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      Re-evaluation of link between interpregnancy interval and adverse birth outcomes: retrospective cohort study matching two intervals per mother

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          Abstract

          Objective To re-evaluate the causal effect of interpregnancy interval on adverse birth outcomes, on the basis that previous studies relying on between mother comparisons may have inadequately adjusted for confounding by maternal risk factors.

          Design Retrospective cohort study using conditional logistic regression (matching two intervals per mother so each mother acts as her own control) to model the incidence of adverse birth outcomes as a function of interpregnancy interval; additional unconditional logistic regression with adjustment for confounders enabled comparison with the unmatched design of previous studies.

          Setting Perth, Western Australia, 1980-2010.

          Participants 40 441 mothers who each delivered three liveborn singleton neonates.

          Main outcome measures Preterm birth (<37 weeks), small for gestational age birth (<10th centile of birth weight by sex and gestational age), and low birth weight (<2500 g).

          Results Within mother analysis of interpregnancy intervals indicated a much weaker effect of short intervals on the odds of preterm birth and low birth weight compared with estimates generated using a traditional between mother analysis. The traditional unmatched design estimated an adjusted odds ratio for an interpregnancy interval of 0-5 months (relative to the reference category of 18-23 months) of 1.41 (95% confidence interval 1.31 to 1.51) for preterm birth, 1.26 (1.15 to 1.37) for low birth weight, and 0.98 (0.92 to 1.06) for small for gestational age birth. In comparison, the matched design showed a much weaker effect of short interpregnancy interval on preterm birth (odds ratio 1.07, 0.86 to 1.34) and low birth weight (1.03, 0.79 to 1.34), and the effect for small for gestational age birth remained small (1.08, 0.87 to 1.34). Both the unmatched and matched models estimated a high odds of small for gestational age birth and low birth weight for long interpregnancy intervals (longer than 59 months), but the estimated effect of long interpregnancy intervals on the odds of preterm birth was much weaker in the matched model than in the unmatched model.

          Conclusion This study questions the causal effect of short interpregnancy intervals on adverse birth outcomes and points to the possibility of unmeasured or inadequately specified maternal factors in previous studies.

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          Most cited references30

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          Effects of birth spacing on maternal, perinatal, infant, and child health: a systematic review of causal mechanisms.

          This systematic review of 58 observational studies identified hypothetical causal mechanisms explaining the effects of short and long intervals between pregnancies on maternal, perinatal, infant, and child health, and critically examined the scientific evidence for each causal mechanism hypothesized. The following hypothetical causal mechanisms for explaining the association between short intervals and adverse outcomes were identified: maternal nutritional depletion, folate depletion, cervical insufficiency, vertical transmission of infections, suboptimal lactation related to breastfeeding-pregnancy overlap, sibling competition, transmission of infectious diseases among siblings, incomplete healing of uterine scar from previous cesarean delivery, and abnormal remodeling of endometrial blood vessels. Women's physiological regression is the only hypothetical causal mechanism that has been proposed to explain the association between long intervals and adverse outcomes. We found growing evidence supporting most of these hypotheses.
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            Effect of the interval between pregnancies on perinatal outcomes.

            A short interval between pregnancies has been associated with adverse perinatal outcomes. Whether that association is due to confounding by other risk factors, such as maternal age, socioeconomic status, and reproductive history, is unknown. We evaluated the interpregnancy interval in relation to low birth weight, preterm birth, and small size for gestational age by analyzing data from the birth certificates of 173,205 singleton infants born alive to multiparous mothers in Utah from 1989 to 1996. Infants conceived 18 to 23 months after a previous live birth had the lowest risks of adverse perinatal outcomes; shorter and longer interpregnancy intervals were associated with higher risks. These associations persisted when the data were stratified according to and controlled for 16 biologic, sociodemographic, and behavioral risk factors. As compared with infants conceived 18 to 23 months after a live birth, infants conceived less than 6 months after a live birth had odds ratios of 1.4 (95 percent confidence interval, 1.3 to 1.6) for low birth weight, 1.4 (95 percent confidence interval, 1.3 to 1.5) for preterm birth, and 1.3 (95 percent confidence interval, 1.2 to 1.4) for small size for gestational age; infants conceived 120 months or more after a live birth had odds ratios of 2.0 (95 percent confidence interval, 1.7 to 2.4);1.5 (95 percent confidence interval, 1.3 to 1.7), and 1.8 (95 percent confidence interval, 1.6 to 2.0) for these three adverse outcomes, respectively, when we controlled for all 16 risk factors with logistic regression. The optimal interpregnancy interval for preventing adverse perinatal outcomes is 18 to 23 months.
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              Preterm birth and attention-deficit/hyperactivity disorder in schoolchildren.

              Previous studies have demonstrated an increased risk for attention-deficit/hyperactivity disorder (ADHD) in follow-up studies of preterm survivors from NICUs. In this study we analyzed the effect of moderate as well as extreme preterm birth on the risk for ADHD in school age, taking into account genetic, perinatal, and socioeconomic confounders. Register study in a Swedish national cohort of 1 180 616 children born between 1987 and 2000, followed up for ADHD medication in 2006 at the age of 6 to 19 years. Logistic regression was used to test hypotheses. A within-mother-between-pregnancy design was used to estimate the importance of genetic confounding in a subpopulation of offspring (N = 34 334) of mothers who had given birth to preterm (≤34 weeks) as well as term infants. There was a stepwise increase in odds ratios for ADHD medication with increasing degree of immaturity at birth; from 2.1 (1.4-2.7) for 23 to 28 weeks' gestation, to 1.6 (1.4-1.7) for 29 to 32 weeks', 1.4 (1.2-1.7) for 33 to 34 weeks', 1.3 (1.1-1.4) for 35 to 36 weeks', and 1.1 (1.1-1.2) for 37 to 38 weeks' gestation compared with infants born at 39 to 41 weeks' gestation in the fully adjusted model. The odds ratios for the within-mother-between-pregnancy analysis were very similar. Low maternal education increased the effect of moderate, but not extreme, preterm birth on the risk for ADHD. Preterm and early term birth increases the risk of ADHD by degree of immaturity. This main effect is not explained by genetic, perinatal, or socioeconomic confounding, but socioeconomic context modifies the risk of ADHD in moderately preterm births.
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                Author and article information

                Contributors
                Role: scientist
                Role: postdoctoral associate
                Role: associate professor
                Role: professor
                Role: professor
                Journal
                BMJ
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2014
                23 July 2014
                : 349
                : g4333
                Affiliations
                [1 ]Telethon Kids Institute, University of Western Australia, PO Box 855, West Perth, WA 6872, Australia
                [2 ]Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Yale University, New Haven, CT 06510, USA
                Author notes
                Article
                bals015597
                10.1136/bmj.g4333
                4137882
                25056260
                29d45711-e166-4b5c-a767-957f21d0c5b3
                © Ball et al 2014

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

                History
                : 22 June 2014
                Categories
                Research

                Medicine
                Medicine

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