Objective
The purpose of this study was to investigate the recurrence risk of preterm birth (<37 weeks’ gestation) in a subsequent singleton pregnancy after a previous nulliparous preterm twin delivery.
Study Design
We included 1957 women who delivered a twin gestation and a subsequent singleton pregnancy from the Netherlands Perinatal Registry. We compared the outcome of subsequent singleton pregnancy of women with a history of preterm delivery to the pregnancy outcome of women with a history of term twin delivery.
Results
Preterm birth in the twin pregnancy occurred in 1075 women (55%) vs 882 women (45%) who delivered at term. The risk of subsequent spontaneous singleton preterm birth was significantly higher after preterm twin delivery (5.2% vs 0.8%; odds ratio, 6.9; 95% confidence interval, 3.1–15.2).
Conclusion
Women who deliver a twin pregnancy are at greater risk for delivering prematurely in a subsequent singleton pregnancy.
In many developed countries, twin birth rates have increased drastically during the past decades. In the United States, the twin rate climbed from 1.9% in 1980 to 3.2% in 2006. Similar trends were found in other developed countries. The increase in twin birth rates is caused mainly by the increase in the use of assisted reproductive techniques and increasing maternal age.
For Editors’ Commentary, see Contents
See related editorial, page 241
Twin pregnancies are associated with higher risks of various pregnancy complications such as preeclampsia, intrauterine growth restriction, and preterm birth. These preterm births either can be a result of intervention in the case of previously mentioned obstetrics complications or can occur spontaneously. Preterm birth, in its turn, is the most important risk factor for perinatal morbidity and death in developed countries. This is mostly due to respiratory immaturity, intracranial hemorrhages, and infections.
Besides having a twin pregnancy, a history of previous preterm birth is the most important risk factor for spontaneous preterm birth. This recurrence risk was demonstrated particularly for singleton pregnancies in women with a preceding preterm singleton delivery. Less is known about the recurrence risk of preterm birth after a preceding twin pregnancy. The few studies that have reported on this phenomenon had contradictory findings and had access to relatively small samples.
Therefore, we aim to investigate the recurrence risk of a spontaneous preterm birth in subsequent singleton pregnancy after previous preterm twin delivery in a nationwide database.
Materials and Methods
Dataset
This study was performed in a prospective nationwide cohort with the use of The Netherlands Perinatal Registry (PRN). The PRN consists of population-based data that contain information on pregnancies, deliveries, and readmissions until 28 days after birth. The PRN database is obtained by a validated linkage of 3 different registries: the midwifery registry, the obstetrics registry, and the neonatology registry of hospital admissions of newborn infants. The coverage of the PRN registry is approximately 96% of all deliveries in The Netherlands. It contains pregnancies of ≥22 weeks’ gestation and a birthweight of ≥500 g and is used primarily for an annual assessment of the quality indicators of obstetric care.
Longitudinal linkage
The records that are included in the PRN registry are entered at the child’s level. There is no unique maternal identifier available in the registry to follow-up on outcomes of subsequent pregnancies of the same mother. Therefore, we performed a longitudinal probabilistic linkage procedure in which we linked records of children of the same mother to create a mother identifier. We subjected all children from second deliveries (n = 509,559) who were registered in the PRN registry to linkage with their siblings who were born during a first delivery that had been registered in the PRN registry. The linkage was based on the variables of the birth date of mother, the birth date of a (previous) child, and the postal code of mother ( Appendix ). The final linked cohort with complete data on first and second deliveries of the same mother consisted of 272,551 women and 545,102 (2 × 272,551) deliveries.
Inclusion and exclusion criteria
From our linked cohort, we included all women who delivered a singleton pregnancy (second delivery) after a previous twin pregnancy (first delivery) in The Netherlands between January 1, 1999, and December 31, 2007. We excluded all cases with major congenital anomalies and all cases with antepartum fetal death. Preterm birth was defined as birth at <37 completed weeks of gestation. We excluded iatrogenic preterm births in the subsequent singleton pregnancies because we were interested only in the subsequent risk of spontaneous preterm birth.
Statistics
We compared women with a preterm twin delivery with women with a term twin delivery.
