J. Physiol. (1969), 203, pp. 13-29 13With 2 plate and 6 text-ftguremPrinted in Great Britain

THE RESPONSEOF THE SWEAT GLANDS OF THE NEW-BORN BABY TO

THERMAL STIMULI AND TO INTRADERMALACETYLCHOLINE

BY K. G. FOSTER, E. N. HEY AND G. KATZFrom the M.R.C. Environmental Physiology Research Unit, London SchoolofHygiene and Tropical Medicine, London, W.C. 1, and the M.R.C. ResearchGroup on Respiration and Energy Metabolism in the Newborn, The LondonHospital Medical College, London, E. 1

(Received 28 October 1968)

SUMMARY

1. Measurements of evaporative sweat loss were made on fifty-sixpremature and full-term babies 1-67 days after birth with an infra-redanalyzer and a ventilated capsule placed on the thigh. Measurements werealso made of total evaporative water loss while in a closed metabolicchamber and of the regional distribution of sweating with starch-iodinepaper.

2. No sweating to thermal stimuli could be detected in infants of lessthan 210 days post-conceptual age, even when rectal temperature rose ashigh as 37.8° C. In older infants sweat was detected first on the foreheadand temple, later on the chest, and usually by 240-260 days post-conceptualage on the legs (term 268 days). Generalized sweating on the limbsappeared at an earlier post-conceptual age in the more prematurely borninfants.

3. The response of sweat glands on the thigh to an intradermal injectionof 2 ,tg acetylcholine (ACh) was tested. No sweat response was detected ininfants under 225 days post-conceptual age, while all infants born within2 weeks of term responded. The response was often augmented after2-5 tests at 5-10 min intervals; all the eight infants born within 2 weeksof term who were examined twice in the first 2 weeks of life showed agreater response on the second occasion.

4. An average of 414 active sweat glands/cm2 were detected on thethigh in eight babies 7-10 days old born within 2 weeks of term. This was61 times the number found in adults. The mean peak sweat rate to chemicalstimulation was however only 2 4 nl./gland. min, which was 3 times lowerthan the maximum rate recorded in adults.

14 K. G. FOSTER, E. N. HEY AND G. KATZ

5. In five infants with congenital defects of the brain and completeabsence of temperature control there was no sweat response to thermal ordirect chemical stimulation of the glands.

6. Functional maturation appears to depend on intact central innerva-tion and is marginally hastened by post-natal factors. Immaturity of thesweat glands can account for the lack of any response to thermal stimuliin premature babies, but not for the modest thermal response obtained inbabies at term.

INTRODUCTION

Recent studies have shown that in the new-born human infant totalevaporative water loss increases to only a limited extent at a high environ-mental temperature, even when rectal temperature rises as high as 37.80 C.This limitation is even more marked in infants born more than 3 weeksbefore term (Hey & Katz, 1969). These findings reinforce the general beliefthat thermal sweating is limited in the human baby at birth, and that theseverely premature infant is unable to sweat at all. We have now extendedthis work by measuring water loss from the skin directly with a ventilatedcapsule, and determined the effect of post-conceptual age on the abilityof the sweat glands to respond to both thermal and chemical stimulation.A preliminary report of some of this work has been given (Foster, Hey &Katz, 1968).

METHODS

A total of fifty-six unrestrained and unsedated healthy babies of known gestation werestudied with the consent of their parents after delivery in the maternity wards of TheLondon Hospital. The parents of nearly one-third of the infants studied were in the medicalor nursing profession. Each infant's post-natal age was calculated from the time and dateof delivery, while post-conceptual age was taken as originating 14 days after the first dayof the mother's last menstrual period. This date was confirmed by sequential neurologicalexamination of the infants after delivery using the methods employed in a previous studyof total evaporative water loss (Hey & Katz, 1969), and by detailed assessment of thephysical appearance (Farr, Mitchell, Neligan & Parkin, 1966). All the infants were of normalweight for gestation.The naked infants were studied in an incubator at various environmental temperatures

while rectal temperature was monitored continuously with a thermistor. The pattern ofregional sweating was studied with starch paper previously impregnated with iodine vapour;the paper was normally applied to the skin for 30 sec. Rectal temperature was not allowedabove 37-80 C (1000 F). A small Perspex capsule 1 cm in diameter was secured to the skinon the lateral aspect of the thigh in order to study the sweat response of this area to thermalstimuli in more detail. (This site is often employed when obtaining sweat by pilocarpineiontophoresis for diagnostic purposes in the neonate. It was chosen for the present investiga-tion because it offered an adequate flat area, even in premature babies, from which thecapsule was unlikely to be dislodged by spontaneous movement.) The capsule was ventilatedwith dry nitrogen, and this gas together with any evaporated sweat then passed through

