The Natural History of Jaundice in PredominantlyBreastfed Infants

WHAT’S KNOWN ON THIS SUBJECT: Newborn infants who arepredominantly breastfed are much more likely to developprolonged hyperbilirubinemia than those fed formula, but theprevalence of prolonged hyperbilirubinemia in a largely white,North American, breastfed population is unknown.

WHAT THIS STUDY ADDS: Practitioners can be reassured that it isnormal for 20% to 30% of predominantly breastfed infants to bejaundiced at age 3 to 4 weeks and for 30% to 40% of these infantsto have bilirubin levels $5 mg/dL.

abstractBACKGROUND AND OBJECTIVES: Breastfed newborns are more likelyto develop prolonged hyperbilirubinemia than those fed formula, butthe prevalence of prolonged hyperbilirubinemia in a largely white,North American breastfed population is unknown. In this population,we documented the natural history of jaundice and the prevalence ofprolonged hyperbilirubinemia, and we evaluated the utility of assess-ing the cephalocaudal progression of jaundice in office-basedpractices.

METHODS: We measured transcutaneous bilirubin (TcB) levels duringthe first month in 1044 predominantly breastfed infants$35 weeks ofgestation and assigned a cephalocaudal zone score to each infant atthe time of the TcB measurement.

RESULTS: TcB level was $5 mg/dL in 43% of infants at age 21 6 3days and 34% were clinically jaundiced. At 28 6 3 days, the TcB was$5 mg/dL in 34% and 21% were jaundiced. There was a strongcorrelation between the TcB level and the jaundice zone score, butthere was a wide range of TcB levels associated with each score.

CONCLUSIONS: Practitioners can be reassured that it is normal for20% to 30% of predominantly breastfed newborns to be jaundicedat age 3 to 4 weeks and for 30% to 40% of these infants to have bilirubinlevels $5 mg/dL. The jaundice zone score does not provide anaccurate assessment of the bilirubin level, but a score of zero(complete absence of jaundice) suggests that the level is unlikely tobe .12.9 mg/dL, whereas a score of $4 usually predicts a level of$10 mg/dL. Pediatrics 2014;134:e340–e345

AUTHORS: M. Jeffrey Maisels, MB, BCh, DSc, Sarah Clune,DO, Kimberlee Coleman, MD, Brian Gendelman, MD, AdaKendall, MD, Sharon McManus, DO, and Mary Smyth, MD

Department of Pediatrics, Oakland University William BeaumontSchool of Medicine, Beaumont Children’s Hospital, Royal Oak,Michigan

KEY WORDSnewborn jaundice, breastfeeding, prolonged jaundice, naturalhistory, cephalocaudal progression

ABBREVIATIONSCI—confidence intervalJZS—jaundice zone scoreTcB—transcutaneous bilirubinTSB—total serum bilirubin

Dr Maisels conceptualized and designed the study, draftedthe initial manuscript, and revised the manuscript criticallyfor important intellectual content. Drs Clune, Coleman,Gendelman, Kendall, McManus, and Smyth participated in theconceptualization and design; they, or their delegates, examinedall of the patients and supervised the collection of data at eachsite; and they reviewed the article for important intellectualcontent. All authors approved the final manuscript as submitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2013-4299

doi:10.1542/peds.2013-4299

Accepted for publication May 2, 2014

Address correspondence to M. Jeffrey Maisels, MB, BCh, DSc,Beaumont Children’s Hospital, 3535 West 13 Mile Rd, Royal Oak, MI48073. E-mail: jmaisels@beaumont.edu

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2014 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they haveno financial relationships relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: M. Jeffrey Maisels has actedas a consultant for Draeger Medical Inc; the other authors haveindicated they have no potential conflicts of interest to disclose.

e340 MAISELS et al by guest on September 7, 2015pediatrics.aappublications.orgDownloaded from

The association between breastfeedingand jaundice is well-known and well-documented,1 as is the observationthat breastfed infants are much morelikely than formula fed infants to havejaundice that persists for severalweeks or months after the infant’sbirth.1–6 Investigators in Turkey5 andTaiwan6 found that, at 4 weeks, some20% to 28% of exclusively breastfedinfants had total serum bilirubin (TSB)levels $5 mg/dL, but no similar dataexist for infants in the United States.The cephalocaudal progression ofjaundice is also well documented,7–11

as is the use of a score to documentthis progression,7,10,12 but the utility ofthis score in documenting a range ofpossible TSB levels, or as a predictor ofsubsequent hyperbilirubinemia, hasbeen evaluated only in hospitalizednewborns and not in infants seen inoffice practice.

