Objective
To analyze the effects of preconception maternal height and weight on the risk of preterm singleton and twin births resulting from in vitro fertilization (IVF).
Study Design
We performed a retrospective cohort analysis of the incidence of very early preterm birth (VEPTB), early preterm birth (EPTB), and preterm birth (PTB), before 28, 32, and 37 completed weeks, respectively, in 60,232 singleton and 24,111 twin live births using 2008-2010 live birth outcome data from the Society for Reproductive Technology Clinic Outcome Reporting System.
Result
Maternal obesity is associated with significantly increased risk of VEPTB, EPTB, and PTB in pregnancies conceived by IVF. For morbidly obese women (body mass index ≥35) with singletons, rates of VEPTB, EPTB, and PTB were 1.7%, 3.6%, and 16.4%, with adjusted risk ratios (aRRs) and 95% confidence levels (CIs) of 2.6 (1.8–3.6), 2.2 (1.8–2.6), and 1.5 (1.4–1.7) using corresponding rates for normal body mass index (95% CI, 18.6–24.9) as referent. For morbidly obese women with twins, rate of VEPTB and EPTB were 6.5% and 12.5%, with aRRs and 95% CIs of 2.4 (1.8–3.0) and 1.5 (1.3–1.8). For singletons, the rate of PTB for short stature women (<150 cm) was 14.2%, as compared with 11.8% in those women with height ranging between 160–167 cm (referent), with aRRs and 95% CIs of 1.2 (1.0–1.4).
Conclusion
Preconception maternal obesity and short stature are associated with significantly increased risk of VEPTB and early preterm singleton and twin births in pregnancies resulting from IVF.
In the United States, preterm births <37 weeks’ gestation account for 68% of all infant deaths in the first year of life. Most of these deaths (54%) occur in infants born before 32 completed weeks of gestation. Early preterm births <32 weeks occur in 1.6% of singleton pregnancies and in 11.4% of twin pregnancies in the general population. Multiple gestations resulting from in vitro fertilization (IVF) and other assisted reproductive technologies (ART) account for nearly 17% of all twin births in the United States and are a leading cause of preterm birth. Elective single embryo transfer (eSET) reduces the risk of twin births but it has been argued that a mandatory SET policy would multiply cost and discomfort for couples who desire 2 children and have no physical impediment to successful completion of a twin pregnancy.
In 2012, we published a study designed to determine whether obese and short stature women were at increased risk of preterm birth compared with women of normal weight and height using the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) report of births resulting from IVF in the United States from 2006 to 2008. The results of that study were compromised by the small percentage of complete records, 2006 (10%), 2007 (37%), and 2008 (82%), and by the method of calculating length of gestation from the date of embryo transfer that did not account for differences in the number of days that embryos remained in cultured. In addition, a greater percentage of patients were obese in 2006 and 2007, compared with 2008, suggesting the possibility of selective entry. The purpose of this study was to reanalyze the effects of preconception maternal height and weight on the risk of preterm singleton and twin births resulting from IVF using SART CORS records for 2008 to 2010 with adjustment for the number of days that embryos remained in culture. Complete height and weight information was entered in greater than 82% of 2008-2010 records doubling the number of records suitable for analysis compared to our earlier study.
Materials and Methods
Study population
The records from the SART CORS dataset included all 60,693 singleton and 25,488 twin births resulting from fresh nondonor oocytes IVF cycles for the years 2008-2010. Data from more than 90% of clinics performing ART in the United States has been collected, verified by SART and reported to the Centers for Disease Control and Prevention (CDC) since 1992 in compliance with the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102-493, 24 October 1992). Approval for this study was obtained from SART and the Louisiana State University School of Medicine and Tulane University institutional review boards.
Inclusion and exclusion criteria
Gestational age (GA) provided by SART CORS was calculated by adding 14 days to the difference between birth and the day oocytes were inseminated to make GA comparable with births in the general population. Records were excluded from analysis if GA was less than 20 completed weeks (140 days) or more than 44 completed weeks (308 days), if body mass index (BMI) was <14 or greater than 60 (kg/m 2 ) or could not be calculated because of missing height or weight, if height was <120 cm (48 inches) or >215 cm (84 inches) and if weight was <36 kg (80 lbs) or ≥150 kg (350 lbs).
Only live born singletons with 1 initial heart rate and live born twins with 2 initial heart rates on ultrasound were used for analysis. After exclusions, 45,342 singleton and 19,549 twin records were included in the analysis. There were no significant differences in average GA between included records and records excluded for missing or out of range height, weight, or BMI.
