- Email: [email protected]
The clinical utility of maternal body mass index in pregnancy
Catalano, Merritt, and Mead Am
3. Wittek AE, Yeager AS, Au DS, Hensleigh PA. Asymptomatic shedding of herpes simplex virus from the cervix and lesion site during pregnancy: correlation of antepartum shedding with shedding at delivery. AJDC 1984;138:43942. 4. Arvin AM, Hensleigh PA, Prober CG, et al. Failure of antepartum maternal cultures to predict the infant's risk of exposure to herpes simplex virus at delivery. N Engl J Med 1986;315:796-800. 5. Prober CG, Sullender WM, Yasukawa LL, et al. Low risk of herpes simplex virus infection in neonates exposed to the virus at the time of vaginal delivery to mothers with
J
May 1991 Obstet Gynecol
recurrent genital herpes simplex virus infections. N Engl J Med 1987;316:240-4. 6. Spruance SL, OverallJC, Kern ER, Krueger GG, Pliam U, Miller W. The natural history of recurrent herpes simplex labiales. N EnglJ Med 1986;314:69-75. 7. American College of Obstetricians and Gynecologists. Perinatal herpes simplex virus infections. Washington DC: American College of Obstetricians and Gynecologists, Nov 1988; ACOG Tech Bull no 122. 8. Stone RM, Brooks CA, Guinan MDE, Alexander ER. National surveillance for neonatal herpes simplex virus infections. Sex Transm Dis 1989;16:152-6.
The clinical utility of maternal body mass index in pregnancy Honor M. Wolfe, MD: Ivan E. Zador, PhD: Thomas L. Gross, MD: Susan S. Martier, MSSA," and Robert J. Sokol, MD" Detroit, Michigan, and Peoria, Illinois To describe maternal body mass index and to compare the use of maternal weight and body mass index for risk assessment at the initial prenatal visit, 6270 graVid women who were consecutively delivered of infants were studied. Body mass index increased with advancing maternal age, parity, and advancing gestational age and was significantly greater in black women than in nonblack women. Risks for the development of adverse outcome associated with maternal obesity, including development of gestational diabetes, preeclampsia, fetal macrosomia, and shoulder dystocia, were comparably predicted by either maternal weight or body mass index >90th percentile. Maternal weight was as predictive of preeclampsia, macrosomia, and shoulder dystocia as was body mass index when these factors were analyzed as continuous variables, whereas increasing body mass index was more predictive of gestational diabetes. The prediction of factors associated with low maternal weights, small-for-gestational-age birth, prematurity, low birth weight, and perinatal death was equivalent for maternal weight and body mass index that was <10th percentile. This study indicates that in the initial risk assessment of outcomes related to maternal weight, the calculation of maternal body mass index otters no advantage over simply weighing the patient. This finding contrasts with results in nonpregnant women. (AM J OBSTET GVNECOL 1991;164:1306-10.)
Key words: Maternal weight, body mass index, perinatal risk, gestational diabetes Many studies examining the effect of maternal size on pregnancy outcome relied on maternal weight «100 and >200 pounds) to define risk categories at the initial prenatal visit. '·3 More recently, risk assessment related to body size has been based on some measure of maternal weight for height.v" Studies in the medical literature suggest that maternal body mass index, calculated as body weight (kilograms)/(height From the Department of Obstetrics and Gynecology, Hutzel Hospital/Wayne State University: and the Department of Obstetrics and Gynecology, University of Illinois College of Medicine at Peoria.' Received for publication June 17, 1990; revised October 12, 1990,accepted December 21, 1990. Reprint requests: Honor M. Wolfe, MD, Department of Obstetrics and Gynecology, Hutzel Hospital, 4707 St. Antoine, Detroit, M1 48201. 6/1/27579 1306
[metersj)", is superior to weight alone for the prediction of morbidity and mortality in nonpregnant populations.i" Because of the direct and continuous relationship of body mass index with outcome, its strong correlation with levels of adiposity, and its independence of height, a recent National Institutes of Health study" has recommended the use of body mass index as a measure of relative leanness in nonpregnant populations. In spite of the widespread use of maternal body mass index in the obstetric literature, we know of no studies to date that compare the relative validity of using maternal weight for height and maternal weight in the initial risk assessment for weight-associated outcomes in pregnancy. Our purpose in this study was to describe body mass index and its determinants in pregnancy and to see
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whether consideration of maternal weight for height (as calculated in the body mass index) leads to the better prediction of perinatal and maternal morbidity than does weight alone. Material and methods
