The clinical prediction of intrauterine growth retardation R. S. GALBRAITH, E. J. W. J.
KARCHMAR,
N. A.
M.D. B.A.
PIERCY, LOW,
Kingston,
Ontario,
M.D.
M.D. Cunctdct
From a total study group of 8,030 deliveries, 2,788 patients with risk factors and 292 representative patients from the 5,242 patients without risk factors were selected for detailed analysis of predictors of intrauterine growth retardation (IUGR). Two thirds of the IUGR infants came from the population with risk factors and a weighting was assigned to individual risk factors. One third of the IUGR infants came from the population without risk factors, and their mothers demonstrated significantly differing maternal characteristics from those with a normally grown infant. The perinatal mortality rate was higher in the IUGR group and particularly in the population with risk factors. (AM. J. OBSTET.
GYNECOL.
133:281,
1979.)
INTRAUTERINE growth retardation (IUGR) accounts for a significant increase in perinatal mortality rates as well as immediate neonatal morbidity and continuing long-term disability in some of the survivors.‘-4 Two thirds of IUGR infants are not recognized antenatally,” although the presumption is that early recognition could change the morbidity and mortality rates associated with this condition. In order to improve the antenatal detection of IUGR, a risk score specific for this problem is needed. This study was designed to provide the clinical data necessary to establish a proper weighting for the factors considered in such a scoring system.
Methodology The charts of all patients delivered at the Kingston General Hospital from January 1, 1974, to December 3 1, 1977. were reviewed at the time of delivery. These totaled 8,186 births. As only those infants felt to be growth retarded due to a suboptimal intrauterine environment were to be included in the study, 156 infants with congenital anomalies, whether major or minor, From the Department Queen i Un wersity.
of Obstetrics
and Gynaecolog,
Presented by invitation at the Thirty-fourth Annual Meeting qf The Society of Obstetricians and Gynaecologzsts of Canada, Winnipeg, Manitoba, Canada, June 15-18, 1978. Reprint requests: Dr. J. A. Low, Department of Obstetrics and Gpaecoloa, Queen’s Uniuersity, Kingston, Ontario, Canada K7L 21’7.
OOOZ-9378179/030281+06$00.60/0~
1979The
C.V.Mosby
Co
were excluded from the study. This left a total population of 8,030 patients for study. These patients produced 395 IUGR infants. (IUGR was defined in this study as any infant born weighing less than the tenth percentile on Gruenwald’s weight-gestational agegrowth curve).‘j The 8,030 patients were assessed for the presence of antenatal clinical complications, hereafter referred to as potential risk factors. There were 2,788 patients who displayed one or more potential risk factors; 5,242 patients did not display recognizable potential risk factors; 122 IUGR infants came from those 5,242 patients. In order to obtain a representative sample from the group without risk factors, the 170 patients who were delivered during the time period of August to September, 1977, and had a normally grown infant, were arbitrarily designated representative of the total group without risk factors. Therefore, the population selected for detailed study included the 2,788 patients who had potential risk factors, the 122 patients from the group without risk factors who delivered a growth-retarded infant, and the 170 representative patients from the group without risk factors. Table I illustrates the distribution of this study population into IUGR and non-IUGR components and shows that in the non-IUGR infants the weight percentile distribution of the 170 representative infants is equivalent to that of the infants from the group with risk factors.
281
282
Galbraith
et al.
Table I. Distribution of infant in pregnancies studied*
weight
percentiles
IUGR No risk factors
Cl0
122
Non-IUGR Risk factors
No risk factors
Risk factors
273
lo-24 25-74 >75
20 a2 68
412 1,248 923
*There were 2,856 infants born to the 2,788 patients with risk factors, and their weight percentiles are compared to the 170 without risk factors. Table II. Incidence of IUGR in the total group, the group without risk factors, and the group with risk factors
Patients-total births Patients-no potential risk factors poPatients-with tential risk factors
1 Incidence(%i
Total
1 IUGR
8,030 5,242
395 122
4.9 2.3
2,788
273
9.8
The data from this total study population included maternal characteristics such as prepregnancy weight, maternal clinical data, delivery, and infant data. These were itemized on individual coding sheets for computer purposes. If the data, as taken from the clinical history sheet and prenatal record, were incomplete, the data were obtained, while the mother was in hospital, by personal interview by the reviewer. The only data coded were those deemed valid on scrutiny at the time of delivery. A concurrent study of drug use, carried on during a 6 month period in 1976, on the antenatal use of alcohol, caffeine, and prescription and nonprescription drugs provided additional information for this study. The data coded were based on clearly defined criteria. Maternal characteristics included prepregnancy weight, defined as the weight immediately prior to pregnancy; weight gain, defined as the total weight gain prior to labor; and smoking, divided into none. less than a package a day, a package a day, or more than a package a day. Risk factors. Risk factors were divided into four categories. Past gestational cornplicatiom. IUGR was defined as applying to any infant weighing less than 2,720 gms at term, or less than the tenth percentile if the exact weight and gestation for that prior pregnancy were known. Recurrent abortion referred to three previable pregnancy failures, usually spontaneous abortion, but
