Envronmental Health PerspectivesVol. 94, pp. 55-S9, 1991

Preventability of Neonatal Cold Injury andIts Contribution to Neonatal Mortalityby John R. Goldsmith,* Yael Arbeli,t and David Stone'

When the body temperature ofa small neonate fbls below 35°C, lasitude can be noted; severe derangements ofcar-doacuar, renal, hepatic, immunologicl,andhmlogl systemsmayalsooccurdependinginpartonthedurationand terity of thiay Dai alow-r thea,a bckingwhichthe canbesuspected,butmostoftenimissed.Fhtalcaseo coldlajuryconunonlybhaeenalpnepumolaorseps_LsPrevenitonlnvovsidenfcatlonandhomev eitoh rknh ensivecareoftosewiththe datSorokaHospdialMedlCenterhasreducedthecase-atalityratefrom30% in 1971 to3% in 1988-1969. Duringtheseperiod inour region, the propor-tionofneonataldeathsocurringinwintermonthsofDecember,January,andFebruaryhasdroppedfrom55to27%. Thenp_cisd25%podlis25%.We tdesUmrpte ig neonauWnmortltyduringwiterniondusesecialyduetoumoniaand sepws or suddeninfant death syndrome (SIDS) banindicatorofmiswdcoldihJury syndrome.Ap-l- n evanation wasmade fromUS dat by sSte, provided by the Na_Iona Center for HealthS , which

records no fataities from cold injury during 196 Contrsted with this are26 cold injury deaths in Israd for 1977-1980.In the U.&, though, ewess winter neonatal deaths In16 from SID, p , and sepss are reported. Tbese deathsamount to 13 out of368det abuted toSIDS and 8 out of 158 deats from influenza and pneumonia and 7 out of770deaths fromsepsis; howver, from the sttofNorth Carolina, South Carolina ippi, Vginia, and Pnnsylvania,the esc is about21 deathscomparedto theyearly number in these states of219from these causes. Thesestates also havesbstntial potios of the p ion th poor education and substanad housng. The use oflow-readn ometersin aran dlinical trial in such states would bejustied. These fIndings are consistent with a possible reduction ofabout 10% in electedcausmofneonataln yfomanactive program ofdetectonofneonal cold injury under high-risk conditions.

IntroductionNeonatal hypothermia was first designated "cold injury" by

Nassau in 1948 (), but even earlier, infants with the same typeofdamage to the skin were designated as sclerema neonatorumby Underwood in 1811, who noted thatbabies presenting with in-duration ofsubcutaneous tissue had alow body temperature anda poor prognosis (2).Mann and Elliot in 1957 wrote (3):Commonly the disorder is miiagosed as hemorrhagic pneumonia or

sclerema, the predominant role of exposure to cold being overlooked.Cases generally arise aferhome onfinements, especialy insevely coldweather.... Presenting features may include increasing apathy, foodrefusal, coldness to touch and oliguria: but the infant does not look ill.The most constant clinical findings are hypothemia, oedema ofthe ex-tremities, pumledt nasal skinaytm. heltreat-ment advised is slow rewarming, liberal glucose administration by in-tragastric drip, and antibiotic cover.

Subsequent studies have been reported from Scotland, andseemingly paradoxically from a variety ofsubtropical countries,such as Israel, Ethiopia, India, and Iraq (4-9). The seeming

*Epidemiology and Health Services Evaluation Unit, Ben Gurion Universityofthe Negev, P.Q. Box 653, Beer Sheva, Israel.

tRegional Office for the Negev of the Ministry of Health.tSocial Pediatic and Obstetric Researh Unit, University ofGlascow.Address reprint requests to J. R. Goldsmith, Epidemiology and Health Ser-

vices Evaluation Unit, Ben Gurion University ofthe Negev, P.Q Box 653, BeerSheva, Israel.

paradox is related to the fact that in these subtropical countries,cold nights are exceptional and therefore supplemental heat insleeping rooms is not usually needed for adults. In addition, inthese countries, many mothers are poorly educated.Only four cases have been reported from the U.S. in the

periodical literature. In the U.S. Vital Statistics for 1986, therewere no deaths for which ICD-9 no. 778.2, "cold injury syn-drome" (CIS) was the principal cause ofdeath, although the con-dition was mentioned, but not considered the underlying causeofdeath on one certificate.

