bluuebunny/crossref_metadata_2025 huggingface dataset:
Necrotizing enterocolitis—multisystem organ failure of the newborn?
Authors: Morecroft JA , Spitz L , Hamilton PA , Holmes SJK
Published: January 2008

Evidence of failure of organ system other than the gastrointestinal tract was reviewed in a series of 46 infants treated for necrotizing enterocolitis (NEC) at a regional combined medical and surgical neonatal unit. Respiratory failure was identified in 42 infants (91%), renal failure in 39 (85%), cardiovascular failure in 15 (33%) and hepatic failure in 7 (15%). The number of systems involved correlated with both severity of disease and outcome. Onset of failure in the above systems was closely related to the diagnosis of NEC and 29 cases predated the clinical onset. We conclude that NEC is part of a syndrome of multisystem failure and that this has important implications for the treatment of NEC.
Neonatal necrotizing enterocolitis, a disease of the immature intestinal mucosal barrier
Authors: Israel EJ
Published: January 2008

Necrotizing enterocolitis (NEC) is an enigmatic process in that one single etiologic factor has been sought and not found. Epidemiologic studies suggest that immaturity of the host plays a very important role. This article reviews the intestinal host defense system and its immature nature early in life in animal models and humans and suggests that it is this immaturity, along with other factors, which allows for the proliferation and invasion of antigens and organism, and the subsequent development of NEC. Data are presented which support the efficacy of pharmacologic maturation of the intestinal barrier with growth factors, either prenatally or postnatally, to decrease the incidence of NEC or, potentially, to provide a more benign course for the disease.
Role of bacterial translocation in necrotizing enterocolitis
Authors: Deitch EA
Published: January 2008

The intestinal mucosa functions as a major local defense barrier preventing bacteria that colonize the gut from invading organs and tissues. Under certain circumstances, bacteria colonizing the gastrointestinal tract can cross the gut mucosal barrier to infect the mesenteric lymph node and systemic organs via a process termed bacterial translocation. Factors that promote the translocation of bacteria or endotoxin from the gut include bacterial overgrowth with gram‐negative enteric bacilli, impaired host immune defenses and injury to the gut mucosa resulting in increased intestinal permeability. These same promoting factors are present in patients at increased risk of developing necrotizing enterocolitis. Consequently, this review focuses on the potential role of bacterial and endotoxin translocation from the gut in the pathogenesis of necrotizing enterocolitis.
The anti‐inflammatory effect of an oral immunoglobulin (IgA‐IgG) preparation and its possible relevance for the prevention of necrotizing enterocolitis
Authors: Wolf HM , Eibl MM
Published: January 2008

An exaggerated release of inflammatory mediators has been implicated in the pathogenesis of necrotizing enterocolitis (NEC). Oral administration of a human immunoglobulin preparation (serum IgA‐IgG) has been demonstrated to be an effective prophylaxis for NEC. The aim of the present study was to examine the regulatory effect of a human IgA‐IgG preparation on the release of inflammatory cytokines in human monocytes. Our results indicate that the immunoglobulin preparation inhibits TNF‐alpha and IL‐6 release in monocytes following stimulation with heat‐inactivated Hib in a dose‐dependent manner. This might have a biological relevance in infants receiving oral immunoglobulin prophylaxis for NEC, since modulation of the release of inflammatory mediators at the level of the gastrointestinal mucosa could interfere with the development of noxious sequelae of acute and/or chronic inflammation initiated by microbial pathogens or their toxins that finally lead to the pathologic changes associated with NEC.
Problems of ileostomy in necrotizing enterocolitis
Authors: Haberlik A , Höllwarth ME , Windhager U , Schober PH
Published: January 2008

Exteriorization of the intestine and resection of the gangrenous bowel are major therapeutic regimens for necrotizing enterocolitis (NEC). Ileostomy associated complications are well known, therefore the time of ileostomy closure is a matter for discussion. Between 1975 and 1992, 84 patients with NEC were treated surgically. Ileostomies were performed in 37 children (44%). Of these 37 neonates, 9 (7M, 2F) died. In the remaining 28 patients (16M, 12F) with a mean gestational age of 35.8 weeks and a mean birth weight of 2412 g, ileostomies were performed between the 2nd and 11th days after birth. On average, the stomies were in function for 91 days, and within this period the average weekly weight gain was 153 g. Nineteen patients of this group did not show any problems attributable to the ileostomy. In 9 patients (32%) complications occurred, requiring a preplanned closure of the stoma. Postinflammatory strictures of bowel were diagnosed in 9 patients and resection of the stenotic intestine was performed at the same time as stoma closure. In conclusion, an appropriate weight gain can be achieved in patients with an ileostomy with an adequate feeding regimen. In otherwise uncomplicated cases, ileostomy closure can be delayed by up to 10 weeks when simultaneous surgical correction of additional intestinal strictures is possible. In one‐third of patients with an ileostomy, however, complications may occur and urge a preplanned closure of the stoma.
Surgical procedures in colonic strictures after necrotizing enterocolitis
Authors: Gobet R , Sacher P , Schwöbel MG
Published: January 2008