Our objective was to document the nat-ural historyof jaundice in thefirstmonthin a predominantly breastfed, whitepopulation of newborns, to identify theprevalence of prolonged hyperbiliru-binemia and the clinical observation ofjaundice in these infants, and toevaluatethe utility of the cephalocaudal zonescoreasascreenforhyperbilirubinemiain office-based pediatric practice.

METHODS

From September 2010 to August 2013we obtained a convenience sample of1732 transcutaneous bilirubin (TcB)measurements on 1044 predominantlybreastfed infants $35 weeks of ges-tation. Some infants seen at follow-uphad repeated TcB measurements atseveral visits. These infants were caredfor in well-infant nurseries in southeastMichigan and followed in 5 pediatricoffice practices and thewell-infant clinicof the Beaumont Children’s Hospital. Weused the Konica Minolta Dräger AirShields JM-103 transcutaneous jaundicemeter (Draeger Medical, Telford, PA)

to measure the TcB. Three TcB mea-surements were obtained from themidsternum and averaged. In our pre-vious study of a mixed race populationwith 41% nonwhite infants,13 TcB mea-surements correlated well with TSB(r = 0.913) andmeasurements from thesternum correlated better with TSBmeasurements than TcB measure-ments from the forehead. Although wenormally use the highest of these 3measurements when screening new-borns for hyperbilirubinemia, for thepurpose of this study the 3 measure-ments were averaged and all TcB dataare presented as the average of 3measurements. Operational electronicchecks were performed daily as rec-ommended by the manufacturer toconfirm that the light output waswithinrange for both long and short wave-lengths of light.14 If the readings wereoutside of the range, the instrumentwas returned for recalibration.

We defined “predominantly breastfedinfants” as infants who received nomore than 1 formula feeding per day.All data recorded from days 3 to 28come from infants who were out-patients. To obtain data that representthe natural history of bilirubinemia inour study population, we also recordedthe TcB levels in 108 hospitalized, ex-clusively breastfed infants in the first 2days after birth. TcB measurementsare obtained daily on all infants in ournursery and are also obtained rou-tinely at follow-up office visits in eachof the participating office practices andthe hospital well-infant clinic. Office-based pediatricians and their nursingstaff were trained in the use of theKramer scale homunculus7 (Fig 1) andthe JM-103. At each office visit, the pe-diatrician assigned a Kramer cepha-locaudal score (hereinafter referred toas the “jaundice zone score” or JZS),and TcB levels were obtained by theoffice nurse, but the TcB measurementwas not available to the pediatrician at

the time the jaundice zone was scored.Jaundice was considered to be presentif the JZS was $1 (Fig 1).

The study was approved by the hospitalHuman Investigation Committee, whichwaved theneed forconsent, but parentswere providedwithwritten informationabout the study and could choose not toparticipate.

