From the Latin American Centre for Perinatology and Human Development (CLAP), Division of Health Promotion and Protection, Pan American Health Organisation, World Health Organisation, Montevideo, Uruguay

Address for correspondence and reprint requests:

Dr Agustin Conde-Agudelo
Calle 58 # 26-60
Palmira-Valle
Colombia
South America

e-mail: condeagu@uniweb.net.co
 

"What this paper adds" box

1. What is already known on this subject?

perinatal outcomes. On the other hand, only four studies have addressed the impact of

interpregnancy interval on maternal morbidity and mortality giving conflicting results.

1. What does this study add?

with an increased risk of adverse maternal outcomes.

Abstract

Objective: To study the impact of interpregnancy interval on maternal morbidity and
mortality.

Design: Retrospective cross-sectional study from the Perinatal Information System
database of the Latin American Centre for Perinatology and Human Development, Montevideo,
Uruguay.

Setting: Latin America and the Caribbean, 1985-1997.

Participants: 456,889 parous women delivering singleton infants.

Main outcome measures: Crude and adjusted relative risks (RR) of the effects of
short and long interpregnancy intervals on maternal death, preeclampsia, eclampsia,
gestational diabetes mellitus, third trimester bleeding, premature rupture of membranes,
postpartum haemorrhage, puerperal endometritis, and anaemia.

Results: After controlling for major confounding factors, women with interpregnancy
intervals of 5 months or less compared with those conceiving at 18 to 23 months after a
previous birth had higher risks for maternal death (relative risk, 2.54 ; 95% confidence
interval, 1.22 to 5.38), third trimester bleeding (relative risk, 1.73 ; 95% confidence interval,
1.42 to 2.24), premature rupture of membranes (relative risk, 1.72 ; 95% confidence interval,
1.53 to 1.93), puerperal endometritis (relative risk, 1.33 ; 95% confidence interval, 1.22 to
1.45), and anaemia (relative risk, 1.30 ; 95% confidence interval, 1.18 to 1.43). Women
conceiving after more than 59 months had significant increase risks of preeclampsia (relative
risk, 1.83 ; 95% confidence interval, 1.72 to 1.94), and eclampsia (relative risk, 1.80 ; 95%
confidence interval, 1.38 to 2.32).

Conclusions: Interpregnancy intervals shorter than 6 months and longer than 59 months
are associated with an increased risk of adverse maternal outcomes.

