Table 1.
| a. Umbilical cord concentration by medication | ||||||||
|---|---|---|---|---|---|---|---|---|
| CBZ | LEV | LTG | OXC | PHT | TPM | VPA | Total | |
| Sample Size (n) | 10 | 10 | 38 | 4 | 4 | 2 | 6 | 74 |
| Total AED Concentration | ||||||||
| [Umbilical Cord] Mean (mcg/mL) | 3.71 ± 1.00 | 22.75 ± 21.81 | 5.79 ± 3.58 | 1.65 ± 0.84 | 10.20 ± 5.24 | 9.95 ± 1.63 | 48.60 ± 17.12 | |
| Range (mcg/mL) | 1.70 – 4.90 | 4.00 – 76.00 | 1.10 – 16.30 | 0.50 – 2.50 | 6.30 – 17.50 | 8.80 – 11.10 | 26.00 – 71.00 | |
| Free (unbound) AED Concentration | ||||||||
| [Umbilical Cord] Mean (mcg/mL) | 1.50 ± 0.31 | N/A | 2.29 ± 1.58* | N/A | 1.50 ± 0.57 | N/A | 3.87 ± 4.22 | |
| Range (mcg/mL) | 0.90 – 2.00 | N/A | 0.30 – 8.00* | N/A | 0.80 – 2.20 | N/A | 0.30 – 10.00 | |
| b. Maternal dose at delivery and placental passage by medication | ||||||||
|---|---|---|---|---|---|---|---|---|
| CBZ | LEV | LTG | OXC | PHT | TPM | VPA | Total | |
| Sample Size (n) | 9 | 10 | 33 | 3 | 3 | 2 | 5 | 65 |
| Maternal AED Dose | ||||||||
| Dose at Delivery Mean (mg/d) | 1216.67 ± 312.25 | 2666.67 ± 1419.73** | 626.52 ± 254.64 | 1650.00 ± 1050.00 | 466.67 ± 76.38 | 700.00 ± 100.00 | 1093.75 ± 373.26*** | |
| Range (mg/d) | 800 – 1750 | 750 – 5000** | 125 – 1200 | 450 – 2400 | 400 – 550 | 600 – 800 | 625 – 1500*** | |
| Total AED Placental Passage | ||||||||
| Placental Passage ([cord]/[maternal]) | 0.79 ± 0.19 | 1.12 ± 0.46 | 1.17 ± 0.48 | 1.11 ± 0.10 | 1.10 ± 0.32 | 0.85 ± 0.02 | 1.20 ± 0.23 | |
| Range | 0.51 – 1.19 | 0.57 – 2.17 | 0.66 – 3.06 | 1.00 – 1.19 | 0.72 – 1.33 | 0.83 – 0.87 | 1.00 – 1.56 | |
| Free (Unbound) AED Placental Passage | ||||||||
| Placental Passage ([cord]/[maternal]) | 1.42 ± 1.22 | N/A | 1.15 ± 0.36**** | N/A | 1.10 ± 0.19 | N/A | 0.86 ± 0.31 | |
| Range | 0.90 – 4.67 | N/A | 0.63 – 2.31**** | N/A | 0.88 – 1.25 | N/A | 0.30 – 1.01 | |
| Factors Associated with Placental Passage | ||||||||
| Molecular Weight6 | 236.27 | 170.21 | 259.09 | 252.27 | 252.26 | 339.37 | 144.21 | |
| Protein Binding6 | 75% | 0% | 55% | 60% (active mtabolite 40%) |
90% | 15% | 90% | |
| Dissociation Constant | 13.97 | −2 (active metabolite 3.67)8 | 5.77 | − 0.657 | 8.337 | 8.539 | 4.87 | |
| c. Neonatal outcomes by medication | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Neonatal outcomes | CBZ | LEV | LTG | OXC | PHT | TPM | VPA | Poly-therapy | Total |
| Sample Size (n) | 8 | 7 | 36 | 4 | 3 | 2 | 6 | 4 | 70 |
| Premature (<37 weeks gestation) | 2 (25%) | 0 (0%) | 1 (2.8%) | 0 (0%) | 0 (0%) | 1 (50%) | 0 (0%) | 0 (0) | 4 (5.7%) |
| Small for Gestational Age (<10th percentile) | 1 (12.5%) | 1 (14.3%) | 3 (8.3%) | 1 (25%) | 0 (0%) | 1 (50%) | 2 (33.3%) | 1 (25%) | 10 (14.3%) |
| Apgar < 7 at 1 minute | 1 (12.5%) | 1 (14.3%) | 2 (5.6%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 3 (75%) | 7 (10%) |
| Apgar < 7 at 5 minutes | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 |
| Admission to NICU or Special Care Nursery | 2 (25%) | 1 (14.3%) | 6 (16.7%) | 0 (0%) | 0 (0%) | 1 (50%) | 0 (0%) | 2 (50%) | 12 (17.1%) |
| Major Malformation | 1 (12.5%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (25%) | 2 (2.9%) |
CBZ = carbamazepine. LEV = levetiracetam. LTG = lamotrigine. OXC = oxcarbazepine. PHT = phenytoin. TPM = topiramate. VPA = valproic acid.
*
n=36
**
n=9
***
n=4
****
n=31
NICU = neonatal intensive care unit.