SWEAT RESPONSES OF THE NEW-BORN BABY 15a calibrated infra-red gas analyser and flowmeter at 0-1-0-3 1./min to measure the rate andvolume of secretion (Foster, 1966).The response of the sweat glands under the capsule to chemical stimulation was studied

by administering 2 Bag acetylcholine in 0-2 ml. saline at room temperature intradermallythrough a needle into the skin under the capsule (Foster & Weiner, 1967) with full asepticprecautions. There was no response to control injections of saline (Text-fig. 1 b). The presenceof the capsule and needle did not appear to upset the child, though the actual injection ofACh occasionally caused the child to wake and cry for a few seconds. The insertion of theneedle caused momentary discomfort, but the procedure adopted seemed to cause lessdisturbance than iontophoresis of drugs into the skin. Care was taken to keep the site ofinjection as superficial as possible in order to elicit the maximum response; when correctlyplaced, each injection caused a transient circular white mark on the surface of the skin.The maximum response was assessed while the baby lay in a warm environment of 33-35° Cwith a rectal temperature of between 37-3 and 37.60 C. Counts of the number of sweat glandsactivated by maximal stimulation with 2 /sg ACh were made on eight of the infants usingthe method of Thomson & Sutarman (1953).A group of eight healthy men and women were also studied for comparative purposes.

The subjects sat, dressed in their normal clothes, in a room at 24-25' C. The response to anintradermal injection of ACh was measured at normal body temperature using an identicaltechnique.

Estimates of the infants' total evaporative water loss and heat production at variousenvironmental temperatures were also obtained at least once on all but nine of the babies,using the method described by Hey & Katz (1969). Direct measurements ofheat flow throughthe skin were made in twenty-seven infants with a heat-flow disk (Hatfield & Wilkins, 1950)on the back of the hand, while the whole arm was surrounded by a thermostated water-jacket maintained at a constant temperature.

Five other infants with gross congenital abnormalities were seen after admission to thehospital for observation. The parents of these babies also gave their consent to all theexperimental procedures undertaken. The ability of these infants to control body tempera-ture was studied comprehensively, but they were only exposed to a range of environmentaltemperature similar to that which they could expect to experience in a hospital nursery orat home. In four of the five infants Quinizarin powder (Guttman, 1937, 1940) was used todetect a thermal sweat response. The response to pilocarpine iontophoresis (Gibson & Cooke,1959) was tested in all five infants. Two infants with lumbar meningomyelocoele were alsostudied.

RESULTS

The thermal responseNo sweating could be detected in healthy infants of less than 210 days

post-conceptual age (term 268 days) in an environment of 36-37' C,even when rectal temperature rose as high as 37.8° C. Tests with starch-iodine paper and Quinizarin powder were all negative, and no rise in totalevaporative water loss occurred. Direct measurement of heat flow showed,however, that the infants were able to control heat loss from the hand evenat this early age (presumably by changing skin blood flow). The infantswere also capable of increasing their heat production in cool surroundings.A significant rise in total evaporative water loss always occurred in

infants of more than 220 days post-conceptual age tested at comparabletemperatures, and sweating could always be detected on the forehead, the

K. G. FOSTER, E. N. HEY AND G. KATZ

anterior part of the scalp and the temples. A progressive increase occurredin the number of areas where sweat could be detected in infants of over230 days post-conceptual age, and there appeared to be an increase in themagnitude of the response in the areas tested. A response was usuallydetected on the shoulders and chest before it was found on the limbs. Inthe majority of infants born within 2 weeks of term sweating could bedetected over most of the exposed areas of the body 4-14 days after birth.

0-3 Sweat secretion (al./min) (a)

02( 2 PgACh s Restless Sleeping Crying Cool air

Sweat secretion (al./min) 0 4 8 (b)0-06 = = s U i

U UU U U0-03 Xo DoboU0 b

Text-fig. 1. Records of the rate and volume of sweat secretion beneath a ventilatedcapsule 1 cm in diameter placed on the lateral aspect of the thigh of two new-bornbabies.

(a) The response on the ninth day after birth of a 3-7 kg infant born 2 weeksbeyond term. There is a large response to 2 jug intradermal ACh in 0 2 ml. saline. Anabnormally large thermal response appeared when rectal temperature exceeded37.-3 C; this irregular response was augmented when the baby woke and cried brieflybut ceased promptly when cool air was blown over the whole body.

(b) The response on the eighth day after birth of a 2-7 kg Singhalese infant born1 week beyond term. There was no thermal response even when rectal temperatureexceeded 37.8 C (a response was present 1 week later). There was no response to thefirst two intradermal injections ofACh and an increasing response to three furtherinjections. There was no response to an equal volume of saline (the small responseseen after the first of the two saline injections is assumed to be due to the smallamount of ACh left in the lumen of the indwelling needle).

