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1.  Folic acid supplements in pregnancy and early childhood respiratory health 
Archives of disease in childhood  2008;94(3):180-184.
Folate supplementation is recommended for pregnant women to reduce the risk of congenital malformations. Maternal intake of folate supplements during pregnancy might also influence childhood immune phenotypes via epigenetic mechanisms.
To investigate the relationship between folate supplements in pregnancy and risk of lower respiratory tract infections and wheeze in children through 18 months of age.
In the Norwegian Mother and Child Cohort Study, questionnaire data collected at several time points in pregnancy and after birth, from 32,077 children born between 2000 and 2005, were used to assess effects of folate supplements during pregnancy on respiratory outcomes up to 18 months of age, accounting for other supplements in pregnancy and supplementation in infancy.
Folate supplements in the first trimester were associated with increased risk of wheeze and respiratory tract infections up to 18 months of age. Adjusting for exposure later in pregnancy and in infancy, the relative risk of wheeze for children exposed to folic acid supplements in the first trimester was 1.06 (95% confidence interval: 1.03, 1.10), for lower respiratory tract infections the relative risk was 1.09 (95% confidence interval: 1.02, 1.15), and for hospitalizations for lower respiratory tract infections the relative risk was 1.24 (95% confidence interval: 1.09, 1.41).
Folic acid supplements in pregnancy were associated with a slightly increased risk of wheeze and lower respiratory tract infections up to 18 months of age. Results support possible epigenetic influences of methyl donors in maternal diet during pregnancy on respiratory health in children.
PMCID: PMC3612898  PMID: 19052032
Dietary Supplements; Folic acid; Pregnancy; Respiratory Tract Infections; Wheezing
Archives of disease in childhood  2008;94(10):768-774.
To assess whether serial measurements of childhood body mass index (BMI) give clinically useful predictions of the risk of developing adult metabolic syndrome and impaired glucose tolerance or type 2 diabetes.
Follow-up of a community-based birth cohort in Delhi, India.
1,492 men and women aged 26-32 years whose BMI was recorded 6-monthly throughout childhood.
Main outcome measures
The predictive value of childhood BMI for adult metabolic syndrome (MS) defined using waist circumference, blood pressure and fasting glucose, triglyceride and HDL-cholesterol concentrations, and impaired glucose tolerance (IGT) and diabetes (DM) diagnosed by oral glucose tolerance tests.
Twenty-five percent of subjects had MS and 15% had IGT/DM. Both outcomes were associated with greater childhood BMI gain (MS: OR 1.63 [95% CI 1.44 to 1.85]; IGT/DM: 1.39 [1.20 to 1.60] per unit increase in within-cohort BMI SD-score between 5-14 years). Best predictions of adult disease were obtained using a combined test comprising i) any increase in BMI SD-score between 5-14 years and ii) a BMI SD-score >0 at 14 years (MS: sensitivity 45%, specificity 78%; IGT/DM: 37%, 73%). Likelihood ratios were low (MS: 1.4-2.0; IGT/DM: 1.2-1.4). A single high BMI measurement at 14 years (overweight or obese, International Obesity Task Force criteria) was highly specific but insensitive (MS: sensitivity 7%, specificity 97%; IGT/DM: 8%, 97%). Charts for plotting BMI SD-scores through childhood were produced.
Serial measurements of childhood BMI give useful predictions of adult risk and could guide advice to children and parents on preventing later disease.
PMCID: PMC2749731  PMID: 19015213
Childhood body mass index; type 2 diabetes; metabolic syndrome; predictions
3.  The effects of bilingualism on stuttering during late childhood 
To document distinct patterns of language use by bilingual children (use of an alternative language exclusively, LE, or along with English, BIL). To establish how these patterns affect onset of stuttering, school performance and recovery rate relative to monolingual speakers who stutter (MONO).
Clinical referral sample with cases classified by speech-language therapists. Supplementary data obtained from speech recordings, interviews with child and family.
