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Biomedical subjects

P Hüppi

Publications and source records attributed to P Hüppi.

At least 19 recordsLinked to original sources

Immunoglobulin subclass concentration in preterm infants treated prophylactically with different intravenous immunoglobins.

The most immature infants have critically low concentrations of all immunoglobulin G (IgG) subclasses, associated with a higher risk for pyogenic, respiratory, and meningeal infection. Selective IgG subclass deficiency is an established indication for intravenous immunoglobulin (IVIG) substitution. However, considering that therapeutic efficacy of IVIG is dependent on its pharmacokinetics, we studied peak and trough IgG subclass serum levels during the neonatal period (28 days) in a group of 34 healthy preterm babies (30.2 +/- 2 weeks gestational age (GA) and 1065 +/- 210 g birthweight (BW) treated prophylactically with three daily standard doses of two different IVIG preparations: Sandoglobulin (SG) (0.5 g/kg/day) and Pentaglobin (PG) (5 mL/kg/day). IgG subclass levels were assayed by radioimmundiffusion (RID) before treatment (day 1) and at days 3, 5, 7, 14, and 28 of life. Statistical analysis was performed by paired t test. In the first week of life only (days 3, 5, 7), for both IVIG preparations, subclass levels were higher than pretreatment values: IgG1, 4.6 +/- 1.7 versus 5.6 +/- 1.6 g/L; IgG2, 1.6 +/- 0.8 versus 2.1 +/- 0.6 g/L; IgG3, 0.2 +/- 0.7 versus 0.3 +/- 0.1 g/L; IgG4, 0.3 +/- 0.1 versus 0.9 +/- 0.1 g/L (p < 0.05). During this time (7 days) IgG2 levels were higher in the SG group and IgG4 was higher in the PG group (p < 0.05). This study shows pretreatment IgG subclass levels 14 days after treatment and different patterns, depending on the used preparation. We conclude that prospective clinical trials should include the study of target serum levels and timing of IVIG administration not only for IgG but also for IgG subclasses.

Bacterial Infections↗

Differential leukocyte count in babies treated with natural surfactant.

The potential of exogenous replacement therapy in surfactant-deficient states such as neonatal respiratory distress syndrome (RDS) is an area of intense clinical interest today. At present, a fundamental problem with any type of exogenous surfactant is the uncertainty about potential effects on physiological defense mechanisms, such as differentiation and mobilization of peripheral leukocytes. Considering that newborn infants with proven bacterial infections have abnormal values of segmented (neutrophil) and nonsegmented (band) polymorphonuclear leukocytes, we studied 42 placebo- versus Curosurf-treated babies with severe RDS. Differential white blood cell (WBC) count was serially performed before and after treatment during the first days of life. The statistically significant increase in the proportion of bands in surfactant-treated babies did not coincide with clinical and bacteriologic evidence of possible infection. Some molecular interaction mechanisms influencing immature to mature WBC ratio are supposed. Among a variety of influences on the leukocyte count, surfactant replacement therapy needs to be considered for proper interpretation of hematologic data in babies treated for RDS.

Bacterial Infections↗

Serial IgG and IgM serum levels after infusion of different Ig-preparations (IgG or IgM-enriched) in preterm infants.

Intravenous administration of Immunoglobulin (IVIG) has been used for prevention or treatment of neonatal sepsis. However, therapeutic efficacy of IVIG is dependent on pharmacokinetic factors. There have been no comparative studies in neonates between licensed IgG and IgM enriched preparations. The aim of this study was to investigate serial IgG and IgM serum levels during the neonatal period in two groups of non-septic, preterm infants treated prophylactically with IVIG. Twenty-two very low birth weight (VLBW) patients (1001-1500g) (gestational age 31.8 +/- 2.0 weeks and 1265 +/- 245g birth weight) and 12 extremely low birth weight (ELBW) patients (< 1000g) (gestational age 28.6 +/- 2.5 weeks and 910-85g birth weight) received at random three standard doses of Sandoglobulin (SG) (0.5 g/kg/day) or IgM enriched Pentaglobin (PG) (5 ml/kg/day). IgG and IgM concentrations were assayed by rate nephelometry before treatment and at day 3, 5, 7, 14 and 28 of life. At any time IgG levels were higher in the SG-VLBW group (p < 0.01), no difference being observed in the ELBW group (p > 0.5). IgM levels were higher at day 3 and 5 in the PG-VLBW group and until day 7 in the ELBW group (p < 0.01). This study indicates a wide range of IgG and IgM kinetics in the healthy premature and suggests frequent monitoring of immunoglobulin serum levels during efficacy studies.

Humans↗

Impact of prematurity and intrauterine growth retardation on neonatal hemorrhagic and ischemic brain damage.

