Areca-Nut Abuse and Neonatal Withdrawal Syndrome

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Areca-Nut Abuse and Neonatal Withdrawal Syndrome
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  DOI: 10.1542/peds.2005-0281; srcinally published online December 15, 2005; Pediatrics Simona Pichini and Antonio MurMaria Angeles López-Vilchez, Veronica Seidel, MagÍ Farré, Oscár García-Algar, Areca-Nut Abuse and Neonatal Withdrawal Syndrome   http://pediatrics.aappublications.org/content/early/2005/12/15/peds.2005-0281.citation located on the World Wide Web at: The online version of this article, along with updated information and services, is   of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2005 by the American Academy published, and trademarked by the American Academy of Pediatrics, 141 Northwest Pointpublication, it has been published continuously since 1948. PEDIATRICS is owned, PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly  by guest on June 8, 2013pediatrics.aappublications.orgDownloaded from   EXPERIENCE&REASON Areca-Nut Abuse and Neonatal WithdrawalSyndrome MariaAngelesLo´pez-Vilchez,MD a,b ,VeronicaSeidel,MD a,b ,MagI´Farre´,MD,PhD c ,Osca´rGarcı´a-Algar,MD,PhD a,b ,SimonaPichini,PhD d ,AntonioMur,MD,PhD a,b a Neonatology Unit, Service of Pediatrics, Hospital Universitari del Mar,  b Departments of Pediatrics, Gynecology, and Obstetrics and Preventive Medicine, and c Pharmacology Unit, Institut Municipal d  Investigacio´ Me`dica, Universitat Auto`noma de Barcelona, Barcelona, Spain;  d Drug Research and Evaluation Department, IstitutoSuperiore di Sanita`, Rome, Italy Financial Disclosure: the authors have indicated that they have no relationships relevant to this article to disclose. ABSTRACT Areca-nut chewing occurs widely in South Asia and the Indian subcontinent. Here we present a case of neonatalwithdrawal syndrome in an infant born to a woman who was a chronic areca-nut user. Arecoline, the principalneuroactive alkaloid in areca nuts, was found in the mother’s placenta. B ETEL-QUID CHEWING IS  common in some areas ofAsia and among immigrant populations living inEurope and North America. 1 It is the fourth most com-monly used drug worldwide after tobacco, alcohol, andcaffeine. 2 Betel is composed of the sliced nut (areca nutor betel nut) of the areca palm (  Areca catechu ), the leaf ofthe betel pepper ( Piper betle ), and lime. 2 Because of the“positive” effects attributed to betel use, some womencontinue to consume this preparation during pregnancy,especially to prevent morning sickness. 3 Because of themigration flux of Asian people to industrialized coun-tries, European hospitals are being faced with pregnantAsian women who consume betel nut during pregnancyand possibly with newborns prenatally exposed to thisdrug. 4 Here we report a case of neonatal withdrawalsyndrome in an infant born to a woman who was achronic areca-nut user. CASEREPORT A female newborn presented with irritability and hyper-tonia 48 hours after a eutocic delivery at 38 weeks ofgestation (Apgar scores at 1, 5, and 10 minutes: 9, 10,and 10, respectively). The infant was born to a healthy38-year-old mother who was an immigrant from Bang-ladesh and came to the obstetrics emergency departmentfor childbirth. The mother reported no toxic habits andno visits to any obstetrician during gestation. The in-fant’s weight was 3090 g, her length was 49 cm, and herhead circumference was 34 cm. She was admitted to thesection of neonatology because of the risk for neonatalinfection of vertical transmission re1ated to the mother’suncontrolled pregnancy. Results of routine laboratorytesting including serum chemistry and electrolytes, se-rologies (HIV, hepatitis C virus, hepatitis B surface anti-gen, toxoplasma, rubella, and syphilis), hematology, andurinalysis were within normal limits or negative. Urinetesting of the mother and the infant for drugs of abuse Key Words:  areca nut, arecoline, neonatal withdrawal syndrome, addiction,pregnancy, newbornwww.pediatrics.org/cgi/doi/10.1542/peds.2005-0281doi:10.1542/peds.2005-0281 