South-East England, 1999-2007.
Children aged 8-12 plus who stuttered (monolingual and bilingual) and fluent bilingual controls (FB).
Main outcome measures
Participants’ stuttering history, SATS scores, measures of recovery or persistence of stuttering.
The sample of 317 children had 69 bilinguals (prevalence rate of bilingualism in the stuttering sample was 21.8%). 38 children used a language other than English primarily or exclusively in the home and 36 of these (94.7%) bilinguals who stuttered did so in both their languages. There were fewer LE than BIL stuttering children at time of first referral to clinic (of the bilinguals who stuttered, 15/38, 39.5%, were LE and 23/38, 60.5%, were BIL). The reverse was the case in the fluent control sample (of the bilinguals who did not stutter, 28/38, 73.7%, were LE and 10/38, 26.3%, were BIL). The association between stuttering and bilingual group (LE/BIL) was significant by χ2 and this is consistent with a higher chance of stuttering for BIL than LE speakers. For speakers who stuttered, age of stuttering onset for LE and BIL was similar to that reported for MONO groups (4 years 9 months, 4 years 10 months and 4 years 3 months for LE, BIL, MONO respectively) and males were affected in each of these groups to about the same extent (the male/female ratio was 4.1:1, 4.75:1 and 4.43:1 for LE, BIL and MONO respectively). For the 29 children who were old enough to complete the assessments, educational achievement at key stages one and two was not affected by either form of bilingualism relative to the MONO and fluent bilingual groups. For these same children, recovery rate for LE and MONO controls was significantly higher by χ2 than for those who were BIL since birth (recovery rate for LE and MONO together was 55%, and for BIL was 25%).
There was an increased chance of stuttering onset for BIL children. The chances of recovery from stuttering were lower for BIL speakers than for LE and MONO speakers.
PMCID: PMC2597689  PMID: 18782846
Bilingualism; persistence; recovery; stuttering
4.  Developing and Introducing Evidence Based Clinical Practice Guidelines for Serious Illness in Kenya 
Archives of disease in childhood  2008;93(9):799-804.
The under-5 mortality rate in most developing countries remains high yet many deaths could be averted if available knowledge was put into practice. For seriously ill children in hospital investigations in low-income countries commonly demonstrate incorrect diagnosis and treatment and frequent prescribing errors. To help improve hospital management of the major causes of inpatient childhood mortality we developed simple clinical guidelines for use in Kenya, a low-income setting. The participatory process we used to adapt existing WHO materials and further develop and build support for such guidelines is discussed. To facilitate use of the guidelines we also developed job-aides and a 5.5 days training programme for their dissemination and implementation. We attempted to base our training on modern theories around adult learning and deliberately attempted to train a ‘critical mass’ of health workers within each institution at low cost. Our experience suggests that with sustained effort it is possible to develop locally owned, appropriate clinical practice guidelines for emergency and initial hospital care for seriously ill children with involvement of pertinent stake holders throughout. Early experience suggests that the training developed to support the guidelines, despite the fact that it challenges many established practices, is well received, appropriate to the needs of front line health workers in Kenya and feasible. To our knowledge the process described in Kenya is among a handful of attempts globally to implement inpatient or referral care components of WHO / UNICEF’s Integrated Management of Childhood Illness approach. However, whether guideline dissemination and implementation result in improved quality of care in our environment remains to be seen.
PMCID: PMC2654066  PMID: 18719161
5.  Health systems research in a low income country - easier said than done 
Archives of disease in childhood  2008;93(6):540-544.
Small hospitals sit at the apex of the pyramid of primary care in many low-income country health systems. If the Millennium Development Goal for child survival is to be achieved hospital care for severely ill, referred children will need to be improved considerably in parallel with primary care in many countries. Yet we know little about how to achieve this. We describe the evolution and final design of an intervention study attempting to improve hospital care for children in Kenyan district hospitals. We believe our experience illustrates many of the difficulties involved in reconciling epidemiological rigour and feasibility in studies at a health system rather than an individual level and the importance of the depth and breadth of analysis when trying to provide a plausible answer to the question - does it work? While there are increasing calls for more health systems research in low-income countries the importance of strong, broadly-based local partnerships and long term commitment even to initiate projects are not always appreciated.
