Twinning and major birth defects, National Birth Defects Prevention Study, 1997–2007

Abstract

Background Twinning has been associated with many types of birth defects, although previous studies have had inconsistent findings. Many studies lack information about potential confounders, particularly use of fertility treatment. Our objective was to assess the association between twinning and birth defects in the National Birth Defects Prevention Study (NBDPS). Methods We used data from the NBDPS, a population-based, case–control study of major birth defects in the USA, to evaluate associations between twinning and birth defects. The study population included mothers of twin and singleton controls (live-born infants without major birth defects), and cases (fetuses or infants with a major birth defect) born October 1997–December 2007. Adjusted ORs and 95% CIs were estimated using multivariable logistic regression stratified by use of fertility treatment. Twin sex-pairing data and a simulation approach were used to estimate the zygosity of twins. Results In the unassisted conception stratum, we observed significant positive associations between twinning and 29 of 45 defect groups. The largest effect estimates were observed for multiple ventricular septal defects and cloacal exstrophy. Among mothers reporting any use of fertility treatments, we observed a significant association with twinning for 5 of 25 defect groups, with the largest effect estimates for hypoplastic left heart syndrome and omphalocele. OR estimates in the estimated monozygotic stratum were generally further from the null than in the dizygotic stratum. Conclusions Compared with singletons, a wide range of birth defects are significantly more common among twins. Birth defect risk in twins may be differential by use of fertility treatment.

Descriptive epidemiology of cerebellar hypoplasia in the National Birth Defects Prevention Study

“…Some of the maternal exposures we identified as associated with cerebellar hypoplasia in the crude analysis, including hypertension, vasoactive medications, and multiple gestations, have been postulated to impact blood flow to the fetus or affect the development of blood vessels, resulting in vascular disruptions that could lead to the development of birth defects (Dawson et al, ; Schinzel, Smith, & Miller, ; van Gelder et al, ; van Gelder, de Jong‐van den Berg, & Roeleveld, ). Although cerebellar hypoplasia has not been examined specifically as a vascular disruption birth defect (van Gelder et al, ), other CNS defects, specifically hydranencephaly and porencephaly, have been (Hoyme, Higginbottom, & Jones, ; Mittelbronn et al, ).…”

Quantification of selection bias in studies of risk factors for birth defects among livebirths

“…Further, we selected exposures with wellestablished relationships to the defects understudy, and our results are consistent with previous reports conducted in various settings. [34][35][36]39,41,49 Consistent methods across centres helped to ensure the quality of case ascertainment and classification.…”

Measurement error is often neglected in medical literature: a systematic review

“…The remaining 11 (61%) of the 18 publications investigated the impact of measurement error on the exposure-outcome relation using sensitivity analyses. In five publications [29][30][31][32][33], an assumption was made about the amount of possible measurement error and its effect on the exposure-outcome relation was quantified. Often this was achieved by looking at a subgroup of the original sample for which the mismeasured variable of interest was assumed to be measured with less or no error.…”