Singleton birthweight by gestational age following in vitro fertilization in the United States




Background


Assisted reproductive technology has been reported to account for a disproportionate higher number of low birthweight infants, even in singleton births. Low birthweight infants occur from preterm birth, decreased intrauterine growth, or both. It is unclear whether infants conceived by in vitro fertilization (IVF) have a reduced intrauterine growth rate or intrauterine growth restriction. Growth-restricted newborns have higher perinatal morbidity and are at increased risk for adult-onset illnesses. To date, there are no national standards for birthweight percentiles by gestational week, allowing for fetal growth assessment of singletons conceived by assisted reproductive technology in the United States.


Objective


The objective of the study was to establish US singleton IVF reference standards using birthweight percentiles by gestational age for singleton live births resulting from IVF in the United States.


Study Design


We studied birthweight by completed weeks of gestation for 93,443 singleton IVF births reported to the Society for Assisted Reproductive Technologies, 2006–2010. The third to 97th birthweight percentiles per completed week of gestation for weeks between 24 and 42 were calculated and were compared with recently published birthweight percentiles by gestational age for 3,812,730 US singleton births in 2011.


Results


Smoothed birthweight for gestational age charts and curves were created for all US IVF singletons and female-male singletons from 24 to 42 weeks. Over the span of 31–41 weeks of gestation, the 10th, 50th, and 90th birthweight percentile values of IVF singletons were comparable with recently published birthweight percentile values of US singletons. At 40 completed weeks of gestation, the 10th, 50th, and 90th birthweight percentiles of all IVF singletons were 3078, 3506, and 4053 g, as compared with corresponding 3005, 3499, and 4057 g of US singletons. The 10th, 50th, and 90th birthweight percentile values for female and male IVF singletons were also comparable with US female and male singletons.


Conclusion


Birthweight percentiles per completed week of gestation of IVF and US singletons are approximately equal from 31 until 41 completed weeks, suggesting that intrauterine growth is not reduced in IVF singleton infants.


Birthweight is an anthropometric measurement used clinically in the prediction of newborn morbidity and mortality. Newborn infants who are small for gestational age (SGA; weight <10th percentile) or large for gestational age (weight >90th percentile) are at increased risk for neurological impairment, insulin resistance, cardiovascular disease, and even reproductive dysfunction later in adulthood.


Assisted reproductive technology (ART) has been reported to account for a disproportionate number of low birthweight and preterm birth infants in the United States and in other developed countries caused primarily by multiple gestations.


In vitro fertilization (IVF) singleton growth abnormalities have also been noted. In a landmark US study, the relative risk of low birthweight for IVF singletons born in 2000 was 1.5 times that of the general US population for births at 37 weeks or later. Since 2000 the incidence of multiple gestation among IVF births has declined coincidentally with a decrease in the average number of embryos transferred.


Low birthweight infants occur from preterm birth, decreased intrauterine growth, or both. Many studies addressing low birthweight in singleton IVF pregnancies do not differentiate between the two. Although it is well known that IVF pregnancies have higher rates of preterm birth, it is not as well established whether the infants conceived by IVF also have a reduced intrauterine growth rate. To date, there are no standards for birthweight percentiles by gestational week, allowing for fetal growth assessment of singletons conceived by ART in the United States. Currently, birthweight of IVF newborns is assessed using general US growth curves for all nonanomalous newborns.


The objectives of the present study were to establish US singleton IVF reference standards using birthweight percentiles by gestational age for singleton live births resulting from IVF in the United States using data more recent than 2000 from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) and to compare them with a general US population.


Materials and Methods


Data on 96,917 singleton live births following IVF treatment with fresh nondonor oocytes between January 2006 and December 2010 were provided from the SART CORS. The Society for Assisted Reproductive Technology has collected, verified, and reported to the Centers for Disease Control and Prevention IVF and birth data from more than 90% of clinics performing ART in the United States since 1992 in compliance with the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102-493, Oct. 24, 1992). Approval for this study was obtained from the Society for Assisted Reproductive Technology, the Louisiana State University Medical School New Orleans, and the Tulane University Health Sciences Center (New Orleans, LA) institutional review boards.


In the Society for Assisted Reproductive Technology data used in our study, gestational age was calculated by adding 14 days to the number of completed weeks since oocyte retrieval and fertilization. Singletons with birth defects (n = 1482), birthweights <300 g (n = 17), >6000 g (n = 6) or not recorded (n = 1058), less than 24 completed gestational weeks (n = 366), longer than 42 weeks (n = 661) and records lacking the day of embryo transfer (n = 354) were excluded. Also excluded were births resulting from transfer day 8 or later (n = 15) because of the possibility that the day of transfer was incorrect. After excluding 3474 records (3.58%) for 1 or more of the reasons listed previously, 93,443 IVF singleton births between 24 and 42 completed weeks of gestation were included for analysis.