Between 1982 and 1992, 22 patients were treated with colonic strictures in the course of necrotizing enterocolitis (NEC). Fourteen newborns in whom a primary enterostomy and, when necessary, resection of necrotic bowel was performed developed strictures in the diverted colon. The strictures were detected by colon contrast enema study performed on average 3 months after the first intervention. Eight additional children suffered from an ileus due to primary strictures after conservatively treated NEC, which was surgically managed by enterostomy. Closure of the enterostomy and resection of the stenotic part of the colon was performed thereafter in all 22 children as a single stage procedure. There was no insufficiency of the anastomosis nor any late stricture at follow‐up 2.7 years after NEC in our patients. It is concluded therefore that reanastomosis of the enterostomy and resection of an intestinal stricture can be performed as a single stage procedure without any risk after an interval of 3 months between onset of acute NEC and reevaluation. During this interval, a close monitoring and an appropriate management of adequate supplement of electrolytes and bicarbonates is necessary. Most of our babies could be nursed at home and showed a good weight gain during this period, despite the enterostomy.
Late intestinal strictures following successful treatment of necrotizing enterocolitis
Authors: Schimpl G , Höllwarth ME , Fotter R , Becker H
Published: January 2008

Between 1975 and 1992, in 16 infants (14%) out of 113 neonates with previous necrotizing enterocolitis (NEC) a total of 25 intestinal strictures had to be treated. Four (16%) were found in the ileum and 21 (84%) in the colon, and in 50% multiple strictures were present. In these 16 patients initial treatment for acute NEC included conservative treatment in 5, primary resection and enterostomies in 6 and proximal diverting enterostomies in 5. Therefore, the incidence of late strictures was 11% after conservative therapy, 11% after primary resection and 55% after primary proximal diverting enterostomies. An average of 49 days elapses between the recovery from NEC and the diagnosis of late strictures in conservatively treated patients. After initial surgical treatment, late strictures were detected on contrast studies on an average of 80 days. In pathologic specimens, marked fibrosis in the submucosa was consistently present in all strictures, whereas inflammatory changes in the mucosa, disruption or hypertrophy of the muscle layers or absence of ganglion cells were seen less frequently. All strictures were resected and primary end‐to‐end anastomosis was performed. But despite the development of late intestinal strictures, bowel preservation was improved after initial restrictive surgical therapy and aggressive medical treatment.
Acute tubular necrosis in a newborn suffering from neonatal necrotizing enterocolitis
Authors: Minelli L , Bernardi M , Locatelli G
Published: January 2008

The case history of a newborn who at birth had a necrotizing enterocolitis, worsened by an acute tubular necrosis and anuresis, is presented. A continuous arteriovenous hemofiltration was instituted for the baby, who had previously undergone abdominal surgery with resection of the necrotic bowel. The hypothesis that necrotizing enterocolitis could be the cause of acute tubular necrosis in infancy is discussed.
A neural circuitry analysis of maternal behavior in the rat
Authors: Numan M
Published: January 2008

This article reviews work that shows that the medial preoptic area of the hypothalamus plays a crucial role in controlling the occurrence of maternal behavior in rats. A primary goal of this report is to fit the medial preoptic area into a larger neural circuitry, examining its critical inputs and outputs. Lesions of the medial preoptic area disrupt maternal behavior and estradiol and prolactin injections into this region activate maternal behavior. The medial amygdala, which is located in the limbic telencephalon, sends a neural projection to the preoptic region. Research indicates that this projection influences maternal behavior by relaying olfactory input to the medial preoptic area. The output of the preoptic area influences maternal behavior through descending projections to the brain stem. One of the influences of such projections might be to regulate neural circuits involved in controlling specific maternal responses, such as retrieval (carrying of pups) behavior.
Milk as the proximal mechanism for behavioral change in the newborn
Authors: Smotherman William P , Robinson Scott R
Published: January 2008

Early experience in the context of suckling at the nipple is a crucial determinant of neurobehavioral development in mammals. In particular, milk has been recognized by developmental psychobiologists as an ecologically relevant sensory stimulus and should be viewed by clinicians as more than a source of nutrition in early human development. Gaining access to and processing milk during suckling serves as a primary focus of activity in the newborn. Because the rat fetus lacks prior exposure to milk or other suckling stimuli, it provides an excellent model system for investigating the development of milk related responses. Fetal exposure to milk results in a cascade of behavioral, physiological and neurochemical consequences. Milk‐induced activation of the endogenous opioid system plays an important role in reorganizing fetal motor activity, altering sensory responsiveness and supporting associative learning in the fetus. Subtle changes in contextual stimulation alter the ability of milk to engage different neurochemical systems. These findings suggest that the infant's first experiences with milk and other suckling stimuli may have lasting consequences for neurobehavioral development.
Behavioral and physiological consequences of suckling in rat and human newborns
Authors: Blass EM
Published: January 2008

