Selective Serotonin Reuptake Inhibitor (SSRI) updated on 07-01-2025

Neonatal medical care

id	Study   Auto Lee (Controls exposed to TCAs), 2025Lee (Controls unexposed, general pop), 2025Raviv, 2025Cornet - SSRIs, 2024Gover, 2023Rommel, 2022Marks - Sertraline (Controls exposed to Bupropion), 2021Ulbrich, 2021Levy, 2020Gungor (Controls exposed to Mirtazapine), 2019Gungor (Controls unexposed, disease free), 2019Gungor (Controls unexposed, sick), 2019Giardinelli (Controls unexposed, disease free), 2018Giardinelli (Controls unexposed, sick), 2018Hogue, 2017Bracero, 2016Kivistö, 2016Norby, 2016Robinson-Wolrath, 2016Salisbury (Controls unexposed, disease free), 2016Salisbury (Controls unexposed, sick), 2016Malm (Controls unexposed, disease free), 2015Malm (Controls unexposed, sick), 2015Engelstad (Controls unexposed, disease free), 2014Engelstad (Controls unexposed, sick), 2014Smith, 2013Colvin, 2012Grzeskowiak a (Controls unexposed, disease free), 2012Grzeskowiak a (Controls unexposed, sick), 2012Klieger-Grossmann - Escitalopram, 2012Calderon-Margalit, 2009Lund (Controls unexposed, disease free), 2009Lund (Controls unexposed, sick), 2009Wisner (Controls unexposed, disease free), 2009Wisner (Controls unexposed, sick), 2009Maschi - Paroxetine, 2008Davis, 2007Lennestal, 2007Pearson (Controls exposed to TCA), 2007Pearson (Controls unexposed, NOS), 2007Suri, 2007Wen, 2006Sivojelezova - Citalopram, 2005Oberlander, 2004Suri - Fluoxetine (Controls unexposed, disease free), 2004Suri - Fluoxetine (Controls unexposed, sick), 2004Casper, 2003Costei - Paroxetine (Controls unexposed, NOS), 2002Costei - Paroxetine (Controls unexposed, sick), 2002Chambers - Fluoxetine, 1996	Lib. in paper	Exposition period  Auto during pregnancy (anytime or not specified)1st trimester2nd trimester3rd trimester2nd and/or 3rd trimesterthroughout pregnancyearly pregnancydays before deliverylate pregnancypreconception-onlypericonceptionalpreconceptional for kinetic reasonat least 1st trimester3 months (or more) before pregnancy or during pregnancy1st and 2nd trimester3 months or more before pregnancy or1st trimesterPaternal exp. genotoxic window only (0–3 months preconception)Paternal exposure: epigenetic window only (3–xxx months preconception)Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception)Paternal exposure: other window	Study type  All studies Case control excluded Only case control	Control type    Auto unexposed (general population or NOS)unexposed, sickunexposed, disease freeexposed to other treatment, sicknot specifiedsiblingwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S18442 R78281	Lee (Controls exposed to TCAs), 2025	Admission to neonatal intensive care unit (NICU)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SSRI only	0.81 [0.48;1.39] C excluded (control group)	41/1,465   21/613	62	1,465		ref
S18408 R77703	Lee (Controls unexposed, general pop), 2025	Admission to neonatal intensive care unit (NICU)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SSRI only	1.03 [0.74;1.43]	41/1,465   8,566/463,440	8,607	1,465		ref
S18131 R76225	Raviv, 2025	Neonatal intensive care unit admission (NICU)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed (general population or NOS)	Adjustment: No Monotherapy: no or not specified	3.07 [2.59;3.65] C	150/2,321   2,278/103,607	2,428	2,321		ref
S18258 R76640	Cornet - SSRIs, 2024	Delayed neonatal adaptation (presence of at least one of the following: 5min Apgar score ≤5; positive pressure ventilation or intubation during delivery room resuscitation; or admission to the NICU with respiratory distress requiring invasive or non-invasive ventilation)	late pregnancy	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: no or not specified	2.14 [1.96;2.33]	847/7,573   12,078/272,517	12,925	7,573		ref
S14988 R61341	Gover, 2023	Delivery room advanced resuscitation	throughout pregnancy	retrospective cohort	unexposed (general population or NOS)	Adjustment: No Matched Monotherapy: no or not specified	1.58 [0.24;10.61] C	3/21   2/21	5	21		ref
