Preterm birth is associated with increases in neonatal morbidity and mortality and the risks of medical and social disabilities later in life.1,2 A short interpregnancy interval after a previous live birth has been associated with increased risks of preterm birth, premature rupture of membranes, low birth weight, and small-for-gestational-age (SGA) neonates in subsequent pregnancy.3–6 It has been shown that neonates conceived 18–23 months after a previous birth have the lowest risks of these adverse events.5,7
Despite the fact that termination of pregnancy is a relatively common procedure, the influence of interpregnancy interval on a subsequent pregnancy after termination of pregnancy has not been established. Current World Health Organization guidelines recommend an interpregnancy interval of at least 6 months after a miscarriage or termination of pregnancy.8 The recommendation is based on the results of a single study from Latin America, which found that the risks of preterm birth, low birth weight, and premature rupture of membranes were higher among women with an interpregnancy interval of less than 6 months after abortion.9 However, the investigators did not make a distinction between miscarriages and terminated pregnancies, which caused heterogeneity in the study group.
Women undergoing termination of pregnancy are predominantly young, and subsequent pregnancies with live births are common. An evident need for research on the risks associated with interpregnancy interval after termination of pregnancy exists. The objective of our study was to assess whether the length of the interpregnancy interval after termination of pregnancy influences the risks of preterm birth, low birth weight, and SGA neonates in subsequent pregnancy.
MATERIALS AND METHODS
Finnish legislation requires hospitals to report all terminations of pregnancies to the Finnish Register of Induced Abortions and all births to the Finnish Medical Birth Register, both maintained by the National Institute for Health and Welfare.10 A detailed description of these registers and Finnish legislation on termination of pregnancy can be found in one of our previous studies.11 In this register-based national study, all women who underwent termination of pregnancy, either medical or surgical, between 2000 and 2009 according to the Register of Induced Abortions and whose subsequent pregnancy ended in a live singleton delivery according to the Medical Birth Register were included. A total of 88,522 women underwent termination of pregnancy between 2000 and 2009 according to the Register of Induced Abortions. Among these, 24,061 women had undergone induced abortion preceding a pregnancy resulting in delivery. Data on pregnancies after termination were obtained up to the end of 2009. Women whose pregnancies continued after attempted termination of pregnancy (ongoing pregnancies) ending in delivery (n=61) and women with multifetal pregnancies (n=342) or stillbirths (n=85) were excluded from the study. Women with stillbirths were excluded because they are often associated with iatrogenic preterm birth. Furthermore, women with miscarriages between termination of pregnancy and subsequent live birth (n=3,533) and women with missing information on miscarriages (n=15) or interpregnancy intervals (n=131) were excluded. The remaining 19,894 women constituted the study population (82.7%).
Women included in this study were divided into five groups according to the interpregnancy interval between termination of pregnancy and the beginning of a subsequent pregnancy resulting in live birth: interpregnancy interval less than 6 months, 6 to less than 12 months, 12 to less than 18 months, 18 to less than 24 months, and 24 months or greater. The start of a subsequent pregnancy was taken to be birth date minus gestational age at the time of birth. Gestational age at birth was obtained from the Medical Birth Register and it is the best clinical estimate at birth based on the last menstruation and in most cases on ultrasonographic examination in early pregnancy. Women with an interpregnancy interval of 18 to less than 24 months were chosen to be the reference group.
The primary outcomes in this study were preterm birth, low birth weight, and SGA neonates. The incidences and unadjusted and adjusted risks of these outcomes were calculated for interpregnancy interval study groups and compared with those in the reference group. Information on gestational age at birth and birth weight was collected from the Medical Birth Register. Birth was classified as preterm if gestational age at birth was below 37 weeks. Low birth weight was defined as a birth weight below 2,500 g. Neonates were considered to be SGA if their birth weight was less than the mean–2 standard deviations compared with the expected birth weight for the same gestational age and sex according to Finnish standards for newborns born between 24 and 43 weeks of gestation.12
When the indication for termination of pregnancy is fetal anomaly or abnormality, a new pregnancy is often wanted as soon as possible. Such a population might represent a different entity compared with women with social or ethical indications and might be overrepresented in short interpregnancy interval groups. To focus on unwanted pregnancies (termination of pregnancy with a social indication), a subgroup analysis was conducted in which women with an indication for termination of fetal anomaly or abnormality were excluded. The incidences and unadjusted and adjusted risks of primary outcomes were calculated again after exclusion of these women.
