We sought to evaluate the risk of intrauterine fetal death (IUFD) in small-for-gestational-age (SGA) fetuses.
We analyzed a retrospective cohort of all births in the United States in 2005, as recorded in a national database. We calculated the risk of IUFD within 3 sets of SGA threshold categories as well as within non-SGA pregnancies using the number of at-risk fetuses as the denominator.
The risk of IUFD increased with gestational age and was inversely proportional to percentile of birthweight for gestational age. The risk for IUFD in those <3rd percentile was as high as 58.0 IUFDs per 10,000 at-risk fetuses, 43.9 for <5th percentile, and 26.3 for <10th percentile compared to 5.1 for non-SGA gestations.
There is an increase in the risk of IUFD in SGA fetuses compared to non-SGA fetuses at all gestational ages with the greatest risk demonstrated in the lowest percentile cohort evaluated.
The concept of appropriate weight for gestational age was first described in the 1960s with the development of birthweight nomograms according to gestational week. Subsequently, small-for-gestational-age (SGA) infants were defined as those with birthweights ≤10th percentile for their gestational age. Using this classification system, it was observed that infants born SGA had increased rates of perinatal morbidity and mortality at each gestational age relative to those infants not SGA.
While these studies and others have made the case that altered fetal growth is associated with adverse perinatal outcomes, recent studies have attempted to determine whether or not the 10th percentile is a clinically useful cutoff. Additionally, research has focused on identifying indicators of pathologic growth restriction compared to normal growth in a constitutionally small fetus. The addition of Doppler velocimetry to perinatal assessment has greatly enhanced clinicians’ ability to identify fetuses with pathologic growth restriction related to altered umbilical artery blood flow. Moreover, the routine use of Doppler in high-risk pregnancies decreases induction of labor and antepartum admission, suggesting that in the absence of abnormal Doppler findings SGA pregnancies may benefit from expectant management rather than early delivery.
Despite these advances, clinical decision making related to timing of delivery for SGA pregnancies remains a challenge for many clinicians. Consider, for instance, a 34-week pregnancy with reassuring umbilical artery Doppler, but an estimated fetal weight (EFW) indicating growth <3rd percentile. The morbidity associated with late preterm delivery is significant and yet many clinicians would be hesitant to commit to expectant management in a fetus at such a low centile. Given this clinical uncertainty, we have attempted to focus on the risk of intrauterine fetal death (IUFD) in SGA pregnancies with a goal of providing estimates of risk for fetuses <3rd, <5th, and <10th percentiles compared to non-SGA pregnancies by week of gestation. To further evaluate and refine the significance of fetal growth, we have also compared the risk of fetal death by cohorts of fetuses <3rd percentile, 3rd-5th percentile, and 5th-10th percentile compared to non-SGA pregnancies. It is our hope that having greater resolution of the risks faced by SGA pregnancies will aid in patient counseling and clinical decision making.
Materials and Methods
To examine the risk of IUFD at a given week of gestation based on fetal growth, we conducted a retrospective cohort study of all singleton neonates born to women in the United States in 2005. The period-linked live birth and fetal death files from the National Center for Health Statistics (NCHS) (Centers for Disease Control and Prevention) for the year 2005 were exported and aggregated to form a single database comprising all fetal deaths and births from Jan. 1 through Dec. 31, 2005. Data were divided based on calculations used to categorize fetuses ≤3rd, 3rd-5th, or 5th-10th percentile for birthweights and those fetuses at or above all remaining percentiles for birthweights. We excluded all multiple gestations and major congenital anomalies. Approval for this study was obtained from the Oregon Health and Science University Institutional Review Board.
The NCHS data set included month and year of birth, gestational age at delivery, birthweight, delivery method, and plurality. Gestational age was calculated according to delivery date and last menstrual period (LMP). If that information was unavailable the clinical estimate of gestational age on the birth certificate was used (the standard technique for data presentation in NCHS publications).
Fetal death was defined as IUFD prior to delivery, excluding cases of voluntary termination. Multiple gestations, anomalous fetuses, and all deliveries <24 weeks’ gestation and >41 6/7 weeks’ gestation were excluded.
Using the entire population of 2005 singleton births without congenital anomalies as the reference, we generated 3 sets of SGA thresholds based on percentiles of birthweight for gestational age: the <10th percentile (as SGA is commonly defined), the <5th percentile, and the <3rd percentile. The risk of IUFD was calculated out of the population of ongoing pregnancies representing at-risk fetuses at a particular gestational age. Thus, risk of fetal death was calculated as the number of IUFDs at a particular week of gestation divided by all ongoing pregnancies at a given gestational age and expressed as rates per 10,000. The number of ongoing pregnancies at the beginning of each week of gestation was calculated by consecutive subtractions of deliveries from the previous week of gestation, live born or otherwise. When examining the risk of IUFD at the 3rd percentile, this cohort included all neonates and stillbirths born with a birthweight <3rd percentile. This was similar for the 5th percentile, 10th percentile, and the non-SGA groups.
