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OBJECTIVE: To examine the association between inter- RESULTS: Analyses using the traditional unmatched
pregnancy interval and maternal–neonate health when design showed significantly increased risks associated
matching women to their successive pregnancies to with short interpregnancy intervals (eg, there were 232
control for differences in maternal risk factors and com- preterm births [12.8%] in 0–5 months compared with 501
pare these results with traditional unmatched designs. [8.2%] in the 18–23 months reference group; adjusted
METHODS: We conducted a retrospective cohort study odds ratio [OR] for preterm birth 1.53, 95% confidence
of 38,178 women with three or more deliveries (two or interval [CI] 1.35–1.73). However, these risks were elim-
greater interpregnancy intervals) between 2000 and 2015 inated in within-woman matched analyses (adjusted OR
in British Columbia, Canada. We examined interpreg- for preterm birth 0.85, 95% CI 0.71–1.02). Matched re-
nancy interval (0–5, 6–11, 12–17, 18–23 [reference], sults indicated that short interpregnancy intervals were
24–59, and 60 months or greater) in relation to neonatal significantly associated with increased risk of gestational
outcomes (preterm birth [less than 37 weeks of gesta- diabetes (adjusted OR 1.35, 95% CI 1.02–1.80 for 0–5
tion], small-for-gestational-age birth [less than the 10th months) and beginning the subsequent pregnancy obese
centile], use of neonatal intensive care, low birth weight (adjusted OR 1.61, 95% CI 1.05–2.45 for 0–5 months and
[less than 2,500 g]) and maternal outcomes (gestational adjusted OR 1.43, 95% CI 1.10–1.87 for 6–11 months).
diabetes, beginning the subsequent pregnancy obese
CONCLUSION: Previously reported associations between
[body mass index 30 or greater], and preeclampsia–
short interpregnancy intervals and adverse neonatal out-
eclampsia). We used conditional logistic regression to
comes may not be causal. However, short interpregnancy
compare interpregnancy intervals within the same
interval is associated with increased risk of gestational
mother and unconditional (unmatched) logistic regres-
diabetes and beginning a subsequent pregnancy obese.
sion to enable comparison with prior research.
(Obstet Gynecol 2017;129:408–15)
DOI: 10.1097/AOG.0000000000001891
See related editorial on page 405.
From the Perinatal Services BC, and the Department of Obstetrics & Gynaecology,
University of British Columbia, Vancouver, British Columbia, Canada.
T he World Health Organization currently recom-
mends that the interval between a woman’s pre-
vious delivery and her subsequent conception (the
Gillian E. Hanley is funded by the Canadian Cancer Society Research Institute interpregnancy interval) should be a minimum of 2
and a New Investigator Award from the Canadian Institutes of Health Research. years.1 This recommendation is based on studies indi-
Jennifer A. Hutcheon holds New Investigator Awards from the Canadian Institutes
of Health Research and the Michael Smith Foundation for Health Research. cating that both short (less than 18 months) and long
The funders played no role in this study. (greater than 59 months) interpregnancy intervals are
Each author has indicated that he or she has met the journal’s requirements for
associated with increased risks of preterm birth, low
authorship. birth weight, small-for-gestational-age birth, and neo-
Corresponding author: Gillian E. Hanley, PhD, Diamond Health Care Centre, natal intensive care unit admission.2–6 Longer inter-
6207A 2775 Laurel Street, Vancouver, British Columbia V5Z 1M9, Canada; pregnancy intervals have also been associated with
email: Gillian.hanley@phsa.ca.
increased risk of preeclampsia.7
Financial Disclosure
The authors did not report any potential conflicts of interest.
