tissue-Po2 corresponding with a fall of HbO2 in the spectroscopic tracing occurred (r = 0.87, p < 0.001). A fall of the Cyt-aa3 level was seen with a lag-time when the tissue-Po2 had reached values of below 10 mmHg. In addition, a rise of blood volume was recorded in all cases of induced hypoxia. In conclusion, the results indicated that cellular redoxe state remains stable over a large range of oxygen partial pressure changes.

Animals↗

Biochemical monitoring of fetal distress with serum-immunoreactive erythropoietin.

The ability of parameters like umbilical arterial pH and Apgar score to predict and/or to reflect fetal distress are limited. It is known that erythropoietin (EPO) increases when partial pressure of oxygen is insufficient for metabolic demand. Therefore we studied the levels of EPO in the cord blood of stressed neonates (n = 75). In addition, reference values for EPO were established in a group of healthy term infants (n = 54) (mean +/- SD: 20.02 +/- [mU/ml]) and in premature infants (n = 77) according to gestational age. A significant increase in EPO concentrations was found in the stressed group: 153.4 +/- 418.8 [mU/ml], p < 0.003 (n = 27) in acute stress; and 102.6 +/- 127.1 [mU/ml], p < 0.002 (n = 48) in chronic stress. However parameters like hemoglobin, hematocrit, umbilical arterial pH and Apgar-score did not correlate with EPO values. A sensitivity of 59% and a specificity of 92% was calculated. We conclude that serum EPO concentrations are capable of detecting acute and chronic stress and could be useful as a screening method. In part EPO concentrations also allow us to grade stress in pregnancies that are complicated by diseases like preeclampsia.

Apgar Score↗