not excluding tubal pregnanq, mole, or therapeutic abortion. Fetal death was defined as an? pre- or intrapartum death occurring after 20 weeks’ gestation. Neonatal death was defined as an)- death occurring post partum and within 28 days of birth. Preterm delivery was defined as applying to an inf‘ant born before 37 weeks from the last menstrual period. All congenital anomalies, whether major or minor, were simpl) considered birth defects. Internal ruedid comnplirntiorts. This category included essential hypertension, defined as a blood pressure greater then 13OiYO mm Hg both before and after the current pregnancy, and severe hypertension, defined as a blood pressure equal to or greater than 1601110 both before and after the current pregnancy. Renal disease was defined as known disease of the kidneys and further subdivided into glomerulonephritis, chronic pyelonephritis, stone, congenital anomaly, and “other,” which included unexplained albuminuria. Diabetes mellitus was subdivided into gestational. diagnosed subsequent to an abnormal glucose tolerance test and not requiring insulin, and clinical. requiring insulin. Urinary tract infection was included if symptomatic urinary tract disease, with or without positive culture, was treated with antibiotics. “Other medical illnesses” included cardiopulmonary disease, mental disease requiring treatment, anemia, surgery during pregnancy, collagen diseases, or malignancies. Obstetric complicrzth~. Antepartum haemorrhage was defined as any known vaginal bleeding. was divided into three trimesters, and in the third trimester was identified as being due to placenta previa. partial placental separation, OI “unknown.” Pre-eclamptic tosemia was defined on the basis of one or more of the following: a systolic blood pressure greater than 140 or a rise of 30 m m Hg. a diastolic blood pressure greatel than 90 or a rise of 20 mm Hg, or significant proteinuria of 300 mg/24 hours or more recorded on two separate occasions. Severe toxemia was defined on the basis of a systolic blood pressure greater than 160 mm Hg, a diastolic blood pressure greater than 110 mm Hg, proteinuria in excess of 5 gm/24 hours, or oliguria less than 400 ml124 hours. “Other obstetric complications” included uterine abnormalities, prolonged membrane rupture, and hpdramnios. Prx~ent ge.rtationnl cornplicntionJ. This category included preterm delivery defined as occurring in an infant born at less than 37 weeks’ gestation, and multiple pregnancy. defined as any pregnancy resulting in two or more infants. The data sheets were then coded and computerized and rhe result3 were analyzed with Student’s t test, Within each complication, or risk factor, the frequency
Volume 133 Number 3
Table
III. Maternal
Clinical prediction of IUGR
characteristics
in patients
studied
IUGR
Maternal weight (lb) Weight gain (lb) Smoking*
283
Nm-IUGR
ND.
Mean
SD
NO.
262 257 198
125 22 2.1
26 11 0.9
1,847 1,830 1,564
Mean
SD
Sign~cance
132 27 1.6
28 12 0.9
0.001 0.001 0.001
*Smoking was coded as: 0, none; 1, less than one package; 2, one package; 3, more than one package per day. Table
IV. Maternal
characteristics
in patients
without
risk factors*
IUGR
Maternal weight (lb) Weight gain (lb) Smoking
Non-IUGR
NO.
Mean
SD
107 100 62
123 22 2.3
24.0 10.6 0.9
No.
Mean
SD
Signijicance
158 153 155
130 27 1.5
23.1 9.0 0.8
0.02 0.001 0.001
*In the 292 patients without risk factors, there were three significantly differing bearing an IUGR infant vs. those 170 patients bearing a non-IUGR infant. Table
V. Significant
characteristics
in patients
without
risk factors* Non-IUGR
IUGR
First pregnancy
Fundal height
maternal characteristics in those 122 patients
No.
%
No.
%
Signz$icance
71/122
58
591170
35
0.001
No.
Mean (cm)
SD
No.
87
32.4
2.5
142
Mean
(cm)
36.4
SD
2.7
0.001
*The two significant characteristics in the group without a risk factor were first pregnancy and fundal height. of interrelationships with other risk factors was analyzed with chi squares to demonstrate significance where it might exist.
Results The incidence of IUGR in the overall obstetric population is 4.9%. In the population with no potential risk factors the incidence is only 2.3%; in the population with potential risk factors it is 9.8% (Table II). In the population studied in detail, certain maternal characteristics stand out as significant when the patients delivered of an IUGR infant are compared to those whose infant was normally grown. Table III illustrates that these were maternal weight, weight gain during pregnancy, and smoking. These three maternal characteristics were again significant in the select population without risk factors (Table IV). In the population without risk factors, more of the patients delivered of growth-retarded infants were primiparous than those delivered of a normally grown infant. Fundal heights were measured by the admitting physician at the time of admission in labor. There was a significant difference in the mean fundal heights between those women
subsequently delivered of an IUGR infant and those delivered of a non-IUGR infant (Table V). There were no significant differences between the mothers producing IUGR and non-IUGR infants as regards the use of alcohol, prescription or nonprescription drugs, or caffeine. The population with risk factors was then looked at. In each factor group, the incidence was determined by comparing the number of IUGR for that factor to the total number of patients with that factor. The risk factors were considered in the categories into which they naturally fell. Each category is considered in Tables VI to IX. Past gestational complications. In order to clarify the importance of the individual factor, all infants with complex, concurrent interrelationships were removed. In the IUGR group those infants with a concurrent congenital anomaly were removed; in the preterm, the fetal death, and the neonatal death groups, those with associated IUGR and/or congenital anomalies were removed from analysis. All six groups in this category showed an increased incidence of IUGR but previous IUGR was by far the strongest indicator. In this cate-
284
Galbraith
F‘ebruary .hn. J. Obstet.
et al.