We selected women for study who were consecutively delivered of infants at Hutzel Hospital over a 30-month period and for whom antepartum and intrapartum records were available. Maternal and neonatal data were obtained from a computerized perinatal data base previously described." Table I lists the variables obtained for each patient. Body mass index was calculated from weight and height measured at the initial prenatal visit as weight (kilograms) / (height [metersj)", The effect of maternal characteristics on body mass index was examined by multiple regression with body mass index from the first prenatal visit as the dependent variable. Independent variables included maternal age, gestational age at the initial visit, race (coded as black vs nonblack), and maternal parity. Maternal body mass index and maternal weight were then examined as continuous variables for their association with adverse outcomes associated with maternal size. To examine the relative predictive validity of maternal body mass index and weight in pregnancy, each factor was allowed to compete as an independent variable in separate discriminant function analyses against outcome variables previously associated with high and low maternal weight. Outcome (dependent) variables related to maternal obesity included gestational diabetes, preeclampsia, and the birth of a macrosomic infant (>4000 gm). Those variables associated with low maternal weight included the birth of a small-forgestational-age infant, birth weight < 10th percentile, very-low birth weight « 1500 gm), preterm birth «37 weeks' gestation), and perinatal mortality. Maternal age, parity, race, marital status, gestational age at initial prenatal visit, and substance use were included as potentially confounding independent variables. The relative risk for these adverse outcomes was then calculated for small maternal size (body mass index or maternal weight < 10th percentile) and large maternal size (body mass index or maternal weight >90th percentile). Relative risks and the 95% confidence intervals" were calculated according to the method of Woolf. Results
Table I summarizes the characteristics of the 6270 women studied. The group studied was predominantly black (79%) with a mean maternal age of 25 ± 6 years. The mean maternal body mass index at the first prenatal visit was 26.5 ± 6.5 kg/rn" (64 inches, 155
Table I. Characteristics of 6270 women studied Factor
Mean :t SD
Range
Age (yr) Gravidity (yr) Parity Race (%) Black Other Marital status (%) Married Nonmarried Gestational age (wk) First prenatal visit Delivery Prepregnancy weight (lb)* Weight first visit (Ib) Maternal height (in) Body mass index
25.1 :t 6.0 3.0 :t 1.9
12-52 1-16 0-11
(kg/m")
Prepregnancy First visit Medical complications (%) History of dibetes History of hypertension Substance use-abuse (%)
Tobacco Marijuana Narcotic Alcohol abuse
l.l :t 1.4
79.0 21.0 34.0 66.0 19.3 :t 8.6 39.1 :t 2.3 142.5 :t 38.0
5-42 20-44 62-411
155.3 :t 40.6 64.2 :t 2.8
78-414 48-75
24.3 ± 6.1 26.5 ± 6.5
13.2-68.5 13.2-69.0
2.8 3.7
23.7 7.4
6.5 4.1
*Patient recall.
pounds). The 10th percentiles for maternal weight and body mass index were 115 pounds and 20.1 kg/m 2 , respectively; the 90th percentiles were 208 pounds and 35.2 kg/m". Results of the multiple regression for determinants of maternal body mass index are summarized in Table II. When considered individually (step 0), body mass index was found to increase with increasing maternal age, parity, and advancing gestational age. Black women had a significantly greater body mass index than did nonblacks (26.8 vs 25.5 kg/m 2 , respectively). This was true in spite of the fact that, on average, black mothers were significantly younger than nonblack mothers (24.2 vs 27.6 years). Body mass index decreased with a maternal history of alcohol, narcotics. or tobacco use. When considered jointly (at the final step). all maternal factors remained significant, with a total of 9.7% of the variance in body mass index explained by these variables. When maternal body mass index and weight were examined as continuous variables, as shown in Table Ill, discriminant analysis revealed that of the outcome variables associated with maternal obesity, only gestational diabetes mellitus was better predicted by increasing maternal body mass index than by weight. Even
1308 Wolfe et al. Am
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May 1991 Obstet Gynecol
Table II. Summary of multiple regression for determinants of maternal body mass index at initial prenatal visit Step 0 Variable
F test
Maternal age Gestational age Maternal race Narcotic use Maternal parity Alcohol use Tobacco use Marital status
158.9 126.8 37.1 24.2 150.9 II.8 5.5 0.9
df I to 5280; total R 2
=
I
FiIWI step p Value
F test
0.001 0.001 0.001 0.001 0.001 0.001 0.02 NS
183.2 185.2 84.0 63.7 16.8 15.8 7.3 8.0
I
Explained uanance p Value
(%)
0.001 0.001 0.001 0.001 0.001 0.001 0.01 0.01
2.9 3.4 1.5 l.l
0.3 0.1 0.1 0.1
9.7%.
