An excellent fellow health care practitioner in a complimentary field recently sent me a question regarding a new study that he had seen published.   He was concerned because he was seeing an increasing number of his pregnant women patients come in on moderate to significant doses of SSRI’s.  The study that he cited specifically linked SSRI use during pregnancy to autism and developmental delays in boys and was released April 15th 2014 by Johns Hopkins Bloomberg School of Public Health.  This got my attention.  I had previously been relatively sanguine about the use of SSRI’s in pregnant women, preferring both fluoxetine (Prozac ® ) and sertraline (Zoloft ® ) because of their decades long use and the lack of emergence of significant birth defects or problems in children born to mothers taking these drugs.

So I did what I always do when faced with a question that I really don’t know the complete answer to, and went to the peer-reviewed medical literature on www.pubmed.gov.  Here is what I found (author and attribution is clearly cited):

Psychol Med. 2010 Oct;40(10):1723-33. doi: 10.1017/S0033291709992194. Epub 2010 Jan 5.

Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data.

Abstract

BACKGROUND:

Concerns have been expressed about possible adverse effects of the use of antidepressant medication during pregnancy, including risk for neonatal pathology and the presence of congenital malformations.

METHOD:

Data from the Swedish Medical Birth Register (MBR) from 1 July 1995 up to 2007 were used to identify women who reported the use of antidepressants in early pregnancy or were prescribed antidepressants during pregnancy by antenatal care: a total of 14 821 women with 15 017 infants. Maternal characteristics, maternal delivery diagnoses, infant neonatal diagnoses and the presence of congenital malformations were compared with all other women who gave birth, using the Mantel-Haenszel technique and with adjustments for certain characteristics.

RESULTS:

There was an association between antidepressant treatment and pre-existing diabetes and chronic hypertension but also with manypregnancy complications. Rates of induced delivery and caesarean section were increased. The preterm birth rate was increased but not that of intrauterine growth retardation. Neonatal complications were common, notably after tricyclic antidepressant (TCA) use. An increased risk of persistent pulmonary hypertension of the newborn (PPHN) was verified. The congenital malformation rate was increased after TCAs. An association between use of paroxetine and congenital heart defects was verified and a similar effect on hypospadias was seen.

CONCLUSIONS:

Women using antidepressants during pregnancy and their newborns have increased pathology. It is not clear how much of this is due to drug use or underlying pathology. Use of TCAs was found to carry a higher risk than other antidepressants and paroxetine seems to be associated with a specific teratogenic property.
And this one….
Br J Clin Pharmacol. 2012 Jan;73(1):126-34. doi: 10.1111/j.1365-2125.2011.04081.x.

Disturbed development of the enteric nervous system after in utero exposure of selective serotonin re-uptakeinhibitors and tricyclic antidepressants. Part 2: Testing the hypotheses.

Abstract

AIMS:

Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects.

METHODS:

The pharmacy prescription database IADB.nl was used for a cohort study in which laxative and antidiarrhoeal medication use in children after in utero exposure to antidepressants (TCA, SSRI, fluoxetine or paroxetine exposed) was compared with no antidepressant exposure. Laxatives and antidiarrhoeal medication use were applied as a proxy for constipation and diarrhoea respectively, which may be associated with disturbed enteric nervous system (ENS) development.

RESULTS:

Children exposed in utero to SSRIs (mainly fluoxetine and paroxetine) in the second and third trimester or to TCAs in the first trimester, more often received laxatives. Combined exposure to TCAs and SSRIs in pregnancy was associated with a 10-fold increase in laxative use. In utero exposure to SSRIs is not associated with antidiarrhoeal medication use compared with non-exposed children. In contrast, antidiarrhoeal medication use was significantly higher in children exposed to TCAs anytime in pregnancy.

CONCLUSIONS:

The increased laxative use after second and third trimester exposure to SSRIs might be explained through the inhibitory effect of the serotonin re-uptake transporter (SERT) and because of selectivity for the 5-HT(2B) receptor which affects the ENS. TCA exposure during the first trimester leads to increased laxative use probably through inhibition of the norepinephrine transporter (NET). Exposure of TCAs anytime in pregnancyleads to increase diarrhoeal use possibly through down-regulation of α₂-adrenoceptors or up-regulation of the pore forming α(1c) subunit.
© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.
——
MY CONCLUSIONS:
The limitations of the Hopkins study were noted succinctly by the authors:
“Regarding treatment, the authors note that maternal depression itself carries risks for the fetus, and the benefits of using SSRI during pregnancy should be considered carefully against the potential harm. The researchers also note that large sample studies are needed to investigate the effects in girls with ASD. Limitations of the study acknowledged include the difficulty in isolating SSRI effects from those of their indications for use, lack of information on SSRI dosage precluded dose-response analyses, and the relatively small sample of DD children resulted in imprecise estimates of association, which should be viewed with caution.”  The problem is that even at 1,000, it’s still a “low n” study (number of study participants), due to the minority of delivered infants that subsequently had links to autism.
As well, it does not state what maternal exposure there was to Rhogam, flu shots, etc, nor what the underlying medical problems (as well as, presumptively, depression) were in the mother.  It also does not specific the toxic load of vaccines that the putatively autistic offspring had received.   Frequently, mothers who subsequently give birth to children with autism have medical illnesses themselves, including autoimmune thyroid disease and autoimmune connective tissue diseases.   These diseases could certainly get a mom-to-be depressed.  It would therefore be the underlying medical problems, not the application of an antidepressant, that could be the root cause of the problem.
This study bring to light again that old bugaboo, “Correlation does not prove causation.”  I recall seeing one study years ago (which I can’t put my hands on) that reviewed neuropsychiatric testing for kids born to mothers either on SSRI’s or TCA’s taken many years previously while they they were pregnant with the index follow-up evaluees.   No perturbations of scores were noted.
And at the psych meetings I’ve gone to, it’s emphasized that there are risks to not adequately treating maternal depression.   However, the Johns Hopkins study that stimulated my thinking and the two previous ones give me pause.  I would much rather a depressed, pregnant woman receive TMS  (transcranial magnetic stimulation – explanatory video HERE) for her depression which absolutely does not expose her to any medication risk during pregnancy.
But as with all medical treatments, consideration must be given to the “risk:benefit ratio” and that can only be done in an informed, empathic, and open discussion between a patient and her physician.