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Front. Pediatr. | doi: 10.3389/fped.2019.00309

NEONATAL OUTCOMES IN MATERNAL DEPRESSION IN RELATION TO INTRAUTERINE DRUG EXPOSURE

 Silvia Corti1, Martina I. Mazzocco1, Paola Pileri1,  Chiara Mandò1, Anna F. Moscatiello1, Dario Cattaneo1, Stefania Cheli2, Sara Baldelli2, Laura Pogliani1, Emilio Clementi2, 3 and  Irene Cetin1*
  • 1ASST Fatebenefratelli Sacco, Italy
  • 2Department of Biomedical Sciences and Clinics Luigi Sacco, Faculty of Medicine and Surgery, University of Milan, Italy
  • 3Eugenio Medea (IRCCS), Italy

Background
SSRIs (Selective Serotonin Reuptake Inhibitors) are the most useful drugs to treat depression during pregnancy. Intrauterine exposure to SSRIs may increase the risk of growth restriction, preterm birth and neonatal complications. However, advantages in treating depression seem to exceed potential drug side effects in respect to not treated depression. SSRIs undergo extensive hepatic first-pass metabolism with the involvement of several cytochrome P450 (CYPs) enzymes. Genetic polymorphisms may influence the expression and activity of CYPs genes.
The first aim of this study was to evaluate neonatal outcomes in depressed mothers exposed to SSRIs during pregnancy. SSRIs pharmacogenetics was also evaluated in a subset of mothers and fetuses.
Methods
In this case-control study, cases (n=43) were Caucasian women with a diagnosis of depression and/or anxiety, treated with SSRIs for the whole pregnancy. Controls (n=86) were Caucasian women without a psychiatric diagnosis and not exposed to SSRIs during pregnancy. Exclusion criteria for both groups were other psychotropic drugs, anti-epileptics, drug of abuse, alcohol addiction, maternal or fetal infectious diseases, fetal/neonatal chromosomal genetic abnormalities. Maternal and fetal blood samples were obtained at delivery to analyse genotype in 33 cases.
Results
The population was homogenous for demographic, anthropometric, socio-economic and obstetric variables except for smoking and mean hemoglobin values before delivery. Obstetric features, were comparable. Newborns exposed to SSRIs during fetal life were significantly more likely to be Low Birth Weight (birth weight<2500 g) (p=0.01), had significantly lower mean Apgar scores at 1’ (p=0.006) and at 5’ (p=0.023) and worse Apgar distribution at 1’ (p=0.017) and at 5’ (p=0.013). 56% of newborns presented one or more symptoms consistent with poor neonatal adaptation syndrome (PNAS).
Pharmacogenetic analysis at delivery did not show significant differences in the frequencies of obstetric or neonatal complications in relation to polymorphisms.
Conclusions
We found that newborns exposed to SSRIs are at increased risk of poor neonatal outcomes in terms of low birth weight, low Apgar scores and, clinically, poor neonatal adaptation syndrome. Preliminary pharmacogenetic analysis showed that the degree of CYPs alterations, that depends on polymorphisms, may influence neonatal outcomes.

Keywords: Selective serotonin reuptake inhibitors (SSRI), Pharmacogenetics, poor neonatal adaptation syndrome, newborns, Pregnancy, depression.

Received: 06 Dec 2018; Accepted: 09 Jul 2019.

Edited by:

Alessandro Favilli, Department of Surgical and Biomedical Sciences, University of Perugia, Italy

Reviewed by:

Jonathan M. Davis, Tufts University, United States
Gil Gutvirtz, Ben-Gurion University of the Negev, Israel  

Copyright: © 2019 Corti, Mazzocco, Pileri, Mandò, Moscatiello, Cattaneo, Cheli, Baldelli, Pogliani, Clementi and Cetin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Irene Cetin, ASST Fatebenefratelli Sacco, Milan, Italy, irene.cetin@unimi.it