AMERICAN JOURNAL OF EPIDEMIOLOGY
Copyright © 1990 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved
Vol. 132, No. 2 Printed in U.S.A.
INTERPREGNANCY INTERVAL AND RISK OF PRETERM LABOR JANET M. LANG,1 ELLICE LLEBERMAN,2-' KENNETH J. RYAN,1 AND RICHARD R. MONSON4 Lang, J. M. (Epidemiology and Biostatistics Section, Boston U. School of Public Health, Boston, MA 02118-2394), E. Lieberman, K. J. Ryan, and R. R. Monson. Interpregnancy interval and risk of preterm labor. Am J Epidemiol 1990;132: 304-9. In 1977-1980, over 12,000 pregnant women being followed at the Boston Hospital for Women were interviewed and had their medical records reviewed. The effect of interpregnancy interval on the risk of preterm labor was estimated in 4,467 of these women whose previous pregnancy had resulted in a full-term live birth. The rate of preterm birth after the spontaneous onset of labor in this cohort was 3.8 percent While the possibility of an increased risk of preterm labor for Interpregnancy intervals of 3 months or less cannot be definitely excluded (adjusted odds ratio = 2.0, 95 percent confidence interval 0.7-5.4), no relation was found between other interpregnancy intervals and the risk of preterm labor. Earlier work from this same cohort showed a strong negative association between interpregnancy interval and small-for-gestational-age birth. Combining this with the results from the present study reinforces the importance of differentiating low birth weight due to preterm birth from that due to Intrauterine growth retardation. Infant, low birth weight; infant, premature; labor, premature; pregnancy outcome
The Institute of Medicine, in its 1985 report on low birth weight, concluded that interpregnancy interval was an independent risk factor for low birth weight (1). However, this report, along with most others that have found an increased risk of low Received for publication April 17,1989, and in final form January 30, 1989. 1 Epidemiology and Biostatistics Section, Boston University School of Public Health, Boston, MA. "Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. * Department of Maternal and Child Health, Harvard School of Public Health, Boston, MA. 4 Department of Epidemiology, Harvard School of Public Health, Boston, MA. Reprint requests to Dr. Janet M. Lang, Epidemiology and Biostatistics Section, Boston University School of Public Health, 80 East Concord Street, Boston, MA 02118-2394. This work was supported by a grant from the March of Dimes Birth Defects Foundation. 304
birth weight for women with short interpregnancy intervals (2, 3), did not differentiate low birth weight due to preterm birth from that due to intrauterine growth retardation. Such a distinction is essential because preterm birth and growth retardation represent separate processes, and, as such, they can be expected to have distinct causal factors (4). Several authors have distinguished between preterm birth and intrauterine growth retardation. Fedrick and Adelstein (5) found a somewhat increased risk of preterm delivery for women whose interpregnancy interval was 6 months or less. In that analysis, however, they did not control for confounding factors. Brody and Bracken (6), in a small prospective study, found a strong negative association between interpregnancy interval and low birth weight, adjusting for gestational age
INTERPREGNANCY INTERVAL AND PRETERM LABOR
and a range of potential confounders; no association of interpregnancy interval with preterm delivery was found. Within the context of a case-control study of women in northwestern Brazil, Ferraz et al. (7) found that interpregnancy interval was a risk factor for the occurrence of intrauterine growth retardation but not for preterm birth. However, none of these studies differentiated preterm birth due to spontaneous preterm labor from that due to complications of pregnancy necessitating medical intervention. In a recent article, we reported a significant negative association between interpregnancy interval and full-term small-for-gestational-age birth in a large hospital-based cohort (8). This paper examines the association of interpregnancy interval with preterm labor within that same parent cohort. MATERIALS AND METHODS
The delivery interview program conducted at the Boston Hospital for Women from August 1977 to March 1980 was designed to study the association of late pregnancy outcome with a range of exposures. During the study period, 12,718 women were interviewed and had their medical records reviewed. Data collected included demographic data, medical and obstetric history, course of the current pregnancy, and pregnancy outcome. Further details of the study methodology are described elsewhere (9). For the current analyses, the study cohort was limited to women whose pregnancies were not artificially interrupted prior to term. This condition was imposed because we wished to investigate the risk factors for preterm labor rather than complications of pregnancy requiring early delivery. During the study period (19771980), effective tocolysis was not available, and women with preterm labor generally progressed to preterm delivery. The study domain was further restricted to eliminate the confounding effects of two factors. First, since prior pregnancy out-