Table VI. Incidence of IUGR in pregnancies in which there had been a past gestational complication* Total
IUGR
384 91 106 64 260 109
77 10 10 6 23 8
IUGR Recurrent abortion Fetal death (S.B.) Neonatal death Preterm Congenital anomaly
IUGR
(%>)
20 11 9.4 9.4 9 8
*The factors considered were singly found. Table VII. Incidence of IUGR in pregnancies a maternal medical complication.
I
Total
with
~~
( IUGR
EGR
93 9
11
24 79 495 73
IUGR
363 39
38 12
10.5 31
640 115
51 13
8 11
250 42
19
8 12
378
41
IVGR
(sl)
hemorrhage
First trimester First trimester with recurrence Second trimester Second trimester with recurrence Third trimester
12.0
4
44.0
5 4 39 11
21.0 5.0 8.0 15.0
Table IX. Incidence of IUGR gestational complication*
I
Renal:
Nephritis Others Urinary tract infection Cardiopulmonary
Total Pre-eclamQtic toxemia Mild-moderate Severe Antepartum
in pregnancies
5
11
(%)
Hy@rkn.&n:
Mild-moderate Severe
Table VIII. Incidence of IUGR with an obstetric complication
I. 1979 Gynecol.
gory each factor was analyzed as to the significance of other variables in other categories and no significant variables were found. Maternal medical complications. Table VII shows the frequency of each complication, with the number of IUGR infants resulting from that complication, and the incidence of IUGR for that complication. The strongest factors here were severe hypertension and nephritis. Cardiopulmonary disease, when considered as one factor, showed a significant increase in the incidence of IUGR. This group included cardiac disease, peripheral vascular disease, asthma, bronchitis, and pneumonia, but each alone had too few numbers to permit meaningful analysis. Urinary tract infection includes the total number of patients who had, at any time, a urinary tract infection. This is a common problem and is associated with an increased risk of IUGR. “Other” medical complications included a wide spectrum of medical disease. Individually, statistical analysis per diagnosis was not valid due to the modest numbers. On wider grouping into those with similar problems, these showed no significant increased incidence of IUGR. Again, in this category, each factor was analyzed as to the significance of other variables and no significant variables were found. Obstetric complications. Those with a significant increase in IUGR incidence are summarized in Table VIII. The incidence of IUGR in the current pregnancy was moderately increased if the pregnancy was complicated by pre-eclamptic toxemia. However, with severe
Multiple pregnancy Preterm
Total
in pregnancies
1 IUGR
with
/ IUGR
(%)
136
29
21
314
35
11
*The multiple pregnancy number in this table refers to the number of infants born. toxemia, the incidence of IUGR rose to 3 1%. The gestational age in this group showed a significant difference between the IUGR and non-IUGR infants: the IUGR infants had a mean gestational age of 38.6 weeks and the non-IUGR infants 39.8 (p < 0.001). Antepartum hemorrhage in the first or second trimester had the same incidence; if it recurred in a subsequent trimester the incidence increased to equal that of antepartum hemorrhage in the third trimester. The antepartum hemorrhage in the third trimester, when due to partial placental separation, had an incidence of 17.4%. In the review of related significant variables, carried out for this category, toxemia was significantly associated with partial placental separation (p < 0.001). “Other” obstetric complications, when broken down into their separate components, had too small numbers per component to permit meaningful analysis. Gestational complications. Table IX shows the frequency of preterm and multiple pregnancies, the number of IUGR infants in each factor, and the resultant incidence per factor. Multiple pregnancy showed a very large increase in the incidence of IUGR. In the study of the significance of other variables, gestational age is another variable that proved interesting, in that the gestational age in the I UGR infants was higher than in the non-IUGR infants (38.6 vs. 35.7 weeks, p < 0.001). There was also an increased incidence of IUGR in the premature group. The outcome of‘ the IUGR pregnancies was com-
Volume Number
133 3
Clinical
Table X. Perinatal mortality rate including all births greater than 500 gm but excluding congenital anomalies* Total births Non-IUGR group IUGR group IUGR with no risk factors IUGR with risk factors *The IUGR had a fourfold those normally
Perkatal death
7,635 395 122 273
prediction
of IUGR
285
5000.
Rate/l ,000 total births
123 22 4 18
16.1 55.7 32.8 65.9
infants from a pregnancy with increase of perinatal mortality grown.
4000
a risk factor compared to 3000.
Table XI. Increasing incidence of IUGR increase in number of risk factors Risk factors
Incidence
0 1 2 3 or more
with
of IUGR
NO. OF PATIENTS
(%) 2000,
2.3 8.0 10.7 14.0
pared to those without IUGR. The mean Apgar score at 1 minute was consistently lower if the infant was growth retarded. Perinatal deaths of all the infants weighing more than 500 gms were reviewed (Table X). All congenital anomalies had been removed to be consistent with the study objectives. The increased frequency
of’ perinatal
death
in
IUGR
infants
0
is again
noted, with the risk being twice that of the non-IUGR infants in those coming from patients without risk factors, and with the risk quadrupling if the infants came from the group with risk factors. The mean gestational age of the IUGR infants who died was 35.9 weeks.