Statistical analysis
Analysis of variance (ANOVA) was used to compare the difference in mean GA in days within each group of height, weight, and BMI. The χ 2 test and χ 2 test for trend were used to compare the percent of very early preterm (VEPTB; ≥20 and <28 completed weeks), early preterm (EPTB; ≥20 and <32 completed weeks), and preterm (PTB; ≥20 and <37 completed weeks) deliveries between each subgroup of height, weight, and BMI. Multiple log-Poisson regression was used to assess the effects of maternal height, weight, and BMI on the risk of VEPTB, EPTB, and PTBs and to control for confounding. We adjusted for maternal age, race, gravidity, smoking status, use of intracytoplasmic sperm injection, day of embryo transfer, number of embryo transfer, infant sex, and prior spontaneous abortion. The adjusted relative risks (aRRs) and 95% confidence intervals (CIs) are derived from the coefficients of the log-Poisson models and their standard errors. All P values were 2-tailed, and the significance level selected was .05. Statistical analyses were performed using SAS, version 9.1 (SAS Institute Inc, Cary, NC).
Results
Singleton pregnancies
Table presents the aRRs with 95% CIs of preterm birth according to height, weight, and BMI for singletons and twins. For singletons, the overall rate of VEPTB, EPTB, and PTB were 0.8%, 1.9%, and 11.8%, respectively. Maternal height was inversely associated with risk of PTB. For women less than 150 cm tall, the rates of VEPTB, EPTB, and PTBs were 1.0%, 2.4%, and 14.2% respectively. For women taller than 175 cm, the rates of VEPTB, EPTB, and PTBs were 0.5%, 1.3% and 9.5%, respectively. With women of average height (160-167 cm) as referent, after adjustment for confounding variables, the aRRs and 95% CIs of VEPTB, EPTB, and PTBs in women with height ≥176 cm were 0.5 (0.3–0.8), 0.6 (0.43–0.8), and 0.7 (0.7–0.8), suggesting that height ≥176 cm is protective against PTBs.
| Variable | n | Gestational days, mean (SD) | % VEPTB <28 wks, aRR (95% CI) a | % EPTB <32 wks, aRR (95% CI) a | % PTB <37 wks, aRR (95% CI) a | ||||
|---|---|---|---|---|---|---|---|---|---|
| Singleton | All | 45,342 | 271.2 (15.7) | 0.8 | 1.9 | 11.8 | |||
| Height, cm | (in) | ||||||||
| <150 | (>60) | 943 | 269.5 (16.6) | 1.0 | 1.3 (0.6–2.4) | 2.4 | 1.3 (0.8–1.9) | 14.2 | 1.2 (1.0–1.4) c |
| 150-159 | (60-62) | 8568 | 270.1 (16.4) | 1.0 | 1.3 (1.0–1.7) b | 2.1 | 1.1 (0.9–1.3) | 13.8 | 1.2 (1.1–1.3) c |
| 160-167 | (63-65) | 18,029 | 271.1 (15.6) | 0.8 | Referent | 1.9 | Referent | 11.8 | Referent |
| 168-175 | (66-68) | 13,762 | 271.6 (15.7) | 0.8 | 0.9 (0.7–1.2) | 2.0 | 1.0 (0.8–1.1) | 11.2 | 0.9 (0.9–1.0) c |
| ≥176 | (≥69) | 4040 | 272.4 (13.9) | 0.5 | 0.5 (0.3–0.8) c | 1.3 | 0.7 (0.4–0.8) c | 9.5 | 0.7 (0.7–0.8) c |
| P value | < .001 (ANOVA) | .012 (χ 2 ) | .012 (χ 2 ) | < .001 (χ 2 ) | |||||
| Weight, kg | (lbs) | ||||||||
| <50 | (<110) | 2088 | 270.5 (15.5) | 0.8 | 1.3 (0.8–2.2) | 2.1 | 1.4 (1.0–1.9) b | 12.7 | 1.1 (1.0–1.3) |
| 50-63 | (110-139) | 19,144 | 271.9 (14.3) | 0.5 | Referent | 1.4 | Referent | 10.6 | Referent |
| 64-76 | (140-169) | 14,418 | 271.5 (15.6) | 0.8 | 1.7 (1.3–2.2) c | 1.9 | 1.4 (1.2–1.6) c | 11.3 | 1.1 (1.0–1.2) c |
