Benzodiazepines (Psy and mixed indications) updated on 02-10-2025

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)1.11 [1.03, 1.19]41%17 studies317,61591,826low ROB1.45 [1.19; .]
Major congenital malformations1.12 [1.04, 1.21]45%14 studies314,85491,280low ROB1.48 [1.23; .]
Congenital heart defects1.15 [1.03, 1.28]47%11 studies147,58290,894low ROB1.57 [1.22; .]
Oro-facial clefts1.30 [0.95, 1.79]56%10 studies12,53996,699low ROB-
Cleft lip with or without cleft palate1.86 [1.22, 2.85]59%10 studies6,4981,218low ROB3.13 [1.74; .]
Cleft palate1.30 [0.89, 1.90]0%9 studies3,4061,180not evaluable ROB-
Nervous system anomalies1.04 [0.78, 1.39]63%5 studies19,01992,305not evaluable ROB-
Ano-rectal atresia and stenosis2.14 [0.65, 7.05]72%5 studies1,8671,083not evaluable ROB-
Eye defects1.11 [0.72, 1.70]16%4 studies8,30742,114not evaluable ROB-
Genital anomalies1.10 [0.98, 1.25]0%4 studies16,43092,277not evaluable ROB-
Microcephaly / Small head circumference for gestational age3.26 [0.90, 11.83]83%3 studies133,8452,143not evaluable ROB-
Urinary malformations1.04 [0.94, 1.15]0%4 studies24,49192,277not evaluable ROB-
Ventricular septal defect1.10 [0.70, 1.71]0%5 studies6,6672,050not evaluable ROB-
Club foot / Talipes equinovarus1.00 [0.69, 1.45]0%3 studies1,6783,517not evaluable ROB-
Diaphragmatic hernia1.17 [0.68, 2.00]0%4 studies1,76941,927not evaluable ROB-
Digestive system anomalies1.16 [1.03, 1.30]0%3 studies16,40192,277not evaluable ROB1.58 [1.20; .]
Ear, face and neck anomalies1.05 [0.74, 1.51]0%3 studies2,01742,005not evaluable ROB-
Hypospadias0.67 [0.36, 1.23]49%3 studies5,913980not evaluable ROB-
Limb defects0.94 [0.82, 1.08]0%3 studies16,58792,277not evaluable ROB-
Limb reduction defects (LRD)2.61 [1.46, 4.68]0%3 studies59016not evaluable ROB4.67 [2.28; .]
Neural Tube Defects1.08 [0.69, 1.68]26%3 studies2,162111not evaluable ROB-
Oesophageal atresia with or without tracheo-oesophageal fistula1.86 [1.06, 3.25]0%4 studies1,1551,088not evaluable ROB3.12 [1.33; .]
Polydactyly1.06 [0.67, 1.68]0%3 studies2,537not evaluable ROB-
Respiratory system anomalies1.01 [0.83, 1.22]0%3 studies6,65992,277not evaluable ROB-
Abdominal wall defects1.09 [0.73, 1.64]0%2 studies1,31542,005not evaluable ROB-
Atrial septal defect1.21 [0.78, 1.89]0%3 studies6,3712,055not evaluable ROB-
Gastroschisis1.24 [0.70, 2.18]0%3 studies1,6431,071not evaluable ROB-
Omphalocele1.07 [0.39, 2.93]0%3 studies7171,080not evaluable ROB-
Atresia or stenosis of other parts of small intestine1.09 [0.41, 2.90]0%2 studies816not evaluable ROB-
Atrioventricular septal defect1.89 [0.83, 4.31]0%2 studies8981,067not evaluable ROB-
Cardiac septal defects1.13 [1.07, 1.19]0%2 studies72,88440,961not evaluable ROB1.51 [1.33; .]
Coarctation of aorta0.63 [0.29, 1.37]0%2 studies1,9321,067not evaluable ROB-
Craniosynostosis0.62 [0.33, 1.17]0%2 studies2,3451,070not evaluable ROB-
Ebstein's anomaly18.96 [1.17, 307.53]-1 study50980not evaluable ROB37.41 [1.61; .]
Hydrocephaly1.08 [0.51, 2.26]0%2 studies51384not evaluable ROB-
Spina bifida0.84 [0.41, 1.73]0%2 studies1,8571,068not evaluable ROB-
Tetralogy of Fallot1.37 [0.75, 2.49]0%2 studies1,7811,075not evaluable ROB-
Genetic syndromes and microdeletions0.43 [0.23, 0.81]-1 study2,280not evaluable ROB4.08 [.; 1.78]
17 non statistically significant endpoints reported in only one study

