FETUS, PLACENTA, AND NEWBORN
Fetal growth retardation in relation to maternal smoking and weight gain in pregnancy HERBERT
C.
KHATAB PAUL Kansas
A.
MILLER,
M.D.
HASSANEIN,
PH.D.
HENSLEIGH,
M.D.,
PH.D.
City, Kansas
Two types of fetal growth retardation were recognized in term infants. One type was characterized by an abnormally low ponder-al index (defined as birth weight in grams x 100 + crown-heel length in cubic centimeters). The other type of growth-retarded infants had abnormally short crown-heel lengths for fetal age. Both types were observed under all conditions studied. However, mothers who smoked cigarettes during pregnancy were more likely to have infants with short body lengths for dates, whereas mothers who had low weight gain in pregnancy were more likely to have infants with low ponderal indices. Social group, prepegnancy weight, parity, marital status, and fetal sex were found to be less determinant of fetal growth than were maternal weight gain and smoking habits.
CIGARETTE SMOKING and low weight gain by pregnant mothers have been associated with more frequent delivery of term infants weighing under 2,500 grams at birth. r-lo The possible effects of smoking and of low weight gain were intermixed in these previous studies; investigations concerned primarily with smoking made no allowances for the possible effects of low weight gain and vice versa. Furthermore, no attempt was made in these previous studies to identify different somatic types of fetal
growth retardation (FGR). The present study was undertaken to compare the incidences of term infants with FGR between smoking and nonsmoking mothers and between mothers with low weight gain and mothers who had greater weight gain. Two somatic types of FGR were identified, and their relationships to maternal smoking and low weight gain were determined. Gruenwald” described two types of FGR. He believed that the “long, thin baby” was the result of wasting that occurred during a period of days prior to birth and that in the second type there was a general cessation of fetal growth extending over a period of weeks before birth, with the result that deficits in body weight and length at birth were proportional. A study in this clinic suggested that the ponderal indices (PI’s) of infants with the first type of FGR were markedly reduced.12 The PI’s of infants with the second type were not markedly reduced, but crown-heel lengths were short for fetal ages. Further studies in this clinic suggested that mothers who were pre-eclamptic or who
From the Departments of Pediatrics, Biometry, and Gynecology and Obstetrics, University of Kansas Medical Center, College of Health Sciences and Hospital. Supported in part 2404 Pennsylvania
by a grant from Mead Johnson U Co., St., Evansville, Indiana 47721.
Received
for publication
Accepted
September
July
23,
1975.
18, 1975.
Reprint requests: Dr. Herbert C. Miller, The University Kansas Medical Center College of Health Sciences and Hospital, Rainbow Blvd. at 39th, Kanw City, Kansas 66103.
of
55
56
Miller, Hassanein, and Hensieigh
Y- 4% $ 47
I 0. s’0 0.
8
o&e. . 0.
46 45 I
0
0.l ..
.
I . 1 . I . I 37. 39 41 43 GESTATION- wks.
Fig. 1. Range of crown-heel lengths (1.5 to 98.5 Percentile) at birth of 590 term infants of both sexes and born to nonsmoking white mothers of all parities who did not have low weight gain or serious complications during pregnancy. o = SHFD infants of nonsmoking mothers: . = SHFD infants of smoking mothers.
had low weight gain in pregnancy had an increased risk of delivering infants with markedly reduced PI’s 13, l4 A later study in this clinic suggested that smoking by mothers during pregnancy was associated with significant reductions in mean crown-heel lengths of term infants but not in the mean PI’s.15 The reduction in mean body lengths of term infants born to smoking mothers led to the hypothesis that maternal smoking was associated with the second type of FGR. Infants in the present study with this second type of FGR have been labeled as “short for dates” (SHFD) to distinguish them from the first type which have been designated by the term “low PI’s”
Muterial and methods The population studied included white mothers with uncomplicated pregnancies, consecutively delivered of their infants at the University of Kansas Medical Center during 1973 and 1974. Infants and their mothers were excluded if the infants had clinically recognizable intrauterine infections or congenital malformations or were multiple births. Mothers with the following complications of pregnancy were also excluded: pre-eclampsia, chronic alcoholism, ingestion of “hard” or addicting drugs, diseases requiring immunosuppressive drug therapy, epilepsy treated with phenobarbital or diphenylhydantoin, chronic renal disease, cancer, chronic hypertension, significant third-trimester vaginal bleeding, diabetes mellitus and gestational diabetes, isoimmunization to bloodgrouping factors, and impaired cardiac function.