| 77-89 | (170-199) | 5692 | 269.8 (17.5) | 1.2 | 2.3 (1.7–3.2) c | 2.8 | 1.9 (1.6–2.4) c | 14.0 | 1.3 (1.2–1.4) c |
| ≥90 | (≥200) | 4000 | 268.6 (18.7) | 1.6 | 3.2 (2.3–4.4) c | 3.3 | 2.4 (1.9–2.9) c | 15.5 | 1.5 (1.4–1.6) c |
| P value | < .001 (ANOVA) | < .001 (χ 2 ) | < .001 (χ 2 ) | < .001 (χ 2 ) | |||||
| BMI, kg/m 2 | |||||||||
| 12.0-18.4 underweight | 1393 | 271.5 (14.0) | 0.4 | 0.6 (0.2–1.5) | 1.4 | 0.9 (0.6–1.5) | 11.4 | 1.1 (1.0–1.3) | |
| 18.5-24.9 normal | 26,661 | 272.1 (14.4) | 0.6 | Referent | 1.5 | Referent | 10.3 | Referent | |
| 25.0-29.9 overweight | 10,258 | 270.4 (16.7) | 1.0 | 1.6 (1.2–2.1) c | 2.4 | 1.5 (1.3–1.8) c | 13.2 | 1.2 (1.2–1.3) c | |
| 30.0-34.9 obese | 4266 | 269.0 (18.3) | 1.4 | 2.1 (1.6–2.9) c | 3.1 | 1.9 (1.6–2.3) c | 15.1 | 1.4 (1.3–1.5) c | |
| ≥35 morbidly obese | 2764 | 268.0 (19.1) | 1.7 | 2.6 (1.8–3.6) c | 3.6 | 2.2 (1.8–2.8) c | 16.4 | 1.5 (1.4–1.7) c | |
| P value | < .001 (ANOVA) | < .001 (χ 2 ) | < .001 (χ 2 ) | < .001(χ 2 ) | |||||
| Twins | All | 19,549 | 249.4 (20.6) | 3.3 | 9.0 | 60.0 | |||
| Height, cm | (in) | ||||||||
| <150 | (<60) ) | 339 | 246.3 (23.8) | 4.4 | 1.6 (1.0–2.7) | 14.5 | 1.7 (1.3–2.3) c | 66.4 | 1.1 (1.0–1.3) |
| 150-159 | (60-62) | 3478 | 248.1 (21.6) | 4.1 | 1.4 (1.2–1.8) c | 10.2 | 1.29 (1.–1.4) c | 62.9 | 1.0 (1.0–1.1) |
| 160-167 | (63-65) | 7612 | 249.4 (20.4) | 3.1 | Referent | 8.9 | Referent | 60.3 | Referent |
| 168-175 | (66-68) | 6191 | 250.1 (20.2) | 3.0 | 0.9 (0.8–1.1) | 8.5 | 0.9 (0.8–1.0) | 58.4 | 1.0 (0.9–1.0) |
| ≥176 | (≥ 69) | 1929 | 250.4 (20.1) | 3.1 | 0.8 (0.6–1.1) | 8.5 | 0.9 (0.8–1.1) | 57.5 | 0.9 (1.0–1.0) |
| P value | < .001 ANOVA | .011 (χ 2 ) | < .001 (χ 2 ) | < .001 (χ 2 ) | |||||
| Weight, kg | (lbs) | ||||||||
| <50 | (<110) | 828 | 250.0 (19.0) | 1.6 | 0.5 (0.3–0.8) b | 7.4 | 0.8 (0.6–1.0) | 60.1 | 1.0 (0.9–1.1) |
| 50-63 | (110-139) | 8004 | 249.8 (19.9) | 2.7 | Referent | 8.5 | Referent | 60.1 | Referent |
| 64-76 | (140-169) | 6330 | 249.9 (20.4) | 3.2 | 1.2 (1.0–1.5) b | 8.8 | 1.1 (1.0–1.2) | 58.6 | 1.0 (0.9–1.0) |
| 77-89 | (170-199) | 2604 | 248.1 (22.2) | 4.5 | 1.7 (1.4–2.2) c | 10.6 | 1.3 (1.1–1.5) c | 61.2 | 1.0 (1.0–1.1) |
| ≥90 | (≥200) | 1783 | 247.4 (22.7) | 5.1 | 2.0 (1.5–2.5) c | 10.8 | 1.3 (1.1–1.5) c | 62.6 | 1.0 (1.0–1.1) |
| P value | < .001 ANOVA | < .001 (χ 2 ) | < .001 (χ 2 ) | .103 (χ 2 ) | |||||
| BMI, kg/m 2 | |||||||||
| 14.0-18.4 underweight | 604 | 248.6 (20.2) | 2.3 | 0.9 (0.5–1.5) | 10.3 | 1.3 (1.0–1.6) | 62.4 | 1.0 (1.0–1.2) | |
| 18.5-24.9 normal | 11361 | 250.2 (19.6) | 2.6 | Referent | 8.0 | Referent | 59.2 | Referent | |
| 25.0-29.9 overweight | 4435 | 248.9 (21.6) | 3.9 | 1.4 (1.2–1.8) c | 10.0 | 1.2 (1.1–1.4) c | 59.0 | 1.0 (0.9–1.0) | |
| 30.0-34.9 obese | 1941 | 247.8 (21.5) | 4.1 | 1.5 (1.2–1.9) c | 10.4 | 1.3 (1.1–1.5) c | 63.5 | 1.1 (1.0–1.1) | |
| ≥35.0 morbidly obese | 1208 | 246.2 (24.4) | 6.5 | 2.4 (1.8–3.0) c | 12.5 | 1.5 (1.3–1.8) c | 63.4 | 1.1 (1.0–1.1) | |
| P value | < .001 ANOVA | < .001 (χ 2 ) | < .001 (χ 2 ) | .001 (χ 2 ) | |||||
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