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Byron C. Calhoun, M.D., FACOG, FACS, MBA
Professor & Vice-Chair, Department of Obstetrics & Gynecology West Virginia University-Charleston
U.S. Surgeon General’s Conference on the Prevention of Preterm Birth June 16 & 17, 2008
The abstracts, referenced studies, and two papers contained in this document provide evidence of a causal link between surgical induced abortion (IA) and subsequent preterm birth. One of the two papers at the conclusion of the document gives further consideration to this causal link with respect to both cost consequences and impact on informed consent. ABSTRACTS The following abstracts represent six studies which demonstrate the strongest and most significant risk association between IA and later preterm birth. (1.) Lumley J. The epidemiology of preterm birth. Bailliere's Clin Obstet Gynecology. 1993;7(3):477-498
ABSTRACT Secular trends in the prevalence of preterm birth and international comparisons of the rates of preterm birth are difficult to interpret because of differences, both formal and informal, in the registration of extremely preterm births. Accurate estimation of gestational age is another problem in the measurement of preterm birth. Preterm birth is heterogeneous in several ways. It is heterogeneous in terms of the extent to which the birth is preterm (20-27 weeks, 28-31 weeks or 32-36 weeks of gestation); in whether the birth was elective or spontaneous; and among spontaneous idiopathic preterm births, in whether there was preterm labour or premature rupture of the membranes. Case-control study designs taking account of these subgroups have been a recent feature of epidemiologic approaches. The classic social associations of preterm birth--low socioeconomic status, extremes of maternal age, primiparity, being unmarried--apply to extremely preterm and moderately preterm births as well as to the mildly preterm group. The strength of these associations is small compared with factors in the prior reproductive history and with medical and obstetric complications of the current pregnancy. Recent epidemiological research activities have focused on the ways in which risk factors such as physical workload, drugs and alcohol, lack of social support and infection might be mediating factors between sociodemographic status and preterm birth. As Eastman (1947) pointed out almost 50 years ago, 'only when the factors causing prematurity are clearly understood can any intelligent attempt at prevention be made'. [References: 74]
(2.) Lumley J. The association between prior spontaneous abortion, prior induced abortion and preterm birth in first singleton births. Prenat Neonat Med 1998;3:21-24.
DISCUSSION (in lieu of Abstract) The evidence for and against a causal relationship between prior shortened pregnancies and preterm birth is as follows. Selection bias into the study can be excluded since the data are population-based with 99.6% of births captured in the data system. Measurement error of the exposures cannot be totally excluded. Though the data have been validated against hospital records there is likely to be incomplete reporting of prior induced abortions in hospital records. Non-differential under-reporting would result in the relative risk being too low. Differential under-reporting is which prior abortions were more completely ascertained when there was a preterm birth could have occurred but the timing of data collection on prior pregnancies is at the first antenatal visit, before the outcome is known. Chance (random error) is unlikely since the 95% confidence intervals for the association with prior abortions do not include 1.00 . Confounding is likely. Maternal age, marital status and the presence of a birth defect in the index birth can be excluded since the associations in Figures 1 to 3 are still present at a similar level in a restricted data stratum of married women, age 20-34 years, with no birth defect in the index birth (unpublished data). Data on socioeconomic status, occupation, smoking, alcohol
consumption and other substance use are not collected routinely. The strength of association of these factors with preterm birth, however, is much smaller than the associations in Figures 1 to 3. The association of abortions with preterm birth cannot be explained by gravidity because the relative risks for prior births are different from prior pregnancies. Data on the gestation of the prior abortions, indications, complications, and inter-pregnancy intervals are not available in the routine perinatal data. Termination of pregnancy has been legal under case interpretation of legislation since 1969 and the procedure is covered by the federal government universal health insurance system . The data meet four of the criteria for causality. The temporal sequence is clear: the abortions preceded the preterm birth. The association is a strong one. There is a dose-response relationship: the greater the number of prior pregnancies the higher the relative risk. The association is plausible: possible mechanisms exist which are outlined below. The other criteria cannot be fully met a present: the study design (a retrospective cohort) is rated as moderate. Reversibility of the exposure is not applicable to these exposures. No other papers have reported an analysis stratified by gestation and by number of prior pregnancies so that the consistency of the findings cannot be assessed. One possible mechanism is that cervical instrumentation can facilitate the passage of organisms into the upper part of the uterus, increasing the probability of inapparent infection and subsequent preterm birth . Another is the removal of the endometrium carries a small risk of damaging the decidual stroma in such a way as to impair trophoblast invasion, migration and the full transformation of the maternal spiral arteries .
(3.) Moreau C, Kaminski M, Ancel PY, Bouyer J, Escande B, et al. Previous induced abortions and the risk of very preterm delivery: results of the EPIPAGE study. British J Obstetrics Gynaecology 2005;112(4):430-437.
ABSTRACT Objectives: To evaluate the risk of very preterm birth (22-32 weeks of gestation) associated with previous induced abortion according to the complications leading to very preterm delivery in singletons. Design: Multicentre, case-control study (the French EPIPAGE study). Setting: Regionally defined population of births in France. Sample: The sample consisted of 1943 very preterm live-born singletons (< 33 weeks of gestation), 276 moderate preterm live-born singletons (33-34 weeks) and 618 unmatched full-term controls (39-40 weeks). Methods: Data from the EPIPAGE study were analysed using polytomous logistic regression models to control for social and demographic characteristics, lifestyle habits during pregnancy and obstetric history. The main mechanisms of preterm delivery were classified as gestational hypertension, antepartum haemorrhage, fetal growth restriction, premature rupture of membranes, idiopathic preterm labor and other causes. Main Outcome Measures: Odds ratios for very preterm birth by gestational age and by pregnancy complications leading to preterm delivery associated with a history of induced abortion. Results: Women with a history of induced abortion were at higher risk of very preterm delivery than those with no such history (OR + 1.5, 95% CI 1.1-2.0); the risk was even higher for extremely preterm deliveries (< 28 weeks). The association between previous induced abortion and very preterm delivery varied according to the main complications leading to very preterm delivery. A history of induced abortion was associated with an increased risk of premature rupture of the membranes, antepartum haemorrhage (not in association with hypertension) and idiopathic spontaneous preterm labour that occur at very small gestational ages (< 28 weeks). Conversely, no association was found between induced abortion and very preterm delivery due to hypertension. Conclusion: Previous induced abortion was associated with an increased risk of very preterm delivery. The strength of the association increased with decreasing gestational age.