All infants were weighed and measured after birth by one of us (H. C. M.) according to methods previously reported from this clinic. i2 The diagnosis of a term birth (2 37 weeks) was made primarily on the presence of the physical signs that characterize term infants. Neurological signs of maturity were also used, but physical signs took precedence, because some of the term infants with FGR showed evidence of immaturity in neurologic examinations. In doubtful situations, the presence of secondary centers of ossification in the knee on roentgen examination and the obstetric estimated date of confinement were taken into consideration. Gestational age was calculated from the first day of the mother’s last menstrual period in terms of completed weeks. In this study the FGR group included not only term infants weighing less than 2,500 grams but also heavier term infants who either had low ponderal indices or were SHFD. The criteria for the heavier infants were either a crown-heel length below the 1..5 percentile for the gestational age (Fig. 1) or a ponderal index below the third percentile. Rohrer’si’j formula was used in calculating ponderal indices of infants: birth weight in grams x 100 + crown-heel length in cubic centimeters. All mothers were interviewed during the postpartum hospitalization by one of us (H. C. M.) to obtain information on the amount of smoking during pregnancy, and the obstetric records were then reviewed for additional medical information. Mothers were placed in the smoking group if they smoked any cigarettes during any part of pregnancy. Mothers were divided into two social groups-high and low-by the following criteria. The tow social group included mothers on welfare and mothers who could not pay full hospital costs for their deliveries; mothers in the low social group corresponded to the poverty group defined by the United States Department of- Labor.‘r All other mothers were placed in the high social group. The prepregnancy weight category of each mother was determined on the basis of weight at conception in relation to height, with Sargent’sIs weight-height table for young women. Mothers were classified as having above average, average, or below average prepregnancy weights, with the use of Sargent’s normal weight rt 7.5 per cent to define the average group. Weight gain was calculated in terms of mean pounds gained per week in the last two trimesters by one of two methods. Method A was used in all mothers whose prenatal visits covered 10 weeks or more of the last two trimesters and whose last prenatal weight was recorded within two weeks of delivery; the weight gained between the first and last prenatal visits in the last two
Fetal growth retardation related to maternal smoking and weight gain
Volume Number
125 1
Table
I. Relationship
of FGR in term white infants
to maternal
Nonsmoking
Social
class
High LOW TOtd
466 222 688
Infants with FGR NO.
8 8 16
in pregnancy
and social class
Smoking mothers
mothers Total infants (No.)
smoking
57
70
Total infant.5 (No.)
1.7 3.6 2.3
205 (a*) 219 (b*) 424
Infants with FGR (No.)
11 15 26
%
5.3 6.8 6.1
Chi-square value
7.64 2.38 10.4
P 0.05 -co.01
*The incidences of smoking mothers in the high social class (a) was 30 per cent and in the low social class(b) was 52 per cent; on application of the chi-square test, the difference was significant (p < 0.001).
trimesters was divided by the number of elapsed weeks to give the mean amount gained per week. Weight gain was determined by Method A in 80 per cent of the mothers. Method B was used in the remaining mothers; three pounds were subtracted from the total weight gain to make allowance for weight theoretically gained in the first trimester; the remainder then was divided by the number of completed weeks of gestation in the last two trimesters of pregnancy to give the mean weight gained per week. A mean weight gain of less than 0.5 pound per week in the last two trimesters was arbitrarily considered a low weight gain (LWG) in the present study. Results There were 1,112 term infants in the present study born to mothers who gained 0.5 pound per week or more on the average in the last two trimesters. The range of weight gain among these 1,112 mothers was wide. The possible effect of wide differences in weight gain on FGR was investigated by dividing the 1,112 mothers into high-weight-gain and medium-weightgain groups. The 5 18 mothers in the high-weight-gain group gained more than one pound per week on the average in the last two trimesters; the mean weight gain was 1.22 pound per week. The 594 mothers in the medium-weight-gain group gained from 0.5 to one pound per week on the average in the last two trimesters; the mean weight gain was 0.81 pound per week. The frequency of infants with FGR was not significantly different between these two weight-gain groups with the use of the chi-square test, for either smoking or nonsmoking mothers. Consequently, the mothers in the high-and medium-weight-gain groups were combined for subsequent analysis. In the combined’ high- and medium-weight-gain groups, there were 42 infants (3.8 per cent) with FGR. Data were collected for several independent variables on the 42 mothers of these infants with FGR and the
1,070 mothers of infants who did not have FGR. On application of the chi-square test, there were no significant differences between the group with FGR and the normal-growth group with respect to the following variables: maternal height (short [
Fetal growth retardation in relation to maternal smoking and weight gain in pregnancy HERBERT
C.
