The importance of objective assessment of prenatal exposure to alcohol through measurement of biomarkers in meconium
Oscar Garcia-Algar1,2,3*, Luigi Tarani4, Francesco Paolo Busardò5, Simona Pichini3,5, Emilia Marchei5
1. Neonatology Unit, Hospital Clinic-Maternitat, ICGON, BCNatal, Barcelona Centre for Maternal Foetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clínic, Barcelona, Spain
2. Department de Cirurgia i Especialitats Mèdico-Quirúrgiques, Universitat de Barcelona, Barcelona, Spain
3. European Foetal Alcohol Spectrum Disorders Alliance (EUFASD), Stockholm, Sweden
4. Department of Pediatrics, Sapienza University of Rome, Rome, Italy
5. National Centre on Addiction and Doping, Istituto Superiore di Sanità, Rome, Italy
Dear Editor,
We read with attention the paper by Henderson et al. concerning comparison of confidential postnatal maternal interview and measurement of alcohol biomarkers in meconium (1). We would like to draw attention on their conclusion: “Fatty acid ethyl esters (FAEEs) and Ethylglucuronide (EtG) measured in meconium have low sensitivity and specificity for self-reported alcohol consumption after 20 weeks’ gestation in an unselected Scottish population and measurement of these alcohol biomarkers in meconium cannot currently be recommended for the identification of newborns at risk of Fetal Alcohol Spectrum Disorders (FASD).”
It has been more than 20 years since meconium analy...
The importance of objective assessment of prenatal exposure to alcohol through measurement of biomarkers in meconium
Oscar Garcia-Algar1,2,3*, Luigi Tarani4, Francesco Paolo Busardò5, Simona Pichini3,5, Emilia Marchei5
1. Neonatology Unit, Hospital Clinic-Maternitat, ICGON, BCNatal, Barcelona Centre for Maternal Foetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clínic, Barcelona, Spain
2. Department de Cirurgia i Especialitats Mèdico-Quirúrgiques, Universitat de Barcelona, Barcelona, Spain
3. European Foetal Alcohol Spectrum Disorders Alliance (EUFASD), Stockholm, Sweden
4. Department of Pediatrics, Sapienza University of Rome, Rome, Italy
5. National Centre on Addiction and Doping, Istituto Superiore di Sanità, Rome, Italy
Dear Editor,
We read with attention the paper by Henderson et al. concerning comparison of confidential postnatal maternal interview and measurement of alcohol biomarkers in meconium (1). We would like to draw attention on their conclusion: “Fatty acid ethyl esters (FAEEs) and Ethylglucuronide (EtG) measured in meconium have low sensitivity and specificity for self-reported alcohol consumption after 20 weeks’ gestation in an unselected Scottish population and measurement of these alcohol biomarkers in meconium cannot currently be recommended for the identification of newborns at risk of Fetal Alcohol Spectrum Disorders (FASD).”
It has been more than 20 years since meconium analysis has been used to objectively assess prenatal exposure to alcohol (2-12). Several studies have been reported in the literature regarding the use of this biological matrix for the determination of alcohol biomarkers such as FAEEs and EtG and to be used in epidemiological studies verifying alcohol drinking during pregnancy and consequentially prenatal exposure. These studies not only assessed prenatal exposure to gestational alcohol, but also demonstrated underreporting and misreporting of pregnant women concerning gestational drinking habits. To this concern, the majority of studies from our group showed no relationship between biomarker measurement and maternal self-reported declarations, at least in the Mediterranean area where investigations were carried out (13-26).
In this paper, an anonymised, observational population-based study questionnaire on alcohol consumption in pregnancy was matched with measurement of alcohol biomarkers in meconium in a cohort of mother/infant dyads from Glasgow, UK. Of 828 women enrolled in the study, 384 (46.4%) reported alcohol consumption at any time in pregnancy and for 114 (13.6%) this was after 20 weeks’ gestation. When meconium was positive for FAEEs (≥ 600 ng/g) and for EtG (≥ 30 ng/g), 14.5% and 10.7% of mothers reported alcohol consumption after 20 weeks’ gestation, respectively. Similar percentages were observed when meconium was negative for FAEEs (13.0%, ≤ 600 ng/g) and for EtG (14.0%, ≤ 30 ng/g). The authors concluded that FAEE and EtG measured in meconium showed low sensitivity and specificity for self-reported alcohol consumption after 20 weeks of gestation.
