Table 2. Association between in-utero carbamazepine exposure and the endpoints duration of pregnancy and size at birth.
| Exposed to Carbamazepine /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 | 1,975 / 2,123 | -1.3 (-2.3 to -0.3) | -1.1 (-3.1 to 0.9) | -0.9 (-1.8 to 0.1) | -0.1 (-1.3 to 1.0) | 1.2 (0.9 to 1.5) |
| Use in first trimestera | 1,686 / 1,930 | -1.6 (-2.7 to -0.5) | -2.3 (-4.5 to -0.1) | -0.9 (-1.8 to 0.0) | -0.5 (-1.5 to 0.6) | 1.3 (1.0 to 1.8) |
| Continuersa | 459 / 1,013 | -1.3 (-3.0 to 0.3) | 0.0 (-3.8 to 3.8) | -0.3 (-2.0 to 1.3) | -0.5 (-1.9 to 0.9) | 1.1 (0.7 to 1.7) |
| Mother with epilepsya | 1,665 / 1,447 | -1.3 (-2.4 to -0.2) | -1.6 (-3.5 to 0.3) | -0.5 (-1.5 to 0.5) | -0.2 (-1.3 to 0.9) | 1.3 (0.9 to 1.7) |
| Mother with chronic paina | 259 / 541 | -1.5 (-4.2 to 1.1) | -4.5 (-10.5 to 1.5) | -0.7 (-2.7 to 1.4) | 0.1 (-2.7 to 2.8) | 1.3 (0.7 to 2.3) |
| Polytherapya | 167 / 336 | -2.4 (-5.8 to 1.0) | -6.1 (-15.1 to 2.8) | -2.0 (-5.4 to 1.4) | -1.5 (-4.0 to 1.0) | 1.7 (0.9 to 3.3) |
| High vs. low dose of carbamazepine | 264 / 275 | -4.6 (-7.5 to -1.6) | -6.8 (-12.6 to -0.9) | -3.4 (-5.8 to -0.9) | -2.1 (-4.7 to 0.4) | 2.8 (1.3 to 6.0) |
| Birth weight z-score | SGA | |||||
| Use any time in pregnancya | 1,988 / 2,147 | -0.1 (-0.2 to -0.0) | -0.0 (-0.1 to 0.1) | -0.1 (-0.2 to -0.0) | -0.2 (-0.3 to -0.1) | 1.4 (0.9 to 2.1) |
| Use in first trimestera | 1,699 / 1,953 | -0.1 (-0.2 to -0.0) | -0.1 (-0.2 to 0.1) | -0.1 (-0.2 to -0.0) | -0.2 (-0.3 to -0.1) | 1.7 (1.0 to 2.6) |
| Continuersa | 466 / 1,021 | -0.1 (-0.2 to -0.0) | -0.1 (-0.3 to 0.1) | -0.1 (-0.2 to 0.0) | -0.2 (-0.3 to -0.0) | 1.3 (0.7 to 2.6) |
| Mother with epilepsya | 1,676 / 1,459 | -0.1 (-0.2 to -0.0) | 0.0 (-0.1 to 0.1) | -0.1 (-0.2 to -0.1) | -0.2 (-0.3 to -0.0) | 1.2 (0.8 to 1.9) |
| Mother with chronic paina | 263 / 552 | -0.2 (-0.3 to 0.0) | -0.1 (-0.4 to 0.3) | -0.1 (-0.3 to 0.1) | -0.1 (-0.4 to 0.1) | 1.8 (0.8 to 4.2) |
| Polytherapya | 167 / 339 | -0.5 (-0.7 to -0.3) | -0.6 (-0.9 to -0.3) | -0.5 (-0.7 to -0.2) | -0.3 (-0.8 to 0.1) | 4.2 (1.2 to 14.4) |
| High vs. low dose of carbamazepine | 267 / 275 | -0.1 (-0.3 to 0.1) | -0.1 (-0.4 to 0.2) | -0.1 (-0.3 to 0.1) | -0.1 (-0.4 to 0.1) | 2.0 (0.7 to 5.6) |
| Birth length z-score | ||||||
| Use any time in pregnancya | 1,963 / 2,119 | -0.1 (-0.2 to -0.0) | -0.1 (-0.2 to 0.0) | -0.1 (-0.2 to 0.0) | -0.2 (-0.3 to -0.0) | |