Comment The definition of IUGR in the literature is not uniform. Various authors have used varying criteria, be it the third or tenth percentile, or 2 SD from the mean, on differing growth curves. This only serves to illustrate the need to define IUGR per individual study. For this study we have defined IUGR as being any infant born weighing less than the tenth percentile on Gruenwald’s birth weight-gestational age-growth curve, which has been used in this center as a reference standard for 10 years. With these criteria the incidence of IUGR is 4.9%‘. In our own Kingston growth curve,? recently completed, the IUGR population in this study falls below our fifth percentile. IUGR is multifactorial in origin.’ Reduced fetal growth may occur secondary to genetic factors, teratogenetic agents, or specific infections such as rubella. It
I
Fig. 1. Distribution patient.
of patients
2
FACTORS
72
based on number
of factors
per
may also be due to a relative deficiency of the intrauterine environment. It is postulated that this chronic intrauterine insult may be a result of altered maternal blood flow, altered maternal nutrient supply, or altered transfer mechanisms of nutrients or energy in the intervillous space. We have specifically excluded all those IUGR pregnancies recognized to be due to genetic, infective, or teratogenetic mechanisms, and the IUGR of the infants included in this study is felt to be due to a suboptimal intrauterine environment. The known significance of IUGR, as reported in the literature, is reemphasized when one notes the increased perinatal mortality rate of IUGR infants in this study. It is interesting to note that in the low-risk group the perinatal mortality rate of IUGR infants was twice that IUGR
of
the infants
total
non-IUGR
of the high-risk
infants, group
whereas the perinatal
in
the mor-
tality rate was four times that of the non-IUGR group. This increased mortality rate becomes more relevant yet when it is recognized that most of these perinatal
286
f
Galbraith et al.
I.U.G.R.
February 1, 1979 Am. J. Obstet. Gyned
I
PAST GESTATIONAL
UT I.
1
IAPH T=
MATERNAL
COMPLICATIONS
MEDICAL
COMPLICATIONS
I
OBSTETRICAL
COMPLICATIONS
Multiple Pregnancy IPreterm
1 GESTATIONAL
n
k
lb
COMPLICATIONS 1’5
2b X Risk
risk in on unmarked populotion Fig. 2. Risk assigned IUGR incidence.
to each factor
significant
for increased
deaths in IUGR infants occur when the infant is close to maturity. The diagnosis of IUGR antenatally is important if the perinatal mortality and morbidity rates are to be reduced. The diagnosis of IUGR requires the anticipa-
tion of this complication in the obstetric population. Identification of ICGR by degrees of risk is difficult. Of our total obstetric population, 65% exhibited no potential risk factors and ma)- be classified as “low risk.” with a low incidence of IUGR. Only 35% of our population exhibited one or more potential risk factors and could be called “high risk.” The incidence here was 9.8%. Suspicion of IUGR requires the appropriate, selective use of laboratory aids, such as ultrasound” and maternal estrogen assays,‘” which are currently available. Although the incidence of IUGR in the low-risk group is low, this group, by comprising the majority of the total obstetric population, manages to produce one third of all the IUGR infants born. The only antenatal measures of risk available in these pregnancies are the maternal characteristics of primiparity, prepregnancy weight, weight gain, and smoking. The clinical prediction of IUGR in these low-risk patients is heavily dependent on the serial measurement of fundal height in order to demonstrate plateauing or static fetal growth. Of the total population, 35% showed one or more risk factors and accounted for two thirds of the total IUGR infants produced. These risk factors are clinical complications, noted on history or physical examination, and are readily apparent during the antenatal period; 21% had one factor and 14% had two or more factors. In Table XI can be seen the cumulative effects of increasing numbers of risk factors on the progressive increase in the incidence of IUGR. Fig. I shows the distribution of the frequent?- of risk factors in the total population. In this preliminary analysis, the degree of risk for each individual factor is shown in Fig. 2 and was derayed from the incidence of IUGR in each factor, compared to the incidence in the unmarked population. This weighting was done by simple analysis. Because 14%’ of our total population showed more than one risk factor, a further analysis of multiple variants is necessary to give a finite weighting to each risk factor. This will allow the formulation of a risk score specific for IUGR, in order to increase the antenatal prediction of this pregnancy complication.
REFERENCES 1. Battaglia, J. C.: AM. J. OBSTET. GYNECOL. 106:1103, 1970. 2. Davies, P., and Stewart, A.: Br. Med. Bull. 31:85, 1975. 3. Fitzhardinge, P. M., and Steven, E. M.: Pediatrics 50:50. 1972. 4. Low, J. A., Galbraith, R. S., Muir, D.. et al.: AM. J. OBSTET.GYNECOL. 130:534, 1978. 5. Tejani, N., Mann, L. I., and Weiss. R. R.: Obstet. Gynecol. 47:31, 1976.
6. Gruenwald, P.: AM. J. OBSTET. GYNECOL. 94: 1112, 1966. 7. Low. J. A., Galbraith, R. S.. and Karchmar, J.: Kingston Growth Curve, unpublished data, 1978. 8. Page, E. W.: AM. J. OBSTET. GYNECOL. 104~378, 1969. 9. Campbell, S.: Perinatol. 1:507, 1974. 10. Galbraith, R. S., and Low, J. A.: AM. J. OBSTET. GYNECOL. 106:352, 1970.