Suckling, in addition to yielding milk, water and calories, exerts profound behavioral effects on newborn rats and humans. In particular, suckling induces feelings of calm, reduces heart rate and metabolic rate, causes infants to bring their hands to their mouths and elevates the pain threshold. These changes are mediated by opioid and non‐opioid systems, each having its own separate behavioral and neurological characteristics. The implications of suckling‐induced changes for long‐term motivational and cognitive change are discussed.
Changes in body composition and bone density after discontinuation of growth hormone therapy in adolescence: an interim report
Authors: Ogle GD , Moore B , Lu PW , Craighead A , Briody JN , Cowell CT
Published: January 2008

Growth hormone deficiency (GHD) in adults and children is associated with decreased lean tissue mass (LTM), increased fat mass and reduced bone mineral density (BMD). The changes in BMD and body composition, 6 and 12 months after ceasing GH treatment, were assessed using dual‐energy X‐ray absorptiometry in eight patients with GHD (age range, 13.8–17.5 years). Seven age‐matched normal subjects who had completed growth were assessed at 0 and 12 months. Total body BMD was low at baseline (p < 0.05) in patients with GHD compared with the predicted values based on sex‐specific regression equations, with height, weight and age taken into account. Total body, lumbar spine and femoral neck BMD increased in the patients and controls at 12 months. LTM decreased significantly by a mean of 1.37 kg in the patients with GHD at 12 months whereas there was a non‐significant increase in LTM in the control group. The percentage of body fat increased in all patients with GHD at 6 and 12 months, from 27.2 ± 11% (mean ± SD) at baseline to 32 ± 9.9% at 12 months (p= 0.009). There was no significant increase in mean percentage body fat in the control group. The ratio of android (trunk):gynoid (legs) fat was calculated using default settings of dual‐energy X‐ray absorptiometry. The mean android:gynoid fat ratio increased, though non‐significantly, in patients with GHD at 12 months, with 6 of 7 showing an increase; no change was observed in the control group. These results indicate that BMD continues to increase 12 months after ceasing GH therapy in adolescents with GHD, but that unfavourable alterations in body composition occur.
Psychosocial adjustment in a large cohort of adults with growth hormone deficiency treated with growth hormone in childhood: summary of a questionnaire survey
Authors: Takano K , Tanaka T , Saito T ,   Committee for the Study Group of Adult GH Deficiency
Published: January 2008

The quality of life of adult patients with growth hormone (GH) deficiency, who ceased GH therapy before the age of 20 years, was surveyed. Questionnaires were sent to 1116 patients and their physicians, asking about socioeconomic status and for medical information, respectively. Response rates were 64% and 69% respectively. The final height of the patients was about −2 SD in 61% of those surveyed. The distributions of occupation and income were similar to those in the general population. Patients with a final adult height below 155 cm (men) and below 140 cm (women) felt disadvantaged in terms of obtaining employment and finding partners. Slight psychological problems in these patients were revealed by the Cornell Medical Index health questionnaire.
Growth response to recombinant human growth hormone in short prepubertal children with chronic renal failure with or without dialysis
Authors: Mehls O , Broyer M ,   European/Australian Study Group
Published: January 2008

The growth‐promoting effect of recombinant human growth hormone (GH) in children with chronic renal failure was assessed in eight clinical trials. A total of 103 prepubertal children participated in the trials, 34 of whom were undergoing dialysis. The children were treated with GH, 30 IU/m2/week (approximately 1 IU/kg/week), for up to 2 years, and various growth parameters, bone age and renal function were assessed before and during treatment. In all trials, the children showed clear catch‐up growth and an improved height SDS after treatment with GH, although the increase in height was less in dialysis patients than in those not receiving dialysis. GH maintained its growth‐promoting effect during the second year of treatment; the effect, however, was less marked than during the first year of treatment. Bone age appeared to advance in parallel with chronological age. Median serum creatinine increased from 204 μmol/1 to 230 and 262 μmol/l after 12 and 24 months of treatment, respectively, due to increased muscle mass and/or progression of the underlying renal disease. The loss of estimated glomerular filtration rate/year was not different before and during GH treatment.
The insulin‐like growth factor I generation test in the investigation of short stature
Authors: Cotterill AM , Camacho‐Hübner C , Woods K , Martinelli C , Duquesnoy P , Savage MO
Published: January 2008

Genotypic and phenotypic heterogeneity in patients with growth hormone (GH) insensitivity syndrome suggests that partial defects exist in the GH receptor. The insulin‐like growth factor I (IGF‐I) generation test was assessed as a means of identifying partial GH receptor defects in a heterogeneous group of 22 prepubertal children with short stature. In a subgroup of nine patients with peak GH levels of 63.7 ± 3.7 mU/l during a glucagon tolerance test, the response to the IGF‐I generation test was no different from that for the group as a whole (peak GH, 43.3 ± 4.5 mU/l), despite the fact that this subgroup exhibited a negative relationship between height SDS and peak GH and a positive relationship between height SDS and IGF binding protein‐3. This preliminary study therefore suggests that the IGF‐I generation test in its present form will not be useful as a primary screening test for partial GH insensitivity. Despite this, the IGF‐I generation test has been extremely useful in the confirmation of the diagnosis of GHIS and may therefore also prove useful in the confirmation of partial defects in the GH receptor. A subgroup of short children with peak GH levels above 40 mU/l had some characteristics of partial GH receptor deficiency. These children, to whom GH therapy would not normally be given, may respond better to recombinant human IGF‐I.
Epidemiology of pediatric Human Immunodeficiency Virus infection in the United States
Authors: Rogers Martha F , Caldwell M Blake , Gwinn Marta L , Simonds RJ
Published: January 2008