Based on the determination of biomarkers, FAEEs were identified in all meconium samples analyzed and 39.6% had a concentration greater than or equal to 600 ng/mg (cut-off used to discriminate positive from negative samples). As far as EtG is concerned, 14.5% of the analyzed meconium samples had a concentration greater than or equal to 30 ng/g (cut-off used to discriminate positive samples from negative ones). In summary, if the biomarkers are also considered, the percentage of potentially exposed children increases, therefore it is possible to intervene also on those who, from the questionnaire, would have appeared to be newborns of non-drinking women and therefore excluded from any follow-up.
Early diagnosis of foetal alcohol spectrum disorders is of crucial importance to perform a targeted follow up of newborns prenatally exposed to alcohol and avoid secondary neurodevelopmental disabilities. A positive meconium testing for the presence of EtG or FAEEs is an objective first element to assess prenatal exposure to alcohol, whereas a maternal self-reported admission of gestational consumption of alcohol is not.
The only use of self-reported questionnaires to disclose alcohol drinking during pregnancy can’t be recommended. In addition, we do not have to forget transplacental passage of this teratogen, which differs in each mother-infant dyad and can either allow or prevent alcohol migration from the mother to the foetus.
In conclusion, we reiterate the importance of objective assessment of gestational drinking and consequent foetal exposure by measuring alcohol metabolites not only in neonatal meconium, but also in maternal hair to associate the results of these measurements to a potential brief intervention on the risks of gestational alcohol to mothers and neurodevelopmental targeted follow up for exposed newborns (18, 26).
References
1. Henderson EM, Tappin D, Young D, et al Assessing maternal alcohol consumption in pregnancy: comparison of confidential postnatal maternal interview and measurement of alcohol biomarkers in meconium. Arch. Dis. Child. 2023, 2022-325028.
2. Bearer CF, Lee S, Salvator AE, et al. Ethyl linoleate in meconium: a biomarker for prenatal ethanol exposure. Alcohol Clin Exp Res. 1999, 23, 487-493.
3. Klein J, Karaskov T, Korent G. Fatty acid ethyl esters: a novel biologic marker for heavy in utero ethanol exposure: a case report. Ther Drug Monit. 1999, 21, 644-646.
4. Ostrea EM Jr, Hernandez JD, Bielawski DM et al. Fatty acid ethyl esters in meconium: are they biomarkers of fetal alcohol exposure and effect? Alcohol Clin Exp Res. 2006, 30, 1152-1159.
5. Gareri J, Lynn H, Handley M, et al.. Prevalence of fetal ethanol exposure in a regional population-based sample by meconium analysis of fatty acid ethyl esters. Ther Drug Monit. 2008, 30, 239-245.
6. Pichini S, Pellegrini M, Gareri J, et al. Liquid chromatography-tandem mass spectrometry for fatty acid ethyl esters in meconium: assessment of prenatal exposure to alcohol in two European cohorts. J Pharm Biomed Anal. 2008, 48, 927-933.
7. Morini L, Marchei E, Pellegrini M, et al. Liquid chromatography with tandem mass spectrometric detection for the measurement of ethyl glucuronide and ethyl sulfate in meconium: new biomarkers of gestational ethanol exposure? Ther Drug Monit. 2008, 30, 725-732.
8. Pichini S, Morini L, Marchei E, et al. Ethylglucuronide and ethylsulfate in meconium to assess gestational ethanol exposure: preliminary results in two Mediterranean cohorts. Can J Clin Pharmacol. 2009, 16, e370-e375.
9. Hastedt M, Krumbiegel F, Gapert R, et al. Fatty acid ethyl esters (FAEEs) as markers for alcohol in meconium: method validation and implementation of a screening program for prenatal drug exposure. Forensic Sci Med Pathol. 2013, 9, 287-295.
10. Pichini S, Morini L, Pacifici R, et al. Development of a new immunoassay for the detection of ethyl glucuronide (EtG) in meconium: validation with authentic specimens analyzed using LC-MS/MS. Preliminary results. Clin Chem Lab Med. 2014, 52, 1179-1185.
