Quantitative impact of frenotomy on breastfeeding: a systematic review and meta-analysis.

BACKGROUND: Symptoms related to infant ankyloglossia/tongue-tie may deter mothers from breastfeeding, yet frenotomy is controversial. METHODS: Databases included PubMed, Embase, CINAHL, PsycINFO, Web of Science, and Google Scholar from 1961-2023. Controlled trials and cohort studies with validated measures of surgical efficacy for breastfeeding outcomes were eligible. Meta-analyses synthesized data with inverse-variance weighting to determine standardized mean differences (SMD) between pre-/postoperative scores. RESULTS: Twenty-one of 1568 screened studies were included. Breastfeeding self-efficacy improved significantly post-frenotomy: medium effect after 5-10 days (SMD 0.60 [95% CI: 0.48, 0.71; P < 0.001]), large effect after 1 month (SMD 0.91 [CI: 0.79, 1.04; P < 0.001]). Nipple pain decreased significantly post-frenotomy: large effect after 5-15 days (SMD -1.10 [CI: -1.49, -0.70; P < 0.001]) and 1 month (SMD -1.23 [CI: -1.79, -0.67; P = 0.002]). Frenotomy had a medium effect on infant gastroesophageal reflux severity at 1-week follow-up (SMD -0.63 [CI: -0.95, -0.31; P = 0.008]), with continued improvement at 1 month (SMD -0.41 [CI: -0.78, -0.05; P = 0.04]). From LATCH scores, breastfeeding quality improved after 5-7 days by a large SMD of 1.28 (CI: 0.56, 2.00; P = 0.01). CONCLUSIONS: Providers should offer frenotomy to improve outcomes in dyads with ankyloglossia-associated breastfeeding difficulties. PROTOCOL REGISTRATION: PROSPERO identifier CRD42022303838 . IMPACT: This systematic review and meta-analysis showed that breastfeeding self-efficacy, maternal pain, infant latch, and infant gastroesophageal reflux significantly improve after frenotomy in mother-infant dyads with breastfeeding difficulties and ankyloglossia. Providers should offer frenotomy to improve breastfeeding outcomes in symptomatic mother-infant dyads who face challenges associated with ankyloglossia.

Childhood outcomes after low-grade intraventricular haemorrhage: A systematic review and meta-analysis.

AIM: To undertake a systematic review and meta-analysis exploring school-age neurodevelopmental outcomes of children after low-grade intraventricular haemorrhage (IVH). METHOD: The published and grey literature was extensively searched to identify observational comparative studies exploring neurodevelopmental outcomes after IVH grades 1 and 2. Our primary outcome was neurodevelopmental impairment after 5 years of age, which included cognitive, motor, speech and language, behavioural, hearing, or visual impairments. RESULTS: This review included 12 studies and over 2036 infants born preterm with low grade IVH. Studies used 30 different neurodevelopmental tools to determine outcomes. There was conflicting evidence of the composite risk of neurodevelopmental impairment after low-grade IVH. There was evidence of an association between low-grade IVH and lower IQ at school age (-4.23, 95% confidence interval [CI] -7.53, -0.92, I2 = 0%) but impact on school performance was unclear. Studies reported an increased crude risk of cerebral palsy after low-grade IVH (odds ratio [OR] 2.92, 95% CI 1.95, 4.37, I2 = 41%). No increased risk of speech and language impairment or behavioural impairment was found. Few studies addressed hearing and visual impairment. INTERPRETATION: This systematic review presents evidence that low-grade IVH is associated with specific neurodevelopmental impairments at school age, lending support to the theory that low-grade IVH is not a benign condition. WHAT THIS PAPER ADDS: The functional impact of low-grade intraventricular haemorrhage (IVH) at school age is unknown. Low-grade IVH is associated with a lower IQ at school age. The risk of cerebral palsy is increased after low-grade IVH. Low-grade IVH is not associated with speech and language impairment.

General health in a cohort of children conceived after assisted reproductive technology in the United Kingdom: a population-based record-linkage study.