RESULTS

Demographic data are shown in Table 1and results in Table 2 and Figs 2 and 3.At 21 6 3 days, 20 of 59 infants (34%;95% confidence interval [CI]: 25%–45%) were jaundiced (JZS$1), and 33of 75 (44%; 95% CI: 33%–55%) had TcBlevels$5 mg/dL. At 286 3 days, 20 of94 (21%; 95% CI: 14%–31%) werejaundiced, and the TcB was $5 mg/dLin 36 of 106 (34%; 95% CI: 26%–43%).(The denominators for the presence ofjaundice are less than the number ofinfants seen because some infants didnot receive a JZS.) There was a strongcorrelation between themean TcB leveland the JZS (Fig 3; r = 0.722, P = .0000)and the correlation was equally strongat 14, 21, and 28 days and in nonwhiteinfants (P = .0000 in each case), butthere was a wide range of TcB levelsassociated with each grade. Neverthe-less, in 525 infants with a JZS of zero,the TcB was .12.9 mg/dL in only 4(0.8%; 95% CI: 0.2%–1.9%) with a rangeof 13.0 to 15.5 mg/dL and.15 mg/dL in1 (0.2%; 95% CI: 0.01%–1.2%). Forty-three infants had a JZS of 4 or 5. Onlyone of these infants (2.3%; 95% CI:0.01%–13.2%) had a TcB,10mg/dL. AllTSB measurements included a directbilirubin measurement and no infanthad an elevated direct bilirubin.

DISCUSSION

Prolonged Jaundice in theBreastfed Infant

Pediatriciansand familyphysicians,withsome regularity, see thriving breastfed

ARTICLE

PEDIATRICS Volume 134, Number 2, August 2014 e341 by guest on September 7, 2015pediatrics.aappublications.orgDownloaded from

infants who are still jaundiced at ages 3to 4 weeks and sometimes beyond but,to date, there are limited published dataon how often this phenomenon occurs.In Fig 2, we provide the first documen-tation, with percentiles, of the naturalhistory of bilirubinemia in a large pop-ulation of healthy, breastfeeding new-borns up to age 28 6 3 days. Kivlahanet al2 documented the natural historyof jaundice with mean TcB index meas-urements (the instrument used did notprovide a bilirubin measurement) in115 white and 25 African American in-fants for the first 21 days. The data did

not include percentiles or the propor-tion of infants with an elevated TSB orobserved jaundice. We could identifyonly 2 studies in which a population ofbreastfed infants was followed for atleast 4 weeks and in whom TSB levelswere measured in all infants. Changet al6 followed 125 Chinese breastfedinfants ($37 weeks) and found that28% had a TSB.5.9 mg/dL beyond age28 days. Tiker et al5 followed 282breastfed, term Turkish infants. At 1month, 57 (20%) had TSB levels .5mg/dL and 17 (6%) .10 mg/dL. Todate, there are no satisfactory datadocumenting the prevalence of ele-vated bilirubin levels or observed jaun-dice in a population of predominantlywhite, breastfed infants. Although, inour study, some 34% of infants at age286 3 days had TcB levels$5 mg/dL,on clinical observation alone (a JZSof $1), only 24% of these infants ap-peared jaundiced to an experiencedobserver.

Several mechanisms have been pro-posed to explain why breastfed infantsaremorelikely tobe jaundiced inthefirst7 to 10 days than those fed formula, but

an explanation forwhy breastfed infantsare more likely to have prolonged jaun-dicehasbeenelusive. Thefirst suggestedmechanism for this phenomenon camefrom the studies of Arias and Gartner15

who identified a progestational steroid,pregnane-3(a), 20(b)-diol in the milk ofmothers whose infants had prolongedhyperbilirubinemia. This steroid wasshown to inhibit bilirubin conjugationin vitro and was capable of producinghyperbilirubinemia when administeredto 2 healthy newborns,16 but subsequentstudies could not confirm these find-ings.17–19 The contemporary era of ge-netic diagnosis, however, has cast a newand fascinating light on the causes ofunexplained hyperbilirubinemia20,21 andprolonged breast milk jaundice is nowa condition for which in some infants,and perhaps the majority,6,22,23 there isa clear genetic pathogenesis charac-terized by polymorphisms of the UGT1A1gene.22,24 This is the gene that deter-mines the structure of the isoenzyme,uridine diphosphate glucuronosyl trans-ferase 1A1 (UGT1A1), that is responsiblefor bilirubin conjugation. There is awell-documented association betweenprolonged breast milk jaundice andexpression of the UGT1A1 promotervariant, UGT1A1*28,22 that is the causeof Gilbert syndrome in white infants,and the UGT1A1 coding sequence vari-ant, UGT1A1*6, that causes Gilbertsyndrome in East Asians.24 In Gilbertsyndrome, the monoconjugated biliru-bin fraction predominates over thediconjugated fraction25 and this en-hances the enterohepatic circulation ofbilirubin because hydrolysis of themonoglucuronide back to unconju-gated bilirubin occurs at rates 4 to 6times that of the diglucuronide.26 Fur-thermore, it has now been demon-strated, that in the presence of theUGT1A1*6 polymorphic mutation ofUGT1A1, the addition of pregnane-3(a),20(b)-diol will inhibit conjugation. Thismechanism could therefore explain pro-longed breast milk jaundice in some