PMCID: PMC2654065  PMID: 18495913
6.  The Relationship Between Maternal Depression, In-Home Violence, And Use Of Physical Punishment: What Is The Role Of Child Behavior? 
Archives of disease in childhood  2008;94(2):138-143.
Maternal depression and in-home violence are independently associated with the use of physical punishment on children; however, the combined impact of these factors on the practice of physical punishment is unknown, as is the extent to which their relationship to physical punishment varies with child behavior.
1) Determine the combined impact of maternal depression and violence exposure on one physical punishment practice, smacking; 2) Explore the role of child behaviors in this relationship.
Multivariable regression analysis of a nationally representative sample of US kindergarten children. Maternal depressive symptoms, violence exposure, and use of smacking as a discipline technique were measured by parent interview. Child behaviors were reported by teachers.
12,764 mother-child dyads were included in the analysis. The adjusted odds ratio (aOR) for smacking among mothers with depressive symptoms was 1.59 (95% CI 1.40, 1.80); among mothers exposed to in-home violence, 1.48 (95% CI 1.18, 1.85); among dually exposed mothers, 2.51 (95% CI 1.87, 3.37). Adjusting these models for child self-control or externalizing behavior yielded no change in these associations, and no effect modification by child behavior was detected. Among mothers reporting to smack their children, depression was associated with an increased smacking frequency (aIRR 1.12; 95% CI 1.01, 1.24); however, this association was reduced to borderline significance when adjusting the models for child self-control or externalizing behavior (aIRRs 1.10; 95% CI 1.00, 1.21). Depressed mothers who were also exposed to violence demonstrated higher rates of smacking (aIRR 1.29; 95% CI 1.09, 1.53); this remained stable when adjusting for child behaviors.
Maternal depression and violence exposure are associated with smacking as a means of punishment. The magnitude of this association is increased when depression and violence occur together. When coexistent, they also appear associated with the frequency of smacking. Child self-control and externalizing behavior do not appear to impact substantially the association between maternal depressive symptoms, violence exposure, and smacking.
PMCID: PMC2829298  PMID: 18786952
Maternal Depression; Violence; Corporal Punishment; Spanking; Smacking; Child Behavior
7.  Parent based language intervention for 2-year-old children with specific expressive language delay: a randomised controlled trial 
Archives of Disease in Childhood  2008;94(2):110-116.
The aim of this randomised controlled trial was to evaluate the effectiveness of a short, highly structured parent based language intervention group programme for 2-year-old children with specific expressive language delay (SELD, without deficits in receptive language).
61 children with SELD (mean age 24.7 months, SD 0.9) were selected between October 2003 and February 2006 during routine developmental check-ups in general paediatric practices, using a German parent-report screening questionnaire (adapted from the MacArthur Communicative Development Inventories). Standardised instruments were used to assess the language and non-verbal cognitive abilities of these children and of 36 other children with normal language development (reference group; mean age 24.6 months, SD 0.8). 58 children with SELD were sequentially randomly assigned to an intervention group (n = 29) or a 12-month waiting group (n = 29). In the intervention group, mothers participated in the 3-month Heidelberg Parent-based Language Intervention (HPLI). All children were reassessed 6 and 12 months after pretest. Assessors were blind to allocation and previous results.
47 children were included in the analysis. At the age of 3 years, 75% of the children in the intervention group showed normal expressive language abilities in contrast to 44% in the waiting group. Only 8% of the children in the intervention group versus 26% in the waiting group met the criteria for specific language impairment (t score ⩽35).