Human Immunodeficiency Virus (HIV) infection is a growing problem for children worldwide. As of 31 December 1992, 4249 children with Acquired Immunodeficiency Syndrome (AIDS) under 13 years of age had been reported to the US Centers for Disease Control and Prevention (CDC). HIV is transmitted to children predominantly from their mothers. Nearly all cases of HIV infection acquired from blood transfusions in the United States occurred before donor‐screening practices were implemented in March 1985. In 1991, approximately 7000 HIV‐infected women gave birth to a liveborn infant in the United States, for a prevalence of 1.7 per 1000 women. Despite recent advances in prophylactic therapy for opportunistic infections, Pneumocystis carinii pneumonia remains the most common AIDS‐defming illness in children in the United States. If these cases are to be prevented, children born to HIV‐infected mothers will need to be identified early and monitored appropriately for CD4+ cell counts to determine the need for prophylaxis.
Epidemiology of HIV infection in children in Europe
Authors: Canosa Cipriano A
Published: January 2008

In Europe the Human Immunodeficiency Virus (HIV) epidemic in children is an important public health problem. Reliable epidemiological information varies widely among countries, and there is no standard method to document the pandemia. By September 1992, a total of 81,849 AIDS cases were identified. France had 21,487, Spain 15,678 and Italy 14,784 (63% of all cases). The highest rate per 100,000 inhabitants occurred in Spain (88.9), France had 70.6 and Italy 63.5. The numbers of HIV+ newborns (NB) in Spain were 4673, in Italy 2,693, in Belgium 368, in Scotland 79 and in Holland 11. The highest rate of HIV+ NBs per 100,000 inhabitants occurred in Spain (120.1), the lowest in Holland (0.73). In Western Europe, 82% of all cases were due to vertical transmission. Mothers’venous drug use was the most common form of HIV transmission.
Application of the polymerase chain reaction for the detection of HIV in specimens from newborn screening programs
Authors: Comeau Anne Marie
Published: January 2008

The use of the polymerase chain reaction (PCR) permits detection of HIV proviral DNA in the universally collected “dried blood spot specimens” of newborn screening programs. Detection of HIV proviral DNA among the annual cohorts of seropositive specimens from ongoing anonymous newborn HIV seroprevalence studies can provide a laboratory‐based estimate of maternal‐infant transmission rates. Preliminary data suggest that maternal‐infant transmission rates may be higher in areas where the newborn seroprevalence rates are highest.
Autoimmune phenomena in children with Human Immunodeficiency Virus infection and Acquired Immunodeficiency Syndrome
Authors: Rodríguez‐Mahou Margarita , López‐Longo Javier , Lapointe Normand , Carreño Luis , Grau Raquel , Gurbindo Dolores , Fernández‐Cruz Eduardo
Published: January 2008

We have studied sera from 44 children with Human Immunodeficiency Virus infection and Acquired Immunodeficiency Syndrome using immunoblotting, radioimmunoassay, enzymoimmunoassay and indirect immunofluorescence. We have detected a low incidence of antinuclear (2.9%), anti‐reticulin (2.9%) and anti‐smooth muscle (14.7%) antibodies by indirect immunofluorescence. By enzymoimmunoassay we have detected anti‐dsDNA (20.5%) and anti‐ENA [anti‐nRNP (61.3%), anti‐Sm (29.5%), anti‐Ro (47.7%) and anti‐La (18.1%)] antibodies. Tests for anti‐dsDNA by radioimmunoassay were negative, suggesting the presence of low‐avidity anti‐DNA antibodies. By immunoblotting we have detected anti‐C (nRNP) (33.3%), anti‐BB′ (Sm) (33.3%), anti‐Ro (60 KD) (4.5%) and anti‐La (11.3%) antibodies. The presence of anti‐Ro antibodies was associated with progressive neurological disease. Long‐term follow‐up studies with larger numbers of patients are necessary to evaluate the clinical significance of the presence of anti‐dsDNA and anti‐ENA antibodies in children infected with Human Immunodeficiency Virus.
Longitudinal follow‐up studies
Authors: Peckham Catherine , Newell Marie‐Louise
Published: January 2008

A longitudinal study should be undertaken only when there is a clear reason to justify this and a reasonable chance of achieving the objectives. A multidisciplinary approach is often required, and continuity of staff and long‐term collaboration with colleagues are important for their success. A longitudinal approach is required to estimate the prevalence of an infection in pregnancy and the rate of vertical transmission and to clarify the natural history in infected children. An example of cytomegalovirus infection is given; the parallels with HIV are obvious.
Trends in research on infant nutrition, past, present and future
Authors: Zetterström R
Published: January 2008