BACKGROUND: Assisted reproductive technology use is increasing annually; however, data on long-term child health outcomes including hospital admissions are limited. OBJECTIVE: This study aimed to examine the potential effects of assisted reproductive technology on any and cause-specific hospital admissions unrelated to perinatal diagnoses. STUDY DESIGN: This was a population-based record-linkage study that included a previously established cohort of children born after assisted reproductive technology in the United Kingdom between 1997 and 2009 (n=63,877), their naturally conceived siblings (n=11,343), and matched naturally conceived population controls (n=127,544) linked to their postnatal health outcomes up to March 31, 2016 to provide robust risk estimates of the potential effects of assisted reproductive technology on any and cause-specific hospital admissions unrelated to perinatal diagnoses. In addition, comparison of hospital admissions by type of treatment was made. Cox regression was used to estimate the risk of hospital admission, and negative binomial regression was used to compare the number of hospital admissions per year. RESULTS: This study had 1.6 million person-years of follow-up (mean, 12.9 years; range, 0-19 years), and the mean age at the time of first hospital admission was 6.5 years (range, 0-19 years). Singletons born after assisted reproductive technology had increased risk of any hospital admission compared with naturally conceived population controls (hazard ratio, 1.08; 95% confidence interval, 1.05-1.10) but not naturally conceived siblings (hazard ratio, 1.01; 95% confidence interval, 0.94-1.09). We observed increased risk of diagnoses related to neoplasms and diseases of the respiratory, musculoskeletal, digestive, and genitourinary systems, and lower risk of injury, poisoning, and consequences of external causes compared with naturally conceived population controls. Children born after intracytoplasmic sperm injection had a lower risk of hospital admission compared with those born after in vitro fertilization, although no such differences were observed between children born after fresh embryo transfers and those born after frozen embryo transfers. CONCLUSION: Children born after assisted reproductive technology had greater numbers of hospital admissions compared with naturally conceived population controls. Attenuation of these differences in relation to their naturally conceived siblings suggested that this could be partially attributed to the influence of parental subfertility on child health, increased parental concerns, and an actual increase in morbidity in children born after assisted conception.

Reduced Presentation of Biliary Atresia During the COVID-19 Lockdown: A Population Based Observational Study.

OBJECTIVE: The aim of this study was to assess whether there has been a change in presentations of biliary atresia (BA) in England and Wales during the first and second coronavirus disease 2019 (COVID-19) lockdowns (January-June 2020 and 2021). DESIGN: This population study assessed all confirmed cases of BA, from January 2020 to December 2021 across the 3 UK pediatric liver centers originating from England and Wales. Data was then compared to the incidence of confirmed BA cases from January to December 2017, 2018, and 2019. RESULTS: During January-June 2020 and 2021, there were only 8 and 12 presenting cases of BA in England and Wales, compared to 16, 13, and 18 for the same time periods in 2017, 2018, and 2019, respectively. This difference was significant in a two-sided t test for 2020 ( P = 0.035) but not for 2021 ( P = 0.385). There was no difference in the mean days to Kasai procedure in January-June 2020 and 2021 compared to 2017-2019; however average time to Kasai after the lockdown periods was significantly higher. CONCLUSIONS: There was a significant reduction in the presenting cases of BA during the first COVID-19 lockdown, with an increased time for BA referrals after the pandemic lockdowns were lifted in England and Wales.

Severity and prevalence of ankyloglossia-associated breastfeeding symptoms: A systematic review and meta-analysis.

AIM: To evaluate breastfeeding symptoms associated with ankyloglossia/tongue-tie. METHODS: Databases included PubMed, Embase, CINAHL, PsycINFO, Web of Science, and Google Scholar. Eligible studies reported baseline breastfeeding symptoms/severity from tongue-tied infants. Two reviewers independently screened studies, extracted data, and assessed quality. Low-quality studies were excluded. Main outcomes were weighted mean severity scores for dyads with ankyloglossia relative to reference values for successful breastfeeding. Meta-analyses used inverse-variance-weighted random-effects models. RESULTS: Of 1328 screened studies, 39 were included (5730 infants with ankyloglossia). The mean LATCH score for patients with untreated ankyloglossia, 7.1 (95% CI: 6.7-7.4), was significantly below the good-breastfeeding threshold. The mean Infant Breastfeeding Assessment Tool score, 10.0 (8.2-11.7), was not significantly below the good-breastfeeding threshold. The mean Infant-Gastroesophageal Reflux Questionnaire-Revised score, 18.2 (10.5-26.0), was consistent with gastroesophageal reflux disease. The mean Breastfeeding Self-Efficacy Scale-Short Form score, 43.7 (39.3-48.1), indicated significant risk of cessation of exclusive breastfeeding within 1-3 months. Mean nipple pain was 4.9 (4.1-5.7) on a 0-10 scale, greater than typical scores for breastfeeding mothers without nipple damage. Total prevalence of breastfeeding difficulties was 49.3% (95% CI: 47.3-51.4%). Early, undesired weaning occurred in 20.3% (18.5-22.2%) of cases before intervention. CONCLUSION: Ankyloglossia is adversely associated with breastfeeding success and maternal well-being.

