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The newborn of diabetic mothers
THE
NEWBORN
ALVAH
OF DIABETIC
L. NEWCOMB, M.D.,
MOTHERS*
WINNETIS,
ILL.
T
HERE have been advances in the medical management of maternal diabetes, obstetric care, and pediatric care, but a relatively high st,illhir%h ant1 neonatal death rate has persisted. The fetal wastage still varies from II per cent to 30 per cent. The pathologic abnormality of the infant of the diabetic woman is most striking in the lungs and pancreas. The pathologic picture in the infant pancreas may be nonspecific, but it is often remarkable. The islets are occasionally huge-generally much larger than the islets of infants with erythroblastosis fetalis. Recently McKay’ has described an eosinophilic cellular infiltrate. Charcot-Leyden crystals, and dispersion of the beta cells throughout the islet. in contrast t,o the usual location of the beta cells in the center of the islet. The inflammatory eosinophilie infiltrate may give rise to Charcot-.Iiryrlen crystals. The pathologic picture in the lungs varies from complete atelectasis oC both lungs in the small premature infant to a lesser degree of pulmonaq hyaline membrane disease in the older, larger infant who survives two 01’three days. There is usually extensive atelectasis in a large percentage of the alveoli; most of the remaining alveoli are lined with hyaline-staining nlatcrial 10 to 20 microns thick. Lowrey” of the University of Michigan reported that infants of diabetic mothers had “extremely variable plasma chloride and total base levels and a high proportion of these had an uncompensated acidosis with a lowered pII when compared to the normal newborn infant,. The high CO, tension indicates that ventilatory control of this factor was lacking whether the fault 1)~ central or pulmonary.” Furthermore, they stated that “there appears to 1,~. a direct correlation between the degree of infantile acidosis and the severit,y of the abnormal clinical picture present.” They state that the exact cause of this acidosis is not at present clear. The clinical picture of these babies varies tremendously. Generally the infants of mothers with the greatest edema, hypertension, and polyhydramnios develop the syndrome with which we are concerned. The newborn infant who develops pulmonary hyaline disease may need some help in respiration, but. the infant who cries spontaneously often does too. The infant may ),e restless and whining or he may be lethargic. Retraction becomes more marked, the *Presented
at
Pediatric Society, and
the joint meeting of the Chicago Diabetic
the Chicago .Association, 74
Gynecological Nov. 19, 19.54.
Society,
the
Chicng~
Volume
71
NEWBORN
1Number 1
OF
DIABETIC
MOTHERS
75
cyanosis deepens, and death ensues shortly thereafter. However, there are some babies who, having had these symptoms, slowly improve in two or three days and make a complete recovery. When convulsions develop in an infant previously doing well, particularly if maternal diabetes has been undiagnosed or poorly managed, hypoglycemia may be the cause. A badly spastic infant or death may be the result occasionally. Experience accumulated lowing management :
in many clinics
over the years
suggests
the fol-
Consultation between the internist, the obstetrician, and the pediatrician t,o determine the optimal day for delivery, which is usually between the thirtysixth and thirty-eighth week. Minimum analgesia and anesthesia. and often acidotic, respiratory depression
Since the infant is usually may be anticipated.
premature
Postural drainage, clearing the airway, and stripping the cord, which are customary procedures, are mandatory in these infants. Gastric aspiration on the resuscitation table is also mandatory, and it shoulcl be repeated for the first few hours if necessary. The infant should be transferred immediately to a humid incubator. Antibiotics may be prescribed, especially if there has been resuscitation anil there are signs of respiratory distress. Feedings are delayed twelve t.o forty-eight hours depending on the condition of the infant. Glucose, 2$$ to 5 per cent, is given by dropper, nipple, or gavage at twelve hours in the stronger infant but is delayed in the infant who is retracting. Half breast milk and then breast milk follow as soon as the infant tolerates glucose. The relatively high fetal death rate of infants of diabetic mothers is attributed to many factors. The exact etiology is not yet fully established. Until such time as more is known of the metabolism of these newborn infants, the foregoing therapeutic measures are our best hope.
References 1. McKay,
Donald 1953. 2. Ido\\rrcy, George
G.,
Benirschke,
H.,
Graham,
Kurt, Bruce
B.,
and
Curtis,
and
Tsao,
George M.