Table III. Summary of discriminant analysis for determinants of gestational diabetes Step 0 Variable
F test
Body mass index* Maternal age Narcotic use Maternal weight* Maternal parity Maternal race
160.4 119.9 3.6 141.1 31.9 4.2
I
FiIWI step p Value
F test
0.001 0.001 NS 0.001 0.001 0.04
160.4 81.5 5.3 0.2 0.3 l.l
I
p Value
0.001 0.001 0.02 NS NS NS
Explained variance (%)
3.0 1.5 0.1
df I to 5280; total R 2 = 4.6%. *At first prenatal visit.
when maternal weight was forced into the model at level I, body mass index significantly improved the prediction of gestational diabetes. Indeed, increasing maternal body mass index was more predictive of the development of gestational diabetes than of advancing maternal age. Macrosomia, shoulder dystocia, and preeclampsia were comparably predicted by increasing maternal weight and body mass index, which were considered as continuous variables. The study also examined outcomes associated with low maternal weight. Discriminant function analysis demonstrated that the birth of small-for-gestationalage infants was most closely associated with narcotic use; decreasing maternal weight explained minimal additional variance. In this study, perinatal mortality, very low birth weight, and preterm births were not predicted by either maternal body mass index or weight, when these were considered as continuous variables. Relative risks for outcomes associated with maternal obesity were comparable for maternal weight or body mass index >90th percentile (Table IV). Similarly, relative risks for adverse outcomes associated with low maternal weight were equal for maternal weight or body mass index < 10th percentile (Table V).
Comment This is the first study, of which we are aware, that describes determinants of maternal body mass index and compares maternal body mass index with maternal body weight for the strength of their associations with perinatal outcomes. Maternal factors, including age, race, parity, substance use, and gestational age, all were significantly related to body mass index and explained approximately 10% of its variance. Although diabetes mellitus was more strongly associated with maternal body mass index than with maternal weight, four of the five outcomes significantly related to maternal size (macrosomia, preeclampsia, and infants who were either small or large for gestational age) were more strongly related to weight than to body mass index. In contrast to previous data in nonpregnant populations, this study suggests that, in the pregnant patient, body weight is comparable to body mass index for the prediction of key adverse, weight-associated outcomes. This study was not designed to examine the wellestablished association between maternal size or weight gain and perinatal or maternal outcome. Rather, data were analyzed to address the more basic question of whether this relationship might be better expressed by the recent trend in the medical and obstetric literature
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Table IV. Comparison of relative risk for occurrence of outcomes associated with maternal obesity for body mass index or weight >90th percentile Outcome
Gestational diabetes Preeclampsia Macrosomic infant Large-for-gestational-age infant Shoulder dystocia
Maternal size assessment
Relative risk
95% Confidence interval
Body mass index >90th percentile Weight >90th percentile Body mass index >90th percentile Weight >90th percentile Body mass index >90th percentile Weight >90th percentile Body mass index >90th percentile Weight >90th percentile Body mass index >90th percentile Weight >90th percentile
5,31 4.18 2.26 2.49 2.54 2,77 2,05 2.49 1.80 3.50
3.83-7.34 3.03-5.75 1.71-2.99 1.93-3.21 1.94-3,33 2,16-3,55 1.62-2,59 2,00-3,09 0,89-3,66 0.14-3.19
Table V. Comparison of relative risk for outcomes associated with low maternal weight for body mass index or weight < 10th percentile Relative Outcome
Maternal size assessment
risk
95% Confidence interval
Small-for-gestational-age infant
Body mass index < 10th percentile Weight < 10th percentile Body mass index < 10th percentile Weight < 10th percentile Body mass index < 10th percentile Weight < 10th percentile Body mass index < 10th percentile Weight < 10th percentile
2.07 2.07 1.64 1.83 2.09 2.31 1.25 1.42
1.58-2.72 1.59-2.70 1.24-2.17 1.41-2.38 1.64-2.66 1.84-2.89 0.88-1.78 1.01-1.98
Premature infant Low-birth-weight infant NICU admission* *Neonatal intensive care unit admission.
toward the use of body mass index. We found that body mass index was superior to maternal weight only for identifying risk for gestational diabetes. It is not surprising that diabetes correlates better with body mass index, because insulin resistance is more a function of fat content than of absolute weight. This may reflect the fact that body mass index is more sensitive than weight to obesity in shorter women. Thus, for example, a woman who is 5 feet tall and weighs 180 pounds has a body mass index in the "obese" range (35.3 kg/rn"), although she does not meet the weight criteria for obesity. Body mass index is used to define relative leanness and weight-associated outcomes in nonpregnant populations. It is not clear why this did not appear to apply to pregnant women. This study was performed with a sample of indigent, black, inner-city gravid women. The mean prepregnancy body mass index in this study (24,3 kg/rn") was higher than the "ideal" body mass index for nonpregnant populations (22.5 kg/m")." Therefore our results may not be entirely applicable to other populations. In addition, although body mass index correlates with the percent of fat, body mass index does not distinguish between various body components
such as muscle and fat. Because our patients sought prenatal care at a relatively late gestational age (20 weeks), this study cannot address the relative utility of maternal body mass index and weight in the first trimester. Although in individual cases maternal body mass index may be helpful in defining risk as it is related to maternal size (particularly among women at either extreme of height), body mass index and weight appear to be of comparable use in large studies. Whereas much remains to be defined with respect to maternal leanness and perinatal outcome, this study suggests that the simple act of weighing the patient constitutes an important part of prenatal care and is adequate for the identification of most perinatal risk factors related to maternal size. REFERENCES I. Hobel cj, Hyvarinen MA, Okada DM, Oh W. Prenatal
and high-risk screening: a prediction of the high-risk neonate. AM] OBSTETGYNECOL 1973;117:1. 2. Sokol R], Stojkov ] , Chik L. Maternal-fetal risk assessment: a clinical guide to monitoring. Clin Obstet Gynecol 1979;22:547-60. 3. Kliegman RM, Gross TL. Perinatal problems of the obese mother and her infant. Obstet Gynecol 1985;66:299-306.
