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ORIGINAL RESEARCH |
From the Department of Obstetrics and Gynecology, Fundacion Clinica Valle del Lili, Cali, Colombia; Latin American Center for Perinatology and Human Development (CLAP), Division of Health Promotion and Protection, Pan American Health Organization, World Health Organization, Montevideo, Uruguay; Institute for Clinical Effectiveness and Health Policy, Buenos Aires, Argentina; Office of Population and Reproductive Health, Bureau for Global Health, USAID, Washington, DC; and Universidad Autonoma de Occidente, Cali, Colombia.
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ABSTRACT |
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 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Methods: We investigated the effect of interpregnancy interval on perinatal outcomes in 1,125,430 pregnancies recorded in the Perinatal Information System database of the Latin American Center for Perinatology and Human Development, Montevideo, Uruguay, between 1985 and 2004. Odds ratios (ORs) were adjusted for 16 major confounding factors using multiple logistic regression models.
Results: Compared with infants with interpregnancy intervals of 18–23 months, those born to women with intervals shorter than 6 months had an increased risk of early neonatal death (adjusted OR 1.49, 95% confidence interval [CI] 1.06–1.96), fetal death (adjusted OR 1.54, 95% CI 1.28–1.83), low birth weight (adjusted OR 1.88, 95% CI 1.78–1.90), very low birth weight (adjusted OR 2.01, 95% CI 1.73–2.31), preterm birth (adjusted OR 1.80, 95% CI 1.71–1.89), very preterm birth (adjusted OR 1.95, 95% CI 1.67–2.26), and small for gestational age (adjusted OR 1.30, 95% CI 1.25–1.36). Intervals of 6–11 months and 60 months and longer were also associated with a significantly greater risk for the 7 adverse perinatal outcomes.
Conclusion: In Latin America, interpregnancy intervals shorter than 12 months and longer than 59 months are independently associated with increased risk of adverse perinatal outcomes. These data suggest that spacing pregnancies appropriately could prevent perinatal deaths and other adverse perinatal outcomes in the developing world.
Level of Evidence: II-2
It is estimated that, worldwide, more than 7.6 million perinatal deaths occur annually, of which 98% take place in developing countries.13 If short and/or long interpregnancy intervals are found to be independently associated with increased risk of perinatal mortality and/or other adverse perinatal outcomes, birth spacing, an intervention that does not depend on highly technical training or sophisticated equipment, might then be considered an intervention to prevent such adverse pregnancy outcomes in the developing world. The objective of the present study was to estimate whether interpregnancy interval is associated with increased risk of early neonatal death, fetal death, and other adverse perinatal outcomes in a large cohort of Latin American women.
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MATERIALS AND METHODS |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Inclusion in the study group was restricted to parous women who were delivering singleton infants and whose previous pregnancy ended after 19 weeks of gestation. Women with multiple gestations were excluded.
Gestational age was estimated as the interval between the date of the first day of the mother’s last normal menstrual period and the infant’s birth date. It was confirmed by means of ultrasonography in 25% of women. Interpregnancy interval was defined as the time elapsed between the woman’s last delivery and the date of the last menstrual period for the index pregnancy. The interval was calculated in days and converted into completed months (30 days was assumed to equal 1 month). Interpregnancy intervals were categorized as less than 6, 6–11, 12–17, 18–23, 24–59, and 60 months or more. Maternal age was defined as completed years at time of delivery. Parity was defined as the number of previous births, including stillbirths. Marital status was dichotomized between those who did and those who did not live with the infant’s father. Mother’s education was categorized into less than 12 years and 12 years or more of education completed. Information on cigarette smoking was recorded at the first antenatal care visit and categorized into smoker and nonsmoker. Maternal height and weight before pregnancy were also recorded by recall at the woman’s first antenatal visit in centimeters and kilograms, respectively. The prepregnancy body mass index (weight [kg]/height [m2]) was categorized as underweight (body mass index < 19.8), normal (19.8–26.0), overweight (26.1–29.0), and obese (> 29.0).
Perinatal outcomes evaluated were early neonatal death (death of a liveborn infant in the first week of life), fetal death (delivery of a dead baby at or after 20 weeks of gestation), LBW (live baby weighing < 2,500 g at birth), very LBW (live baby weighing < 1,500 g at birth), preterm birth (live baby delivered at < 37 weeks of gestation), very preterm birth (live baby delivered at < 32 weeks of gestation), and SGA (live baby with birth weight below the 10th percentile for the gestational age and gender, according to the Williams et al15 reference curve).