The NCHS database included 3,399,816 nonanomalous singletons delivered between 24 0/7-41 6/7 weeks’ gestation. Of these, 96,825 were <3rd percentile, 157,922 were <5th percentile, 322,161 were <10th percentile, and 3,077,655 were ≥10th percentile. Maternal age, parity, race, smoking history, and educational status differed in the birthweight groups ( Table 1 ).
|Characteristic||<3rd percentile n (%)||<5th percentile n (%)||<10th percentile n (%)||≥10th percentile n (%)|
|Nulliparous||47,988 (50.5)||77,968 (50.1)||155,889 (48.9)||1,136,112 (39.1)|
|Primiparous, multiparous||47,040 (49.5)||77,583 (49.9)||162,699 (51.1)||1,763,472 (60.9)|
|Maternal age, y|
|<35||85,559 (88.4)||139,871 (88.6)||285,855 (87.6)||2,504,635 (86.0)|
|≥35||11,266 (11.6)||18,051 (11.4)||36,306 (12.4)||408,781 (14.0)|
|White (non-Hispanic)||43,457 (44.9)||71,303 (45.2)||148,169 (46.0)||1,659,279 (57)|
|Black||23,780 (24.6)||37,506 (23.7)||72,010 (22.4)||373,685 (12.8)|
|Hispanic||20,399 (21.1)||33,644 (21.3)||69,770 (21.7)||652,888 (22.4)|
|Asian/Pacific Islander||6592 (6.8)||11,347 (7.2)||24,048 (7.5)||157,947 (5.4)|
|Native American||883 (0.9)||1373 (0.9)||2732 (0.8)||28,014 (1)|
|Other||1714 (1.8)||2749 (1.7)||5432 (1.7)||41,603 (1.4)|
|Unwed||50,255 (52.4)||80,309 (51.2)||156,714 (48.9)||1,030,732 (35.4)|
|Married||45,685 (47.6)||76,522 (48.8)||164,056 (51.1)||1,881,112 (64.6)|
|No college||60,299 (63.3)||96,632 (62.2)||191,150 (60.2)||1,420,154 (49.3)|
|Some college||34,892 (36.7)||58,787 (37.8)||126,267 (39.8)||1,458,554 (50.7)|
|None||61,348 (79.3)||100,950 (80.2)||211,183 (82.1)||2,113,975 (90.8)|
|Any||15,974 (20.7)||24,922 (19.8)||46,063 (17.9)||215,031 (9.2)|
The risk of IUFD is greater for lower percentile thresholds of SGA pregnancies at all weeks of gestation ( Table 2 ). The 3rd-percentile risk reaches a nadir at 31 weeks’ gestational age with a risk of 12.2 IUFDs per 10,000 at-risk fetuses. The 5th, 10th, and ≥10th percentiles all reached nadirs at 32 weeks with risks of 9.3, 6.4, and 0.8 IUFDs per 10,000 at-risk fetuses, respectively. As the risk begins to climb after 32 weeks, the rate of change is fairly stable until 39 weeks, after which point the steepness of the slope increases. Maximum risk of IUFD was among postterm pregnancies for all percentile groups with the 3rd percentile as high as 58.0 IUFDs per 10,000 at-risk fetuses, 43.9 for the 5th percentile, and 26.3 for the 10th percentile compared to 5.1 for non-SGA gestations.
|GA, wk||Deliveries||OP||Fetal deaths||Risk of fetal death (per 10,000 at-risk pregnancies)||95% CI||GA, wk||Deliveries||OP||Fetal deaths||Risk of fetal death (per 10,000 OP)||95% CI|
|<3rd percentile||<5th percentile|
|<10th percentile||≥10th percentile|
To further characterize those fetuses facing the greatest risk of IUFD, additional comparisons were made using birthweights between the 3rd-5th percentiles and between the 5th-10th percentiles ( Table 3 ). Unsurprisingly, the 3rd-percentile group faced the highest risk with an approximately 3-fold increased risk over the 3rd-5th–percentile group in nearly all gestational ages and a 4- to 7-fold increased risk over the 5th-10th–percentile group. When presented graphically, the risk of IUFD is J-shaped for each category with the greatest risk of IUFD in the late-term and postterm periods ( Figure ).
|3rd-5th percentiles||5th-10th percentiles|
|GA, wk||Deliveries||Ongoing pregnancies||Fetal deaths||Risk of fetal death (per 10,000 at-risk pregnancies)||95% CI||GA, wk||Deliveries||Ongoing pregnancies||Fetal deaths||Risk of fetal death (per 10,000 at-risk pregnancies)||95% CI|