The risks of birth defects and childhood cancer with conception by assisted reproductive technology.

STUDY QUESTION: Is there an association between fertility status, method of conception and the risks of birth defects and childhood cancer? SUMMARY ANSWER: The risk of childhood cancer had two independent components: (i) method of conception and (ii) presence, type and number of birth defects. WHAT IS KNOWN ALREADY: The rarity of the co-occurrence of birth defects, cancer and ART makes studying their association challenging. Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects or cancer but have been limited by small sample size and inadequate statistical power, failure to adjust for or include plurality, differences in definitions and/or methods of ascertainment, lack of information on ART treatment parameters or study periods spanning decades resulting in a substantial historical bias as ART techniques have improved. STUDY DESIGN, SIZE, DURATION: This was a population-based cohort study linking ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 1 January 2004 to 31 December 2017 that resulted in live births in 2004-2018 in Massachusetts and North Carolina and live births in 2004-2017 in Texas and New York. A 10:1 sample of non-ART births were chosen within the same time period as the ART birth. Non-ART siblings were identified through the ART mother's information. Children from non-ART births were classified as being born to women who conceived with ovulation induction or IUI (OI/IUI) when there was an indication of infertility treatment on the birth certificate, and the woman did not link to the SART CORS; all others were classified as being naturally conceived. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population included 165 125 ART children, 31 524 non-ART siblings, 12 451 children born to OI/IUI-treated women and 1 353 440 naturally conceived children. All study children were linked to their respective State birth defect registries to identify major defects diagnosed within the first year of life. We classified children with major defects as either chromosomal (i.e. presence of a chromosomal defect with or without any other major defect) or nonchromosomal (i.e. presence of a major defect but having no chromosomal defect), or all major defects (chromosomal and nonchromosomal), and calculated rates per 1000 children. Logistic regression models were used to generate adjusted odds ratios (AORs) and 95% CIs of the risk of birth defects by conception group (OI/IUI, non-ART sibling and ART by oocyte source and embryo state) with naturally conceived children as the reference, adjusted for paternal and maternal ages; maternal race and ethnicity, education, BMI, parity, diabetes, hypertension; and for plurality, infant sex and State and year of birth. All study children were also linked to their respective State cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of cancer by birth defect status (including presence of a defect, type and number of defects), and conception group. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 29 571 singleton children (2.0%) and 3753 twin children (3.5%) had a major birth defect (chromosomal or nonchromosomal). Children conceived with ART from autologous oocytes had increased risks for nonchromosomal defects, including blastogenesis, cardiovascular, gastrointestinal and, for males only, genitourinary defects, with AORs ranging from 1.22 to 1.85; children in the autologous-fresh group also had increased risks for musculoskeletal (AOR 1.28, 95% CI 1.13, 1.45) and orofacial defects (AOR 1.40, 95% CI 1.17, 1.68). Within the donor oocyte group, the children conceived from fresh embryos did not have increased risks in any birth defect category, whereas children conceived from thawed embryos had increased risks for nonchromosomal defects (AOR 1.20, 95% CI 1.03, 1.40) and blastogenesis defects (AOR 1.74, 95% CI 1.14, 2.65). The risk of cancer was increased among ART children in the autologous-fresh group (HR 1.31, 95% CI 1.08, 1.59) and non-ART siblings (1.34, 95% CI 1.02, 1.76). The risk of leukemia was increased among children in the OI/IUI group (HR 2.15, 95% CI 1.04, 4.47) and non-ART siblings (HR 1.63, 95% CI 1.02, 2.61). The risk of central nervous system tumors was increased among ART children in the autologous-fresh group (HR 1.68, 95% CI 1.14, 2.48), donor-fresh group (HR 2.57, 95% CI 1.04, 6.32) and non-ART siblings (HR 1.84, 95% CI 1.12, 3.03). ART children in the autologous-fresh group were also at increased risk for solid tumors (HR 1.39, 95% CI 1.09, 1.77). A total of 127 children had both major birth defects and cancer, of which 53 children (42%) had leukemia. The risk of cancer had two independent components: (i) method of conception (described above) and (ii) presence, type and number of birth defects. The presence of nonchromosomal defects increased the cancer risk, greater for two or more defects versus one defect, for all cancers and each type evaluated. The presence of chromosomal defects was strongly associated with cancer risk (HR 8.70 for all cancers and HR 21.90 for leukemia), further elevated in the presence of both chromosomal and nonchromosomal defects (HR 21.29 for all cancers, HR 64.83 for leukemia and HR 4.71 for embryonal tumors). Among the 83 946 children born from ART in the USA in 2019 compared to their naturally conceived counterparts, these risks translate into an estimated excess of 761 children with major birth defects, 31 children with cancer and 11 children with both major birth defects and cancer. LIMITATIONS, REASONS FOR CAUTION: In the SART CORS database, it was not possible to differentiate method of embryo freezing (slow freezing versus vitrification), and data on ICSI were only available in the fresh embryo ART group. In the OI/IUI group, it was not possible to differentiate type of non-ART treatment utilized, and in both the ART and OI/IUI groups, data were unavailable on duration of infertility. Since OI/IUI is underreported on the birth certificate, some OI/IUI children were likely included among the naturally conceived children, which will decrease the difference between all the groups and the naturally conceived children. WIDER IMPLICATIONS OF THE FINDINGS: The use of ART is associated with increased risks of major nonchromosomal birth defects. The presence of birth defects is associated with greater risks for cancer, which adds to the baseline risk in the ART group. Although this study does not show causality, these findings indicate that children conceived with ART, non-ART siblings, and all children with birth defects should be monitored more closely for the subsequent development of cancer. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by grant R01 HD084377 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development, or the National Institutes of Health, nor any of the State Departments of Health which contributed data. M.L.E. reports consultancy for Ro, Hannah, Dadi, Sandstone and Underdog; presidency of SSMR; and SMRU board member. The remaining authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Obesity as a driver of international differences in COVID-19 death rates.