Rates of adverse perinatal outcomes were calculated for each interpregnancy interval. Estimates of crude odds ratios (ORs) with 95% confidence intervals (CI) were computed as measures of association between each interpregnancy interval and adverse perinatal outcome considered. The interval 18–23 months was used as the reference category because this was the interval during which perinatal death was least likely to occur. The influence of potential confounding factors associated with interpregnancy interval and adverse perinatal outcomes was conceptually based on a hierarchical model16 summarized in Figure 1. The variable in the first and more distal level is interpregnancy interval, and in the second level the variables are maternal age and proxies for socioeconomic status (mother’s education and marital status). In the third level there are 4 variables of similar hierarchical importance: parity, outcome of the most recent recognized pregnancy (healthy live baby, LBW, fetal death, or early neonatal death), use of antenatal care (gestational age at first attendance for antenatal care and number of antenatal visits), and maternal nutritional status (prepregnancy body mass index). In the fourth level are history of chronic hypertension, geographic area, hospital type, and year of delivery. In the fifth hierarchical level are listed adverse perinatal outcomes. Adjusted odds ratios were derived through logistic regression models. We simultaneously controlled for all variables from the hierarchical model by using a separate logistic regression model for each of the 7 adverse perinatal outcomes. Variables that were selected by regression procedures were included in the final model. Fetal death and early neonatal death were additionally adjusted for birth weight and gestational age at birth.
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The study was approved by the research ethics committee at Latin American Center for Perinatology and Human Development. All analyses were performed with the SPSS 8.0 program package (SPSS Inc, Chicago, IL).
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RESULTS |
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Among the study population, there were 20,920 fetal deaths (rate 18.6 per 1,000) and 9,843 early neonatal deaths (8.9 per 1,000 live births). Moreover, of the 1,104,510 live birth infants, 7.9% had a low birth weight, 9.3% were born prematurely, and 13.9% were SGA; 17.8% were conceived less than 12 months after the previous birth, and 18.6% were conceived 60 months or longer after the previous birth. The median interpregnancy interval was 27.8 months.
Interpregnancy intervals less than 12 months were more common among women who were younger, had later start of prenatal care, and had lower number of prenatal visits, as well as among women with history of miscarriage or whose previous pregnancy was complicated by low birth weight, fetal death, or early neonatal death (Table 1). Women with intervals longer than 59 months were more likely to be older, with adequate prenatal care, with greater body mass index before pregnancy, and with a previous pregnancy that resulted in a healthy live birth. There were no obvious differences among the interpregnancy interval groups with regard to parity, marital status, mother’s education, and cigarette smoking during pregnancy.
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Table 2 depicts rates of adverse perinatal outcomes according to interpregnancy interval. We found a J-shaped association between the interpregnancy interval and all 7 adverse perinatal outcomes: the rates were highest when the interpregnancy interval was less than 6 months, decreased as the interval increased, and were lowest when the interval was 18–23 months. As the interval increased, rates of most adverse perinatal outcomes increased.
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Adjusted ORs for the association between interpregnancy interval and adverse perinatal outcomes are shown in Table 3. Compared with infants conceived 18–23 months after a previous birth, infants conceived less than 6 months after a birth faced about 50% increase in risk of both early neonatal death and fetal death, 80–100% increased risk for LBW, very LBW, preterm birth, and very preterm birth, and 30% increase in risk of SGA. Moreover, infants conceived 6–11 months after a birth were 15–33% more likely to suffer any of the adverse perinatal outcomes considered. The minimal increase in the risk for adverse perinatal outcomes associated with intervals of 12–17 months (3–8%) was not statistically significant. Compared with results from the multivariable analysis with adjustment for only maternal characteristics, the risk of early neonatal death associated with interpregnancy intervals of less than 6 months (adjusted OR 1.57, 95% CI 1.18–1.98) and 6–11 months (adjusted OR 1.31, 95% CI 1.19–1.43) was only slightly attenuated when adjustments for infant’s birth weight and gestational age were included in the model (adjusted ORs, 95% CIs 1.49, 1.06–1.96, and 1.27, 1.12–1.44, respectively). On the other hand, infants conceived 60 months or more after a birth had about a 20% increased risk of early neonatal death, fetal death, LBW, preterm birth, and SGA, and a 15% increased risk of very LBW and very preterm birth.
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DISCUSSION |
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Results from the present study corroborate the findings from earlier reports that women with short and long interpregnancy intervals are at increased risk of LBW, preterm birth, and SGA. As reported in previous studies, we also found a J-shaped relationship between interpregnancy interval and the 7 adverse perinatal outcomes, with the lowest risks for women with intervals of 18–23 months. Few studies have explored the association between interpregnancy interval and both fetal death and early neonatal death. In a Swedish nationwide study,11 women with short interpregnancy intervals were not at increased risk of stillbirth (defined as fetal death occurring at 28 or more completed weeks of gestation) and early neonatal death, whereas women with interpregnancy intervals longer than 71 months were associated with increased risk of stillbirth and possibly early neonatal death (adjusted ORs, 95% CIs 1.5, 1.1–2.1, and 1.3, 0.9–2.1, respectively). A recent retrospective cohort study from Scotland7 reported that short interpregnancy interval (< 6 months) was an independent risk factor for neonatal death (adjusted OR 3.6, 95% CI 1.2–10.7) but not for stillbirth (defined as fetal death occurring at 24 or more completed weeks of gestation). One study from India9 found an increased risk of perinatal death associated with interpregnancy intervals shorter than 23 months, whereas another from Jamaica10 did not find a relationship between interpregnancy interval and perinatal death. Because the risks of late fetal death and early neonatal death are strongly and inversely related to length of gestation, we must control for the confounding effects of gestation length when evaluating the perinatal risks associated with close interpregnancy intervals.17 None of the above-mentioned studies adjusted for such a confounding factor. After the confounding effects of infant’s birth weight and gestational age at birth were controlled for, our study found that infants conceived less than 12 months after a preceding birth were at increased risk for both fetal death and early neonatal death.
