Objective
Preeclampsia and intrauterine growth restriction (IUGR) are correlated in singleton pregnancies. The objective of this study was to estimate their relationship in twin pregnancies.
Study Design
Cohort of 578 patients with twin pregnancies delivered by 1 maternal fetal medicine practice from 2005-2013. Patients with chronic hypertension, monochorionic-monoamniotic placentation, twin-twin transfusion, and major congenital anomalies were excluded. Standard definitions were used for gestational hypertension and preeclampsia. We defined IUGR as any twin birthweight less than the 5th percentile for gestational age, as well as any twin birthweight less than the 10th percentile for gestational age.
Results
The incidence of preeclampsia was 14.9%, the incidence of birthweight <10% was 50.0%, and the incidence of birthweight <5% was 27.5%. Comparing patients with and without preeclampsia, the rate of birthweight <5th percentile did not differ (27.9% vs 27.4%, P = .929), nor did the rate of birthweight <10th percentile (48.8% vs 50.2%, P = .815). We had 80% power with an alpha error of 5% to show a difference in the likelihood of IUGR <10th percentile from 50% to 66% and a difference in the likelihood of IUGR <5th percentile from 27% to 42% in patients without and with preeclampsia.
Conclusion
In patients with twin pregnancy, there is no correlation between preeclampsia and IUGR. This suggests that in twin pregnancies, as opposed to singleton pregnancies, the pathophysiology may differ between these 2 common conditions.
Patients with twin pregnancies are at increased risk of many pregnancy complications compared with singleton pregnancies. Because twins account for 3.3% of all live births in the United States, it is important to have a good understanding of these complications in these high-risk pregnancies. Two common complications of twin pregnancies are preeclampsia and intrauterine growth restriction (IUGR).
In singleton pregnancies, there is a strong association between preeclampsia and IUGR. Several studies showed that the presence of preeclampsia is associated with a 2 to 4-fold increase in the risk of IUGR. Similarly, pregnancies complicated by IUGR are at increased risk of developing preeclampsia, and the likelihood of developing preeclampsia is positively correlated with the severity of the fetal growth restriction. There is also evidence that the biologic pathways leading to preeclampsia and IUGR are similar. For example, first and second trimester abnormal uterine artery Doppler measurements demonstrating increased impedance to flow is associated with an increased risk of developing preeclampsia as well as IUGR. Also, several first and second trimester maternal serum markers for aneuploidy are associated with both preeclampsia and IUGR, as are various serum angiogenic factors such as soluble fms-like tyrosine kinase-1 and PIGF. Finally, there is evidence that low dose aspirin started early in pregnancy in at-risk patients can reduce the risk of both preeclampsia and IUGR.
Despite the large pool of evidence supporting an association between preeclampsia and IUGR in singleton pregnancies, there is limited data regarding this association in twin pregnancies. The strength of this association, or lack thereof, in twin pregnancies could influence our management of these pregnancies when either preeclampsia or IUGR develops, and may also increase our understanding of the pathophysiology of these 2 common complications in twin pregnancies.
The objective of this study was to estimate the association between preeclampsia and IUGR in twin pregnancies.
Materials and Methods
After Biomedical Research Alliance of New York Institutional Review Board approval was obtained, the charts of all patients with twin pregnancies and live births of both twins >24 weeks delivered by a single maternal-fetal medicine practice between June 2005 (when our electronic medical record was established) and June 2013 were reviewed. We excluded patients with chronic hypertension (defined as prepregnancy hypertension, or hypertension diagnosed before 20 weeks of gestation ), monochorionic-monoamniotic placentation, twin-twin transfusion syndrome, and patients with major congenital fetal anomalies discovered before or after birth.
Baseline characteristics and pregnancy outcomes were obtained from our computerized medical record. Gestational age was determined by last menstrual period and confirmed by ultrasound in all patients. The pregnancy was redated if there was a >5 day discrepancy up to 14 weeks or a >7 day discrepancy after 14 weeks. If the pregnancy was the result of in vitro fertilization (IVF), gestational age was determined from IVF dating.
Standard definitions were used for the diagnosis of gestational hypertension and preeclampsia. We used 2 definitions of IUGR for twin pregnancies: (1) either twin with a birthweight less than the 10th percentile for gestational age; (2) either twin with a birthweight less than the 5th percentile for gestational age. We chose birthweight, as opposed to sonographic estimated fetal weights, to remove the known error associated with estimated sonographic measurements, as well as not to miss any diagnoses of IUGR because of lack of ultrasound immediately before delivery. To define birthweight percentiles for gestational age we used standard tables for singleton pregnancies. We chose singleton tables as they are the standard tables used for twins in the United States in defining growth restriction and determining neonatal outcomes.