AIM: To determine what proportion of the inter-country variation in death rates can be explained in terms of obesity rates and other known risk factors for coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: COVID-19 death rates from 30 industrialized countries were analysed using linear regression models. Covariates modelled population density, the age structure of the population, obesity, population health, per capita gross domestic product (GDP), ethnic diversity, national temperature and the delay in the government imposing virus control measures. RESULTS: The multivariable regression model explained 63% of the inter-country variation in COVID-19 death rates. The initial model was optimized using stepwise selection. In descending order of absolute size of model coefficient, the covariates in the optimized model were the obesity rate, the hypertension rate, population density, life expectancy, the percentage of the population aged older than 65 years, the percentage of the population aged younger than 15 years, the diabetes rate, the delay in imposing national COVID-19 control measures, per capita GDP and mean temperature (with a negative coefficient indicating an association between higher national temperatures and lower death rates). CONCLUSIONS: A large proportion of the inter-country variation in COVID-19 death rates can be explained by differences in obesity rates, population health, population densities, age demographics, delays in imposing national virus control measures, per capita GDP and climate. Some of the unexplained variation is probably attributable to inter-country differences in the definition of a COVID-19 death and in the completeness of the recording of COVID-19 deaths.

Consensus statements on the information to deliver after a febrile seizure.

Febrile seizures (FS) are usually self-limiting and cause no morbidity. Nevertheless they represent very traumatic events for families. There is a need to identify key messages that reassure carers and help to prevent inappropriate, anxiety-driven behaviors associated with "fever phobia." No recommendations have been proposed to date regarding the content of such messages. Using a Delphi process, we have established a consensus regarding the information to be shared with families following a FS. Twenty physicians (child neurologists and pediatricians) from five European countries participated in a three-step Delphi process between May 2018 and October 2019. In the first step, each expert was asked to give 10 to 15 free statements about FS. In the second and third steps, statements were scored and selected according to the expert ranking of importance. A list of key messages for families has emerged from this process, which offer reassurance about FS based on epidemiology, underlying mechanisms, and the emergency management of FS should they recur. Interestingly, there was a high level of agreement between child neurologists and general pediatricians.Conclusion: We propose key messages to be communicated with families in the post-FS clinic setting. What is Known: • Febrile seizures (FS) are traumatic events for families. • No guidelines exist on what information to share with parents following a FS. What is New: • A Delphi process involving child neurologists and pediatricians provides consensual statement about information to deliver after a febrile seizure. • We propose key messages to be communicated with families in the post-FS clinic setting.

Risks of nonchromosomal birth defects, small-for-gestational age birthweight, and prematurity with in vitro fertilization: effect of number of embryos transferred and plurality at conception versus at birth.