11. Abernethy C, McCall KE, Cooper G, et al. Determining the pattern and prevalence of alcohol consumption in pregnancy by measuring biomarkers in meconium. Arch Dis Child Fetal Neonatal Ed. 2018, 103, F216-F220.
12. Woźniak MK, Banaszkiewicz L, Aszyk J, et al. Development and validation of a method for the simultaneous analysis of fatty acid ethyl esters, ethyl sulfate and ethyl glucuronide in neonatal meconium: application in two cases of alcohol consumption during pregnancy. Anal Bioanal Chem. 2021, 413, 3093-3105.
13. Derauf C, Katz AR, Easa D. Agreement between maternal self-reported ethanol intake and tobacco use during pregnancy and meconium assays for fatty acid ethyl esters and cotinine. Am J Epidemiol. 2003, 158, 705-709.
14. Garcia-Algar O, Kulaga V, Gareri J, et al. Alarming prevalence of fetal alcohol exposure in a Mediterranean city. Ther Drug Monit. 2008, 30, 249-254.
15. Pichini S, Garcia-Algar O, Klein J, et al. FAEEs in meconium as biomarkers of maternal drinking habit during pregnancy. Birth Defects Res A Clin Mol Teratol. 2009, 85, 230; author reply 231-232.
16. Bakhireva LN, Savage DD. Focus on: biomarkers of fetal alcohol exposure and fetal alcohol effects. Alcohol Res Health. 2011, 34, 56–63.
17. Zelner I, Shor S, Lynn H, et al. Clinical use of meconium fatty acid ethyl esters for identifying children at risk for alcohol-related disabilities: the first reported case. J Popul Ther Clin Pharmacol. 2012, 19, e26-31.
18. Pichini S, Marchei E, Vagnarelli F, et al. Assessment of prenatal exposure to ethanol by meconium analysis: results of an Italian multicenter study. Alcohol Clin Exp Res. 2012, 36, 417-424.
19. Manich A, Velasco M, Joya X, et al. Validez del cuestionario de consumo materno de alcohol para detectar la exposición prenatal [Validity of a maternal alcohol consumption questionnaire in detecting prenatal exposure]. An Pediatr (Barc). 2012, 76, 324-328.
20. Memo L, Gnoato E, Caminiti S, et al. Fetal alcohol spectrum disorders and fetal alcohol syndrome: the state of the art and new diagnostic tools. Early Hum Dev. 2013, 89, S40-3.
21. Joya X, Marchei E, Salat-Batlle J, et al. Fetal exposure to ethanol: relationship between ethyl glucuronide in maternal hair during pregnancy and ethyl glucuronide in neonatal meconium. Clin Chem Lab Med. 2016, 54, 427-435.
22. Chiandetti A, Hernandez G, Mercadal-Hally M, et al. Prevalence of prenatal exposure to substances of abuse: questionnaire versus biomarkers. Reprod Health. 2017, 14, 137.
23. Gomez-Roig MD, Marchei E, Sabra S, et al. Maternal hair testing to disclose self-misreporting in drinking and smoking behavior during pregnancy. Alcohol. 2018, 67, 1-6.
24. Min MO, Minnes S, Momotaz H, et al. Fatty acid ethyl esters in meconium and substance use in adolescence. Neurotoxicol Teratol. 2021, 83,106946.
25. Maschke J, Roetner J, Goecke TW, et al. Prenatal Alcohol Exposure and the Facial Phenotype in Adolescents: A Study Based on Meconium Ethyl Glucuronide. Brain Sci. 2021, 11, 154.
26. La Maida N, Di Giorgi A, Pellegrini M, et al. Reduced prevalence of fetal exposure to alcohol in Italy: a nationwide survey. Am J Obstet Gynecol MFM. 2023, 25:100944.
Many thanks for an important study. It raises the question if a distinction between Reactive Attachment Disorder and autism based on the presumed aetiology can be sustained. The genetic aetiology of autism spectrum conditions was established on the impressive difference in concordance rates between MZ and DZ twins but there are epigenetic mechanisms which could explain this difference. MZ twins have exactly equal biochemical exposures before conception (preconception environment) whereas DZ twins do not. A number of environmental exposures in prior generations are associated with autism (Magdelena 2020, Golding 2021). A huge study of the MSSNG database finds a genetic cause involving different 134 genes in only 14% of autistic individuals (Trost 2023). What then is being acquired or inherited? If the answer is early childhood stress, the rise in autism need not be spurious.
