Objective
The evidence for delivering small-for-gestational-age (SGA) fetuses at 37 weeks remains conflicting. We examined the risk of stillbirth per week of gestation beyond 37 weeks for pregnancies complicated by SGA.
Study Design
Singleton pregnancies undergoing routine second trimester ultrasound from 1990-2009 were examined retrospectively. The risk of stillbirth per 10,000 ongoing SGA pregnancies with 95% confidence intervals (CIs) was calculated for each week of gestation ≥37 weeks. Using a life-table analysis with correction for censoring, conditional risks of stillbirth, cumulative risks of stillbirth per 10,000 ongoing SGA pregnancies and relative risks (RRs) were calculated with 95% CIs for each week of gestation.
Results
Among 57,195 pregnancies meeting inclusion criteria the background risk of stillbirth was 56/10,000 (95% CI, 42.3−72.7) with stillbirth risk for SGA pregnancies of 251/10,000 (95% CI, 221.2−284.5). The risk of stillbirth after the 37th week was greater compared with pregnancies delivered in the 37th week (47/10,000, 95% CI, 34.6−62.5 vs 21/10,000, 95% CI, 13.0−32.1; RR, 2.2; 95% CI, 1.3−3.7). The cumulative risk of stillbirth rose from 28/10,000 ongoing SGA pregnancies at 37 weeks to 77/10,000 at 39 weeks (RR, 2.75; 95% CI, 1.79−4.2). Among pregnancies complicated by SGA <5% the cumulative risk of stillbirth at 38 weeks was significantly greater than the risk at 37 weeks (RR, 2.3; 95% CI, 1.4−3.8).
Conclusion
There is a significantly increased risk of stillbirth in pregnancies complicated by SGA delivered after the 37th week. Given these findings, we advocate a policy of delivery of SGA pregnancies 37-38 weeks.
Nearly 3 million stillbirths occur worldwide each year. In high-income countries stillbirth rates have remained constant in recent decades with significant global variations in stillbirth rates among affluent nations, suggesting further reduction in stillbirth rates is possible. Fetal growth restriction has been established as a major cause of stillbirth. In a metaanalysis published in 2011, the risk of stillbirth in high-income countries was demonstrated to be 4-times higher in fetuses measuring small-for-gestational-age (SGA) compared with non-SGA fetuses and SGA was noted to have the greatest population-attributable risk compared to other risks of stillbirth.
The delivery timing of SGA pregnancies weighs competing risks. Early delivery avoids stillbirth but increases risks of respiratory distress syndrome, hypoglycemia, and neonatal sepsis while continued gestation risks stillbirth. Recent clinical trials with long-term follow-up have sought to clarify optimal timing of delivery for SGA fetuses. A recent randomized controlled trial evaluated expectant management versus induction of labor of SGA fetuses at term, but because of the rarity of stillbirth, the trial was not powered to study this important outcome. Given the impact of stillbirth both globally and nationally, defining the risk of stillbirth after 37 weeks is fundamental to answering the question of optimal timing of delivery for pregnancies complicated by SGA, and ultimately, an important step in stillbirth prevention. The specific aim of our study was to estimate the risk of stillbirth for each week of gestation beyond 37 weeks in pregnancies complicated by SGA.
Materials and Methods
We conducted a retrospective cohort study within our prospectively collected perinatal database at Washington University School of Medicine. Before initiation of the study, we obtained approval from the institutional review board. Sociodemographic, obstetric, medical and pregnancy follow-up data were obtained via self-report questionnaires at the initiation of prenatal care, at the time of ultrasound and from the hospital medical record on delivery. Detailed patient information was entered into the database by trained research nurses. Patients and/or primary obstetricians were contacted via telephone to obtain complete follow-up information if necessary, or in the rare event when the patient delivered at an outside facility. The study included all singleton pregnancies seen for anatomy survey between 16 and 23 weeks from January 1990 to December 2009. Approximately 97% of our study population are seen during this period. We excluded pregnancies complicated by prenatally diagnosed major congenital anomalies and aneuploidy and those without documented birthweight ( Figure 1 ).
Ultrasounds were performed by certified, dedicated obstetric sonographers and final ultrasound interpretation and diagnosis made after review by a fellowship trained maternal fetal medicine specialist. Gestational age was assigned by last menstrual period (LMP) and confirmed with ultrasound. Gestational age was assigned by ultrasound when the LMP was noted to be discrepant by ≥7 days in the first trimester or ≥10 days in the second trimester. If LMP was unknown, gestational age was assigned by ultrasound.
The primary outcome was stillbirth, defined as intrauterine fetal death at or beyond 20 weeks’ gestation. SGA was defined as birthweight <10th percentile based on the Alexander growth standard. The incidence of stillbirth per week of gestation was calculated as the number of SGA stillbirths per 10,000 ongoing SGA pregnancies at the start of that gestational week. The choice of ongoing pregnancies as the denominator is a logical approach because compared with the traditional stillbirth risk assessment that uses the number of deliveries occurring in a given week as the denominator, ongoing pregnancies are the pregnancies that continue to be at risk of stillbirth. Thus, this is the contemporary method of calculating stillbirth risk.
Although the number of stillbirths/10,000 ongoing pregnancies will assess the risk of stillbirth per week of gestation, it does not assess the cumulative risk of stillbirth. The cumulative risk of stillbirth becomes more clinically relevant than the conditional risk of stillbirth when one is trying to decide between a recommendation for delivery or expectant management. Furthermore, the risk of stillbirth/10,000 ongoing pregnancies includes in the denominator the pregnancies that might deliver live births during the proposed week. Therefore, including these pregnancies in the denominator will tend to under estimate the risk of stillbirth. This effect of censoring, while not significant in the conditional probability estimate of stillbirth, is magnified and may become clinically significant when one calculates cumulative probability. Therefore, to calculate a cumulative risk of stillbirth beyond 37 weeks and to account for censoring, we further analyzed our data using the method of life-table analysis as proposed by Smith in 2001.