A review of general trends in early infant feeding is presented, with particular focus on the importance of breast feeding. That the promotion of breast feeding is highly effective is borne out by the tendency toward its prevalence in Sweden during the period 1972–94.
Nutritional aspects of soy formula
Authors: Lönnerdal B
Published: January 2008

Soy formula is a commonly used alternative to cows’milk formula. While its primary use has been for infants with milk protein allergy and lactose intolerance, soy formula is used increasingly for infants with gastrointestinal discomfort. The nutritional composition of soy formula has been designed to cover the nutrient needs of the newborn infant; however, some aspects of its composition need further consideration. The protein level of soy formula is usually higher than that of milk‐based formulae, partially because of differences in protein digestibility and partly because of differences in amino acid composition. The presence of phytic acid in soy formula presents a problem with regard to mineral and trace element bioavailability. Several steps can be taken to minimize this problem, either by reducing the phytate content of soy protein isolate or by changing levels of minerals/trace elements in the formula. Finally, the high levels of manganese in soy formula present a potential problem in that manganese absorption and retention are high during infancy.
Cocaine use in pregnancy in Amsterdam
Authors: Smit BJ , Boer K , van Huis AM , Lie‐A‐Ling ISE , Schmidt SC
Published: January 2008

To study the effects of cocaine use in pregnancy in Amsterdam, clinical data on cocaine‐using pregnant women (n= 21) and their offspring (n= 23) were obtained retrospectively (1987–1994) at the Academic Medical Center, Amsterdam. Infants exposed to cocaine had a median gestational age of 39 weeks and a median birth weight of 3090 g. There were six preterm infants, two small‐for‐gestational‐age infants and five infants with a small head circumference. Three infants had a congenital malformation. One infant (Potter's syndrome) died shortly before birth. One infant had congenital syphilis, four had intracerebral abnormalities on ultrasound and four had abnormal neurologic symptoms in the neonatal period. One infant died after 21 days of life. At follow‐up four infants showed abnormal development. In 12 of the 23 infants (52%), one or more possible effects of cocaine were found.
Public health care policies for drug addicts in Amsterdam
Authors: van Brussel GHA
Published: January 2008

Recognizing that drug addiction is a chronic health problem for which, in the majority of cases, no curative, effective treatment exists, Amsterdam developed a coherent system of public health measures. Data on the course of the local drug epidemic, including medical complications such as AIDS, tuberculosis and mortality, are presented.
Development of human intestinal and gastric enzymes
Authors: Ménard D
Published: January 2008

In humans as opposed to rodents development of the gastrointestinal tract is much less coordinated with functional changes occurring at different times during the fetal period. This article reviews developmental patterns of intestinal brush border enzymes, lysosomal enzymes, peroxisomal enzymes and de novo synthesis of intestinal lipoproteins. It also describes the developmental patterns of gastric lipase and pepsin during early fetal life. Data are presented on the most recent observations related to the regulatory mechanisms in the development of human intestinal brush border hydrolases. A clearer understanding of the ontogeny and of the regulatory mechanism of the functional development of the gastrointestinal tract will enable researchers and clinicians to improve nutritional support in a fashion appropriate for the digestive and metabolic capabilities of an infant at any developmental stage.
Water, energy and early postnatal growth in preterm infants
Authors: Micheli J‐L , Pfister R , Junod S , Laubscher B , Tolsa J‐F , Schutz Y , Calame A
Published: January 2008

Non‐invasive methods, including stable isotope techniques, indirect calorimetry, nutritional balance and skinfold thickness, have given a new insight into early postnatal growth in neonates. Neonates and premature infants in particular, create an unusual opportunity to study the fluid and metabolic adaptation to extrauterine life because their physical environment can be controlled, fluid and energy balance can be measured and the link between metabolism and the energetics of their postnatal growth can be assessed accurately. Thus the postnatal time course of total body water, heat production, energy cost of growth and composition of weight gain have been quantified in a series of “healthy” low‐birth‐weight premature infants. These results show that total body water is remarkably stable between postnatal days 3‐21. Energy expenditure and heat production rates increase postnatally from mean values of 40 kcal/kg/day during the first week to 60 kcal/kg/day in the third week. An apparent energy balance deficit of 180 kcal/kg can be ascribed to premature delivery. The cost of protein metabolism is the highest energy demanding process related to growth. The fact that nitrogen balance becomes positive within 72 h after birth places the newborn in a transitional situation of dissociated balance between energy and protein metabolism during early postnatal growth: skinfold thickness, dry body mass and fat decrease, while there is a gain in protein and increase in supine length. This particular situation ends during the second postnatal week and soon thereafter the rate of weight gain matches statural growth. The goals of the following review are to summarize data on total body water and energy metabolism in premature infants and to discuss how they correlate with physiological aspects of early postnatal growth
Sodium, potassium and chloride needs in low‐birth‐weight infants
Authors: Herin P , Zetterström R
Published: January 2008