Introduction

Objects and methods

The Perinatal Information System (SIP) database in Montevideo, Uruguay was devised by the
Latin American Centre for Perinatology and Human Development (CLAP) in 1983.¹⁰ Currently,
this database is used for over 0.5 million births each year. From 1985 through 1997, our
database have recorded pregnancies of women who were themselves born in Uruguay,
Argentina, Peru, Colombia, Honduras, Paraguay, El Salvador, Chile, Bolivia, Costa Rica, Panama,
Dominican Republic, Nicaragua, Brazil, Ecuador, Mexico, Bahamas, and Venezuela.
Only parous women delivering singleton infants and whose previous pregnancy ended in
livebirth or stillbirth of at least 20 weeks' gestation were included in the study. A completed
description of the database has been published elsewhere.^11,12 From the first antenatal visit
until discharge of both mother and neonate, the attendant physicians or nurses collect data in
the perinatal clinical record in check-box format which includes demographic information,
reproductive history, maternal characteristics, prenatal care, labour management, maternal
complications during pregnancy, delivery, and the puerperium, and neonatal outcomes. Then,
data are entered in on site computer and quality control of them is done. Later, they are sent
to the CLAP where a further data entry, quality control check, and validation is performed.
Maternal age was defined as completed years at time of delivery. Mother's education was
categorised into none, elementary, secondary, and university. Marital status was
dichotomised between those who did and did not live with infant's father. Maternal height
and prepregnancy weight were recorded at the woman's first antenatal visit in centimetres
and kilograms, respectively. The body-mass index, defined as prepregnancy weight in
kilograms divided by height in meters squared, was categorised as follows: underweight (body-
mass index less than 19.8); normal weight (19.8 through 26.0); overweight (26.1 through 29.0);
and obese (greater than 29.0).¹³ Information on cigarette smoking was also recorded at the
first antenatal care visit and categorised into smoker and non-smoker.
Gestational age was estimated from the date of last menstrual period, possibly amended by
means of ultrasonography. 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.
Intervals were computed in weeks and then converted to months. Interpregnancy intervals
were categorised in months as follows: 5 or less, 6 to 11, 12 to 17, 18 to 23, 24 to 59, and 60
or more.
Adverse maternal outcomes were classified according to the English version of the
International Classification of Diseases, tenth revision (ICD-10).¹⁴ Preeclampsia and
eclampsia were coded as ICD-10 codes O14 and O15, respectively. Third trimester bleeding
included placenta previa with haemorrhage (ICD-10 code O44.1) and abruptio placenta (ICD-10
code O45). Anaemia, premature rupture of membranes, gestational diabetes mellitus,
postpartum haemorrhage, and puerperal endometritis were coded as ICD-10 codes O99.0,
O42, O24.4, O72 and O85, respectively.
Maternal death was defined as the death of a woman while pregnant or within 42 days after
delivery, from any cause related to or aggravated by the pregnancy or its management, but
not from accidental or incidental causes.
Adverse maternal outcomes rates were calculated for each interpregnancy interval.
Estimates of crude relative risk with 95% confidence interval were computed as measures of
association between each interpregnancy interval and adverse maternal outcomes considered.
The interval 18 to 23 months was used as the referent category because this was the interval
during which was least likely to occur a maternal death. Adjusted odds ratios were derived
through logistic regression models as estimates of adjusted relative risks. Multiple logistic-
regression analysis was used to evaluate the association between interpregnancy interval and
adverse maternal outcomes. The estimates were adjusted for 16 major confounding factors.
All analyses were done using the SPSS 8.0 programme package (SPSS Inc., Chicago, IL)

Results

A total of 520,689 parous women delivering singleton infants between 1985 and 1997 were
recorded at our database. The final study population included 456,889 women whose records
contained complete data on interpregnancy interval and adverse maternal outcomes.
The median interpregnancy interval was 27 months. Short (shorter than 6 months) and long
(longer than 59 months) intervals between pregnancies were observed for 2.8% and 19.5% of
women, respectively. Almost a third of the women had an interpregnancy interval of less than
18 months.
The characteristics of the mothers at the index pregnancy according to interpregnancy
interval are shown in table 1. Younger maternal age, histories of abortion, stillbirth, and early
neonatal death, low rate of previous caesarean delivery, late prenatal care onset, low number
of prenatal visits, and lower prepregnancy body-mass index were associated with short
intervals between pregnancies. Conversely, women with a long interpregnancy interval were
more likely to be older, with greater prepregnancy body-mass index, and with history of chronic hypertension. Prenatal care onset and number of prenatal visits were correlated with
interpregnancy interval. The shorter the interval, the later care started and the lower
number of prenatal visits was. There were no obvious differences among the interpregnancy
interval groups with regard to number of previous deliveries, mother's education, marital
status, and cigarette smoking during pregnancy.
Women with short interpregnancy intervals had the highest rates of third trimester
bleeding, premature rupture of membranes, puerperal endometritis, anaemia, and maternal
death (table 2). There were 220 maternal deaths in the study population The rates of
preeclampsia, eclampsia, and gestational diabetes mellitus were highest among women with
intervals longer than 59 months. A slight increase in the rates of third trimester bleeding and
maternal death was also seen in this interpregnancy interval group.
The results of the multiple logistic regression analyses of the relation of interpregnancy
intervals to adverse maternal outcomes are shown in table 3. As compared with mothers
with interpregnancy intervals of 18 to 23 months, mothers with intervals shorter than 6
months had an approximately 70% increased risk of third trimester bleeding and premature
rupture of membranes and a 30% increased risk of anaemia and puerperal endometritis.
Moreover, a short interval between pregnancies was associated with a significantly greater
risk of maternal death (adjusted relative risk, 2.54 ; 95% confidence interval, 1.22 to 5.38).
When interpregnancy intervals were dichotomised to shorter than 6 months versus 6 months
or more, women with short intervals between pregnancies were significantly more likely to die
than women conceiving after 5 months (adjusted relative risk, 2.04 ; 95% confidence interval,
1.13 to 3.78). On the other hand, women with interpregnancy intervals of 60 or more months
were 1.8 times more likely than women with intervals of 18 to 23 months to develop eclampsia
and preeclampsia. After adjustment for confounders, the effect of long interpregnancy
intervals on gestational diabetes mellitus disappeared. Thus, the increased rate of gestational
diabetes mellitus associated with intervals greater than 59 months could be mediated through
older maternal age and higher prepregnancy body-mass index. No relation was found between
interval between pregnancies and the risk of postpartum haemorrhage.