305
come can strongly influence both interpregnancy interval and pregnancy outcome, we included in this analysis only women whose last pregnancy resulted in a full-term (>37 weeks) live birth with offspring still living at the time of the study pregnancy. Second, small-for-gestational-age birth confounds the relation between interpregnancy interval and spontaneous preterm labor, being associated with both interpregnancy interval (8) and spontaneous preterm labor. With only 17 babies who were both premature and small for gestational age, we chose to examine the association of interpregnancy interval and preterm labor only among appropriate-for-gestational-age births. Infants were defined as being appropriate for gestational age if their birth weight was greater than or equal to the tenth percentile for gestational age using the criteria defined by Brenner et al. (10). There were 4,467 women (and their babies) who met the above criteria. Infants were defined as premature if their gestational age at birth was less than 37 weeks. The interpregnancy interval was calculated as the number of months between the woman's last previous delivery date of a live infant and the date of the last menstrual period for the current pregnancy. Interpregnancy interval was then categorized as follows: 3-6 months (4-6 months), >6-12 months (712 months), >12-18 months (13-18 months), >18-24 months (19-24 months), >24-36 months (25-36 months), >36-48 months (37-48 months), and >48 months (>49 months). Interpregnancy intervals will be referred to in the text as noted above in parentheses. The occurrence of premature labor was calculated for the 4,467 women whose previous pregnancy resulted in a full-term birth and whose current pregnancy resulted in either a premature birth after the spontaneous onset of labor or a full-term birth, with all infants being appropriate for gestational age. From these data, we calculated the rates of prematurity for each interpregnancy interval. To illustrate the influence
306
LANG ETT A L .
RESULTS
Of the 4,467 women in the cohort, 168 (3.8 percent) gave birth to preterm (appropriate-for-gestational-age) infants after the spontaneous onset of labor. This rate varied, however, with the duration between the last prior delivery and subsequent conception (figure 1). The highest risk of prematurity occurred in women who had had an interpregnancy interval of 3 months or less; 8.3 percent of those women gave birth to premature infants. The risk of prematurity decreased with increasing interpregnancy intervals up to approximately 24 months. The risk was lowest when the interpregnancy interval was 19-36 months, with a 2.4 percent rate of prematurity with interpregnancy intervals of 19-24 months and 2.7 percent prematurity with interpregnancy intervals of 25-36 months. When the interpregnancy interval was longer than 36 months, the prematurity rate again increased. The distribution of interpregnancy intervals for women with appropriate-forgestational-age premature and full-term
1
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1
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o
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.
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tervals from the standard errors of those coefficients.
11
of the size of the groups on the stability of the observed rates, we constructed 95 percent confidence intervals around each rate (11). Within this group of appropriate-forgestational-age infants, the distribution of interpregnancy interval for premature infants was compared with that of full-term infants. The interval of 25-36 months was chosen as the referent category to estimate the relative effects of both shorter and longer interpregnancy intervals. Unadjusted odds ratios were estimated and 95 percent confidence intervals were calculated. The crude odds ratios were then adjusted for confounding effects by means of a logistic regression model which included factors known to cause or be associated with both prematurity and interpregnancy interval. So as not to constrain the relation between interpregnancy interval and prematurity by any specific mathematical model, each interpregnancy interval other than the referent category was represented by a separate dichotomous variable (indicator variable) in the logistic regression. In the logistic regression analysis, we calculated the odds ratios from regression coefficients and the 95 percent confidence in-
a (H
cu c
o o u o (X
s
nrd [ 1
4 2 0
0-3
4-6
7-18
•
1
,
-
n
13-18 19-B4 20-38 37-48
[
rL i
•
48+
Interpregnancy Interval (In months) FIGURE 1. Percentage of women with spontaneous premature labor (and 95% confidence intervals), by interpregnancy interval, Boston Hospital for Women, 1977-1980.
307
INTERPREGNANCY INTERVAL AND PRETERM LABOR TABLE 1
Numbers of premature and full-term births and odds ratios (crude and adjusted) for premature labor among appropriate-for-gestational-age births, by interpregnancy interval, Boston Hospital for Women, 1977-1980 Interpregnancy interval (months)
Copyright © 1990 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved
Vol. 132, No. 2 Printed in U.S.A.