Low birth weight and intrauterine growth retardation are well-recognized risk factors for increased mortality, morbidity and poor neurologic outcome. Risk assessment is different considering true preterm (appropriate-for-gestational-age, AGA) or growth-retarded (small-for-gestational-age, SGA) infants. Therefore, we carried out a study on the incidence of hemorrhagic (peri-intraventricular hemorrhage, PIVH) and ischemic (periventricular leukomalacia) brain lesions in two groups of AGA and SGA very-low-birth-weight (VLBW) infants. In the study period (1987-1990), 111 VLBW babies (< 1,500 g body weight) were serially studied at days 1, 3 and 7 and weekly until discharge by cerebral ultrasonography (ATL, MK 4, 7.5 MHz). 57 were VLBW-AGA babies (mean gestational age 28 weeks, mean body weight 1,106 g). 54 were VLBW-SGA babies (mean gestational age 31 weeks, mean body weight 990 g). PIVH was graded according to the system of Papile et al. Periventricular leukomalacia was defined as an echodensity (> 3 mm) adjacent to the lateral border of the ventricular body. We noted a higher incidence of PIVH in the AGA group (36.8%) than in SGA babies (18.5%; p < 0.01, Fisher test). The AGA subgroup < 1,000 g body weight had 72.2% PIVH compared to AGA babies > 1,000 g (20.5%; p < 0.01). The same relationship was observed in SGA babies (34.8% in < 1,000 g and 6.4% in > 1,000 g babies). Ischemic brain lesions (periventricular leukomalacia) were equally distributed between AGA and SGA babies (10.5 vs. 3.7%, p > 0.5) independently of body weight category.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Damage, Chronic↗

Influence of perinatal risk factors on the involution of the irido-pupillary membrane.

The aim of this study was to assess the influence of common perinatal risk factors on the disappearance of the anterior vascular capsule of the lens (AVCL). Direct ophthalmologic examinations were performed on 75 neonates (27 to 35 weeks gestational age) in the first 24 hours after birth, using the degree of involution of the AVCL to estimate gestational age in high risk pregnancy. Our results show that the gradual disappearance of the AVCL is not influenced by perinatal risk factors, such as maternal preeclampsia, prenatal administration of steroids, neonatal infection and low birth weight, confirming the clinical value of this test in the assessment of gestational age in high risk babies.

Female↗

Perinatal hip assessment in very low birth weight infants.

Fifty healthy low birth weight infants (less than 1500 g) without risk factors for congenital hip dysplasia (CHD) were examined by ultrasonography (100 hips) at 40 weeks corrected age and controlled at 3 months postnatal age. Sonographic assessment was performed using the classification of Graf. A physiological delay of hip maturation was observed in 10% of the patients (type IIa). At follow-up all of them had normal hip morphology without any pathological finding. Our results suggest that prematurity alone should not be considered a risk factor for CHD.

Female↗

Serum creatine-kinase-BB concentration in very low birth weight babies with posthemorrhagic ventricular dilatation.

The association between measurements of lateral ventricle dilatation determined by serial ultrasound and brain specific creatine-kinase isoenzyme patterns (CK-BB) is studied in 60 very low birth weight preterm neonates of 1,500 g birth weight or 32 weeks gestation or less. The patients were divided into three groups according to cranial ultrasonographic findings: Group A (n = 20) had isolated peri-intraventricular hemorrhage (PIVH); group B (n = 20) had PIVH and dilated ventricles (VM); group C (n = 20) were normal matched preterms and formed the control group. Compared to control babies or those with isolated PIVH, high serum concentrations of CK-BB were observed after birth in babies with persistent dilated ventricles at two weeks postnatal age (p less than 0.01). No difference was found between CK-BB levels of babies with isolated PIVH and control group (p greater than 0.05). We suggest that an elevated CK-BB value is found in babies with persistent ventricular dilatation suggesting severe and diffuse brain damage after post-hemorrhagic ventriculomegaly (VM).

Cerebral Hemorrhage↗

[The assessment of perinatal brain damage in premature infants at risk by serial creatine kinase BB measurements].

Peri-intraventricular bleeding (PIVH) is considered the most common cause of neurologic damage or death in low birthweight infants (less than 1000 g birth weight and 31 weeks of gestation). High-resolution real-time ultrasound scan is used for early diagnosis of PIVH in neonates. Furthermore, increase of serum creatine-kinase BB (CK-BB) values has been found to be clinically useful for diagnosis and prognosis of several perinatal cerebrovascular injuries. Eighty-eight preterm infants with different grades of PIVH (I-IV) were studied by serial measurements of CK-BB levels in serum. No statistical correlation was found between enzymatic levels and severity of PIVH (p greater than 0.5).

Analysis of Variance↗

Immunoglobulin serum levels in very low birth weight infants treated with different intravenous preparations.

