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Fulltext The Risk of Congenital Heart Anomalies Following Prenatal Exposure to Serotonin Reuptake Inhibitors-Is Pharmacogenetics the Key?

Daud AN, Bergman JE, Kerstjens-Frederikse WS, Groen H, Wilffert B

Int J Mol Sci, 2016 Aug 13;17(8).
PMID: 27529241 DOI: 10.3390/ijms17081333

Serotonin reuptake inhibitors (SRIs) are often prescribed during pregnancy. Previous studies that found an increased risk of congenital anomalies, particularly congenital heart anomalies (CHA), with SRI use during pregnancy have created concern among pregnant women and healthcare professionals about the safety of these drugs. However, subsequent studies have reported conflicting results on the association between CHA and SRI use during pregnancy. These discrepancies in the risk estimates can potentially be explained by genetic differences among exposed individuals. In this review, we explore the potential pharmacogenetic predictors involved in the pharmacokinetics and mechanism of action of SRIs, and their relation to the risk of CHA. In general, the risk is dependent on the maternal concentration of SRIs and the foetal serotonin level/effect, which can be modulated by the alteration in the expression and/or function of the metabolic enzymes, transporter proteins and serotonin receptors involved in the serotonin signalling of the foetal heart development. Pharmacogenetics might be the key to understanding why some children exposed to SRIs develop a congenital heart anomaly and others do not.
Elastic constant determination of hardwoods using ultrasonic insertion technique

Mat Daud AN, Jaafar R, Ayop SK, Yaacob MIH, Rohani MS

Ultrasonics, 2017 03;75:194-198.
PMID: 28006660 DOI: 10.1016/j.ultras.2016.11.025

Ultrasonic insertion technique (IT) is an ultrasonic technique which involves sample immersion in a solution to determine its acoustic properties. IT is normally used to determine the acoustic properties of a medical phantom. We proposed the use of IT as an alternative technique to the common contact ultrasonic technique: through-transmission technique (TT) for determining the elastic constant of hardwoods in longitudinal, tangential and radial directions. The elastic constant of twelve rectangular-shaped Malaysian hardwoods from three different categories; heavy, medium and light with the density ranging from 602 to 992kgm-3 were determined using IT and TT. Both techniques were carried out at 24.0°C surrounding temperature and utilized 2.25MHz ultrasonic transducers. Data from both techniques were compared to validate the use of the proposed technique. Findings indicated that IT offers consistent and accurate results for, tangential and radial elastic constants (TEC and REC) within 8.89% and 5.86% differences, respectively compared to TT for all tested hardwoods. IT offers an alternative technique for TEC and REC determinations of precious wood samples.
Fulltext Maternal use of drug substrates of placental transporters and the effect of transporter-mediated drug interactions on the risk of congenital anomalies

Daud AN, Bergman JE, Oktora MP, Kerstjens-Frederikse WS, Groen H, Bos JH, et al.

PLoS One, 2017;12(3):e0173530.
PMID: 28288183 DOI: 10.1371/journal.pone.0173530

BACKGROUND: A number of transporter proteins are expressed in the placenta, and they facilitate the placental transfer of drugs. The inhibition of P-glycoprotein (P-gp) was previously found to be associated with an increase in the risk of congenital anomalies caused by drug substrates of this transporter. We now explore the role of other placental transporter proteins.
METHODS: A population-based case-referent study was performed using cases with congenital anomalies (N = 5,131) from EUROCAT Northern Netherlands, a registry of congenital anomalies. The referent population (N = 31,055) was selected from the pregnancy IADB.nl, a pharmacy prescription database.
RESULTS: Ten placental transporters known to have comparable expression levels in the placenta to that of P-gp, were selected in this study. In total, 147 drugs were identified to be substrates, inhibitors or inducers, of these transporters. Fifty-eight of these drugs were used by at least one mother in our cases or referent population, and 28 were used in both. The highest user rate was observed for the substrates of multidrug resistance-associated protein 1, mainly folic acid (6% of cases, 8% of referents), and breast cancer resistance protein, mainly nitrofurantoin (2.3% of cases, 2.9% of referents). In contrast to P-gp, drug interactions involving substrates of these transporters did not have a significant effect on the risk of congenital anomalies.
CONCLUSIONS: Some of the drugs which are substrates or inhibitors of placental transporters were commonly used during pregnancy. No significant effect of transporter inhibition was found on fetal drug exposure, possibly due to a limited number of exposures.

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