Great work Nicki. I have long argued the need for more paediatric respirologists to service this expanding population. There is a shortage of pediatric pulmonologists [sic] in the USA and most in practice are graying. Now we have data to support this argument. Of greater concern is the (lack of) availability of home nursing support, placing tremendous stress on family. In part due to the “mass resignation” arising during and after the pandemic, there is critical shortage of trained personnel to care for such children in their homes. We have been forced to start weaning patients from mechanical ventilatory support – chiefly those with chronic lung disease of prematurity – while they are still hospitalized before initial NICU discharge. Indeed, we may have our first decannulation of one such child in the next few months! Thank you for undertaking this study and reporting the trend we all foresaw.
Pubertal staging is rarely needed in a general paediatric clinic and I wonder if there is a way to avoid the difficult issues in examining older children and young people.
I think the issues around chaperones are complex, as a male doctor, male patients often do not want a female nurse as a chaperone and on the whole peri-pubertal girls do not want to be examined at all by a male doctor.
My strategy, when needed, is therefore to ask older children and young people to let me know what they think their pubertal stage is - testicular size can be self-assessed using a standard orchidometer, all other changes can be described with reference to standard drawings from a growth chart.
I realise this is not evidence based practice but wonder if there is the possibility of a trial to compare paediatrician-assessed as opposed to self-assessed staging in non-specialist clinics?
Dear authors, the article made for some interesting reading especially as the current DKA ICP recommended by BSPED has now been in force for almost 2 years. It provides some perspective on whether the difference in liberalized vs conservative management is clinically significant or otherwise. Our question relates to whether the authors found any data in the studies regarding change in osmolarity / rate of rise of sodium which are early predictors for risk of cerebral oedema.
By excluding all deaths, it is possible that a significant number of high-cost high-need patients were missed? Some deaths will follow a prolonged admission and care may have been escalated, for example to PICU, prior to death.
Dear editor, we read with interest the randomised controlled trial by Borgström et al.1 showing the lack of effectiveness of daytime urotherapy as first-line treatment of nocturnal enuresis. While the study has the remarkable point of strength of a prospective trial with a control, we take exception with some of the authors’ statements, and believe that some limits should be acknowledged.
Reduction of enuresis frequency was evaluated after 7 and 8 weeks since the beginning of the study while previous studies showed effectiveness for longer treatments, lasting four months, with a 60% success rate2. While the authors acknowledge this difference they simply state that a longer duration would disqualify the therapy as a first-line choice anyway, increasing the risks of drop out. We believe that this is, as the author state in the discussion, simply their view, which is not based on any evidence. The length of a treatment should not necessarily rule out it as a first line option, especially when weighted against the costs of other options, specifically unpleasantness of the alarm and possible adverse effects of desmopressin. As a matter of fact, it could be speculated that 8 weeks are a too short period in a physiological perspective to develop different voiding patterns after years of an enuretic bladder function.
Moreover, patients’ follow-up consisted only in contact by phone after 2 and 6 weeks, without clinical examination, and this could have contributed t...
Dear editor, we read with interest the randomised controlled trial by Borgström et al.1 showing the lack of effectiveness of daytime urotherapy as first-line treatment of nocturnal enuresis. While the study has the remarkable point of strength of a prospective trial with a control, we take exception with some of the authors’ statements, and believe that some limits should be acknowledged.
Reduction of enuresis frequency was evaluated after 7 and 8 weeks since the beginning of the study while previous studies showed effectiveness for longer treatments, lasting four months, with a 60% success rate2. While the authors acknowledge this difference they simply state that a longer duration would disqualify the therapy as a first-line choice anyway, increasing the risks of drop out. We believe that this is, as the author state in the discussion, simply their view, which is not based on any evidence. The length of a treatment should not necessarily rule out it as a first line option, especially when weighted against the costs of other options, specifically unpleasantness of the alarm and possible adverse effects of desmopressin. As a matter of fact, it could be speculated that 8 weeks are a too short period in a physiological perspective to develop different voiding patterns after years of an enuretic bladder function.
Moreover, patients’ follow-up consisted only in contact by phone after 2 and 6 weeks, without clinical examination, and this could have contributed to poor effectiveness of urotherapy too.