S18233 R76476	Rommel, 2022	Neonatal admission (inpatient contact with the first 28 days, excluding contact with the ICD-10 Z38 or Z76)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: Yes Monotherapy: SSRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	1.43 [1.35;1.51]	-/16,429   -/23,676	-	16,429		ref
S13112 R49960	Marks - Sertraline (Controls exposed to Bupropion), 2021	Neonatal intensive care unit admission	during pregnancy (anytime or not specified)	retrospective cohort	exposed to other treatment, sick	Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...)	1.08 [0.81;1.45]	384/1,653   91/406	475	1,653		ref
S10057 R36520	Ulbrich, 2021	Neonatal intensive care unit (NICU) admission	3rd trimester	retrospective cohort	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: no or not specified	2.13 [1.18;3.32]	20/163   282/4,770	302	163		ref
S5461 R24127	Levy, 2020	Neonatal intensive care unit	throughout pregnancy	retrospective cohort	unexposed (general population or NOS)	Adjustment: No Matched Monotherapy: no or not specified	8.34 [3.78;18.39] C	44/82   10/82	54	82		ref
S12918 R49003	Gungor (Controls exposed to Mirtazapine), 2019	Staying at Neonatal Intensive Care Unit (NCU)	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SSRI only	1.48 [0.27;8.06] C excluded (control group)	7/40   2/16	9	40		ref
S8158 R25130	Gungor (Controls unexposed, disease free), 2019	Staying at Neonatal Intensive Care Unit (NCU)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: No Monotherapy: SSRI only	0.48 [0.15;1.62] C excluded (control group)	7/40   7/23	14	40		ref
S8159 R25136	Gungor (Controls unexposed, sick), 2019	Staying at Neonatal Intensive Care Unit (NCU)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No Monotherapy: SSRI only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified	1.41 [0.33;6.10] C	7/40   3/23	10	40		ref
S7921 R23970	Giardinelli (Controls unexposed, disease free), 2018	Neonatal intensive care unit	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: No Monotherapy: no or not specified	5.93 [0.27;130.35] C excluded (control group)	2/24   0/26	2	24		ref
S7916 R23961	Giardinelli (Controls unexposed, sick), 2018	Neonatal intensive care unit	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy)	0.95 [0.12;7.41] C	2/24   2/23	4	24		ref
S7569 R22727	Hogue, 2017	Neonatal Intensive Care Unit admission (in full-term neonates)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SSRI only	4.90 [1.30;18.70]	16/117   4/116	20	117		ref
S10062 R36569	Bracero, 2016	Neonatal intensive care unit (NICU) admissions	days before delivery	retrospective cohort	unexposed, sick	Adjustment: No Monotherapy: no or not specified	12.17 [2.00;73.89] C	4/6   12/85	16	6		ref
S7570 R22768	Kivistö, 2016	Neonatal intensive care	during pregnancy (anytime or not specified)	retrospective cohort	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SSRI only	2.20 [1.67;2.88]	82/358   2,431/24,402	2,513	358		ref
S5430 R16579	Norby, 2016	Admission to Neonatal intensive care unit	3rd trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: no or not specified	1.70 [1.60;1.80]	1,501/9,100   59,210/718,533	60,711	9,100		ref
S14992 R61351	Robinson-Wolrath, 2016	Need for any resuscitation	during pregnancy (anytime or not specified)	retrospective cohort	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SSRI only	2.20 [1.67;2.89]	-/-   -/-	-	-		ref
S8053 R24537	Salisbury (Controls unexposed, disease free), 2016	Neonatal intensive care unit admission	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: No Monotherapy: no or not specified	2.02 [0.54;7.58] C excluded (control group)	6/52   4/66	10	52		ref
S8071 R24580	Salisbury (Controls unexposed, sick), 2016	Neonatal intensive care unit admission	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No Monotherapy: no or not specified Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified	7.17 [0.83;61.77] C	6/52   1/56	7	52		ref