KARCHMAR,
N. A.
M.D. B.A.
PIERCY, LOW,
Kingston,
Ontario,
M.D.
M.D. Cunctdct
From a total study group of 8,030 deliveries, 2,788 patients with risk factors and 292 representative patients from the 5,242 patients without risk factors were selected for detailed analysis of predictors of intrauterine growth retardation (IUGR). Two thirds of the IUGR infants came from the population with risk factors and a weighting was assigned to individual risk factors. One third of the IUGR infants came from the population without risk factors, and their mothers demonstrated significantly differing maternal characteristics from those with a normally grown infant. The perinatal mortality rate was higher in the IUGR group and particularly in the population with risk factors. (AM. J. OBSTET.
GYNECOL.
133:281,
1979.)
INTRAUTERINE growth retardation (IUGR) accounts for a significant increase in perinatal mortality rates as well as immediate neonatal morbidity and continuing long-term disability in some of the survivors.‘-4 Two thirds of IUGR infants are not recognized antenatally,” although the presumption is that early recognition could change the morbidity and mortality rates associated with this condition. In order to improve the antenatal detection of IUGR, a risk score specific for this problem is needed. This study was designed to provide the clinical data necessary to establish a proper weighting for the factors considered in such a scoring system.
Methodology The charts of all patients delivered at the Kingston General Hospital from January 1, 1974, to December 3 1, 1977. were reviewed at the time of delivery. These totaled 8,186 births. As only those infants felt to be growth retarded due to a suboptimal intrauterine environment were to be included in the study, 156 infants with congenital anomalies, whether major or minor, From the Department Queen i Un wersity.
of Obstetrics
and Gynaecolog,
Presented by invitation at the Thirty-fourth Annual Meeting qf The Society of Obstetricians and Gynaecologzsts of Canada, Winnipeg, Manitoba, Canada, June 15-18, 1978. Reprint requests: Dr. J. A. Low, Department of Obstetrics and Gpaecoloa, Queen’s Uniuersity, Kingston, Ontario, Canada K7L 21’7.
OOOZ-9378179/030281+06$00.60/0~
1979The
C.V.Mosby
Co
were excluded from the study. This left a total population of 8,030 patients for study. These patients produced 395 IUGR infants. (IUGR was defined in this study as any infant born weighing less than the tenth percentile on Gruenwald’s weight-gestational agegrowth curve).‘j The 8,030 patients were assessed for the presence of antenatal clinical complications, hereafter referred to as potential risk factors. There were 2,788 patients who displayed one or more potential risk factors; 5,242 patients did not display recognizable potential risk factors; 122 IUGR infants came from those 5,242 patients. In order to obtain a representative sample from the group without risk factors, the 170 patients who were delivered during the time period of August to September, 1977, and had a normally grown infant, were arbitrarily designated representative of the total group without risk factors. Therefore, the population selected for detailed study included the 2,788 patients who had potential risk factors, the 122 patients from the group without risk factors who delivered a growth-retarded infant, and the 170 representative patients from the group without risk factors. Table I illustrates the distribution of this study population into IUGR and non-IUGR components and shows that in the non-IUGR infants the weight percentile distribution of the 170 representative infants is equivalent to that of the infants from the group with risk factors.
281
282
Galbraith
et al.
Table I. Distribution of infant in pregnancies studied*
weight
percentiles
IUGR No risk factors
Cl0
122
Non-IUGR Risk factors
No risk factors
Risk factors
273
lo-24 25-74 >75
20 a2 68
412 1,248 923
*There were 2,856 infants born to the 2,788 patients with risk factors, and their weight percentiles are compared to the 170 without risk factors. Table II. Incidence of IUGR in the total group, the group without risk factors, and the group with risk factors
Patients-total births Patients-no potential risk factors poPatients-with tential risk factors
1 Incidence(%i
Total
1 IUGR
8,030 5,242
395 122
4.9 2.3
2,788
273
9.8
The data from this total study population included maternal characteristics such as prepregnancy weight, maternal clinical data, delivery, and infant data. These were itemized on individual coding sheets for computer purposes. If the data, as taken from the clinical history sheet and prenatal record, were incomplete, the data were obtained, while the mother was in hospital, by personal interview by the reviewer. The only data coded were those deemed valid on scrutiny at the time of delivery. A concurrent study of drug use, carried on during a 6 month period in 1976, on the antenatal use of alcohol, caffeine, and prescription and nonprescription drugs provided additional information for this study. The data coded were based on clearly defined criteria. Maternal characteristics included prepregnancy weight, defined as the weight immediately prior to pregnancy; weight gain, defined as the total weight gain prior to labor; and smoking, divided into none. less than a package a day, a package a day, or more than a package a day. Risk factors. Risk factors were divided into four categories. Past gestational cornplicatiom. IUGR was defined as applying to any infant weighing less than 2,720 gms at term, or less than the tenth percentile if the exact weight and gestation for that prior pregnancy were known. Recurrent abortion referred to three previable pregnancy failures, usually spontaneous abortion, but
