Objective
The purpose of this study was to evaluate whether the association between short interpregnancy intervals and perinatal outcome varies with maternal age.
Study Design
We performed a retrospective cohort study among 263,142 Dutch women with second deliveries that occurred between 2000 and 2007. Outcome variables were preterm delivery (<37 weeks of gestation), low birthweight in term deliveries (<2500 g) and small-for-gestational age (<10th percentile for gestational age on the basis of sex- and parity-specific Dutch standards).
Results
Short interpregnancy intervals (<6 months) was associated positively with preterm delivery and low birthweight, but not with being small for gestational age. The association of short interpregnancy interval with the risk of preterm delivery was weaker among older than younger women. There was no clear interaction between short interpregnancy interval and maternal age in relation to low birthweight or small for gestational age.
Conclusion
The results of this study indicate that the association of short interpregnancy interval with preterm delivery attenuates with increasing maternal age.
Short interpregnancy interval (IPI) is associated with both maternal and fetal risks. Maternal risks include premature rupture of membranes, third-trimester bleeding, and placental abruption. Adverse fetal outcomes that are associated with short IPI include preterm delivery, low birthweight (LBW), and small-for-gestational age (SGA). Long-term associations have also been described that have included increased risks of schizophrenia, menstrual disorders, and subfecundity in female offspring. Short IPI is typically defined as an interval of <6 months between the end of 1 pregnancy (ended by delivery, abortion, fetal death, or any other outcome) and the conception of the next.
During the past decades, maternal age at first delivery has increased in many Western countries. In The Netherlands, for example, maternal age increased from 24.3 years in 1969 to 29.4 years in 2008. The proportion of women who delay childbearing until their thirties has increased as well. Previous research has shown that high maternal age is a risk factor for adverse pregnancy outcome, such as fetal death, preterm delivery, LBW, and SGA.
Women who are delaying childbearing until their thirties are more likely to have short IPIs, compared with women 20-29 years old at the time of their first delivery, which possibly is attributable to the desire to have >1 child in combination with the acknowledgment that conception chances decline with age.
Theoretically, a combination of both high maternal age and short IPI can lead to various scenarios. One scenario is that the factors enhance each other’s effect. The uterine vasculature in older women has a decreased ability to sufficiently adapt to increased hemodynamic demands during pregnancy, which causes greater risk of adverse pregnancy outcome. When a pregnancy is established after a short IPI, stores of micronutrients possibly are not fully repleted after the previous pregnancy, which leads to maternal depletion syndrome. Another possible scenario is that older women with short IPI achieve better pregnancy outcomes, compared with older women with longer IPI. The ability to become pregnant again after a short IPI indicates that ovarian reserve has not declined to a level that fecundability or oocyte quality are affected. On a population level, the adverse influence of short IPIs on pregnancy outcomes could then be weaker among older than among younger women. A third possibility is that both the aforementioned scenarios coexist and balance each other, which results in no difference as to the effect of short IPIs among older and younger mothers.
Little research has been done into the interplay of maternal age and IPI in the causation of adverse perinatal outcome. Only 1 previous study, which was performed in the United States, focused on this interaction. The authors found that short IPI and high maternal age were independent risk factors of adverse perinatal outcomes. Increased risks for LBW and preterm delivery were observed in maternal age groups of 30-34 years and >34 years, compared with maternal age of 20-29 years. This increase was not observed for SGA after adjustment for confounders. Short IPI of 0-5 months was associated with increased risk of all 3 outcomes, when compared with IPI of ≥6 months. The authors, however, did not find any statistically significant interaction between maternal age and IPI.
In the present study, we examined the association of adverse birth outcome with IPI and maternal age at first delivery in the Netherlands, both individually and in combination. The study population comprised all women who gave birth to their second singleton child in Dutch hospitals between 2000 and 2007.
Materials and Methods
Patients
For this retrospective cohort study we used data from The Netherlands Perinatal Registry, which is a national registry that contains population-based detailed information on pregnancies, deliveries, and readmissions, that were collected by caregivers. We identified women who gave birth between January 1, 2000, and December 31, 2007. Only data of hospital births that were under supervision of a gynecologist (approximately 65% of all births) were selected because these records contain the date of previous delivery linked to the index delivery, which makes it possible to calculate IPIs. Women with no known previous delivery date were excluded. These cases included primiparous women and a small group (5%) whose previous delivery date was not registered or was registered incorrectly. Coverage of the registration of hospital births is very high; approximately 99% of all pregnancies with a gestational age of >15 weeks are registered. For our analyses, we included only pregnancies with a gestational age of ≥20 weeks. Eligible cases were women of any age with a singleton delivery during the study period (including stillbirths and any birthweight), and 1 previous delivery.
The study was performed with the explicit permission of the holder of the patient registration data (Netherlands Perinatal Registry), which consists of representatives of all professional caregivers who are involved in the registry. The permission was subject to the strict requirement of nondisclosure of the identity of any individual hospital, either directly or indirectly. Patient data in the Netherlands Perinatal Registry are anonymous.
