Genetic Analysis in Children with Transient Thyroid Dysfunction or Subclinical Hypothyroidism Detected on Neonatal Screening

About 30% of children with elevated TSH levels during neonatal screening have a transient form of disorder. On the other hand, it has been reported that subclinical hypothyroidism persists in late childhood in about 30% of children found to be false-positive during neonatal screening. The aim of this study was to determine whether transient thyroid dysfunction and subclinical hypothyroidism detected during neonatal screening are influenced by genetic background. The TSH receptor (TSHR), thyroid peroxidase (TPO) and dual oxidase 2 (DUOX2) genes, for which it has been reported that heterozygous defects cause neonatal transient thyroid dysfunction, were analyzed. Nine children with transient thyroid dysfunction or subclinical hypothyroidism detected during neonatal screening were studied. One child was heterozygous for a TSHR gene mutation (R450H), and another child was heterozygous for a TPO gene mutation (P883S). No children with mutation of the DUOX2 gene were identified. Genetic background may contribute to development of transient thyroid dysfunction and subclinical hypothyroidism detected during neonatal screening.     

Diagnostic and therapeutic aspects of dihydrobiopterin deficiency

The first Scandinavian hyperphenylalaninaemic patient with a cofactor deficiency is described. By neonatal screening the Guthrie test showed a serum phenylalanine of 302 mumol/1 (5 mg/dl), which at age 6 weeks had fallen to high normal values. At age 5 1/2 months the serum phenylalanine was around 2000 mumol/1 and the child presented with severe neurological symptoms. The diagnosis of defect dihydrobiopterin biosynthesis was made by high performance liquid chromatography of the urine. Loading tests followed by daily treatment of the missing cofactor was able to keep the serum phenylalanine in the normal level. Because of persisting, yet diminishing neurological symptoms neurotransmitter treatment was started. Breast feeding as the cause of the low neonatal levels of serum phenylalanine and the late start of clinical symptoms is proposed and the importance of screening all hyperphenylalaninaemic newborns for defect biopterin metabolism is stressed.     

Neuropsychological follow-up in neonatal screening: issues, methods and findings

There are several ongoing studies of psychological outcome in children identified through neonatal screening with phenylketonuria, congenital hypothyroidism or congenital adrenal hyperplasia. These studies document the reduction in mental retardation, learning difficulties and behaviour problems associated with neonatal screening. They also describe other behavioural changes resulting from these disorders. Some behavioural changes are transient or preventable with early diagnosis and treatment, whereas some appear to be irreversible, reflecting permanent brain effects of abnormalities associated with the disease. Despite the variety of disorders studied, there are commonalities in approach and issues, including a developmental neuropsychological perspective resulting in behavioural assessments specific to the disorder and its likely manifestations, a recognition that behaviour may change across time in association with brain development and an understanding of the neural mechanisms underlying the behavioural changes. Assessments go beyond IQ, and include specific intellectual abilities, social behaviour, temperament, behaviour problems and identity. Behavioural changes are related to specific characteristics of the disease and its treatment, including the timing of exposure to abnormal hormones and/or neurotransmitters, the severity of the disease, and the age at initiation and adequacy of treatment. These studies provide information about the ways in which hormones and neurotransmitters affect the development and ongoing function of the brain, and an understanding of the ways in which neonatal screening results in improved psychological outcome. They also provide models for psychological follow-up of other disorders detected through neonatal screening.     

Neuropsychological follow-up in neonatal screening: issues, methods and findings

There are several ongoing studies of psychological outcome in children identified through neonatal screening with phenylketonuria, congenital hypothyroidism or congenital adrenal hyperplasia. These studies document the reduction in mental retardation, learning difficulties and behaviour problems associated with neonatal screening. They also describe other behavioural changes resulting from these disorders. Some behavioural changes are transient or preventable with early diagnosis and treatment, whereas some appear to be irreversible, reflecting permanent brain effects of abnormalities associated with the disease. Despite the variety of disorders studied, there are commonalities in approach and issues, including a developmental neuropsychological perspective resulting in behavioural assessments specific to the disorder and its likely manifestations, a recognition that behaviour may change across time in association with brain development and an understanding of the neural mechanisms underlying the behavioural changes. Assessments go beyond IQ, and include specific intellectual abilities, social behaviour, temperament, behaviour problems and identity. Behavioural changes are related to specific characteristics of the disease and its treatment, including the timing of exposure to abnormal hormones and/or neurotransmitters, the severity of the disease, and the age at initiation and adequacy of treatment. These studies provide information about the ways in which hormones and neurotransmitters affect the development and ongoing function of the brain, and an understanding of the ways in which neonatal screening results in improved psychological outcome. They also provide models for psychological follow-up of other disorders detected through neonatal screening.     