KHATAB PAUL Kansas
A.
MILLER,
M.D.
HASSANEIN,
PH.D.
HENSLEIGH,
M.D.,
PH.D.
City, Kansas
Two types of fetal growth retardation were recognized in term infants. One type was characterized by an abnormally low ponder-al index (defined as birth weight in grams x 100 + crown-heel length in cubic centimeters). The other type of growth-retarded infants had abnormally short crown-heel lengths for fetal age. Both types were observed under all conditions studied. However, mothers who smoked cigarettes during pregnancy were more likely to have infants with short body lengths for dates, whereas mothers who had low weight gain in pregnancy were more likely to have infants with low ponderal indices. Social group, prepegnancy weight, parity, marital status, and fetal sex were found to be less determinant of fetal growth than were maternal weight gain and smoking habits.
CIGARETTE SMOKING and low weight gain by pregnant mothers have been associated with more frequent delivery of term infants weighing under 2,500 grams at birth. r-lo The possible effects of smoking and of low weight gain were intermixed in these previous studies; investigations concerned primarily with smoking made no allowances for the possible effects of low weight gain and vice versa. Furthermore, no attempt was made in these previous studies to identify different somatic types of fetal
growth retardation (FGR). The present study was undertaken to compare the incidences of term infants with FGR between smoking and nonsmoking mothers and between mothers with low weight gain and mothers who had greater weight gain. Two somatic types of FGR were identified, and their relationships to maternal smoking and low weight gain were determined. Gruenwald” described two types of FGR. He believed that the “long, thin baby” was the result of wasting that occurred during a period of days prior to birth and that in the second type there was a general cessation of fetal growth extending over a period of weeks before birth, with the result that deficits in body weight and length at birth were proportional. A study in this clinic suggested that the ponderal indices (PI’s) of infants with the first type of FGR were markedly reduced.12 The PI’s of infants with the second type were not markedly reduced, but crown-heel lengths were short for fetal ages. Further studies in this clinic suggested that mothers who were pre-eclamptic or who
From the Departments of Pediatrics, Biometry, and Gynecology and Obstetrics, University of Kansas Medical Center, College of Health Sciences and Hospital. Supported in part 2404 Pennsylvania
by a grant from Mead Johnson U Co., St., Evansville, Indiana 47721.
Received
for publication
Accepted
September
July
23,
1975.
18, 1975.
Reprint requests: Dr. Herbert C. Miller, The University Kansas Medical Center College of Health Sciences and Hospital, Rainbow Blvd. at 39th, Kanw City, Kansas 66103.
of
55
56
Miller, Hassanein, and Hensieigh
Y- 4% $ 47
I 0. s’0 0.
8
o&e. . 0.
46 45 I
0
0.l ..
.
I . 1 . I . I 37. 39 41 43 GESTATION- wks.
Fig. 1. Range of crown-heel lengths (1.5 to 98.5 Percentile) at birth of 590 term infants of both sexes and born to nonsmoking white mothers of all parities who did not have low weight gain or serious complications during pregnancy. o = SHFD infants of nonsmoking mothers: . = SHFD infants of smoking mothers.
had low weight gain in pregnancy had an increased risk of delivering infants with markedly reduced PI’s 13, l4 A later study in this clinic suggested that smoking by mothers during pregnancy was associated with significant reductions in mean crown-heel lengths of term infants but not in the mean PI’s.15 The reduction in mean body lengths of term infants born to smoking mothers led to the hypothesis that maternal smoking was associated with the second type of FGR. Infants in the present study with this second type of FGR have been labeled as “short for dates” (SHFD) to distinguish them from the first type which have been designated by the term “low PI’s”
Muterial and methods The population studied included white mothers with uncomplicated pregnancies, consecutively delivered of their infants at the University of Kansas Medical Center during 1973 and 1974. Infants and their mothers were excluded if the infants had clinically recognizable intrauterine infections or congenital malformations or were multiple births. Mothers with the following complications of pregnancy were also excluded: pre-eclampsia, chronic alcoholism, ingestion of “hard” or addicting drugs, diseases requiring immunosuppressive drug therapy, epilepsy treated with phenobarbital or diphenylhydantoin, chronic renal disease, cancer, chronic hypertension, significant third-trimester vaginal bleeding, diabetes mellitus and gestational diabetes, isoimmunization to bloodgrouping factors, and impaired cardiac function.