U.:
W.:
Obst.
Pediatrics
& Gj-ne~. 13:
527,
2:
1:13,
19%.
Discussion DR. MATTHEW M. STEINER.-The high fetal mortality still remains problem in the management of diabetes during pregnancy. Many factors posed, some based on purely anatomical alterations in the infant-while rived from biochemical investigations on rather small groups of infants. in the newborn infant no general agreement as to the basic disturbances mother, and particularly the role of diabetes per se in the frequency of cyanosis from respiratory distress, and at times fatal shock in the infant.
a perplexing have been proothers are deThere is as yet of a diabetic stillbirth
or of
76
NEWCOMB
Am. I. Obst. & Gynec. January. 1956
with vascular changes 1s The juvenile patient with severe diabetes Toxemia is then one of the prone to toxemia and to high fetal wastage. The high incidence of factors in fetal mortality but it is not the sole factor. deaths between the thirty-fourth and thirty-seventh weeks hns prompttd man) the pregnancy with whatever method is deemerl advisable-but this has ereatetl lems for the premature infant. Many adequately Syndromes hyperplasia commonly
particularly contributing intrallterine 10 interrupt new proI)-
anatomical aberrations have been proposed, none of which collectivc~l: e.uljlairl factor which must be responsible for the increased fetal mortality. the “lethal” hematopoiesis of the li\,cxr, and of maerosomia, cardiomegaly, visceromegalp, While exccssivcly large l,nllicls tlo orel~f of the islets have been described. in the diabetic patient, it is unusual that ilystocia aIone is the CXUS~ of death.
Again, not all diabetic mothers give birth to large babies---nor is there a direct correla tion between the size of the infant and the cardiomegaly or visceromegaly. There is 110 to some c&ma, ant1 doubt that these heavy infants have more adipose tissue in addition which in the mother ma? IIC r(‘the etiology may well be the increased growvth hormone, sponsible for the diabetes while in the infant it gives rise to macrosomia. and Wilson, Init there The incidence of cardiomegaIy has bten stressed by Miller are decided objections to attributing the fetal mortality to changes in the heart.,, viscera, islets, or liver. For one, there is the prime dificulty in judging the size of the heart b: bgain, evidence of cardiac failure and/or em the roentgcn shadow in the young infant. Islet hyperplasia ma>- be noted in conditions other than barrassment was notably lacking. diabetes-and it is possible that the whole syndrome may not be related to an) single factor. It is perplexing to note that the infants reported by Miller and Wilson did well when placed in oxygen because of respiratory distress and cyanosis, had large hearts on x-ray, and at autopsy no definite pulmonary lesions were reported. Pulmonary hyaline membrane has been proposed by Winter and Gellis as the chara<,teristic pathology in the infant, with respiratory distress, and there is general agreement that this is the pat,hological picture in large series of infants examined. Yet Some of the “hvaline L membrane disease ” go on to infants who clinically have something resembling recover slowlp. It is interest.ing that the European literflture has little reference to tks entity. One may ask what environmental or intrinsic factor are responsible for the l,rr,. and also what. biochemical changes :tr~ duction of the intra-alveolar hyaline membrane:, evidenced when an infant recovers from hyaline mpml~rane disease. In the figures rt’ported by Winter and Gellis as to the frequent)of hyalirre membrane in infants dcliverell by cesarean section of diabetic and nondiabetic mothers it is not clear what role diabetes itself plays in setting the intra-alveolar stage for the formation of a membranc~. If’ WC compare the figures of Blystad and others as to the frequer1c.v in casarean section in norn~al women we find that there is not much diffcLrc>ncap. Some clue as to the mechanism of l,r+ duction of hyaline membrane may be found in :L recent report by Stevenson and I,anfe ,lri the experimental production of hyaline membrane which suggests that aspiration of :L~Y!niotic fluid plus intra-alveolar exudation (from intense capillary engorgement! may b(a necessxry. This brings up a vascular element which will lye referred to Inter. In recent years, biochemical investigations have demonstrated many int.ersst.irrg facts about the newborn of the diabetic mother, but t,he 6’lothal” factor still remains a myster). It was customary at one time to attribute fetal mortality to hypoglycemic shock, and the initial therapy with concentrated glucose was directed to overcoming the threatening fall in blood glucose. Recent studies of the normal variation of blood glucose in normal infants have minimized the role of hypoglycemia. Similarly, Miller and Wilson, Geltis and Smith found no correlation between the clinicsal picture, clinical syndrome or electrolyte pattern, and the level of the blood sugar. Marc recently, Komrower of Manchester found wide variations in the blood sugar of these infants as compared with that ill normal ill-fants. A very interesting study of the blood sugar during the first da,y of life in infants of diabetic mothers has been done by Pedersen of Copenhagen. The configuration of blood
