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Method
Danish register data
We linked data on all pregnancies from 1996 to 2006 from the
Medical Birth Register with data from the Psychiatric Central
Register, the Medicinal Product Statistics register and Statistics
Denmark.
The Medical Birth Register16 includes data on date of birth,
gestational age, Apgar score 5 min after birth, birth weight, length
of fetus, maternal smoking status during pregnancy, parity and
maternal age on all deliveries in Denmark. Data from births of
more than one child from 1996 to 2006 were included whereas
twin births were excluded, implying that the same woman could
be included more than once.
The Medicinal Product Statistics is a nationwide prescription
database containing individual information on all prescriptions
filled at all Danish pharmacies from 1995 and onwards.17 Data
included and distinguished between ATC codes (Anatomical
Therapeutical Chemical classification system) for antidepressant,
antipsychotics, anti-epileptics and other kinds of drugs. Antidepressants were classified as selective serotonin reuptake
inhibitors (SSRIs: fluoxetine, citalopram, escitalopram, paroxetine,
sertraline, fluvoxamine: ATC N06AB0310), newer antidepressants
(nefazodone, mirtazapine, venlafaxine, reboxetine: ATC N06AX06,
347
Jensen et al
Table 1
Characteristics of pregnant women and offspring according to antidepressant therapy and depressive diagnosis
Maternal characteristics
Antidepressant medication
before pregnancya
(n = 33 084)
Antidepressant medication
during pregnancya
(n = 8375)
Depression diagnosis
before end of pregnancya
(n = 3916)
All pregnancies
(n = 664 089)
30 (2734)
30 (2734)
30 (2634)
30 (2633)
Parity, %
First child
Second child
5Third child
41.7
34.4
23.9
43.1
32.1
24.9
41.2
36.5
22.3
42.8
37.6
19.7
Smoking status, %
Non-smoker
Smoking
Quit smoking
Unknown
64.2
27.2
2.7
5.9
57.7
31.5
2.8
8.0
60.8
29.1
3.1
7.0
68.9
16.2
1.8
13.1
Lithium-treatment, %
No
Yes
99.9
0.1
99.8
0.2
99.6
0.4
100.0
0.01
Anti-epileptic treatment, %
No
Yes
98.7
1.3
97.2
2.8
97.9
2.1
99.6
0.4
Antipsychotic treatment, %
No
Yes
98.1
2.0
94.3
5.7
95.3
4.7
99.8
0.2
Other medication, %
No
Yes
21.5
78.5
17.5
82.6
20.0
80.1
32.1
67.9
Characteristics child, %
Female child
Gestational age, weeks: median (IQR)
Apgar score, %
57
57
48.4
48.1
48.3
48.7
39 (3840)
39 (3840)
39 (3840)
39 (3939)
99.3
0.7
98.9
1.1
99.4
0.6
99.4
0.6
348
Discussion
We found that a low Apgar score was attributed to the use of SSRIs
during pregnancy and not to the effect of the disease or associated
lifestyle factors. Non-SSRI antidepressants were not associated
with a low Apgar score. No increased rates were found among
women who used antidepressants prior to pregnancy (but not
during; risk group 2) or who had a diagnosis of depression but
used no antidepressants during pregnancy (risk groups 5 and 6).
The Apgar score 5 min after birth is a clear index of problems
in adult life; studies have shown that infants with low Apgar scores
(57 at 5 min) are at increased risk of a low IQ score at age 18
(OR = 1.35, 95% CI 1.071.69),11 never receiving graduation
grades (OR = 1.93, 95% CI 1.752.14),12 never attending university
Table 2 Adjusted odds rate of a low Apgar score (06 v. 710) according to depressive diagnosis and antidepressant therapy
before or during pregnancy a
Diagnosis before Antidepressants Antidepressants
end of pregnancy before pregnancy during pregnancy
Model 1
Risk group
1
2
3
4
5
6
7
8
Anti-epileptics during pregnancy
Antipsychotics during pregnancy
Other medication during pregnancy
Model 2
Antidepressants before pregnancy
Antidepressants during pregnancy
Diagnosis of depression before end of pregnancy
+
+
+
+
+
+
+
+
Unadjusted OR
(95% CI)
628 898
24 185
1 212
5 878
731
1 900
164
1 121
ORb (95%CI)
1 (reference)
0.96 (0.811.14)
1.53 (0.862.72)
1.72 (1.342.20)
0.44 (0.111.77)
1.03 (0.581.83)
0
1.35 (0.742.47)
1.24 (0.841.82)
1.26 (0.742.13)
1.11 (1.041.19)
0.95 (0.791.14)
1.87 (1.412.47)
0.69 (0.411.15)
1.00 (0.851.17)
1.67 (1.302.14)
0.80 (0.531.20)
a. The eight groups in Model 1 are mutually exclusive and sum up to 100%. The three groups in Model 2 are not mutually exclusive.
b. Odds ratio adjusted for: maternal age, social status, smoking status, calendar year, gender of newborn, and use of anti-epileptics, antipsychotics and other types of medication.
349
Jensen et al
OR (95% CI)b
During pregnancy
Selective serotonin reuptake inhibitors
Newer antidepressants
Older antidepressants
7 208
982
780
1.96 (1.522.54)
0.83 (0.401.74)
0.53 (0.191.45)
Before pregnancy
Selective serotonin reuptake inhibitors
Newer antidepressants
Older antidepressants
27 466
5 875
6 282
0.93 (0.781.12)
1.21 (0.881.67)
1.14 (0.851.54)
350
First received 5 Jun 2012, final revision 12 Oct 2012, accepted 12 Dec 2012
26 Wisner KL, Sit DK, Hanusa BH, Moses-Kolko EL, Bogen DL, Hunker DF, et al.
Major depression and antidepressant treatment: impact on pregnancy and
neonatal outcomes. Am J Psychiatry 2009; 166: 55766.
Funding
Funding was provided by The Lundbeck Foundation.
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351
Hans Mrch Jensen, Randi Grn, jvind Lidegaard, Lars Henning Pedersen, Per Kragh Andersen and
Lars Vedel Kessing
BJP 2013, 202:347-351.
Access the most recent version at DOI: 10.1192/bjp.bp.112.115931
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