S6107 R15971	Malm (Controls unexposed, disease free), 2015	Neonatal care unit	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, disease free excluded	Adjustment: Yes Monotherapy: no or not specified	1.38 [1.29;1.48] excluded (control group)	2,405/15,729   3,032/31,394	5,437	15,729		ref
S5374 R15955	Malm (Controls unexposed, sick), 2015	Neonatal care unit	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: Yes Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	1.24 [1.14;1.35]	2,405/15,729   1,160/9,652	3,565	15,729		ref
S12947 R49133	Engelstad (Controls unexposed, disease free), 2014	Admission to the neonatal intensive care unit (NICU)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, disease free excluded	Adjustment: Yes Monotherapy: SSRI only	1.14 [0.69;1.91] excluded (control group)	55/126   50/222	105	126		ref
S12948 R49134	Engelstad (Controls unexposed, sick), 2014	Admission to the neonatal intensive care unit (NICU)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No Monotherapy: SSRI only	1.17 [0.71;1.93] C	55/126   51/128	106	126		ref
S13258 R51065	Smith, 2013	Neonatal intensive care unit (NICU)	3rd trimester	prospective cohort	unexposed, disease free	Adjustment: No Monotherapy: no or not specified	2.85 [0.27;30.62] C	1/6   4/61	5	6		ref
S5428 R20521	Colvin, 2012	Intensive care unit admissions	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Monotherapy: no or not specified	1.40 [1.26;1.55]	438/3,764   8,125/94,561	8,563	3,764		ref
S5961 R15335	Grzeskowiak a (Controls unexposed, disease free), 2012	Neonate admitted to hospital	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, disease free excluded	Adjustment: Yes Monotherapy: SSRI only	2.37 [1.76;3.19] excluded (control group)	87/221   6,114/32,004	6,201	221		ref
S5367 R15330	Grzeskowiak a (Controls unexposed, sick), 2012	Neonate admitted to hospital	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: Yes Monotherapy: SSRI only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy)	1.92 [1.39;2.65]	87/221   414/1,566	501	221		ref
S5395 R16288	Klieger-Grossmann - Escitalopram, 2012	Neonatal intensive care unit admission	late pregnancy	prospective cohort	unexposed (general population or NOS)	Adjustment: No Matched Monotherapy: SSRI only	1.32 [0.59;2.94] C	14/172   12/191	26	172		ref
S5406 R15092	Calderon-Margalit, 2009	Neonatal Intensiv Care Unit (NICU)	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: no or not specified	1.36 [0.70;2.67]	-/132   -/2,493	-	132		ref
S491 R16208	Lund (Controls unexposed, disease free), 2009	Neonatal intensive care unit admission	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: Yes Monotherapy: no or not specified	2.39 [1.69;3.39] excluded (control group)	54/329   3,845/51,770	3,899	329		ref
S6162 R16212	Lund (Controls unexposed, sick), 2009	Neonatal intensive care unit admission	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No Monotherapy: no or not specified Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified	2.00 [1.47;2.72] C	54/329   439/4,902	493	329		ref
S5408 R16600	Wisner (Controls unexposed, disease free), 2009	Admission to Neonatal Intensive care unit	throughout pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No Monotherapy: no or not specified	2.77 [1.05;7.31] C excluded (control group)	9/48   10/130	19	48		ref
S6249 R16608	Wisner (Controls unexposed, sick), 2009	Admission to Neonatal Intensive care unit	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy)	0.85 [0.19;3.67] C	9/48   3/14	12	48		ref
S7288 R21081	Maschi - Paroxetine, 2008	Neonatal Intensive Care Unit (NICU)/Special Care Nursery (SCN) admissions	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: No Matched Monotherapy: no or not specified	1.00 [0.12;8.46] C	1/58   6/348	7	58		ref