Wolfe et al.
4. Garbaciak JA, Richter M, Miller S, Barton JJ. Maternal weight and pregnancy complications. Obstet Gynecol 1985; 152:238-45. 5. Shepard MJ, Hellenbrand KG, Bracken MB. Proportional weight gain and complications of pregnancy, labor and delivery in healthy women of normal prepregnant stature. AMJ OBSTET GYNECOL 1986;155:947-54. 6. Frentzen BH, Dimperio DL, Cruz AC. Maternal weight gain: effect on infant birth weight among overweight and average-weight low-income women. AM J OBSTET GYNECOL 1988; 159: 1114-7. 7. Keys A, Fidanza F, Karvonen MJ, et al. Indices ofrelative weight and obesity. J Chronic Dis 1972;25:329-43.
May 1991
Am
J Obstet Gynecol
8. Billewicz WZ, Kemsley WFF, Thomson AM. Indices of obesity. Br J Prev Soc Med 1962;16:183-8. 9. Burton BT, Foster WR, HirschJ, Van Itallie TB. Health implications of obesity: an NIH consensus development conference. IntJ Obes 1985;9:155-69. 10. Chik L, Sokol RJ, Kooi R, et al. A perinatal database management system. Methods Inf Med 1981;20:133-41. 11. Schlesselman JJ. Case-control studies: design, conduct, analysis. New York: Oxford University Press, 1982: 174-7.
Complexes of activated protein C with aI-antitrypsin in normal pregnancy and in severe preeclampsia Francisco Espana, PhD: Juan Gilabert, MD, PhD,b Justo Aznar, MD, PhD,C Amparo Estelles, MD, PhD: Takao Kobayashi, MD,c and John H. Griffin, PhDd Valencia, Spain, and La Jolla, California Protein C is a vitamin K-dependent regulator of blood coagulation. Activated protein C is regulated in plasma in large part by two inhibitors, protein C inhibitor and u,-antitrypsin. Complexes of activated protein C with both inhibitors in plasma samples from subjects with normal or pathologic pregnancy were measured. In normal pregnancy we observed a progressive and significant increase in activated protein C/u,-antitrypsin complex levels, from 9 ± 3 nglml in the first trimester to 16 ± 3 nglml in the third trimester, as well as an increase in u"antitrypsin plasma levels. In severe preeclampsia, but not in chronic hypertension with superimposed severe preeclampsia, there was a greater increase in activated protein C/u,-antitrypsin levels (25 ± 10 ng/ml) (p < 0.001) and a decrease in protein C and protein C inhibitor levels as compared with normal pregnant women at similar gestational ages. These data show an increase in the activation of the protein C pathway in both normal and pathologic pregnancy and provide evidence for an enhancement of thrombin generation in severe preeclampsia compared with chronic hypertension with superimposed severe preeclampsia. (AM J OBSTET GYNECOL 1991;164:1310-6.)
Key words: Protein C complexes, aI-antitrypsin, pregnancy, preeclampsia, chronic hypertension Alterations in hemostasis during normal gestation are widely known, and some obstetric complications, for example, preeclampsia, may increase the hypercoagulability state observed in pregnancy. Thus increased levels of coagulation factors" 2 and reduced fibrinolysis' have been demonstrated in preeclampsia. From the Research Center' and the Departments of Obstetrics and Gynecology'and Clinical Pathology,' Hospital "La Fe," and the Committee on Vascular Biology and the Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic,' Supported by a research grant from Fondo de Investigaciones Sanitarias de la Seguridad Social (9010586), Spain. Receivedfor publication April 25, 1990; revised October 31,1990; accepted December 21, 1990. Reprint requests: Francisco Espana, PhD, Hospital "La Fe," Centro de 1nvestigaci6n, Av. Campanar 21, 46009 Valencia, Spain. 611127580
1310
Disseminated intravascular coagulation has also been demonstrated in some cases of severe preeclampsia and eclampsia: the action of the enzyme thrombin on fibrinogen being crucial in this process. Activated protein C, the product of thrombin's action on protein C in the presence of endothelial cell thrombomodulin, together with its cofactor, protein S, regulates blood clotting by inhibiting the clotting cascade at the levels offactors Va and VlIla. 5 • 6 Activated protein C is regulated in plasma by two inhibitors, protein C inhibitor? and a 1-antitrypsin,8 and complexes of activated protein C with both inhibitors have been reported to be circulating in vivo." 9 The importance of the protein C anticoagulant system is illustrated by the fact that newborns with homozygous protein C deficiency suffer severe and generalized thrombotic disease,'? and
3. Wittek AE, Yeager AS, Au DS, Hensleigh PA. Asymptomatic shedding of herpes simplex virus from the cervix and lesion site during pregnancy: correlation of antepartum shedding with shedding at delivery. AJDC 1984;138:43942. 4. Arvin AM, Hensleigh PA, Prober CG, et al. Failure of antepartum maternal cultures to predict the infant's risk of exposure to herpes simplex virus at delivery. N Engl J Med 1986;315:796-800. 5. Prober CG, Sullender WM, Yasukawa LL, et al. Low risk of herpes simplex virus infection in neonates exposed to the virus at the time of vaginal delivery to mothers with
J
May 1991 Obstet Gynecol
recurrent genital herpes simplex virus infections. N Engl J Med 1987;316:240-4. 6. Spruance SL, OverallJC, Kern ER, Krueger GG, Pliam U, Miller W. The natural history of recurrent herpes simplex labiales. N EnglJ Med 1986;314:69-75. 7. American College of Obstetricians and Gynecologists. Perinatal herpes simplex virus infections. Washington DC: American College of Obstetricians and Gynecologists, Nov 1988; ACOG Tech Bull no 122. 8. Stone RM, Brooks CA, Guinan MDE, Alexander ER. National surveillance for neonatal herpes simplex virus infections. Sex Transm Dis 1989;16:152-6.