However, shorter interpregnancy intervals may
simply reflect differences in socioeconomic status,
© 2017 by The American College of Obstetricians and Gynecologists. Published
by Wolters Kluwer Health, Inc. All rights reserved. lifestyle, and access to contraception—all conditions
ISSN: 0029-7844/17 that also tend to correlate with differences in
VOL. 129, NO. 3, MARCH 2017 Hanley et al Interpregnancy Interval and Adverse Outcomes 409
Table 1. Characteristics of the Study Population by Interpregnancy Interval for Both Second and Third
Births
410 Hanley et al Interpregnancy Interval and Adverse Outcomes OBSTETRICS & GYNECOLOGY
Preterm birth
2nd birth 3,422 (9.0) 232 (12.8) 714 (8.7) 707 (7.6) 501 (8.1) 1,024 (9.7) 244 (12.1)
3rd birth 3,665 (9.6) 227 (15.9) 650 (10.2) 607 (8.2) 505 (8.6) 1,305 (9.3) 371 (12.0)
SGA birth
2nd birth 1,946 (5.1) 108 (6.0) 411 (5.0) 420 (4.5) 291 (4.7) 593 (5.7) 123 (6.1)
3rd birth 1,659 (4.4) 82 (5.8) 258 (4.1) 287 (3.9) 237 (4.0) 624 (4.5) 171 (5.5)
Neonatal intensive
care use (n520,664)
2nd birth 1,109 (5.4) 51 (6.7) 212 (5.4) 230 (4.8) 142 (4.5) 330 (5.4) 144 (7.6)
3rd birth 1,701 (5.3) 72 (7.1) 272 (5.8) 261 (4.6) 241 (5.0) 650 (5.1) 205 (6.6)
Low birth weight
2nd birth 1,886 (4.9) 143 (7.9) 346 (4.2) 369 (4.0) 304 (4.9) 589 (5.6) 135 (6.7)
3rd birth 1,645 (4.3) 107 (7.5) 293 (4.6) 267 (3.6) 197 (3.4) 604 (4.3) 177 (5.7)
Gestational diabetes
2nd birth 2,202 (5.8) 119 (6.6) 399 (4.8) 452 (4.8) 338 (5.5) 718 (6.8) 176 (8.7)
3rd birth 3,319 (8.7) 128 (9.0) 426 (6.7) 565 (7.6) 442 (7.5) 1,345 (9.6) 413 (13.3)
Entering pregnancy
obese (n518,407)
2nd birth 3,501 (14.2) 184 (17.4) 717 (13.5) 720 (11.7) 529 (12.8) 1,104 (16.3) 247 (18.8)
3rd birth 4,256 (17.0) 173 (21.6) 701 (18.1) 721 (14.9) 607 (15.3) 1,613 (17.1) 441 (20.5)
Preeclampsia–eclampsia
2nd birth 796 (2.1) 28 (1.5) 132 (1.6) 161 (1.7) 118 (1.9) 284 (2.7) 73 (3.6)
3rd birth 1,093 (2.9) 30 (2.1) 127 (2.0) 169 (2.3) 187 (3.2) 441 (3.2) 139 (4.5)
SGA, small for gestational age.
Data are n (%).
Rates of all adverse neonatal outcomes were (adjusted OR 1.53, 95% CI 1.35–1.73), to have a neo-
higher among women with the shortest and longest nate born SGA (adjusted OR 1.26, 95% CI 1.06–1.50),
interpregnancy intervals than those in the middle and to have a low-birth-weight neonate (adjusted OR
categories (Table 2). Gestational diabetes and pre- 1.64, 95% CI 1.39–1.94). Longer interpregnancy inter-
pregnancy obesity were more common among val was also significantly associated with increased risk
women with both shorter and longer intervals, of preterm birth, SGA birth, a low-birth-weight neo-
whereas preeclampsia–eclampsia was more common nate, and neonatal intensive care use with an adjusted
among women with the longest intervals. Given that OR of 1.44 (95% CI 1.23–1.67) for an interpregnancy
conditional logistic regression models primarily take intervals of 60 months or greater. Increased risks were
advantage of discordance within the same mother, we reported for women with interpregnancy intervals of
present tables outlining the discordance between in- 24–59 months for preterm birth, SGA birth, and low
terpregnancy interval categories and the outcomes of birth weight (adjusted OR 1.11, 95% CI 1.02–1.20;
interest across the two pregnancies in the same adjusted OR 1.13, 95% CI 1.02–1.26; and adjusted
mother in Appendices 1 and 2, available online at OR 1.14, 95% CI 1.03–1.27, respectively).