S5394 R20677	Davis, 2007	Respiratory distress syndrome and other respiratory conditions	3rd trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Monotherapy: no or not specified	1.97 [1.65;2.35]	112/874   5,300/75,219	5,412	874		ref
S15011 R61495	Lennestal, 2007	Respiratory problems (Includes a diagnosis of respiratory problems and/or use of mechanical ventilation or continuous positive airway pressure)	late pregnancy	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: no or not specified	1.72 [1.41;2.11]	99/-   -/-	-	-		ref
S11220 R41289	Pearson (Controls exposed to TCA), 2007	Admission in Special care nursery of neonatal intensive care unit	during pregnancy (anytime or not specified)	retrospective cohort	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SSRI only	0.32 [0.10;1.03] C excluded (control group)	5/42   11/37	16	42		ref
S11219 R41286	Pearson (Controls unexposed, NOS), 2007	Admission in Special care nursery of neonatal intensive care unit	during pregnancy (anytime or not specified)	retrospective cohort	unexposed (general population or NOS)	Adjustment: No Monotherapy: SSRI only	1.20 [0.42;3.46] C	5/42   17/168	22	42		ref
S5989 R17674	Suri, 2007	Special care nursery admission	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free	Adjustment: No Monotherapy: no or not specified	10.36 [0.58;186.64] C	10/48   0/19	10	48		ref
S5405 R16053	Wen, 2006	Mechanical ventilation in neonates	3 months (or more) before pregnancy or during pregnancy excluded	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Matched Monotherapy: no or not specified	1.14 [0.74;1.75] excluded (exposition period)	34/972   87/3,878	121	972		ref
S508 R17594	Sivojelezova - Citalopram, 2005	Neonatal intensive care unit admission	3rd trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: No Matched Monotherapy: no or not specified	4.20 [1.70;10.30]	10/63   6/158	16	63		ref
S7969 R24468	Oberlander, 2004	Poor neonatal adaptation (high level of medical care and observation)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free	Adjustment: No Monotherapy: SSRI only	3.50 [0.65;18.85] C	7/28   2/23	9	28		ref
S7764 R22971	Suri - Fluoxetine (Controls unexposed, disease free), 2004	Neonatal Intensive Care Unit (NICU) admissions	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: No Monotherapy: SSRI only	0.52 [0.09;2.95] C excluded (control group)	3/28   3/16	6	28		ref
S7581 R22970	Suri - Fluoxetine (Controls unexposed, sick), 2004	Neonatal Intensive Care Unit (NICU) admissions	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No Monotherapy: SSRI only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified	0.96 [0.14;6.39] C	3/28   2/18	5	28		ref
S510 R15166	Casper, 2003	Admission to neonatal intensive care units	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy)	7.98 [0.42;151.51] C	7/31   0/13	7	31		ref
S5954 R15276	Costei - Paroxetine (Controls unexposed, NOS), 2002	Neonate respiratory distress	3rd trimester	prospective cohort	unexposed (general population or NOS) excluded	Adjustment: No Matched Monotherapy: no or not specified	11.07 [0.62;197.91] C excluded (control group)	9/55   0/27	9	55		ref
S5953 R15272	Costei - Paroxetine (Controls unexposed, sick), 2002	Neonate respiratory distress	3rd trimester	prospective cohort	unexposed, sick	Adjustment: No Matched Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy)	5.09 [0.61;42.43] C	9/55   1/27	10	55		ref
S490 R15172	Chambers - Fluoxetine, 1996	Admission to a special-care nursery	late pregnancy	prospective cohort	unexposed (general population or NOS)	Adjustment: No Monotherapy: no or not specified	4.74 [2.41;9.30] C	23/73   20/226	43	73		ref
					Total	36 studies	1.84 [1.63;2.07]		106,889	61,231
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

Sensitivity analysis

Publication bias and p-hacking diagnosis

Sub-groups analysis using all included studies

excluded 5954, 7764, 11220, 491, 5408, 5961, 12947, 6107, 8053, 7921, 12918, 8158, 18442

Umbrella review (other published meta-analyses)