Pregnancy is a time of physical and emotional vulnerability, which can potentially lead to or exacerbate depression. Sadly, suicide is a leading cause of death in both high- and low-income countries.1,2  Although psychological therapies are effective and may be sufficient treatment for depression in pregnancy, for some women, antidepressant treatment may be required. Research also suggests that when women abruptly cease antidepressants in pregnancy, suicidal ideation may increase.3 

Clinicians rely on research to accurately help patients weigh the risks and benefits of treatment options for depression that may save lives. For many women, the potential longer-term impacts on child outcomes are key deciding factors in whether to initiate or continue a specific type of antidepressant treatment.4,5 

In a study published in this month’s issue of Pediatrics, Singal et al6  begin by stating that antidepressant exposure during pregnancy may be associated with “sustained cognitive impairment” in the child. However, other studies have not found this to be the case.710  The animal studies cited in this report differ from other animal studies that have found protective effects from antidepressant exposure during gestation.11,12  In their report, Singal et al find that antidepressant exposure is associated with “increased risks of deficits in language and/or cognition” on the basis of a screening measure of school readiness in kindergarten.6  How should clinicians interpret this concerning finding?

It is important to recognize that the main outcome measure is school readiness, and this is different from a neuropsychological direct assessment of cognition or language neurodevelopment. Although the Early Development Index is a widely used and well-studied measure of school readiness, other studies have found that it has only modest specificity for developmental vulnerability and is not strongly correlated with language development.13,14  Other potential confounders (eg, parental cognitive ability, exposure to parental smoking, child health, parent involvement, and disorganized attachment) were not included in the analysis. No statistical approach can completely eliminate this risk of bias.

Critical new research is needed to inform how to help women with significant depression during pregnancy while avoiding risk to their developing fetuses. Additional research that examines pregnancy exposure to illness and pharmacologic treatment may shed light on how we should proceed. For instance, in the area of epilepsy and anticonvulsant treatment, a series of well-designed and well-executed studies examining pharmacologic treatments for seizures in pregnancy resulted in specific and scientifically sound information for making decisions about treatments. From this research, we know which agents and doses do and do not pose a risk for children’s cognitive outcomes. This allows for careful planning and consideration of treatment in women across the childbearing years. These outcomes are well characterized and measured with gold standard, neuropsychologically administered measures of cognitive development within replicated, prospective studies.15 

Researchers such as Casper et al16  and Nulman et al9  led the early research into antenatal antidepressant exposure and used neuropsychological measures of child outcomes. The challenge now to those in mental health research is to broaden and develop those early studies. Only then will women be able to understand the implications of agent, dose, and timing of exposure to antidepressant medication in pregnancy and be able to weigh both the risks and benefits of treatment for both their health and their children.

Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.

FUNDING: No external funding.

COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2019-1157.

1
Austin
MP
,
Kildea
S
,
Sullivan
E
.
Maternal mortality and psychiatric morbidity in the perinatal period: challenges and opportunities for prevention in the Australian setting
.
Med J Aust
.
2007
;
186
(
7
):
364
367
2
Oates
M
.
Perinatal psychiatric disorders: a leading cause of maternal morbidity and mortality
.
Br Med Bull
.
2003
;
67
(
1
):
219
229
3
Einarson
A
.
Abrupt discontinuation of psychotropic drugs following confirmation of pregnancy: a risky practice
.
J Obstet Gynaecol Can
.
2005
;
27
(
11
):
1019
1022
4
Einarson
A
,
Selby
P
,
Koren
G
.
Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counselling
.
J Psychiatry Neurosci
.
2001
;
26
(
1
):
44
48
5
Misri
S
,
Eng
AB
,
Abizadeh
J
,
Blackwell
E
,
Spidel
A
,
Oberlander
TF
.
Factors impacting decisions to decline or adhere to antidepressant medication in perinatal women with mood and anxiety disorders
.
Depress Anxiety
.
2013
;
30
(
11
):
1129
1136
6
Singal
D
,
Chateau
D
,
Struck
S
, et al
.
In utero antidepressants and neurodevelopmental outcomes in kindergarteners
.
Pediatrics
.
2020
;
145
(
5
):
e20191157
7
Gentile
S
,
Galbally
M
.
Prenatal exposure to antidepressant medications and neurodevelopmental outcomes: a systematic review
.
J Affect Disord
.
2011
;
128
(
1–2
):
1
9
8
Prady
SL
,
Hanlon
I
,
Fraser
LK
,
Mikocka-Walus
A
.
A systematic review of maternal antidepressant use in pregnancy and short- and long-term offspring’s outcomes
.
Arch Women Ment Health
.
2018
;
21
(
2
):
127
140
9
Nulman
I
,
Koren
G
,
Rovet
J
, et al
.
Neurodevelopment of children following prenatal exposure to venlafaxine, selective serotonin reuptake inhibitors, or untreated maternal depression
.
Am J Psychiatry
.
2012
;
169
(
11
):
1165
1174
10
Galbally
M
,
Lewis
AJ
,
Buist
A
.
Child developmental outcomes in preschool children following antidepressant exposure in pregnancy
.
Aust N Z J Psychiatry
.
2015
;
49
(
7
):
642
650
11
Knaepen
L
,
Rayen
I
,
Charlier
TD
, et al
.
Developmental fluoxetine exposure normalizes the long-term effects of maternal stress on post-operative pain in Sprague-Dawley rat offspring
.
PLoS One
.
2013
;
8
(
2
):
e57608
12
Rayen
I
,
van den Hove
DL
,
Prickaerts
J
,
Steinbusch
HW
,
Pawluski
JL
.
Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence
.
PLoS One
.
2011
;
6
(
9
):
e24003
13
Janus
M
,
Brinkman
S
,
Duku
E
, et al
.
The Early Development Instrument: A Population-Based Measure for Communities. A Handbook on Development, Properties, and Use
.
Hamilton, Canada
:
Offord Centre for Child Studies
;
2007
14
Janus
M
,
Brinkman
SA
,
Duku
EK
.
Validity and psychometric properties of the early development instrument in Canada, Australia, United States, and Jamaica
.
Soc Indic Res
.
2011
;
103
(
2
):
283
15
Haskey
C
,
Galbally
M
.
Mood stabilizers in pregnancy and child developmental outcomes: a systematic review
.
Aust N Z J Psychiatry
.
2017
;
51
(
11
):
1087
1097
16
Casper
RC
,
Fleisher
BE
,
Lee-Ancajas
JC
, et al
.
Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy
.
J Pediatr
.
2003
;
142
(
4
):
402
408

Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.