Parenteral human immunoglobulin (IVIG) administration is widely used in low birth weight (LBW) infants for prevention and therapy of neonatal infection. In previous studies, IVIG preparations containing IgG and low IgM concentrations were commonly used. In this study we compare immunoglobulin serum levels in two groups of healthy preterm infants receiving prophylactically standard IVIG (Sandoglobulin, 0.1 mg/kg IgM) or IgM-enriched IVIG (Pentaglobin, 30 mg/kg IgM). Immunoglobulin levels were assayed by rate nephelometry at birth and at 3, 5, 7, and 14 days after birth. The two groups of patients were matched for gestational age (31 +/- 2.3 weeks), birth weight (1320 +/- 340 g), and serum IgG (4.1 +/- 1.9 milligram) and IgM (0.22 +/- 0.18 milligram) levels at birth. Significantly higher IgM levels were observed at 3 and 5 days after IgM-enriched IVIG administration (p less than 0.01). Higher IgG levels were attained and persisted for 2 weeks after standard IVIG administration (p less than 0.01). These data indicate different IgG and IgM target levels in LBW infants treated with different immunoglobulin preparations.

Bacterial Infections↗

Percutaneous caffeine application in the treatment of neonatal apnoea.

Topical application of caffeine for the treatment of neonatal apnoea was considered in 57 low birth weight infants (less than 1500 g birth weight). The rationale for the study was that transdermal absorption of drugs and chemical agents has been demonstrated in neonates depending on anatomical and functional immaturity of the epidermal barrier. Considering these issues we studied the efficacy of percutaneous application of caffeine using high pressure liquid chromatography (HPLC) for evaluation of its plasma levels. 2 x 7.5 mg (babies less than 1000 g, extremely low birth weight [ELBW] or 2 x 10 mg (babies greater than 1000 g, very low birth weight [VLBW]) of caffeine were applied transcutaneously in form of a gel to the abdominal skin (Standard dose = 0.06 g of gel equivalent to 10 mg of caffeine citrate). Gestational age of our patients was 29.4 +/- 1.7 weeks, mean birth weight 1025 +/- 240 g. Mean postnatal age at beginning of treatment was 25.5 +/- 18 h. Of the treated babies, 73% had serum levels in therapeutic range about 48 h after the first dose of caffeine application. After 10 doses 97% of patients had serum levels in the therapeutic range. We conclude that percutaneous caffeine application is a safe and useful approach for treatment of apnoea in VLBW and ELBW infants.

Administration, Cutaneous↗

Neurological function of immature babies after surfactant replacement therapy.

Surfactant replacement therapy in patients with neonatal respiratory distress syndrome (RDS) is a new therapeutic approach. There is now convincing evidence that the incidence and severity of RDS can be reduced. Surfactant (CUROSURF) was intratracheally applied to a group of fifteen intubated preterm infants with severe RDS (29 +/- 2.1 weeks of gestation and 1204 +/- 301 g birth weight) at 9.1 +/- 2.5 hours of life. For detection of potential neurological risk we performed serial ultrasound examinations (US), serial measurements of Creatine-Kinase Isoenzyme levels (CK-BB) looking for the presence of human antibodies to different brain antigens (BSA) as markers for neonatal cerebral injury. Using these diagnostic methods, there was no evidence of any negative influence of surfactant therapy on cerebral function of treated preterm infants.

Autoantibodies↗

Prenatal stroke suggested by intrauterine ultrasound and confirmed by magnetic resonance imaging.

Cerebral infarction is rare in premature newborns and is most commonly the result of arterial embolization from the placenta. A focal echodense area was identified on prenatal cranial ultrasonography (US) in a premature infant (34 weeks of gestation). After birth, cerebral infarction was confirmed by magnetic resonance imaging (MRI). The clinical findings, imaging findings and pathogenesis are discussed. New diagnostic methods such as MRI show to be a useful approach in the neonatal period facilitating recognition of cerebrovascular accidents also in low-birth-weight infants.

Cerebral Infarction↗

Rapid biometric assessment of gestational age in very low birth weight infants.

Foot length and intermamillary distance were compared to gestational age assessment using obstetrical dates, physical criteria of Ballard score and the evaluation of the anterior vascular capsule of the lens (IPM). Thirty-eight healthy and appropriate for gestational age preterm infants (30 +/- 2.4 weeks) with a birth weight of 1280 +/- 410 g were studied. Internipple distance (IM) and foot length (FL) were measured with a sliding caliper graduated in millimeters. Results were analyzed using the linear regression analysis. Obstetrical dates, physical Ballard score and IMP correlated significantly with both biometric measurements. Mean IM was 58.5 +/- 8.5 mm (range: 45 mm-89 mm) and mean FL was 60.6 +/- 7.9 mm (range: 45 mm-75 mm). The data indicate that the appropriate use of biometric parameters in the early postnatal period can be used to improve assessment of gestational age in VLBW infants.

