History Of Intrauterine Growth Retardation Research Articles

Home enteral nutrition does not decrease oral feeding in children during the first year of nutritional support

Enteral nutrition is necessary when nutritional status is poor and oral intake is insufficient or impossible. Although it has been suspected to reduce spontaneous oral feeding, no study has formally assessed the influence of enteral nutrition on pediatric oral intake. The present study aimed to evaluate variation in oral feeding intake after enteral nutrition initiation, and to identify factors influencing oral feeding. This retrospective cohort study included 149 pediatric patients from two French tertiary care hospitals, who received home enteral nutrition from 2009 to 2022. The patients were aged 2 months to 17 years (median age 3 years, interquartile range 1.3-9.2). Oral and enteral intakes were assessed when enteral nutrition was initiated (M0), and again at M3 (n=123), M6 (n=129), and M12 (n=134) follow-ups, based on dieticians' and home services' reports. Oral feeding and body mass index z score variations during follow-ups were evaluated using a linear mixed regression model, including "time" as a fixed effect and "patient" as a random effect. Factors associated with oral feeding changes were assessed using a model interaction term. Oral intake did not vary significantly (P=0.99) over time and accounted for 47.4%±27.4%, 46.9%±27.4%, 48.4%±28.2%, and 46.6%±26.9% of the ideal recommended daily allowance (calculated for the ideal weight for height) at M0, M3, M6, and M12, respectively. Delivery method (nasogastric tube versus gastrostomy), prematurity, underlying disease, history of intrauterine growth retardation, and speech therapy intervention did not influence oral intake. Administration (i.e., exclusively continuous nocturnal infusion versus daytime bolus) led to different oral intake development, although oral intake also differed at M0. Enteral nutrition, although increasing total energy intake, does not alter oral feeding during the first year of administration. Only the mode of administration might influence oral intake.

THU211 Novel SIN3A Loss-Of-Function Variant As Potentially Pathogenic For Hypogonadotropic Hypogonadism In Witteveen-Kolk Syndrome

Abstract Disclosure: L.M. Correa Brito: None. A.C. Keselman: None. N.M. Sanguineti: None. P.A. Scaglia: None. M. Esnaola Azcoiti: None. F. Villegas: None. M. Maier: None. I. Bergada: None. M.G. Ropelato: None. R.A. Rey: None. Witteveen-Kolk Syndrome (WITKOS, MIM #613406) is an autosomal dominant disorder characterized by short stature, typical facial dysmorphism, microcephaly and mild intellectual disability, initially associated with 15q24 microdeletions encompassing SIN3A gene. Subsequently, WITKOS was found in individuals with loss-of-function (LOF) variants in SIN3A. Central or hypogonadotropic hypogonadism (HH) has been described in patients with WITKOS due to 15q24 microdeletions, but whether HH was due to haploinsufficiency of SIN3A or of any of the other five genes located in the shortest region of overlap (∼260 kb) of 15q24 could not be ascertained. A 6-year-old girl was referred to us for short stature. She had a history of intrauterine growth retardation and presented with microcephaly, broad forehead, wide nasal base, prominent nasal bridge, short philtrum, overfolded helix, clinodactyly of the 5th finger, joint laxity, neurodevelopmental delay, attention deficit hyperactivity disorder (ADHD), sensorineural hearing impairment, bicuspid aortic valve and ulcerative proctitis. She was treated with recombinant growth hormone, with good response. At the age of 14, she showed absence of thelarche and was evaluated for delayed puberty. Serum estradiol was undetectable, and gonadotropins were low after a GnRH infusion test (LH basal 0.2 IU/L, peak 0.7 IU/L; FSH basal 0.1 IU/L, peak 0.6 IU/L). HH was diagnosed. An MRI scan revealed a bilateral agenesis of the olfactory bulbs and olfactometry detected anosmia, leading to the clinical diagnosis of Kallmann syndrome (HH with anosmia). Whole exome sequencing (WES) identified a novel heterozygous frameshift variant, NM_001145358.2:c.3045_3046dup, NP_001138830.1:p.(Ile1016ArgfsTer6) in SIN3A. The insertion creates a frameshift expected to lead to a stop codon and a loss of function due to nonsense-mediated mRNA decay. Her mother, who had no history of HH, was while type for SIN3A. Unfortunately, his father was not available. The variant was absent in GnomAD, and has not been reported in dbSNP, ClinVar and Uniprot. It was classified as pathogenic according to the ACMG criteria, with a score of 10 points (8 points for PVS1_very strong, 1 point for PM2_supporting and 1 point for PP4_supporting). No other variant was found in 82 genes potentially related to HH. This is the first case report of a patient with WITKOS and HH carrying a pathogenic single nucleotide variant in SIN3A. Our results are strongly suggestive that HH in patients with WITKOS is due to SIN3A haploinsufficiency, thus ruling out a contiguous gene syndrome as causative for HH. Presentation: Thursday, June 15, 2023

Clinical and molecular description of two cases of neonatal diabetes secondary to mutations in PDX1.