A review of the daily requirements of sodium, potassium and chloride in preterm infants with particular emphasis on very low‐birth‐weight (VLBW) infants is given against the background of our present knowledge of the homeostatic regulation of these electrolytes during early postnatal life. Particular attention has been given to the importance of balanced fluid and electrolyte homeostasis in the control of compartment volumes and tonicity. The risk of rapid changes of extracellular fluid osmolality for many organs, and particularly for the brain, has been stressed. In order to obtain an adequate sodium and fluid balance during the first postnatal weeks in preterm infants of varying gestational age, recommendations for sodium intake during the first 4‐5 postnatal weeks are given.
Metabolic and energy balance in small‐ and appropriate‐for‐gestational‐age, very low‐birth‐weight infants
Authors: Picaud J‐C , Putet G , Rigo J , Salle BL , Senterre J
Published: January 2008

This study compared nutrient utilization and postnatal weight gain composition in eight appropriate for gestational age (AGA: birth weight 1293 ± 107 g; gestational age 28.8 ± 1.4 weeks) and eight symmetrically growth‐retarded (SGA: birth weight 1110 ± 230 g; gestational age 32.7 ± 1.9 weeks), very low‐birth‐weight (VLBW) infants. There was no significant difference in protein, mineral and energy intake between AGA and SGA infants. Nitrogen absorption (84 ± 3 and 83 ± 4%) and nitrogen retention (356 ± 48 and 352 ± 43 mg/kg/day) were similar in both groups. Fat absorption tended to be lower in AGA (78 ± 15%) than in SGA (87 ± 4%) infants. Calcium, phosphorus and magnesium absorptions were similar in AGA and SGA infants. Metabolizable energy utilization was similar in both groups; about 55% was expended and 45% stored in new tissues. Energy expenditure was 58 ± 4 kcal/kg/day in SGA infants and 61 ± 9 kcal/kg/day in AGA infants. Weight gain and its composition were similar in both groups. We conclude that nutrient and energy utilization are similar in AGA and symmetrically growth‐retarded, VLBW infants.
Growth hormone treatment of idiopathic short stature: analysis of the database from KIGS, the Kabi Pharmacia International Growth Study
Authors: Ranke MB , Lindberg A ,   On behalf of the International Board of the Kabi Pharmacia International Growth Study
Published: January 2008

Within the Kabi Pharmacia International Growth Study (KIGS) database, there is information on 1017 (700 male/317 female) patients with idiopathic short stature (ISS). These patients were started on recombinant human growth hormone (GH) at a median age of 10.8 years, a bone age of ‐1.8 SDS, a height of ‐2.6 SDS and a predicted adult height (PAH) (Bailey–Pinneau method) of ‐2.5 SDS. The median dose of GH was 0.6 IU/kg body weight/week and the frequency of injections was six/week. According to the relationship with target height the patients were classified into‘familial short stature (FSS)’(height SDS > target height SDS ‐ 1.28) and into‘non‐FSS’(height SDS < target height SDS ‐ 1.28). During the first year of GH treatment there was an overall increment in the median height velocity from 4.4 to 7.4 cm/year. Over 3 years of GH treatment, cross‐sectional analysis demonstrated an overall increment in median PAH of 1.2 SDS. There was a positive correlation between gain in PAH and the GH dose (n = 202,r= 0.18,p< 0.01) during the first year. Longitudinal analysis in 84 patients showed an overall increment of PAH of 0.7 SDS over 2 years of treatment. When applying the KIGS first‐year prediction model for patients with idiopathic GH deficiency on cohorts of prepubertal children with FSS and non‐FSS, a lower responsiveness to GH in the non‐FSS group was observed. It is concluded that higher than substitutive doses of GH are required for the long‐term improvement of growth in ISS.
Adolescence in evolutionary perspective
Authors: Bogin B
Published: January 2008

This article reviews progress in the application of evolution theory to human growth and development, particularly adolescence. Evolution theory includes a variety of topics and only two of these are treated here: life history and biocultural modelling. “A broad definition of life history includes not only the traditional foci such as age–related fecundity and mortality rates, but also the entire sequence of behavioural, physiological, and morphological changes that an organism passes through during its development from conception to death” (1). This approach may be applied to both the study of the stages of life of modern people and to the evolution of the human pattern of growth.
Science, medicine and phenylketonuria
Authors: Scriver CR
Published: January 2008

Science addresses ignorance; medicine uses facts. The scientific approach to phenylketonuria (PKU) led to the discovery of its causes, both ultimate (allelic heterogeneity at the PAH locus) and proximate (dietary phenylalanine), the proximal phenotype (phenylalanine hydroxylase deficiency), the associated metabolic phenotype and the major distal phenotype (impaired cognitive development and neuropsychological function) for which the pathogenesis is still being investigated. By applying knowledge through newborn screening, early diagnosis and treatment, the brain disease of PKU has been greatly ameliorated. The population approach, which converted incidence into cases, revealed genetic heterogeneity in hyperphenylalaninemia involving four other loci, controlling cofactor (BH4) synthesis and recycling, and non‐random geographic distribution of mutant PAH alleles of which more than 170 were known in April 1994. Various mechanisms including founder effect, genetic drift, hypermutability and selection (perhaps) explain the polymorphic aggregate frequency (∼ 0.01) and spectrum of PKU mutations in human populations.
Protein intake affects phenylalanine requirements and growth of infants with phenylketonuria
Authors: Acosta PB , Yannicelli S
Published: January 2008