Volume Number
71 I
NEWBORN
OF
DIABETIC
MOTHERS
77
sugar curves was the same in diabetic and normal cases when the infants were kept under The average blood sugar during the first day is inversely prop”“standard conditions. tiOnal to the average blood sugar level of the mother during the last months Of I)regnan”? and directly proportional to the average blood sugar level at delivery. The l)lood suga’ levels are also proportional to the birth weights-inversely proportional in infants Ot diabetic mothers and directly proportional in those of normal mothers. %Canx of thr‘ varying blood sugar levels and the correlations found in this Studv, no genera]izatiOll~ C:lii be made concerning the question whether the hlood sugar is lower in the infant of tht’ There was also no correlation between the pathOlogical S~nlptoms a~(1 diabetic mother. the blood sugar level during neonatal periods. Hioehenlical data and electrolyte survt:~s have failed to demonstrale thal iI1 lht' of hyperpituitarism with sec~onll:ll~> infant of the diabetic mother there o~urli :< state hyperadrenocorticism and consequent hypernatremia and hypokalemia. Tt ~o11lrl 1~ YI’~> gratifying to attribute the entire clinical picture in t,he severely distressed infant to slll:h Observations of Cook and Smith and others havr alterations in electrolytes and water. shown that h’a, R, and Cl excretion was greater in infants of diabetic mothers when com pared with that of normal infants of comparable weight, but was the same ai in n0rm81 TJriue volumes and weight losses were greater in infants of comparable gestational age. Here, too, if thy sodium and chloride excretions follon-i$z infants of diabetic mothers. birth are used as indices of edema per kilogram of body w-eight, it is seen that infants of diabetic mothers have approximately t.he ~:+mp amount of edema per kilogram that ontX definitcxly more than the rlorrrl:ll infaril would expect for their gestational age, althou$I Agail), individual variations within the group of diabetit, illfaflth of the same weight. were considerable, and there was no constant relationship between the ~x~.e.csive birtll XOW weight and the water or electrolyte excretiolls (luring the first three postnatal cl:iy~ over, these conclusions are conditioned hp the fact that. this work was done ~)II infautznot too severely distressed after birth. Rjorklund, in a study of 10 of 15 cascrj! liounll * * abuormxl gestive of hyperkalemia. In 4 of these cases the serum I< was well agreed that the ECG is an unreliable inflicator of serum pretation of F:CX+ even in the norma infant often leads to errors.
” 1~lectrocartlioglanis sug low. However, it is fair]>I< changes ant1 the iut.rr-
1-n a study of the chemical homeostxsis of infants of diabetic mothers, Lowray anrl ot,hers concluded that there is a lowered pH ar~(l uncompensated acidoh in nlany (ji&.ressed infants while there is great variability in ihe range of plasma chloride and total base. These findings do not indicate that there is retention of total base and hence I]() not support a hypothesis that there is overactivity of the adrenal cortex with sodium retentiotl, lowered K, anr7 consequent. edema. The lowered pH and relatively normal bicarbonate lvould also teud to rule against the accumulation of large amounts of acid metabolites as a cause of the uncompensated acidosis; i.e., there exists rather a high partial pressure of co,. This might he the result of pulmonary edema aurl/or atelectasis causing retentioll of CO, or the result of cerebral edema. Rue11 a metallolic disturbance would tie in wit11 hyalinc membrane disease but the exact mechanism is also not definitely establishe~l. l)itWl, White, and Duckers recently reported on the changes in the pat,tern of the smaller h]OOd vessels in the bulbar eonjrmetiva in children of diabetic mothers. Thest! changes were noted particularly in the capillaries and venales and ranged from elongatioli and irregularities to edema, hyaline infiltrat,ion, distention agith slowing of the blood flow, and hemorrhage. There appeared to be a positive correlation between t,he severit)of th
NEWBORN
ALVAH
OF DIABETIC
L. NEWCOMB, M.D.,
MOTHERS*
WINNETIS,
ILL.