Pancreatic dysgenesis (PD) is a rare congenital disease, with less than 100 cases reported in the literature. In most cases, patients are asymptomatic and the diagnosis is made incidentally. In this report, we present the case of two brothers with a history of intrauterine growth retardation, low birth weight, hyperglycemia, and poor weight gain. The diagnosis of PD and neonatal diabetes mellitus was made by an interdisciplinary team composed of an endocrinologist, a gastroenterologist, and a geneticist. Once the diagnosis was made, treatment with an insulin pump, pancreatic enzyme replacement therapy, and supplementation with fat-soluble vitamins was decided. The use of the insulin infusion pump facilitated the outpatient treatment of both patients. Pancreatic dysgenesis is a relatively rare congenital anomaly; most of the time, patients are asymptomatic and are diagnosed incidentally. The diagnosis of pancreatic dysgenesis and neonatal diabetes mellitus should be made with an interdisciplinary team. Due to its flexibility, the use of an insulin infusion pump facilitated the management of these two patients.

Cognitive profiles and brain volume are affected in patients with Silver–Russell syndrome

Silver–Russell syndrome (SRS) is a rare condition associated with pre and postnatal growth retardation. The most common causes of SRS are 11p15 ICR1 loss of methylation (LOM) and maternal uniparental disomy of chromosome 7 (mUPD7). Almost all patients with SRS have a history of intrauterine growth retardation (IUGR) and may be born small for gestational age (SGA). Children with SRS show typical features, including relative macrocephaly, prominent forehead, body asymmetry, feeding difficulties and cognitive delay (1)(2). SRS patients with 11p15 LOM show high IGF1 levels suggestive of IGF1 insensitivity. IGF1 is implicated in brain development, in particular with neural proliferation and cognitive function (2)(3).

Two novel compound heterozygous mutations in NGLY1as a cause of congenital disorder of deglycosylation: a case presentation

BackgroundNGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG) is a multisystemic neurodevelopmental disorder in which affected individuals show developmental delay, epilepsy, intellectual disability, abnormal liver function, and poor growth. This study presents a 10-month-old female infant with elevated liver transaminases, developmental delay, epilepsy (subclinical seizures), and constipation who possesses two compound heterozygous mutations in NGLY1.Case presentationThe proband was admitted to the Department of Gastroenterology, Children’s Hospital of Soochow University, with elevated liver transaminases. She had a history of intrauterine growth retardation and exhibited elevated transaminases, global developmental delay, seizures and light constipation during early infancy. Whole-exome sequencing (WES) and Sanger sequencing revealed two compound heterozygous mutations in NGLY1 that had been inherited in an autosomal recessive manner from her parents. One was a termination mutation, c.1168C > T (p.R390*), and the other was a missense mutation, c.1156G > T (p.D386Y). NGLY1-CDDG is a rare disorder, with a few dozen cases. The two mutations of this proband has not been previously identified.ConclusionsThis study investigated a Chinese proband with NGLY1-CDDG born from healthy parents who was studied using WES and Sanger sequencing to identify the causative mutations. We identified two novel compound heterozygous mutations in NGLY1, c.1168C > T (p.R390*)/c.1156G > T (p.D386Y), which are probably causative of disease.

Intestinal permeability is increased in ex-premature children with a history of intrauterine growth retardation

Background and aim: Intestinal permeability (IP) is increased in animal models of prematurity and Intrauterine Growth Retardation (IUGR), suggesting an impaired intestinal barrier integrity leading to growth delay. No study exists in humans. We aimed to perform a pilot study to assess IP in a pediatric population with persistent growth retardation and a history of preterm birth and IUGR.