Discussion

Our results indicate that women with interpregnancy intervals shorter than 6 months
are at increased risk of maternal death, third trimester bleeding, premature rupture of
membranes, puerperal endometritis, and anaemia. Likewise, intervals longer than 59 months
were associated with higher risks of preeclampsia and eclampsia. The findings of this
investigation are supported by its large sample size which confers the sufficient power to
evaluate the relationship between interpregnancy interval and adverse maternal outcomes and
by its ability to control for the influence of many possible confounding factors.
Few studies have examined the effect of interpregnancy interval on maternal outcomes. An
earlier study⁶ from the United States did not find effect of interpregnancy interval on
maternal anaemia, puerperal fever, postpartum haemorrhage, and maternal mortality, although
the number of maternal deaths (N=16) was small. An increased risk of maternal mortality
among Hindu women with intervals between pregnancies of less than 24 months (relative risk,
2.5 ; 95 percent confidence interval, 1.5 to 4.3) has been reported in a case-control study⁷ of
252 maternal deaths matched to 252 survivors by age, parity, and booking status. However, a
strong association between maternal death and both age and parity was also reported
suggesting mistaken analyses. A recent nested case-control study⁹ from Bangladesh evaluating
risk factors for 390 maternal deaths found that short interpregnancy intervals did not
increase the risk of maternal death, after adjustment for maternal age, area of residence,
maternal education, religion, and year of birth. Nonetheless, women dying within 90 days
after termination of pregnancy and with external causes of death such as induced abortion or
suicide were included in the study, which may have hidden the existence of an association. In
ddition, gestational age was unknown for 44% of cases, thereby biasing calculation of
interpregnancy interval.
our finding of higher rates of anaemia among women with short interpregnancy intervals
agrees with findings of previous studies.^8,15 With regard to third trimester bleeding, a recent
population-based study¹⁶ found a greater risk of uteroplacental bleeding disorders among
young multiparous women. The authors attributed it to a higher frequency of short interval
between pregnancies in these women. Our results confirmed such association.
The reasons for the association between a short interval between pregnancies and adverse
maternal outcomes are unclear. Most of our findings might be explained by the maternal
depletion hypothesis which suggests that short intervals between pregnancies do not allow to
he mother to recover from the physiologic stresses imposed by the previous pregnancy.^17-19
This results in depletion of maternal nutrient stores and anaemia which have been found to
play a role in the pathogenesis of premature rupture of membranes and puerperal
endometritis.^20,21With regard to the increased risk of third trimester bleeding, we
postulate that a short interval between pregnancies might interferes in normal processes of
endometrial blood vessels remodelling after delivery with subsequent uteroplacental
underperfusion,²² thereby increasing the likelihood for placental abruption and placenta
previa. All the previously mentioned conditions may contribute to the increased risk of
maternal death among women with short interpregnancy intervals found in our study.
Results from our study corroborate the finding from an earlier report showing that women
with long intervals between pregnancies are at increased risk of preeclampsia. Eastman⁶
reported that, compared with mothers with interpregnancy intervals of 12 to 23 months,
others with intervals longer than 48 months had a significant greater risk of toxaemia
(relative risk, 1.3 ; 95% confidence interval, 1.1 to 1.5). Interestingly, the rate of
preeclampsia among nulliparous women recorded in our database (N= 325,146) was very similar
to that of parous women conceiving 5 or more years after a previous birth (6.5% versus 6.6%,
respectively). It would seem that parous women with long interpregnancy intervals behave as
nulliparous women with regard to the risk of preeclampsia as if the "protective" effect for
preeclampsia acquired by a woman through a previous birth is lost after a long interval.
However, certain variables that may confound or modify the relations between interpregnancy
interval and preeclampsia, such as change in paternity,²³ were not available to us for analysis.
Regardless of what causes this association, pregnancies following long interpregnancy intervals
are at higher risk of preeclampsia and eclampsia and need to be carefully monitored during
antenatal care, several limitations and potential biases of this study must be considered.
Firstly, our study is not population- based. Rather, it is based at several different hospitals spread across Latin American and the Caribbean. However, it is unlikely that the effect of interpregnancy
interval on adverse maternal outcomes had been confounded by this matter since the results
were similar among countries considered in our study.
Secondly, the accuracy of specific diagnoses registered in this large database has not been extensively made and only local medical record verifications have been performed.²⁴ As such, SIP data are limited to a certain extent. Thirdly, despite we adjusted for several variables, there is still potential for
confounding by other unknown factors. Fourthly, inaccuracy of gestational age estimated
from the date of last menstrual period is a well recognised problem in epidemiological
research addressing interpregnancy intervals. However, when we replicated the entire
analyses using gestational age estimated from physical and neurologic assessments of the
new-born instead of that based on last menstrual period, the results were essentially
unchanged.
Finally, it should be emphasised that our study is based on a population coming
from developing countries and its findings may not be generalised to other populations.
Based on the findings of the present study, we underscore the importance of birth spacing
using the available family planning methods, particularly after a birth, to promote safe
motherhood and achieve better pregnancy outcomes. In addition, women should be advised of
the potential harms to them and their infants of short and long intervals between pregnancies.

