Valproate (All indications)

Table   Graphic     exposition period:

Congenital malformations
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
All congenital malformations (majors, minors, majors and minors, or unspecified)3.16 [2.64, 3.78]38%33 studies198,7168,172critical ROB5.77 [4.72; .]
Ano-rectal atresia and stenosis11.70 [3.09, 44.30]-1 study547913not evaluable ROB22.89 [5.63; .]
Atrial septal defect9.00 [5.40, 15.00]-1 study3,283913not evaluable ROB17.49 [10.27; .]
Cardiac septal defects2.67 [1.74, 4.10]0%2 studies16,5781,030not evaluable ROB4.78 [2.87; .]
Cleft lip with or without cleft palate5.08 [1.87, 13.82]0%3 studies1,6471,204not evaluable ROB9.64 [3.15; .]
Cleft palate4.85 [1.37, 17.12]0%2 studies1,181941not evaluable ROB9.16 [2.08; .]
Club foot / Talipes equinovarus4.97 [3.12, 7.91]17%3 studies3,8103,641not evaluable ROB9.41 [5.70; .]
Congenital heart defects2.74 [2.19, 3.44]13%15 studies18,3897,248low ROB4.93 [3.80; .]
Craniosynostosis6.12 [1.26, 29.85]0%2 studies768914not evaluable ROB11.72 [1.82; .]
Digestive system anomalies1.46 [0.65, 3.30]0%3 studies231,894not evaluable ROB-
Ebstein's anomaly20.35 [1.25, 330.13]-1 study50913not evaluable ROB40.20 [1.82; .]
Eye defects0.45 [0.12, 1.72]0%2 studies10309not evaluable ROB-
Genital anomalies3.25 [1.54, 6.89]0%3 studies1,045810not evaluable ROB5.96 [2.44; .]
Hypoplastic left heart (HLH/HLHS)19.60 [3.59, 107.13]-1 study218913not evaluable ROB38.69 [6.63; .]
Hypospadias5.88 [4.60, 7.51]1%10 studies9,5676,978low ROB11.24 [8.68; .]
Limb defects2.85 [1.79, 4.55]0%7 studies1,3342,695not evaluable ROB5.15 [2.98; .]
Major congenital malformations3.01 [2.46, 3.68]44%25 studies198,5287,694critical ROB5.46 [4.36; .]
Microcephaly / Small head circumference for gestational age1.36 [0.67, 2.78]0%6 studies4721,112not evaluable ROB-
Minor congenital malformations5.11 [2.13, 12.25]0%3 studies4383not evaluable ROB9.69 [3.68; .]
Nervous system anomalies3.08 [1.88, 5.03]0%4 studies3742,919not evaluable ROB5.61 [3.18; .]
Neural Tube Defects9.34 [4.08, 21.40]0%7 studies523,298not evaluable ROB18.17 [7.62; .]
Oro-facial clefts3.67 [2.51, 5.38]0%7 studies5,6186,898not evaluable ROB6.81 [4.46; .]
Polydactyly2.55 [0.48, 13.67]30%5 studies3,0952,112not evaluable ROB-
Pulmonary valve atresia27.80 [4.99, 154.94]-1 study154913not evaluable ROB55.10 [9.45; .]
Spina bifida13.80 [7.20, 26.46]0%6 studies6401,764not evaluable ROB27.10 [13.88; .]
Tetralogy of Fallot7.20 [1.33, 38.92]-1 study586913not evaluable ROB13.88 [2.00; .]
Urinary malformations1.18 [0.56, 2.49]0%4 studies292,318not evaluable ROB-
Valproate syndrome--0 study-
Ventricular septal defect4.00 [2.08, 7.71]-1 study4,652913not evaluable ROB7.46 [3.57; .]
15 non statistically significant endpoints reported in only one study

Growth parameters and prematurity
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Large for gestational age (weight)1.21 [0.74, 1.98]22%3 studies158845not evaluable ROB-
Low birth weight (< 2500g)1.49 [1.23, 1.82]15%6 studies94,9122,363not evaluable ROB2.35 [1.76; .]
Macrosomia (> 4000g)0.91 [0.55, 1.51]28%3 studies577,4071,059not evaluable ROB-
Preterm (< 37 weeks)1.08 [0.99, 1.17]0%15 studies252,9784,796low ROB-
Small for gestational age (weight)1.32 [1.00, 1.74]74%12 studies210,1166,632low ROB-
4 non statistically significant endpoints reported in only one study

Maternal consequences
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Assisted deliveries (forceps, vacuum, ...)1.18 [0.73, 1.90]0%2 studies177220not evaluable ROB-
Caesarean0.93 [0.76, 1.14]0%3 studies831926not evaluable ROB-
Gestational diabetes1.60 [0.23, 10.91]48%4 studies14110not evaluable ROB-
Maternal consequences (as a whole)1.35 [1.03, 1.77]0%2 studies12,260238not evaluable ROB2.03 [1.19; .]
Postpartum hemorrhage1.44 [1.01, 2.06]-1 study319215not evaluable ROB2.23 [1.08; .]
Preeclampsia0.95 [0.78, 1.15]0%4 studies53,7602,489not evaluable ROB-
3 non statistically significant endpoints reported in only one study

Neonatal disorders
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Feeding difficulty24.38 [1.49, 397.73]0%2 studies23not evaluable ROB48.26 [2.35; .]
Low Apgar score (< 7) (at 1 min)2.39 [0.84, 6.81]50%4 studies134673not evaluable ROB-
Low Apgar score (< 7) (at 5 min)1.76 [1.06, 2.91]0%7 studies1371,026not evaluable ROB2.91 [1.33; .]
Neonatal disorders (as a whole)