PURPOSE: Excess embryos transferred (ET) (> plurality at birth) and fetal heartbeats (FHB) at 6 weeks' gestation are associated with reductions in birthweight and gestation, but prior studies have been limited by small sample sizes and limited IVF data. This analysis evaluated associations between excess ET, excess FHB, and adverse perinatal outcomes, including the risk of nonchromosomal birth defects. METHODS: Live births conceived via IVF from Massachusetts, New York, North Carolina, and Texas included 138,435 children born 2004-2013 (Texas), 2004-2016 (Massachusetts and North Carolina), and 2004-2017 (New York) were classified by ET and FHB. Major birth defects were reported by statewide registries within the first year of life. Logistic regression was used to estimate adjusted odds ratios (AORs) and 95% CIs of the risks of a major nonchromosomal birth defect, small-for-gestational age birthweight (SGA), low birthweight (LBW), and preterm birth (≤36 weeks), by excess ET, and excess ET + excess FHB, by plurality at birth (singletons and twins). RESULTS: In singletons with [2 ET, FHB =1] and [≥3 ET, FHB=1], risks [AOR (95% CI)] were increased, respectively, for major nonchromosomal birth defects [1.13 (1.00-1.27) and 1.18 (1.00-1.38)], SGA [1.10 (1.03-1.17) and 1.15 (1.05-1.26)], LBW [1.09 (1.02-1.13) and 1.17 (1.07-1.27)], and preterm birth [1.06 (1.00-1.12) and 1.14 (1.06-1.23)]. With excess ET + excess FHB, risks of all adverse outcomes except major nonchromosomal birth defects increased further for both singletons and twins. CONCLUSION: Excess embryos transferred are associated with increased risks for nonchromosomal birth defects, reduced birthweight, and prematurity in IVF-conceived births.

Childhood Health and Educational Outcomes After Neonatal Abstinence Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically review and meta-analyze the association between neonatal abstinence syndrome (NAS) and adverse health or educational childhood outcomes. STUDY DESIGN: An all-language search was conducted across 11 databases between January 1, 1975, and September 3, 2019; 5865 titles were identified. Observational studies of children between 28 days and 16 years of age, in whom a diagnosis of NAS was documented, were included. Outcomes included reasons for hospital admissions, childhood diagnoses, developmental outcomes, and academic attainment scores. All studies underwent independent review by 2 trained reviewers, who extracted study data and assessed risk of bias using the Newcastle Ottawa Tool. RESULTS: Fifteen studies were identified that included 10 907 children with previous NAS and 1 730 213 children without previous NAS, aged 0-16 years. There was a strong association between NAS and subsequent child maltreatment (aOR, 6.49; 95% CI, 4.46-9.45; I2 = 52%), injuries and poisoning (aOR, 1.34; 95% CI, 1.21-1.49; I2 = 0%), and a variety of mental health conditions. Studies consistently demonstrated an increased incidence of strabismus and nystagmus among those with previous NAS. Children with NAS also had lower mean academic scores than the control group in every domain of testing across age groups. CONCLUSIONS: NAS is significantly associated with future child maltreatment, mental health diagnoses, visual problems, and poor school performance. Owing to the necessary inclusion of nonrandomized studies, incomplete reporting among studies, and likely unadjusted confounding, this review does not suggest causation. However, we highlight associations requiring further investigation and targeted intervention, to positively impact the life course trajectories of this growing population of children.

In vitro fertilization and risk for hypertensive disorders of pregnancy: associations with treatment parameters.