INTERPREGNANCY INTERVAL AND RISK OF PRETERM LABOR JANET M. LANG,1 ELLICE LLEBERMAN,2-' KENNETH J. RYAN,1 AND RICHARD R. MONSON4 Lang, J. M. (Epidemiology and Biostatistics Section, Boston U. School of Public Health, Boston, MA 02118-2394), E. Lieberman, K. J. Ryan, and R. R. Monson. Interpregnancy interval and risk of preterm labor. Am J Epidemiol 1990;132: 304-9. In 1977-1980, over 12,000 pregnant women being followed at the Boston Hospital for Women were interviewed and had their medical records reviewed. The effect of interpregnancy interval on the risk of preterm labor was estimated in 4,467 of these women whose previous pregnancy had resulted in a full-term live birth. The rate of preterm birth after the spontaneous onset of labor in this cohort was 3.8 percent While the possibility of an increased risk of preterm labor for Interpregnancy intervals of 3 months or less cannot be definitely excluded (adjusted odds ratio = 2.0, 95 percent confidence interval 0.7-5.4), no relation was found between other interpregnancy intervals and the risk of preterm labor. Earlier work from this same cohort showed a strong negative association between interpregnancy interval and small-for-gestational-age birth. Combining this with the results from the present study reinforces the importance of differentiating low birth weight due to preterm birth from that due to Intrauterine growth retardation. Infant, low birth weight; infant, premature; labor, premature; pregnancy outcome
The Institute of Medicine, in its 1985 report on low birth weight, concluded that interpregnancy interval was an independent risk factor for low birth weight (1). However, this report, along with most others that have found an increased risk of low Received for publication April 17,1989, and in final form January 30, 1989. 1 Epidemiology and Biostatistics Section, Boston University School of Public Health, Boston, MA. "Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. * Department of Maternal and Child Health, Harvard School of Public Health, Boston, MA. 4 Department of Epidemiology, Harvard School of Public Health, Boston, MA. Reprint requests to Dr. Janet M. Lang, Epidemiology and Biostatistics Section, Boston University School of Public Health, 80 East Concord Street, Boston, MA 02118-2394. This work was supported by a grant from the March of Dimes Birth Defects Foundation. 304
birth weight for women with short interpregnancy intervals (2, 3), did not differentiate low birth weight due to preterm birth from that due to intrauterine growth retardation. Such a distinction is essential because preterm birth and growth retardation represent separate processes, and, as such, they can be expected to have distinct causal factors (4). Several authors have distinguished between preterm birth and intrauterine growth retardation. Fedrick and Adelstein (5) found a somewhat increased risk of preterm delivery for women whose interpregnancy interval was 6 months or less. In that analysis, however, they did not control for confounding factors. Brody and Bracken (6), in a small prospective study, found a strong negative association between interpregnancy interval and low birth weight, adjusting for gestational age
INTERPREGNANCY INTERVAL AND PRETERM LABOR
and a range of potential confounders; no association of interpregnancy interval with preterm delivery was found. Within the context of a case-control study of women in northwestern Brazil, Ferraz et al. (7) found that interpregnancy interval was a risk factor for the occurrence of intrauterine growth retardation but not for preterm birth. However, none of these studies differentiated preterm birth due to spontaneous preterm labor from that due to complications of pregnancy necessitating medical intervention. In a recent article, we reported a significant negative association between interpregnancy interval and full-term small-for-gestational-age birth in a large hospital-based cohort (8). This paper examines the association of interpregnancy interval with preterm labor within that same parent cohort. MATERIALS AND METHODS
The delivery interview program conducted at the Boston Hospital for Women from August 1977 to March 1980 was designed to study the association of late pregnancy outcome with a range of exposures. During the study period, 12,718 women were interviewed and had their medical records reviewed. Data collected included demographic data, medical and obstetric history, course of the current pregnancy, and pregnancy outcome. Further details of the study methodology are described elsewhere (9). For the current analyses, the study cohort was limited to women whose pregnancies were not artificially interrupted prior to term. This condition was imposed because we wished to investigate the risk factors for preterm labor rather than complications of pregnancy requiring early delivery. During the study period (19771980), effective tocolysis was not available, and women with preterm labor generally progressed to preterm delivery. The study domain was further restricted to eliminate the confounding effects of two factors. First, since prior pregnancy out-