(4.) Stang P, Hammond AO, Bauman P. Induced Abortion Increases the Risk of Very Preterm Delivery; Results from a Large Perinatal Database. Fertility Sterility Sept 2005;S159
ABSTRACT Objective: 49% of pregnancies among American women are unintended; 1/2 of these are terminated by abortion. In 2000, 1.31 million abortions took place in the USA. There has been debate over the impact of induced abortions (VTP) on future pregnancy outcome, particularly the risk of very preterm birth (<28 weeks). Sequelae of very preterm delivery remain a major public health burden. The objective of our study was to evaluate the association between prior induced abortions and birth before 28 weeks gestation. Design: Retrospective analysis of a perinatal data base. Materials and methods: Setting: 29 delivery units in the State of Schleswig-Holstein, Germany, between 1991 and 1997. Patients: 170,254 women with singleton pregnancies. Intervention: Univariate cross table analysis and logistic regression were conducted to determine the association between previous induced first trimester abortions and delivery before 28 weeks gestation. Main outcome measures: Maternal age, smoking, cervical incompetence, preterm premature rupture of membranes (PPROM), history of uterine hemorrhage before 28 weeks, maternal hypertension, delivery before 28 weeks. Results: 64586 nulliparous women were included, 4572 (7.1 %) of whom had up to 9 VTPs . Maternal age was 27.4 ± 4.7 years in controls and 29.1 ± 5.2 in the subjects. There was no difference in gestational age[(25.9 ± 1.9 weeks (controls), 25.4 ± 2.1 (subjects)]. Univariate relations between VTP and risk factors for preterm delivery are shown in table 1. Logistic regression demonstrated the following associations with delivery before 28 weeks: Cervical incompetence OR 4.46, CI 3.18-6.27; hemorrhage < 28 wks, OR 3.33, CI 2.37 - 2.69; hypertension, OR 3.18, CI 2.17-4.67; PPROM, OR 4.67, CI 3.45-6.33, first trimester miscarriage, OR 1.67, CI 1.25-2.21, and VTP, OR 1.55, CI 1.07-2.34. There was no association between smoking or AMA and very preterm delivery.
(5.) Smith GCS, Shah I, White IR, Pell JP, Crossley JA, Dobbie R. Maternal and biochemical predictors of spontaneous preterm birth among nulliparous women: a systematic analysis in relation to degree of prematurity. Intl J Epidem 2006;35(5):1169-1177.
ABSTRACT Background: Nulliparous women are at increased risk of spontaneous preterm birth. Other maternal and biochemical risk factors have also been described. However, it is unclear whether these associations are strong enough to offer clinically useful prediction. It is also unclear whether the predictive power of these factors varies in relation to the degree of prematurity. Methods: The risk of spontaneous preterm birth associated with maternal characteristics and second trimester serum screening data was analysed in a dataset of 84 391 first births in Scotland between 1992 and 2001 using Cox and logistic regression. Variation in the relative risk of preterm birth over the period 24–36 weeks was assessed using a test of the proportional hazards assumption. Results: The risk of spontaneous preterm birth was positively associated with maternal serum levels of alpha-fetoprotein, socioeconomic deprivation, number of previous therapeutic abortions, smoking, and being unmarried and was negatively associated with height and body mass index. The risk of preterm birth at 24–28 weeks, but not later gestations, was increased in association with maternal levels of human chorionic gonadotrophin >95th percentile, maternal age <20, and two or more previous miscarriages. The area under the receiver operating characterise curve (95% CI) for models based on these factors was 0.67 (0.63–0.71) for 24–28 weeks, 0.65 (0.62–0.68) for 29–32 weeks, and 0.62 (0.61–0.63) for 33–36 weeks. Conclusions: Time to event analytic methods can identify factors that are differentially associated with spontaneous preterm birth according to the
degree of prematurity. However, models based on maternal and biochemical data perform poorly as a screening test for any degree of spontaneous preterm birth.
(6.) Levin AA, Schoenbaum SC, Monson RR, Stubblefield PG, Ryan JA. Association of Induced Abortion with Subsequent Pregnancy Loss. JAMA 1980;243(24):2495-2499
ABSTRACT We compared prior pregnancy histories of two groups of multigravidas--240 women having a pregnancy loss up to 28 weeks' gestation and 1,072 women having a term delivery. Women who had had two or more prior induced abortions had a twofold to threefold increase in risk of firsttrimester spontaneous abortion, loss between 14 to 19 and 20 to 27 weeks. The increased risk was present for women who had legal induced abortions since 1973. It was not explained by smoking status, history of prior spontaneous loss, prior abortion method, or degree of cervical dilatation. No increase in risk of pregnancy loss was detected among women with a single prior induced abortion. We conclude that multiple induced abortions do increase the risk of subsequent pregnancy losses up to 28 weeks' gestation.