There is controversy in the literature about the factors responsible for higher risk of adverse perinatal outcomes associated with short intervals between pregnancies. Maternal nutritional depletion,17,18 including folate depletion,19 maternal stress produced by the new pregnancy,3 postpartum hormonal imbalance continuing into the new pregnancy,20 and preovulatory aging of the oocyte due to an extended follicular phase of the first ovulatory cycle,21 have generally been put forward as the most plausible explanations for the increased risk of adverse perinatal outcomes among women who space pregnancies closely. Some investigators have attributed the higher risk of poor perinatal outcomes to several factors associated with short intervals, such as low socioeconomic status, adverse outcome of the previous pregnancy, unstable lifestyles, failure to use health care services or inadequate use of such services, unplanned pregnancies, and other behavioral or psychological determinants (Erickson and Bjerkedal 1979).12 Nevertheless, it is unlikely that the associations were entirely due to these factors because our study and other large ones adjusted for the great majority of them. It is unknown why a long interpregnancy interval is associated with adverse perinatal outcomes. Several hypotheses have also been proposed to explain the relationship between long intervals and adverse perinatal outcomes. Zhu et al4 have hypothesized that, after delivery, woman’s physiologic reproductive capacities gradually decline, becoming similar to those of primigravid women. This hypothesis is supported by the observation that perinatal outcomes for infants conceived after a long interpregnancy interval are similar to outcomes of infants born to primigravid women. Another possibility is that unmeasured factors, such as sexually transmitted infections, may cause both delayed fertility and adverse perinatal outcomes.4,9
Some limitations should be considered when the results of this study are interpreted. First, our study is not population-based. Rather, it was based in several different hospitals spread across Latin America. Second, our study is based on a population coming from developing countries, and therefore, caution should be used when generalizing our results to other populations. However, most of the associations identified in the present study have been described in reports from developed countries. Third, we were unable to evaluate other potential confounders for the relation between interpregnancy interval and adverse perinatal outcomes such as race, breastfeeding, and other socioeconomic factors (family income, housing, occupation, and work status) because these data were not available from the database. Fourth, inaccuracy of gestational age estimated from the date of last menstrual period is a well-recognized problem in epidemiological research addressing interpregnancy intervals. However, when we replicated the entire analyses using gestational age estimated from physical and neurological assessments of the newborn instead of that based on last menstrual period, the results were essentially unchanged (data not shown). Fifth, Uruguay and Argentina contributed almost half of the births registered in the database, so our results might not be generalizable to the entire Latin American population. Finally, even although we adjusted for several factors, there is still potential for confounding and bias by other unknown factors.
In the last decade, a great deal of attention has been focused on whether birth spacing can play a significant role in the improvement of infant health. The hypothetical impact of pregnancy spacing as an intervention to prevent perinatal deaths can be calculated by using the concept of population attributable-risk-percent, which expresses the proportion of perinatal deaths in the study population that are attributable to both short and long interpregnancy intervals and thus could be eliminated if such exposure were eliminated. If Latin American families choose to delay a new pregnancy for 12–59 months after the preceding birth, it is estimated that perinatal mortality would drop 12.1%; if families choose to delay the new pregnancy for 18–59 months, the perinatal mortality would drop 15.0% (Table 4). According to the Pan American Health Organization,22 the total number of perinatal deaths in Latin America during 2002 was 390,493, of which 57% were fetal deaths and 43% were early neonatal deaths. Thus, if interpregnancy intervals shorter than 18 months and longer than 59 months were eliminated in Latin America, the total number of perinatal deaths would hypothetically fall by about 60,000 annually.
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Counseling women about the risk of both short and long interpregnancy intervals associated with perinatal morbidity and mortality is not currently included in most family planning or health programs, and few developing countries have policies that explicitly recognize birth spacing as a perinatal health intervention. Technical agencies, donors, foundations, and nongovernmental organizations should bring the evidence on interpregnancy intervals and adverse perinatal outcomes to the attention of developing country policy makers and provide assistance to strengthen birth spacing education, counseling, and services as integral elements of perinatal mortality reduction strategies.
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Footnotes |
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doi:10.1097/01.AOG.0000171118.79529.a3
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REFERENCES |
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2. Kallan JE. Reexamination of interpregnancy intervals and subsequent birth outcomes: evidence from U.S. Linked Birth/Infant Death records. Soc Biol 1997;44:205–12.[Medline]
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