Sweat always appeared most profuse on the forehead; it was often de-tected there when the rectal temperature was only a little above 370 C andbefore sweat was evident anywhere else on the body.A particular analysis was made of the sweat response on the lateral

aspect of the thigh: there was good general agreement between the resultsobtained with starch-iodine paper and the results obtained with theventilated capsule. Most infants born within 2 weeks of term sweated here.Occasionally there was a latent period during which temperature was highbut apparently constant before the thermal response appeared. Theresponse obtained on the thigh was characteristically irregular; it wasoften initiated or augmented when the child became restless or cried

16

SWEAT RESPONSES OF THE NEW-BORN BABY

(Text-fig. 1 a), but sweating appeared to cease abruptly when cool air wasblown over the body. Most, but not all, infants of more than 260 dayspost-conceptual age sweated slightly on the thigh before rectal temperaturerose to 37.80 C. In infants born several weeks before term, the responseappeared on the thigh at an earlier post-conceptual age; these infantswhen tested more than 2 weeks after birth began to sweat about 240 daysafter conception (Text-fig. 2). It seems clear that the onset of a thermalresponse on the thigh is related to both post-conceptual and post-natal age;tests with starch-iodine paper suggested that other areas of skin behavedin a similar way.The highest rate of secretion at a rectal temperature of 37.6-37.8° C

varied with post-conceptual age in the manner outlined in Text-fig. 3a;0

Less than 2 weeks 00 o 000 0@o°@o0--after birth 0 000 00000000

More than 2 weeks o 0 0 Oreo** ...after birth 00000 0

TermPost-conceptual I I I I I I I I

age (days) 180 220 260 300Text-fig. 2. The thermal response on the thigh under the ventilated capsule ininfants of differing post-conceptual and post-natal age. Rectal temperature was37 80 C except in a few infants who sweated profusely at a lower rectal temperature.*, Secretion ofsweat to thermal stimuli definitely recorded; 0, not observed at thehighest temperature employed. A X2 test on the twenty-three results obtained frombabies between 239 and 259 days after conception indicated that the onset of athermal response was related to post-natal age as well as post-conceptual age(P = 005).

the peak rate recorded in fifteen infants 1-14 days old born within 2weeks of term was 0-109 + 0-031 ,il./cm2 .min (mean + S.E.). Such ratesof secretion were, however, usually only detected while the child wascrying and active, and were seldom maintained for more than a fewminutes; little sweating was observed on the thigh at this temperaturewhen the infants were quiet, in contrast to the fairly copious sweatresponse detected on the head, and, on occasion, the trunk. The sweatrates in Text-fig. 3a may be compared with a calculated estimate for basaltransepidermal water loss of a little over 0-01 /td./cm2 .min under mostconditions of low air movement and normal humidity (Hey & Katz, 1969).

Response to acetylcholineThe response of the skin on the thigh of each baby was also tested to an

intradermal injection of 2 ,ag ACh in 0-2 ml. saline. This strength of drugwas selected because studies had shown that although secretion was pro-

17

K. C. FOSTER, E. N. HEY AND G. KATZ

longed by a larger dose in adults, the rate of secretion recorded under acapsule 1 cm in diameter only increased by an average of 7-5 % afterinjection of 20 jtg ACh (Table 1). Tests on seven babies failed to demon-strate a significantly greater maximum rate of secretion after the intra-dermal injection of 20 instead of 2 /tg ACh in the same volume of saline(Table 1).No response to ACh was detected on the thigh of infants under 225 days

post-conceptual age, while the response of infants between 225 and 250 daysold was variable (Table 2). However, all infants born within two weeks ofterm (between 254 and 282 days after conception) and tested within

TABLE 1. The maximum sweat rate in adults and babies recorded with a ventilated capsule1 cm in diameter after an intradermal injection of 2 or 20 Itg ACh in 0-2 ml. saline. Meanresults (±+S.E. of mean)

Full-term Healthybabies 3-10 adults 18-36days old years old

Number of subjects ... 7 7Response to 2 /tg ACh (,ul./min) 0-214 + 0-078 0-377 + 0-058Response to 20 jug ACh (/zl./min) 0-238 + 0-083 0-405 + 0-061Mean paired difference in 0-024 + 0-011 0 028 + 0-011maximum sweat rateSignificance of this difference P 0 07 P < 0-05

14 days of birth responded to this stimulus, though the maximum rate ofsecretion varied greatly (Text-fig. 3b). In many of the infants the responseto the first injection was small but an augmented response was obtainedafter 2-5 tests were performed at 5-10 min intervals (Text-fig. lb). Nosex differences were detected. In eight mature infants the response to AChwas tested twice in the first 14 days after birth when rectal temperaturewas 37 437 6° C. In each case the response was greater on the secondoccasion (Text-fig. 4) and in five of the infants the increase was significantat the 5% level. Sweat-gland counts were made in four of the infants: theincrease in response with post-natal age could not be accounted for bychanges in the number of activated glands.In fourteen infants born within 2 weeks of term the test was undertaken

in the first 2 weeks after birth both at normal body temperature, when thechild was vasoconstricted, and at high temperature on the same occasionwhile vasodilated. The order of the tests was random; in the majority ofthe experiments heat flow through the hand was measured continuouslyduring the study. The secretary response was slightly greater at highrectal temperature in ten of the fourteen studies (paired variate test:P < 0-01); the mean difference was 0-04 /Ll./min.

There was a clear correlation between the highest rate of secretionrecorded under the capsule in response to thermal stimuli and the maximumrate achieved in response to 2 fig ACh. However, the response to ACh

18

SWEAT RESPONSES OF THE NEW-BORN BABY 19

always exceeded the response to thermal stimuli with rectal temperaturebetween 37X6 and 37.80 C. Sixteen infants who responded slightly to 2 ,agACh did not respond to the highest thermal stimulus applied; the conversenever occurred.