Study outcomes
Outcome measures included preterm delivery, LBW, and SGA. Gestational age was determined on the basis of either date of last menstrual period or ultrasound examination. Preterm delivery was defined as delivery at <37 completed weeks of gestation. LBW was defined as birthweight of <2500 g in term pregnancies. Women with preterm deliveries were excluded in calculations of LBW risk. SGA was defined as birthweight <10th percentile for gestational age on the basis of sex- and parity-specific Dutch standards.
Variables
Main determinants of the outcome measures were IPI and maternal age at first delivery. IPI was calculated from the records as the time in months between first delivery date and date of conception of the index pregnancy. Date of conception was calculated as predicted term delivery date minus 266 days. IPI categories were 0-5, 6-11, 12-17, 18-23, and ≥24 months. The predicted delivery date was verified by first-trimester ultrasound examination for almost 98% of the cases. Cases with unsure term delivery dates were also included; however, we performed a separate analysis without these cases to assess the influence of uncertainty of term date. Maternal age categories were <20, 20-24, 25-29, 30-34, 35-39, and ≥40 years.
Potentially confounding variables included ethnicity (as assessed by the obstetrician or midwife), the use of any artificial reproductive techniques (except artificial insemination with donor sperm, which was considered to be spontaneous conception), year of delivery, and socioeconomic status. We classified ethnicity as white European, Mediterranean (mainly Turkish and Moroccan), and other. Socioeconomic status was based on the mean household income level of the neighborhood, which was determined by the first 4 digits of the woman’s postal code. We performed a separate analysis that included only women with 2 pregnancies and 2 deliveries and excluded women with a termination of pregnancy at <20 weeks of gestation in their history.
Statistical analysis
Frequencies of the studied variables across the various IPI categories and maternal age groups and for the codistribution of IPI and maternal age were analyzed in contingency tables with χ 2 statistics. The Kruskal-Wallis test was used to test for significance in difference of interval length between maternal age categories. Probability values of < .05 were considered statistically significant.
Uni- and multivariable logistic regression analysis was used to assess associations of perinatal outcomes with maternal age and IPI categories. Both crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with an interval of 18-23 months as reference category for IPI and 25-29 years as reference category for maternal age. We also evaluated interaction between IPI categories and maternal age groups. In this interaction analysis, we merged maternal age groups with small numbers of cases (<20 with 20-25 years and ≥40 with 35-39 years) to prevent instability of the effect measures. We also used models with maternal age as a continuous variable to evaluate significance of a trend in interaction across age. All analyses were performed with SAS software (version 9.1.3; SAS Institute Inc, Cary, NC).
Results
Main characteristics of the study population
In total 263,142 woman-child pairs were included in the study ( Figure 1 ). Four percent of all second pregnancies were conceived after an IPI of <6 months. Mean maternal age at first delivery was 28.6 years. IPI and maternal age were associated with each other NS with ethnic origin, socioeconomic status, and the use of artificial reproductive techniques ( Tables 1 and 2 ). The prevalence of short IPIs showed an increasing trend with maternal age and was almost 3 times as high among women of ≥40 years, compared with women between 25 and 29 years of age (10.0% vs 3.4%; χ 2 -test, P < .0001).
| Characteristic | Interpregnancy interval, mo | |||||
|---|---|---|---|---|---|---|
| 0-5 (n = 10,211) | 6-11 (n = 31,614) | 12-17 (n = 45,148) | 18-23 (n = 43,093) | ≥24 (n = 127,814) | Total (n = 263,142) a | |
| Ethnic origin, % b | ||||||
| White European | 78.2 | 87.5 | 90.2 | 90.5 | 81.2 | 85.1 |
| Mediterranean | 10.5 | 5.9 | 4.7 | 4.6 | 9.1 | 7.2 |
| Other | 11.3 | 6.7 | 5.1 | 4.9 | 9.7 | 7.7 |
| Socioconomic status, % b | ||||||
| Very high | 17.0 | 20.1 | 21.5 | 21.8 | 19.2 | 19.9 |
| High | 18.0 | 20.0 | 20.6 | 20.6 | 18.0 | 19.2 |
| Average | 17.6 | 19.1 | 19.1 | 18.8 | 16.6 | 18.1 |
| Low | 18.5 | 19.0 | 18.9 | 18.7 | 18.4 | 18.6 |
| Very low | 28.9 | 21.9 | 20.0 | 20.0 | 27.8 | 24.2 |
| Artificial reproductive techniques, % b | 1.3 | 1.9 | 2.5 | 2.5 | 4.1 | 3.1 |
| Maternal age at first delivery, % b | ||||||
| <20 y | 3.4 | 1.9 | 1.3 | 1.6 | 4.7 | 3.2 |
| 20-24 y | 17.7 | 11.9 | 10.6 | 10.7 | 19.9 | 15.6 |
| 25-29 y | 32.1 | 32.5 | 34.8 | 38.1 | 38.6 | 36.9 |
| 30-34 y | 32.8 | 39.6 | 41.7 | 40.5 | 31.2 | 35.7 |
| 35-39 y | 12.6 | 13.2 | 10.9 | 8.7 | 5.4 | 8.2 |
| ≥40 y | 1.2 | 1.1 | 0.7 | 0.5 | 0.2 | 0.5 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