The clinical utility of maternal body mass index in pregnancy Honor M. Wolfe, MD: Ivan E. Zador, PhD: Thomas L. Gross, MD: Susan S. Martier, MSSA," and Robert J. Sokol, MD" Detroit, Michigan, and Peoria, Illinois To describe maternal body mass index and to compare the use of maternal weight and body mass index for risk assessment at the initial prenatal visit, 6270 graVid women who were consecutively delivered of infants were studied. Body mass index increased with advancing maternal age, parity, and advancing gestational age and was significantly greater in black women than in nonblack women. Risks for the development of adverse outcome associated with maternal obesity, including development of gestational diabetes, preeclampsia, fetal macrosomia, and shoulder dystocia, were comparably predicted by either maternal weight or body mass index >90th percentile. Maternal weight was as predictive of preeclampsia, macrosomia, and shoulder dystocia as was body mass index when these factors were analyzed as continuous variables, whereas increasing body mass index was more predictive of gestational diabetes. The prediction of factors associated with low maternal weights, small-for-gestational-age birth, prematurity, low birth weight, and perinatal death was equivalent for maternal weight and body mass index that was <10th percentile. This study indicates that in the initial risk assessment of outcomes related to maternal weight, the calculation of maternal body mass index otters no advantage over simply weighing the patient. This finding contrasts with results in nonpregnant women. (AM J OBSTET GVNECOL 1991;164:1306-10.)
Key words: Maternal weight, body mass index, perinatal risk, gestational diabetes Many studies examining the effect of maternal size on pregnancy outcome relied on maternal weight «100 and >200 pounds) to define risk categories at the initial prenatal visit. '·3 More recently, risk assessment related to body size has been based on some measure of maternal weight for height.v" Studies in the medical literature suggest that maternal body mass index, calculated as body weight (kilograms)/(height From the Department of Obstetrics and Gynecology, Hutzel Hospital/Wayne State University: and the Department of Obstetrics and Gynecology, University of Illinois College of Medicine at Peoria.' Received for publication June 17, 1990; revised October 12, 1990,accepted December 21, 1990. Reprint requests: Honor M. Wolfe, MD, Department of Obstetrics and Gynecology, Hutzel Hospital, 4707 St. Antoine, Detroit, M1 48201. 6/1/27579 1306
[metersj)", is superior to weight alone for the prediction of morbidity and mortality in nonpregnant populations.i" Because of the direct and continuous relationship of body mass index with outcome, its strong correlation with levels of adiposity, and its independence of height, a recent National Institutes of Health study" has recommended the use of body mass index as a measure of relative leanness in nonpregnant populations. In spite of the widespread use of maternal body mass index in the obstetric literature, we know of no studies to date that compare the relative validity of using maternal weight for height and maternal weight in the initial risk assessment for weight-associated outcomes in pregnancy. Our purpose in this study was to describe body mass index and its determinants in pregnancy and to see
Body mass index and pregnancy 1307
Volume 164 Number 5, Part I
whether consideration of maternal weight for height (as calculated in the body mass index) leads to the better prediction of perinatal and maternal morbidity than does weight alone. Material and methods
We selected women for study who were consecutively delivered of infants at Hutzel Hospital over a 30-month period and for whom antepartum and intrapartum records were available. Maternal and neonatal data were obtained from a computerized perinatal data base previously described." Table I lists the variables obtained for each patient. Body mass index was calculated from weight and height measured at the initial prenatal visit as weight (kilograms) / (height [metersj)", The effect of maternal characteristics on body mass index was examined by multiple regression with body mass index from the first prenatal visit as the dependent variable. Independent