Social–Emotional Screening Protocol Implementation: A Trauma-Informed Response for Young Children in Child Welfare

Adverse childhood experiences in young children result in negative outcomes as trauma affects brain development. In child welfare services, early recognition of delayed social–emotional skills and treatment referral is essential in reducing the effects of trauma. This quality improvement pilot project implemented an evidence-based social–emotional screening protocol using the Ages and Stages Questionnaire: Social Emotional-2 screening tool for very young children placed in out-of-home care through the county's child welfare system. Findings showed significant improvement in identification of children younger than 3 years with social–emotional concerns (p < .0001) and significant improvement in referral of those children positively identified (p = .0130). Ongoing use of the protocol was recommended, because it showed improved identification and referral for young children in the child welfare system with social–emotional concerns that were potentially trauma related. Further collaboration between child protective services, pediatric medical systems, and pediatric mental health systems is needed to facilitate trauma-informed care for children in the child welfare system.     

Three children with congenital toxoplasmosis: early report from a Swedish prospective screening study

The aim of this prospective study was to define the incidence of congenital toxoplasmosis in Sweden. Blood eluates collected on filter papers, Guthrie cards, from 40978 newborn babies were analysed for specific immunoglobulin M (IgM) and IgG antitoxoplasma antibodies. This is a preliminary report of three children with congenital toxoplasmosis, defined by the occurrence of antitoxoplasma-specific IgM antibodies. Two children were asymptomatic at birth. They were both normally developed at the age of 12 and 15 months, respectively. The third child had unidentified but uncomplicated symptoms of infection in the neonatal period. As a result of the screening congenital toxoplasmosis was confirmed and treatment instituted. Microphthalmus and peripheral chorioretinitis were detected in one eye. In spite of the chemotherapeutic treatment he developed hydrocephalus needing neurosurgical intervention at the age of 3 months. His development at 14 months was normal. The incidence in Sweden of congenital toxoplasmosis detected by specific IgM antitoxoplasma antibodies in blood from filter papers is less than 1:10000.     

ANTIBODY-COATED BACTERIA IN THE URINE OF CHILDREN WITH URINARY TRACT INFECTIONS

Abstract. The test for antibody-coated bacteria in urine for the diagnosis of the anatomical level of urinary tract infections was evaluated in children with UTI. The ability of the test to differentiate between an upper and lower infection is influenced by the antiglobulin preparation used, since too sensitive an antiglobulin probably detects nonspecifically bound antibodies. Staphylococcal protein A seems to be well suited for use as an antiglobulin in this test. Using staphylococcal protein A all children with X-ray findings suggesting renal damage had antibody-coated bacteria in the urine, however, nine infants and 5 children with clinical symptoms of pyelonephritis had a negative test. Of 28 children with clinical symptoms of cystitis only one had a positive test. Of 50 children with asymptomatic bacteriuria 9 had antibody-coated bacteria in the urine; 41 had not. The findings indicate that the method might be useful in establishing the anatomical level of urinary tract infection and might also be useful for screening children with asymptomatic bacteriuria who risk developing kidney infections.     