BIBLIOGRAPHY The following list provides 51 peer-reviewed studies demonstrating a significant risk between IA and subsequent preterm birth since 1989. This list is not exhaustive.
* studies that included spontaneous and induced abortions but did not report preterm birth and low birth weight (LBW) risk separately for each. + studies that found a dose response effect (signifying an increased risk of preterm birth following increased number of induced abortions.)
1990s +A01 Vasso L-K, Chryssa T-B, Golding J. Previous obstetric history and subsequent preterm delivery in Greece. European J Obstetrics & Gynecology Reproductive Biology 1990;37:99-109. A02 A03 Li YJ, Zhou YS. Study of factors associated with preterm delivery. Zhongjua Liu Xing Bing Xue Za Chi. Aug 1990;11(4):229-234. Harger JH, Hsing AW, Tuomala RE, Gibbs RS, Mead PG et al. Risk factors for preterm premature rupture of fetal membranes: A multicenter case-control study. Am J Obstet Gynec 1990;163:130-137. McGregor JA, French J, Richter R. Antenatal microbiologic and maternal risk factors associated with prematurity. Amer J Obstet Gynecol 1990;163:1465-1473 Pickering RM, Deeks JJ. Risks of Delivery during 20th to the 36th Week of Gestation. Intl. J Epidemiology 1991;20:456-466.
*+A06 Zhang J, Savitz DA. Preterm Birth Subtypes among Blacks and Whites. Epidemiology 1992;3:428-433.
*A07 Michielutte R, Ernest JM, Moore ML, Meis PJ, Sharp PC, Wells HB, Buescher PA. A Comparison of Risk Assessment Models for Term and Preterm Low Birthweight. Preventive Medicine 1992;21:98-109. A08 A09 Gong JH. Preterm delivery and its risk factors. Zhounghua Fu Chan Ke Za Chi Jan. 1992;27(1):22-24 Mandelson MT, Maden CP, Daling JR. Low Birth Weight in Relation Multiple Induced Abortions. Am J Public Health 1992;82;391-394
+A10 Lumley J. The epidemiology of preterm birth. Bailliere's Clin Obstet Gynecology. 1993;7(3):477-498 A11 Algert C, Roberts C, Adelson P, Frammer M. Low birth weight in New South Wales, 1987: a Population-Based Study. Aust New Zealand J Obstet Gynaecol 1993;33:243-248. Ekwo EE, Grusslink CA, Moawad A. Previous pregnancy outcomes and subsequent risk of premature rupture of amniotic sac membranes. Brit J Obstet Gynecol 1993;100(6):536-541. Lekea-Karanika V, Tzoumaka-Bangoula C. Past obstetric history of the mother and its association with low birth weight of a subseaquent child: a populationbased study. Paediatric Perinat Epidemiol 1994;8:173-187 Guinn D, Goldenberg RL, Hauth JC, Andrews WA, Thom E, Romero R. Risk factors for the development of preterm premature rupture of membranes after arrest of preterm labor. AJOG 1995;173(4):1310-1315.
*A15 Hillier SL, Nugent RP, Eschenbach DA, Krohn MA,et al. Association Between Bacterial Vaginosis And Preterm Delivery Of A Low-Birth-Weight Infant. NEJM 1995;333:1737-1742. A16 Khalil AK, El-Amrawy SM, Ibrahim AG, et al. Pattern of growth and development of premature children at the age of two and three years in Alexandria, Egypt. Eastern Mediterranean Health Journal 1995;1(2):186-193. Meis PJ, Michielutte R, Peters TJ, Wells HB. Factors associated with preterm birth in Cardiff, Wales. Amer J Obstet Gynecol 1995;173:590-596.
+A18 Lang JM, Lieberman E, Cohen A. A Comparison of Risk Factors for Preterm Labor and Term Small-for-Gestational-Age Birth. Epidemiology 1996;7:369-376. *A19 Hagan R, Benninger H, Chiffings D. Evans S, French H. Very preterm birth - a regional study. Part 1: Maternal and obstetric factors. BJOG 1996;103:230-238.
Chie-Pein Chen, Kuo-Gon Wang, Yuh-Cheng Yang, Lai-Chu See. Risk factors for preterm birth in an upper middle class Chinese population. Eur J Obstet Gynecol Reprod Bio 1996;70(1):53-59. Jacobsen G, Schei B, Bakketeig LS. Prepregnant reproductive risk and subsequent birth outcome among Scandinavian parous women. Norsk Epidemiol 1997;7(1):33-39.
+A22 Lumley J. The association between prior spontaneous abortion, prior induced abortion and preterm birth in first singleton births. Prenat Neonat Med 1998;3:2124. +A23 Martius JA, Steck T, Oehler MK, Wulf K-H. Risk factors associated with preterm (<37+0 weeks) and early preterm (<32+0 weeks): univariate and multi-variate analysis of 106 345 singleton births from 1994 statewide perinatal survey of Bavaria. European J Obstetrics & Gynecology Reproductive Biology 1998;80: 183-189. A24 Small Babies in Scotland A Ten Year Overview 1987-1996. Information and Statistics Division. The National Health Service in Scotland. Scottish Program for Clinical Effectiveness. Edinburgh 1998 ISBN 1-902076-07-9. Lee KS, Lee WC, Meng KH, Lee Ch, Kim SP. Maternal Factors Associated with the Premature Rupture of Membrane in the Low Birth Weight Infant Deliveries. Korean J Prev Med 1998;21(2):207-216.
