Supplement I
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Sensitivity analyses methods
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Examination of the covariate distribution among pregnancies to women with hormonal
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contraceptive use, as compared to non-users, indicated that women using hormonal contraceptives were
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generally younger and less likely to be parous than non-users, however these differences varied by
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contraceptive formulation (Supplementary Table S2). We conducted several sensitivity analyses to
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address the potential that the estimates observed could be biased from residual confounding resulting
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from these differences. Specifically, we explored the robustness of our primary results using three
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different comparator groups, selected to more closely approximate the counterfactual population for
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exposed pregnancies. These included 1) a comparator group consisting of women without hormonal
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contraceptive use in early pregnancy and whose pregnancy was reported to be unplanned, to assess for the
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potential for bias resulting from residual factors associated with having an unplanned pregnancy that are
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also associated with offspring overweight or obesity, 2) a comparator group of women who were former
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users of the same contraceptive (within 12 - >4 months before conception), to assess for the potential for
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confounding by indication -- a bias resulting from factors associated with both the type of hormonal
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contraceptive prescribed and with offspring overweight or obesity), and 3) an analysis comparing two oral
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contraceptive groups: combination vs progestin-only, to account for factors associated with oral
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contraceptive use and childhood overweight that are not related to the particular hormone used.
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Assuming that any factors contributing to contraceptive failure may be similar for different contraceptive
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types (and that these factors may also be associated with offspring overweight or obesity), comparison of
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progestin-only oral contraceptive users as compared to combination oral contraceptive users assesses the
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potential from bias as result of this unmeasured confounding.
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In our sensitivity analysis of exposure to hormonal contraceptive use before pregnancy, we
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evaluated use of the vaginal ring as compared to the combination oral contraceptive. The distribution of
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study covariates among women obtaining a prescription for the vaginal ring was comparable to the
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distribution of covariates among women obtaining a prescription for a combination oral contraceptive
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(Supplementary Table S2).
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Supplement I
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Pregnancies with exposure to a hormonal contraceptive within the first 12 weeks after the
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estimated date of conception were more likely to have been lost to follow-up than pregnancies with no
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exposure. For example, while 43% of those with no hormonal contraceptive use had data at year 3, 33%
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of those reporting use of a combination oral contraceptive in early pregnancy were not lost to follow-up
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(Supplementary Table S3). We conducted additional sensitivity analyses to evaluate the potential for bias
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through loss to follow-up, first using multiple imputation and second, using inverse probability weighting.
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We used multiple imputation1 (SAS PROC MI - Monte Carlo Multiple Chain) to impute 10 data sets with
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imputed covariate and follow-up data. The model results for each data set were then synthesized to obtain
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final estimates (SAS PROC MIANALYZE). For the inverse probability weighting analysis we
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constructed weights based on the predicted probability of staying in the study. These were scaled by
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dividing the marginal probability of staying in the study by the predicted probability.2, 3
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We also conducted a sensitivity analysis to evaluate the potential for misclassification of
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exposure. Hormonal contraceptive use was self-reported on the first MoBa questionnaire, with limited
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detail on type or timing of formulation used. Our own examination of the self-reported data indicated
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incongruences in the type of formulation used as self-reported compared to the formulation documented
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as obtained in the NorPD. We identified moderate agreement between self-reported and NorPD-indicated
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use, for any type of hormonal contraceptive, for each of the exposure periods for which self-reported data
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was provided (12 months, 4 months, and early pregnancy) (Kappa=0.45 for early pregnancy, 0.60 for use
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within 4 months of conception, and 0.69 for use within 12 months of conception. As a sensitivity
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analysis, we characterized self-reported use of a combination type oral contraceptive as those women
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indicating use of a combination oral contraceptive at the time of conception but for whom the NorPD did
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not indicate she was using a progestin-only formulation instead. Similarly, for women reporting use of
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the progestin-only mini pill, we characterized use according to self-report but without inclusion of those
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pregnancies where the NorPD indicated the formulation used was actually a combination type
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formulation. In other words, these were women with either no documentation of use in the NorPD at the
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time of conception (but who did have evidence of having obtained the formulation at another period of
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Supplement I
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time within 12 months of conception) or were in agreement with the NorPD that conception occurred
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while taking the oral contraceptive.
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Finally, we evaluated the sensitivity of estimates to subtle changes in adjustment sets, including
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adjustment for maternal diabetes (Type I or II), pre-pregnancy weight versus maternal prepregnancy BMI,
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income, and age -- more finely characterized in 5, versus 10, age group increments. We also assessed
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whether a log-binomial model, for estimating relative risks, generated estimates that were materially
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different from estimates obtained in the logit model estimating odds ratios.
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