The role of elevated central-peripheral temperature difference in early detection of late-onset sepsis in preterm infants.

AIMS: The study investigated the association between clinical symptoms and late-onset sepsis (LOS) in preterm infants with the aim of identifying a non-invasive tool for the early detection of LOS. METHODS: This was a prospective study of 83 episodes of suspected LOS in 67 preterm infants. At the time LOS was suspected, we recorded a standardized set of clinical symptoms. A diagnosis of "clinical LOS" (Clin-LOS), "culture-proven LOS" (Prov-LOS) or "LOS not present" (No-LOS) was made on the basis of C-reactive protein (CrP) and blood culture results where Clin-LOS was defined as CrP>10mg/l, Prov-LOS was defined as CrP>10mg/l AND positive blood cultures, or it was established that there was no sepsis present (No-LOS). We examined univariable associations between clinical signs and LOS using odds ratio (OR) analysis and then adjusted the odds ratio (adOR) through binary regression analysis. RESULTS: Clin-LOS was diagnosed in 20/83 episodes, 19 cases were found to have Prov-LOS. Clinical signs which had a significant association with Clin-LOS were capillary refill time >2s (OR 2.9) and decreased responsiveness (OR 5.2), whereas there was a negative association between gastric residuals and LOS (OR 0.35). However, the most marked association was found for a greater central-peripheral temperature difference (cpTD) >2°C (OR 9). In Prov-LOS an increased heart rate (OR 3.1), prolonged capillary refill time (OR 3.3) and again an increased cpTD (OR 16) had a significant association with LOS, whereas gastric residuals were negatively associated (OR 0.29). Regression analysis showed that cpTD was the most striking clinical sign associated with both Clin- (adOR 6.3) and Prov-LOS (adOR 10.5). CONCLUSIONS: Prolonged capillary refill time and - more impressive - elevated cpTD were the most useful clinical symptoms for detection of LOS in preterm infants. We especially suggest using cpTD as a predictor of LOS. It is a cheap, non-invasive and readily available tool for daily routines.

Prenatal hemodynamic disturbances -- pathophysiological background of intestinal motility disturbances in small for gestational age infants.

Uteroplacental insufficiency leads to fetal growth retardation which is a major cause of perinatal and postnatal morbidity. In the present study we investigated the relationship between prenatal hemodynamic disturbances and postnatal intestinal perfusion and gastrointestinal function in small for gestational age neonates. Prospectively, 124 preterm neonates with a birth weight below 1500 g were assigned to one of two groups according to the prenatal Doppler sonographic measurements: neonates with or without prenatal hemodynamic disturbances. We defined a pathological fetal perfusion using a pulsatility index of uterine arteries, umbilical artery and fetal thoracic aorta above the 90th percentile and a pulsatility index of the middle cerebral artery below the 10th percentile of a normal group. We compared intestinal adaptation in both groups as well as the blood flow velocity wave forms of the superior mesenteric artery in all neonates. Postnatally, all 42 neonates with prenatal hemodynamic disturbances were classified to be small for gestational age. Thirty-seven of these neonates developed abdominal problems with delayed meconium passage, abdominal distension, bilious vomiting and a delay in tolerating enteral feeding within the first days of life. Five of them needed surgical intervention, but none of these infants revealed typical signs of necrotizing enterocolitis. In contrast, all neonates born after normal prenatal perfusion were classified as appropriate for gestational age. Only 19 of 82 neonates of this group showed signs of intestinal disturbances postnatally. Doppler sonography demonstrated significantly lower systolic, mean and END-diastolic flow velocities, and higher pulsatility indices of the superior mesenteric artery in neonates with prenatal hemodynamic disturbances. This may occur as a result of a postnatally persistent redistribution of regional blood flow and results in gastrointestinal problems and may adversely affect gut motility.

[Drug withdrawal in newborns - clinical data of 49 infants with intrauterine drug exposure: what should be done?]. / Drogenentzug beim Neugeborenen - klinische und soziodemografische Daten von 49 Neugeborenen drogenabhängiger Mütter: Was kann und soll getan werden?