Inconclusive Cystic Fibrosis neonatal screening results: long-term psychosocial effects on parents

Aim:  Cystic Fibrosis (CF) Newborn Screening occasionally identifies neonates where a CF diagnosis can neither be confirmed nor excluded. To assess how parents of these infants cope with this ambiguous situation.
Methods:  Parents of 11 children with Ambiguous Diagnosis (group AD) were compared with parents of 11 children diagnosed with CF through neonatal screening [group Cystic Fibrosis Diagnosis (CFD)] and with parents of 11 Healthy Control children (group HC) matched for gender and age.
Results:  The emotional reaction to the inconclusive result was less pronounced in AD than in CFD (p = 0.003), and AD parents considered their infants as healthy as controls. Parents' anxiety about their child's health is stronger in CFD than in AD (p < 0.05) and HC (p < 0.001). Long-term emotional distress was rated similarly in AD and CFD, and greater than in HC (p = 0.0003). The parent/child relationship was less influenced in AD than in the CF group (p = 0.03). Seven AD and CFD parents changed their family planning projects.
Conclusion:  Inconclusive neonatal screening results appear to be understood and associated with lower anxiety levels than CF diagnosis. Concern about the child's health is similar to healthy controls and lower than in parents of CF children.     

A population‐based investigation of behavioural and emotional problems and maternal mental health: associations with autism spectrum disorder and intellectual disability

Background: While research indicates elevated behavioural and emotional problems in children with autism spectrum disorders (ASD) and decreased well‐being in their parents, studies do not typically separate out the contribution of ASD from that of associated intellectual disabilities (ID). We investigated child behavioural and emotional problems, and maternal mental health, among cases with and without ASD and ID in a large population‐representative sample. Methods: Cross‐sectional comparison of child behavioural and emotional problems and maternal mental health measures among 18,415 children (5 to 16 years old), of whom 47 had an ASD, 51 combined ASD with ID, 590 had only ID, and the remainder were the comparison group with no ASD or ID. Results: The prevalence of likely clinical levels of behavioural and emotional problems was highest among children with ASD (with and without ID). After controlling for age, gender, adversity, and maternal mental health, the presence of ASD and ID significantly and independently increased the odds for hyperactivity symptoms, conduct, and emotional problems. Emotional disorder was more prevalent in mothers of children with ASD (with or without ID). The presence of ASD, but not ID, significantly increased the odds for maternal emotional disorder. As has been found in previous research, positive maternal mental health was not affected by the presence of ASD or ID. Conclusions: ASD and ID are independent risk factors for behavioural and emotional problems. ASD (but not ID) is positively associated with maternal emotional disorder. Approaches to diagnosing hyperactivity and conduct problems in children with ASD may need to be reconsidered.     

Schistosomiasis in German children

Reports on schistosomiasis in children growing up in Europe are rare despite increased travel activity. We report on eight male and three female German children aged 50 months to 15 years with schistosomiasis. Six children were asymptomatic, whereas two presented with typical signs of Katayama fever. Persisting haematuria, headache with eosinophilia and pyelonephritis were observed in one child each. An exposure was reported for six of the children. Two were examined solely because schistosomiasis was diagnosed in a family member. All had antibodies against schistosomal antigens in at least two of three screening tests. However, schistosomal ova (Schistosoma haematobium) were detected in urine and faecal specimens from only three children. A tumour-like lesion of the bladder was found by ultrasound in only one of the children who also exhibited haematuria. Neither eosinophilia nor elevated IgE levels were constant findings. Six to 12 months after praziquantel treatment, parasitological and ultrasound checks were negative and levels of specific antibodies decreased. However, 2 years later, elevated antibody levels were detected in one girl without evidence of any new exposure. She became antibody-negative 1 year after a second course of treatment. Conclusion In contrast to residents of endemic areas, parasitological and ultrasound examinations seem to be inferior to immunodiagnostics in children from non-endemic areas at temporary risk for schistosomiasis. Received: 24 November 1999 and in revised form: 19 January 2000 / Accepted: 31 January 2000     

Costs of different strategies for neonatal hearing screening: a modelling approach