TABLE 1 Study Population Demographics

Characteristics N %

Boy 526 50.4Girl 506 48.5Unknown 12 1.10RaceWhite 797 76.3African American 75 7.20East Asian 45 4.30Other/mixed 22 2.10Unknown 105 10.1

Gestation, wk,37 54 5.2037–42 945 90.5Unknown 45 4.30

FIGURE 1Homunculus used to assign JZS.

e342 MAISELS et al by guest on September 7, 2015pediatrics.aappublications.orgDownloaded from

Asian infants.27 Perhaps there is a similaradditive role for pregnane-3(a), 20(b)-diolin breast milk and Gilbert syndrome inwhite infants.

Cephalocaudal Progression

As illustrated in Fig 3, although there isa strong correlation between the TcBlevel and the JZS,10,28 there is a widerange of TcB levels associated witheach grade10,29,30 so that it is not pos-sible to provide an accurate visualestimate of a bilirubin level. Neverthe-less, this does not completely negatethe value of the JZS. In a mixed racial

population of term and late preterminfants, Keren et al10 found that if theJZS was 0 (complete absence of jaun-dice), there was a 99% probability thatsignificant hyperbilirubinemia wouldnot develop. In our population, if theJZS was 0, 99.2% of infants had a TSBlevel # 12.9 mg/dL. Thus, if a 4- or 5-day-old infant is examined in good light,and no jaundice seen, it is reasonableto rely on clinical judgment regardingthe need for a TSB level and subsequentfollow-up, but the same cannot be saidfor a newborn before discharge. Be-cause TSB levels that call for additional

evaluation or intervention are low inthe first 36 to 48 hours, the range ofvalues that corresponds to a JZS of 0(Fig 3) is simply too wide to allow ap-propriate follow-up decisions to bemade.31 A JZS of 2 to 5 at any agesuggests the need for a TcB or TSBmeasurement to determine if addi-tional investigation or intervention isnecessary.

The pathogenesis of the cephalocaudalprogression of jaundice has never beenfully explained. Purcell and Beeby32

measured the TcB, skin temperature,and capillary refill time at the forehead,

TABLE 2 TcB Bilirubin Levels

Age, d 1 2 3 7 6 3 14 6 3 21 6 3 28 6 3

N 58 115 208 841 306 75 106TcB mg/dL, mean

6 SD (range)4.7 6 2.7 (0–13.3) 9.2 6 3.2 (0–18.3) 11.1 6 3.8 (0–19.4) 9.1 6 4.4 (0–18.6) 5.4 6 4.0 (0–16.5) 4.9 6 4.2 (0–16.7) 3.8 6 3.7 (0–13.1)

TcB $5.0 mg/dL (%) 22 (38) 107 (93) 196 (94) 685 (81) 158 (52) 33 (43) 36 (34)TcB $7.5 mg/dL (%) 7 (12) 84 (73) 174 (83) 585 (70) 101 (33) 24 (32) 18 (17)TcB $10 mg/dL (%) 3 (5) 50 (43) 142 (68) 404 (48) 41 (13) 13 (17) 10 (9)TcB $12.9 mg/dL (%) 1 (2) 13 (11) 77 (37) 158 (19) 12 (2) 1 (1) 1 (0.9)

FIGURE 2TcB percentiles at each age. Numbers in parentheses are the number of measurements obtained at each age.