Mais do que uma insuficiência de crescimento: relato de caso

Introduction: Failure to thrive is a common reason for referral of children for pediatric consultation. There are many causes and the correct diagnosis is essential for the treatment and prevention of secondary complications. Although genetic diseases as a cause of failure to thrive are rare, awareness of this possibility is necessary. Case report: A 2-year-old boy, with history of intrauterine growth retardation and feeding difficulties from the neonatal period, was seen in a general practice consultation due to failure to thrive and global psychomotor developmental delay. In addition to these medical problems, the child had craniofacial dysmorphism, a stellate iris pattern, a hoarse voice, lax joints, and an overfriendly and talkative personality. The diagnosis of Williams syndrome was proposed. The patient was referred to a medical genetics consultation and the diagnosis was confirmed by demonstrating a chromosomal microdeletion at 7q11.23. The child was referred for appropriate follow-up of the child and his young parents received genetic counselling. Comment: The presence of psychomotor developmental delay and multiple physical anomalies should raise the possibility of a genetic syndrome as a cause of failure to thrive. Family physicians should have basic knowledge of genetic disorders to allow the recognition of clinical signs suggestive of inborn genetic diseases in order to enable early diagnosis and referral of the patient and the family for medical genetic consultation.

Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene

Cerebro-retinal microangiopathy with calcifications and cysts (CRMCC) or Coats plus syndrome is a pleiotropic disorder affecting the eyes, brain, bone and gastrointestinal tract. Its primary pathogenesis involves small vessel obliterative microangiopathy. Recently, autosomal recessively inherited mutations in CTC1 have been reported in CRMCC patients. We herein report an adolescent referred to our hospital following new seizures in a context of an undefined multisystem disorder. Cerebral imaging disclosed asymmetrical leukopathy, intracranial calcifications and cysts. In addition, he presented other typical CRMCC features i.e. a history of intrauterine growth retardation, skeletal demineralization and osteopenia, bilateral exudative vitreo-retinopathy reminiscent of Coats disease, recurrent gastrointestinal hemorrhages secondary to watermelon stomach and variceal bleeding of the esophagus due to idiopathic portal hypertension and telangiectatic and angiodysplasic changes in the small intestine and colon, and anemia due to recurrent bleeding and bone marrow abnormalities. The patient was diagnosed with Coats plus syndrome. CTC1 gene screening confirmed the diagnosis with the identification of heterozygous deleterious mutations. CRMCC due to CTC1 mutations has a broad clinical expressivity. Our case report illustrates the main possible associated phenotypes and their complications, demonstrating the need for a careful etiological search in order to initiate appropriate therapeutic and preventive measures.

Congenital chloride diarrhea: a review of twelve Arabian children

BackgroundCongenital chloride diarrhea (CCD), a rare autosomal recessive disorder, is characterized by sustained watery diarrhea (due to defect of active Chloride/HCO3 exchange in the ileum and colon) with high fecal chloride.ObjectiveTo spotlight the common presentation of CCD for early management and prevention of complications.Subjects and methodsThis is a retrospective case series study of patients diagnosed as CCD who were followed up in the pediatric department of Al-Adan Hospital, Kuwait.ResultsTwelve patients diagnosed with CCD were born to consanguineous parents; had antenatal history of intrauterine growth retardation (IUGR); polyhydramnios; and distended hypoechoic fetal bowel; and presented with abdominal distension, hypotonia and muscle wasting. 90% of patients had maternal hypertension and 75% of patients had absence of normal meconium at birth. Our patients showed a decrease in serum sodium, potassium, chloride and urine chloride.ConclusionA high level of suspicion for an early diagnosis of CCD should be considered for any infant presenting with chronic diarrhea, especially in the presence of consanguineous marriage, and the characteristic features in antenatal ultrasound. Thus, allowing for early investigations and appropriate management.