OBJECTIVE: To compare the cost effectiveness of various strategies for neonatal hearing screening by estimating the cost per hearing impaired child detected. DESIGN: Cost analyses with a simulation model, including a multivariate sensitivity analysis. Comparisons of the cost per child detected were made for: screening method (automated auditory brainstem response or otoacoustic emissions); number of stages in the screening process (two or three); target disorder (bilateral hearing loss or both unilateral and bilateral loss); location (at home or at a child health clinic). SETTING: The Netherlands TARGET POPULATION: All newborn infants not admitted to neonatal intensive care units. MAIN OUTCOME MEASURE: Costs per child detected with a hearing loss of 40 dB or more in the better ear. RESULTS: Costs of a three stage screening process in child health clinics are 39.0 pounds (95% confidence interval 20.0 to 57.0) per child detected with automated auditory brainstem response compared with 25.0 (14.4 to 35.6) pounds per child detected with otoacoustic emissions. A three stage screening process not only reduces the referral rates, but is also likely to cost less than a two stage process because of the lower cost of diagnostic facilities. The extra cost (over and above a screening programme detecting bilateral losses) of detecting one child with unilateral hearing loss is 1500-4000 pounds. With the currently available information, no preference can be expressed for a screening location. CONCLUSIONS: Three stage screening with otoacoustic emissions is recommended. Whether screening at home is more cost effective than screening at a child health clinic needs further study.     

VISUAL DISORDERS IN 7-YEAR-OLD CHILDREN WITH AND WITHOUT PREVIOUS VISION SCREENING

ABSTRACT. An analysis of visual defects among 310 children referred from a vision screening of 2178 7-year-old children revealed a 50% frequency of significant eye defects among the referrals (7% of screened children). Of the screened children, one group (1530 children) had previous visual screening three years earlier. The other group (648 children) had no previous vision screening until the age of seven. A comparison between the two groups showed that the risk of finding a new significant eye disorder in a school entrant was more than 6 times greater for a child who was not examined in his preschool years, and the risk of finding an ambiyopic child was more than 10 times greater. The results do indicate the need for continuation of the present vision screening program of pre-school children.     

Visual disorders in 7-year-old children with and without previous vision screening

An analysis of visual defects among 310 children referred from a vision screening of 2 178 7-year-old children revealed a 50% frequency of significant eye defects among the referrals (7% of screened children). Of the screened children, one group (1 530 children) had previous visual screening three years earlier. The other group (648 children) had no previous vision screening until the age of seven. A comparison between the two groups showed that the risk of finding a new significant eye disorder in a school entrant was more than 6 times greater for a child who was not examined in his preschool years, and the risk of finding an amblyopic child was more than 10 times greater. The results do indicate the need for continuation of the present vision screening program of pre-school children.     

Reproductive decisions after neonatal screening identifies cystic fibrosis

AIMS: To document the reproductive choices made by women in New South Wales, Australia, after neonatal screening has identified cystic fibrosis (CF). METHODS: A sample of women attending cystic fibrosis clinics in New South Wales who had a child (or children) diagnosed by neonatal screening between 1981 and 1996 were interviewed. RESULTS: Two thirds of the women chose to avoid having another child with CF. The uptake of prenatal diagnosis was 66% in women who had a subsequent pregnancy; of these 69% terminated or would have terminated an affected fetus. Fifty nine per cent of the women who decided against a further pregnancy made this decision in order to avoid having another child with CF. CONCLUSIONS: These data show that having a child with CF influenced subsequent reproductive choices. In addition to the medical advantages of an early diagnosis offered by neonatal screening, this also allows informed future reproductive decisions.     

SECONDARY CYSTATHIONINURIA

Cystathioninuria was detected in 6 of 230 hospitalized children. Three had convulsions when admitted to the hospital, two severe liver malfunction of unknown cause (suspect neonatal hepatitis), and one child had severe congenital malformations and bronchopneumonia and was in a terminal stage. Cystathioninuria disappeared in 4 children (two with convulsions and two with liver malfunction) treated with pyridoxine orally. Pyridoxine treatment (2×40 mg daily) also resulted in disappearence of convulsions. The possible background to these findings is discussed.     

Children with inborn errors of phenylalanine metabolism: prognosis and phenylalanine tolerance

Twenty-three children, who were detected by neonatal PKU screening, were followed for 8-18 years in one paediatric centre. Dietary treatment was started if the blood phenylalanine level exceeded 0.72 mmol/l. All 23 infants were initially given a low phenylalanine diet. The growth and development rates of the children did not differ significantly from those in a reference population, although one child had mild mental retardation and another had a short attention span. Fourteen children were still on a strict phenylalanine-restricted diet on their last follow-up (at 8-18 years of age). In nine children who were initially put on a low phenylalanine diet, it was possible to normalize the diet between 1/2 and 10 years of age, while maintaining the blood phenylalanine levels between 0.25 and 0.72 mmol/l. It seems likely that those of our patients who markedly increased their phenylalanine tolerance during childhood had a regulatory mutation of the phenylalanine hydroxylase system. A continuous reevaluation of each child treated with a low phenylalanine diet reduces the use of unnecessarily restricted diets.     