For these 2 groups, we compared demographic and obstetric baseline characteristics like maternal age (mean ± SD), white maternal ethnicity (yes vs no), socioeconomic status (low (<p25) vs >p25), living in a deprived area (yes vs no), use of assisted reproductive techniques (yes vs no), and pregnancy interval (mean ± SD).
We subdivided previous preterm deliveries into iatrogenic and spontaneous deliveries. Furthermore, we subdivided previous preterm birth into 3 subgroups (22 +0 -29 +6 weeks’ gestation, 30 +0 -33 +6 weeks’ gestation, and 34 +0 -36 +6 weeks gestation). Univariate analyses were performed with the Student t test for normally distributed continuous variables and Fisher exact test for categoric variables. Normality of continuous variables was assessed by visual inspection of Q-Q plots. All statistical tests were 2-sided; a probability value of .05 was chosen as the threshold for statistical significance. We measured the association between history of preterm birth and subsequent risk of spontaneous preterm birth by calculating an adjusted odds ratio (aOR). We adjusted only for variables that appeared to be distributed unequally in the baseline characteristics of the study population. The probabilistic linkage procedure was performed with the R statistical software environment (version 2.13.1; R Foundation for Statistical Computing, Vienna, Austria), and the data were analyzed with the SAS statistical software package (version 9.2; SAS Institute Inc, Cary, NC).
Results
To determine which children had similar mothers, the PRN dataset was divided into 2 datasets. Dataset A contained records of second deliveries (n = 509.559), and dataset B contained records (n = 667.053) of first deliveries. By performing a probabilistic record linkage procedure, we determined which second delivery from dataset A belonged to a first delivery from dataset B. After the longitudinal linkage procedure ( Appendix ), we were able to identify 272,551 pairs of first and second deliveries. The linked dataset consisted of 254,776 singleton-singleton pairs (97.7%), 4071 singleton-twin pairs (1.6%), 57 twin-twin pairs (0.02%), and 2097 (0.8%) mothers who had a twin delivery that was followed by a singleton delivery.
We selected the 2097 women with a twin delivery followed by a singleton delivery for our study. We excluded mothers with iatrogenic preterm births in the second pregnancy (1.8%), severe congenital anomalies in first or second pregnancy (1.8% and 1.1%, respectively), and antepartum fetal death (2.1% and 0.4%, respectively). Our final dataset consisted of 1957 women.
Baseline characteristics of this cohort are presented in Table 1 . In the twin pregnancy group, 1075 women (55%) delivered at <37 completed weeks of gestation. In most cases, these preterm births were a result of obstetric intervention (n = 597; 56%) but occurred spontaneously in the remaining 478 women (44%). Demographic characteristics of the women with preterm (n = 1075) and term (n = 882) twin deliveries were comparable when we considered maternal age, socioeconomic status, living in a deprived area, and the use of artificial reproductive technology. Nonetheless, there were significantly fewer women with a white maternal ethnicity in the group with preterm twin deliveries (88.7% vs 91.4%; P < .05). The time interval to the subsequent singleton pregnancy was statistically significantly shorter in the women who delivered their twins preterm (33 vs 36 months; P < .001). As expected, the mean gestational age was also significantly different between the 2 groups.
| Characteristics of the twin delivery | Preterm twin delivery at <37 weeks (n = 1075) | Term twin delivery at ≥37 weeks (n = 882) | P value |
|---|---|---|---|
| Gestational age at twin delivery, wk a | 32.5 ± 3.9 | 38.0 ± 1.1 | < .0001 |
| Maternal age at twin delivery, y a | 29.1 ± 4.0 | 29.2 ± 4.1 | .54 |
| White maternal ethnicity, n (%) | 982 (88.7) | 782 (91.4) | < .05 |
| Low socioeconomic status, n (%) | 207 (19.3) | 185 (21.0) | .36 |
| Living in a deprived area, n (%) | 44 (4.1) | 43 (4.9) | .44 |
| Artificial reproductive technology, n (%) | 521 (48.5) | 426 (48.3) | .96 |
| Interval to subsequent singleton delivery, mo a | 33 ± 17 | 36 ± 16 | < .001 |
Of the 1075 women who had a preterm twin delivery, 56 women (5.2%) had a spontaneous preterm birth in the subsequent singleton pregnancy, and 1019 women (94.8%) women delivered at term. The spontaneous singleton preterm birth rate in the 882 women who delivered their twins at term was 0.8% (n = 7). Delivery of preterm twins was associated therefore with a significant increased risk of spontaneous preterm birth in a subsequent singleton pregnancy (aOR, 6.9; 95% CI, 3.1–15.2). Table 2 shows the subdivision in spontaneous vs iatrogenic preterm twin delivery and that the increased risk of subsequent singleton preterm birth is even higher after a spontaneous preterm twin delivery (aOR, 9.9; 95% CI, 4.4–22.4) instead of an iatrogenic preterm twin delivery. Nevertheless, even after an iatrogenic preterm twin delivery, there is still an increased risk of spontaneous preterm birth in the next singleton pregnancy (aOR, 4.6; 95% CI, 1.9–10.8).