+A26 Ancel PY, Saurel-Cubizolles M-J, Renzo GCD, Papiernik E, Breart G. Very and moderate preterm births: are the risk factors different? British J Obstetrics and Gynaecology 1999;106:1162-1170. +A27 Zhou W, Sorenson HT, Olsen J. Induced Abortion and Subsequent Pregnancy Duration. Obstetrics & Gynecology 1999;94:948-953. A28 Ancel PY, Saurel-Cubizolles, Di Renzo GC, Papiernik E, Breart G Social Differences of very preterm birth in Europe: interaction with obstetric history. American J Epi 1999;149(10):908-915.
2000-2007 A29 Foix-L'Helias L, Ancel PY, Blondel B. Changes in risk factors of preterm delivery in France between 1981 and 1995. Paediatric and Perinatal Epidemiology. Oct 2000;14(4):314-323. Foix-L'Helias L, Ancel, Blondel B. Risk factors for prematurity in France and
comparisons betweeen spontaneous prematurity and induced labor; results from the National Perinatal Survey 1995. J Gynecol Obstet Bio Reprod (Paris) Feb 2000;29(1);55-65. *A31 Gardosi J, Francis A. Early Pregnancy predictors of preterm birth: the role of a prolonged menstruation-conception interval. BJOG 2000;107(2):228-237. A32 Bettiol H, Rona RJ, Chin S, Goldani M, Barberi M. Risk Factors Associated with preterm births in Southeast Brazil: a comparison of two birth cohorts born 15 years apart. Paediatric Perinatal Epidemiol 2000;14(1):30-38.
+A33 Henriet L, Kaminski M. Impact of induced abortions on subsequent pregnancy outcome: the 1995 French national perinatal survey. British J Obstetrics Gynaecology 2001;108:1036-1042. A34 A35 Letamo G, Majelantle RG. Factors Influencing Low Birth Weight and Prematurity in Botswana. J Biosoc Sci 2001;33(3):391-403. Grimmer I, Buhrer C, Dudenhausen JW. Preconceptional factors associated with very low birth weight delivery: a case-control study. BMC Public Health 2002; 2:10 [Germany]. Balaka B, Boeta S, Aghere AD, Boko K, Kessie K, Assimadi K. Risk factors associated with prematurity at the University of Lme, Togo. Bull Soc Pathol Exot Nov 2002;95(4):280-283. Han WH, Chen LM, Li CY. Incidences of and Predictors for Preterm Births and Low Birth Weight Infants in Taiwan. Chinese Electronic Periodical Services 2003:131-141. Reime B, Schuecking BA, Wenzlaff P. Perinatal outcomes of teenage pregnancies according to gravidity and obstetric history. Annals of Epidemiology 2004;14(8):619-619 [German subjects].
+A39 Ancel PY, Lelong N, Papiernik E, Saurel-Cubizolles MJ, Kaminski M. History of induced abortion as a risk factor for preterm birth in European countries: results of EUROPOP survey. Human Repro 2004; 19(3): 734-740. A40 Umeora OUJ, Ande ABA, Onuh SO, Okubor PO et al. Incidence and risk factors for preterm delivery in a tertiary health institution in Nigeria. J Obstet Gynaecol 2004;24(8):895-896.
+A41 Moreau C, Kaminski M, Ancel PY, Bouyer J, Escande B, et al. Previous induced abortions and the risk of very preterm delivery: results of the EPIPAGE study. British J Obstetrics Gynaecology 2005;112(4):430-437. A42 Conde-Agudelo A, Belizan JM, Breman R, Brockman SC, Rosas-Bermudez.
Effect of the interpregnancy interval after an abortion on maternal and perinatal health in Latin America. Int J Gynaecol & Obstet 2005;89 (Supp. 1):S34-S40. A43 Stang P, Hammond AO, Bauman P. Induced Abortion Increases the Risk of Very Preterm Delivery; Results from a Large Perinatal Database. Fertility Sterility Sept 2005;S159. Etuk SJ, Etuk IS, Oyo-Ita AE. Factors Influencing the Incidence of Pre-term Birth in Calabar, Nigeria. Nigerian J Physiological Sciences 2005;20(1-2):63-68. Poikkens P. Unkila-Kallio L, Vilska S, Repokari L. et al. Impact of Infertility Characteristics and treatment modalities on singleton pregnancies after assisted reproduction. Reprodutive Biomed July 2006;13(1):135-144. Samin A, Al-Dabbagh, Wafa Y Al-Taee. Pregnancy and Childbirth. BMC 2006;6:13. Smith GCS, Shah I, White IR, Pell JP, Crossley JA, Dobbie R. Maternal and biochemical predictors of spontaneous preterm birth among nulliparous women: a systematic analysis in relation to degree of prematurity. Intl J Epidem 2006;35(5):1169-1177. Briunsma F, Lemley J, Tan J, Quinn M. Precancerious changes in the cervix and risk of subsequent preterm birth. BJOG Jan. 2007;114(1):70-80 Jackson JE, Grobman WA, Haney E, Casele H. Mid-trimester dilation and evacuation with laminaria does not increase the risk for severe subsequent pregnancy complications. Intl J Gynecol Obstet 2007;96:12-15.
*+A50 Brown TS, Adera T, Masho SW. Previous abortion and the risk of low birth weight and preterm births. J Epidemiol Commun Health 2008;62:16-22 A51 Reime B, Schuecking BA, Wenzlaff P. Reproductive Outcomes in Adolescents Who Had a Previous Birth or an Induced Abortion Compared to Adolescents' First Pregnancies. BMC Pregnancy and Childbirth 2008;8:4.
Induced Abortion and Risk of Later Premature Births
Brent Rooney Byron C. Calhoun, M.D.