04

a _4D0'- 0-3

0 2

0*1(a)

2 200 oL0...l..i- mo

200 250T

0.3r* W

a-_* m2

- 200 W

0 0 0-1

g .000 +o00~~~~~~~~~~~~~

a * 10t 300!rm

I.

0*

0000*

* 00

00 0

0 .0.0(b) .

000& 0 0 00 o0 %* :0

200 250 t 300Term

Post-conceptual age (days)

Text-fig. 3. The relation between post-conceptual age and the maximum rate ofsweat secretion beneath a ventilated capsule on the lateral aspect of the thigh.

(a) Maximum response to thermal stimuli in pul./cm2 . min at a rectal temperatureof 37.6-37-8° C in full-term and premature infants 1-14 days old. Responses thislarge were only transiently recorded. The environmental temperature was between360 and 370 C.

(b) Maximum response to an intradermal injection of 2 jig ACh in 0 2 ml. saline.Since there is evidence that this stimulus activated the glands in only a small andvariable area of skin under the capsule the response has been expressed as gl./min.The conditions were as defined in Table 2. *, Full-term and premature infants0-14 days old; 0, premature infants 15-67 days old.

TABLE 2. The maximum sweat response recorded after an intradermal injection of 2 jug AChin 0-2 ml. saline into the lateral aspect of the thigh in premature and full-term new-bornbabies. The tests were undertaken in a warm environment of 33-35° C when the rectaltemperature was between 37.30 and 37-6° C. Mean results (± s.E. of mean)

Subjects

Group NumberBabies born 43-70 6days before term and1-14 days old

Babies born 14-42 12days before term and1-14 days old

Babies born within 1314 days of term when12-72 hours old

Babies born within 2014 days of term when4-14 days old

Total sweatvolume

(Ud.)0

Duration ofresponse(min)0

Maximumsweat rate(Pl./min)

0

0-076 + 0-029 36 + 0-8 0-026 + 0-012

0-263 + 0-087 4-9 + 0-4 0 090 + 0-025

0-491 + 0-072 6-6 + 0-4 0-158 + 0-021

-R W. -W

Cs 0I11. k

K. C. FOSTER, E. N. HEY AND a. KATZ

The response to intradermal ACh in infants born within 2 weeks of termwas also compared with the response obtained in young adults. The volumeof sweat secreted was very much greater in the adults, the sweat responsepersisted for very much longer, and the maximum rate of secretion underthe capsule was almost always higher (Text-fig. 5). The mean differenceswere significant at the 0.1% level (Table 3), but this could have resultedfrom a difference in the way the injected drug spread or was inactivated,

003

c 02

0

9 0-10

0

0 5 10 isPost-natal age (days)

Text-fig. 4. The effect of post-natal age on the maximum rate of sweat secretionafter an injection of 2 Iug ACh in 0-2 ml. saline. Results obtained in eight infantsborn within 2 weeks of term who were studied twice under comparable conditionsin the first 2 weeks after birth. The vertical bars indicate the s.E. of the means(0) where n 3 4.

rather than a difference in the responsiveness of the glands. The briefresponse in the baby was certainly not the result of glandular exhaustionbecause the response to a further immediate injection was normal (Text-fig. 1 b). The number of active sweat glands under the capsule was countedafter the injection of 2 lag ACh in eight babies and eight adults. There were61 times as many active glands in the babies per unit surface area, but theglands were activated over a wider area of skin in the adults (Plates 1, 2).

Infants with developmental defects of the c.N.s.Five mature infants were seen who had severe congenital defects of the

brain: one infant was anencephalic, one had severe hydranencephaly, andthree had large occipital encephalocoeles and microcephaly. The infantsneither shivered, became active, nor increased their heat production abovebasal when exposed to a cool environment; no change in the thermal con-ductivity of the skin occurred in response to changes in environmental andbody temperature. It is likely that these observed defects of temperature

20

SWEAT RESPONSES OF THE NEW-BORN BABY

control were caused by some derangement of the brain mechanisms in-volved in temperature regulation.The five infants failed to sweat anywhere on the body in response to

thermal stimuli, and the total evaporative water loss never rose above thenormal basal level even at high environmental and body temperature. The

E 0-6-7 . 2 #eg ACh0 4 8

o 0-40 .<. 1 ~~~~~~~~~~~~~Min.u 0-2U, 02.

Text-fig. 5. Records ofthe rate and volume of sweat secretion beneath a ventilatedcapsule on the lateral aspect of the thigh, showing the typical response to theintradermal injection of 2 jug ACh in 0-2 ml. saline in an adult (-) and in a normal8-day-old infant (...... ). The number of glands activated under the capsule in thesetwo subjects by injection of ACh is recorded in Plates 1 and 2.