The natural history of screening detected IgA glomerulonephritis in children.

The clinical course of 43 children with IgA glomerulonephritis detected by mass urine screening was followed for a mean period of 8.1 years. Histological findings were graded according to the severity of glomerular and tubulointerstitial lesions. There was no correlation in the severity of histological grade and clinical outcome between subjects with microscopic hematuria and those with microscopic hematuria and proteinuria nor between those with and without one or more episodes of macroscopic hematuria during the follow-up period. None of the 35 children with proteinuria less than or equal to 1 g/m2/day had severe histological findings or developed renal impairment. In contrast, the 8 children with proteinuria greater than 1 g/m2/day had moderate and severe histological findings. Four of these 8 children developed hypertension or renal insufficiency during the follow-up period. Our study indicates that the outcome of screening detected IgA glomerulonephritis in children correlates with the level of proteinuria and the severity of renal pathology.     

Children with Inborn Errors of Phenylalanine Metabolism: Prognosis and Phenylalanine Tolerance

ABSTRACT. Twenty-three children, who were detected by neonatal PKU screening, were followed for 8-18 years in one paediatric centre. Dietary treatment was started if the blood phenylalanine level exceeded 0.72 mmolA. All 23 infants were initially given a low phenylalanine diet. The growth and development rates of the children did not differ significantly from those in a reference population, although one child had mild mental retardation and another had a short attention span. Fourteen children were still on a strict phenylalanine-restricted diet on their last follow-up (at 8-18 years of age). In nine children who were initially put on a low phenylalanine diet, it was possible to normalize the diet between 1/2 and 10 years of age, while maintaining the blood phenylalanine levels between 0.25 and 0.72 mmol/1. It seems likely that those of our patients who markedly increased their phenylalanine tolerance during childhood had a regulatory mutation of the phenylalanine hydroxylase system. A continuous reevaluation of each child treated with a low phenylalanine diet reduces the use of unnecessarily restricted diets.     

CHILDREN WITH PSYCHIATRIC DISORDERS IN PRIMARY CARE

A substantial minority (23%) of children between 7 and 12 years of age attending general practice were found to have psychiatric disorders. Disturbance was slightly more frequent in girls than in boys, and emotional disorder was the most common diagnosis. Psychiatric disorder was associated with psychological disadvantage (broken homes, the child had lived away from the family, family history of psychiatric disorder) and with current high levels of parental stress in relation to their children. Disturbed children tended to present with symptoms of anxiety, bed-wetting, hayfever, nosebleeds or scabies. Amongst a subsample of children consulting in general practice, psychiatric disorder may be a relevant factor contributing to somatic consultation.     

Maternal expressed emotion and adjustment in children with epilepsy

Epilepsy in childhood may alter family relationships but the relevance of these changes for the increased rates of psychopathology has been little investigated. This study uses maternal expressed emotion (EE) to examine family relationships of children with epilepsy and the association with high risk for psychiatric disorder. EE was assessed using the Camberwell Family Interview carried out with the mothers of 22 schoolchildren with chronic epilepsy who were attending a general hospital outpatient clinic. Sixteen of these children had similarly aged healthy siblings who served as controls. High risk for psychiatric disorder in the children and mothers was assessed using behavioural, mood, and self-esteem questionnaires completed by mothers, teachers, and children. It was found that mothers showed significantly more emotional overinvolvement and a trend for more hostility towards their children with epilepsy than towards sibling controls. For the 22 children with epilepsy, maternal emotional overinvolvement was not associated with child behavioural deviance. High levels of criticism and, to a lesser extent, hostility did show associations with child behavioural deviance, and the strongest links were between maternal criticism and maternal rated antisocial and overactive behaviour in the child. Fewer positive comments by mothers towards the children were associated with child emotional symptoms and lower self-esteem in a number of areas. This study suggests that further research could consider the appropriateness of psychological intervention for families in which mothers are critical and hostile and whose children show antisocial behaviour.