T
HERE have been advances in the medical management of maternal diabetes, obstetric care, and pediatric care, but a relatively high st,illhir%h ant1 neonatal death rate has persisted. The fetal wastage still varies from II per cent to 30 per cent. The pathologic abnormality of the infant of the diabetic woman is most striking in the lungs and pancreas. The pathologic picture in the infant pancreas may be nonspecific, but it is often remarkable. The islets are occasionally huge-generally much larger than the islets of infants with erythroblastosis fetalis. Recently McKay’ has described an eosinophilic cellular infiltrate. Charcot-Leyden crystals, and dispersion of the beta cells throughout the islet. in contrast t,o the usual location of the beta cells in the center of the islet. The inflammatory eosinophilie infiltrate may give rise to Charcot-.Iiryrlen crystals. The pathologic picture in the lungs varies from complete atelectasis oC both lungs in the small premature infant to a lesser degree of pulmonaq hyaline membrane disease in the older, larger infant who survives two 01’three days. There is usually extensive atelectasis in a large percentage of the alveoli; most of the remaining alveoli are lined with hyaline-staining nlatcrial 10 to 20 microns thick. Lowrey” of the University of Michigan reported that infants of diabetic mothers had “extremely variable plasma chloride and total base levels and a high proportion of these had an uncompensated acidosis with a lowered pII when compared to the normal newborn infant,. The high CO, tension indicates that ventilatory control of this factor was lacking whether the fault 1)~ central or pulmonary.” Furthermore, they stated that “there appears to 1,~. a direct correlation between the degree of infantile acidosis and the severit,y of the abnormal clinical picture present.” They state that the exact cause of this acidosis is not at present clear. The clinical picture of these babies varies tremendously. Generally the infants of mothers with the greatest edema, hypertension, and polyhydramnios develop the syndrome with which we are concerned. The newborn infant who develops pulmonary hyaline disease may need some help in respiration, but. the infant who cries spontaneously often does too. The infant may ),e restless and whining or he may be lethargic. Retraction becomes more marked, the *Presented
at
Pediatric Society, and
the joint meeting of the Chicago Diabetic
the Chicago .Association, 74
Gynecological Nov. 19, 19.54.
Society,
the
Chicng~
Volume
71
NEWBORN
1Number 1
OF
DIABETIC
MOTHERS
75
cyanosis deepens, and death ensues shortly thereafter. However, there are some babies who, having had these symptoms, slowly improve in two or three days and make a complete recovery. When convulsions develop in an infant previously doing well, particularly if maternal diabetes has been undiagnosed or poorly managed, hypoglycemia may be the cause. A badly spastic infant or death may be the result occasionally. Experience accumulated lowing management :
in many clinics
over the years
suggests
the fol-
Consultation between the internist, the obstetrician, and the pediatrician t,o determine the optimal day for delivery, which is usually between the thirtysixth and thirty-eighth week. Minimum analgesia and anesthesia. and often acidotic, respiratory depression
Since the infant is usually may be anticipated.
premature
Postural drainage, clearing the airway, and stripping the cord, which are customary procedures, are mandatory in these infants. Gastric aspiration on the resuscitation table is also mandatory, and it shoulcl be repeated for the first few hours if necessary. The infant should be transferred immediately to a humid incubator. Antibiotics may be prescribed, especially if there has been resuscitation anil there are signs of respiratory distress. Feedings are delayed twelve t.o forty-eight hours depending on the condition of the infant. Glucose, 2$$ to 5 per cent, is given by dropper, nipple, or gavage at twelve hours in the stronger infant but is delayed in the infant who is retracting. Half breast milk and then breast milk follow as soon as the infant tolerates glucose. The relatively high fetal death rate of infants of diabetic mothers is attributed to many factors. The exact etiology is not yet fully established. Until such time as more is known of the metabolism of these newborn infants, the foregoing therapeutic measures are our best hope.
References 1. McKay,
Donald 1953. 2. Ido\\rrcy, George
G.,
Benirschke,
H.,
Graham,
Kurt, Bruce
B.,
and
Curtis,
and
Tsao,
George M.
U.:
W.:
Obst.
