Selective Serotonin Reuptake Inhibitors in Human Pregnancy: To Treat or Not to Treat?

Selective serotonin reuptake inhibitors (SSRIs) are increasingly prescribed during pregnancy. The purpose of the present paper is to summarize and evaluate the current evidence for the risk/benefit analysis of SSRI use in human pregnancy. The literature has been inconsistent. Although most studies have not shown an increase in the overall risk of major malformations, several studies have suggested that SSRIs may be associated with a small increased risk for cardiovascular malformations. Others have noted associations between SSRIs and specific types of rare major malformations. In some studies, there appears to be a small increased risk for miscarriages, which may be associated with the underlying maternal condition. Neonatal effects have been described in up to 30% of neonates exposed to SSRIs late in pregnancy. Persistent pulmonary hypertension of the newborn has also been described with an absolute risk of <1%. The risk associated with treatment discontinuation, for example, higher frequency of relapse and increased risk of preterm delivery, should also be considered. The overall benefit of treatment seems to outweigh the potential risks

Methods for Prenatal Sex Determination and Their Importance in Understanding and Prevention of Gender-Related Birth Defects

Various hormones, chemicals, and teratogenic agents exhibit gender-related effects in utero as well as postnatally. Among such gender-specific teratogens are endocrine disruptors, especially phthalates that affect male gonads, diabetes-induced oxidative stress with more deleterious effects on male offspring, procarbazine-induced cleft palate affecting more male fetal rats compared to females, and VPA-induced autism-like behavior that affects differently males than females. Hence, there are many needs for the accurate determination of genetic gender. In newborn animals, the morphological methods that exist for sex determination (i.e., anogenital distance) are generally inaccurate. Hence, an accurate and simple method for the prenatal and early postnatal assessment of the genetic sex, prior to reliable evaluation from the external genitalia, is of utmost importance. Indeed, several methods have been developed for accurate assessment of genetic sex, which are discussed in this chapter. Findings from studies in our laboratory have shown that the method described by McFarlan et al. for the assessment of genetic sex in adult mice by PCR of Sly/Xlr genes can be reliably used for the genetic sex determination of any tissue, including embryos and fetuses, with an accuracy of about 100%

The Role of Reactive Oxygen Species in Diabetes-Induced Anomalies in Embryos of Cohen Diabetic Rats

The role of the antioxidant defense mechanism in diabetesinduced anomalies was studied in the Cohen diabetes-sensitive (CDs) and -resistant (CDr) rats, a genetic model of nutritionally induced type 2 diabetes mellitus. Embryos, 12.5-day-old, of CDs and CDr rats fed regular diet (RD) or a diabetogenic high-sucrose diet (HSD) were monitored for growth retardation and congenital anomalies. Activity of superoxide dismutase (SOD) and catalaselike enzymes and levels of ascorbic acid (AA), uric acid (UA), and dehydroascorbic acid (DHAA) were measured in embryonic homogenates. When fed RD, CDs rats had a decreased rate of pregnancy, and an increased embryonic resorption. CDs embryos were smaller than CDr embryos; 46% were maldeveloped and 7% exhibited neural tube defects (NTDs). When fed HSD, rate of pregnancy was reduced, resorption rate was greatly increased (56%; P < .001), 47.6% of the embryos were retrieved without heart beats, and 27% exhibited NTD. In contrast, all the CDr embryos were normal when fed RD or HSD. Activity of SOD and catalase was not different in embryos of CDs and CDr rats fedRD. When fed HSD, levels of AA were significantly reduced, the ratio DHAA/AA was significantly increased, and SOD activity was not sufficiently increased when compared to embryos of CDr. The reduced fertility of the CDs rats, the growth retardation, and NTD seem to be genetically determined. Maternal hyperglycemia seems to result in environmentally induced embryonic oxidative stress, resulting in further embryonic damage

Alcohol Abuse in Pregnant Women: Effects on the Fetus and Newborn, Mode of Action and Maternal Treatment