Growth and metabolic status of 25 infants with PKU were evaluated based on protain intake. Food A‐fed infants received a medical food containing 3.12g protein equivalent per 100 kcal and Food B‐fed infants received a medical food containing 2.74 g protein equivalent per 100 kcal. Growth percentiles of infants in the Food A group were significantly greater than those for infants in the Food B group at 6 months of age (Food A percentiles: crown‐heel length 55, head circumference 60, weight 73. Food B percentiles: crown‐heel length 28; head circumference 29, weight 39). At study entrance, only crown‐heel length of the two groups differed; Food B infants had a significantly greater mean crown‐heel length percentile (p < 0.05). Mean phenylalanine (PHE) intake was 38% greater by Food A‐fed infants than by Food B‐fed infants. Plasma PHE concentrations and mean energy intakes of the two groups did not differ. Mean protein intake of Food A‐fed infants was greater during the first three months of life and significantly greater (p < 0.05) during the second three months of life than by Food B‐fed infants. Mean protein intake 24% greater than Recommended Dietary Allowances (RDA) was associated with better PHE tolerance and growth than was found when mean protein intake was 9% greater than RDA.
The phenylalanine response curve in relation to growth and mental development in the first years of life
Authors: van der Schot LW , Doesburg WH , Sengers RCA
Published: January 2008

Thirty‐three children with classical phenylketonuria were treated from 9 to 21 days of age onward. The standard for phenylalanine concentration was 0.2‐0.5 mmol/1. During the first years of life phenylalanine concentrations were measured once every two to six weeks. For each child these values were graphically plotted in so‐called phenylalanine response curve. Growth and mental development indices were assessed at about one and two years of age. Measurements for weight, height and head circumference were normal at one month of age, showed significant decline at the age of one year but were restored for normal values at the age of two. No associations were found with phenylalanine parameters. Mental development indices at one and two years were not different from normal. Significant negative correlations were found between mental development indices at one year and phenylalanine values above 0.5 mmol/1. Changes in mental development indices between the first and second years of life are significantly related to the phenylalanine levels during the second year of life.
Predictors of mean phenylalanine levels during the first five years of life in patients with phenylketonuria who were treated early
Authors: Verkerk PH , van Spronsen FJ , van Houten M , Smit GPA , Sengers RCA ,   On behalf of the Dutch National PKU Steering Committee
Published: January 2008

We studied the relationship between plasma phenylalanine level at first diagnostic visit, country of origin of the mother, birth cohort, child clinic, sex, and social class on the one hand and mean plasma phenylalanine levels in the first five years of life on the other hand in patients with phenylketonuria (PKU) who were treated early. The study population consisted of 131 early treated patients with PKU born during the period from September 1st, 1974 to December 31st, 1988 in The Netherlands. Plasma phenylalanine levels from first diagnostic visit (usually before the age of three weeks) up until the fifth birthday were registered. For each patient the mean phenylalanine level during that period was calculated. Our results suggest that 1) it is more difficult to maintain low phenylalamine levels in patients with a more severe form of PKU, 2) in recent years paediatricians have treated their patients with a stricter diet, 3) there are differences in perception between paediatricians of different clinics as to what levels are acceptable, and 4) treatment of patients from non‐Dutch mothers is more difficult than treatment of patients with Dutch mothers.
Feeding problems in young PKU children
Authors: MacDonald A , Rylance GW , Asplin DA , Hall K , Harris G , Booth IW
Published: January 2008

Behavioural feeding problems were found to be more prevalent in a group of 15 PKU children aged 1‐5 years when compared to non‐PKU controls. The parents of PKU children identified poorer appetites (p < 0.01), a more limited range of foods consumed (p < 0.03) and more gastrointestinal symptoms such as vomiting and constipation (p < 0.03) than control children. The children were slower to feed (p < 0.03), were more likely to dislike sweet foods and some ate separately from the rest of the family at mealtime (p < 0.03). The effects on normal feeding behaviour should be considered when advocating strict diet therapy for young PKU children.
PKU in adolescents: rationale and psychosocial factors in diet continuation
Authors: Levy HL , Waisbren SE
Published: January 2008

Follow‐up of early‐treated children with PKU has shown that diet discontinuation in childhood presents risks of cognitive and emotional dysfunction in a substantial number of adolescents and young adults. This dysfunction includes IQ loss, mental processing abnormalities, learning difficulties, anxiety and personality disorders. In addition, neurologic deterioration has been reported in several such individuals. As consequence of this current understanding of PKU, diet continuation, at least through adolescence and in the young adult years, is now recommended. Many centers are extending this to policy of “diet for life”. This represents major challenge to adolescents and their families. Metabolic control using the criteria applied during childhood is virtually impossible to achieve past 12 years of age. Time constraints, social pressures, financial limitations and growing independence from the family combine to interfere with dietary control. Added to these difficulties are the biological changes during teenage years which reduce phenylalanine tolerance. To meet these challenges, we have identified number of psychosocial factors that interfere with adherence to medical recommendations. The factors most highly related to metabolic control were social support for the diet and positive perceptions of treatment. This information has led to the development of support programs for adolescents and young adults with PKU. These programs include an annual New England maternal PKU camp, resource mothers program in which mothers of young children with PKU are matched to women with PKU who are either planning pregnancy or are pregnant and assist with meal planning, cooking, metabolic monitoring, and transportation to medical appointments as well as provide enormous emotional support to these young women, and PKU CORPS which brings together on‐diet adolescents for training and emotional support and then matches them with younger phenylketonuric children on diet. The benefits of these programs are becoming clear in terms of improved metabolic control, successful re‐institution of diet, a more comfortable acceptance of PKU and better self‐image.
Loss of neurotransmitter receptors by hyperphenylalaninemia in the HPH‐5 mouse brain
Authors: Hommes FA
Published: January 2008