Exclusion of outliers


A variety of methods have been used to exclude outliers in large data sets because of errors in recording gestational age or birthweight. In this study, the method of Tukey was chosen because of its applicability of more objective ways to identify outliers and its wide use in publications, including most recently in comparison of Australian and New Zealand IVF birthweights by gestational week with Australian National birthweights.


By Tukey’s methodology, birthweights that fall below the first quartile minus twice the interquartile range, or above the third quartile plus twice the interquartile range were considered as outliers and were excluded from analysis. Of 541 (0.58%) excluded records, 84% were above and 16% were below Tukey’s limits. Before 33 weeks, 8.4% of records were excluded for high birthweights compared with 0.3% after 33 weeks. The rate of exclusion for low birthweights was 0.5% before and 0.8% after 33 weeks.


After exclusion of outlier records with implausible birthweights for gestational age, a total of 92,902 births from 24 to 42 completed weeks were available to study. Of these births, 46,241 were female, 46,483 were male, and in 178 the sex was not identified. Included in the analysis are 19 birthweights ≥300 g but <500 g, all born before 30 completed weeks of gestation. Of these births, 5 resulted in neonatal deaths, survival was not reported for 2 births, and 12 survived the neonatal period.


US national birthweight comparison groups


Birthweight percentiles for US singletons between 24 and 42 weeks of gestation already have been reported in 2014 using 2011 data. In this data set, the gestational age on the birth certificate was corrected for the obstetric estimate of gestational age, providing more accurate birthweight data for gestational age. The corrected data set, published by Duryea et al included all 2011 US nonanomalous singleton births with recorded birthweights between 500 and 6000 g. The 2011 study of US National birth weight data set did not differentiate IVF from spontaneous pregnancies (estimated to be 0.8% of the data set). Given the large number of spontaneous pregnancies in the US data set, the inclusion of IVF births was not anticipated to substantially change the findings.


Data analysis and preparation of birthweight percentile charts and tables


To prepare birthweight percentiles by completed week of gestation for all IVF singleton pregnancies, we used births between 24 and 42 weeks of gestation, to be comparable with recently published birthweight percentiles for US singletons. We calculated average birthweight with SD and smoothed third, fifth, 10th, 25th, 50th, 75th, 90th, 95th, and 97th percentiles. Smoothing was done by using the polynomial curve that best fit the IVF data. Our comparison group revised US birthweight 10th, 50th, and 90th percentiles for singleton births between 24 and 42 weeks of gestation and were superimposed on IVF percentile curves for comparison with IVF 10th, 50th, and 90th percentiles. We also present smoothed birthweight percentiles by week of gestation for IVF females and males.




Results


The demographic characteristics of IVF singletons from 2006 to 2010 and US singletons in 2011 are shown in Table 1 . The proportion of male births was slightly higher in US singletons than in IVF singletons. There were certain demographic population differences in the IVF singleton group compared with US singletons in 2011. IVF mothers tended to be older and had more preterm births and spontaneous abortions. A greater proportion of the IVF singleton group gave their race as white.



Table 1

Population characteristics of IVF and US singletons































































































































All IVF singleton, 2006–2010 US singleton, 2011 a
Number % Number %
93,926 100 3,812,730 100
Gender
Female 46,476 49.7 1,929,538 48.8
Male 47,038 50.3 2,024,052 51.2
Maternal age, y
<30 14,736 15.7 2,386,529 60.5
30–34 35,392 37.7 986,682 25.0
35–39 34,311 36.5 4,638,391 11.8
40–44 9494 10.1 108,920 2.8
Parity
Primiparous 43,882 46.8 3,139,260 70.5
>1 PTB or Ab 36,807 38.9 73,055 1.6
>1 Term only 12,997 13.7 1,239,690 27.8
Ethnicity
White 45,319 75.8 3,020,355 62.0
Afro-American 3232 5.4 632,901 13.0
Hispanic 3983 6.7 918,129 18.8
Asian 5842 9.8 253,915 5.2
Other b 1350 2.2 46,419 1.0

Ab , abortion; IVF , in vitro fertilization; PTB , preterm birth.

Dickey et al. Birthweight of in vitro fertilization singletons. Am J Obstet Gynecol 2016 .

a US natality reports 2011 (includes all nonanomalous births, including IVF)


b Other (American Indian, Alaskan, Hawaiian, Pacific Islander, or more than one reported).