Pediatrics
& Gj-ne~. 13:
527,
2:
1:13,
19%.
Discussion DR. MATTHEW M. STEINER.-The high fetal mortality still remains problem in the management of diabetes during pregnancy. Many factors posed, some based on purely anatomical alterations in the infant-while rived from biochemical investigations on rather small groups of infants. in the newborn infant no general agreement as to the basic disturbances mother, and particularly the role of diabetes per se in the frequency of cyanosis from respiratory distress, and at times fatal shock in the infant.
a perplexing have been proothers are deThere is as yet of a diabetic stillbirth
or of
76
NEWCOMB
Am. I. Obst. & Gynec. January. 1956
with vascular changes 1s The juvenile patient with severe diabetes Toxemia is then one of the prone to toxemia and to high fetal wastage. The high incidence of factors in fetal mortality but it is not the sole factor. deaths between the thirty-fourth and thirty-seventh weeks hns prompttd man) the pregnancy with whatever method is deemerl advisable-but this has ereatetl lems for the premature infant. Many adequately Syndromes hyperplasia commonly
particularly contributing intrallterine 10 interrupt new proI)-
anatomical aberrations have been proposed, none of which collectivc~l: e.uljlairl factor which must be responsible for the increased fetal mortality. the “lethal” hematopoiesis of the li\,cxr, and of maerosomia, cardiomegaly, visceromegalp, While exccssivcly large l,nllicls tlo orel~f of the islets have been described. in the diabetic patient, it is unusual that ilystocia aIone is the CXUS~ of death.
Again, not all diabetic mothers give birth to large babies---nor is there a direct correla tion between the size of the infant and the cardiomegaly or visceromegaly. There is 110 to some c&ma, ant1 doubt that these heavy infants have more adipose tissue in addition which in the mother ma? IIC r(‘the etiology may well be the increased growvth hormone, sponsible for the diabetes while in the infant it gives rise to macrosomia. and Wilson, Init there The incidence of cardiomegaIy has bten stressed by Miller are decided objections to attributing the fetal mortality to changes in the heart.,, viscera, islets, or liver. For one, there is the prime dificulty in judging the size of the heart b: bgain, evidence of cardiac failure and/or em the roentgcn shadow in the young infant. Islet hyperplasia ma>- be noted in conditions other than barrassment was notably lacking. diabetes-and it is possible that the whole syndrome may not be related to an) single factor. It is perplexing to note that the infants reported by Miller and Wilson did well when placed in oxygen because of respiratory distress and cyanosis, had large hearts on x-ray, and at autopsy no definite pulmonary lesions were reported. Pulmonary hyaline membrane has been proposed by Winter and Gellis as the chara<,teristic pathology in the infant, with respiratory distress, and there is general agreement that this is the pat,hological picture in large series of infants examined. Yet Some of the “hvaline L membrane disease ” go on to infants who clinically have something resembling recover slowlp. It is interest.ing that the European literflture has little reference to tks entity. One may ask what environmental or intrinsic factor are responsible for the l,rr,. and also what. biochemical changes :tr~ duction of the intra-alveolar hyaline membrane:, evidenced when an infant recovers from hyaline mpml~rane disease. In the figures rt’ported by Winter and Gellis as to the frequent)of hyalirre membrane in infants dcliverell by cesarean section of diabetic and nondiabetic mothers it is not clear what role diabetes itself plays in setting the intra-alveolar stage for the formation of a membranc~. If’ WC compare the figures of Blystad and others as to the frequer1c.v in casarean section in norn~al women we find that there is not much diffcLrc>ncap. Some clue as to the mechanism of l,r+ duction of hyaline membrane may be found in :L recent report by Stevenson and I,anfe ,lri the experimental production of hyaline membrane which suggests that aspiration of :L~Y!niotic fluid plus intra-alveolar exudation (from intense capillary engorgement! may b(a necessxry. This brings up a vascular element which will lye referred to Inter. In recent years, biochemical investigations have demonstrated many int.ersst.irrg facts about the newborn of the diabetic mother, but t,he 6’lothal” factor still remains a myster). It was customary at one time to attribute fetal mortality to hypoglycemic shock, and the initial therapy with concentrated glucose was directed to overcoming the threatening fall in blood glucose. Recent studies of the normal variation of blood glucose in normal infants have minimized the role of hypoglycemia. Similarly, Miller and Wilson, Geltis and Smith found no correlation between the clinicsal picture, clinical syndrome or electrolyte pattern, and the level of the blood sugar. Marc recently, Komrower of Manchester found wide variations in the blood sugar of these infants as compared with that ill normal ill-fants. A very interesting study of the blood sugar during the first da,y of life in infants of diabetic mothers has been done by Pedersen of Copenhagen. The configuration of blood