The binding of the muscarinic acetylcholine antagonist quimiclinidylbensilate to its specific receptors was measured by quantitative autoradiography in the brain of the HPH‐5 mouse, a phenylalanine hydroxylase‐deficient mouse mutant, as a model for human PKU. Three types of response to a hyperphenylalaninemic condition were observed: no effect as in the putamen; a gradual decrease over time such as in several areas of the cerebral cortex and the hippocampus; a transient increase, followed by a decrease, such as in the frontal area of the cerebral cortex. Of particular significance is the effect on the CA1 and CA3 layer of the hippocampus, since this structure has been implicated in the acquisition and storage of long‐term memory. Hyperphenylalaninemia leads to a decrease in neuro‐transmitter receptor density and, therefore, to a decrease in connectivity, which may form the basis for the mental retardation in this condition.
Intestinal Absorption of Vitamin E in Low Birth Weight Infants
Authors: JANSSON L. , LINDROTH M. , TYÖPPÖNEN J.
Published: January 2008

ABSTRACT. Intestinal absorption of dl‐α‐a‐tocopheryl acetate was studied in low birth weight infants. Vitamin E was given from the first day of life, either as a water‐soluble (Ephynal®) or as a lipid‐soluble preparation (E‐vitamin®). Serum‐α‐tocopherol concentrations were determined before treatment and on days three and seven. Treatment with both vitamin E preparations increased serum‐a‐tocopherol on day three and seven. The mean serum‐a‐tocopherol ± SD on day seven were 41.4±10.7 umol/l for the Ephynal® group and 26.7±12.5 umol/l for the E‐vitamin® group, this difference being statistically significant (p < 0.025). Oral feeding seems to influence the absorption of tocopherol from E‐vitamin®, as the infants with the highest serum‐a‐tocopherol concentrations were those with the highest oral/total feeding ratios. In infants with birth weight <1000 g treatment with 25 mg Ephynal®/day was found to increase serum‐a‐tocopherol on day seven to 46.9± 12.3 umol/l (mean ± SD). This concentration is comparable to those reported by others using higher doses of oral vitamin E.
Low Superoxide Levels in Blood Phagocytic Cells in Down's Syndrome
Authors: ANNEREN G. , BJORKSTEN B.
Published: January 2008

ABSTRACT. Superoxide anion was measured in polymorphonuclear neutrophils (PMNs) from 10 patients with Down's syndrome (DS) and 10 healthy controls after stimulation with phorobol‐myris‐tate‐acetate (PMA). The superoxide (O2‐:) levels were lower in PMNs from nine of 10 DS patients, than in simultaneously tested control cells (p<0.01). The findings may in part explain the increased susceptibility of DS patients to infections with certain microorganisms, e.g. S. aureus and C. albicans.
The usefulness of serial C‐reactive protein measurement in managing neonatal infection
Authors: Kawamura M , Nishida H
Published: January 2008

Recent advances in laboratory technology have enabled us to measure C‐reactive protein with a higher sensitivity in a short period using a minimal amount of blood. Thus C‐reactive protein can be measured easily several times a day. In this study, serial changes in C‐reactive protein values were evaluated in 108 term and 240 preterm newborn infants with suspicion of infection, and the changing patterns of C‐reactive protein values were compared with clinical outcome. For a diagnosis of infection, the negative predictive values in term and preterm infants were 99.0% and 97.8%, respectively, although the sensitivities were 61.5% and 75.0%, respectively. Antibiotic therapy was started at birth and discontinued when the changing pattern of C‐reactive protein and clinical findings did not suggest infection. As a result, mean durations of administration of antibiotics in the term and preterm infants were 3 and 4 days, respectively. Recognition of the changing pattern of C‐reactive protein was very useful in excluding infection and minimizing unnecessary antibiotic therapy in managing neonatal infection.
Surfactant replacement therapy in neonates with respiratory failure due to bacterial sepsis
Authors: Fetter WPF , Baerts W , Bos AP , Lingen RA van
Published: January 2008

We describe four newborns (gestational ages 29‐37 weeks; birthweights 1380‐3040 grams) who were mechanically ventilated for respiratory insufficiency because of bacterial sepsis. A beneficial effect of bovine surfactant (Alvofact, dosages 50 or lOOmg/kg) was found, as shown by decreases in mean airway pressures and oxygen demands. No side effects were seen after instillation.