ABSTRACT At least 49 studies have demonstrated a statistically significant increase in premature births (PB) or low birth weight (LBW) risk in women with prior induced abortions (IAs). This paper will focus on the risk of early premature births (EPBs) (< 32 weeks gestation) and extremely early premature births (XPBs) (< 28 weeks gestation). Large studies have reported a doubling of EPB risk from two prior IAs. Women who had four or more IAs experienced, on average, nine times the risk of XPB, an increase of 800 percent. These results suggest that women contemplating IA should be informed of this potential risk to subsequent pregnancies, and that physicians should be aware of the potential liability and possible need for intensified prenatal care.
A 1986 review concluded that “more research is needed before it is clear whether multiple induced abortions carry an increased 11 risk of adverse pregnancy outcomes.” The more recent, large studies discussed here help supply this lack. Australian Study 12 A 1993 study in Victoria, Australia, involved 121,305 total births and compared the risk of PB and XPB in women with various numbers of IAs, compared with a control group of women who had no prior pregnancies (see Table 1, derived from data in this report).
Informed consent for an elective surgical procedure must generally cover long-term consequences and not just immediate risk. A woman considering an induced abortion (IA) should thus expect to be informed of potential effects on her fertility and the health of future infants, as well as her own future health. An elevated risk of bearing a child afflicted with a serious disability such as cerebral palsy might influence her decision, as well as future liability determinations by courts. Low birth weight (LBW) and premature birth (PB) are the most important risk factors for infant mortality or later disabilities1 as well as for lower cognitive abilities and greater behavioral problems2 and thus contribute importantly to the liability exposure of obstetricians. A literature review retrieved 49 studies that demonstrated at least 95 percent confidence in an increased risk of preterm birth (PB), or surrogates such as low birth weight or second-trimester spontaneous abortion, in association with previous induced abortions. A list of these studies, which probably does not comprise all such studies, is appended to this article. If these 49 statistically significant associations were the result of chance alone, as may happen in 5 of 100 tests, IA should be associated with a reduction in PBs, with P<.05, in an equivalent number of tests. Not one such instance has been found in the literature. A MedLine search from 1966 to March, 2003, retrieved 8 studies that purportedly failed to show a significant increase in premature births after IA.3-10 Most showed an increase that did not reach statistical significance because of the small sample size: fewer than 1,000 pregnancies following an IA. In one, an increased risk of PB in women who had had an IA was nonsignificant when controlled for parity.3 These studies did not consider separately the risk of EPBs or XPBs, or the effect of multiple IAs, except one that showed a statistically significant increase of EPB, despite the statement in the abstract that “in the Netherlands there are no significant indications that spontaneous midtrimester abortions or premature deliveries are caused by a previous induced abortion.”6
Table 1: Premature birth risk by number of prior induced abortions (IAs) 12 compared with outcome of first pregnancies, Victoria, 1986-1990
As Lumley explains: The associations are different in the three gestation categories (20-27, 28-31, and 32-36 weeks), being particularly striking for births before 28 weeks. In this category, there is also evidence for a dose-response relationship between number of prior lost pregnancies and the prevalence of preterm birth: relative risks of 1.66 and 1.55 for one spontaneous or induced abortion, of 2.94 and 2.46 for two, and of 5.89 and 5.58 for three or more. These last four relative risks are substantially greater than any of those associated with maternal age, marital status, parity or socioeconomic status: that is, the association is most unlikely to be explained by con12 founding factors of a sociodemographic kind. Lumley's argument that “small single possible confounders cannot explain big risk factors such as 2.46 and 5.58” would also apply to any attempt to pose smoking or drug abuse as an explanation for the entire abortion-premature birth association. The great majority of theAustralian IAs were via vacuum aspiration; thus the PB risk cannot be attributed to dilation & curettage IAs. The author noted that cross-sectional studies show that the relative risk of preterm delivery increases with the number of the previous preterm births, but that the risk of subsequent preterm 12 births diminishes with each full-term delivery. Thus, IA removes the protective potential of a full-term delivery, as others 13 have also observed.
Number 2 Summer 2003
Journal of American Physicians and Surgeons Volume 8
In 1998, with twice the number of births (243,679) to analyze as 14 in 1993, Lumley validated her 1993 results and additionally showed that women with four or more prior IAs had an XPB risk nine times that of primigravidas. German Study Another large study of 106,345 births in Bavaria,15 including 85 percent of births in the state and 1,146 EPBs, showed a comparable dose-response curve (see Table 2, extracted from Table 2 in the Bavarian study), confirming the Australian finding of the greatest increased risk for the earliest premature infants. In a multivariate analysis that included many of the possible confounding variables, including previous stillborns, infertility treatment, age under 18 or over 35 years, malpresentation, premature rupture of membranes, and preeclampsia, the effect of even a single IAremained significant.