Acknowledgments

The authors acknowledge Mr Roberto Porro and Dr Felipe Santana for the preparation of the
database. We would also to acknowledge health workers and health related workers in many
settings of the Latin American and Caribbean region for their efforts to collect and send
Perinatal Information System (SIP) data to the Latin American Centre for Perinatology and
Human Development (CLAP).

Contributors

ACA originated the study, designed the study, analysed the data, and was
mainly responsible for writing the paper; he will act as guarantor of the paper. JMB
participated in the discussion of the study hypothesis and study design, contributed to the
analyses and helped write the paper.

Conflict of interest: None

References

1. Rawlings JS, Rawlings VB, Read JA. Prevalence of low birth weight and preterm delivery

in relation to the interval between pregnancies among white and black women. N Engl J Med

1995;332:69-74.

2. Klerman LV, Cliver SP, Goldenberg RL. The impact of short interpregnancy intervals on

pregnancy outcomes in a low-income population. Am J Public Health 1998;88:1182-1185.

3. Khoshnood B, Lee KS, Wall S, Hsieh HL, Mittendorf R. Short interpregnancy intervals and

the risk of adverse birth outcomes among five racial/ethnic groups in the United States. Am

J Epidemiol 1998;148:798-805.

4. Zhu B-P, Rolfs RT, Nangle BE, Horan JM. Effect of the interval between pregnancies on

perinatal outcomes. N Engl J Med 1999;340:589-594.

5. Shults RA, Arndt V, Olshan AF, Martin CF, Royce RA. Effects of short interpregnancy

intervals on small-for.gestational age and preterm births. Epidemiology 1999;10:250-254.

6. Eastman NJ. The effect of the interval between births on maternal and fetal outlook.

Am J Obstet Gynecol 1944;47:445-466.