Genetic selection of embryos that later develop the metabolic syndrome

The Barker hypothesisIs an excellent explanation of the process where human and animal foetuses exposed to malnutrition, either by maternal malnutrition or placental insufficiency, are metabolically programmed, with selective stunting of cell differentiation and organ growth. With the postnatal excess of nutrition observed in developed countries, this irreversible programming causes metabolic syndrome, including obesity, type 2 diabetes, and hypertension. Metabolic programming involves epigenetic changes including imprinting which might be transmitted through more than one generation rather than being completely re-set or erased during reproduction. The Barker hypothesis was supported by epidemiological data that recognised no excess fetal or postnatal mortality when pregnant women were starved during the Dutch famine in World War II. This argued against the “thrifty genotype” theory introduced in 1962, which proposed that starvation selected against members of the population with less “thrifty” genes, but the survivors who had “thrifty” genes developed metabolic syndrome if they were subsequently over-nourished. Embryonic/fetal selectionEmbryos or early foetuses could be selected very early in pregnancy on the basis of their genotype, by maternal malnutrition, hypertension, obesity or other causes of placental insufficiency. The genotype that allows embryos, or cells within them, to survive a less hospitable environment in the decidua after implantation might contribute to the later development of metabolic syndrome.This article hypothesises that an adverse intrauterine environment, caused by maternal malnutrition or placental insufficiency, kills a proportion of embryos and selects a surviving population of early embryos whose growth in utero is retarded by their genotype, their environment or a combination of both. The metabolic syndrome follows if the offspring is over-nourished later in life.The embryonic selection hypothesis presented here could be tested by using single nucleotide polymorphism (SNP) microarrays to study adults who had a history of intrauterine growth retardation (IUGR) and subsequent metabolic syndrome. Their SNP array could be compared with their parents and unaffected unrelated or related controls. If there were no selection based on a “thrifty genotype”, all parental sequences would be expected to appear in their surviving children, whether or not they had IUGR or developed metabolic syndrome. SNP sequences present in parents or controls but missing from adult offspring with metabolic syndrome who had IUGR, could be associated with or linked to genes that influence susceptibility to metabolic syndrome. This hypothesis proposes that missing genotypes would be lost if the embryos that inherited them died very early in pregnancy.

Severe Variant of X‐linked Dyskeratosis Congenita (Hoyeraal‐Hreidarsson Syndrome) Causes Significant Enterocolitis in Early Infancy

Severe Variant of X‐linked Dyskeratosis Congenita (Hoyeraal‐Hreidarsson Syndrome) Causes Significant Enterocolitis in Early Infancy

From hyperinsulinaemic hypoglycaemia to ketotic hypoglycaemia: the range of glucose abnormalities in patients born with intrauterine growth retardation

Newborns with intrauterine growth retardation (IUGR) have multiple risk factors for developing hypoglycaemia. Hyperinsulinism, both transient and prolonged, is one of the major risk factors responsible for the hypoglycaemia observed in some newborns with IUGR. Once the child has progressed beyond the infancy period, the most common cause of hypoglycaemia is ketotic hypoglycaemia. We report our observations of ketotic hypoglycaemia in six children who were born with IUGR and developed hyperinsulinaemic hypoglycaemia (HH) that required treatment with diazoxide and chlorothiazide. In one of these children the ketotic hypoglycaemia was found to be due to growth hormone deficiency; in the remaining five patients, however, no cause for the hypoglycaemia could be found, despite extensive investigations. These observations suggest that ketotic hypoglycaemia may be more common in children with a history of IUGR. Further studies are required to understand why some newborns with IUGR and HH have an increased risk of ketotic hypoglycaemia in childhood. Newborns with a history of IUGR and HH have an increased risk of developing ketotic hypoglycaemia in the childhood period.

Hepatomegaly in neonates and children.

1. Ann D. Wolf, MD* 2. Joel E. Lavine, MD, PhD† 1. 2. *Chief Resident. 3. 4. †Associate Professor of Pediatrics and Chief, Joint Program in Gastroenterology and Nutrition, Department of Pediatrics, UCSD School of Medicine, San Diego, CA. After completing this article, readers should be able to: 1. Identify the possible causes of simultaneous hepatomegaly and splenomegaly. 2. List the important diagnostic considerations in patients who have hepatomegaly. 3. Delineate the most helpful initial radiographic test. 4. Describe what clinical findings occurring concomitantly in a patient who has hepatomegaly suggest metabolic or storage disease. 5. List the risk factors for infectious hepatitis. Hepatomegaly can represent intrinsic liver disease or may be the presenting physical finding of a generalized disorder. Early diagnosis and treatment of children who have liver disease is important because specific treatments are available for some diseases that can prevent disease progression or hepatic failure. The presence of a palpable liver does not always indicate hepatomegaly. Normal liver size is based on normative values of liver span by percussion, degree of extension below the right costal margin, or length of the vertical axis estimated from imaging techniques. In general, a liver edge greater than 3.5 cm in newborns and greater than 2 cm in children below the right costal margin suggests enlargement. Liver span is determined by measuring the distance between the upper edge, determined by percussion, and the lower edge, determined by palpation, in the midclavicular line. The lower border also may be determined by auscultation. With the stethoscope placed below the xiphoid, the examiner should gently scratch superiorly, starting in from the right lower quadrant, and listen for sound enhancement as the finger passes over the liver edge. Liver span increases linearly with body weight and age in both genders and correlates more with weight than with height. The normal range for liver span by percussion at 1 week of age is 4.5 to 5 cm. At 12 years, the normal value for boys is 7 to 8 cm and for girls is 6 to 6.5 cm. The liver …