305
come can strongly influence both interpregnancy interval and pregnancy outcome, we included in this analysis only women whose last pregnancy resulted in a full-term (>37 weeks) live birth with offspring still living at the time of the study pregnancy. Second, small-for-gestational-age birth confounds the relation between interpregnancy interval and spontaneous preterm labor, being associated with both interpregnancy interval (8) and spontaneous preterm labor. With only 17 babies who were both premature and small for gestational age, we chose to examine the association of interpregnancy interval and preterm labor only among appropriate-for-gestational-age births. Infants were defined as being appropriate for gestational age if their birth weight was greater than or equal to the tenth percentile for gestational age using the criteria defined by Brenner et al. (10). There were 4,467 women (and their babies) who met the above criteria. Infants were defined as premature if their gestational age at birth was less than 37 weeks. The interpregnancy interval was calculated as the number of months between the woman's last previous delivery date of a live infant and the date of the last menstrual period for the current pregnancy. Interpregnancy interval was then categorized as follows: 3-6 months (4-6 months), >6-12 months (712 months), >12-18 months (13-18 months), >18-24 months (19-24 months), >24-36 months (25-36 months), >36-48 months (37-48 months), and >48 months (>49 months). Interpregnancy intervals will be referred to in the text as noted above in parentheses. The occurrence of premature labor was calculated for the 4,467 women whose previous pregnancy resulted in a full-term birth and whose current pregnancy resulted in either a premature birth after the spontaneous onset of labor or a full-term birth, with all infants being appropriate for gestational age. From these data, we calculated the rates of prematurity for each interpregnancy interval. To illustrate the influence
306
LANG ETT A L .
RESULTS
Of the 4,467 women in the cohort, 168 (3.8 percent) gave birth to preterm (appropriate-for-gestational-age) infants after the spontaneous onset of labor. This rate varied, however, with the duration between the last prior delivery and subsequent conception (figure 1). The highest risk of prematurity occurred in women who had had an interpregnancy interval of 3 months or less; 8.3 percent of those women gave birth to premature infants. The risk of prematurity decreased with increasing interpregnancy intervals up to approximately 24 months. The risk was lowest when the interpregnancy interval was 19-36 months, with a 2.4 percent rate of prematurity with interpregnancy intervals of 19-24 months and 2.7 percent prematurity with interpregnancy intervals of 25-36 months. When the interpregnancy interval was longer than 36 months, the prematurity rate again increased. The distribution of interpregnancy intervals for women with appropriate-forgestational-age premature and full-term
1
1
1
1
1
1
1 4 ••
1
1
1
10
1
B
1
3 5
>
16
o
1
I,
1
1
.
IB
tervals from the standard errors of those coefficients.
11
of the size of the groups on the stability of the observed rates, we constructed 95 percent confidence intervals around each rate (11). Within this group of appropriate-forgestational-age infants, the distribution of interpregnancy interval for premature infants was compared with that of full-term infants. The interval of 25-36 months was chosen as the referent category to estimate the relative effects of both shorter and longer interpregnancy intervals. Unadjusted odds ratios were estimated and 95 percent confidence intervals were calculated. The crude odds ratios were then adjusted for confounding effects by means of a logistic regression model which included factors known to cause or be associated with both prematurity and interpregnancy interval. So as not to constrain the relation between interpregnancy interval and prematurity by any specific mathematical model, each interpregnancy interval other than the referent category was represented by a separate dichotomous variable (indicator variable) in the logistic regression. In the logistic regression analysis, we calculated the odds ratios from regression coefficients and the 95 percent confidence in-
a (H
cu c
o o u o (X
s
nrd [ 1
4 2 0
0-3
4-6
7-18
•
1
,
-
n
13-18 19-B4 20-38 37-48
[
rL i
•
48+
Interpregnancy Interval (In months) FIGURE 1. Percentage of women with spontaneous premature labor (and 95% confidence intervals), by interpregnancy interval, Boston Hospital for Women, 1977-1980.
307
INTERPREGNANCY INTERVAL AND PRETERM LABOR TABLE 1
Numbers of premature and full-term births and odds ratios (crude and adjusted) for premature labor among appropriate-for-gestational-age births, by interpregnancy interval, Boston Hospital for Women, 1977-1980 Interpregnancy interval (months)