curred in 1980, 1981, and 1982.16 Reversibility of the exposure is not applicable to this circumstance. Consistency of findings with earlier studies cannot be assessed because these were not stratified by length of gestation, number of prior pregnancies, and number of IAs.14 However, the large studies in Germany, Denmark, and Australia consistently support multiple prior IAs as boosting EPB risk.14-16 Only theAustralian studies included an XPB category.12,14 Liability and Informed Consent Recent litigation by women who claim that they were not fully informed about all the risks of an elective abortion, especially a possible increased lifetime risk of breast cancer, has drawn attention to the process of obtaining informed consent for this procedure. Moreover, even a signed consent form does not suffice to relieve a physician in the U.S. or Canada of the responsibility to withhold a treatment that he knows, or ought to know, is medically contraindicated.20 What level of risk will courts determine to constitute a medical contraindication? Liability costs are especially high in cases involving damaged babies. The median damage award in cases of medical negligence in attending at childbirth was $2,050,000 between 1994 and 2000.21 Women are warned in a classic book covering 50 risk factors for PB that “if you have had one or more induced abortions, your risk of prematurity with this pregnancy increases by about 30 percent.”22 As shown here, the risk could be substantially higher than that, depending on the number of abortions and the method used. It has been claimed that “induced abortion...is directly responsible for many thousands of cases of cerebral palsy–in North America alone–that otherwise would not have occurred.”23 Supporting this assertion is the fact that the cerebral palsy risk in XPB is about 38 times higher than in the overall population of newborns,1 in which the risk of cerebral palsy is approximately 2-3 per 1,000 births.24 As the liability costs for cerebral palsy are exceptionally high, induced abortion, particularly without very detailed informed consent, may carry an unsupportable legal liability. Courts may not require definitive proof of causation; the existence of a number of positive studies, in the absence of definitive refutation, may be sufficient reason to include discussion of a potential serious adverse effect in obtaining informed consent. A consent form that simply lists such items as “incompetent cervix” or “infection” as potential complications, but does not inform women of the elevated future risk of a preterm delivery, and that the latter constitutes a risk factor for devastating complications such as cerebral palsy, may not satisfy courts. The authors of a recent CME review survey article, which evaluated 24 studies of abortion and PB, strongly affirmed the need for informed consent. They stated that prior IAs boost the risk of PB and that 7 of 12 significant studies that they reviewed identified a dose-response effect, with risks increasing with the number of IAs.25
Brent Rooney is a medical researcher. He may be contacted at the Reduce Preterm Risk Coalition, 3456 Dunbar St. (146), Vancouver, Canada V6S 2C2. E-mail address: email@example.com or firstname.lastname@example.org. Byron C. Calhoun, M.D., F.A.C.O.G., F.A.C.S., is Director, Perinatal Assessment Unit, Rockford Memorial Medical Center in Rockford, IL; Visiting Clinical Professor in Obstetrics and Gynecology, University of Illinois at Chicago; and Adjunct Professor of Obstetrics and Gynecology, Midwestern University, Chicago College of Osteopathic Medicine. Editorial assistance by Jane M. Orient, M.D., is gratefully acknowledged.
Table 2: Odds ratio (OR) for premature births by number 15 of prior induced abortions (IAs)
Danish Study A 1999 study of Danish women16 is especially important because it used an IA registry, thus eliminating recall bias, the hypothesis that women with prior IAs who deliver prematurely are more accurate in reporting reproductive history than women who deliver at full term, as a possible explanation for the results. This study of 61,753 women found an odds ratio for preterm birth at <34 weeks gestation of 1.99 (95% CI 1.64-2.43) for one prior IA and 2.03 (95% CI 1.36-3.04) for two or more prior IAs. Vacuum aspiration (VA) was the method used in 92.3 percent of all abortions. For VA, PB (gestation <37 weeks) odds ratios for 1, 2, 3 or more IAs were: 1.82, 2.45, and 2.00, respectively. Dilation and evacuation increased the risk substantially. One evacuation was associated with a PB odds ratio of 2.27 whereas two prior evacuations had a very large odds ratio of 12.55. Mechanisms forAbortions Causing a Premature Birth Risk An accepted risk of surgical IA is incompetent cervix, which is a PB risk factor.17 Nulliparous women who have multiple IAs boost their odds of being over age 35 at their first term delivery, a risk factor for PB.14,15 Additional risk factors for PB that may be increased by abortion include uterine adhesions,14,23 infection,17-19 and mental distress.17 The evidence meets four of the criteria for determining causality:14 (1) the abortions preceded the premature births; (2) the association is strong; (3) there is a dose-response relationship; and (4) the association is plausible. A criterion for causality that could not be met in 1998 was confirmation by a prospective study. However, the Danish study identified all subsequent pregnancies until 1994 of the women under study, whose first pregnancies ocJournal of American Physicians and Surgeons Volume 8 Number 2
Escobar GJ, Littenberg B, Petitti DB. Outcome among surviving very low birthweight infants; a meta-analysis. Arch Dis Child 1991;66:204-211. Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJS. Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA 2002;288:728-737. Park TK, Strauss LT, Hogue CJ, Kim IS. Previous experience of induced abortion as a risk factor for fetal death and preterm delivery. Int J Gynaecol Obstet 1984;22:195-202. Meirik O, Bergstrom R. Outcome of delivery subsequent to vacuumaspiration abortion in nulliparous women. Acta Obstet Gynecol Scand 1983;62:499-509. Frank PI, Kay CR, Lewis TL, Parish S. Outcome of pregnancy following induced abortion. Report from the joint study of the Royal College of General Practitioners and the Royal College of Obstetricians and Gynaecologists. Br J Obstet Gynaecol 1985;92:308-316. Van der Slikke JW, Treffers PE. Influence of induced abortion on gestational duration in subsequent pregnancies. BMJ 1978;1(6108):270-272. Daling JR, Emanuel I. Induced abortion and subsequent outcome of pregnancy in a series of American women. N Engl J Med 1977;297:1241-1245. Schott G, Ehrig E, Wulff V. Prospective studies into pregnancies of primiparae with record of therapeutic termination of previous pregnancies or of spontaneous abortion and assessment of fertility. Zentralbl Gynaekol 1980;102:932-938, 939-944 [German]. Kalish RB, Chasen ST, Rosenzweig LB, Rashbaum WK, Chervenak FA. Impact of midtrimester dilation and evacuation on subsequent pregnancy outcome. Am J Obstet Gynecol 2002;187:882-885. Lao TT, Ho LF. Induced abortion is not a cause of subsequent preterm delivery in teenage pregnancies. Hum Reprod 1998;13:758-761. Hogue CJ. Impact of abortion on subsequent fecundity. Clin Obstet Gynaecol 1986;13:95-103. Lumley J. The epidemiology of preterm birth. Bailliere's Clin Obstet Gynecol 1993;7(3):477-498.