Offspring of mothers using ethanol during pregnancy are known to suffer from developmental delays and/or a variety of behavioral changes. Ethanol, may affect the developing fetus in a dose dependent manner. With very high repetitive doses there is a 6–10% chance of the fetus developing the fetal alcoholic syndrome manifested by prenatal and postnatal growth deficiency, specific craniofacial dysmorphic features, mental retardation, behavioral changes and a variety of major anomalies. With lower repetitive doses there is a risk of “alcoholic effects” mainly manifested by slight intellectual impairment, growth disturbances and behavioral changes. Binge drinking may impose some danger of slight intellectual deficiency. It is advised to offer maternal abstinence programs prior to pregnancy, but they may also be initiated during pregnancy with accompanying close medical care. The long term intellectual outcome of children born to ethanol dependent mothers is influenced to a large extent by the environment in which the exposed child is raised

Primary versus Nonprimary Cytomegalovirus Infection during Pregnancy, Israel

We examined prospectively the outcome of primary and nonprimary maternal cytomegalovirus (CMV) infection during pregnancy among 88 and 120 women, respectively. The risk for vertical transmission was 1.83× higher for primary infection than for nonprimary infection. Nonetheless, congenital CMV disease was diagnosed in both infection groups at similar rates

An association between Helicobacter pylori infection and cognitive function in children at early school age: a community-based study

<p>Abstract</p> <p>Background</p> <p><it>H. pylori </it>infection has been linked to iron deficiency anemia, a risk factor of diminished cognitive development. The hypothesis on an association between <it>H. pylori </it>infection and cognitive function was examined in healthy children, independently of socioeconomic and nutritional factors.</p> <p>Methods</p> <p>A community-based study was conducted among 200 children aged 6-9 years, from different socioeconomic background. <it>H. pylori </it>infection was examined by an ELISA kit for detection of <it>H. pylori </it>antigen in stool samples. Cognitive function of the children was blindly assessed using Stanford-Benit test 5^thedition, yielding IQ scores. Data on socioeconomic factors and nutritional covariates were collected through maternal interviews and from medical records. Multivariate linear regression analysis was performed to obtain adjusted beta coefficients.</p> <p>Results</p> <p><it>H. pylori </it>infection was associated with lower IQ scores only in children from a relatively higher socioeconomic community; adjusted beta coefficient -6.1 (95% CI -11.4, -0.8) (P = 0.02) for full-scale IQ score, -6.0 (95% CI -11.1, -0.2) (P = 0.04) for non-verbal IQ score and -5.7 (95% CI -10.8, -0.6) (P = 0.02) for verbal IQ score, after controlling for potential confounders.</p> <p>Conclusions</p> <p><it>H. pylori </it>infection might be negatively involved in cognitive development at early school age. Further studies in other populations with larger samples are needed to confirm this novel finding.</p

SSRIs and SNRIs (SRI) in Pregnancy: Effects on the Course of Pregnancy and the Offspring: How Far Are We from Having All the Answers?

Serotonin has important roles in the development of the brain and other organs. Manipulations of synaptic serotonin by drugs such as serotonin reuptake inhibitors (SRI) or serotonin norepinephrine reuptake inhibitors (SNRI) might alter their development and function. Of interest, most studies on the outcome of prenatal exposure to SRI in human have not found significant embryonic or fetal damage, except for a possible, slight increase in cardiac malformations. In up to a third of newborns exposed to SRI, exposure may induce transient neonatal behavioral changes (poor neonatal adaptation) and increased rate of persistent pulmonary hypertension. Prenatal SRI may also cause slight motor delay and language impairment but these are transient. The data on the possible association of prenatal SRIs with autism spectrum disorder (ASD) are inconsistent, and seem to be related to pre-pregnancy treatment or to maternal depression. Prenatal SRIs also appear to affect the hypothalamic hypophyseal adrenal (HPA) axis inducing epigenetic changes, but the long-term consequences of these effects on humans are as yet unknown. SRIs are metabolized in the liver by several cytochrome P450 (CYP) enzymes. Faster metabolism of most SRIs in late pregnancy leads to lower maternal concentrations, and thus potentially to decreased efficacy which is more prominent in women that are rapid metabolizers. Studies suggest that the serotonin transporter SLC6A4 promoter is associated with adverse neonatal outcomes after SRI exposure. Since maternal depression may adversely affect the child&#8217;s development, one has to consider the risk of SRI discontinuation on the fetus and the child. As with any drug treatment in pregnancy, the benefits to the mother should be considered versus the possible hazards to the developing embryo/fetus