Biometry↗

Fetal ventriculomegaly due to isolated brain malformations.

Management of 32 consecutive cases of fetal hydrocephalus diagnosed prenatally during a five years period is presented. Thirteen cases (40%) being patients with ventriculomegaly due to isolated brain malformation are the topic of this paper. In this group, management was conservative and consisted of termination of pregnancy by elective cesarean section after prenatal fetal assessment. Agenesis of corpus callosum (6 cases) and Dandy-Walker malformation (7 cases) were the most common observed forms. Antenatal sonography improved intrauterine follow-up. Skillful perinatal management and support facilities after birth have been found a reliable approach to conservative management of fetal hydrocephalus by lacking of satisfactory techniques for in utero permanent cerebrospinal fluid shunting.

Abnormalities, Multiple↗

Biochemical timing of peri-intraventricular hemorrhage assessed by perinatal CPK-BB isoenzyme measurements.

Precise diagnosis of peri-intraventricular hemorrhage (PIVH) requires brain real-time ultrasound imaging procedure (US). However, maximal diagnostic efficiency of US lies between day 4 and 14 since fresh blood may initially appear sonolucent. Because of this supposed interval required for clot formation to become visible on US, serum CPK-BB estimations were performed in the first 60 hours of life to determine precise biochemical timing of PIVH. A group of 50 preterm infants less than 1500 g birth weight (1120 +/- 320 g) and 34 weeks gestation (30 +/- 3.7 weeks) was studied. Serial CPK-BB measurements were performed in serum immediately after birth (T0), then serially at time T1 (6-10 h), T2 (20-30 h), T3 (40-60 h). The incidence of PIVH diagnosed on the third day of life was 30%. Total CPK-BB values at T0 in infants who developed PIVH were significantly higher than those of patients without cerebral bleeding (70.8 +/- 30.5 vs 20.9 +/- 10.7 U/l) (p less than 0.05). The same statistically significant results were not observed analysing the CPK-BB values at T1, T2 and T3. These results suggest that most pathological conditions responsible for enzyme release occur in the pre- or perinatal period.

Brain↗

Hypoxic risk in twins assessed by serum creatinine kinase brain isoenzyme measurement.

A marked intrapair discordance in placentas and in many body and organ measurements are risk factors influencing perinatal mortality and morbidity in twins. Asphyxia is the single most important perinatal cause of neurologic morbidity in newborn infants. The higher hypoxic risk for the second twin arises, however, from conclusions based on studies that did not consider the new diagnostic possibility of using blood measurements of the brain-type isoenzyme of creatine kinase (CK-BB) as a marker of perinatal asphyxia. CK-BB levels were measured in cord blood of 60 preterm infants (mean birth weight 1670 +/- 390 g, and mean gestational age 33 +/- 1.9 weeks) born of twin gestation in the last 3 years. The mean CK-BB values were 48 +/- 40 U/l versus 29 +/- 31 U/l (p less than 0.5). Skilful antepartum and perinatal care are the keys for optimal management of both babies, as demonstrated by similar CK-BB values obtained in their cord-blood specimens after birth.

Asphyxia Neonatorum↗

[Creatine-kinase MM in the perinatal period].

One hundred eight newborns (gestational age 36 + 1.8 weeks and birth weight 2860 +/- 240 g) had muscle type Creatine-Kinase activity (CK-MM) assayed immediately after birth (CK-I) and serially at 6-10 h (CK-II), 20-30 h (CK-III) and 40-60 h (CK-IV) of age. Using statistical Regression analysis, CK-MM levels were correlated to four perinatal parameters: gestational age, birth weight, neonatal acidosis (pH less than 7.15), mode of delivery (vaginal/cesarean section). It was observed that CK-MM activity was dependent on gestational age and correlated to the mode of delivery at time III (600 U/l) and IV (400 U/l) comparing the mean serum values of 156 + 44 U/l observed in atraumatic delivery (p less than or equal to 0.05). Our results demonstrate markedly higher levels of CK-MM following vaginal delivery especially if complicated by forceps, vacuum and breech presentation, suggesting that birth trauma may be responsible for this phenomenon.

Acidosis↗

Developmental aspects of percutaneous caffeine absorption in premature infants.

Caffeine is commonly used in the treatment of apnea of prematurity. The skin of preterm infants varies considerably in its level of maturity. To understand skin absorption in low birthweight infants (less than 1500 gm) with gestational age between 26 and 34 weeks, a group of 56 preterm babies was studied after percutaneous application of 7.5 mg twice daily of caffeine for babies with birthweight less than 1000 gm and 10 mg twice daily for babies with birthweight more than 1000 gm. The reported technique is a useful alternative method of drug administration in premature babies. This study indicates an inverse relationship between gestational age and skin absorption contributing to a better understanding of skin barrier function in the newborn.

Administration, Cutaneous↗