By applying the short, highly structured HPLI in children with SELD, the rate of treatment for language impairment at the age of 3 years can be significantly reduced.
PMCID: PMC2614563  PMID: 18703544
8.  Macrogol (polyethylene glycol) laxatives in children with functional constipation and faecal impaction: a systematic review 
Archives of Disease in Childhood  2008;94(2):156-160.
As the evidence base supporting the use of laxatives in children is very limited, we undertook an updated systematic review to clarify the issue. A comprehensive literature search was carried out to identify randomised controlled trials of polyethylene glycol (PEG) versus either placebo or active comparator, in patients aged <18 years with primary chronic constipation. Outcomes were assessed as either global assessments of effectiveness or differences in defaecation rates. Seven qualifying studies involving 594 children were identified. Five were comparisons of PEG with lactulose, one with milk of magnesia and one with placebo. Study duration ranged from 2 weeks to 12 months. PEG was significantly more effective than placebo and either equivalent to (two studies) or superior to (four studies) active comparator. Differences in study design precluded meaningful meta-analysis. Lack of high quality studies has meant that the management of childhood constipation has tended to rely on anecdote and empirical treatment choice. Recent publication of well designed randomised trials now permits a more evidence-based approach, with PEG-based treatments having been proven to be effective and well-tolerated first-line treatment.
PMCID: PMC2614562  PMID: 19019885
9.  Early introduction of fish decreases the risk of eczema in infants 
Atopic eczema in infants has increased in western societies. Environmental factors and the introduction of food may affect the risk of eczema.
To investigate the prevalence of eczema among infants in western Sweden, describe patterns of food introduction and assess risk factors for eczema at 1 year of age.
Data were obtained from a prospective, longitudinal cohort study of infants born in western Sweden in 2003; 8176 families were randomly selected and, 6 months after the infant’s birth, were invited to participate and received questionnaires. A second questionnaire was sent out when the infants were 12 months old. Both questionnaires were completed and medical birth register data were obtained for 4921 infants (60.2% of the selected population).
At 1 year of age, 20.9% of the infants had previous or current eczema. Median age at onset was 4 months. In multivariable analysis, familial occurrence of eczema, especially in siblings (OR 1.87; 95% confidence interval (CI) 1.50 to 2.33) or the mother (OR 1.54; 95% CI 1.30 to 1.84), remained an independent risk factor. Introducing fish before 9 months of age (OR 0.76; 95% CI 0.62 to 0.94) and having a bird in the home (OR 0.35; 95% CI 0.17 to 0.75) were beneficial.
One in five infants suffer from eczema during the first year of life. Familial eczema increased the risk, while early fish introduction and bird keeping decreased it. Breast feeding and time of milk and egg introduction did not affect the risk.
PMCID: PMC2597687  PMID: 18818269
10.  The effects of bilingualism on stuttering during late childhood 
To examine stuttering by children speaking an alternative language exclusively (LE) or with English (BIL) and to study onset of stuttering, school performance and recovery rate relative to monolingual speakers who stutter (MONO).
Clinical referral sample with supplementary data obtained from speech recordings and interviews.
South-East England, 1999–2007.
Children aged 8–12 plus who stuttered (monolingual and bilingual) and fluent bilingual controls (FB).
Main outcome measures:
Participants’ stuttering history, SATS scores, measures of recovery or persistence of stuttering.
69 (21.8%) of 317 children were bilingual. Of 38 children who used a language other than English at home, 36 (94.7%) stuttered in both languages. Fewer LE (15/38, 39.5%) than BIL (23/38, 60.5%) children stuttered at first referral to clinic, but more children in the fluent control sample were LE (28/38, 73.7%) than BIL (10/38, 26.3%). The association between stuttering and bilingual group (LE/BIL) was significant by χ2 test; BIL speakers have more chance of stuttering than LE speakers. Age at stuttering onset and male/female ratio for LE, BIL and MONO speakers were similar (4 years 9 months, 4 years 10 months and 4 years 3 months, and 4.1:1, 4.75:1 and 4.43:1, respectively). Educational achievement was not affected by bilingualism relative to the MONO and FB groups. The recovery rate for the LE and MONO controls together (55%) was significantly higher by χ2 test than for the BIL group (25%).