Lastly and above all, the authors considered daytime incontinence and voiding dysfunction among the exclusion criteria of the study, but it is well known that many enuretic children present daytime symptoms too in up to 90% of cases2 or bladder dysfunction even with enuresis as the only detectable symptom.3 These disorders, once identified, must be treated because they can lead to urological dysfunctions in adulthood4 and behavioural therapy still represents a cornerstone of treatment. We believe that this is a further reason why urotherapy should not be disqualified as a first-line treatment only without the evidence of long term treatment data.
In conclusion, we suggest that daytime urotherapy studies need to be carried out for longer periods to confirm or rule out its effectiveness. Until then urotherapy should not be considered an alternative choice to alarm therapy and pharmacological treatment but a complementary one, in order to obtain a global approach to nocturnal enuresis in children.
Bibliography
1. Borgström M, Bergsten A, Tunebjer M, et al. Daytime urotherapy in nocturnal enuresis: a randomised, controlled trial. Archives of Disease in Childhood Published Online First: 24 January 2022. doi: 10.1136/archdischild-2021-323488
2. Pennesi M, Pitter M, Bordugo A, Minisini S, Peratoner L. Behavioral therapy for primary nocturnal enuresis. J Urol. 2004; 171(January):408-410. doi:10.1097/01.ju.0000097497.75022.e8
3. Yeung CK, Chiu HN, Sit FKY. Bladder dysfunction in children with refractory monosymptomatic primary nocturnal enuresis. J Urol. 1999; 162:1049-1055.
4. Bower WF, Sit FKY, Yeung CK. Nocturnal Enuresis in Adolescents and Adults is Associated With Childhood Elimination Symptoms. J Urol. 2006; 176(October):1771-1775. doi:10.1016/j.juro.2006.04.087
re Diagnosing urinary tract infection in children: time to ditch the pad?
Harkensee C, Clennett J, Wilkinson S, et al
Arch Dis Child 2021; 106: 935-936
We read with interest the article by Harkensee et al, (1) suggesting that the urinary collection pad (UCP) no longer had a role in obtaining samples for diagnosis of urinary tract infections (UTI). Whilst it is well established that there is an unacceptably high rate of contamination with UCPs making them unsuitable for microbiological culture, and that the preferred (non-invasive) method for obtaining a sample for culture is by 'clean catch' +/- stimulation or Quick-Wee method, we would suggest that the UCP has a role in screening for UTI, by dipstick analysis of the aspirated pad sample for leucocyte esterase (LE) and nitrites (2). It would be useful, in a paediatric 'acute referral clinic' or Emergency Department, in infants or children, with non-specific abdominal pain, or fever without a focus, where a combination of a negative test for both LE and nitrites can be reasonably used to exclude UTI, and equally a positive LE and nitrite result would indicate a high likelihood of a UTI and the need to obtain a 'clean catch' or catheter specimen for microbiological analysis (3). The advantages of the UCP are that it allows 'point of care' dipstick analysis with inf...
re Diagnosing urinary tract infection in children: time to ditch the pad?
Harkensee C, Clennett J, Wilkinson S, et al
Arch Dis Child 2021; 106: 935-936
We read with interest the article by Harkensee et al, (1) suggesting that the urinary collection pad (UCP) no longer had a role in obtaining samples for diagnosis of urinary tract infections (UTI). Whilst it is well established that there is an unacceptably high rate of contamination with UCPs making them unsuitable for microbiological culture, and that the preferred (non-invasive) method for obtaining a sample for culture is by 'clean catch' +/- stimulation or Quick-Wee method, we would suggest that the UCP has a role in screening for UTI, by dipstick analysis of the aspirated pad sample for leucocyte esterase (LE) and nitrites (2). It would be useful, in a paediatric 'acute referral clinic' or Emergency Department, in infants or children, with non-specific abdominal pain, or fever without a focus, where a combination of a negative test for both LE and nitrites can be reasonably used to exclude UTI, and equally a positive LE and nitrite result would indicate a high likelihood of a UTI and the need to obtain a 'clean catch' or catheter specimen for microbiological analysis (3). The advantages of the UCP are that it allows 'point of care' dipstick analysis with information to guide clinical decision-making immediately, is passive with minimal parental effort and disruption to the child, there is less likelihood of missing a sample (compared with 'clean catch') and is the preferred collection method of parents.