TABLE 3. Comparison of the sweat response to an intradermal injection of 2 Iug ACh inadults and in new-born babies. The records were obtained from the lateral aspect of thethigh using a ventilated capsule 1 cm in diameter. Mean results ( s.E. of mean)

Full-term Healthybabies 7-10 adults 17-34days old years old

Number of subjects ... 8 8Total sweat volume (1A.) 0-52 + 0-10 3-66+ 0-34Duration of response (min) 6-2 + 0-4 19-1 + 1-3Maximum sweat rate (gl./min) 0-17 + 0-03 0-35 + 0-03Estimated number of active sweat 414 + 49 64 + 6glands per cm2

Estimated number of glands 98 + 25 48 + 4activated under the capsule byinjection of 2 /esg ACH in 0-2 ml.salineMaximum sweat rate per activated 2-40 + 0-57 7-51 + 0-63sweat gland (nl./min)

infants also failed to secrete any sweat When tested with pilocarpine on thethigh on at least two occasions. Both the children who were tested also failedto respond to injections of 2, 20 or 200 ,ug ACh in 0-2 ml. saline into theskin of the thigh under a ventilated capsule. The four youngest childrenhave since died. No abnormalities were found in the sympathetic nervoussystem, the skin, or the sweat glands at autopsy.Two other full-term infants were seen who had lumbar meningo-

myelocoeles and a complete flaccid paralysis of the legs. Whereas the sweatglands on the arm responded to both thermal and chemical stimulation,those on the leg responded to neither.

21

K. G. FOSTER, E. N. HEY AND G. KATZ

DISCUSSION

Sweat responses at birthUchino (1939a, b) failed to detect sweating on the chest to thermal

stimuli on the first day of life, but sweating was recorded by the fourteenthday after birth in twenty-seven out of fifty-seven full-term infants. Noneof the five premature infants born 3-6 weeks before term sweated untilat least 13 days after birth. Bruck (1961), however, reported that in ninefull-term infants studied on the first day of life 'beads of sweat appearedon the forehead at rectal temperatures between 37X5 and 37.90 C; in threecases sweat was also observed on the arms, legs and trunk'. Adamsons,Gandy & James reported similar observations in 1965. Again, all theinfants born within 3 weeks of term studied by Hey & Katz (1969) on theday of birth were able to more than double their total evaporative waterloss when rectal temperature rose above 37.50 C.

It has been thought that these reports conflict with those of Uchino,but the findings are not necessarily inconsistent. The observations reportedhere indicate that sweating nearly always occurs first and most profuselyon the head, and only later on the trunk and limbs to any significantextent. In several of the infants studied here and born within 2 weeks ofterm no sweat was detected on the chest or limbs using starch-iodinepaper, and none recorded under the capsule on the thigh, until the infantwas several days old, although the rectal temperature was taken as highas 37.80 C. In other infants generalized sweating was seen on the day ofbirth, but only when rectal temperature rose above 37.5° C; in many ofUchino's studies rectal temperature never rose above this value during thefirst few days. We may conclude that all full-term babies were capable ofsweating on the day of birth, but that thermal sweating was more general-ized and occurred at a lower body temperature in infants a few days old.The sweat response to thermal stimuli of babies born more than 3 weeks

before term was small, and largely limited to the head. The change inresponse to thermal and chemical stimulation summarized in Text-fig. 3closely parallels the increase in total evaporative water loss at highenvironmental temperature with increasing post-conceptual age (Hey &Katz, 1969, Fig. 10). Seven infants capable of sweating on the head whenhot did not respond to intradermal ACh on the thigh, but this appears tobe related to the fact that babies sweat on the head to thermal stimuliat an earlier post-conceptual age than elsewhere on the body. Every babythat sweated on the thigh to thermal stimuli also responded at the samesite to ACh. That the converse did not hold suggests that 2 ,tg intradermalACh was a more effective stimulus than the highest temperature employed.Uchino (1939a, b) found a clear and persistent sweat response in full-

22

SWEAT RESPONSES OF THE NEJW-BORN BABY

term infants even on the day of birth to an intradermal injection ofbetween 100 and 750 Itg pilocarpine hydrochloride, and a rather smallerresponse in three infants born 3-7 weeks before term. These observationsare similar to those reported here. Using Minor's method (1928) Uchinoalso saw 'a very small spot of sweat with the aid of a simple lens in aninfant of 27 weeks gestation' after an intradermal injection of pilocarpine,but he did not give any further details of this isolated observation. Wehave never detected any response to ACh on the thigh in infants quite asyoung as this.

Immediate post-natal changesThe observations now reported suggest that the responsiveness of the

sweat mechanism is related to post-natal as well as post-conceptual age.A thermal sweat response appeared on the thigh at an earlier post-con-ceptual age in those infants who were born several weeks before term(Text-fig. 2). There was no evidence that the first response to chemicalstimulation occurred any earlier in those infants who were particularlypremature at the time of delivery (Text-fig. 3b), butpthere was clear evi-dence that in infants born near term responsiveness increased rapidlyduring the first fortnight after birth (Text-fig. 4); this increased sensitivityparallels the progressive rise in the response to thermal stimulation notedby Uchino (1939b) and also demonstrated by Hey & Katz (1969:Figs. 6b, 9).