BACKGROUND: Infants of drug abusing mothers are at high risk to suffer from neonatal abstinence syndrome (NAS). Depending on the drug signs of neonatal withdrawal vary but mainly include central nervous system irritability. NAS causes long duration of hospital stay. Severe withdrawal signs are seen in infants exposed to methadone, infants exposed to other opioids like heroin or buprenorphine have been shown to be less symptomatic. Between the years 1997 and 2003 following the border opening there was a dramatic increase in drug exposed newborns seen in the area of Leipzig (East Germany). METHODS: In a retrospective study maternal and infant characteristics, severity of symptoms, duration of withdrawal and hospital stay, duration and kind of treatment as well as modalities for release from hospital were analyzed. RESULTS: From 1997 to 2003 49 drug exposed newborns were admitted to our neonatal care unit. There was an increase of the number of affected infants within these years ( ). Maternal drug abuse (n=48) included mainly methadone (n=33), in second line heroine and benzodiazepines, in a few cases also cocaine and cannabinoides. 3 mothers received substitution therapy with buprenorphine. Additional drug use to substitution therapy was seen in 15 mothers. Drugs of abuse were detected in infant urine specimen (36/48). 35 of exposed newborns showed signs of NAS (incidence of NAS 71%). For evaluation of withdrawal signs and conduction of therapy the Finnegan score was used. As first line pharmacological treatment phenobarbitone was administered (n=42), secondary morphine was used (n=14, treatment failure 33%). Mean duration of hospital stay was 21 days. Mean duration of pharmacological treatment was 14 days with longer duration for methadone exposed infants vs. non-methadone exposed infants (16 vs. 10 days). Hospital stay was longer for non-methadone exposed infants. Maternal intake of more than 20 mg methadone per day vs. up to 20 mg per day caused longer duration of hospital stay (28 vs. 20 days, p=0,015). CONCLUSION: Long duration of hospital stay and pharmacological treatment call for optimised principal guide lines for diagnosis, treatment and long term follow-up. The results also underline the need for further research for an effective pharmacological treatment.

[From resuscitation space in the delivery room of the Women's hospital to the perinatal center of the Leipzig University]. / Vom Reanimationsplatz im Kreisssaal der Frauenklinik zum Perinatalzentrum der Universität Leipzig.

Historical review on the development of neonatal intensive care and new-born nursing at the women hospital of Leipzig University from 1969 up to 1995 and the foundation of a Perinatal Center. The successes of perinatal care are demonstrated best by the decline of neonatal mortality of extremely low birth weight infants from more than 90% up to 20% in 1995. It is attributed to the progress in perinatal medicine as well as to a perfect functioning regionalization of high risk pregnancies.

Three cases with different presentation of fentanyl-induced muscle rigidity--a rare problem in intensive care of neonates.

We report about two newborns with sudden onset of inability of mechanical ventilation due to transient chest wall rigidity after fentanyl i.v. bolus of 2 and 4 microg/kg, respectively, resulting in severe hypoxemia and secondary bradycardia. A third case developed a rigidity of the tongue after fentanyl bolus, which created some unusual difficulties in bypassing the tongue for insertion an endotracheal tube. Because of common usage of this agent for analgesia we direct attention to the possibility of fentanyl-induced muscle rigidity. We underline the necessity of a slow bolus injection to prevent this dangerous adverse effect and we recommend the administration of naloxone and/or muscle relaxants as therapy in conjunction with mechanical ventilation.

[Use of hypertonic solutions through umbilical cord vessels]. / Zur Applikation hypertoner Lösungen über die Nabelschnurgefässe

The authors report on a newborn with skin necroses and fibularis paresis after postnatal administration of NaHCO3 via the umbilical cord. Then some problems of postnatal buffer therapy are discussed. After a review of advantages and disadvantages of puncture or cannulation of the umbilical vein on the one hand and its catheterization on the other, the former procedures are preferred for an effective buffer therapy, provided strict indications are followed.

[Anaesthesia and therapy for gestosis - impact on the newborn (author's transl)]. / Auswirkungen von Gestosetherapie und Anästhesie auf das Neugeborene.

Adaptation of 33 newborns and their clinical symptoms during the first weeks of age were studied retrospectively, with reference to cases in which the pregnant mothers had undergone treatment for hypertension, anaesthesia, and caesarean section. Primary adaptability was unambiguously limited in all newborns, with symptoms of impaired sensual motoricity being additionally recorded from 16 of them. Apnoeic seizures occurred to six children on their first day of age and called for continuous cardiorespiratory monitoring. Premature and hypotrophic newborns were primarily affected. Those delayed symptoms were attributed, first of all, to medicamentous effects. More caution should be exercised in prescribing neurodepressors of the Diazepam type, particularly in early pregnancy, say, prior to the 37th week. - An analysis was made of blood gas data in the blood of umbilical arteries of infants whose birth had been preceded by gestosis or eclampsia. Yet, their intranatal respiratory situation was not found to be basically worse than that of a control group.

[Recommendations for the diagnosis and therapy of bacterial infections in premature and newborn infants]. / Empfehlungen zur Diagnostik und Therapie bakterieller Infektionen bei Früh- und Neugeborenen.