For the life-table analysis, the estimation of stillbirth risk was calculated as follows: if P n is the number of ongoing pregnancies at gestational week n , B n is the number of births during gestational week n and S n is the number of stillbirths during gestational week n then the conditional probability of stillbirths PS n at gestational week n: PS n = S n /[P n – (0.5 × B n )], and the cumulative probability of stillbirths CS n is calculated as the product of the conditional probabilities of survival, where survival is 1 − Probability of death, at gestational week n : CS n = 1 − [(1 − PS 37 ) × (1 − PS 38 ) … ×(1 − PS n )].
Descriptive statistics were used to provide an overview of the study population and estimate the baseline risk of stillbirth. Maternal demographic, medical and obstetric information were described among SGA pregnancies <37 weeks, SGA pregnancies ≥37 weeks, and non-SGA pregnancies. To provide a more detailed overview of the SGA population, we also compared maternal demographics and obstetric information between SGA stillbirths and SGA live births. Descriptive statistics were performed using χ 2 for categorical variables and student t test for continuous variables. The risk of stillbirth with 95% confidence interval (CI) as calculated for each week of gestation 37-37 6/7, 38-38 6/7, 39-39 6/7, and ≥40 weeks. The relative risk (RR) of stillbirth with 95% CI was calculated for SGA pregnancies delivered after the 37th week compared with the risk of stillbirth in pregnancies delivered in the 37th week. Conditional risks and cumulative risks of stillbirth per week of gestation with 95% CIs were calculated using life-table analysis with correction for censoring as stated above. Risk ratios for stillbirth with 95% CIs were calculated for each week of gestation relative to the risk of stillbirth at 37 weeks using the cumulative risks for stillbirth. To evaluate the cumulative risk of stillbirth among neonates with a lower threshold of SGA, the risk of SGA for neonates with birthweight <5% was also determined by life-table analysis.
To estimate if changes in clinical management or technology over the period of the study affected stillbirth risks, we calculated and compared risks of stillbirth among SGA fetuses ≥37 weeks’ gestation between 2 time periods determined by days from initiation of enrollment of 50% of the study population, approximately 1990-2000 and 2001-2009.
The risk of neonatal morbidity in association with early term delivery was evaluated in a subanalysis for all neonates admitted to the neonatal intensive care unit or special care nurseries after delivery. Postnatally diagnosed aneuploidy and congenital anomalies were excluded. Adverse neonatal outcomes measured included intensive care unit admission, respiratory distress syndrome, meconium aspiration syndrome, and length of stay >5 days. The risk of adverse outcomes at 38, 39, and ≥40 weeks relative to the risk at 37 weeks was calculated with 95% CI. Statistical analysis was performed with STATA 12 (StataCorp, College Station, TX).
Results
Among 57,195 pregnancies meeting inclusion criteria, the background risk of stillbirth was 56/10,000 (95% CI, 42.3−72.7). SGA complicated 4217 (7.4%) pregnancies, of which 3333 (5.8%) delivered ≥37 weeks. Table 1 demonstrates relevant demographic information of the study cohort including the SGA pregnancies delivered <37 weeks, the SGA pregnancies delivered ≥37 weeks and the non-SGA population. The primary concern of this investigation was the SGA group delivered ≥37 weeks of which the average gestational age at the time of delivery was 39.1 ± 1.1 weeks. Table 2 compares maternal demographic characteristics of SGA stillbirths delivered ≥37 weeks and SGA live births delivered ≥37 weeks. There was no significant difference in maternal age, race, parity, diabetes, or hypertensive disorders, including preeclampsia, among women who delivered SGA stillbirths after 37 weeks and those who delivered SGA live births after 37 weeks. As expected, SGA stillbirths were significantly smaller at delivery than SGA live births (2370 ± 314 vs 2596 ± 237, P < .01).
| Characteristic | SGA delivered <37 wks n = 884 (1.5%) | SGA delivered ≤37 wks n = 3333 (5.8%) | Non-SGA n = 52,978 (92.6%) |
|---|---|---|---|
| Maternal age, y (SD) | 29.3 ± 6.6 | 29.0 ± 7.0 | 30.4 ± 6.2 |
| AMA | 226 (25.6) | 877 (26.3) | 15,779 (29.8) |
| Race | |||
| Black | 378 (42.8) | 1253 (37.6) | 11,370 (21.5) |
| White | 384 (43.4) | 1536 (46.1) | 33,397 (63.0) |
| Other | 122 (13.8) | 544 (16.3) | 8211 (15.5) |
| Nulliparous | 450 (50.9) | 1644 (49.3) | 19,981 (37.7) |
| Chronic hypertension | 86 (9.7) | 93 (2.8) | 1248 (2.4) |
| Preeclampsia | 327 (37.3) | 340 (10.3) | 3919 (7.5) |
| Pregestational diabetes | 37 (4.2) | 22 (0.7) | 1051 (2.0) |
| Gestational diabetes | 40 (4.6) | 139 (4.2) | 2841 (5.4) |
| Gestational age at delivery, wk | 33.4 ± 4.1 | 39.1 ± 1.1 | 38.8 ± 2.3 |
| Birthweight, g | 1601 ± 618 | 2659 ± 238 | 3397 ± 730 |
| Stillbirth, n (%) | 86 (9.7) | 20 (0.6) | 217 (0.4) |
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