There could be various reasons for the progressive increase in theresponse of the sweat glands to thermal stimulation during the first fewdays after birth. The increase may reflect a change in the level of sympa-thetic stimulation, but the increase in response to ACh now demonstratedindicates a definite change in the responsiveness of the glands tostimulation.Although the placenta is probably quite an efficient heat exchanger,

both environmental and body temperature are high while the baby isin utero (Adamsons & Towell, 1965; Mann, 1968). If mature babies do notsweat before birth it would seem that the threshold temperature at whichstimulation occurs must be set higher than it is after birth, or that someoverriding means of suppression operates. Sweat glands produce pro-gressively less sweat when the skin is soaked in water or dilute salt solu-tions at 36-37° C (Hertig, Riedesel & Belding, 1961; Brebner & Kerslake1968). It seems possible that the same process could operate before birth.The decrease in sweat output may be due to swelling of the sweat ductswhen the skin is thoroughly wet (Randall & Peiss, 1957). However, ifcontinued sweat gland stimulation occurs under these circumstances, avisible miliaria normally develops (Shelley & Horvath, 1950), though it isnot observed after short-term experiments. The fact that miliaria is not

23

K. G. FOSTER, E. N. HEY AND G. KATZ

seen at birth, although a 'sweat rash' often develops soon after birth, mayindicate that the secretary process itself is inhibited before birth.

Infants with c.N.s. defectsThe absence of any thermal sweat response in the five children with

developmental defects of the brain was not unexpected, as other evidenceof temperature control was also lacking. A lesion in the central nervoussystem that abolished all vasomotor response to thermal stimulation mightwell be expected to abolish the sweat response as well. What was moreunexpected was the lack of any response to direct chemical stimulation.It is known that human sweat glands become insensitive toACh, the normalchemical transmitter, after post-ganglionic sympathectomy (Coon &Rothman, 1941; Kahn & Rothman, 1942; Janowitz & Grossman, 1950)although only minor morphological changes have been detected in theglands (Silver, Montagna, & Versaci, 1964). The response to pilocarpine is,however, normally retained after preganglionic sympathectomy (Hynd-man & Wolkin, 1941; Chalmers & Keele, 1952). Since there is no reason tobelieve that the post-ganglionic fibres were anatomically abnormal in thefull-term infants with C.N.s. defects, the absence of any response seems toindicate that full functional maturation of the sweat gland at birth probablydepends on an intact central innervation in utero. The findings in the twoinfants who had congenital lesions in the spinal cord are consistent withthis view.

Development of the ability to sweatThe evidence of Taniguchi & Mochizuki (1937), K6yama (1937), and

Taniguchi & Kurita (1938) shows that formation of eccrine sweat glandsis complete before term in Japanese subjects and that no further glandsdevelop after birth. As a result gland density decreases progressively withgrowth (Text-fig. 6b). Szabo (1962) has shown that the same is probablytrue of the white races. Estimates of the number of functional glands are,however, usually lower than these histological counts. Ogata (1935)showed that a significant proportion of the glands on the thigh and else-where never secrete sweat in the adult even with maximal stimulation,although they appear to be fully developed on histological examination.The number of functional glands in the adults in Table 3 is similar to thatfound by others using this technique (J. S. Weiner, personal communica-tion). There were 6L times as many active glands on the thighs of thebabies per unit surface area. However, the surface area of the lower limbincreases tenfold with age (Boyd, 1935) so it would seem that, if the sampledensities were representative, the total number of functional glands mustincrease slightly after birth. Kawahata (1939) has produced similar

24

SWEAT RESPONSES OF THE NEW-BORN BABY 25evidence to suggest that the total number of active glands increasesduring the first 2 years of life.

Because of the limited area stimulated by the injection in the babies itwas clear that some of the glands under the capsule were not maximallystimulated. It was also probable that some minimally stimulated glands

30005000

(a) i ,i _

~~2000~~~~Thigh 0 b

2000 10ofI_,

X ~~I 00 I IO @0I"00 200 300a 501 01bo I 000 0s~rI

0 1000~~~~~~~~~~~~~

10 200 Term.0 'b-0 0 r1 0I 1

Post-conceptual age (days) Total body surface area (M2)

Text-fig. 6. The number of sweat gland ducts/cm2 in histological sections of skinfrom 114 Japanese foetuses, children and adults, collated from the data ofK6yama(1937), Taniguchi & Mochizuki (1937) and Taniguchi & Kurita (1938).

(a) Mean gland counts in Japanese foetuses at various gestational ages. Countsreach a maximum on the crown of the head several weeks earlier than on the thigh,suggesting that gland formation occurs rather later on the thigh. The vertical barsindicate the s.E. of means.