Perhaps, it's not time to ditch the pad: pads have a place!
Mervyn S Jaswon
James Diviney
Dept of Paediatrics, Whittington Hospital, London1.Diagnosing urinary tract infection in children: time to ditch the pad?
1.Diagnosing urinary tract infection in children: time to ditch the pad?
Clennett J, Wilkinson S, et al Arch Dis Child 2021; 106: 935-936
2. Urine collection methods and dipstick testing in non-toilet-trained children.
Diviney J, Jaswon M S, Pediatric Nephrology 2021; 36; 1697-1708
3. Clinical effectiveness and cost-effectiveness of tests for the diagnosis and investigation of UTI in children: a systematic review and economic model.
Whiting P, Westwood M, et al HEalth Technol Assess 10:iii-iv, xi-xiii" "
Child mortality in Europe dropped considerably in the first year of the pandemic, but since mid-2021 it is increasing considerably, as the data from the euromomo registry suggest. https://www.euromomo.eu/graphs-and-maps/ I first thought that Corona "saves children´s life" (for an intolerable expense), but now the contrary is true. While by the end of 2020 almost 400 Children (0-14) less died in the participating countries, excess mortality in Europa was about 500 Children at the end of 2021. So it was to early to draw conclusions.
We read with great interest recent study by Vergnano et al.1 investigating the epidemiology, age at infection, clinical characteristics, and outcome of listeria infection in the young infant. We congratulate the authors on providing a novel and interesting study that is relevant to the UK population and agree that the empirical use of amoxicillin in the paediatric infant should be reconsidered given the conclusions of their data.
However, when considering how we might be able to incorporate your novel findings into our centres practice, we required further clarification on table 2. The table describes increased oxygen requirement/respiratory support in 2/27 infants and yet, within results, report a prevalence of increased oxygen requirement/respiratory support of 89%. Furthermore, hypotension requiring inotropes is reported to occur in 4/27 infants but has a reported prevalence of 115%. These reported data appear to be miscalculated.
Clinical identification of invasive listeriosis through the understanding of symptoms within the infant is a key finding of this study given its poor description within the current literature2. We conducted a focused literature search and found scarce information on infant symptom prevalence; one notable exception includes the MONALISA study by Charlier et al.3 which recorded detailed clinical features (appendix p 21). Early diagnosis of invasive listeriosis has been demonstrated to have key prognostic value...
We read with great interest recent study by Vergnano et al.1 investigating the epidemiology, age at infection, clinical characteristics, and outcome of listeria infection in the young infant. We congratulate the authors on providing a novel and interesting study that is relevant to the UK population and agree that the empirical use of amoxicillin in the paediatric infant should be reconsidered given the conclusions of their data.
However, when considering how we might be able to incorporate your novel findings into our centres practice, we required further clarification on table 2. The table describes increased oxygen requirement/respiratory support in 2/27 infants and yet, within results, report a prevalence of increased oxygen requirement/respiratory support of 89%. Furthermore, hypotension requiring inotropes is reported to occur in 4/27 infants but has a reported prevalence of 115%. These reported data appear to be miscalculated.
Clinical identification of invasive listeriosis through the understanding of symptoms within the infant is a key finding of this study given its poor description within the current literature2. We conducted a focused literature search and found scarce information on infant symptom prevalence; one notable exception includes the MONALISA study by Charlier et al.3 which recorded detailed clinical features (appendix p 21). Early diagnosis of invasive listeriosis has been demonstrated to have key prognostic value in the literature4. Consequently, we submit that clearly described clinical presentations, and an understanding of their respective prevalence, could reduce the high mortality associated with invasive listeriosis3 and improve patient outcomes in the future.
Given the relative lack of understanding and the debate within the literature relating to the symptomatic presentation and clinical picture of listeria infection in the infant, especially in a UK population, your article has the potential to clarify clinical signs of useful predictive value. We would be very grateful for clarification on this matter to incorporate into our own practice.