In our practice, expectant management of patients with preeclampsia does not differ in twin pregnancies, as compared with singleton pregnancies. Patients with mild preeclampsia are delivered at 37 weeks, and patients with severe preeclampsia without contraindications to expectant management are delivered at 34 weeks. All patients with twin pregnancies have their blood pressure routinely checked in our office every 2-4 weeks until 28 weeks, then every 2 weeks until 36 weeks, and then every week until delivery. Ultrasound for fetal growth is done every 4 weeks for dichorionic twins and every 2 weeks for monochorionic twins. Uncomplicated dichorionic twin pregnancies are delivered at approximately 38 weeks and uncomplicated monochorionic twin pregnancies are delivered at approximately 37 weeks. The recommendation for low-dose aspirin was not uniform over the study period.
We compared the likelihood of IUGR in patients with and without preeclampsia. We also compared the likelihood of gestational hypertension and preeclampsia in patients with and without IUGR. Becauuse we planned on including every patient over the course of the study period, the power analysis was done post hoc. Student t test, χ 2 , and Pearson correlation were used when appropriate (SPSS for Windows 16.0, Chicago, IL). A P value of < .05 was considered significant.
Results
There were a total of 606 patients with twin pregnancies >24 weeks delivered over the course of the study period. Twenty-eight patients were excluded (10 monochorionic-monoamniotic, 8 with chronic hypertension, 5 with twin-twin transfusion, and 5 with major fetal anomalies), leaving a total of 578 patients for analysis. The characteristics of the study population are shown in Table 1 . The mean age was 34.1 years, and 64.7% were conceived via IVF. The population was mostly white and not obese.
| Characteristic | Value |
|---|---|
| Number of patients | 578 |
| Maternal age | 34.1 ± 6.5 |
| Chorionicity | |
| Dichorioic-Diamniotic | 86.9% |
| Monochorionic-Diamniotic | 13.1% |
| Conception | |
| Spontaneous | 23.7% |
| Ovulation induction | 11.6% |
| In vitro fertilization | 64.7% |
| Egg donor | 8.8% |
| Multifetal reduction | 7.3% |
| White race | 87.9% |
| Nulliparity | 61.8% |
| Uterine anomaly | 2.8% |
| Anticoagulation | 4.7% |
| Prepregnancy BMI, kg/m 2 | 23.4 ± 4.5 |
| Obesity (prepregnancy BMI ≥30 kg/m 2 ) | 8.3% |
| Gestational age at delivery | 35.8 ± 2.5 |
| Any diabetes | 8.7% |
| Preeclampsia | |
| Total | 14.9% |
| <32 wks | 0.7% |
| 32-34 wks | 2.6% |
| >34 wks | 11.6% |
| Any newborn weight <10th percentile | 50.0% |
| Any newborn weight <5th percentile | 27.5% |
Eighty-six (14.9%) patients in the study population were diagnosed with preeclampsia. The incidence of IUGR was compared between these patients and the 492 patients without preeclampsia and the results are shown in Table 2 . The incidence of IUGR was similar between the 2 groups, both when defined as birthweight less than the 10th percentile (50.2% vs 48.8%, P = .815), as well as when defined as birthweight less than the 5th percentile (27.4% vs 27.9%, P = .929). The only significant baseline differences between the patients who did and did not develop preeclampsia were the incidence of egg donation (16.3% vs 7.5%, P = .008) and prepregnancy obesity (14.1% vs 7.4%, P = .038). When controlling for egg donation and prepregnancy obesity, IUGR <10th percentile was not associated with preeclampsia (adjusted odds ratio, 0.941; 95% confidence interval, 0.638–1.623), nor was IUGR <5th percentile (adjusted odds ratio, 1.143; 95% confidence interval, 0.678–1.926).
| Variable | No preeclampsia n = 492 | Preeclampsia n = 86 | P value |
|---|---|---|---|
| Any birthweight <10% | 50.2% | 48.8% | .815 |
| Any birthweight <5% | 27.4% | 27.9% | .929 |
The likelihood of gestational hypertension and preeclampsia, based on the presence or absence of IUGR is shown in Table 3 . Patients with IUGR, regardless of the definition used, were not more likely to have gestational hypertension or preeclampsia than patients without IUGR.
| Variable | No birthweight <10% n = 289 | Any birthweight <10% n = 289 | P value |
|---|---|---|---|
| Any gestational hypertension | 19.4% | 20.8% | .678 |
| Preeclampsia | 15.2% | 14.5% | .815 |
| No birthweight <5% n = 419 | Any birthweight <5% n = 159 | ||
|---|---|---|---|
| Any gestational hypertension | 19.6% | 21.4% | .627 |
| Preeclampsia | 14.8% | 15.1% | .929 |
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