variables included maternal age, gestational age at the initial visit, race (coded as black vs nonblack), and maternal parity. Maternal body mass index and maternal weight were then examined as continuous variables for their association with adverse outcomes associated with maternal size. To examine the relative predictive validity of maternal body mass index and weight in pregnancy, each factor was allowed to compete as an independent variable in separate discriminant function analyses against outcome variables previously associated with high and low maternal weight. Outcome (dependent) variables related to maternal obesity included gestational diabetes, preeclampsia, and the birth of a macrosomic infant (>4000 gm). Those variables associated with low maternal weight included the birth of a small-forgestational-age infant, birth weight < 10th percentile, very-low birth weight « 1500 gm), preterm birth «37 weeks' gestation), and perinatal mortality. Maternal age, parity, race, marital status, gestational age at initial prenatal visit, and substance use were included as potentially confounding independent variables. The relative risk for these adverse outcomes was then calculated for small maternal size (body mass index or maternal weight < 10th percentile) and large maternal size (body mass index or maternal weight >90th percentile). Relative risks and the 95% confidence intervals" were calculated according to the method of Woolf. Results
Table I summarizes the characteristics of the 6270 women studied. The group studied was predominantly black (79%) with a mean maternal age of 25 ± 6 years. The mean maternal body mass index at the first prenatal visit was 26.5 ± 6.5 kg/rn" (64 inches, 155
Table I. Characteristics of 6270 women studied Factor
Mean :t SD
Range
Age (yr) Gravidity (yr) Parity Race (%) Black Other Marital status (%) Married Nonmarried Gestational age (wk) First prenatal visit Delivery Prepregnancy weight (lb)* Weight first visit (Ib) Maternal height (in) Body mass index
25.1 :t 6.0 3.0 :t 1.9
12-52 1-16 0-11
(kg/m")
Prepregnancy First visit Medical complications (%) History of dibetes History of hypertension Substance use-abuse (%)
Tobacco Marijuana Narcotic Alcohol abuse
l.l :t 1.4
79.0 21.0 34.0 66.0 19.3 :t 8.6 39.1 :t 2.3 142.5 :t 38.0
5-42 20-44 62-411
155.3 :t 40.6 64.2 :t 2.8
78-414 48-75
24.3 ± 6.1 26.5 ± 6.5
13.2-68.5 13.2-69.0
2.8 3.7
23.7 7.4
6.5 4.1
*Patient recall.
pounds). The 10th percentiles for maternal weight and body mass index were 115 pounds and 20.1 kg/m 2 , respectively; the 90th percentiles were 208 pounds and 35.2 kg/m". Results of the multiple regression for determinants of maternal body mass index are summarized in Table II. When considered individually (step 0), body mass index was found to increase with increasing maternal age, parity, and advancing gestational age. Black women had a significantly greater body mass index than did nonblacks (26.8 vs 25.5 kg/m 2 , respectively). This was true in spite of the fact that, on average, black mothers were significantly younger than nonblack mothers (24.2 vs 27.6 years). Body mass index decreased with a maternal history of alcohol, narcotics. or tobacco use. When considered jointly (at the final step). all maternal factors remained significant, with a total of 9.7% of the variance in body mass index explained by these variables. When maternal body mass index and weight were examined as continuous variables, as shown in Table Ill, discriminant analysis revealed that of the outcome variables associated with maternal obesity, only gestational diabetes mellitus was better predicted by increasing maternal body mass index than by weight. Even
1308 Wolfe et al. Am
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May 1991 Obstet Gynecol
Table II. Summary of multiple regression for determinants of maternal body mass index at initial prenatal visit Step 0 Variable
F test
Maternal age Gestational age Maternal race Narcotic use Maternal parity Alcohol use Tobacco use Marital status
158.9 126.8 37.1 24.2 150.9 II.8 5.5 0.9
df I to 5280; total R 2
=
I
FiIWI step p Value
F test
0.001 0.001 0.001 0.001 0.001 0.001 0.02 NS
183.2 185.2 84.0 63.7 16.8 15.8 7.3 8.0
I
Explained uanance p Value
(%)
0.001 0.001 0.001 0.001 0.001 0.001 0.01 0.01
2.9 3.4 1.5 l.l
0.3 0.1 0.1 0.1
9.7%.