(b) The relation between sweat-gland density on the lateral aspect of the thighand total body surface area (log. scales). 0, data obtained from single foetuses;(®, twin foetuses; 0, children and adults. The regression through the filledsymbols is y = 285x-1062; the exponent (-1-062+ 0.087) does not differ signifi-cantly from unity. In so far as the surface area of the leg grows slightly more thanthat of the rest of the body both in utero and in later life (Boyd, 1935), this wouldbring the true exponent relating density to surface area closer to unity. The resultssuggest that the sweat glands are all formed by the time the foetus achieves a surfacearea of about 0-12 M2, but that only about 60 % of the glands on the thigh haveformed some 170 days after conception when surface area is approximately0 07 M2.

were not detected by the method used to count the number of glandsactive. On the simplifying assumption that these two effects largely canceleach other out, it can be calculated (Table 3) that the maximum secretaryrate of each active gland in the baby is about one third of that achievedin the adult (P < 0O00l). The observations of Huebner, Lobeck &McSherry (1966) also indicate that glandular ability increases steadilyduring childhood. We have recently obtained evidence that the maximumsweat response of the adult to chemical stimulation is influenced by skintemperature. Since in this comparative study the skin temperature of the

K. G. FOSTER, E. N. HEY AND G. KATZadults was less than that of the babies it is possible that we have somewhatunderestimated the difference in the maximum secretary rate of the glands.

In full-term babies Hey & Katz (1969) showed that total evaporativewater loss seldom rose above 70 nl./cm2 . min in a warm environment evenwhen rectal temperature rose as high as 37.80 C. The sweat response tothermal stimulation in the first 10 days after birth is thus very muchlower than in later life. From the peak response to chemical stimulationand the active gland density (Table 3) it would seem that the full-termbaby should be capable of a higher sweat output from the skin than theadult. We conclude that the modest thermal response actually found inmature infants is probably not governed by glandular limitations.

In babies born 2-3 months before term the situation is very different.Many of these babies seem unable to sweat at all, although we know thatin other respects they are remarkably well equipped to control their bodytemperature at birth: they are able to increase heat production in a coolenvironment, and are able to control skin blood flow very effectively, asalso shown by Bruck (1961). These aspects of nervous control over bodytemperature are therefore already well developed. The observations madeon the five infants with defects of the central nervous system suggest thatsweat glands may only develop fully when effectively and centrallyinnervated; the lack of any response to intradermal ACh into the thigh inmany premature babies may therefore reflect a lack of glandular maturityor a lack of peripheral or central nervous development. However, the factthat a thermal sweat response can often be detected on the face at a timewhen no sweat can be detected on the thigh to either thermal or chemicalstimulation suggests that the delay in maturation is peripheral rather thancentral. Since sympathetic nervous control of skin blood flow appearsvery adequate at this time, the delayed sweat response can, by extension,probably be attributed to immaturity of the gland itself.

This would accord with what is known of the histological maturation ofeccrine sweat glands over the general body surface. The glands of the fore-head and scalp are the first to develop (Borsetto, 1951). Gland develop-ment can be detected soon afterwards on the palms and soles and in theaxillae; the glands in these latter areas seem to be less involved in thermo-regulation (Kuno, 1956). Counts of the number of the sweat ducts showthat glandular formation continues during the sixth and seventh month ofgestation; the glands achieve their highest density on the crown of thehead during the sixth month of gestation (Text-fig. 6a), but rather lateron the trunk and not until the eighth lunar month on the limbs (Taniguchi& Mochizuki, 1937). Few glands anywhere develop a continuous lumenrecognizable by light microscopy until the seventh month of gestation(Kblliker, 1850; Borsetto, 1951). The glands are innervated at an early

26

SWEAT RESPONSES OF THE NEW-BORN BABY

stage, but differentiation and development continue until well after birth(Tsuchiya, 1954; Machida, 1964).

Sixteen infants responded slightly to intradermal ACh who did notsweat on the thigh in response to the highest thermal stimulus employed.Most of these babies were born before term. It has been argued (Uchino,1939b; Kuno, 1956) that lack of a thermal response in glands capable ofsecretion to chemical stimulation is a sign of imperfect reflex control,probably due to late maturation of the cerebral centres. Doubt is cast onthe certainty of this argument by the lack of all glandular function insome babies with congenital defects of the brain. Although the glands ofsome normal babies responded slightly to intradermal injection of AChbut not to warmth, this does not prove that the glands were imperfectlyinnervated since the two forms of stimulation may not have been strictlyequivalent. The lack of any sweat response in the most premature babiesand the gradual increase in responsiveness observed in those rather lesspremature could be accounted for by glandular development in the twomonths before term.

We wish to thank Professors K. W. Cross and J. S. Weiner for their encouragement andadvice, and the Obstetric and Paediatric staff of the London Hospital for their support.We are most grateful to Professor Yas Kuno for sending us reprints ofsome very important

Japanese papers which had not previously been available in this country, to Professor H.Urich for his detailed post-mortem study of the four infants with congenital abnormalitieswho died and to Dr D. McEwan Jenkinson for his opinion on the skin histology material.We are also extremely grateful to Miss E. Bardell and Mr J. 0. C. Willson for their help.

REFERENCES

ADAMSONS, K., GANDY, G. M. & JAMES, L. S. (1965). The influence of thermal factors uponoxygen consumption of the newborn human infant. J. Pediat. 66, 495-508.

ADAMSONS, K. & TOWELL, M. E. (1965). Thermal homeostasis in the foetus and newborn.Anesthesiology 26, 531-548.