In the U.S. in 1987 there were 368 neonatal deaths attributedto sudden infant death syndrome (ICD-9, 798.0), whereas inIsrael for 1977-1980 among all infant deaths, 26 were attributedto 778.2, while 99 were attributed to SIDS. Ifwe limit the com-parison in Israel to neonatal deaths the ratio of CIS deaths toSIDS deaths would be greater. There are subtropical areas oftheU.S. with mothers oflow educational level and cold snaps. CISdeaths must be occurring in the U.S., but are not being recog-nized. Unless CIS is recognized, it will not be prevented, and,as we will show, CIS is preventable. We will look at possible in-dices that suggest where and when to look.

Natural History of Cold Injury SyndromeSeveral studies in Israel called attention to important features

ofthe natul history ofCIS. Cohen (4) called attention to the im-portance ofcoagulation abnormalities. Dagan and Gorodischer

GOLDSMrITHETAL.

(10) reported on the frequency of infection among hypothermicinfants. Meanwhile, a debate was going on as to whether it waspreferable to rapidly or slowly warm the infants.

Soferetal. (11 ) reviewed thehospitalizationof56hypothermicinfants seen at Soroka Medical Center over three winters. Theyreported:

Oneormore severeassociated disturbances, including metabolic abnor-malities, bleeding tendency, infectionandrespiraoryfailurewereobservedin most cases. 38 received slow wanming, but 18ofthe worstcases receivedrapidwarming. These 18wereamongthe24casestreatedinapediatric in-tensive care unit. Fourteen required assisted mechanical ventilation. 53ofthe56 survived, andofthe reewhodiednonewas rapidlywarmed, andtwo had severe underlying central nervous system infection.

Thus, thenaturalhistorybeginswithadropofbodytemperaturebelow 359C, which ifcontinued or aggravated, leads to clottingdeficiency, severe hypoglycemia, cardiac, respiratory, or renalfailure, complicatedby infectionorpneumonia. Rewarmingmayfail toreverse these, anddeathmayensue, whichmaybeattributedto SIDS, pneumonia, or sometypeof infection. Treatmentofthefailingbodily symptomsand antibioticsprovidethebestchancesfor survival, regardless ofthe rate ofrewarming. Figure 1 showstheageatdiagnosisofJewishandBedouininfantsintheNegevin

PERCENT OF ALL-AGE INaDENOE

0-8 7-30 30+AGE IN DAYS

FIGURE 1. Age at diagnosis of Jewish (solid bars, n = 32) and Bedouin(hatched bars, n = 29) infants with cold injury in the Negev during 1987to 1989, inclusive.

NOV DEC JAN FEB

MonthMAR APR

FIGURE 2. Incidence rate of cold injury per 1000 live births by monthamong Jewish and Bedouin infants during 1987 to 1989. The rates are bas-ed on an assumed 9500 births per year without adjusting for seasonalvariation in birth rate.

1987-1989, andFigure 2showsthemonthofdiagnosis forthesameinfants.

HypothesisIt must follow that if in the presence of recognized hypother-

mia (24-34°C), one or more severe distubances are found, ifthehypothermia is not recognized, these severe abnormalities wouldstill be present and without vigorous treatment, are likely to befatal. Under these circumstances, pneumonia, sepsis, respiratoryfailure, or SIDS are the most likely diagnoses.This hypothesis will be examined under two circumstances.

First, as CIS becomes more consistently recognized (and treated)in the Negev, we will look to see what happens to mortality frompneumonia, sepsis, respiratory failures and SIDS in the neonatalperiod. A parallel examination will be made for the residents ofthe Gaza strip. If indeed, winter excess deaths from these con-ditions drops as CIS in recognized and treated or prevented, itwill suggest that some cases ofCIS may have been missed in theearlier period but not in the later period.

Second, we will examine the neonatal mortality data for U.S.by state for the year 1986, looking for winter excess in suchdiagnoses as discussed previously. In locations with such awinter excess, it is reasonable to suspect that missed CIS is thecause, and an attempt to identify it would be justified.Observations on Cold Injury in theNegev (South) of IsraelThe incidence ofcold injury among infants has been a matter

of serious concern among public health nursing personnel in theNegev Regional Office of the Ministry of Health for nearly 15years. The nurses are equipped with low-reading thermometers(Fig. 3) and as part of the routine postnatal care, make homevisits, with special attention being given to babies with smallbirth weight during the periods of cold weather. When babieswith a body temperature of34°C or less are identified, they aresent to the Soroka Hospital Medical Center.Dagan and Gorodischer (10) reported on 51 such infants who

were less than 3 months old and admitted during the years of 1976ffirough 1981. Twenty-eight were males and 23 females; 41 wereadmitted during the first month oflife. Forty-three ofthem werefrom rural areas and villages, and 8 were born at home ratherthan in the hospital. Thirty-four were at least partially breast fedat the time of admission. Twenty-seven of them had someevidence of infection.