References
1. Vergnano S, Godbole G, Simbo A, et al. Listeria infection in young infants: results from a national surveillance study in the UK and Ireland. Archives of Disease in Childhood 2021;106(12):1207-10. doi: 10.1136/archdischild-2021-321602
2. de Noordhout CM, Devleesschauwer B, Angulo FJ, et al. The global burden of listeriosis: a systematic review and meta-analysis. The Lancet Infectious Diseases 2014;14(11):1073-82. doi: https://doi.org/10.1016/S1473-3099(14)70870-9
3. Charlier C, Perrodeau É, Leclercq A, et al. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study. The Lancet Infectious Diseases 2017;17(5):510-19. doi: https://doi.org/10.1016/S1473-3099(16)30521-7
4. Hof H. An update on the medical management of listeriosis. Expert Opinion on Pharmacotherapy 2004;5(8):1727-35. doi: 10.1517/14656566.5.8.1727
The importance of objective assessment of prenatal exposure to alcohol through measurement of biomarkers in meconium
Oscar Garcia-Algar1,2,3*, Luigi Tarani4, Francesco Paolo Busardò5, Simona Pichini3,5, Emilia Marchei5
1. Neonatology Unit, Hospital Clinic-Maternitat, ICGON, BCNatal, Barcelona Centre for Maternal Foetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clínic, Barcelona, Spain
2. Department de Cirurgia i Especialitats Mèdico-Quirúrgiques, Universitat de Barcelona, Barcelona, Spain
3. European Foetal Alcohol Spectrum Disorders Alliance (EUFASD), Stockholm, Sweden
4. Department of Pediatrics, Sapienza University of Rome, Rome, Italy
5. National Centre on Addiction and Doping, Istituto Superiore di Sanità, Rome, Italy
Dear Editor,
Show MoreWe read with attention the paper by Henderson et al. concerning comparison of confidential postnatal maternal interview and measurement of alcohol biomarkers in meconium (1). We would like to draw attention on their conclusion: “Fatty acid ethyl esters (FAEEs) and Ethylglucuronide (EtG) measured in meconium have low sensitivity and specificity for self-reported alcohol consumption after 20 weeks’ gestation in an unselected Scottish population and measurement of these alcohol biomarkers in meconium cannot currently be recommended for the identification of newborns at risk of Fetal Alcohol Spectrum Disorders (FASD).”
It has been more than 20 years since meconium analy...
Many thanks for an important study. It raises the question if a distinction between Reactive Attachment Disorder and autism based on the presumed aetiology can be sustained. The genetic aetiology of autism spectrum conditions was established on the impressive difference in concordance rates between MZ and DZ twins but there are epigenetic mechanisms which could explain this difference. MZ twins have exactly equal biochemical exposures before conception (preconception environment) whereas DZ twins do not. A number of environmental exposures in prior generations are associated with autism (Magdelena 2020, Golding 2021). A huge study of the MSSNG database finds a genetic cause involving different 134 genes in only 14% of autistic individuals (Trost 2023). What then is being acquired or inherited? If the answer is early childhood stress, the rise in autism need not be spurious.
Great work Nicki. I have long argued the need for more paediatric respirologists to service this expanding population. There is a shortage of pediatric pulmonologists [sic] in the USA and most in practice are graying. Now we have data to support this argument. Of greater concern is the (lack of) availability of home nursing support, placing tremendous stress on family. In part due to the “mass resignation” arising during and after the pandemic, there is critical shortage of trained personnel to care for such children in their homes. We have been forced to start weaning patients from mechanical ventilatory support – chiefly those with chronic lung disease of prematurity – while they are still hospitalized before initial NICU discharge. Indeed, we may have our first decannulation of one such child in the next few months! Thank you for undertaking this study and reporting the trend we all foresaw.
Pubertal staging is rarely needed in a general paediatric clinic and I wonder if there is a way to avoid the difficult issues in examining older children and young people.
I think the issues around chaperones are complex, as a male doctor, male patients often do not want a female nurse as a chaperone and on the whole peri-pubertal girls do not want to be examined at all by a male doctor.
My strategy, when needed, is therefore to ask older children and young people to let me know what they think their pubertal stage is - testicular size can be self-assessed using a standard orchidometer, all other changes can be described with reference to standard drawings from a growth chart.
I realise this is not evidence based practice but wonder if there is the possibility of a trial to compare paediatrician-assessed as opposed to self-assessed staging in non-specialist clinics?
Dear authors, the article made for some interesting reading especially as the current DKA ICP recommended by BSPED has now been in force for almost 2 years. It provides some perspective on whether the difference in liberalized vs conservative management is clinically significant or otherwise. Our question relates to whether the authors found any data in the studies regarding change in osmolarity / rate of rise of sodium which are early predictors for risk of cerebral oedema.
