Table 3. Association between in-utero pregabalin exposure and the endpoints duration of pregnancy and size at birth.
| Exposed to Pregabalin /Reference, n/n | Difference (95% CI) | Odds Ratio (95% CI) | ||||
|---|---|---|---|---|---|---|
| Mean | 10th Percentile | 50th Percentile | 90th Percentile | |||
| Pregnancy duration (days) | Preterm birth | |||||
| Use any time in pregnancya | 522 / 2,190 | -1.1 (-3.0 to 0.8) | -2.7 (-6.7 to 1.2) | -0.5 (-2.5 to 1.4) | 0.3 (-1.6 to 2.3) | 1.5 (1.0 to 2.4) |
| Use in first trimestera | 484 / 1,977 | -1.8 (-3.7 to 0.2) | -3.2 (-7.5 to 1.1) | -0.5 (-2.4 to 1.3) | -0.1 (-2.2 to 2.0) | 1.9 (1.2 to 3.0) |
| Continuersa | 142 / 1,025 | -1.2 (-4.7 to 2.3) | -0.5 (-7.2 to 6.2) | 0.4 (-3.4 to 4.2) | -0.6 (-4.7 to 3.5) | 2.3 (1.0 to 5.3) |
| Mother with epilepsya | 33 / 1,537 | -5.6 (-10.7 to -0.4) | -11.2 (-35.7 to 13.3) | -4.2 (-10.0 to 1.6) | 3.3 (-4.7 to 11.2) | 4.2 (1.6 to 11.4) |
| Female infantsa | 265 / 1,146 | -2.0 (-4.6 to 0.7) | -3.2 (-8.7 to 2.2) | -1.9 (-4.2 to 0.5) | -2.4 (-5.1 to 0.3) | 1.9 (1.0 to 3.4) |
| Male infantsa | 257 / 1,044 | -0.2 (-3.1 to 2.6) | 0.4 (-4.6 to 5.4) | -0.2 (-3.5 to 3.1) | 1.2 (-1.7 to 4.2) | 1.2 (0.6 to 2.4) |
| High vs. low dose of pregabalin | 175 / 174 | 0.6 (-2.7 to 3.9) | 0.4 (-7.0 to 7.7) | 1.1 (-1.9 to 4.2) | 1.2 (-2.3 to 4.7) | 1.1 (0.6 to 2.3) |
| Birth weight z-score | SGA | |||||
| Use any time in pregnancya | 528 / 2,215 | -0.1 (-0.3 to 0.0) | -0.0 (-0.3 to 0.2) | -0.2 (-0.3 to 0.0) | -0.2 (-0.4 to 0.0) | 1.3 (0.6 to 3.0) |
| Use in first trimestera | 489 / 2,001 | -0.2 (-0.3 to -0.0) | -0.0 (-0.3 to 0.2) | -0.2 (-0.4 to -0.0) | -0.2 (-0.5 to -0.0) | 1.3 (0.6 to 3.1) |
| Continuersa | 142 / 1,033 | -0.1 (-0.4 to 0.1) | -0.2 (-0.7 to 0.3) | -0.1 (-0.4 to 0.2) | -0.2 (-0.6 to 0.1) | 0.6 (0.1 to 3.0) |
| Mother with epilepsya | 33 / 1,550 | 0.1 (-0.3 to 0.5) | 0.2 (-0.9 to 1.2) | 0.2 (-0.2 to 0.6) | -0.3 (-0.7 to 0.2) | Not applicable |
| High vs. low dose of pregabalin | 177 / 176 | 0.0 (-0.2 to 0.3) | -0.3 (-0.8 to 0.1) | 0.2 (-0.1 to 0.5) | 0.2 (-0.1 to 0.6) | 1.3 (0.4 to 4.6) |
| Birth length z-score | ||||||
| Use any time in pregnancya | 521 / 2,186 | -0.1 (-0.2 to 0.0) | -0.0 (-0.3 to 0.2) | -0.1 (-0.3 to 0.0) | -0.1 (-0.4 to 0.1) | |
| Use in first trimestera | 484 / 1,977 | -0.1 (-0.2 to 0.0) | -0.1 (-0.4 to 0.1) | -0.2 (-0.4 to 0.0) | -0.1 (-0.3 to 0.2) | |
| Continuersa | 140 / 1,018 | -0.1 (-0.4 to 0.1) | -0.1 (-0.5 to 0.4) | -0.1 (-0.4 to 0.3) | -0.2 (-0.7 to 0.2) | |
| Mother with epilepsya | 32 / 1,530 | -0.1 (-0.5 to 0.3) | -0.1 (-0.9 to 0.8) | 0.1 (-0.3 to 0.6) | -0.1 (-0.7 to 0.5) | |
| High vs. low dose of pregabalin | 172 / 175 | 0.0 (-0.2 to 0.2) | -0.3 (-0.7 to 0.0) | -0.0 (-0.3 to 0.2) | 0.1 (-0.2 to 0.5) | |
| Birth head circumference z-score | Microcephaly | |||||
| Use any time in pregnancya | 516 / 2,160 | -0.0 (-0.1 to 0.1) | 0.1 (-0.1 to 0.3) | -0.0 (-0.2 to 0.1) | -0.1 (-0.3 to 0.1) | 1.2 (0.5 to 2.9) |
| Use in first trimestera | 480 / 1,951 | -0.0 (-0.2 to 0.1) | 0.1 (-0.1 to 0.4) | -0.1 (-0.2 to 0.1) | 0.0 (-0.2 to 0.3) | 1.3 (0.5 to 3.4) |
| Continuersa | 136 / 1,012 | -0.1 (-0.3 to 0.2) | -0.1 (-0.7 to 0.6) | -0.0 (-0.3 to 0.3) | -0.1 (-0.5 to 0.2) | 5.3 (0.9 to 30.8) |
| Mother with epilepsya | 32 / 1,508 | -0.0 (-0.4 to 0.4) | 0.0 (-1.0 to 1.1) | 0.1 (-0.3 to 0.4) | 0.4 (-0.5 to 1.3) | Not applicable |
| Female infantsa | 264 / 1,128 | 0.0 (-0.2 to 0.2) | 0.3 (-0.1 to 0.6) | -0.1 (-0.3 to 0.1) | 0.0 (-0.3 to 0.3) | 1.2 (0.3 to 4.5) |
| Male infantsa | 252 / 1,032 | -0.0 (-0.3 to 0.2) | -0.3 (-0.6 to 0.1) | 0.0 (-0.2 to 0.2) | -0.1 (-0.4 to 0.2) | 1.6 (0.5 to 5.7) |
| High vs. low dose of pregabalin | 170 / 174 | 0.0 (-0.2 to 0.2) | 0.1 (-0.2 to 0.5) | 0.1 (-0.2 to 0.4) | -0.3 (-0.8 to 0.1) | Not applicable |
AED, antiepileptic drug; CI, confidence interval; SGA, small for gestational age.
a The reference is lamotrigine in the same exposure window.
AED use was ascertained at any time in pregnancy, except where noted (indented rows). Analyses on continuers are based on data from deliveries in 2006–2013. In dose-response analyses, the reference was the bottom tertile of mean daily dose of pregabalin (2006–2013). All results are adjusted for birth year, maternal age at delivery, education, country of origin, marital status, body mass index, smoking in current pregnancy, alcohol dependence, diabetes, hypertension, epilepsy, depression, bipolar disorder, migraine, chronic pain, and other psychiatric disorders. When the smallest cell count was < 5, we did not produce adjusted results (“not applicable”).