Three‐year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r‐hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067 mg/kg) s.c, during 3 y and the children in Group 2 started the study with a 1‐y observation period followed by a 3‐y treatment period. At birth, their mean weight standard deviation score (SDS) was ‐2.5 and their mean length SDS ‐3.5. At baseline, the patients were prepubertal, non‐GHdeficient, with no known dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was ‐3.4, height velocity (HV) SDS was ‐1.6, and body mass index SDS was ‐1.4. After 1 y of treatment, linear HV in Group 1 increased in comparison with the pre‐treatment period (from 5.7 ± 2.0 to 10.1 ± 1.7cm/y;p < 0:001)and with the firstyear of observation in Group2(p < 0:001). Increased HV was sustained during the second and third year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3y of GH treatment in Group 2. Mean height SDS for chronological age increased by 2.0 ± 0.7 in the two groups after 3 y of treatment. HV after 1 y of treatment was negatively correlated with growth velocity at baseline. Bone age remained retarded but increased with a mean of almost 4 y after 3y of treatment in both groups. Even at a dose that is three times the replacement dose treatment with r‐hGH was well tolerated. From these results, we conclude that r‐hGH treatment over 3 y can induce sustained catch‐up growth in young children with severe short stature and a history of IUGR. Long‐term studies are needed to assess ultimate effects on final height.

Growth Hormone in the Treatment of Short Stature in Young Children with Intrauterine Growth Retardation

Growth acceleration and bone maturation were studied in children with severe short stature and a history of intrauterine growth retardation (IUGR) to determine the effect of growth hormone (GH)-treatment. Patients were enrolled in an open randomized, multicenter trial and allocated to either the treated group (group 1, n = 38) or the control group (group 2, n = 31). Both groups were treated daily with 0.2 IU/kg/body weight during 3 years. The children in group 2 started the study with a 1-year observation period followed by a 3-year treatment period. At baseline, the mean age was 4.5 years, bone age was 3.3 years, height standard deviation score (SDS) was –3.4, height velocity (HV) SDS was –1.6. Auxologic data were measured every 3 months and bone age was assessed at the start of the study (baseline) and then every 12 months thereafter. After 1 year of treatment, linear HV in group 1 increased significantly in comparison with the pretreatment period (from 5.7 ± 2.0 to 10.1 ± 1.7 cm/year; p < 0.001). Increased HV was sustained during the 2nd and 3rd year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3 years of growth hormone (GH) treatment in group 2. The mean height SDS for chronological age increased by 2.0 ± 0.7 in the 2 groups after 3 years of treatment. Bone age remained retarded but increased with a mean of almost 4 years after 3 years of treatment in both groups. Even at a dose that is three times the replacement dose, treatment with recombinant human GH was well tolerated. From these results, we conclude that recombinant human GH treatment over 3 years can induce sustained catch-up growth in young children with severe short stature and a history of IUGR.

The short child.

1. Maria G. Vogiatzi, MD* 2. Kenneth C. Copeland, MD† 1. 2. *Instructor of Pediatrics, New York Hospital-Cornell Medical College, New York, NY. 3. 4. †Professor of Pediatrics, Baylor College of Medicine, Houston, TX. 1. Determination of height velocity is the most critical factor in evaluating the growth of a child. 2. A decreased height velocity after the third year of life indicates pathology unless proven otherwise. 3. Constitutional delay of growth and adolescence (CDGA) and familial short stature (FSS), the two most common entities associated with short stature, are characterized by deceleration of linear growth during the first 2 or 3 years of life. 4. Weight-for-height ratio may help distinguish “systemic” disorders (including gastrointestinal, renal, cardiopulmonary, and immunologic) from endocrinopathies. 5. Dysmorphic features are variable but important clues supportive of a diagnosis of genetic disorders. 6. Children who have congenital growth hormone (GH) deficiency often present in the newborn period with hypoglycemia in combination with prolonged hyperbilirubinemia. Growth represents a sentinel for the general health of a child. However, the distinction between normal and abnormal growth may be difficult to make at times. The purpose of this review is to highlight differences between growth patterns associated with normal variations and those associated with pathologic conditions. A method of categorizing growth patterns is used that is based principally on analyses of height velocity, weight for height, and abnormal physical features. Determination of height velocity is the single most critical factor in evaluating the growth of a child, and the simplest way to determine whether a height velocity is normal for age is to observe whether a height is “crossing” percentiles on the linear growth curve. Weight-for-height ratio may be helpful in distinguishing “systemic” disorders (including gastrointestinal, renal, cardiopulmonary, and immunologic) from endocrinopathies. The short child who has one of the “systemic” disorders typically is short and thin; the child who has an endocrinopathy usually is short and well-nourished or frankly obese. Dysmorphic features, disproportionate shortening, a history of intrauterine growth retardation (IUGR), and mental retardation are variable but important clues …