By excluding all deaths, it is possible that a significant number of high-cost high-need patients were missed? Some deaths will follow a prolonged admission and care may have been escalated, for example to PICU, prior to death.
Dear editor, we read with interest the randomised controlled trial by Borgström et al.1 showing the lack of effectiveness of daytime urotherapy as first-line treatment of nocturnal enuresis. While the study has the remarkable point of strength of a prospective trial with a control, we take exception with some of the authors’ statements, and believe that some limits should be acknowledged.
Reduction of enuresis frequency was evaluated after 7 and 8 weeks since the beginning of the study while previous studies showed effectiveness for longer treatments, lasting four months, with a 60% success rate2. While the authors acknowledge this difference they simply state that a longer duration would disqualify the therapy as a first-line choice anyway, increasing the risks of drop out. We believe that this is, as the author state in the discussion, simply their view, which is not based on any evidence. The length of a treatment should not necessarily rule out it as a first line option, especially when weighted against the costs of other options, specifically unpleasantness of the alarm and possible adverse effects of desmopressin. As a matter of fact, it could be speculated that 8 weeks are a too short period in a physiological perspective to develop different voiding patterns after years of an enuretic bladder function.
Moreover, patients’ follow-up consisted only in contact by phone after 2 and 6 weeks, without clinical examination, and this could have contributed t...
Show More26th January 2022
To the Editor
Archives of Disease in Childhood
re Diagnosing urinary tract infection in children: time to ditch the pad?
Harkensee C, Clennett J, Wilkinson S, et al
Arch Dis Child 2021; 106: 935-936
We read with interest the article by Harkensee et al, (1) suggesting that the urinary collection pad (UCP) no longer had a role in obtaining samples for diagnosis of urinary tract infections (UTI). Whilst it is well established that there is an unacceptably high rate of contamination with UCPs making them unsuitable for microbiological culture, and that the preferred (non-invasive) method for obtaining a sample for culture is by 'clean catch' +/- stimulation or Quick-Wee method, we would suggest that the UCP has a role in screening for UTI, by dipstick analysis of the aspirated pad sample for leucocyte esterase (LE) and nitrites (2). It would be useful, in a paediatric 'acute referral clinic' or Emergency Department, in infants or children, with non-specific abdominal pain, or fever without a focus, where a combination of a negative test for both LE and nitrites can be reasonably used to exclude UTI, and equally a positive LE and nitrite result would indicate a high likelihood of a UTI and the need to obtain a 'clean catch' or catheter specimen for microbiological analysis (3). The advantages of the UCP are that it allows 'point of care' dipstick analysis with inf...
Show MoreChild mortality in Europe dropped considerably in the first year of the pandemic, but since mid-2021 it is increasing considerably, as the data from the euromomo registry suggest. https://www.euromomo.eu/graphs-and-maps/ I first thought that Corona "saves children´s life" (for an intolerable expense), but now the contrary is true. While by the end of 2020 almost 400 Children (0-14) less died in the participating countries, excess mortality in Europa was about 500 Children at the end of 2021. So it was to early to draw conclusions.
Dear Editor,
We read with great interest recent study by Vergnano et al.1 investigating the epidemiology, age at infection, clinical characteristics, and outcome of listeria infection in the young infant. We congratulate the authors on providing a novel and interesting study that is relevant to the UK population and agree that the empirical use of amoxicillin in the paediatric infant should be reconsidered given the conclusions of their data.
However, when considering how we might be able to incorporate your novel findings into our centres practice, we required further clarification on table 2. The table describes increased oxygen requirement/respiratory support in 2/27 infants and yet, within results, report a prevalence of increased oxygen requirement/respiratory support of 89%. Furthermore, hypotension requiring inotropes is reported to occur in 4/27 infants but has a reported prevalence of 115%. These reported data appear to be miscalculated.
Clinical identification of invasive listeriosis through the understanding of symptoms within the infant is a key finding of this study given its poor description within the current literature2. We conducted a focused literature search and found scarce information on infant symptom prevalence; one notable exception includes the MONALISA study by Charlier et al.3 which recorded detailed clinical features (appendix p 21). Early diagnosis of invasive listeriosis has been demonstrated to have key prognostic value...
Show MorePages