| Twin delivery (n = 1957) | Subsequent singleton delivery (n = 1957) | |||
|---|---|---|---|---|
| Spontaneous preterm birth | Odds ratio a (95% CI) | |||
| Gestational age at delivery | n | N | % | |
| Total term delivery at ≥37 weeks | 882 | 7 | 0.8 | Reference |
| Total preterm delivery at <37 weeks | 1075 | 56 | 5.2 | 6.9 (3.1–15.2) |
| Spontaneous preterm delivery, wk | ||||
| <37 | 478 | 35 | 7.3 | 9.9 (4.4–22.4) |
| 34 +0 –36 +6 | 199 | 7 | 3.5 | 4.6 (1.6–13.3) |
| 30 +0 –33 +6 | 116 | 9 | 7.8 | 10.7 (3.9–29.5) |
| 22 +0 –29 +6 | 163 | 19 | 11.7 | 17.8 (7.2–44.1) |
| Iatrogenic preterm delivery | ||||
| <37 | 597 | 21 | 3.5 | 4.6 (1.9–10.8) |
| 34 +0 –36 +6 | 407 | 9 | 2.2 | 2.8 (1.04–7.6) |
| 30 +0 –33 +6 | 144 | 7 | 4.9 | 6.4 (2.2–18.5) |
| 22 +0 –29 +6 | 46 | 5 | 10.9 | 16.2 (4.9–54.1) |
Table 2 shows that, for both spontaneous and iatrogenic preterm twin deliveries, the recurrence risk also depends on the gestational age at the time of preterm twin delivery. The risk of preterm birth increases as the gestational age at preterm twin delivery decreases. The ORs in Table 2 are adjusted for maternal ethnicity and pregnancy interval.
Results
To determine which children had similar mothers, the PRN dataset was divided into 2 datasets. Dataset A contained records of second deliveries (n = 509.559), and dataset B contained records (n = 667.053) of first deliveries. By performing a probabilistic record linkage procedure, we determined which second delivery from dataset A belonged to a first delivery from dataset B. After the longitudinal linkage procedure ( Appendix ), we were able to identify 272,551 pairs of first and second deliveries. The linked dataset consisted of 254,776 singleton-singleton pairs (97.7%), 4071 singleton-twin pairs (1.6%), 57 twin-twin pairs (0.02%), and 2097 (0.8%) mothers who had a twin delivery that was followed by a singleton delivery.
We selected the 2097 women with a twin delivery followed by a singleton delivery for our study. We excluded mothers with iatrogenic preterm births in the second pregnancy (1.8%), severe congenital anomalies in first or second pregnancy (1.8% and 1.1%, respectively), and antepartum fetal death (2.1% and 0.4%, respectively). Our final dataset consisted of 1957 women.
Baseline characteristics of this cohort are presented in Table 1 . In the twin pregnancy group, 1075 women (55%) delivered at <37 completed weeks of gestation. In most cases, these preterm births were a result of obstetric intervention (n = 597; 56%) but occurred spontaneously in the remaining 478 women (44%). Demographic characteristics of the women with preterm (n = 1075) and term (n = 882) twin deliveries were comparable when we considered maternal age, socioeconomic status, living in a deprived area, and the use of artificial reproductive technology. Nonetheless, there were significantly fewer women with a white maternal ethnicity in the group with preterm twin deliveries (88.7% vs 91.4%; P < .05). The time interval to the subsequent singleton pregnancy was statistically significantly shorter in the women who delivered their twins preterm (33 vs 36 months; P < .001). As expected, the mean gestational age was also significantly different between the 2 groups.