not excluding tubal pregnanq, mole, or therapeutic abortion. Fetal death was defined as an? pre- or intrapartum death occurring after 20 weeks’ gestation. Neonatal death was defined as an)- death occurring post partum and within 28 days of birth. Preterm delivery was defined as applying to an inf‘ant born before 37 weeks from the last menstrual period. All congenital anomalies, whether major or minor, were simpl) considered birth defects. Internal ruedid comnplirntiorts. This category included essential hypertension, defined as a blood pressure greater then 13OiYO mm Hg both before and after the current pregnancy, and severe hypertension, defined as a blood pressure equal to or greater than 1601110 both before and after the current pregnancy. Renal disease was defined as known disease of the kidneys and further subdivided into glomerulonephritis, chronic pyelonephritis, stone, congenital anomaly, and “other,” which included unexplained albuminuria. Diabetes mellitus was subdivided into gestational. diagnosed subsequent to an abnormal glucose tolerance test and not requiring insulin, and clinical. requiring insulin. Urinary tract infection was included if symptomatic urinary tract disease, with or without positive culture, was treated with antibiotics. “Other medical illnesses” included cardiopulmonary disease, mental disease requiring treatment, anemia, surgery during pregnancy, collagen diseases, or malignancies. Obstetric complicrzth~. Antepartum haemorrhage was defined as any known vaginal bleeding. was divided into three trimesters, and in the third trimester was identified as being due to placenta previa. partial placental separation, OI “unknown.” Pre-eclamptic tosemia was defined on the basis of one or more of the following: a systolic blood pressure greater than 140 or a rise of 30 m m Hg. a diastolic blood pressure greatel than 90 or a rise of 20 mm Hg, or significant proteinuria of 300 mg/24 hours or more recorded on two separate occasions. Severe toxemia was defined on the basis of a systolic blood pressure greater than 160 mm Hg, a diastolic blood pressure greater than 110 mm Hg, proteinuria in excess of 5 gm/24 hours, or oliguria less than 400 ml124 hours. “Other obstetric complications” included uterine abnormalities, prolonged membrane rupture, and hpdramnios. Prx~ent ge.rtationnl cornplicntionJ. This category included preterm delivery defined as occurring in an infant born at less than 37 weeks’ gestation, and multiple pregnancy. defined as any pregnancy resulting in two or more infants. The data sheets were then coded and computerized and rhe result3 were analyzed with Student’s t test, Within each complication, or risk factor, the frequency
Volume 133 Number 3
Table
III. Maternal
Clinical prediction of IUGR
characteristics
in patients
studied
IUGR
Maternal weight (lb) Weight gain (lb) Smoking*
283
Nm-IUGR
ND.
Mean
SD
NO.
262 257 198
125 22 2.1
26 11 0.9
1,847 1,830 1,564
Mean
SD
Sign~cance
132 27 1.6
28 12 0.9
0.001 0.001 0.001
*Smoking was coded as: 0, none; 1, less than one package; 2, one package; 3, more than one package per day. Table
IV. Maternal
characteristics
in patients
without
risk factors*
IUGR
Maternal weight (lb) Weight gain (lb) Smoking
Non-IUGR
NO.
Mean
SD
107 100 62
123 22 2.3
24.0 10.6 0.9
No.
Mean
SD
Signijicance
158 153 155
130 27 1.5
23.1 9.0 0.8
0.02 0.001 0.001
*In the 292 patients without risk factors, there were three significantly differing bearing an IUGR infant vs. those 170 patients bearing a non-IUGR infant. Table
V. Significant
characteristics
in patients
without
risk factors* Non-IUGR
IUGR
First pregnancy
Fundal height
maternal characteristics in those 122 patients
No.
%
No.
%
Signz$icance
71/122
58
591170
35
0.001
No.
Mean (cm)
SD
No.
87
32.4
2.5
142
Mean
(cm)
36.4
SD
2.7
0.001
*The two significant characteristics in the group without a risk factor were first pregnancy and fundal height. of interrelationships with other risk factors was analyzed with chi squares to demonstrate significance where it might exist.
Results The incidence of IUGR in the overall obstetric population is 4.9%. In the population with no potential risk factors the incidence is only 2.3%; in the population with potential risk factors it is 9.8% (Table II). In the population studied in detail, certain maternal characteristics stand out as significant when the patients delivered of an IUGR infant are compared to those whose infant was normally grown. Table III illustrates that these were maternal weight, weight gain during pregnancy, and smoking. These three maternal characteristics were again significant in the select population without risk factors (Table IV). In the population without risk factors, more of the patients delivered of growth-retarded infants were primiparous than those delivered of a normally grown infant. Fundal heights were measured by the admitting physician at the time of admission in labor. There was a significant difference in the mean fundal heights between those women
subsequently delivered of an IUGR infant and those delivered of a non-IUGR infant (Table V). There were no significant differences between the mothers producing IUGR and non-IUGR infants as regards the use of alcohol, prescription or nonprescription drugs, or caffeine. The population with risk factors was then looked at. In each factor group, the incidence was determined by comparing the number of IUGR for that factor to the total number of patients with that factor. The risk factors were considered in the categories into which they naturally fell. Each category is considered in Tables VI to IX. Past gestational complications. In order to clarify the importance of the individual factor, all infants with complex, concurrent interrelationships were removed. In the IUGR group those infants with a concurrent congenital anomaly were removed; in the preterm, the fetal death, and the neonatal death groups, those with associated IUGR and/or congenital anomalies were removed from analysis. All six groups in this category showed an increased incidence of IUGR but previous IUGR was by far the strongest indicator. In this cate-
284
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F‘ebruary .hn. J. Obstet.
et al.