Accepted for publication Jul 8, 2005Address correspondence to Maria Angeles Lo´pez-Vilchez, MD, Neonatology Unit, Service of Pediatrics, Hospital Universitari del Mar, Passeig Marı´tim 25–29, E-08003 Barcelona, Spain.E-mail: 93488@imas.imim.esPEDIATRICS (ISSN 0031 4005). Copyright © 2005 by the American Academy of Pediatrics PEDIATRICS Volume 117, Number 1, January 2006  e129  by guest on June 8, 2013pediatrics.aappublications.orgDownloaded from   inc1uding opiates, cocaine, cannabis, amphetamines, benzodiazepines, barbiturates, and ethanol producednegative results. Neonatal abstinence syndrome was as-sessed every 3 hours by using the scoring system ofKaltenbach and Finnegan. 5 An ultrasonographic study ofthe brain through the anterior fontanelle was unreveal-ing. On the third day of life, treatment with phenobar- bital (intramuscular bolus of 15 mg/kg followed by 8mg/kg per day orally) was started because Finneganscores were   8. The mother showed a brownish-reddiscoloration of the oral mucosa and tongue (see Figs 1and 2), and it became known that she was a chronicareca chewer even during pregnancy. After 5 days oftreatment with phenobarbital, withdrawal symptoms inthe infant improved. Suspected fetal exposure was con-firmed by detection of arecoline in the placenta (0.012  g/g of placental tissue), the only biological matrix avail-able at the time of the analysis, by high-performanceliquid chromatography/electrospray quadrupole massspectrometry. 4 The diagnosis of neonatal abstinence syn-drome resulting from maternal consumption of arecanut was established. DISCUSSION It is estimated that 600 million people worldwide chewareca nut in some form. The betel-nut quid or pan, apiece of areca nut chewed alone or mixed with tobaccoand slaked lime (calcium hydroxide) wrapped in betel-vine leaf, is widely used as a stimulant (because of thecholinergic agent, arecoline) or a relaxant (because ofthe arecaidine and guvacine) as an endemic habitthroughouttheIndiansubcontinent,largepartsofSouthAsia, and Melanesia. 1,2 This habit is also apparent inmigrant communities from these areas. Studies on Asiancommunities living in the United Kingdom (almost 3%of the total United Kingdom population) show that be-tel-quid chewing habits are highly diffused among theUnited Kingdom Bangladeshi population (79–96%),moderate among mixed Asian groups (27–47%), andprevalent among Asian adolescents (from 22% to 77%depending on ethnic group). 6 Betel-quid chewing has been claimed to produce asense of well-being, euphoria, warm sensation of the body, sweating, salivation, palpitations, heightenedalertness, and increased capacity to work. 7 These effectsseem to be habit related and dose dependent. Addictionand withdrawal syndrome were also observed togetherwith cholinergic toxicity, toxic psychosis, and neurologiccomplications. 7,8 Arecoline, the areca-nut principal alka-loid, acts as an agonist at the muscarinic and nicotinicacetylcholine receptors and seems to be responsible forthe central cholinergic stimulation. 7,8 Both arecoline andarecaidine increased the release of catecholamines fromchromaffin cells. Betel-quid chewing was found to pro-duce an elevation in the plasma concentrations of nor-epinephrine and epinephrine, causing sympathetic acti-vation. 7 Acute significant toxicity after betel-nut chewing has been reported as a rare event. From a total of 42 000calls received at the Taiwan Poison Control Center, therewere 17 cases that were possibly related to betel con-sumption. The majority of patients (11 of 17) developedsymptoms of mild to moderate severity (nausea, vomit-ing, dizziness, tachycardia/palpitations); however, se-vere symptoms such as coma, respiratory failure, andacute myocardial infarction and related manifestationswere also reported (6 cases). 9 Treatment of betel-nutoverdose is symptomatic with supportive measures.Routine use of atropine is not recommended but could be administered in cases of severe acute cholinergic cri-sis. 3 Chewing areca nut on an habitual basis is known to be deleterious to human health, especially in relation tothe increased risk for developing oral cancer. 