American Journal of Obstetrics & Gynecology
Volume 197, Issue 3 , Pages 253.e1-253.e3, September 2007

Are women who have had a preterm twin delivery at greater risk of preterm birth in a subsequent singleton pregnancy?

Presented at the 27th Annual Clinical Meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, Feb. 5-10, 2007.

Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL.

Received 19 February 2007; received in revised form 23 May 2007; accepted 25 June 2007.

Article Outline

Objective

The purpose of this study was to determine whether preterm birth of twins is associated with an increased risk of preterm birth in a subsequent singleton pregnancy.

Study Design

All patients who delivered a twin gestation and a subsequent singleton pregnancy at Northwestern Memorial Hospital during a 10-year period were identified. We used a cohort study design, comparing the outcomes of the singleton pregnancies in women with preterm twin deliveries to those pregnancies with term twin deliveries.

Results

One hundred sixty-seven women delivered twins followed by a singleton pregnancy. Women whose twin delivery was preterm (n = 99) were more likely than those who had delivered a term twin pregnancy (n = 68) to deliver a subsequent preterm singleton pregnancy (13.1% vs 2.9%; odds ratio, 5.0; 95% CI, 1.1, 22.9).

Conclusion

Preterm birth of twins is associated with an increased risk of preterm delivery in a subsequent singleton pregnancy.

Key words: premature, preterm birth, twin gestation

 

In the United States, 12% of births are preterm.1 Preterm birth is the leading cause of neonatal death and birth-related morbidity.2 Of the multiple risk factors for preterm birth that have been delineated, the 1 factor that has been shown to have the highest population attributable risk is “previous preterm delivery.” More specifically, multiple investigators have demonstrated that an idiopathic preterm delivery of a singleton fetus is associated with a high risk of idiopathic preterm delivery in a subsequent singleton pregnancy.3, 4

However, the risk of subsequent preterm delivery is uncertain when the previous preterm delivery is of a twin gestation. This question is of particular relevance because the frequency of twin gestations has been increasing steadily and because the indication for prophylactic progesterone supplementation is a history of preterm birth.1, 5 Studies to determine whether a preterm twin delivery is associated with an increased risk of a preterm singleton birth have reported conflicting results. Menard et al6 found that preterm birth of a twin gestation was associated with a nearly 3-fold increased risk of a preterm delivery in a subsequent singleton pregnancy. Rydhstroem7 and Bloom et al8 did not observe an association between a premature twin birth and the subsequent risk of a premature delivery in a singleton pregnancy. We sought to investigate further the risk of preterm birth in women with this history.

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Materials and Methods 

All women who delivered a twin pregnancy followed by a singleton pregnancy at >20 weeks of gestation at Northwestern Memorial Hospital between June 1, 1995, to May 31, 2005, were identified by a search of a database of all hospital discharges for the appropriate V-codes for outcome of delivery. Delivery records were then obtained and reviewed. Preterm delivery was defined as delivery at <37 completed weeks of gestation. Women were excluded from further analysis if either their twin or singleton pregnancy was delivered iatrogenically preterm (eg, after an induction for preeclampsia) or had a fetus with a major anomaly or an intrauterine death. Also excluded were women who, before their pregnancies during the study period, had other premature deliveries. This exclusion was performed so that any associations would not be confounded by previous preterm births.

The data were analyzed in 2 groups: those who had a term twin delivery and those who had a preterm twin delivery. Demographic data and pregnancy outcomes were abstracted from the medical record.

Univariable comparisons were made with the Student t test and chi-square analysis for continuous and categoric variables, respectively. All statistical tests were 2-sided, and a probability value of <.05 was used to define the statistical significance of associations. All analyses were performed with Minitab software (version 13; Minitab, Inc, State College, PA). This study was approved by the institutional review board of Northwestern University.

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Results 

Two hundred thirty-six women with the required history of a previous twin birth followed by a singleton birth were identified. Of these, 21 women (9%) were excluded because either the twin or singleton pregnancy was delivered iatrogenically preterm; 34 women (14%) were excluded because of a delivery at <20 weeks of gestation, fetal anomalies, or an intrauterine fetal death; and 5 women (2%) were excluded because of a history of a preterm birth. There were 176 women who met inclusion criteria and had a spontaneous singleton delivery. Of these, the medical records of 9 women (5 %) did not allow reliable ascertainment of gestational age at delivery in at least 1 pregnancy; thus, these women were also excluded from further analyses.

Of the 167 women who delivered twins before a singleton infant, the initial twin delivery was preterm in 99 cases (59%). These preterm deliveries were related to premature preterm rupture of the membranes in 49 women (49.5%) and spontaneous labor in the remaining 50 women (50.5%). Demographic characteristics of the cohort, which were stratified by whether their twin delivery was preterm or term, are presented in the Table. As expected, the mean gestational age at delivery of the twin pregnancy was significantly different between the 2 groups. Other demographic characteristics, which included maternal ages of the 2 groups at their subsequent singleton delivery (33.1 ± 4.4 years vs 33.2 ± 4.7 years, respectively; P = .7) were not different.