In a survey the authors present the most important facts of diagnostic and therapy of bacterial infections in term and preterm neonates. It is a synthesis of an extensive study of the literature and of own experiences. Besides microbiological diagnostic and antibacterial chemotherapy one can find also suggestions concerning hematological and chemical diagnostic methods as well as of parenteral and oral nutrition and immunotherapy.

Aminophylline influences cerebral hyperperfusion after severe birth hypoxia.

Doppler sonographic investigations have presented cerebral hyperperfusion in neonates after severe asphyxia. Neonates with disturbed cerebral blood flow velocity (CBFV) tend to have poor outcomes. The purpose of this clinical study was to examine the influence of aminophylline on cerebral hyperperfusion. An intravenous bolus of 4 mg/kg aminophylline was given to nine neonates with Doppler sonographic signs of cerebral hyperperfusion. CBFV was determined before, 5 min, 60 min and 120 min after aminophylline administration and on the following day. After aminophylline the mean systolic (56.5 vs. 41.6 cm/s) and end diastolic (21.0 vs. 12.3 cm/s) blood flow velocity decreased and the mean pulsatility index (0.83 vs. 1.1) increased significantly. Repeated measurements showed a decrease in blood flow velocities and an increase in pulsatility index on the following days. Heart rate, mean arterial blood pressure and pCO2 were not significantly changed. We conclude that aminophylline influences cerebral hyperperfusion in neonates with disturbed autoregulation.

[External ventricular drainage--a possibility in therapy of progressive posthemorrhagic hydrocephalus in extremely premature newborn infants]. / Die externe Ventrikeldrainage--eine Möglichkeit der Therapie des progredienten posthämorrhagischen Hydrozephalus bei extrem unreifen Frühgeborenen.

7 premature infants with progressive posthaemorrhagic hydrocephalus were treated by means of external ventricular drainage (birth weight: 1050 gms, gestational age: 27.7 wks). All infants were generally unwell and were ventilated. The progression of hydrocephalus was well controlled during the drainage period in each patient. We believe external ventricular drainage is an effective form of therapy in premature infants with posthaemorrhagic hydrocephalus until the time of insertion of a ventriculo-peritoneal shunt.

[Value of brain ultrasound studies of newborn infants for prediction of neurological development in the 1st year of life]. / Der Wert hirnsonographischer Untersuchungen von Neugeborenen zur Prädiktion der neurologischen Entwicklung im ersten Lebensjahr.

BACKGROUND: Recent advances in perinatology have been associated with a decrease in perinatal mortality. However, nowadays detailed assessments are of major importance for accurate prediction of neurologic development of extreme low birth weight infants and term infants with severely disturbed postnatal adaptation. This study examined the role of cranial ultrasound for the prediction of developmental progress during the first year of life. PATIENTS AND METHODS: Fifty nine infants with gestational age less than 33. weeks and fifty seven infants with gestational age above 32. weeks were studied. Each infant was classified as normal, suspect or abnormal using cranial ultrasound and a specialized scoring system during the first days and twelve month of life. Repeated structured neurological examination were carried out during the first year of corrected age. By statistical analysis was investigated the correlation between the degree of ultrasound abnormalities and neurological outcome of neonates of both different gestational age groups. RESULTS: We diagnosed the same share of pathological ultrasound scans in both groups within the first days of life. In contrast there were remarkable differences concerning the results of sonographic investigation at the end of the first year of life. We demonstrated a significant higher incidence of abnormal findings in neonates with a gestational age less than 33 weeks at this point of time. The neurological progress of neonates of both groups was significantly disturbed in cases of major sonographic abnormalities. Cases of mild or moderate ultrasound abnormalities were significantly associated with a poor neurologic outcome only in neonates with a gestational age less than 33 weeks. By statistical analysis we proved a significant value of cranial ultrasound for prediction of neurological development of preterm neonates with gestational age less than 33 weeks. The certainty prediction of neurodevelopmental sequelae in neonates with gestational age above 32 weeks was associated with major sonographic abnormalities but not with mild or moderate sonographic pathology. CONCLUSION: The prognostic accuracy of ultrasound scans performed in the first week of life is important for preterm neonates with gestational age less than 33 weeks. In neonates with gestational age above 32 weeks we revealed no significant predictive value of the method. This limits the value of this technique in this patients as a reliable method for recognising of the infants with the need of early rehabilitation.

[Impaired postnatal cerebral perfusion after prenatal centralization-- increased risk of neonatal brain injury?]. / Gestörte postnatale cerebrale Perfusion nach pränataler Zentralisation--erhöhtes Risiko einer neonatalen Gefährdung?