BonsETTo, P. L. (1951). Osservazioni sullo sviluppo delle ghiandole sudoripare nelle diverseregioni della cute umana. Archo ital. Anat. Embriol. 56, 332-348.

BOYD, E. (1935). The Growth of the Surface Area of the Human Body. Minnesota: Universityof Minnesota Press.

BREBNER, D. F. & KERSLAKE, D. McK. (1968). The effects of soaking the skin in water atvarious temperatures on the subsequent ability to sweat. J. Phy8iol. 194, 1-11.

BRETCK, K. (1961). Temperature regulation in the newborn infant. Biologia Neonat. 3,65-119.

CHATMERs, T. M. & KEELE, C. A. (1952). The nervous and chemical control of sweating.Br. J. Derm. 64, 43-54.

COON, J. M. & ROTHMAN, S. (1941). Sweat response to drugs with nicotine-like action.J. Pharmac. exp. Ther. 73, 1-11.

FARR, V., MITCHELL, R. G., NELIGAN, G. A. & PARKIN, J. M. (1966). The definition of someexternal characteristics used in the assessment of gestational age in the newborn infant.Devel. Med. Child Neurol. 8, 507-511.

FOSTER, K. G. (1966). Composition of the secretion from the eccrine sweat glands of thecat's foot pad. J. Phy8iol. 184, 106-119.

FOSTER, K. G., HEY, E. N. & KATZ, G. (1968). Eccrine sweat function in the new-born baby.J. Physiol. 198, 36-37P.

27

28 K. G. FOSTER, E. N. HEY AND G. KATZFOSTER, K. G. & WEINER, J. S. (1967). The continuous monitoring of sweat secretion ofman and cat using a ventilated capsule and an infra-red analyzer. J. Physiol. 191, 1-2P.

GIBSON, L. E. & COOKE, R. E. (1959). A test for concentration of electrolytes in sweat incystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics, Spring-field 23, 545-549.

GuTTMANN, L. (1937). Ein neues einfaches colorimetriches Verfahren zur Untersuchung derSchweissdriserfunktion. Klin. Wschr. 16, 1212-1213.

GuTTMANN, L. (1940). Topographic studies of disturbances of sweat secretion after completelesions of peripheral nerves. J. Neurol. Psychiat., Lond. 3, 197-210.

HATFIELD, H. S. & WILKINS, F. J. (1950). A new heart-flow meter. J. scent. Inmtrum. 27,1-3.HERTIG, B. A., RIEDESEL, M. L. & BELDING, H. S. (1961). Sweating in hot baths. J. apple.

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of eccrine sweat glands in patients with cystic fibrosis and in healthy controls. Pediatrics,Springfield 38, 613-618.

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KOLLIKER, A. (1850). Zur Entwicklungeschichte der Aussern Haut. Z. wi8s. Zool. 2, 67-96.K6YAMA, K. (1937). 'Ober die Verteilung der Schweissdrusen bei der Japaner. Okajimas

Folia anat. jap. 15, 571-594.KUNo, Y. (1956). Human Perspiration, chaps. 4 and 5. Springfield: Thomas.MACHIDA, H. (1964). A histochemical study on the skin of human embryo. Okajimas Folia

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regional difference in the amount of sweat. (In Japanese.) J. orient. Med. 23, 1155-1186.(Also English abstract 98-101.)

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SzAB6, G. (1962). The number of eccrine sweat glands in human skin. Adv. Biol. Skin 3, 1-5.TANIGUCHI, T. & KURITA, Y. (1938). tiber die Verteilung der Schweissdrcisen bei den

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japanischen Feten. Okajimas Folia anat. jap. (Erg.-bd.) 15, 265-293.THOMSON, M. L. & SUTARMAN (1953). The identification and enumeration of active sweat

glands in man from plastic impressions of the skin. Trans. R. Soc. trop. Med. Hyg. 47,412-417.

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The Journal of Physiology, Vol. 203, No. 1

Babv

K. G. FOSTER, E. N. HEY AN-D G. KATZ

Plate 1

(Facing p. 28)

The Journal of Physiology, Vol. 203, No. I

Adult

K. 0. FOSTER, E. N. HEY AND G. KATZ

Plate 2

SWEAT RESPONSES ON THE NEW-BORN BABY 29

EXPLANATION OF PLATES

Records of the numbers of sweat glands activated by the injection of 2 jug ACh in 0-2 ml.saline intradermally into the lateral aspect of the thigh in a full-term baby 8 days old(Plate 1) and an adult (Plate 2). The position occupied by the ventilated capsule immediatelybefore the record was obtained is indicated by the circle 1 cm in diameter. The plates showthe appearance of the plastic skin impression obtained by the method of Thomson &Sutarman (1953); the white pin-holes mark the position of the ducts of activated sweatglands. The line block below each plate shows how the record has been interpreted; thepecked line indicates the approximate position of the indwelling needle. The density ofactive glands is much greater in the baby than in the adult, but in the baby the glands haveonly been stimulated over a limited area close to the needle track.