ARTICLE

PEDIATRICS Volume 134, Number 2, August 2014 e343 by guest on September 7, 2015pediatrics.aappublications.orgDownloaded from

sternum, lower abdomen, midthigh,and sole of the foot. They observeda similar cephalocaudal progression ofdecreasing TcB and skin temperatureand increasing capillary refill time,suggesting that the cephalocaudalprogression of jaundice is a conse-quence of better perfusion of the headand proximal parts of the body anddiminished capillary blood flow in dis-tal parts. Nevertheless, we found thatat 7, 14, 21, and 28 days, there was stilla strong correlation between the JZSand the TcB. We would anticipate thatby 14 days, at least, peripheral perfu-sion should be normal although thishas not been measured.

Most recently, Azzuqa and Watchko33

remind us to look at the eyes of jaun-

diced newborns. In their preliminarystudy, every one of 21 infants who hadscleral icterus had a TSB .15 mg/dL(range, 15.3–24 mg/dL). If confirmed,this should be a useful sign for identi-fying infants with significant hyper-bilirubinemia.

CONCLUSIONS

We provide the first data on the naturalhistory of bilirubinemia in a populationof predominantly breastfed, mainlywhite infants, for the first month afterbirth. The knowledge that, at 1 month,∼1:3 infants has a TcB $5 mg/dL and∼1:5 appears jaundiced, should be ofpractical value to practitioners whocare for newborns and reassuring tothe parents of infants who are still

jaundiced at age 4 weeks. We also showthat there is a strong relationship be-tween the cephalocaudal JZS and ris-ing bilirubin levels and that thisrelationship persists up to age 28 days.Although the range of values withineach zone is too large to allow an ac-curate determination of the actual bil-irubin value, a score of 0 is highlypredictive of a TcB value of,12.9mg/dL,and a score of $4 will usually predicta TcB of$10 mg/dL.

ACKNOWLEDGMENTSWe gratefully acknowledge the experthelp of Beth Kring, RN, Jeni Deridder,RN, and Dr Tanha Jansari, and DrsJon Watchko and Valerie Flahermanfor their review of this article.

FIGURE 3TcB levels corresponding toeach JZS. Bolddotsaremedian values. Numbers inparenthesesare thenumberof infants in each zone. There is astrongcorrelationbetween the JZSs and the TcB measurements (linear regression y = 2.9398x + 4.6778, r = 0.722, P = .0000).

e344 MAISELS et al by guest on September 7, 2015pediatrics.aappublications.orgDownloaded from

REFERENCES

1. Maisels MJ, Newman TB. The epidemiologyof neonatal hyperbilirubinemia. In: StevensonDK, Maisels MJ, Watchko JF, eds. Care of theJaundiced Neonate. New York, NY: McGrawHill; 2012:97–113

2. Kivlahan C, James EJP. The natural historyof neonatal jaundice. Pediatrics. 1984;74(3):364–370

3. Gourley GR, Kreamer B, Arend R. The effectof diet on feces and jaundice during thefirst 3 weeks of life. Gastroenterology.1992;103(2):660–667

4. Hall RT, Braun WJ, Callenbach JC, et al.Hyperbilirubinemia in breast-versus formula-fed infants in the first six weeks of life:relationship to weight gain. Am J Perinatol.1983;1(1):47–51

5. Tiker F, Gürakan B, Tarcan A, Kinik S. Serumbilirubin levels in 1-month-old, healthy,term infants from southern Turkey. AnnTrop Paediatr. 2002;22(3):225–228

6. Chang P-F, Lin Y-C, Liu K, Yeh S-J, Ni YH.Prolonged unconjugated hyperbilirubinemiain breast-fed male infants with a muta-tion of uridine diphosphate-glucuronosyltransferase. J Pediatr. 2009;155(6):860–863

7. Kramer LI. Advancement of dermal icterusin the jaundiced newborn. Am J Dis Child.1969;118(3):454–458

8. Ebbesen F. The relationship between thecephalo-pedal progress of clinical icterusand the serum bilirubin concentration innewborn infants without blood type sensi-tization. Acta Obstet Gynecol Scand. 1975;54(4):329–332

