Assisted Reproductive Technology and Birth Defects Among Liveborn Infants in Florida, Massachusetts, and Michigan, 2000-2010

Boulet, Sheree L.; Kirby, Russell S.; Reefhuis, Jennita; Zhang, Yujia; Sunderam, Saswati; Cohen, Bruce; Bernson, Dana; Copeland, Glenn; Bailey, Marie; Jamieson, Denise J.; Kissin, Dmitry M.

doi:10.1001/jamapediatrics.2015.4934

Cited by 91 publications

(80 citation statements)

References 38 publications

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“…The adjusted prevalence ratio of 1.5 for birth defects with ART that we observed is similar to the relative risk reported in a meta‐analysis by Wen et al () and in another meta‐analysis among studies considered high quality (Qin et al, ). Consistent with previous studies (Reefhuis et al, , Boulet et al, ), we observed a greater effect of ART among singletons for several defects, likely because the baseline prevalence rates of most birth defects examined were lower for singleton births than for multiples. The association of ART and TOF was confined to singletons in our study, although the number of ART‐exposed TOF cases was small.…”

Section: Discussionsupporting

confidence: 91%

“…The results of several studies and metaanalyses have suggested that ART is associated with an increased risk of birth defects, although the magnitude of these associations and the spectrum of defects involved remain unclear (Kallen et al, 2010;Wen et al, 2012;Hansen et al, 2013;Yin et al, 2013;Qin et al, 2015). ART has been associated with several specific cardiac birth defects, including septal heart defects and tetralogy of Fallot, as well as several noncardiac defects, including cleft lip with or without cleft palate, hypospadias, neural tube defects, and esophageal, anorectal and large intestinal atresias (Reefhuis et al, 2009;Funke et al, 2010;Davies et al, 2012;Tararbit et al, 2013;Benedum et al, 2016;Boulet et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Assisted Reproductive Technology and Birth Defects: Effects of Subfertility and Multiple Births

Liberman

Getz

Heinke

et al. 2017

Birth Defects Research

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Background Assisted reproductive technology (ART) has been associated with birth defects, but the contributions of multiple births and underlying subfertility remain unclear. We evaluated the effects of subfertility and mediation by multiple births on associations between ART and nonchromosomal birth defects. Methods We identified a retrospective cohort of Massachusetts live births and stillbirths from 2004–2010 among ART-exposed, ART-unexposed subfertile, and fertile mothers using linked information from fertility clinics, vital records, hospital discharges, and birth defects surveillance. Log-binomial regression was used to estimate prevalence ratios and 95% confidence intervals. Mediation analyses were performed to deconstruct the ART-birth defects association into the direct effect of ART, the indirect effect of multiple births, and the effect of ART-multiples interaction. Results Of 17,829 ART-exposed births, 355 had a birth defect, compared with 162 of 9431 births to subfertile mothers and 6183 of 445,080 births to fertile mothers. The adjusted prevalence ratio was 1.5 (95% confidence interval, 1.3–1.6) for ART and 1.3 (1.1–1.5) in subfertile compared with fertile deliveries. We observed elevated rates of several birth defects with ART, including tetralogy of Fallot and hypospadias. Subfertility and multiple births affect these associations, with multiple births explaining 36% of the relative effect of ART on nonchromosomal birth defects. Conclusion Although the risk of birth defects with ART is small, a substantial portion of the relative effect is mediated through multiple births, with subfertility contributing an important role. Future research is needed to determine the impact of newer techniques, such as single embryo transfer, on these risks.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Assisted Reproductive Technology and Birth Defects: Effects of Subfertility and Multiple Births

Liberman

Getz

Heinke

et al. 2017

Birth Defects Research

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“…The greater risk in IVF-treated women may reflect more severe infertility, more extensive underlying pathology, or other unfavorable factors not measured in this study. The frequency and magnitude of the risks of adverse outcomes we found in the IVF group are in accord with prior results from clinical studies (1, 6, 7, 10, 12, 21, 46, 47) and meta-analyses (2, 3, 5, 8). These findings also extend the results from the original analysis (30) which limited adverse outcomes to preterm birth, low birthweight, small-for-gestational age, and perinatal death, demonstrating that compared to fertile women, women with subfertility or treated with IVF are at significantly greater risk for gestational diabetes, pregnancy hypertension, uterine bleeding, placental complications, prenatal hospitalizations, primary cesarean delivery, and their infants are at greater risk for very low birthweight, very preterm birth, birth defects, and neonatal death.…”