Table III. Summary of discriminant analysis for determinants of gestational diabetes Step 0 Variable
F test
Body mass index* Maternal age Narcotic use Maternal weight* Maternal parity Maternal race
160.4 119.9 3.6 141.1 31.9 4.2
I
FiIWI step p Value
F test
0.001 0.001 NS 0.001 0.001 0.04
160.4 81.5 5.3 0.2 0.3 l.l
I
p Value
0.001 0.001 0.02 NS NS NS
Explained variance (%)
3.0 1.5 0.1
df I to 5280; total R 2 = 4.6%. *At first prenatal visit.
when maternal weight was forced into the model at level I, body mass index significantly improved the prediction of gestational diabetes. Indeed, increasing maternal body mass index was more predictive of the development of gestational diabetes than of advancing maternal age. Macrosomia, shoulder dystocia, and preeclampsia were comparably predicted by increasing maternal weight and body mass index, which were considered as continuous variables. The study also examined outcomes associated with low maternal weight. Discriminant function analysis demonstrated that the birth of small-for-gestationalage infants was most closely associated with narcotic use; decreasing maternal weight explained minimal additional variance. In this study, perinatal mortality, very low birth weight, and preterm births were not predicted by either maternal body mass index or weight, when these were considered as continuous variables. Relative risks for outcomes associated with maternal obesity were comparable for maternal weight or body mass index >90th percentile (Table IV). Similarly, relative risks for adverse outcomes associated with low maternal weight were equal for maternal weight or body mass index < 10th percentile (Table V).
Comment This is the first study, of which we are aware, that describes determinants of maternal body mass index and compares maternal body mass index with maternal body weight for the strength of their associations with perinatal outcomes. Maternal factors, including age, race, parity, substance use, and gestational age, all were significantly related to body mass index and explained approximately 10% of its variance. Although diabetes mellitus was more strongly associated with maternal body mass index than with maternal weight, four of the five outcomes significantly related to maternal size (macrosomia, preeclampsia, and infants who were either small or large for gestational age) were more strongly related to weight than to body mass index. In contrast to previous data in nonpregnant populations, this study suggests that, in the pregnant patient, body weight is comparable to body mass index for the prediction of key adverse, weight-associated outcomes. This study was not designed to examine the wellestablished association between maternal size or weight gain and perinatal or maternal outcome. Rather, data were analyzed to address the more basic question of whether this relationship might be better expressed by the recent trend in the medical and obstetric literature
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Volume 164 Number 5, Part I
Table IV. Comparison of relative risk for occurrence of outcomes associated with maternal obesity for body mass index or weight >90th percentile Outcome
Gestational diabetes Preeclampsia Macrosomic infant Large-for-gestational-age infant Shoulder dystocia
Maternal size assessment
Relative risk
95% Confidence interval
Body mass index >90th percentile Weight >90th percentile Body mass index >90th percentile Weight >90th percentile Body mass index >90th percentile Weight >90th percentile Body mass index >90th percentile Weight >90th percentile Body mass index >90th percentile Weight >90th percentile
5,31 4.18 2.26 2.49 2.54 2,77 2,05 2.49 1.80 3.50
3.83-7.34 3.03-5.75 1.71-2.99 1.93-3.21 1.94-3,33 2,16-3,55 1.62-2,59 2,00-3,09 0,89-3,66 0.14-3.19
Table V. Comparison of relative risk for outcomes associated with low maternal weight for body mass index or weight < 10th percentile Relative Outcome
Maternal size assessment
risk
95% Confidence interval
Small-for-gestational-age infant
Body mass index < 10th percentile Weight < 10th percentile Body mass index < 10th percentile Weight < 10th percentile Body mass index < 10th percentile Weight < 10th percentile Body mass index < 10th percentile Weight < 10th percentile
2.07 2.07 1.64 1.83 2.09 2.31 1.25 1.42
1.58-2.72 1.59-2.70 1.24-2.17 1.41-2.38 1.64-2.66 1.84-2.89 0.88-1.78 1.01-1.98
Premature infant Low-birth-weight infant NICU admission* *Neonatal intensive care unit admission.
toward the use of body mass index. We found that body mass index was superior to maternal weight only for identifying risk for gestational diabetes. It is not surprising that diabetes correlates better with body mass index, because insulin resistance is more a function of fat content than of absolute weight. This may reflect the fact that body mass index is more sensitive than weight to obesity in shorter women. Thus, for example, a woman who is 5 feet tall and weighs 180 pounds has a body mass index in the "obese" range (35.3 kg/rn"), although she does not meet the weight criteria for obesity. Body mass index is used to define relative leanness and weight-associated outcomes in nonpregnant populations. It is not clear why this did not appear to apply to pregnant women. This study was performed with a sample of indigent, black, inner-city gravid women. The mean prepregnancy body mass index in this study (24,3 kg/rn") was higher than the "ideal" body mass index for nonpregnant populations (22.5 kg/m")." Therefore our results may not be entirely applicable to other populations. In addition, although body mass index correlates with the percent of fat, body mass index does not distinguish between various body components
such as muscle and fat. Because our patients sought prenatal care at a relatively late gestational age (20 weeks), this study cannot address the relative utility of maternal body mass index and weight in the first trimester. Although in individual cases maternal body mass index may be helpful in defining risk as it is related to maternal size (particularly among women at either extreme of height), body mass index and weight appear to be of comparable use in large studies. Whereas much remains to be defined with respect to maternal leanness and perinatal outcome, this study suggests that the simple act of weighing the patient constitutes an important part of prenatal care and is adequate for the identification of most perinatal risk factors related to maternal size. REFERENCES I. Hobel cj, Hyvarinen MA, Okada DM, Oh W. Prenatal
and high-risk screening: a prediction of the high-risk neonate. AM] OBSTETGYNECOL 1973;117:1. 2. Sokol R], Stojkov ] , Chik L. Maternal-fetal risk assessment: a clinical guide to monitoring. Clin Obstet Gynecol 1979;22:547-60. 3. Kliegman RM, Gross TL. Perinatal problems of the obese mother and her infant. Obstet Gynecol 1985;66:299-306.