BACKGROUND: Although in vitro fertilization has been associated with an increased risk for hypertensive disorders of pregnancy, the association of risk with in vitro fertilization treatment parameters is unclear. OBJECTIVE: To evaluate risk for hypertensive disorders of pregnancy by maternal fertility status and in vitro fertilization treatment parameters. MATERIALS AND METHODS: Women in 8 states who underwent in vitro fertilization resulting in a live birth during 2004-2013 were linked to their infant's birth certificates. A 10:1 sample of births from non-in vitro fertilization deliveries were selected for comparison. Those with an indication of infertility treatment on the birth certificate were categorized as subfertile and omitted from the study population; all others were categorized as fertile. The in vitro fertilization pregnancies were additionally categorized by oocyte source (autologous versus donor) and embryo state (fresh versus thawed). Both the fertile and in vitro fertilization births were limited to singletons only, and the in vitro fertilization pregnancies were limited to those using partner sperm. Hypertensive disorders of pregnancy (including gestational hypertension and preeclampsia) were identified from the birth certificate, modeled using logistic regression, and reported as adjusted odds ratios and 95% confidence intervals. For analyses of in vitro fertilization pregnancies from autologous oocytes-fresh embryos, the reference group was fertile women (subgroup analysis 1). For analyses within the in vitro fertilization group, the reference group was autologous oocytes-fresh embryos (subgroup analysis 2). RESULTS: The study population included 1,465,893 pregnancies (1,382,311 births to fertile women and 83,582 births to in vitro fertilization-treated women). Compared to fertile women, in vitro fertilization-treated women with autologous-fresh cycles were not at increased risk for hypertensive disorders of pregnancy (adjusted odds ratio, 1.04; 95% confidence interval, 0.99, 1.08). Among in vitro fertilization births (subgroup analysis 2), the risk for hypertensive disorders of pregnancy was increased for the autologous-thawed (adjusted odds ratio, 1.30; 95% confidence interval, 1.20, 1.40); donor-fresh (adjusted oddds ratio, 1.92; 95% confidence interval, 1.71, 2.15); and donor-thawed (adjusted odds ratio, 1.70; 95% confidence interval, 1.47, 1.96) groups. Excluding women with pregestational diabetes or chronic hypertension as well as adjusting for body mass index and infertility diagnoses did not substantially change the results. When stratified by <34 weeks (early-onset hypertensive disorders of pregnancy) versus ≥34 weeks (late-onset hypertensive disorders of pregnancy), only the donor-fresh group had an increased risk of early-onset hypertensive disorders of pregnancy, but the risks for all other oocyte source-embryo state groups compared to autologous-fresh were increased for late-onset hypertensive disorders of pregnancy. CONCLUSION: The risk for hypertensive disorders of pregnancy is increased for in vitro fertilization-treated women in pregnancies conceived via frozen embryo transfer (with both autologous or donor oocyte) and fresh donor oocyte embryo transfer. No increase in risk was seen with autologous oocyte-fresh embryo transfers in vitro fertilization cycles. Excluding women with pregestational diabetes or chronic hypertension as well as adjusting for body mass index and infertility diagnoses did not substantially change the results.

Clinical and cost effectiveness of a parent mediated intervention to reduce challenging behaviour in pre-schoolers with moderate to severe intellectual disability (EPICC-ID) study protocol: a multi-centre, parallel-group randomised controlled trial.

BACKGROUND: Children with intellectual disabilities are likely to present with challenging behaviour. Parent mediated interventions have shown utility in influencing child behaviour, although there is a paucity of UK research into challenging behaviour interventions in this population. NICE guidelines favour Stepping Stones Triple P (SSTP) as a challenging behaviour intervention and this trial aims to evaluate its clinical and cost effectiveness in preschool children with moderate to severe intellectual disabilities. METHODS: This trial launched in 2017 at four sites across England, with the aim of recruiting 258 participants (aged 30-59 months). The Intervention Group receive nine weeks of SSTP parenting therapy (six group sessions and three individualised face to face or telephone sessions) in addition to Treatment as Usual, whilst the Treatment as Usual only group receive other available services in each location. Both study groups undergo the study measurements at baseline and at four and twelve months. Outcome measures include parent reports and structured observations of behaviour. Service use and health related quality of life data will also be collected to carry out a cost effectiveness and utility evaluation. DISCUSSION: Findings from this study will inform policy regarding interventions for challenging behaviour in young children with moderate to severe intellectual disabilities. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, NCT03086876. Registered 22nd March 2017, https://clinicaltrials.gov/ct2/show/NCT03086876.

Defining critical factors in multi-country studies of assisted reproductive technologies (ART): data from the US and UK health systems.

As the worldwide use of assisted reproductive technologies (ART) continues to grow, there is a critical need to assess the safety of these treatment parameters and the potential adverse health effects of their use in adults and their offspring. While key elements remain similar across nations, geographic variations both in treatments and populations make generalizability challenging. We describe and compare the demographic factors between the USA and the UK related to ART use and discuss implications for research. The USA and the UK share some common elements of ART practice and in how data are collected regarding long-term outcomes. However, the monitoring of ART in these two countries each brings strengths that complement each other's limitations.

A child in shock: carotid blowout syndrome.