Figure 1 and Table 2 present the detailed percentiles of birthweight per completed gestational week for IVF singletons after statistical smoothing and the corresponding 10th, 50th, and 90th percentiles for all US singletons. From weeks 24 to 41, smoothed IVF singleton and US singleton 50th and 90th birthweight percentiles are nearly identical; this is particularly true for week 30 and 39. From weeks 31 to 41, smoothed IVF singleton and US singleton 10th birthweight percentiles are also nearly identical; however, before 31 weeks the 10th percentile for IVF singletons averaged 11% lower that for US singletons.




Figure


Singleton birthweight percentiles: IVF, 2006–2010 smoothed, United States, 2011

Shown are the singleton birthweight percentiles for IVF, 2006–2010 smoothed ( blue ), and the United States 2011 ( red ).

IVF , in vitro fertilization.

Dickey et al. Birthweight of in vitro fertilization singletons. Am J Obstet Gynecol 2016 .

Data from Duryea et al.


Table 2

Singletons birthweight percentiles 24–42 weeks: IVF, 2006-2010 smoothed, United States, 2011 a































































































































































































































































































































































IVF singleton, 2006–2010 United States, 2011 a
Number and average Percentile smoothed Percentile
Week n Average, g SD Third Fifth 10th 25th 50th 75th 90th 95th 97th 10th 50th 90th
24 100 627 141 393 416 470 566 669 735 793 854 941 567 680 850
25 148 747 148 425 452 512 618 759 825 910 979 1039 584 765 938
26 130 826 214 456 483 566 705 855 952 1050 1133 1200 637 872 1080
27 144 956 218 500 550 645 807 976 1090 1219 1311 1386 719 997 1260
28 181 1093 239 596 666 743 923 1106 1247 1389 1500 1611 822 1138 1462
29 205 1265 319 691 781 880 1072 1275 1434 1627 1753 1860 939 1290 1672
30 300 1391 317 827 902 1024 1223 1452 1627 1843 1990 2131 1068 1455 1883
31 358 1661 340 980 1062 1200 1410 1644 1855 2115 2296 2447 1214 1635 2101
32 510 1851 391 1143 1236 1373 1590 1843 2084 2365 2570 2721 1380 1833 2331
33 771 2088 412 1346 1437 1587 1814 2069 2324 2636 2835 2989 1573 2053 2579
34 1410 2348 428 1559 1654 1814 2042 2325 2584 2892 3100 3268 1793 2296 2846
35 2420 2592 447 1776 1882 2041 2277 2560 2837 3124 3357 3509 2030 2549 3119
36 4591 2799 434 2015 2098 2267 2500 2778 3061 3368 3571 3727 2270 2797 3380
37 9260 3005 434 2245 2337 2488 2741 3012 3288 3585 3784 3931 2500 3025 3612
38 19,419 3240 427 2466 2534 2721 2948 3231 3512 3782 3968 4089 2706 3219 3799
39 29,193 3398 421 2664 2749 2880 3118 3373 3669 3941 4138 4239 2877 3374 3941
40 17,771 3505 420 2779 2860 3024 3241 3506 3795 4053 4260 4345 3005 3499 4057
41 5565 3613 428 2807 2900 3078 3307 3590 3880 4154 4327 4420 3082 3600 4167
42 426 4458 464 2721 2806 2993 3260 3571 3851 4167 4329 4422 3099 3686 4290

Dickey et al. Birthweight of in vitro fertilization singletons. Am J Obstet Gynecol 2016 .

a Reproduced, with permission, from Duryea et al.



After week 41, 10th, 50th, and 90th birthweight percentiles decrease or plateau for IVF singletons but continue to increase for US singletons. At 40 completed weeks of gestation, the 50th birthweight percentiles of all IVF singletons averaged 3505 g compared with 3499 g for US singletons. The 10th and 90th percentiles of birthweight for IVF singletons at 40 weeks are 3024 and 4053 g, respectively, compared with 3005 and 4057 g for US singletons.


The detailed percentiles of birthweight per completed gestational week for IVF female and male singletons after statistical smoothing and the corresponding 10th, 50th, and 90th percentiles for US female and male singletons are shown in Tables 3 and 4 . At 40 completed weeks of gestation, 50th birthweight percentiles of IVF female and male singletons averaged 3438 g and 3578 g, respectively, compared with 3431 and 3572 g, respectively, for US female and male singletons.