Growth parameters and prematurity
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Preterm (< 37 weeks)1.51 [1.29, 1.77]74%13 studies411,47866,644critical ROB2.38 [1.89; .]
Low birth weight (< 2500g)1.99 [1.42, 2.79]79%11 studies232,2802,662low ROB3.39 [2.19; .]
Small for gestational age (weight)1.20 [1.05, 1.38]61%7 studies898,85764,678not evaluable ROB1.70 [1.28; .]
Extremely preterm (< 28 weeks)1.56 [0.19, 12.75]35%2 studies2,0483,763not evaluable ROB-
Very preterm (28 to 32 weeks)1.32 [0.80, 2.15]0%2 studies10,6663,763not evaluable ROB-
Macrosomia (> 4000g)0.86 [0.76, 0.97]0%2 studies577,5331,358not evaluable ROB1.61 [.; 1.23]
1 non statistically significant endpoints reported in only one study

Maternal consequences
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Caesarean1.78 [1.15, 2.77]5%5 studies84148not evaluable ROB2.97 [1.56; .]
Preeclampsia0.95 [0.56, 1.62]0%3 studies148216not evaluable ROB-
Assisted deliveries (forceps, vacuum, ...)3.75 [1.06, 13.26]-1 study1817not evaluable ROB6.96 [1.31; .]
Postpartum hemorrhage3.51 [2.61, 4.73]-1 study3,131542not evaluable ROB6.48 [4.65; .]
1 non statistically significant endpoints reported in only one study

Neonatal disorders
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Neonatal medical care2.55 [1.56, 4.17]47%7 studies398389not evaluable ROB4.55 [2.50; .]
Low Apgar score (< 7) (at 5 min)2.19 [1.94, 2.48]0%4 studies8,864453not evaluable ROB3.81 [3.29; .]
Low Apgar score (< 7) (NOS)1.44 [0.23, 9.13]0%2 studies422not evaluable ROB-
Jaundice / Icterus1.21 [0.98, 1.48]0%2 studies117not evaluable ROB-
Neonatal disorders (as a whole)1.48 [1.08, 2.04]91%2 studies222,3981,246not evaluable ROB2.33 [1.38; .]
Neonatal hypoglycemia1.38 [1.19, 1.60]0%2 studies17not evaluable ROB2.11 [1.67; .]
Withdrawal syndrome / Neonatal abstinence syndrome / Poor neonatal adaptation3.24 [0.40, 26.39]76%2 studies2,4025,361not evaluable ROB-
Low Apgar score (< 7) (at 1 min)--0 study-
4 non statistically significant endpoints reported in only one study

Long term consequences
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
1 non statistically significant endpoints reported in only one study

Intrauterine deaths
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Early intrauterine deaths (< 22 weeks) / Spontaneous abortions1.74 [1.53, 1.98]58%9 studies156,0357,661serious ROB2.87 [2.43; .]
Late intrauterine deaths (> 22 weeks) / Stillbirths1.16 [1.07, 1.26]0%3 studies29,83562,257not evaluable ROB1.60 [1.35; .]
Perinatal death2.47 [1.07, 5.68]43%3 studies733,452not evaluable ROB4.37 [1.35; .]
Elective/induced termination of pregnancy2.45 [1.36, 4.43]79%2 studies853,852not evaluable ROB4.34 [2.06; .]
Intrauterine deaths (as a whole or unspecified)2.72 [1.85, 4.00]-1 study148460not evaluable ROB4.89 [3.11; .]

Neuro-developmental disorders
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk1.20 [0.99, 1.46]52%6 studies27,9609,156serious ROB-
ASD (Autism spectrum disorder): Diagnosis1.10 [0.75, 1.61]80%5 studies42,78413,103not evaluable ROB-
ADHD (Attention deficit hyperactivity disorder): Diagnosis1.11 [0.93, 1.32]35%4 studies28,8739,117not evaluable ROB-
ASD (Autism spectrum disorder): Diagnosis/Risk1.11 [0.72, 1.72]85%4 studies42,75010,920not evaluable ROB-
Psychomotor developmental disorders/delay3.17 [0.73, 13.75]83%3 studies43116not evaluable ROB-
Childhood autism (F84.0)0.93 [0.42, 2.05]0%2 studies2,0892,786not evaluable ROB-
Cognitive developmental disorders/delay (< 3 years old)3.26 [1.46, 7.26]0%2 studies34not evaluable ROB5.97 [2.28; .]
ADHD (Attention deficit hyperactivity disorder): Risk1.96 [0.59, 6.50]54%2 studies739not evaluable ROB-
Cognitive developmental disorders/delay (> 6 years old)1.76 [1.06, 2.92]-1 study16,3991,182not evaluable ROB2.92 [1.31; .]
Neuro-developmental disorders (as a whole)1.31 [1.03, 1.66]0%2 studies78,3712,428not evaluable ROB1.94 [1.21; .]
Severe cognitive developmental delay (Mental retardation) (> 6 years old)1.76 [1.06, 2.92]-1 study16,3991,182not evaluable ROB2.92 [1.31; .]
Learning disorders 1.14 [1.00, 1.29]-1 study101not evaluable ROB1.54 [1.06; .]
3 non statistically significant endpoints reported in only one study

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