| Use in first trimestera | 1,681 / 1,930 | -0.1 (-0.2 to -0.0) | -0.1 (-0.2 to 0.0) | -0.1 (-0.2 to -0.0) | -0.2 (-0.3 to -0.1) | |
| Continuersa | 461 / 1,006 | -0.2 (-0.3 to -0.1) | -0.2 (-0.4 to 0.0) | -0.2 (-0.3 to -0.1) | -0.2 (-0.4 to -0.1) | |
| Mother with epilepsya | 1,655 / 1,441 | -0.1 (-0.2 to -0.0) | -0.1 (-0.3 to -0.0) | -0.1 (-0.2 to 0.0) | -0.1 (-0.3 to -0.0) | |
| Mother with chronic paina | 260 / 542 | -0.2 (-0.4 to -0.0) | -0.1 (-0.3 to 0.2) | -0.2 (-0.4 to 0.1) | -0.3 (-0.6 to -0.0) | |
| Polytherapya | 163 / 331 | -0.3 (-0.5 to -0.1) | -0.2 (-0.5 to 0.1) | -0.2 (-0.5 to 0.0) | -0.6 (-0.8 to -0.3) | |
| High vs. low dose of carbamazepine | 260 / 273 | -0.1 (-0.3 to 0.0) | -0.1 (-0.4 to 0.1) | -0.2 (-0.4 to -0.0) | -0.0 (-0.3 to 0.2) | |
| Birth head circumference z-score | Microcephaly | |||||
| Use any time in pregnancya | 1,883 / 2,096 | -0.2 (-0.3 to -0.1) | -0.2 (-0.3 to -0.0) | -0.2 (-0.3 to -0.1) | -0.2 (-0.3 to -0.1) | 1.2 (0.7 to 1.9) |
| Use in first trimestera | 1,605 / 1,906 | -0.2 (-0.3 to -0.2) | -0.2 (-0.4 to -0.1) | -0.3 (-0.4 to -0.2) | -0.3 (-0.4 to -0.2) | 1.3 (0.8 to 2.1) |
| Continuersa | 456 / 1,002 | -0.3 (-0.4 to -0.2) | -0.3 (-0.5 to -0.1) | -0.4 (-0.5 to -0.2) | -0.4 (-0.6 to -0.2) | 1.3 (0.6 to 3.3) |
| Mother with epilepsya | 1,585 / 1,421 | -0.2 (-0.3 to -0.1) | -0.2 (-0.4 to -0.1) | -0.2 (-0.3 to -0.1) | -0.2 (-0.3 to -0.1) | 1.2 (0.7 to 1.9) |
| Mother with chronic paina | 256 / 543 | -0.2 (-0.4 to -0.0) | -0.2 (-0.6 to 0.1) | -0.2 (-0.4 to -0.1) | 0.0 (-0.2 to 0.3) | 2.7 (0.8 to 9.1) |
| Polytherapya | 155 / 329 | -0.6 (-0.8 to -0.4) | -0.5 (-0.8 to -0.2) | -0.6 (-0.8 to -0.3) | -0.7 (-1.0 to -0.4) | 2.6 (0.9 to 7.3) |
| High vs. low dose of carbamazepine | 256 / 271 | -0.2 (-0.4 to 0.0) | -0.2 (-0.6 to 0.1) | -0.3 (-0.6 to -0.0) | -0.2 (-0.5 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.
Note = AED use was ascertained at any time in pregnancy, except where noted (indented rows). Analyses on continuers used data from deliveries in 2006–2013. In dose-response analyses, the reference was the bottom tertile of mean daily dose of carbamazepine (2006–2013). All results were 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”). Models restricted to polytherapy compared infants exposed to carbamazepine and another AED (except lamotrigine) with those exposed to lamotrigine and another AED (except carbamazepine).