BIL children had an increased risk of stuttering and a lower chance of recovery from stuttering than LE and MONO speakers.
PMCID: PMC2597689  PMID: 18782846
11.  Cerebrovascular disease and stroke 
Archives of Disease in Childhood  2008;93(10):890-898.
Stroke and cerebrovascular disorders are important causes of morbidity and mortality in children; they are already amongst the top 10 causes of childhood death and are probably increasing in prevalence. Acute treatment of stroke syndromes in adults is now evidence based. However, paediatric stroke syndromes are far less common and the differential diagnosis is very wide, but the individual health resource implications are much greater because of the life-long treatment costs in survivors. Recognition and consultation with a paediatric neurologist should be rapid so that children can benefit from regional services with emergency neurological, neuroradiological and neurosurgical intervention and paediatric intensive care. This review focuses on the epidemiology, presentation, differential diagnosis, generic/specific emergency management and prognosis of acute stroke in children. Its aim is to educate and guide management by general paediatricians and to emphasise the importance of local guidelines for the initial investigation and treatment and appropriate transfer of these children.
PMCID: PMC2677268  PMID: 18591185
12.  Impact of universal varicella vaccination on 1-year-olds in Uruguay: 1997–2005 
Archives of Disease in Childhood  2008;93(10):845-850.
Varicella vaccination was introduced at the end of 1999 into the Uruguayan immunisation schedule for children aged 12 months. Varilrix (Oka strain; GlaxoSmithKline Biologicals) has been the only vaccine used since then and coverage has been estimated to exceed 90% since the start of the universal varicella vaccination programme. We assessed the impact of the Uruguayan varicella vaccination programme during 2005, 6 years after its introduction.
Information on hospitalisations was collected from the main paediatric referral hospital and information on medical consultations for varicella was collected from two private health insurance systems in Montevideo. The proportion of hospitalisations due to varicella and the proportion of ambulatory visits for varicella since the introduction of the vaccine were compared between 1999 and 2005 and 1997 and 1999 in the following age groups: <1 year, 1–4 years, 5–9 years and 10–14 years.
By 2005, the proportion of hospitalisations due to varicella among children, was reduced by 81% overall and by 63%, 94%, 73% and 62% in the <1, 1–4, 5–9 and 10–14 years age groups, respectively. The incidence of ambulatory visits for varicella among children was reduced by 87% overall and by 80%, 97%, 81% and 65% in the <1, 1–4, 5–9 and 10–14 years age groups, respectively.
The burden of varicella has decreased substantially in Uruguayan children since the introduction of the varicella vaccination, including those groups outside the recommended vaccination age. It is expected to decrease further as more cohorts of children are vaccinated and herd immunity increases.
PMCID: PMC2563416  PMID: 18456699
13.  The management of pulmonary hypertension in children 
Archives of Disease in Childhood  2008;93(7):620-625.
Pulmonary hypertension is relatively common in children and has many causes. The management of the condition has changed dramatically in the past 5 years with the introduction of new medicines. However, diagnosis, investigation and choice of therapy remain a challenge. In 2002 the United Kingdom Pulmonary Hypertension Service for Children was established and this has become the mainstay of management in this country. This service, based at Great Ormond Street Hospital for Children, provides advice, expertise and infrastructure support for the most severely affected patients, particularly those with idiopathic pulmonary arterial hypertension for whom chronic intravenous prostacyclin remains the most effective medication. New medicines are being developed which, rather than focussing on dilating a diseased pulmonary vascular bed, aim to structurally remodel the pulmonary vasculature towards normal.
PMCID: PMC2532955  PMID: 18381346

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