Hogue CJ, Cates W Jr., Tietze C. Impact of vacuum aspiration on future childbearing: a review. Fam Planning Perspect 1983;15:119-126. Lumley J. The association between prior spontaneous abortion, prior induced abortion and preterm birth in first singleton births. Prenat Neonat Med 1998;3:21-24. Martius JA, Steck T, Oehler MK, Wulf K-H. Risk factors associated with preterm (<37+0 weeks) and early preterm (<32+0 weeks): univariate and multi-variate analysis of 106,345 singleton births from 1994 statewide perinatal survey of Bavaria. Eur J Obstet Gynecol Reprod Biol 1998;80:183-189. Zhou W, Sorenson HT, Olsen J. Induced Abortion and subsequent pregnancy duration. Obstet Gynecol 1999;94:948-953. Berkowitz GS, Papiernik E. Epidemiology of preterm birth. Epidemiol Rev 1993;15:414-443. Muhlemann K, Germain M, Krohn M. Does an abortion increase the risk of intrapartum infection in the following pregnancy? Epidemiol 1996;7:194-198. Daling JR, Krohn MA, Miscarriage or termination in the immediately preceding pregnancy increases the risk of intraamniotic infection in the following pregnancy. Am J Epidemiol 1992;136:1013 SER Abstracts. Picard E, Robertson G. Legal Liabilities of Doctors and Hospitals in Canada. Scarsborough, Ontario: Carswell; 1996:264-265. Zimmerman R, Oster C. Assigning liability: insurers' missteps helped provoke malpractice “crisis.” Wall St J 2002;June 24:A1. Luke B. Every Pregnant Woman's Guide to Preventing Premature Birth. New York, N.Y.: Times Books; 1995. Ring-Cassidy E, Gentles I. Woman's Health after Abortion. Toronto, Ontario: de Veber Institute; 2002. Smith WS, Camfield C, Camfield P Living with cerebral palsy and tube . feeding: a population-based follow-up study. J Pediatr 1999;135:307-310. Thorp JM, Hartmann KE, Shadigian E. Physical and psychological health consequences of induced abortion: review of the evidence. Obstet Gynecol Survey 2003;58(1):66-79.
APPENDIX: Studies that showed a statistically
significant increase in preterm birth after induced abortion *Ancel P-V, Saurel-Cubizolles M-J, Renzo GCD, Papiernik E, Breart G. Very and moderate preterm births: are the risk factors different? Br J Obstet Gynaecol 1999;106:1162-1170. Barsy G, Sarkany J. Impact of induced abortion on the birth rate and infant mortality. Demografia 1963;6:427-467. Berkowitz GS. An epidemiologic study of pr e t erm d elivery. A m J Ep id e miol 1981;113:81-92. Bognar Z, Czeizel A. Mortality and morbidity associated with legal abortions in Hungary, 19601973. Am J Public Health 1976;66:568-575. Czeizel A, Bognar Z, Tusnady G, et al. Changes in mean birth weight and proportion of lowweight births in Hungary. Br J Prev Soc Med 1970;24:146-153. Drac P Nekvasilova Z. Premature termination of , pregnancy after previous interruption of pregnancy. Cesk Gynekol 1970;35:332-333. Furusawa Y, Koya Y. The influence of artificial abortion on delivery. In: Koya Y, ed. Harmful Effects of Induced Abortion. Tokyo: Family Planning Federation of Japan; 1966:74-83. 48
Grindel B, Lubinski H, Voigt M. Induced abortion in primigravidae and subsequent pregnancy, with particular attention of underweight. Zentralbl Gynaekol 1979;101:1009-1114. Harlap S, Davies AM. Late sequelae of induced abortion: complications and outcome of pregn a n c y a n d l a b o r. A m J E p i d e m i o l 1975;102:219-224. Henriet L, Kaminski M. Impact of induced abortions on subsequent pregnancy outcome: the 1995 French national perinatal survey. Br J Obstet Gynaecol 2001;108:1036-1042. *Hillier SL, Nugent RP, Eschenbach DA, Krohn MA, et al. Association between bacterial vaginosis and preterm delivery of a lowbirth-weight infant. N Engl J Med 1995;333: 1737-1742. Hungarian Central Statistical Office. Perinatalishalazons. Budapest: Hungarian Central Statistical Office; 1972. Koller O, Eikhom SN. Late sequelae of induced abortion in primigravidae. Acta Obstet Gynecol Scand 1977;56:311-317. Kreibich H, Ludwig A. Early and late complications of abortion in juvenile primigravidae (including recommended measures). Z Aerztl Fortbild (Jena) 1980;74:311-316.
