metaPreg - Proton Pump Inhibitors during pregnancy

Proton Pump Inhibitors updated on 10-13-2025

Table Graphic exposition period:

Adverse outcome	OR 95%CI	I2	k	No. cases	No. exposed	publication bias	ROB	E-value
Congenital malformations
All congenital malformations (majors, minors, majors and minors, or unspecified)	1.07 [1.02, 1.12]	0%	10 studies	120,789	47,198	low	ROB	1.35 [1.17; .]
Major congenital malformations	1.07 [1.02, 1.13]	0%	7 studies	120,020	46,158	not evaluable	ROB	1.35 [1.18; .]
Congenital heart defects	1.09 [1.01, 1.17]	0%	4 studies	51,192	43,701	not evaluable	ROB	1.39 [1.12; .]
Cleft palate	1.17 [0.75, 1.83]	11%	4 studies	2,845	44,348	not evaluable	ROB	-
Hypospadias	1.37 [0.67, 2.79]	61%	5 studies	2,481	24,977	not evaluable	ROB	-
Club foot / Talipes equinovarus	1.30 [0.75, 2.25]	0%	3 studies	573	3,816	not evaluable	ROB	-
Congenital hydronephrosis	0.60 [0.27, 1.32]	0%	3 studies	3	4,065	not evaluable	ROB	-
Atrial septal defect	1.28 [0.90, 1.81]	0%	3 studies	763	5,085	not evaluable	ROB	-
Cardiac septal defects	2.33 [0.36, 14.99]	78%	2 studies	33,911	40,679	not evaluable	ROB	-
Cleft lip with or without cleft palate	0.70 [0.07, 7.28]	50%	2 studies	1	3,790	not evaluable	ROB	-
Down syndrom / Trisomy 21	4.12 [0.34, 49.29]	0%	2 studies	1	414	not evaluable	ROB	-
Eye defects	0.97 [0.67, 1.40]	0%	2 studies	2,094	40,679	not evaluable	ROB	-
Hydrocephaly	1.47 [0.60, 3.60]	78%	2 studies	1,272	48,302	not evaluable	ROB	-
Limb defects	1.07 [0.93, 1.22]	0%	2 studies	13,715	40,679	not evaluable	ROB	-
Microcephaly / Small head circumference for gestational age	1.52 [0.42, 5.56]	36%	2 studies	138	166	not evaluable	ROB	-
Nervous system anomalies	1.24 [1.00, 1.55]	0%	2 studies	4,790	40,679	not evaluable	ROB	-
Polydactyly	0.97 [0.27, 3.48]	0%	2 studies	4	3,790	not evaluable	ROB	-
Syndactyly	1.28 [0.04, 37.41]	59%	2 studies		3,790	not evaluable	ROB	-
Ventricular septal defect	1.09 [0.76, 1.56]	0%	3 studies	1,188	5,085	not evaluable	ROB	-
Abdominal wall defects	2.74 [1.14, 6.58]	-	1 study	236	40,540	not evaluable	ROB	4.92 [1.54; .]
Respiratory system anomalies	1.77 [1.12, 2.79]	-	1 study	891	40,540	not evaluable	ROB	2.94 [1.49; .]
17 non statistically significant endpoints reported in only one study
Growth parameters and prematurity
Adverse outcome	OR 95%CI	I2	k	No. cases	No. exposed	publication bias	ROB	E-value
Preterm (< 37 weeks)	1.18 [0.93, 1.51]	60%	8 studies	8,281	1,363	not evaluable	ROB	-
Low birth weight (< 2500g)	0.95 [0.90, 0.99]	0%	5 studies	116,128	42,409	not evaluable	ROB	1.30 [.; 1.11]
Small for gestational age (weight)	1.12 [0.86, 1.46]	5%	3 studies	89	98	not evaluable	ROB	-
Very preterm (28 to 32 weeks)	0.64 [0.29, 1.40]	0%	2 studies	293	91	not evaluable	ROB	-
3 non statistically significant endpoints reported in only one study
Maternal consequences
Adverse outcome	OR 95%CI	I2	k	No. cases	No. exposed	publication bias	ROB	E-value
Preeclampsia	1.08 [0.81, 1.44]	85%	3 studies	18,716	30,188	not evaluable	ROB	-
Postpartum hemorrhage	0.54 [0.15, 1.91]	0%	2 studies	14	99	not evaluable	ROB	-
3 non statistically significant endpoints reported in only one study
Neonatal disorders
Adverse outcome	OR 95%CI	I2	k	No. cases	No. exposed	publication bias	ROB	E-value
Low Apgar score (< 7) (at 5 min)	0.60 [0.30, 1.23]	48%	3 studies	1,068	59	not evaluable	ROB	-
Bone fractures / bone mineralisation anomalies	0.73 [0.59, 0.90]	-	1 study	4,472	10,547	not evaluable	ROB	2.08 [.; 1.47]
Neonatal infections	0.62 [0.05, 7.91]	78%	2 studies	27	99	not evaluable	ROB	-
Neonatal medical care	1.43 [0.75, 2.75]	0%	2 studies	65	99	not evaluable	ROB	-
6 non statistically significant endpoints reported in only one study
Long term consequences
Adverse outcome	OR 95%CI	I2	k	No. cases	No. exposed	publication bias	ROB	E-value
Childhood asthma	1.23 [1.01, 1.49]	91%	7 studies	30,156	42,401	not evaluable	ROB	1.75 [1.08; .]
Infant allergies	1.21 [0.91, 1.61]	94%	3 studies	38,031	39,764	not evaluable	ROB	-
Intrauterine deaths
Adverse outcome	OR 95%CI	I2	k	No. cases	No. exposed	publication bias	ROB	E-value
Late intrauterine deaths (> 22 weeks) / Stillbirths	1.60 [0.56, 4.54]	0%	5 studies	73	700	not evaluable	ROB	-
Early intrauterine deaths (< 22 weeks) / Spontaneous abortions	1.29 [0.84, 1.97]	7%	2 studies	114	524	not evaluable	ROB	-
Perinatal death	0.80 [0.16, 3.98]	74%	2 studies	1,350	1,529	not evaluable	ROB	-
Ectopic pregnancy	-	-	0 study					-
Elective/induced termination of pregnancy	2.99 [1.79, 5.00]	-	1 study	63	411	not evaluable	ROB	5.43 [2.98; .]
2 non statistically significant endpoints reported in only one study
Neuro-developmental disorders
Adverse outcome	OR 95%CI	I2	k	No. cases	No. exposed	publication bias	ROB	E-value
1 non statistically significant endpoints reported in only one study