Confounding factors included parity, prepregnancy body mass index (BMI, calculated as weight (kg)/[height (m)]2), cohabitation, type of residence, socioeconomic status, maternal age, smoking, type of termination of pregnancy, and gestational age at termination of pregnancy because these factors are known to potentially associate with adverse pregnancy outcomes and demonstrated significant baseline differences. Information on maternal age, cohabitation status, occupation, type of residence, prepregnancy BMI, smoking during pregnancy, and number of previous births and pregnancies was obtained from the Medical Birth Register, which had been recorded at the time of pregnancy ending in delivery. Socioeconomic status was defined by using the stated occupation or the highest educational level reported to the Medical Birth Register. Coding was based on national standards published by Statistics Finland.13–15 According to this coding, women were further segregated into five socioeconomic status grades: upper white collar workers, lower white collar workers, blue collar workers, students, and others (such as entrepreneurs, farmers, unemployed women, housewives). Data on type of termination of pregnancy (medical or surgical), indication for termination, and gestational age at termination were obtained from the Register of Induced Abortions.
The study was approved by the Ethics Committee of the Northern Ostrobothnia Hospital District (no. 28/2010). The National Institute for Health and Welfare gave permission (THL/659/5.05.00/2010) to use confidential personal-level data from the national health registers. Personal identification numbers, used for data linkage, were removed before all analyses.
Statistical analyses were performed by using SPSS 23.0. To compare the demographic characteristics of the interpregnancy interval groups, the χ2 test or Fisher exact test was used as appropriate for categorical variables and the Kruskal–Wallis test for continuous variables. Furthermore, to compare the outcome incidences, the χ2 test or Fisher exact test was used as appropriate for categorical variables. Analyses were performed without multiple comparison adjustment.16 For comparison of the mean gestational ages at birth and mean birth weights, the analysis of variance and post hoc Dunnett test were used. Logistic regression analysis was used to assess the risks of preterm birth, low birth weight, and SGA neonates in the interpregnancy interval groups. In logistic regression models, the variable representing the interpregnancy interval was used as one classified variable (a total of five classes, of which 18 to less than 24 months was the reference group). The results are presented as P values and unadjusted odds ratios (ORs) and adjusted ORs with 95% confidence intervals (CIs) using univariable and multivariable logistic regression. Potential multicollinearity among the confounding factors was examined by calculating the variance inflation factor. A P value of <.05 was considered to be significant.
The frequencies of the five interpregnancy intervals were as follows: less than 6 months, 14.9% (n=2,956), 6 to less than 12 months, 16.1% (n=3,203), 12 to less than 18 months, 13.2% (n=2,623), 18 to less than 24 months, 10.4% (n=2,076), and 24 months or greater, 45.4% (n=9,036). The median interpregnancy interval was 21 months. Differences in demographic characteristics were statistically significant between the different interpregnancy interval groups (Table 1). Young women and women with termination of pregnancy in the second trimester tended to have shorter interpregnancy intervals. Among nulliparous women, the interpregnancy interval tended to be longer.
In the subsequent pregnancy, the overall incidences of preterm birth, low birth weight, and SGA neonates were 4.5%, 3.6%, and 2.5%, respectively. Of all the births, 0.7% were very preterm (less than 32 weeks of gestation) and 0.2% extremely preterm (less than 28 weeks of gestation). Mean birth weight was 3,493 g. The median gestational age at birth was 40 weeks (interquartile range 39–41). There were clinically minor but statistically significant differences in the mean birth weights and mean gestational ages at birth between interpregnancy interval groups less than 6 months and the reference group (Table 2). Women with an interpregnancy interval of less than 6 months had the highest incidence of preterm birth, and when compared with the reference group, the difference was statistically significant (5.6% compared with 4.0%, P=.008) (Fig. 1 and Table 2). There were no significant differences between the study groups with regard to incidences of low birth weight or SGA neonates in any interpregnancy interval group.
In univariable analysis, the estimated risk of preterm birth was higher if the interpregnancy interval was less than 6 months when compared with the reference group (Table 3). No elevated risks were seen in longer interpregnancy interval groups or regarding other adverse events. When adjusted for parity, prepregnancy BMI, cohabitation, type of residence, socioeconomic status, maternal age, smoking, type of termination of pregnancy, and gestational age at termination, the increased estimated risk of preterm birth remained statistically significant among women with an interpregnancy interval of less than 6 months (adjusted OR 1.35, 95% CI 1.02–1.77) (Table 4). No increased risk of preterm birth was found after longer interpregnancy intervals in multivariable analysis. No evidence of multicollinearity was found among the confounding factors.
The indication for termination of pregnancy was fetal anomaly or abnormality in 20.7% (n=612) of cases in the interpregnancy interval group of less than 6 months, 9.9% (n=318) in the group of 6 to less than 12 months, 4.7% (n=123) in the group of 12 to less than 18 months, 2.9% (n=61) in the reference group, and 1.0% (n=88) in the group of 24 months or greater.
