The risk of intrauterine fetal death in the small-for-gestational-age fetus




Objective


We sought to evaluate the risk of intrauterine fetal death (IUFD) in small-for-gestational-age (SGA) fetuses.


Study Design


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.


Results


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.


Conclusion


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.




Results


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 ).



TABLE 1

Maternal characteristics














































































































































Characteristic <3rd percentile n (%) <5th percentile n (%) <10th percentile n (%) ≥10th percentile n (%)
Parity
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)
Maternal race
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)
Marital status
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)
Educational status
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)
Tobacco use
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)

Pilliod. The risk of intrauterine fetal death in the SGA fetus. Am J Obstet Gynecol 2012.


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.



TABLE 2

Intrauterine fetal death risk by <3rd, <5th, <10th, and ≥10th percentiles











































































































































































































































































































































































































































































































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
24 282 96,825 207 21.38 18.47–24.29 24 382 157,922 253 16.02 14.05–17.99
25 260 96,543 174 18.02 15.35–20.70 25 343 157,540 210 13.33 11.53–15.13
26 261 96,283 168 17.45 14.81–20.08 26 375 157,197 211 13.42 11.61–15.23
27 239 96,022 135 14.06 11.69–16.43 27 336 156,822 164 10.46 8.86–12.06
28 273 95,783 127 13.26 10.95–15.56 28 400 156,486 155 9.91 8.35–11.46
29 322 95,510 148 15.50 13.00–17.99 29 469 156,086 176 11.28 9.61–12.94
30 399 95,188 156 16.39 13.82–19.96 30 588 155,617 179 11.50 9.82–13.19
31 406 94,789 116 12.24 10.01–14.46 31 667 155,029 153 9.87 8.31–11.43
32 554 94,383 119 12.61 10.43–14.87 32 861 154,362 143 9.26 7.75–10.78
33 852 93,829 152 16.20 13.63–18.77 33 1331 153,501 185 12.05 10.32–13.79
34 1427 92,977 161 17.32 14.64–19.99 34 2300 152,170 193 12.68 10.89–14.47
35 2319 91,550 168 18.35 15.58–21.12 35 3708 149,870 207 13.81 11.93–16.69
36 4187 89,231 191 21.41 18.37–24.44 36 6665 146,162 214 14.64 12.68–16.60
37 9018 85,044 159 18.70 15.79–21.60 37 14,045 139,497 193 13.84 11.88–15.79
38 18,376 76,026 176 23.15 19.73–26.57 38 32,016 125,452 225 17.94 15.59–20.28
39 27,426 57,650 186 32.26 27.63–36.89 39 42,776 93,436 212 22.69 19.64–25.74
40 20,567 30,224 98 32.42 26.02–38.83 40 35,490 50,660 127 25.07 20.71–29.42
41 9657 9657 56 57.99 42.84–73.13 41 15,170 15,170 65 42.85 32.45–53.24
<10th percentile ≥10th percentile
24 578 322,161 315 9.78 8.70–10.86 24 2929 3,077,655 423 1.37 1.24–1.51
25 567 321,583 277 8.61 7.60–9.63 25 3142 3,074,726 368 1.20 1.07–1.32
26 590 321,016 257 8.01 7.03–8.98 26 3514 3,071,584 342 1.11 1.00–1.23
27 552 320,426 214 6.68 5.78–7.57 27 3651 3,068,070 333 1.09 0.97–1.20
28 705 319,874 214 6.69 5.79–7.59 28 4974 3,064,419 300 0.98 0.87–1.09
29 805 319,169 228 7.14 6.22–8.07 29 5879 3,059,445 278 0.91 0.80–1.02
30 1069 318,364 243 7.63 6.67–8.59 30 8165 3,053,566 297 0.97 0.86–1.08
31 1216 317,295 209 6.59 5.69–7.48 31 10,233 3,045,401 284 0.93 0.82–1.04
32 1679 316,079 203 6.42 5.54–7.31 32 14,523 3,035,168 237 0.78 0.68–0.88
33 2527 314,400 242 7.70 6.73–8.67 33 22,535 3,020,645 283 0.94 0.83–1.05
34 4348 311,873 251 8.05 7.05–9.04 34 40,488 2,998,110 294 0.98 0.87–1.09
35 7462 307,525 255 8.29 7.27–9.31 35 69,196 2,957,622 310 1.05 0.93–1.16
36 13,214 300,063 278 9.26 8.18–10.35 36 131,742 2,888,426 364 1.26 1.13–1.39
37 28,767 286,849 253 8.82 7.73–9.91 37 281,877 2,756,684 403 1.46 1.32–1.60
38 66,016 258,082 287 11.12 9.83–12.41 38 626,335 2,474,807 473 1.91 1.74–2.08
39 91,295 192,066 256 13.33 11.70–14.96 39 869,260 1,848,472 420 2.27 2.05–2.49
40 68,862 100,771 165 16.37 13.88–18.87 40 673,874 979,212 328 3.35 2.99–3.71
41 31,909 31,909 84 26.32 20.70–31.95 41 305,338 305,338 155 5.08 4.28–5.88

CI, confidence interval; GA, gestational age; OP, ongoing pregnancies.

Pilliod. The risk of intrauterine fetal death in the SGA fetus. Am J Obstet Gynecol 2012.


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 ).



TABLE 3

Intrauterine fetal death risk by 3rd-5th and 5th-10th percentile groups






























































































































































































































































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
24 54 60,529 46 7.60 5.40–9.80 24 132 163,269 61 3.74 2.80–4.67
25 47 60,475 36 5.95 4.01–7.90 25 155 163,137 67 4.11 3.12–5.09
26 67 60,428 43 7.12 4.99–9.24 26 169 162,982 46 2.82 2.01–3.64
27 68 60,361 29 4.80 3.06–6.55 27 166 162,813 50 3.07 2.22–3.92
28 99 60,293 28 4.64 2.92–6.36 28 246 162,647 59 3.63 2.70–4.55
29 119 60,194 28 4.65 2.93–6.37 29 284 162,401 52 3.20 2.33–4.07
30 166 60,075 23 3.83 2.26–5.39 30 417 162,117 64 3.95 2.98–4.91
31 224 59,909 37 6.18 4.19–8.17 31 493 161,700 56 3.46 2.56–4.37
32 283 59,685 24 4.02 2.41–5.63 32 758 161,207 60 3.72 2.78–4.66
33 446 59,402 33 5.56 3.66–7.45 33 1139 160,449 57 3.55 2.63–4.47
34 841 58,956 32 5.43 3.55–7.31 34 1990 159,310 58 3.64 2.70–4.58
35 1350 58,115 39 6.71 4.61–8.82 35 3706 157,320 48 3.05 2.19–3.91
36 2455 56,765 23 4.05 2.40–5.71 36 6485 153,614 64 4.17 3.15–5.19
37 4997 54,310 34 6.26 4.16–8.36 37 14,662 147,129 60 4.08 3.05–5.11
38 13,591 49,313 49 9.94 7.16–12.72 38 33,938 132,467 62 4.68 3.52–5.85
39 15,324 35,722 26 7.28 4.48–10.08 39 48,475 98,529 44 4.47 3.15–5.78
40 14,894 20,398 29 14.22 9.05–19.39 40 33,334 50,054 38 7.59 5.18–10.00
41 5504 5504 9 16.35 5.68–27.03 41 16,720 16,720 19 11.36 6.26–16.47

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May 15, 2017 | Posted by in GYNECOLOGY | Comments Off on The risk of intrauterine fetal death in the small-for-gestational-age fetus

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