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4. Garbaciak JA, Richter M, Miller S, Barton JJ. Maternal weight and pregnancy complications. Obstet Gynecol 1985; 152:238-45. 5. Shepard MJ, Hellenbrand KG, Bracken MB. Proportional weight gain and complications of pregnancy, labor and delivery in healthy women of normal prepregnant stature. AMJ OBSTET GYNECOL 1986;155:947-54. 6. Frentzen BH, Dimperio DL, Cruz AC. Maternal weight gain: effect on infant birth weight among overweight and average-weight low-income women. AM J OBSTET GYNECOL 1988; 159: 1114-7. 7. Keys A, Fidanza F, Karvonen MJ, et al. Indices ofrelative weight and obesity. J Chronic Dis 1972;25:329-43.
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8. Billewicz WZ, Kemsley WFF, Thomson AM. Indices of obesity. Br J Prev Soc Med 1962;16:183-8. 9. Burton BT, Foster WR, HirschJ, Van Itallie TB. Health implications of obesity: an NIH consensus development conference. IntJ Obes 1985;9:155-69. 10. Chik L, Sokol RJ, Kooi R, et al. A perinatal database management system. Methods Inf Med 1981;20:133-41. 11. Schlesselman JJ. Case-control studies: design, conduct, analysis. New York: Oxford University Press, 1982: 174-7.
Complexes of activated protein C with aI-antitrypsin in normal pregnancy and in severe preeclampsia Francisco Espana, PhD: Juan Gilabert, MD, PhD,b Justo Aznar, MD, PhD,C Amparo Estelles, MD, PhD: Takao Kobayashi, MD,c and John H. Griffin, PhDd Valencia, Spain, and La Jolla, California Protein C is a vitamin K-dependent regulator of blood coagulation. Activated protein C is regulated in plasma in large part by two inhibitors, protein C inhibitor and u,-antitrypsin. Complexes of activated protein C with both inhibitors in plasma samples from subjects with normal or pathologic pregnancy were measured. In normal pregnancy we observed a progressive and significant increase in activated protein C/u,-antitrypsin complex levels, from 9 ± 3 nglml in the first trimester to 16 ± 3 nglml in the third trimester, as well as an increase in u"antitrypsin plasma levels. In severe preeclampsia, but not in chronic hypertension with superimposed severe preeclampsia, there was a greater increase in activated protein C/u,-antitrypsin levels (25 ± 10 ng/ml) (p < 0.001) and a decrease in protein C and protein C inhibitor levels as compared with normal pregnant women at similar gestational ages. These data show an increase in the activation of the protein C pathway in both normal and pathologic pregnancy and provide evidence for an enhancement of thrombin generation in severe preeclampsia compared with chronic hypertension with superimposed severe preeclampsia. (AM J OBSTET GYNECOL 1991;164:1310-6.)
Key words: Protein C complexes, aI-antitrypsin, pregnancy, preeclampsia, chronic hypertension Alterations in hemostasis during normal gestation are widely known, and some obstetric complications, for example, preeclampsia, may increase the hypercoagulability state observed in pregnancy. Thus increased levels of coagulation factors" 2 and reduced fibrinolysis' have been demonstrated in preeclampsia. From the Research Center' and the Departments of Obstetrics and Gynecology'and Clinical Pathology,' Hospital "La Fe," and the Committee on Vascular Biology and the Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic,' Supported by a research grant from Fondo de Investigaciones Sanitarias de la Seguridad Social (9010586), Spain. Receivedfor publication April 25, 1990; revised October 31,1990; accepted December 21, 1990. Reprint requests: Francisco Espana, PhD, Hospital "La Fe," Centro de 1nvestigaci6n, Av. Campanar 21, 46009 Valencia, Spain. 611127580
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Disseminated intravascular coagulation has also been demonstrated in some cases of severe preeclampsia and eclampsia: the action of the enzyme thrombin on fibrinogen being crucial in this process. Activated protein C, the product of thrombin's action on protein C in the presence of endothelial cell thrombomodulin, together with its cofactor, protein S, regulates blood clotting by inhibiting the clotting cascade at the levels offactors Va and VlIla. 5 • 6 Activated protein C is regulated in plasma by two inhibitors, protein C inhibitor? and a 1-antitrypsin,8 and complexes of activated protein C with both inhibitors have been reported to be circulating in vivo." 9 The importance of the protein C anticoagulant system is illustrated by the fact that newborns with homozygous protein C deficiency suffer severe and generalized thrombotic disease,'? and