Paediatricians commonly encounter neck lumps during their routine clinical practice; vascular abnormalities, such as (pseudo)aneurysms, are a rare cause of these. Pseudoaneurysms of the carotid artery in children are usually the result of blunt or penetrating trauma, infection or vasculitis/connective tissue disorders. They can present with a variety of symptoms including neck pain, as a pulsatile neck mass or with compressive symptoms (for example, cranial nerve palsies or dyspnoea). Pseudoaneurysms carry a risk of rupture in which case they are fatal, unless immediate treatment is provided.We report a 17-month-old male child with idiopathic carotid artery blowout syndrome presenting with acute oropharyngeal haemorrhage leading to asystolic cardiac arrest. He was successfully resuscitated and emergency embolisation controlled the bleeding. Despite extensive left hemispheric infarct, he has survived.Carotid artery blowout syndrome needs to be recognised as a potential cause of major haemorrhage in childhood. The purpose of this case report is to remind readers of the differential diagnosis and work-up of a child presenting with a neck lump, to highlight important aspects of the acute management of major haemorrhage and massive blood transfusion in paediatrics, to describe the aetiology, presentation and management of carotid artery pseudoaneurysm in children and to discuss long term rehabilitation in patients with consequent neurological sequelae (including the need for input from multiple specialty teams).

A systematic review of sudden unexpected death in epilepsy (SUDEP) in childhood.

BACKGROUND: Sudden Unexpected Death in Epilepsy (SUDEP) is a significant cause of death in childhood epilepsy, and causes considerable concern to patients and their families. Despite this, the condition remains poorly understood. This systematic review investigates the risk factors, pathophysiology, and circumstances associated with childhood SUDEP. It aimed to explore the etiology of SUDEP and inform clinicians approaching SUDEP risk disclosure. METHODS: A structured electronic database search of MEDLINE, CENTRAL, EMBASE, and ISI web of science was conducted. Studies were included if they described clinical details of one or more patients, aged 18 years of age and below, who had SUDEP. Two reviewers independently reviewed each article for data extraction and quality assessment. RESULTS: Information on 108 cases of pediatric SUDEP was extracted from 22 included studies. These comprised five cohort studies, four retrospective case control studies, seven case series, and five case reports. Factors that appeared to be linked to pediatric SUDEP included those associated with severe epilepsy (early age of onset, high seizure frequency, intellectual impairment and developmental delay, multiple antiepileptic drug therapy, and structural abnormalities). The majority of included studies was noncomparative and had significant risk of bias. CONCLUSIONS: There is currently insufficient evidence to determine the etiology of pediatric SUDEP. Current best practice to prevent pediatric SUDEP is to optimize the management of epilepsy. A national SUDEP registry would provide invaluable high-quality data and insights into modifiable risk factors, genetic predispositions, and novel prevention strategies.

What does the world think of ankyloglossia?

AIM: The diagnosis of tongue-tie (or ankyloglossia) has increased more than 10-fold in some countries. Whether this is a global phenomenon or related to cultural and professional differences is uncertain. METHODS: An online survey in English, Japanese, Chinese and Spanish was disseminated between May and November 2016 via 27 international professional bodies to >30 clinical professions chosen a priori to represent occupations involved in the management of neonatal ankyloglossia. RESULTS: A total of 1721 responses came from nursing (51%), medical (40%), dental (6%) and allied health (4%) clinicians. Nurses (40%) and allied health (34%) professionals were more likely than doctors (8%) to consider ankyloglossia as important for lactation problems, as were western (83%) compared to Asian (52%) clinicians. Referrals to clinicians for ankyloglossia management originated mainly from parents (38%). Interprofessional referrals were not clearly defined. Frenectomies were most likely to be performed by surgeons (65%) and dentists (35%), who were also less likely to be involved in lactation support. Clinicians performing frenectomies were more likely to consider analgesia as important compared to those not performing frenectomies. CONCLUSION: The diagnosis and treatment of ankyloglossia vary considerably around the world and between professions. Efforts to standardise management are required.

Costs of vitamin D testing and prescribing among children in primary care.