Table VI. Incidence of IUGR in pregnancies in which there had been a past gestational complication* Total
IUGR
384 91 106 64 260 109
77 10 10 6 23 8
IUGR Recurrent abortion Fetal death (S.B.) Neonatal death Preterm Congenital anomaly
IUGR
(%>)
20 11 9.4 9.4 9 8
*The factors considered were singly found. Table VII. Incidence of IUGR in pregnancies a maternal medical complication.
I
Total
with
~~
( IUGR
EGR
93 9
11
24 79 495 73
IUGR
363 39
38 12
10.5 31
640 115
51 13
8 11
250 42
19
8 12
378
41
IVGR
(sl)
hemorrhage
First trimester First trimester with recurrence Second trimester Second trimester with recurrence Third trimester
12.0
4
44.0
5 4 39 11
21.0 5.0 8.0 15.0
Table IX. Incidence of IUGR gestational complication*
I
Renal:
Nephritis Others Urinary tract infection Cardiopulmonary
Total Pre-eclamQtic toxemia Mild-moderate Severe Antepartum
in pregnancies
5
11
(%)
Hy@rkn.&n:
Mild-moderate Severe
Table VIII. Incidence of IUGR with an obstetric complication
I. 1979 Gynecol.
gory each factor was analyzed as to the significance of other variables in other categories and no significant variables were found. Maternal medical complications. Table VII shows the frequency of each complication, with the number of IUGR infants resulting from that complication, and the incidence of IUGR for that complication. The strongest factors here were severe hypertension and nephritis. Cardiopulmonary disease, when considered as one factor, showed a significant increase in the incidence of IUGR. This group included cardiac disease, peripheral vascular disease, asthma, bronchitis, and pneumonia, but each alone had too few numbers to permit meaningful analysis. Urinary tract infection includes the total number of patients who had, at any time, a urinary tract infection. This is a common problem and is associated with an increased risk of IUGR. “Other” medical complications included a wide spectrum of medical disease. Individually, statistical analysis per diagnosis was not valid due to the modest numbers. On wider grouping into those with similar problems, these showed no significant increased incidence of IUGR. Again, in this category, each factor was analyzed as to the significance of other variables and no significant variables were found. Obstetric complications. Those with a significant increase in IUGR incidence are summarized in Table VIII. The incidence of IUGR in the current pregnancy was moderately increased if the pregnancy was complicated by pre-eclamptic toxemia. However, with severe
Multiple pregnancy Preterm
Total
in pregnancies
1 IUGR
with
/ IUGR
(%)
136
29
21
314
35
11
*The multiple pregnancy number in this table refers to the number of infants born. toxemia, the incidence of IUGR rose to 3 1%. The gestational age in this group showed a significant difference between the IUGR and non-IUGR infants: the IUGR infants had a mean gestational age of 38.6 weeks and the non-IUGR infants 39.8 (p < 0.001). Antepartum hemorrhage in the first or second trimester had the same incidence; if it recurred in a subsequent trimester the incidence increased to equal that of antepartum hemorrhage in the third trimester. The antepartum hemorrhage in the third trimester, when due to partial placental separation, had an incidence of 17.4%. In the review of related significant variables, carried out for this category, toxemia was significantly associated with partial placental separation (p < 0.001). “Other” obstetric complications, when broken down into their separate components, had too small numbers per component to permit meaningful analysis. Gestational complications. Table IX shows the frequency of preterm and multiple pregnancies, the number of IUGR infants in each factor, and the resultant incidence per factor. Multiple pregnancy showed a very large increase in the incidence of IUGR. In the study of the significance of other variables, gestational age is another variable that proved interesting, in that the gestational age in the I UGR infants was higher than in the non-IUGR infants (38.6 vs. 35.7 weeks, p < 0.001). There was also an increased incidence of IUGR in the premature group. The outcome of‘ the IUGR pregnancies was com-
Volume Number
133 3
Clinical
Table X. Perinatal mortality rate including all births greater than 500 gm but excluding congenital anomalies* Total births Non-IUGR group IUGR group IUGR with no risk factors IUGR with risk factors *The IUGR had a fourfold those normally
Perkatal death
7,635 395 122 273
prediction
of IUGR
285
5000.
Rate/l ,000 total births
123 22 4 18
16.1 55.7 32.8 65.9
infants from a pregnancy with increase of perinatal mortality grown.
4000
a risk factor compared to 3000.
Table XI. Increasing incidence of IUGR increase in number of risk factors Risk factors
Incidence
0 1 2 3 or more
with
of IUGR
NO. OF PATIENTS
(%) 2000,
2.3 8.0 10.7 14.0
pared to those without IUGR. The mean Apgar score at 1 minute was consistently lower if the infant was growth retarded. Perinatal deaths of all the infants weighing more than 500 gms were reviewed (Table X). All congenital anomalies had been removed to be consistent with the study objectives. The increased frequency
of’ perinatal
death
in
IUGR
infants
0
is again
noted, with the risk being twice that of the non-IUGR infants in those coming from patients without risk factors, and with the risk quadrupling if the infants came from the group with risk factors. The mean gestational age of the IUGR infants who died was 35.9 weeks.