Section: Discussionsupporting

confidence: 90%

Pregnancy, birth, and infant outcomes by maternal fertility status: the Massachusetts Outcomes Study of Assisted Reproductive Technology

Luke

Gopal

Cabral

et al. 2017

American Journal of Obstetrics and Gynecology

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Background Births to subfertile women, with and without infertility treatment, have been reported to have lower birthweights and shorter gestations, even when limited to singletons. It is unknown whether these decrements are due to parental characteristics or aspects of infertility treatment. Objective To evaluate the effect of maternal fertility status on the risk of pregnancy, birth, and infant complications. Study Design All singleton live births of ≥22 weeks’ gestation and ≥350 grams birthweight to Massachusetts resident women in 2004–10 were linked to hospital discharge and vital records. Women were categorized by their fertility status as in vitro fertilization (IVF), subfertile, or fertile. Women whose births linked to IVF cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System were classified as IVF. Women with indicators of subfertility but not treated with IVF were classified as subfertile. Women without indicators of subfertility or IVF treatment were classified as fertile. Risks of fifteen adverse outcomes (gestational diabetes, pregnancy hypertension, antenatal bleeding, placental complications (placenta abruptio and placenta previa), prenatal hospitalizations, primary cesarean, very low birthweight (<1,500g), low birthweight (<2,500g), small-for-gestation birthweight (Z-score ≤−1.28), large-for-gestation birthweight (Z-score ≥1.28), very preterm (<32 weeks), preterm (<37 weeks), birth defects, neonatal death (0–27 days), and infant death (0–364 days of life) were modeled by fertility status with the fertile group as reference, and the subfertile group as reference, using multivariate log binomial regression and reported as adjusted risk ratios (ARRs) and 95% confidence intervals. Results The study population included 459,623 women (441,420 fertile, 8,054 subfertile, and 10,149 IVF). Women in the subfertile and IVF groups were older than their fertile counterparts. Risks for six out of six pregnancy outcomes and six out of nine infant outcomes were increased for the subfertile group, and five out of six pregnancy outcomes and seven out of nine infant outcomes were increased for the IVF group. For four of the six pregnancy outcomes (uterine bleeding, placental complications, prenatal hospitalizations, and primary cesarean) and two of the infant outcomes (low birthweight and preterm) the risk was greater in the IVF group, with non-overlapping confidence intervals to the subfertile group, indicating a substantially higher risk among IVF-treated women. The highest risks for the IVF women were uterine bleeding (ARR 3.80, 95% CI 3.31, 4.36) and placental complications (ARR 2.81, 95% CI 2.57, 3.08), and for IVF infants, very preterm birth (ARR 2.13, 95% CI 1.80, 2.52) and very low birthweight (ARR 2.15, 95% CI 1.80, 2.56). With subfertile women as reference, risks for the IVF group were significantly increased for uterine bleeding, placental complications, prenatal hospitalizations, primary cesarean, low and very low birthweight, and preterm and very preterm bir...

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“…Although studies to date have overall been reassuring as to the long‐term health of children born following ART, there is a small but significant increase in birth defects and differences in markers of cardiovascular and metabolic health noted in some large studies (Boulet et al, ; Fauser et al, ). Whether these differences are a result of the fertility procedures themselves or other factors, such as infertility itself, is still a matter of debate, although there are several proposed mechanisms for how ART may influence in‐utero development.…”

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confidence: 99%

In vitro fertilization (IVF): Where are we now?

Weinerman

2018

Birth Defects Research

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Assisted Reproductive Technology and Birth Defects Among Liveborn Infants in Florida, Massachusetts, and Michigan, 2000-2010

Cited by 91 publications

References 38 publications

Assisted Reproductive Technology and Birth Defects: Effects of Subfertility and Multiple Births

Assisted Reproductive Technology and Birth Defects: Effects of Subfertility and Multiple Births

Pregnancy, birth, and infant outcomes by maternal fertility status: the Massachusetts Outcomes Study of Assisted Reproductive Technology

In vitro fertilization (IVF): Where are we now?

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