Lang JM, Lieberman E, Cohen A. A Comparison of Risk Factors for Preterm Labor and Term Small-for-Gestational-Age Birth. Epidemiology 1996;7:369-376. Lean TH, Hogue CJR, Wood J. Low birth weight after induced abortion in Singapore. Presented at the 105th Annual Meeting of the American Public Health Association, Washington D.C., Oct. 31, 1977. Legrillo V. Quickenton P Therriault GD, et al. , Effect of induced abortion on subsequent reproductive function. Final report to NICHD. Albany, N.Y.: New York State Health Department; 1980. Lerner RC, Varma AO. Prospective study of the outcome of pregnancy subsequent to previous induced abortion. Final report, Contract no. (N01-HD-62803). New York: Downstate Medical Center, SUNY, January 1981. Levin A, Schoenbaum S, Monson R, Stubblefield P Ryan K. Association of abortion with subse, quent pregnancy loss. JAMA 1980;243(24): 2495-2499. L i e b e r m a n E , R y a n K J, M ons on RR, Schoenbaum SC. Risk factors accounting for racial differences in the rate of premature birth. N Engl J Med 1987;317: 743-748. Number 2 Summer 2003
Journal of American Physicians and Surgeons Volume 8
Lumley J. Very low birth-weight (less than 1500g) and previous induced abortion: Victoria 19821983. Aust NZ J Obstet Gynecol 1986;26:268-272. Lumley J. The epidemiology of preterm birth. Bailliere's Clin Obstet Gynecol 1993;7(3): 477-498. Lumley J. The association between prior spontaneous abortion, prior induced abortion and preterm birth in first singleton births. Prenat Neonat Med 1998;3:21-24. Martius JA, Steck T, Oehler MK, Wulf K-H. Risk factors associated with preterm (<37+0 weeks) and early preterm (<32+0 weeks): univariate and multivariate analysis of 106 345 singleton births from 1994 statewide perinatal survey of Bavaria. Eur J Obstet Gynecol Reprod Biol 1998;80:183-189. Meirik O, Bergstrom R. Outcome of delivery subsequent to vacuum aspiration abortion in nulliparous women. Acta Obstet Gynecol Scand 1982;61:415-429. *Michielutte R, Ernest JM, Moore ML, Meis PJ, Sharp PC, Wells HB, Buescher PA. A Comparison of Risk Assessment Models for Term and Preterm Low Birthweight. Prev Med 1992;21:98-109. Miltenyi K. On the effects of induced abortion. Demografia 1964;7:73-87. Mocsary P Csapo AI. Effect of menstrual induc, tion on prematurity rate. Lancet 1978;1:11591160. Mueller-Heubach E, Guzick DS. Evaluation of risk scoring in a preterm birth prevention study of indigent patients. Am J Obstet Gynecol 1989;160:829-837. Obel E, et al. Pregnancy complications following legally induced abortion with special reference to abortion technique. Acta Obstet Gynecol Scand 1979;58:147-152. Pantelakis SN, Papadimitriou GC, Doxiadis SA. Influence of induced and spontaneous abortions on the outcome of subsequent pregnancies. Am J Obstet Gynecol 1973;116:799-805.
Papaevangelou G, Vrettos AS, Papadatos D, Alexiou C. The effect of spontaneous and induced abortion on prematurity and birthweight. J Obstet Gynaecol Br Commonwealth. 1973;80(May):418-422. Pickering RM, Forbes J. Risk of preterm delivery and small-for-gestational age infants following abortion: a population study. Br J Obstet Gynecol 1985;92:1106-1112. Pickering RM, Deeks JJ. Risks of Delivery during 20th to the 36th Week of Gestation. Int J Epidemiol 1991;20:456-466. Puyenbroek J, Stolte L. The relationship between spontaneous and induced abortions and the occurrence of second-trimester abortion in subsequent pregnancies. Eur J Obstet Gynecol Reprod Biol 1983;14:299-309.[This is the only study in this complete list that uses secondtrimester abortion as a surrogate for PTB.] Ratten G et al. Effect of abortion on maturity of subsequent pregnancy. Med J Aust 1979(June):479-480. Richardson JA, Dixon G. Effect of legal termination on subsequent pregnancy. BMJ 1976;1:1303-1304. Roht LH, Aoyama H, Leinen GE, et al. The association of multiple induced abortions with subsequent prematurity and spontaneous abortion. Acta Obstet Gynaecol Jpn 1976;23:140-145 Schoenbaum LS, Monson RR. No association between coffee consumption and adverse outcomes of pregnancy. N Engl J Med 1982;306:141-145. Seidman DS, Ever-Hadani P Slater PE, Harlap S, , et al. Child-bearing after induced abortion: reassessment of risk. J Epidemiology Community Health 1988;42:294-298. Shiono PH, Lebanoff MA. Ethnic differences and very preterm delivery. Am J Public Health 1986;76:1317-1321.
Slater PE, Davies AM, Harlap S. The effect of abortion method on the outcome of subsequent pregnancy. J Reprod Med 1981;28:123-128. Van der Slikke JW, Treffers PE. Influence of induced abortion on gestational duration in subsequent pregnancies. BMJ 1978;1:270-272. Vasso L-K, Chryssa T-B, Golding J. Previous obstetric history and subsequent preterm delivery in Greece. Eur J Obstet Gynecol Reprod Biol 1990;37:99-109. World Health Organization. Special Programme of Research, Development and Research Training in Human Reproduction: Seventh Annual Report, Geneva, Nov. 1978. World Health Organization Task Force on the Sequelae of Abortion. Gestation, birthweight and spontaneous abortion. Lancet 1979;1:142-145. *Zhang J, Savitz DA. Preterm birth subtypes among blacks and whites. Epidemiology 1992;3:428-433. Zwahr C, Voigt M, Kunz L, et al. Relationships between interruption abortion, and premature birth and low birth weight. Zentralbl Gynaekol 1980;102: 738-747. Zhou W, Sorenson HT, Olsen J. Induced abortion and subsequent pregnancy duration. Obstet Gynecol 1999;94:948-953.
*Studies that included spontaneous and induced abortions but did not report PTB/LBW risk separately for each
“Since among practitioners there will prove to be so much difference of opinion about acute diseases that the remedies which one physician gives in the belief that they are the best are considered by a second to be bad, laymen are likely to object to such that their art resembles divination; for diviners too think that the same bird, which they hold to be a happy omen on the left, is an unlucky one when on the right, while other diviners maintain the opposite.” Hippocrates Regimen in Acute Diseases [Fortunately AAPS can discern right from left, and open debate is welcome.]
– Lawrence R. Huntoon, M.D., Ph.D.
Journal of American Physicians and Surgeons Volume 8
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