Comment The definition of IUGR in the literature is not uniform. Various authors have used varying criteria, be it the third or tenth percentile, or 2 SD from the mean, on differing growth curves. This only serves to illustrate the need to define IUGR per individual study. For this study we have defined IUGR as being any infant born weighing less than the tenth percentile on Gruenwald’s birth weight-gestational age-growth curve, which has been used in this center as a reference standard for 10 years. With these criteria the incidence of IUGR is 4.9%‘. In our own Kingston growth curve,? recently completed, the IUGR population in this study falls below our fifth percentile. IUGR is multifactorial in origin.’ Reduced fetal growth may occur secondary to genetic factors, teratogenetic agents, or specific infections such as rubella. It
I
Fig. 1. Distribution patient.
of patients
2
FACTORS
72
based on number
of factors
per
may also be due to a relative deficiency of the intrauterine environment. It is postulated that this chronic intrauterine insult may be a result of altered maternal blood flow, altered maternal nutrient supply, or altered transfer mechanisms of nutrients or energy in the intervillous space. We have specifically excluded all those IUGR pregnancies recognized to be due to genetic, infective, or teratogenetic mechanisms, and the IUGR of the infants included in this study is felt to be due to a suboptimal intrauterine environment. The known significance of IUGR, as reported in the literature, is reemphasized when one notes the increased perinatal mortality rate of IUGR infants in this study. It is interesting to note that in the low-risk group the perinatal mortality rate of IUGR infants was twice that IUGR
of
the infants
total
non-IUGR
of the high-risk
infants, group
whereas the perinatal
in
the mor-
tality rate was four times that of the non-IUGR group. This increased mortality rate becomes more relevant yet when it is recognized that most of these perinatal
286
f
Galbraith et al.
I.U.G.R.
February 1, 1979 Am. J. Obstet. Gyned
I
PAST GESTATIONAL
UT I.
1
IAPH T=
MATERNAL
COMPLICATIONS
MEDICAL
COMPLICATIONS
I
OBSTETRICAL
COMPLICATIONS
Multiple Pregnancy IPreterm
1 GESTATIONAL
n
k
lb
COMPLICATIONS 1’5
2b X Risk
risk in on unmarked populotion Fig. 2. Risk assigned IUGR incidence.
to each factor
significant
for increased
deaths in IUGR infants occur when the infant is close to maturity. The diagnosis of IUGR antenatally is important if the perinatal mortality and morbidity rates are to be reduced. The diagnosis of IUGR requires the anticipa-
tion of this complication in the obstetric population. Identification of ICGR by degrees of risk is difficult. Of our total obstetric population, 65% exhibited no potential risk factors and ma)- be classified as “low risk.” with a low incidence of IUGR. Only 35% of our population exhibited one or more potential risk factors and could be called “high risk.” The incidence here was 9.8%. Suspicion of IUGR requires the appropriate, selective use of laboratory aids, such as ultrasound” and maternal estrogen assays,‘” which are currently available. Although the incidence of IUGR in the low-risk group is low, this group, by comprising the majority of the total obstetric population, manages to produce one third of all the IUGR infants born. The only antenatal measures of risk available in these pregnancies are the maternal characteristics of primiparity, prepregnancy weight, weight gain, and smoking. The clinical prediction of IUGR in these low-risk patients is heavily dependent on the serial measurement of fundal height in order to demonstrate plateauing or static fetal growth. Of the total population, 35% showed one or more risk factors and accounted for two thirds of the total IUGR infants produced. These risk factors are clinical complications, noted on history or physical examination, and are readily apparent during the antenatal period; 21% had one factor and 14% had two or more factors. In Table XI can be seen the cumulative effects of increasing numbers of risk factors on the progressive increase in the incidence of IUGR. Fig. I shows the distribution of the frequent?- of risk factors in the total population. In this preliminary analysis, the degree of risk for each individual factor is shown in Fig. 2 and was derayed from the incidence of IUGR in each factor, compared to the incidence in the unmarked population. This weighting was done by simple analysis. Because 14%’ of our total population showed more than one risk factor, a further analysis of multiple variants is necessary to give a finite weighting to each risk factor. This will allow the formulation of a risk score specific for IUGR, in order to increase the antenatal prediction of this pregnancy complication.
REFERENCES 1. Battaglia, J. C.: AM. J. OBSTET. GYNECOL. 106:1103, 1970. 2. Davies, P., and Stewart, A.: Br. Med. Bull. 31:85, 1975. 3. Fitzhardinge, P. M., and Steven, E. M.: Pediatrics 50:50. 1972. 4. Low, J. A., Galbraith, R. S., Muir, D.. et al.: AM. J. OBSTET.GYNECOL. 130:534, 1978. 5. Tejani, N., Mann, L. I., and Weiss. R. R.: Obstet. Gynecol. 47:31, 1976.
6. Gruenwald, P.: AM. J. OBSTET. GYNECOL. 94: 1112, 1966. 7. Low. J. A., Galbraith, R. S.. and Karchmar, J.: Kingston Growth Curve, unpublished data, 1978. 8. Page, E. W.: AM. J. OBSTET. GYNECOL. 104~378, 1969. 9. Campbell, S.: Perinatol. 1:507, 1974. 10. Galbraith, R. S., and Low, J. A.: AM. J. OBSTET. GYNECOL. 106:352, 1970.
