[TREATMENT OF SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS (SSRIS AND SNRIS) DURING PREGNANCY AND LACTATION].

INTRODUCTION: Women are more likely to develop depression during the perinatal period than at any other time in their lives. Studies from recent years raise significant concerns regarding the potential of a depressive disorder in the pregnant mother to cause adverse obstetric results for the mother and the newborn. As antidepressants can penetrate the placenta to different degrees, concern has been raised regarding their teratogenic potential. In recent years various inconsistent and ambiguous reports specifying mild risks to the fetus and newborn from exposure to serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) during pregnancy have been published. This paper provides a review of current medical knowledge regarding the pharmacological treatment with common antidepressants such as SSRIs and SNRIs in pregnant women. Based on this review we also present treatment and follow-up recommendations of the major published guidelines for the treatment of serotonin and norepinephrine reuptake inhibitors (SSRIs and SNRIs) during pregnancy for the medical care providers.

The Association between Advanced Maternal Age and the Manifestations of Preeclampsia with Severe Features.

This retrospective cohort study aimed to explore the association between advanced maternal age and the clinical manifestations as well as laboratory parameters of preeclampsia with severe features. This study included 452 patients who were diagnosed with preeclampsia with severe features. The clinical and laboratorial characteristics of patients with preeclampsia with severe features aged ≥40 years old (study group) were compared to those of patients aged <40 years old (control group). Multivariant analysis was applied to assess the association between advanced maternal age and the manifestations of preeclampsia with severe features, adjusting for the variables that exhibited significant differences between the study and control groups. The multivariate analysis revealed that a maternal age of ≥40 years old was an independent risk factor for acute kidney injury (OR = 2.5, CI = 1.2-4.9, p = 0.011) and for new-onset postpartum preeclampsia (OR = 2.4, CI = 1.0-5.6, p = 0.046). Conversely, a maternal age ≥ 40 years old was associated with a reduced risk of HELLP syndrome (OR = 0.4, CI = 0.2-0.9, p = 0.018) and thrombocytopenia (OR = 0.5, CI = 0.3-0.9, p = 0.016) compared to that of the patients < 40 years of age. In conclusion, this study demonstrates that maternal age is significantly associated with the clinical manifestations and laboratory parameters of preeclampsia with severe features, highlighting the importance of age-specific management.

Maternal and Newborn Thyroid Hormone, and the Association With Polychlorinated Biphenyls (PCBs) Burden: The EHF (Environmental Health Fund) Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants found in human tissues. PCBs can be transferred through the placenta and may disrupt the maternal thyroid homeostasis, and affect fetal thyroid hormone production. Several studies have shown that intrauterine exposure to PCBs might be associated with abnormal levels of thyroid hormones in mothers and their offspring. Objectives: To examine the associations between environmental exposure to PCBs and thyroid hormone levels in mothers and newborns. Methods: The EHF-Assaf-Harofeh-Ichilov cohort includes 263 mothers-newborns dyads. A total of 157 mother-newborn dyads had both PCBs and thyroid function measures. Regression models were used to estimate associations between maternal PCB exposure and maternal and newborn thyroid function, controlling for possible confounders. Results: Four PCBs congeners were analyzed: PCBs 118, 138, 153, and 180. ∑PCBs median (IQR) level was 14.65 (2.83-68.14) ng/g lipids. The median maternal thyroid-stimulating hormone (TSH) level was 2.66 (0.70-8.23) µIU/ml, the median maternal free thyroxine (FT4) level was 12.44 (11.27-13.53) µg/dL, the median maternal thyroid peroxidase antibodies (TPO Ab) level was 9.6 (7.36-12.51) IU/mL. Newborns' median total thyroxine (T4) level was 14.8 (7.6-24.9) µg/dL. No association was found between exposure to different congeners or to ∑PCBs and maternal TSH, FT4, thyroglobulin autoantibodies (Tg Ab), TPO Ab and newborn total T4 levels. In multivariable analysis a 1% change in ∑PCBs level was significantly associated with a 0.57% change in maternal TSH levels in women with body mass index (BMI) < 19. The same association was observed for each of the studied PCB congeners. Maternal TPO Ab levels statistically significantly increased by 0.53 and 0.46% for 1% increase in PCB 118 and 153 congeners, respectively. In women with BMI > 25, the association between the PCBs levels and maternal TSH levels was in the opposite direction. No association was found in women with normal BMI (19-24.9). Conclusions: Background exposure to environmentally relevant concentrations of some PCBs can alter thyroid hormone homeostasis in pregnant women and might be associated with abnormal TSH levels and TPO-Ab in women with low BMI. However, these findings require further investigation.