Predicting the growth response to growth hormone in patients with intrauterine growth retardation

Human GH treatment of short children who had intrauterine growth retardation (IUGR) results in a highly variable growth response. The object of this study was to test the hypothesis that differences in responsiveness to exogenously administered GH might reflect differences in endogenous GH secretion or sensitivity. Prospective study evaluating th growth response to GH therapy in short individuals with prior IUGR. Ten short, prepubertal children with prior IUGR were studied. Mean age was 6 years (3.39-8.61). Mean bone age was 4.6 years (2.3-8.3). Mean body mass index was 13.2 kg/m2 (9.9-14.0; normal 13.5-19.0). Overnight spontaneous GH release was measured using a constant withdrawal pump and stimulated GH release was measured following clonidine (0.15 mg/m2) administration. IGF-I concentrations were measured at baseline and 12, 24, 36 and 48 hours after sequential doses of GH (0.05 and 0.2 mg/kg/dose) given 48 hours apart. Patients were treated with GH (0.125 mg/kg three times a week) and growth response was assessed. In the second and third year, attempts were made to improve the growth rate by nutritional supplementation and increasing the dose of GH to 0.25 mg/kg three times a week. All patients had normal integrated nocturnal GH secretion (> 3 micrograms/l, 6mU/l) and normal peak GH secretion in response to clonidine (> 7 micrograms/l). In the first year of the trial, mean growth velocity (GV) increased from 5.39 cm/year +/- 0.29 to 7.32 cm/year +/- 0.39 (P = 0.004). Changes in GV correlated inversely with integrated GH (r = -0.69; P = 0.038), baseline IGF-I concentration (r = -0.88; P = 0.002) and baseline GV-SDS (r = -0.68; P = 0.043). There was no correlation between change in GV and GH binding protein, baseline height SDS or age. The effect of GH waned in the second year, but tended to remain greater than the pretreatment growth rate (6.54 +/- 0.49 vs 5.53 cm/year +/- 0.29; P = 0.09). No significant advancement of bone age over chronological age was observed over the first 2 years. Increasing nutritional intake by 17% did not result in significant weight gain nor increase in height velocity. Doubling the dose of GH in the second or third year did not result in a significant increase in GV. The variable response to GH therapy in short children with a history of intrauterine growth retardation may partly reflect relative sufficiency or insufficiency of GH. Baseline IGF-I levels and baseline growth velocity appear to be useful and practical predictors of response to GH.

Aspirin and Other Platelet-Active Drugs: The Relationship Among Dose, Effectiveness, and Side Effects

Aspirin and Other Platelet-Active Drugs: The Relationship Among Dose, Effectiveness, and Side Effects

Ischaemic brain lesions diagnosed at birth in preterm infants: clinical events and developmental outcome.

In 232 newborn babies of less than 32 weeks' gestational age ultrasound brain scans were carried out shortly after birth, daily for the first week of life, and at least twice weekly thereafter. Periventricular echogenicity associated with or progressing to periventricular leukomalacia (ischaemic brain lesions) was present in nine babies within two hours of birth (early onset); 30 other babies subsequently developed similar lesions (late onset). Babies with early onset lesions were more likely to have a history of intrauterine growth retardation and to have recurrent apnoea in the first few hours after birth. By contrast, late onset lesions were associated with hyaline membrane disease. In later childhood four of six survivors with early onset periventricular leukomalacia, and seven of 14 survivors with late onset periventricular leukomalacia, had various disabilities including spastic diplegia, impaired vision, squints, sensorineural hearing loss, and developmental delay. In a third of the children with disabilities ischaemic brain lesions were noted within two hours of birth, raising the possibility that some of this damage had taken place before or during birth.