Within the last years Doppler sonographic studies in high risk pregnancies had been included into obstetrical management strategies. Especially the high fetal risk in cases with severe intrauterine perfusion disturbances with signs of hemodynamic centralization--the brain sparing effect--had been established. In 11 premature newborns with prenatal sonographic recorded vasodilatation of cerebral vessels as a sign of hemodynamic centralization flow velocity waveforms of the anterior cerebral artery as well as left cardiac functional parameters (LVET, PEP) were measured at the 1st, 2nd, 3rd, 5th and 6th day of life. For the evaluation of the peripheral circulation the perfusion of the superior mesenteric artery was recorded by Doppler ultrasound. Additionally, the blood pressure, heart rate, pH and acid base status was considered. We used 25 premature newborns of corresponding gestational age and normal prenatal Doppler sonographic findings as a control group. In the group with prenatal brain sparing effect we could demonstrate a remarkable increase of the pulsatility index as a result of extreme diminished diastolic blood flow velocity. 5 newborns showed signs of reverse diastolic flow. The difference to the control group was highly significant. Perfusion measurements in the superior mesenteric artery demonstrated corresponding results at the first day of life with significant increased PI and diminished diastolic flow velocities. Our results demonstrate the great importance of prenatal diagnosis for the understanding of postnatal disturbances. The birth is not the endpoint of fetal hemodynamic centralization and the compensational mechanism is still continuing. Despite a well adapted cardiac function, normal hemodynamic situation and balanced metabolic findings remarkable changes of the impedance of the cerebral vessels are evident. Especially for the very immature newborns this may lead to the risk of leasions of the germinal matrix with following hemorrhage or ischaemic injury.

[Prematurity and placental insufficiency in twin pregnancies. Results during the care of multiple pregnancies at a center for premature births]. / Frühgeburtlichkeit und Plazentainsuffizienz bei Geminischwangerschaft Ergebnisse bei der Betreuung von Mehrlingsschwangerschaften in einem Frühgeburtenzentrum.

An analysis was made of 151 twin pregnancies, in 1975, 1978 and 1979, to study the effectiveness of obstetrico-neonatological attention to bigeminal pregnancies in a premature infant centre. -- Significant rise in early detection of bigeminal pregnancy due to much wider use of ultrasonic diagnosis and intensification of hospital treatment have drastically reduced the number of extremely immature twin births by delaying delivery to somewhere between the 34th and 36th weeks of gravidity. With the use of tocolysis nearly unchanged throughout the period of observation, change in average gestational age at birth should be interpreted primarily as the result of more long-time prepartum hospitalisation, with attention being offered for periods of more than three weeks. This conclusion was supported by unsatisfactory results regarding average gestational age and birth weight, following exclusive outpatient attention to women with bigeminal pregnancies. Improvement of foetal prognosis was found to depend primarily on proper therapeutic approach to prematurity. -- The authors' own experience differed from reports of other workers, in that the rate of hypotrophy declined in the wake of intensive prepartum care. Substantial reduction of the gap between average birth weights of first multiple foetuses and those of second multiple foetuses as well as declining differences between average birth weights of heavier twins, on the one hand, and those of less heavy twins, on the other, were recorded from all gestational age groups and attributed to improvement in intra-uterine care for all multiple foetuses due to intensified treatment. -- Significant rise in survival rates (after deduction of all foetal loss up to the 28th day of age) of all premature twins is considered an expression of increasingly improving life chances of twins, in general. It was based on growing numbers of highly immature survivors, but even more on significant rise in the number of premature survivors between the 34th and 36th weeks of gestation.

[Choice of delivery methods for cases of breech presentation, with particular reference to premature birth (author's transl)]. / Zur Wahl des Entbindungsverfahrens bei Beckenendlagen unter besonderer Berücksichtigung der Frühgeburt.

Overall mortality, stillbirths and neonatal deaths up to the 28th day of age included, were tested together with selected morbidity parameters, depending on delivery methods used (vaginal route or caesarean section). The group of probands included 112 single births on terms and 136 genuine single premature births (31st to 35th weeks of pregnancy), all of them delivered from breech presentation. Caesarean section for breech presentation deliveries on full term was found to be indicated primarily for cases of cephalopelvic disproportionality and severe risk factors and secondarily on account of cardiotocographic monitoring. Caesarean section has been the method of choice from 1979 for premature births from breech presentation, delivery dates being between the 31st and 35th weeks of pregnancy.--Breech presentation delivery goes along with higher morbidity or mortality risk and, therefore, has become a priority problem in the context of prematurity and its prevention. Efforts should be made to achieve vaginal birth on full term by abandonment of oxytocics and with general cardiotocographic monitoring, despite higher risk of acidosis, however, only in the absence of cephalopelvic disproportionally and grave risk factors. Higher mortality and acidosis risks, accumulation of pulmonary complications, and the need for neonatal intensive care for newborns vaginally delivered from breech presentation were all found by more detailed analysis to be concentrated in the period just before the 35th week of pregnancy. In cases of premature births from breech presentation which could not be therapeutically prevented, caesarean section should be performed up to the 35th week of pregnancy. Vaginal delivery of newborns from breech presentation is considered acceptable beyond the 35th week of pregnancy, with due consideration to be given to the selection criteria generally valid for births on term.