7. Anandalakshmy PN, Talwar PB, Buckshee K, Hingorani V. Demographic, socio-economic

and medical factors affecting maternal mortality--An Indian experience. J Fam Welf

1993;39:1-4.

8. Lazoviv N, Pocekovac P. The importance of time intervals between childbirth and anemia

in pregnancy. (In Serbo-Croatian). Srp Arh Celok Lek 1996;124:307-310.

9. Ronsmans C, Campbell O. Short birth intervals don't kill women: evidence from Matlab,

Bangladesh. Stud Fam Plann 1998;29:282-290.

10. Schwarcz R, Diaz AG, Fescina R, Diaz JL, Martell M, Simini F. The perinatal information

System I: The simplified perinatal clinical record. J Perinat Med 1987;15(Suppl 1):9.

11. Diaz-Rosello JL. Health services research, outcomes, and perinatal information systems.

Curr Opin Pediatr 1998;10:117-122.

12. Simini F. Perinatal information system (SIP): a clinical database in Latin America and the

Caribbean. Lancet 1999;354:75.

13. Institute of Medicine, National Academy of Sciences. Nutrition during pregnancy and

lactation. An implementation guide. Washington, DC: National Academy Press, 1992.

14. World Health Organization. English version of International Classification of Diseases,

15. Mahfouz AA, el-Said MM, Alakija W, Badawi IA, al-Erian RA, Moneim MA. Anemia among

pregnant women in the Asir region, Saudi Arabia: an epidemiologic study. Southeast Asian J

Trop Med Public Health 1994;25:84-87.

16. Ananth CV, Wilcox AJ, Savitz DA, Bowes WA Jr, Luther ER. Effect of maternal age and

parity on the risk of uteroplacental bleeding disorders in pregnancy. Obstet Gynecol

1996;88:511-516.

17. Miller JE. Birth intervals and perinatal health: an investigation of three hypotheses.

Fam Plann Perspect 1991;23:62-70.

18. Winkvist A, Rasmussen KM, Habicht JP. A new definition of maternal depletion

syndrome. Am J Public Health 1992;82:691-694.

19. Khan KS, Chien PF, Khan NB. Nutritional stress of reproduction. Acta Obstet Gynecol

Scand 1998;77:395-401.

20. Alger LS, Pupkin MJ. Etiology of preterm premature rupture of the membranes.

Clin Obstet Gynecol 1986;29:758-770.

21. Libombo A, Folgosa E, Bergstrom S. Risk factors in puerperal endometritis-myometritis.

An incident case-referent study. Gynecol Obstet Invest. 1994;38:198-205.

22. Naeye RL. Maternal age, obstetric complications, and the outcome of pregnancy. Obstet

Gynecol 1983;61:210-216.

23. Trupin LS, Simon LP, Eskenazi B. Change in paternity: a risk factor for preeclampsia in

multiparas. Epidemiology 1996;7:240-244.

24. Cobo E. Aplicación de un modelo de historia clínica perinatal. Rev Col Obstet Ginecol

1985;36:79-94.

Table 1 Distribution of sociodemographic and obstetric characteristics according to interpregnancy interval in a cohort of 456 889 Latin American and Caribbean women delivering singleton infants, 1985-1997
 

Table 2 Rates of adverse maternal outcomes according to interpregnancy interval in a cohort of 456 889 Latin American and Caribbean parous women delivering singleton infants, 1985-1997
 

*Rate × 10 000 women.

Table 3 Adjusted relative risk and 95% confidence intervals for adverse maternal outcomes according to interpregnancy interval in a cohort of 456 889 Latin American and Caribbean parous women delivering singleton infants, 1985-1997*
 

*Adjusted for maternal age, number of previous deliveries, histories of abortion, stillbirth, and early neonatal death, previous caesarean delivery, marital status, education, cigarette smoking, prepregnancy body-mass index, trimester at which prenatal care was started, number of prenatal care visits, geographic area, hospital type, and year of delivery. Preeclampsia, eclampsia, gestational diabetes mellitus, and third trimester bleeding were also adjusted for history of chronic hypertension.

†Reference group.