http://links.lww.com/AOG/A921. In the matched design of conditional logistic
We report in detail on the between-women regression, interpregnancy intervals shorter than the
analyses to facilitate comparison with previous research reference category were no longer associated with
that has used this statistical approach and to highlight significantly increased risk of any of the adverse
how the associations change when using a within- neonatal outcomes (Table 4). Rather, short interpreg-
woman approach. In unconditional (unmatched) logis- nancy intervals appeared protective for low birth
tic regression analyses, short interpregnancy interval weight for women in the two shortest interpregnancy
was associated with increased risk of preterm birth, interval categories (adjusted OR 0.57, 95% CI 0.46–
SGA birth, and low birth weight (Table 3). Women 0.72 for interpregnancy interval of 0–5 months and
with an interpregnancy interval of 0–5 months were adjusted OR 0.79, 95% CI 0.66–0.95 for women with
significantly more likely to have neonates born preterm an interpregnancy interval of 6–11 months). Long
VOL. 129, NO. 3, MARCH 2017 Hanley et al Interpregnancy Interval and Adverse Outcomes 411
interpregnancy intervals of 60 months or greater re- were significantly associated with a short interpreg-
mained significantly associated with increased risk of nancy interval. The highest adjusted OR was for
neonatal intensive care use (adjusted OR 1.39, 95% CI entering a pregnancy obese among women with an
1.02–1.90) and low birth weight (adjusted OR 1.31, interpregnancy interval of 0–5 months (adjusted OR
95% CI 1.02–1.68). 1.61, 95% CI 1.05–2.45). Entering a pregnancy obese
The unmatched analyses (Table 4) indicate that was also significantly associated with an interpreg-
women were at increased risk of gestational diabetes nancy interval of 6–11 months (adjusted OR 1.43,
and prepregnancy obesity if their interpregnancy inter- 95% CI 1.10–1.87). The risk of gestational diabetes
vals were 0–5 months (adjusted OR 1.47, 95% CI 1.26– was also significantly increased among women with
1.72 and adjusted OR 1.29, 95% CI 1.06–1.50, respec- an interpregnancy interval of 0–5 months (adjusted
tively) or greater than 24 months. Only women with OR 1.35, 95% CI 1.02–1.80). Women with an inter-
interpregnancy intervals 60 months or greater were at pregnancy interval of 12–18 months had significantly
increased risk of preeclampsia–eclampsia (adjusted OR lower odds of preeclampsia–eclampsia (adjusted OR
1.31, 95% CI 1.09–1.58). Women with interpregnancy 0.71, 95% CI 0.54–0.94).
intervals less than 18–23 months all appeared to be at Sensitivity analyses conducted using unconditional
slightly lower risk of preeclampsia–eclampsia. logistic regression models among all women who had
In conditional logistic regression models, only at least two births are reported in Appendices 3 and 4,
gestational diabetes and entering the pregnancy obese available online at http://links.lww.com/AOG/A921.
412 Hanley et al Interpregnancy Interval and Adverse Outcomes OBSTETRICS & GYNECOLOGY
These results are very similar to those reported for the socioeconomic status, lifestyle factors, and access to
unmatched (between-women) analyses in our cohort of care) are important confounders in the relationship
women with three or more births. The ORs suggest between interpregnancy interval and the adverse
a strong effect of short and long interpregnancy interval neonatal outcomes of preterm birth, SGA, low birth
on preterm birth, neonatal intensive care use, and low weight, and use of neonatal intensive care.
birth weight (Appendix 3, http://links.lww.com/AOG/ With respect to maternal outcomes, the findings
A921). With respect to maternal adverse outcomes, were more nuanced. In the unconditional (between-
Appendix 4, available online at (http://links.lww. women) models, women with short and long inter-
com/AOG/A921), indicates that short interpregnancy pregnancy intervals were more likely to have
intervals increase risk of gestational diabetes and enter- gestational diabetes and to enter a pregnancy obese.
ing a pregnancy obese. Long interpregnancy intervals Women with long interpregnancy intervals were
were associated with an increased risk of gestational more likely to have preeclampsia–eclampsia. How-
diabetes, entering a pregnancy obese, and ever, in the matched analysis, the relationships that
preeclampsia–eclampsia. remained statistically significant were between short
interpregnancy interval and gestational diabetes or
DISCUSSION entering the pregnancy obese. Given that short in-
Our study found that the majority of associations terpregnancy intervals provide less time to lose
between interpregnancy interval and adverse neonatal weight from a previous pregnancy, this may increase
outcomes (preterm birth, SGA birth, and low birth the likelihood of beginning the next pregnancy obese
weight) observed using the conventional between- and, given the relationship between prepregnancy
women analysis was no longer significant when BMI and gestational diabetes,13 short intervals then
women were used as their own controls. This suggests also increase the likelihood of developing gestational
that factors that remain constant or relatively stable diabetes. Previous work has reported that weight
for a given woman over successive pregnancies (eg, retention between first and second pregnancies is
VOL. 129, NO. 3, MARCH 2017 Hanley et al Interpregnancy Interval and Adverse Outcomes 413
414 Hanley et al Interpregnancy Interval and Adverse Outcomes OBSTETRICS & GYNECOLOGY
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