[Studies of the clinical effectiveness of intravenous long-term tocolysis]. / 2Untersuchungen zur klinischen Effektivität intravenöser Langzeittokolyse.

Possible retardation of delivery following different periods of intravenous Partusisten tocolysis was studied in 701 premature births, between the 28th and 36th weeks of pregnancy. The studies were conducted separately, for all probands together and by gestational age groups. Various symptoms of imminent premature birth were not weighed. The rate of failure amounted to 23 per cent, that is delivery occurred within 24 hours from beginning of treatment. Extension of pregnancy by something between two and seven days was achieved in 45 per cent of the probands or by more than seven days in 32 per cent. Growing length of intravenous tocolysis was followed by significant rise in the number of women with genuine prolongation of pregnancy (between eight and 28 days or even more), however, without any unambiguous evidence to differentiation between gestational age groups with regard to therapeutic responsiveness. Significant percentual rise in prematurity between the 34th and 36th weeks of pregnancy by almost 30 per cent (with 20 per cent in the 36th week of pregnancy alone) seems to indicate a measurable clinical benefit of intravenous long-term tocolysis in terms of higher life expectancy and better survival quality. --The above findings were compared with results that had been obtained from 1,037 prematurely born infants of the same gestational age groups without preceding tocolysis. The conclusion was that intravenous tocolysis in general and long-term tocolysis in particular failed to have the slightest negative impact in terms of acidosis and RDS morbidity, average birth weight, hypotrophy, and survival chance. The need for properly timed detection of prematurity as part of routine care may be seen from the great number of untreated premature births, that is cases beyond any possibility of treatment. The point is made that the effectiveness of tocolytic therapy can be measured only by those premature newborns who had received treatment rather than by the totality of premature newborns.

[15 years Perinatal Center of the Leipzig University]. / 15 Jahre Perinatalzentrum der Universität Leipzig.

Report about experiences with developing a perinatal center step by step an the University of Leipzig, primarily directed to improve the results of premature labour, then expanded by intensive diagnostics and treatment and uniform documentation of all risk pregnancies. Perinatal and neonatal mortality decreases following this management.

Postnatal intestinal disturbances in small-for-gestational-age premature infants after prenatal haemodynamic disturbances.

Uteroplacental insufficiency leads to fetal growth retardation, which is a major cause of perinatal and postnatal morbidity. In the present study we investigated the relationship between prenatal haemodynamic disturbances and postnatal intestinal perfusion and gastrointestinal function in small-for-gestational-age neonates. Prospectively, 114 preterm neonates with a birthweight below 1500 g were assigned to one of two groups according to their prenatal Doppler sonographic measurements: neonates with or without prenatal haemodynamic disturbances. We defined a pathological fetal perfusion by a pulsatility index of uterine arteries, umbilical artery and fetal thoracic aorta above the 90th percentile and by a pulsatility index of middle cerebral artery below the 10th percentile of a normal group. We compared the postnatal respiratory and intestinal adaptation in both groups as well as the blood flow velocity waveforms of the superior mesenteric artery in all neonates. Postnatally, all 36 neonates with prenatal haemodynamic disturbances were classified to be small for gestational age. Thirty-one of these neonates developed abdominal problems with delayed meconium passage, abdominal distension, bilious vomiting and a delay in tolerating in enteral feeding within the first days of life. Six of them needed surgical intervention, but none of these infants revealed typical signs of necrotizing enterocolitis. In contrast, all neonates after normal prenatal perfusion were classified to be appropriate for gestational age. Only 19 of 78 neonates of this group showed signs of intestinal disturbances postnatally. By Doppler sonographic investigations we found significant lower systolic, mean and end-diastolic flow velocities and higher pulsatility indices of the superior mesenteric artery in neonates with prenatal haemodynamic disturbances. This may occur as a result of postnatal persistent redistribution of regional blood flow and results in gastrointestinal problems and may adversely affect gut motility.