Table 3

Female singletons birthweight percentiles, 24–42 weeks: IVF, 2006-2010, smoothed, United States, 2011 a































































































































































































































































































































































IVF singleton, female, 2006–2010 United States, 2011 a
Number and average Percentile smoothed Percentile
Week n Average, g SD Third Fifth 10th 25th 50th 75th 90th 95th 97th 10th 50th 90th
24 47 593 109 378 403 475 521 595 666 709 758 782 545 652 820
25 73 721 123 391 436 500 605 704 800 865 919 942 557 740 912
26 66 780 205 424 475 551 681 804 934 1018 1080 1110 622 845 1047
27 71 909 244 481 528 628 773 935 1080 1190 1263 1309 702 967 1217
28 104 1060 230 559 620 727 896 1077 1233 1360 1462 1524 800 1102 1410
29 100 1223 319 666 735 835 1020 1219 1400 1562 1692 1784 911 1250 1616
30 125 1356 309 789 873 978 1172 1378 1585 1776 1922 2037 1033 1411 1831
31 167 1589 315 926 1026 1149 1363 1559 1785 1991 2167 2320 1179 1588 2055
32 250 1807 392 1100 1204 1325 1554 1776 2013 2242 2435 2619 1335 1784 2291
33 347 2030 460 1304 1417 1539 1769 2014 2257 2511 2718 2894 1526 2001 2540
34 654 2272 426 1516 1639 1761 2012 2236 2500 2757 2979 3162 1747 2240 2801
35 1095 2536 438 1746 1871 1991 2236 2495 2757 3009 3239 3415 1987 2489 3063
36 2182 2738 421 1983 2106 2228 2466 2722 3004 3260 3458 3629 2230 2734 3311
37 4395 2931 422 2221 2305 2450 2688 2929 3224 3500 3700 3836 2461 2961 3533
38 9408 3172 411 2438 2523 2665 2891 3155 3430 3713 3883 4000 2677 3155 3714
39 14,715 3333 409 2608 2688 2834 3061 3316 3600 3882 4053 4142 2829 3311 3856
40 9107 3438 404 2721 2806 2940 3175 3430 3713 4005 4173 4242 2950 3431 3973
41 2863 3530 416 2757 2863 3005 3254 3515 3783 4082 4242 4300 3020 3517 4082
42 211 3496 428 2728 2833 2948 3232 3487 3742 4082 4250 4311 3033 3572 4198

Dickey et al. Birthweight of in vitro fertilization singletons. Am J Obstet Gynecol 2016 .

a United States: Reproduced, with permission, from Duryea et al.



Table 4

Male singletons birth weight percentiles 24–42 weeks: IVF, 2006–2010, smoothed, United States, 2011 a































































































































































































































































































































































IVF singleton male: 2006–2010 United States, 2011 a
Number and average Percentile smoothed Percentile
Week n Average, g SD Third Fifth 10th 25th 50th 75th 90th 95th 97th 10th 50th 90th
24 53 706 216 398 441 493 595 708 770 830 882 926 580 706 855
25 74 766 155 433 472 566 680 793 878 936 973 1021 595 790 964
26 63 863 196 467 528 631 779 907 1001 1073 1116 1159 652 900 1110
27 75 1007 187 516 571 718 882 1020 1142 1211 1263 1341 741 1031 1284
28 76 1131 216 580 649 813 992 1151 1283 1389 1462 1540 851 1177 1479
29 101 1278 270 683 761 936 1125 1304 1445 1600 1700 1791 972 1332 1686
30 171 1421 320 825 895 1073 1272 1471 1635 1834 1972 2042 1102 1496 1901
31 188 1709 483 978 1038 1263 1462 1670 1869 2076 2229 2336 1247 1674 2128
32 257 1876 385 1163 1228 1436 1672 1889 2097 2362 2540 2647 1414 1871 2367
33 426 2142 399 1361 1446 1658 1871 2137 2353 2638 2834 2933 1608 2091 2622
34 750 2413 424 1615 1687 1860 2100 2381 2600 2900 3114 3209 1834 2335 2892
35 1300 2633 435 1843 1938 2100 2352 2608 2872 3175 3373 3486 2078 2592 3165
36 2397 2854 441 2076 2154 2324 2569 2835 3118 3426 3625 3746 2325 2846 3426
37 4819 3072 432 2318 2405 2569 2806 3061 3345 3651 3841 3971 2560 3082 3661
38 9928 3304 433 2517 2608 2778 3004 3288 3564 3856 4026 4152 2766 3283 3856
39 14,372 3466 423 2708 2806 2948 3175 3458 3742 4025 4195 4309 2935 3445 4010
40 8577 3578 425 2837 2933 3071 3288 3571 3884 4152 4309 4412 3062 3572 4135
41 2689 3690 428 2889 3004 3140 3356 3668 3945 4252 4400 4481 3143 3669 4242
42 212 3634 482 2785 2889 3062 3316 3628 3913 4230 4377 4464 3175 3740 4345

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May 4, 2017 | Posted by in GYNECOLOGY | Comments Off on Singleton birthweight by gestational age following in vitro fertilization in the United States

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