10 Areca-nut FIGURE1 View of the mother’s brownish-red tongue. FIGURE2 View of the mother’s brownish-red gums. e130  LO´PEZ-VILCHEZ, et al  by guest on June 8, 2013pediatrics.aappublications.orgDownloaded from   withdrawalhasbeenidentifiedonlyinheavyusers, 11  butas far as we are aware, neonatal withdrawal syndromehas not been reported previously. This case adds evi-dence to adverse pregnancy outcome associated withchronic areca-nut exposure. 12 In pregnant women who are immigrants from Asiancountries, the possibility of areca-nut use must be inves-tigated by asking about toxic habits and by checking forred stains on the teeth, gingiva, and oral mucosa. REFERENCES 1. Gupta PC, Ray CS. Epidemiology of betel quid usage.  Ann Acad  Med Singapore.  2004;33(4 suppl):31–362. Gupta PC, Warnakulasuriya S. Global epidemiology of arecanut usage.  Addict Biol.  2002;7:77–833. Nelson BS, Heischober B. Betel nut: a common drug used bynaturalized citizens from India, Far East Asia, and the SouthPacific Islands.  Ann Emerg Med.  1999;34:238–2434. Pichini S, Pellegrini M, Pacifici R, et al. Quantification of areco-line (areca nut alkaloid) in neonatal biological matrices byhigh-performance liquid chromatography/electrospray quad-rupole mass spectrometry.  Rapid Commun Mass Spectrom.  2003;17:1958–19645. Kaltenbach K, Finnegan LP. Neonatal abstinence syndrome,pharmacotherapy and developmental outcome.  Neurobehav Toxicol Teratol.  1986;8:353–3556. Warnakulasuriya S. Areca nut use following migration and itsconsequences.  Addict Biol.  2002;7:127–1327. Chu NS. Effects of betel chewing on the central and autonomicnervous system.  J Biomed Sci.  2001;8:229–2368. Winstock A. Areca nut-abuse liability, dependence and publichealth.  Addict Biol.  2002;7:133–1389. Deng JF, Ger J, Tsai WJ, Kao WF, Yang CC. Acute toxicities of betel nut: rare but probably overlooked events.  J Toxicol ClinToxicol.  2001;39:355–36010. Trivedy CR, Craig G, Warnakulasuriya S. The oral health con-sequences of chewing areca nut.  Addict Biol.  2002;7:115–12511. Winstock AR, Trivedy CR, Warnakulasuriya S, Peters TJ. Adependency syndrome related to areca nut use: some medicaland psychological aspects among areca nut users in the Gujaratcommunity in the UK.  Addict Biol.  2000;5:173–17912. Yang MS, Chung TC, Yang MI, Hsu TY, Ko YC. Betel quidchewing and risk of adverse birth outcomes among absrcinesin eastern Taiwan.  J Toxicol Environ Health A.  2001;64:465–472 PEDIATRICS Volume 117, Number 1, January 2006  e131  by guest on June 8, 2013pediatrics.aappublications.orgDownloaded from   DOI: 10.1542/peds.2005-0281; srcinally published online December 15, 2005; Pediatrics Simona Pichini and Antonio MurMaria Angeles López-Vilchez, Veronica Seidel, MagÍ Farré, Oscár García-Algar, Areca-Nut Abuse and Neonatal Withdrawal Syndrome   ServicesUpdated Information &   /peds.2005-0281.citationhttp://pediatrics.aappublications.org/content/early/2005/12/15including high resolution figures, can be found at: Citations   /peds.2005-0281.citation#related-urlshttp://pediatrics.aappublications.org/content/early/2005/12/15This article has been cited by 1 HighWire-hosted articles: Permissions & Licensing  mlhttp://pediatrics.aappublications.org/site/misc/Permissions.xhttables) or in its entirety can be found online at: Information about reproducing this article in parts (figures,  Reprints  http://pediatrics.aappublications.org/site/misc/reprints.xhtmlInformation about ordering reprints can be found online:rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.Grove Village, Illinois, 60007. Copyright © 2005 by the American Academy of Pediatrics. All and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elkpublication, it has been published continuously since 1948. PEDIATRICS is owned, published, PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly  by guest on June 8, 2013pediatrics.aappublications.orgDownloaded from 
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