9. Knudsen A. The cephalocaudal progressionof jaundice in newborns in relation to thetransfer of bilirubin from plasma to skin.Early Hum Dev. 1990;22(1):23–28

10. Keren R, Tremont K, Luan X, Cnaan A. Visualassessment of jaundice in term and latepreterm infants. Arch Dis Child Fetal Neo-natol Ed. 2009;94:F317–F322

11. Hegyi T, Hiatt IM, Gertner I, Indyk L. Trans-cutaneous bilirubinometry. The cephalocaudalprogression of dermal icterus. Am J Dis Child.1981;135(6):547–549

12. Bhutani VK, Stark AR, Lazzeroni LC, et al;Initial Clinical Testing Evaluation and RiskAssessment for Universal Screening for

Hyperbilirubinemia Study Group. Pre-discharge screening for severe neonatalhyperbilirubinemia identifies infants whoneed phototherapy. J Pediatr. 2013;162(3):477–482, e1

13. Maisels MJ, Ostrea EM Jr, Touch S, et al.Evaluation of a new transcutaneous bilirubin-ometer. Pediatrics. 2004;113(6):1628–1635

14. Yasuda S, Itoh S, Isobe K, et al. New trans-cutaneous jaundice device with two opticalpaths. J Perinat Med. 2003;31(1):81–88

15. Arias IM, Gartner LM, Seifter SA, Furman M.Prolonged neonatal unconjugated hyper-bilirubinemia associated with breastfeed-ing and a steroid, pregnane-3-alpha 20beta-diol in maternal milk that inhibitsglucuronide formation in vitro. J Clin In-vest. 1964;43:2037–2047

16. Arias IM, Gartner LM. Production of un-conjugated hyperbilirubinemia in full-termnewborn infants following administrationof pregnane-3(a), 20 (b)-diol. Nature. 1964;203:1292–1293

17. Murphy JF, Hughes I, Verrier Jones ER,Gaskell S, Pike AW. Pregnanediols andbreast milk jaundice. Arch Dis Child. 1981;56(6):474–476

18. Ramos A, Silverberg M, Stern L. Pregnanediolsand neonatal hyperbilirubinemia. Am J DisChild. 1966;111(4):353–356

19. Adlard BPF, Lathe GH. The effect of steroidsand nucleotides on solubilized bilirubinuridine diphosphate-glucuronyltransferase.Biochem J. 1970;119(3):437–445

20. Watchko JF. Genetics and pediatric un-conjugated hyperbilirubinemia. J Pediatr.2013;162(6):1092–1094

21. Skierka JM, Kotzer KE, Lagerstedt SA,O’Kane DJ, Baudhuin LM. UGT1A1 geneticanalysis as a diagnostic aid for individualswith unconjugated hyperbilirubinemia. JPediatr. 2013;162(6):1146–1152, e1–e2

22. Monaghan G, McLellan A, McGeehan A, et al.Gilbert’s syndrome is a contributory factorin prolonged unconjugated hyperbilirubinemiaof the newborn. J Pediatr. 1999;134(4):441–446

23. Ulgenalp A, Duman N, Schaefer FV, et al.Analyses of polymorphism for UGT1*1 exon1 promoter in neonates with pathologic

and prolonged jaundice. Biol Neonate. 2003;83(4):258–262

24. Maruo Y, Nishizawa K, Sato H, Sawa H, ShimadaM. Prolonged unconjugated hyperbilirubinemiaassociated with breast milk and muta-tions of the bilirubin uridine diphosphate-glucuronosyltransferase gene. Pediatrics.2000;106(5). Available at: www.pediatrics.org/cgi/content/full/106/5/e59

25. Muraca M, Fevery J, Blanckaert N. Rela-tionships between serum bilirubins andproduction and conjugation of bilirubin.Studies in Gilbert’s syndrome, Crigler-Najjardisease, hemolytic disorders, and rat mod-els. Gastroenterology. 1987;92(2):309–317