TABLE. Demographic characteristics of the study group stratified by gestational age at the twin delivery
CharacteristicPreterm twin delivery (n = 99)Term twin delivery (n = 68)P value
Gestational age at twin delivery (wks)⁎32.3 ± 4.638.3 ± 0.7<.01
Maternal age at twin delivery (y)⁎30.9±4.930.0±4.5.2
White (n)69(69.7%)48(70.6%).9
Significant medical history (n)†9(9.1%)9(13.2%).4
Cesarean delivery (n)33(33.3%)22(32.4%).9
Previous term birth (n)28(28.3%)21(30.9%).7

⁎Data are presented as mean ± SD.

†History of hypertension, pregestational diabetes mellitus, or autoimmune disease.

Of the 99 women who had delivered preterm twins, 13 women (13.1%) delivered prematurely in a subsequent singleton pregnancy. Of the 68 women who had delivered term twins, 2 women (2.9%) delivered subsequent premature singleton infants. Delivery of a preterm twin pregnancy was associated significantly with the delivery of a subsequent preterm singleton pregnancy (odds ratio, 5.0; 95% CI, 1.1, 22.9; P = .039).

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Comment 

Preterm birth of a singleton infant is associated consistently with a significantly increased risk of a preterm delivery in a subsequent singleton gestation.3, 4 The preterm delivery of twins has been associated inconsistently with an increased risk for preterm birth of a subsequent singleton infant.6, 7, 8 We found that the idiopathic preterm birth of twins is associated with an increased risk of idiopathic preterm birth in a subsequent singleton infant.

Our results are consistent with data from a retrospective review of twin deliveries followed by a singleton gestation reported by Menard et al,6 who found that preterm birth of a twin gestation was associated with a significantly increased risk of preterm delivery in a subsequent singleton pregnancy (relative risk, 2.87; 95% CI, 1.02-8.09). Previous obstetric history preceding the index twin delivery was not described. We excluded women with a preterm birth before the index twin pregnancy.

Our results differ from those of Rydhstroem,7 who found that a preterm twin birth did not significantly affect the gestational duration of a subsequent singleton pregnancy. No explicit comparison of the frequency of preterm birth in singleton gestations that occurred after a previous preterm twin birth with those pregnancies that occurred after a previous term twin birth was made. Rydhstroem’s study also did not exclude women whose preterm births were iatrogenic. Because some indications for iatrogenic preterm delivery may not be recurrent, the inclusion of this patient population in the study may obscure the true recurrence risk of idiopathic preterm delivery. In addition, this was a population-based study from Sweden; therefore, the conclusions may not be generalizable to the current US population, in which the preterm birth rate is significantly higher than that in Sweden.

Bloom et al8 reported results similar to those of Rydhstroem’s from a population in Dallas, Texas, and concluded that a previous twin delivery at <35 weeks of gestation did not significantly increase the risk of preterm birth in a subsequent singleton pregnancy. However, their sample size was 82 twin pregnancies and did not have sufficient power to detect the difference in the preterm delivery rates that we detected in our study population.

Given the significant number of multiple gestation deliveries at Northwestern Memorial Hospital, we were able to identify a large population of women who met our study criteria and who could allow the discernment of a difference in outcomes. We are also confident that we were able to eliminate the confounding issue of iatrogenic preterm birth by reviewing each subject’s original medical record and excluding from the analysis any subjects with an iatrogenic preterm delivery of either their twin or singleton gestation.

We also excluded women with a preterm delivery before their twin gestation in an effort to prevent possible confounding of our results by other nontwin preterm deliveries. It is possible that the causes that led to preterm birth in this excluded population are different than those in our cohort because the biologic condition of women with a history of a previous preterm singleton vs twin birth may differ. For example, preterm singleton deliveries may be related to inflammation; preterm twin births may be attributed partially to excessive myometrial stretch.9, 10, 11, 12, 13 If these patients were not excluded, it is possible that the association between preterm twin delivery and subsequent singleton delivery could be even higher.

A possible limitation of this study is the potential for referral bias. Our hospital is a tertiary care and referral center. Therefore, it is possible that our study cohort represents a particularly high-risk population with results that are not applicable to a more general population. However, the rate of preterm delivery in twin gestations that were recorded in our population is similar to that reported in the general population, which suggests that external validity should be intact. Moreover, the rate of preterm delivery in singleton pregnancies is 10.4%, which is a frequency that is very similar to the overall 9% (15/167) frequency seen in our study.1

In conclusion, the data suggest that preterm birth of a twin pregnancy is associated with a higher risk of preterm delivery in a subsequent singleton pregnancy. These data can help physicians and patients better quantify the risk of preterm delivery and aid in the counseling of patients with a history of preterm birth of twins. Meis et al14 studied women with a previous preterm delivery of a singleton pregnancy and demonstrated that weekly injections of 17 alpha-hydroxyprogesterone caproate resulted in a significant reduction in the rate of recurrent preterm delivery in a subsequent singleton gestation. It remains uncertain whether women with a previous preterm delivery of twins, currently pregnant with a singleton fetus, would benefit from treatment with progesterone.

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References 

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 Cite this article as: Facco FL, Nash K, Grobman WA. Are women who have had a preterm twin delivery at greater risk of preterm birth in a subsequent singleton pregnancy? Am J Obstet Gynecol 2007;197:253.e1-253.e3.

PII: S0002-9378(07)00825-3

doi:10.1016/j.ajog.2007.06.049

American Journal of Obstetrics & Gynecology
Volume 197, Issue 3 , Pages 253.e1-253.e3, September 2007

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