Hypoglycemics: pharmacokinetic considerations during pregnancy.

A wide range of physiological and hormonal changes occur during pregnancy. Most begin early in the first trimester and increase by the last trimester. These changes can significantly affect pharmacokinetics and pharmacodynamics of drugs and thus may alter their safety and efficacy. Approximately 5% of pregnant women are affected by some form of diabetes, with gestational diabetes being the most prevalent. Several classes of antidiabetic drugs are currently available for the treatment of diabetes, including human insulin, its short and long analogues, and oral hypoglycemic agents. Maternal and fetal responses to these drugs can be affected by changes in absorption, distribution, and elimination in both the mother and the placental-fetal unit. This can dictate the amount of drug that can cross and the amount that is metabolized or eliminated by the placenta. Further studies are needed on the safety of antidiabetic drugs in pregnancy to clarify the extent of their transplacental passage. Specifically, in vitro placental perfusion studies in combination with controlled trials and cord blood measurements can provide insight in to the pharmacokinetics of drug transport across the placenta. This article reviews common types of antidiabetic drugs, focusing on pharmacokinetic considerations that need to be incorporated into the decision on treatment in pregnancy.

Treating the mother--protecting the unborn: the safety of hypoglycemic drugs in pregnancy.

The purpose of this review is to provide a brief overview of the safety of antidiabetics in pregnancy. Specifically, concerns over teratogenicity due to the possible placental transfer of antidiabetics as well as maternal and neonatal outcomes are addressed. Several new insulin analogs are currently available for the treatment of diabetes. Due to the improved glycemic control demonstrated in non pregnant patients, these analogs may also prove to be beneficial in pregnancy. Insulin lispro is the only insulin analog that has been systematically studied in pregnancy. Results of these studies show a lack of transfer across the placenta and no adverse fetal and neonatal outcomes. The use of oral hypoglycemic agents in pregnancy is also generating interest. To date, there has been only one randomized controlled trial investigating the use of glyburide which found it to be safe and effective in the management of gestational diabetes mellitus. The lack of randomized controlled trials for antidiabetics in pregnancy highlights the need for more comprehensive investigation regarding their safety and efficacy.

Folic acid: the right dose.

ABSTRACTQUESTION The new Motherisk Guidelines suggest 5 mg/d of folic acid. Why was the dose increased? What is the time frame for taking such a dose?ANSWER Recent data from Ontario reveal that 40% of women of reproductive age still do not achieve therapeutic systemic levels of folate needed to prevent neural tube defects. Compliance is less than optimal among women using prenatal vitamins, rendering many women unprotected against neural tube defects. Taking a higher dose of folate will allow achievement of protective folate levels, even with partial compliance. Five mg of folate should be used daily several months before conception until the end of the first trimester.

Toward improved pregnancy labelling.

Information about the use of a medication in pregnancy is part of overall drug labelling as prepared by the pharmaceutical company and approved by the regulators. It is aimed at assisting clinicians in prescribing, however, very few drugs are labelled for specific indications in pregnancy, since there is rarely information about the use of a drug in this condition. Recently the FDA has drafted new guidelines for the labeling of drugs in pregnancy and breastfeeding, to replace the A,B,C,D,X system that was used for more than 30 years. Here we document the use of the new system through 3 different medications; each representing a different clinical situation in pregnancy--acute infection, chronic pain, and drug use during labor. Advantages and challenges in the new system are being highlighted.