In subgroup analysis after exclusion of women whose indication for termination of pregnancy was fetal anomaly or abnormality, the association between an interpregnancy interval of less than 6 months and preterm birth persisted. In subgroup analysis, the rate of preterm birth (at less than 37 weeks of gestation) was higher in women with a short interpregnancy interval (less than 6 months; 5.7%) compared with the reference group (4.0%; P=.009). The estimated risk of preterm birth in connection with a short interpregnancy interval (less than 6 months) was increased (OR 1.46, 95% CI 1.10–1.93) and it remained elevated even after adjustment for confounding factors (adjusted OR 1.37, 95% CI 1.03–1.83, P=.031). No increased risk of preterm birth was found after longer interpregnancy intervals in univariable or multivariable subgroup analyses. Furthermore, the length of the interpregnancy interval was not associated with low birth weight or SGA neonates in any of the interpregnancy interval groups.
Women who conceived less than 6 months after termination of pregnancy had a slightly but significantly increased estimated risk of preterm birth compared with women who conceived at 18 to less than 24 months after termination. No such association emerged between preterm birth and longer interpregnancy intervals. The interpregnancy interval did not influence the risk of subsequent low birth weight or SGA neonates. Young women, women with second-trimester termination of pregnancy, and women with previous deliveries had shorter interpregnancy intervals. When the indication for termination is fetal anomaly or abnormality, a new pregnancy as soon as possible is often wanted. These women were overrepresented in short interpregnancy interval groups. Nevertheless, the association between an interpregnancy interval of less than 6 months and preterm birth persisted even after excluding these women and was similar to that of the entire study population.
The main strength of this study is the large population-based cohort with high-quality data.10,17,18 In Finland, terminations of pregnancies are performed by medically qualified professionals according to national guideline.19 The importance of the interpregnancy interval as an independent risk factor can be assessed only when other confounding factors are considered. We controlled for nine confounding factors known to be associated with adverse pregnancy outcomes. Confounding still remains possible owing to factors for which we could not adjust such as previous preterm birth and ethnic background. Another limitation is that we could not stratify preterm births into spontaneous compared with medically indicated.
Most of the previous studies have assessed the effects of a short interpregnancy interval after live birth or miscarriage. Preterm birth, low birth weight, and SGA neonates have been found to be associated with a short interval after live birth.3–6 However, recently Ball et al20 questioned the causal effects of interpregnancy interval on adverse pregnancy outcomes by using within-mother analysis. In this matched model, a short interval was not associated with adverse outcomes. The results suggest that associations between a short interval and adverse birth outcomes may be the result of unmeasured confounding by maternal factors.
Unlike after live birth, women who conceive within 6 months after miscarriage have been shown to have better outcomes in subsequent pregnancy compared with women with longer interpregnancy intervals. Possibly factors associated with underlying subfertility can lead to longer intervals resulting in adverse perinatal outcomes after miscarriage.21
Evidence regarding birth spacing after termination of pregnancy is scant. One large-scale study from Latin America concluded that interpregnancy intervals of 0–2 months and 3–5 months after abortion were associated with increased risks of preterm and very preterm birth and low birth weight compared with an interval of 18–23 months. No increased risk of SGA was found.9 Unlike in our study, no distinction between spontaneous and induced abortion was made. Furthermore, the information on previous abortions was dependent on self-reported data, which may have caused recall bias. Another study concerning the effect of interpregnancy interval after medical termination of pregnancy on the risk of adverse birth outcomes among nulliparous women found an increased risk of SGA neonates when the interval was less than 6 months.22 There was no association between interval and other adverse outcomes. The authors hypothesized that necrotic decidua retained in the uterus after medical termination might lead to decreased uteroplacental–fetal blood flow in the next pregnancy and influence the risk of SGA. Also, this study relied on self-reported abortion history. In our study, the risk of giving birth to a SGA neonate was not increased and the analyses were adjusted for the method of termination of pregnancy.
Zhou et al23 conducted two studies concerning termination of pregnancy and duration of subsequent pregnancy and low birth weight. Women with first-trimester termination were compared with women whose pregnancies were not terminated. In contrast to our results, they found an increased risk of preterm delivery when the interpregnancy interval was longer than 12 months. In addition, the risk of low birth weight was elevated if the interval was longer than 6 months.24 The limitation of these studies was the fact that a comparison was made between women who underwent termination of pregnancy and women whose pregnancy ended in stillbirth, spontaneous abortion, or live birth. Heterogeneity of the control group might introduce bias, and unequal fecundity may affect the results.
Our results highlight the importance of contraception after termination of pregnancy. Although the possibility of unmeasured confounding in our study cannot be ruled out and most preterm births cannot be predicted, well-timed subsequent pregnancy may help to avoid complications associated with preterm birth. Information concerning the potential risk of preterm birth after a short interpregnancy interval is of value to women undergoing termination of pregnancy as well as to health care providers involved in abortion care.
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