All were within the first 10th percentile ofweight for age, and11 had diarrhea and dehydration. The tendency to dehydrationwas evidenced by the high prevalence ofelevated hematocrit (34greater than 16 g hemoglobin/dL). Six died, of which 5 hadinfection.A further 56 hypothermic infants were observed in the Soroka

Hospital by Sofer et al., covering the period from November 1,1982, to October 31, 1985 (11). Of these, 29 were Bedouin and27 Jews, which represents a slight shifttward Jews compared to29 Bedouin and 22 Jews studiedby Dagan and Gorodischer (JO).Forty-six of the babies studied by Sofer et al. were seen duringthe first 30 days of life (11). In contrast to the mortality rate ofhospitalized infants prior to 1974, which was 31%, only 3 oftheinfants treated by Sofer et al. succumbed (11).During the two winters, 1987-1988 and 1988-1989, the Public

56

PREVENTIONOFNEONATAL COLDINJURYAND MORTALrIY

Table 1. Diagis ofcold injury syndrome.Symptoms: placid, poor nursing, good color, cool skinTemperature lower than 35°CMany body systems impaired: clotting deficiency, renal impairment,

cardiovascular impairment, metabolic impairmentComplications ofpneumonia, sepsisYOnly low body temperature is diagnostic.

lkble 2. Risk factors for cold ijury by host and by environment.

Host EnvironmentPIor education Temperature < 50CFirst births Unheated housingHome delivery Swaddling (?)Scant prenatal careLow birth weight

¶bble 3. Nenataldeadt by month in the Negev of Iaelby time period andfor cold injury (CIS) or pneumonia and sepsis (PS).'

1971-1973 1977-1980 1983-1985Month Total CIS PS Total CIS PS Total CIS PSJan 14 5 7 8 3 3 2 0 1Feb 14 3 2 7 0 3 3 1 0Mar 5 0 1 7 1 0 4 1 0Apr 7 0 2 5 1 1 1 0 0May 6 0 1 6 0 0 2 0 0Jun 4 0 2 4 0 0 4 0 0Jul 3 0 0 6 0 0 5 0 1Aug 4 0 2 9 0 1 3 0 0Sep 5 0 2 9 1 0 1 0 0Oct 7 0 0 4 0 1 2 0 0Nov 4 0 0 9 0 2 3 0 0Dec 3 0 1 12 0 2 2 0 1

Total 56 8 20 86 6 13 32 2 3aExcluding deaths firom prematurity, birth injury, or congenital abnonnality.

PERCENT IN WINTER MONTHS

1001-8/8

80e-

V1

2/3

601-

40k

20[-

FIGURE 3. A low-reading thermometer.

Health Nurses identified 61 incident cases, of which 55 were

under 30 days ofage; 29 were Jewish and 32 Bedouin. Ofthese,24 Jews and 31 Bedouin were hospitalized. The estimated annualrates were for Jews, 2.4/1000 live births in 1987-1988 and 1.7 in1988-1989, and for Bedouin, 8.0 for 1987-1988 and 4.8 for1988-1989. Of this group there were 2 deaths.

Ifone restricts the consideration to high-risk infants born dur-ing cold weather, the incidence may be as high as 3%. Table 1

shows the criteria for diagnosis of CIS. Table 2 shows the riskfactors for cold injury by host and environment.

Table 3 shows themonthly incidenceofneonataldeathsduetoCIS and to pneumonia and sepsis in the Negev for 1971-1973,

01971-73 1077-80 1981-86 1986-88

TIME PERIODS

FIGURE 4. Proportions of neonatal deaths in winter months of December,January, andFebruaryforvarioustimeperiodsandattributedtovariouscauses.Solid bars, cold injury; hatched bars, pneumonia and sepsis; dotted bars,neonatal deaths. Theproportionofcold injury deaths inthewinter isexpectedto be high, and the proportion and numbers are shown. The proportion at-tributed topneumoniaandsepsisandtheproportion ofall neonatal deathsoc-currin duringthese monthshasdropped towardtheexpected value of25% astheeffectiveness ofcase-findingandpreventionofcold injury has improved.

l977-1980and 1983-1985. Figure 4 showstheproportionsofthesedeahstatoccurduringthewintermonthsofDecember, January,and February. Figure5 shows themonthly incidenceofthesedatafortwo timeperiods for the population ofthe Negev, and Figure6 shows similar data for the Gaza Strip.