Vitamin D has attracted considerable interest in recent years, with a marked increase in diagnosis of vitamin D deficiency seen among children in clinical practice in the UK. The economic implications of this change in diagnostic behaviour have not been explored. We performed a cohort study to examine longitudinal trends in healthcare expenditure arising from vitamin D testing and prescribing for children in primary care in England, using the electronic healthcare records of 722,525 children aged 0-17 years held in The Health Improvement Network database. Combined costs of vitamin D tests and prescriptions increased from £1647 per 100,000 person-years in 2008 (95% CI, £934 to £3007) to £28,913 per 100,000 person-years in 2014 (95% CI, £26,361 to £31,739). The total cost of vitamin D prescriptions and tests for children in primary care at the national level in England in 2014 was estimated to be £4.31 million (95% CI, £2.96-£6.48 million). CONCLUSION: There has been a marked increase in healthcare expenditure on vitamin D tests and prescriptions for children in primary care over the past decade. Future research should explore the drivers for this change in diagnostic behaviour and the reasons prompting investigation of vitamin D status in clinical practice. What is Known: • Vitamin D deficiency has attracted considerable interest in recent years, with a marked increase in diagnosis seen in children. • The economic implications of this change in diagnostic behaviour have not been explored. What is New: • There has been a large increase in healthcare expenditure on vitamin D tests and prescriptions for children in primary care in England over the past decade (> 15 fold between 2008 and 2013). • Screening of vitamin D status in children without specific risk factors or clinical features of deficiency may represent avoidable healthcare expenditure.

Cancer risk among children born after assisted conception.

BACKGROUND: Accurate population-based data are needed on the incidence of cancer in children born after assisted conception. METHODS: We linked data on all children born in Britain between 1992 and 2008 after assisted conception without donor involvement with data from the United Kingdom National Registry of Childhood Tumours to determine the number of children in whom cancer developed before 15 years of age. Cohort cancer rates were compared with population-based rates in Britain over the same period, with stratification for potential mediating and moderating factors, including sex, age at diagnosis, birth weight, singleton versus multiple birth, parity, parental age, type of assisted conception, and cause of parental infertility. RESULTS: The cohort consisted of 106,013 children born after assisted conception (700,705 person-years of observation). The average duration of follow-up was 6.6 years. Overall, 108 cancers were identified, as compared with 109.7 expected cancers (standardized incidence ratio, 0.98; 95% confidence interval [CI], 0.81 to 1.19; P=0.87). Assisted conception was not associated with an increased risk of leukemia, neuroblastoma, retinoblastoma, central nervous system tumors, or renal or germ-cell tumors. It was associated with an increased risk of hepatoblastoma (standardized incidence ratio, 3.64; 95% CI, 1.34 to 7.93; P=0.02; absolute excess risk, 6.21 cases per 1 million person-years) and rhabdomyosarcoma (standardized incidence ratio, 2.62; 95% CI, 1.26 to 4.82; P=0.02; absolute excess risk, 8.82 cases per 1 million person-years), with hepatoblastoma developing in 6 children and rhabdomyosarcoma in 10 children. The excess risk of hepatoblastoma was associated with low birth weight. CONCLUSIONS: There was no increase in the overall risk of cancer among British children born after assisted conception during the 17-year study period. Increased risks of hepatoblastoma and rhabdomyosarcoma were detected, but the absolute risks were small. (Funded by Cancer Research UK and others.).

Prokinetics prescribing in paediatrics: evidence on cisapride, domperidone, and metoclopramide.

OBJECTIVES: Domperidone and metoclopramide are prokinetics commonly prescribed off-label to infants and younger children in an attempt to treat gastro-oesophageal reflux symptoms. Another prokinetic drug, cisapride, was used but withdrawn in 2000 in the United Kingdom because of serious arrhythmic adverse events. Medicines and Healthcare Products Regulatory Agency issued safety warnings for domperidone in May 2012 and restricted its indications. We report here national primary care prescribing trends and safety signals of these drugs in children. METHODS: We used data from the General Practice Research Database between 1990 and 2006 for children <18 years. Descriptive statistics and Poisson regressions were performed to characterise prescribing trends. We examined safety signals in nested case-control studies. RESULTS: The proportion of children <2 years old being prescribed one of the medications doubled during the study period. Prescriptions of domperidone increased 10-fold, mainly following the withdrawal of cisapride in 2000. Prescriptions of metoclopramide did not change significantly. Despite the increase in prescriptions of domperidone, no new safety signals were identified. CONCLUSIONS: These data showed dramatic changes in prescribing of cisapride and domperidone despite the lack of good-quality supporting evidence. It is possible that these prescribing trends were influenced by published guidelines. Even if produced without robust efficacy and safety evidence, published guidelines can influence clinicians and consequently affect prescribing. Therefore, improving the evidence base on prokinetics to inform future guidelines is vital. The lack of new safety signals during this period would support the development of suitable powered clinical studies.