All infants were weighed and measured after birth by one of us (H. C. M.) according to methods previously reported from this clinic. i2 The diagnosis of a term birth (2 37 weeks) was made primarily on the presence of the physical signs that characterize term infants. Neurological signs of maturity were also used, but physical signs took precedence, because some of the term infants with FGR showed evidence of immaturity in neurologic examinations. In doubtful situations, the presence of secondary centers of ossification in the knee on roentgen examination and the obstetric estimated date of confinement were taken into consideration. Gestational age was calculated from the first day of the mother’s last menstrual period in terms of completed weeks. In this study the FGR group included not only term infants weighing less than 2,500 grams but also heavier term infants who either had low ponderal indices or were SHFD. The criteria for the heavier infants were either a crown-heel length below the 1..5 percentile for the gestational age (Fig. 1) or a ponderal index below the third percentile. Rohrer’si’j formula was used in calculating ponderal indices of infants: birth weight in grams x 100 + crown-heel length in cubic centimeters. All mothers were interviewed during the postpartum hospitalization by one of us (H. C. M.) to obtain information on the amount of smoking during pregnancy, and the obstetric records were then reviewed for additional medical information. Mothers were placed in the smoking group if they smoked any cigarettes during any part of pregnancy. Mothers were divided into two social groups-high and low-by the following criteria. The tow social group included mothers on welfare and mothers who could not pay full hospital costs for their deliveries; mothers in the low social group corresponded to the poverty group defined by the United States Department of- Labor.‘r All other mothers were placed in the high social group. The prepregnancy weight category of each mother was determined on the basis of weight at conception in relation to height, with Sargent’sIs weight-height table for young women. Mothers were classified as having above average, average, or below average prepregnancy weights, with the use of Sargent’s normal weight rt 7.5 per cent to define the average group. Weight gain was calculated in terms of mean pounds gained per week in the last two trimesters by one of two methods. Method A was used in all mothers whose prenatal visits covered 10 weeks or more of the last two trimesters and whose last prenatal weight was recorded within two weeks of delivery; the weight gained between the first and last prenatal visits in the last two
Fetal growth retardation related to maternal smoking and weight gain
Volume Number
125 1
Table
I. Relationship
of FGR in term white infants
to maternal
Nonsmoking
Social
class
High LOW TOtd
466 222 688
Infants with FGR NO.
8 8 16
in pregnancy
and social class
Smoking mothers
mothers Total infants (No.)
smoking
57
70
Total infant.5 (No.)
1.7 3.6 2.3
205 (a*) 219 (b*) 424
Infants with FGR (No.)
11 15 26
%
5.3 6.8 6.1
Chi-square value
7.64 2.38 10.4
P 0.05 -co.01
*The incidences of smoking mothers in the high social class (a) was 30 per cent and in the low social class(b) was 52 per cent; on application of the chi-square test, the difference was significant (p < 0.001).
trimesters was divided by the number of elapsed weeks to give the mean amount gained per week. Weight gain was determined by Method A in 80 per cent of the mothers. Method B was used in the remaining mothers; three pounds were subtracted from the total weight gain to make allowance for weight theoretically gained in the first trimester; the remainder then was divided by the number of completed weeks of gestation in the last two trimesters of pregnancy to give the mean weight gained per week. A mean weight gain of less than 0.5 pound per week in the last two trimesters was arbitrarily considered a low weight gain (LWG) in the present study. Results There were 1,112 term infants in the present study born to mothers who gained 0.5 pound per week or more on the average in the last two trimesters. The range of weight gain among these 1,112 mothers was wide. The possible effect of wide differences in weight gain on FGR was investigated by dividing the 1,112 mothers into high-weight-gain and medium-weightgain groups. The 5 18 mothers in the high-weight-gain group gained more than one pound per week on the average in the last two trimesters; the mean weight gain was 1.22 pound per week. The 594 mothers in the medium-weight-gain group gained from 0.5 to one pound per week on the average in the last two trimesters; the mean weight gain was 0.81 pound per week. The frequency of infants with FGR was not significantly different between these two weight-gain groups with the use of the chi-square test, for either smoking or nonsmoking mothers. Consequently, the mothers in the high-and medium-weight-gain groups were combined for subsequent analysis. In the combined’ high- and medium-weight-gain groups, there were 42 infants (3.8 per cent) with FGR. Data were collected for several independent variables on the 42 mothers of these infants with FGR and the
1,070 mothers of infants who did not have FGR. On application of the chi-square test, there were no significant differences between the group with FGR and the normal-growth group with respect to the following variables: maternal height (short [