57

GOLDSMITHETAL.

NEONATAL DEATHS20

16

10

JN FE MA AP MA JN JL AU SE 00 NO DO

MONTH

FIGURE 5. The neonatal mortality by month in the Negev for two time periods,1971-1973 (solid bars) and 1983-1985 (hatched bars). During the interval, case

finding and prevention ofcold injury were initiated. Other improvements werealso being made. The data excludes deaths due to congenital abnormalities,prematurity, or birth trauma.

NEONATA DEAHS20

16

10

JN FE MA AP MA JN JL AU SE 00 NO DO

MONTH

FIGURE 6. Neonatal mortality by month for selected causes for Gaza for twotime periods, 1981-1982 (solid bars) and 1984-1985 (hatched bars). Duringthe interval, case finding and prevention for cold injury were introduced.Causes include all respiratory conditions and all infectious conditions.

Data for the U.S., 1986 and 1987Table 4 shows the 20 states ofthe U.S. with elevated neonatal

mortality rates in 1986, along with the numbers of such deaths,as well as the numbers in 1987 attributed to SIDS (ICD 798.0),influenza and pneumonia (ICD 480-487), and to other infectionsspecific to the perinatal period (ICD 771.8). This latter categoryis elsewhere identified as "sepsis." The District ofColumbia hadthe highest neonatal death rate and is included although notstrictly a state.The expected numbers of winter deaths can be obtained by

multiplying the denominator data by 90/365 = 0.2466, the pro-portion ofdays in the year that occurs in the three winter monthsof Liecember, January, and February. The 20 states with neonatalmortality above the U.S. average shown in Tables 4 and 5 ac-count for 18 ofthe 28 excess neonatal deaths, indicating that totalneonatal mortality is not a very strong predictor ofwinter excessneonatal mortality from these causes. Ofcourse, statewide data

Table 4. Neonatal deaths and neonatal death rates for the U.S. and forstates with elevated neonatal rates, 1986, and numbers of neonatal deathsattributed in 1987 to S)DS, influenza and pneumonia, and to other infec-

tions specific to the perinatal period.'1986 1987

Neonatalrate/

Neonatal 100,000 Pneumonia Otherdeaths live births SIDS and flu infections

U.S. 25,212 6.7 368 158 770District of 162 16.1 0 0 5Columbia

Alabama 541 9.1 12 3 19Delaware 86 8.8 2 1 2SouthCarolina 456 8.8 3 4 17Georgia 835 8.5 10 8 27Maryland 576 8.3 8 2 14Illinois 1437 8.1 25 16 42Louisiana 605 7.8 9 7 22Michigan 1080 7.8 15 5 24NorthCarolina 691 7.7 14 3 32Mississippi 324 7.7 9 2 19Vermont 61 7.5 2 0 1Indiana 597 7.5 11 3 21Virginia 651 7.5 10 3 13Florida 1652 7.5 10 12 34New York 1937 7.3 19 10 54Ohio 1086 6.9 11 3 32Tennessee 457 6.9 10 1 22Pennsylvania 1092 6.8 23 6 47Connecticut 303 6.8 1 1 8Missouri 512 6.8 11 1 14aSource: H. Rosenberg, National Center for Health Statistics (personal

communication).

TblMe . Proportion of neonatal deaths due to SIDS, pneumonia or influenza,or sepsis which occurs during the winter months of December, January,and February, 1987, in the U.S. and in states with high neonatal mortality.'

Influenza-SIDS pneumonia Sepsis Total Percent

U.S 104/368 47/158 197/770 348/1296 26.9District of Columbia 0 0 1/5 1/5 20.0Alabama 4/12 0/3 2/19 6/34 17.6Delaware 1/2 1/1 1/2 3/5 60.0South Carolina 1/3 2/4 6/17 9/24 37.5Georgia 5/10 1/8 4/27 10/45 22.2Maryland 3/8 0/2 3/14 6/24 25.0Illinois 4/25 4/16 12/42 20/83 24.1Louisiana 3/9 1/7 7/22 11/38 28.9Michigan 4/15 1/5 3/24 8/44 18.2North Carolina 6/14 1/3 12/32 19/49 38.8Mississippi 4/9 1/2 7/19 12/30 40.00Vermont 0/2 0 0/1 0/3 0.0Indiana 2/11 0/3 4/21 6/35 17.1Virginia 4/10 0/3 5/13 9/26 34.6Florida 1/10 6/12 9/34 16/56 28.6New York 5/19 3/12 15/54 23/85 27.1Ohio 5/11 0/3 7/32 12/46 26.1Tennessee 2/10 1/1 2/22 5/33 15.2Pennsylvania 5/23 3/6 16/47 24/76 31.6Connecticut 0/1 1/1 3/8 4/10 40.0Missouri 3/11 1/1 2/14 6/26 23.1

Total 62/215 27/93 121/469 210/77Percent 28.8 29.0 25.8 27.0

'Source: H. Rosenberg, National Center for Health Statistics (personalcommunication).