26. Spivak W, DiVenuto D, Yuey W. Non-enzymichydrolysis of bilirubin mono- and diglucuronideto unconjugated bilirubin in model and nativebile systems. Potential role in the formation ofgallstones. Biochem J. 1987;242(2):323–329

27. Ota Y, Maruo Y, Matsui K, Mimura Y, Sato H,Takeuchi Y. Inhibitory effect of 5b-pregnane-3a,20b-diol on transcriptional activity andenzyme activity of human bilirubin UDP-glucuronosyltransferase. Pediatr Res. 2011;70(5):453–457

28. Hansen TWR, Bratlid D. Physiology of neo-natal unconjugated hyperbilirubinemia. In:Stevenson DK, Maisels MJ, Watchko JF, eds.Care of the Jaundiced Neonate. New York,NY: McGraw Hill; 2012:65–95

29. Davidson LT, Merritt KK, Weech AA. Hyper-bilirubinemia in the newborn. Am J DisChild. 1941;61:958–980

30. Moyer VA, Ahn C, Sneed S. Accuracy ofclinical judgment in neonatal jaundice. ArchPediatr Adolesc Med. 2000;154(4):391–394

31. Riskin A, Tamir A, Kugelman A, Hemo M,Bader D. Is visual assessment of jaundicereliable as a screening tool to detect sig-nificant neonatal hyperbilirubinemia? JPediatr. 2008;152(6):782–787, e1–e2

32. Purcell N, Beeby PJ. The influence of skintemperature and skin perfusion on thecephalocaudal progression of jaundice innewborns. J Paediatr Child Health. 2009;45(10):582–586

33. Azzuqa A, Watchko JF. Scleral (conjunctival)icterus in neonates: A marker of significanthyperbilirubinemia. E-PAS. 2013;3841.708

ARTICLE

PEDIATRICS Volume 134, Number 2, August 2014 e345 by guest on September 7, 2015pediatrics.aappublications.orgDownloaded from

DOI: 10.1542/peds.2013-4299; originally published online July 21, 2014; 2014;134;e340Pediatrics

Kendall, Sharon McManus and Mary SmythM. Jeffrey Maisels, Sarah Clune, Kimberlee Coleman, Brian Gendelman, Ada

The Natural History of Jaundice in Predominantly Breastfed Infants  

ServicesUpdated Information &

tmlhttp://pediatrics.aappublications.org/content/134/2/e340.full.hincluding high resolution figures, can be found at:

References

tml#ref-list-1http://pediatrics.aappublications.org/content/134/2/e340.full.hat:This article cites 30 articles, 6 of which can be accessed free

Citations

tml#related-urlshttp://pediatrics.aappublications.org/content/134/2/e340.full.hThis article has been cited by 1 HighWire-hosted articles:

Subspecialty Collections

gy_subhttp://pediatrics.aappublications.org/cgi/collection/neonatoloNeonatology

ubinemia_subhttp://pediatrics.aappublications.org/cgi/collection/hyperbilirHyperbilirubinemia

orn_infant_subhttp://pediatrics.aappublications.org/cgi/collection/fetus:newbFetus/Newborn Infantthe following collection(s):This article, along with others on similar topics, appears in

Permissions & Licensing

tmlhttp://pediatrics.aappublications.org/site/misc/Permissions.xhtables) 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.xhtml

Information about ordering reprints can be found online:

rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.Grove Village, Illinois, 60007. Copyright © 2014 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 September 7, 2015pediatrics.aappublications.orgDownloaded from

DOI: 10.1542/peds.2013-4299; originally published online July 21, 2014; 2014;134;e340Pediatrics

Kendall, Sharon McManus and Mary SmythM. Jeffrey Maisels, Sarah Clune, Kimberlee Coleman, Brian Gendelman, Ada

The Natural History of Jaundice in Predominantly Breastfed Infants  

  http://pediatrics.aappublications.org/content/134/2/e340.full.html

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 © 2014 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 September 7, 2015pediatrics.aappublications.orgDownloaded from