Volume Number
71 I
NEWBORN
OF
DIABETIC
MOTHERS
77
sugar curves was the same in diabetic and normal cases when the infants were kept under The average blood sugar during the first day is inversely prop”“standard conditions. tiOnal to the average blood sugar level of the mother during the last months Of I)regnan”? and directly proportional to the average blood sugar level at delivery. The l)lood suga’ levels are also proportional to the birth weights-inversely proportional in infants Ot diabetic mothers and directly proportional in those of normal mothers. %Canx of thr‘ varying blood sugar levels and the correlations found in this Studv, no genera]izatiOll~ C:lii be made concerning the question whether the hlood sugar is lower in the infant of tht’ There was also no correlation between the pathOlogical S~nlptoms a~(1 diabetic mother. the blood sugar level during neonatal periods. Hioehenlical data and electrolyte survt:~s have failed to demonstrale thal iI1 lht' of hyperpituitarism with sec~onll:ll~> infant of the diabetic mother there o~urli :< state hyperadrenocorticism and consequent hypernatremia and hypokalemia. Tt ~o11lrl 1~ YI’~> gratifying to attribute the entire clinical picture in t,he severely distressed infant to slll:h Observations of Cook and Smith and others havr alterations in electrolytes and water. shown that h’a, R, and Cl excretion was greater in infants of diabetic mothers when com pared with that of normal infants of comparable weight, but was the same ai in n0rm81 TJriue volumes and weight losses were greater in infants of comparable gestational age. Here, too, if thy sodium and chloride excretions follon-i$z infants of diabetic mothers. birth are used as indices of edema per kilogram of body w-eight, it is seen that infants of diabetic mothers have approximately t.he ~:+mp amount of edema per kilogram that ontX definitcxly more than the rlorrrl:ll infaril would expect for their gestational age, althou$I Agail), individual variations within the group of diabetit, illfaflth of the same weight. were considerable, and there was no constant relationship between the ~x~.e.csive birtll XOW weight and the water or electrolyte excretiolls (luring the first three postnatal cl:iy~ over, these conclusions are conditioned hp the fact that. this work was done ~)II infautznot too severely distressed after birth. Rjorklund, in a study of 10 of 15 cascrj! liounll * * abuormxl gestive of hyperkalemia. In 4 of these cases the serum I< was well agreed that the ECG is an unreliable inflicator of serum pretation of F:CX+ even in the norma infant often leads to errors.
” 1~lectrocartlioglanis sug low. However, it is fair]>I< changes ant1 the iut.rr-
1-n a study of the chemical homeostxsis of infants of diabetic mothers, Lowray anrl ot,hers concluded that there is a lowered pH ar~(l uncompensated acidoh in nlany (ji&.ressed infants while there is great variability in ihe range of plasma chloride and total base. These findings do not indicate that there is retention of total base and hence I]() not support a hypothesis that there is overactivity of the adrenal cortex with sodium retentiotl, lowered K, anr7 consequent. edema. The lowered pH and relatively normal bicarbonate lvould also teud to rule against the accumulation of large amounts of acid metabolites as a cause of the uncompensated acidosis; i.e., there exists rather a high partial pressure of co,. This might he the result of pulmonary edema aurl/or atelectasis causing retentioll of CO, or the result of cerebral edema. Rue11 a metallolic disturbance would tie in wit11 hyalinc membrane disease but the exact mechanism is also not definitely establishe~l. l)itWl, White, and Duckers recently reported on the changes in the pat,tern of the smaller h]OOd vessels in the bulbar eonjrmetiva in children of diabetic mothers. Thest! changes were noted particularly in the capillaries and venales and ranged from elongatioli and irregularities to edema, hyaline infiltrat,ion, distention agith slowing of the blood flow, and hemorrhage. There appeared to be a positive correlation between t,he severit)of th