58

PREVEN77ON OFNEONATAL COLD INJURYAND MORTALITY 59

can obscure more striking problems in a low-income, badlyhoused minority group. The data show more striking effects forthe first two categories, SIDS and influenza and pneumonia, thanfor the category designated as "sepsis." For New York City, totake an example, the data for SIDS are 4/9, for influenza andpneumonia 2/7, and for sepsis 7/32. For the SIDS and influenzaand pneumonia, together, the winter ratio is 6/16 or 37.5%,whereas for the state includingNew York City, it is 8/31 or25.8%.

Overall, there are about 28 excess winter neonatal deaths fromthese three causes in the U.S. About half are due to SIDS andabout equal numbers but proportionally more due to influenzaand pneumonia than to sepsis.The excess is greater in states ofthe southeastern region, where

other risk factors for cold injury are likely to be high. A clinicaltrial ofthe use oflow-reading thermometers in such states wouldbe justified.

DiscussionMost of cases of SIDS occur after the neonatal period, so it

must follow that only a small proportion ofthe otherwise unex-plained sudden infant deaths could be due to undiagnosed coldinjury. According to our hypothesis, that proportion would begreatest in winter and in locations with high risk populations.Neonatal mortality data by state in the U.S. must include manydeaths due to immaturity and congential abnormalities, as wellas deaths from populations not at high risk. Despite this dilution,the data suggest that as much as 10% ofneonatal deaths attributedto SIDS or to influenza or pneumonia in certain states may be ac-tually due to unrecognized cold injury. Since we have shown thatdeaths from cold injury, and to some extent, morbidity from coldinjury, are preventable, the effort to detect and prevent thesedeaths seems worthwhile.

We suggest that a clinical trial be conducted in order to see ifdetection ofCIS can be accomplished. The trial would involveintroducing the use of low-reading thermometers to nurses inrandomized jurisdictions with excess neonatal deaths in wintermonths.

The authors express their gratitude to Viola Torek, Regional Public Health Of-ficer for the Negev, under whose direction this initiative in the Negev began; YehiaAbed, Health Officer, Gaza, District, who provided the data forGaza; and HarryRosenberg, Chief, Mortality Statistics Branch, U.S. National Center for HealthStatistics, who provided the data by states in the U.S.

REFERENCES

1. Nassau, E. Kalteschaden im subtropischen Klima. Ann. Pediatr. (Basel) 171:167 (1948).

2. Underwood, M. A Treatise on Diseases ofChildren, Vol. 1. London, 1811,p. 188. [Later edition published by James Webster, Philadelphia, 1818J.

3. Mann, T. P., and Elliott, R. I. K. Neonatal cold injury due to accidental ex-posures to cold. Lancet i: 229-234 (1957).

4. Cohen, I. J. Cold injury in early infancy: relationship between mortalityand disseminated intravascular coagulation. Isr. J. Med. Sci. 13: 405-409(1977).

5. El-Rahdi, A. S., and Al-Kafaj, N. Neonatal cold injury inadeveloping coun-try. Clin. Pediatr. 19: 401-404 (1980).

6. Karan, S., Rao, M. N., Urmila, S., and Rajaji, S. The incidence, clinical pro-file, morbidity and mortality ofhypothermia in the newborn. Ind. Pediatr.12: 1205-1210(1975).

7. Yu, J. S., and Jackson, R. Neonatal hypothermia in Australia. Practitioner213: 790-794 (1974).

8. Tafari, N., and Olsson, E. Neonatal cold injury in the Tropics. EthiopianMed. J. 11: 57 (1973).

9. Tafari, N., and Gentz, J. Aspects on rewarmning newborn infants with severeaccidental hypothermia. Acta Pediatr. Scan. 63: 595-600 (1974).

10. Dagan, R., and Gorodischer, R. Infections in hypothermic infants youngerthan three months. Am. J. Dis. Child. 138: 483-485 (1984).

11. Sofer, S., Yagupsky, R. Hershkowitz, J., and Bearman, J. E. Improved out-come of hypothermic infants. Pediatr. Emerg. Care 2: 211-214 (1986).