Women are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that occur during pregnancy, it is expected that pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion of drugs) would also be affected in ways that may necessitate changes in dosing schedules. The objective of this study was to systematically identify existing clinically relevant evidence on PK changes during pregnancy. Systematic searches were conducted in MEDLINE (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), and Web of Science (Thomson Reuters), from database inception to August 31, 2015. An update of the search from September 1, 2015, to May 20, 2016, was performed, and relevant data were added to the present review. No language or date restrictions were applied. All publications of clinical PK studies involving a group of pregnant women with a comparison to nonpregnant participants or nonpregnant population data were eligible to be included in this review. A total of 198 studies involving 121 different medications fulfilled the inclusion criteria. In these studies, commonly investigated drug classes included antiretrovirals (54 studies), antiepileptic drugs (27 studies), antibiotics (23 studies), antimalarial drugs (22 studies), and cardiovascular drugs (17 studies). Overall, pregnancy-associated changes in PK parameters were often observed as consistent findings among many studies, particularly enhanced drug elimination and decreased exposure to total drugs (bound and unbound to plasma proteins) at a given dose. However, associated alterations in clinical responses and outcomes, or lack thereof, remain largely unknown. This systematic review of pregnancy-associated PK changes identifies a significant gap between the accumulating knowledge of PK changes in pregnant women and our understanding of their clinical impact for both mother and fetus. It is essential for clinicians to be aware of these unique pregnancy-related changes in PK, and to critically examine their clinical implications.

Objective To investigate whether a diagnosis of gestational diabetes mellitus (GDM) is a risk factor for subsequent long-term cardiovascular morbidity. Design A population-based study. Setting Soroka University Medical Center, a tertiary centre in the southern region of Israel. Patients A cohort of women with and without a diagnosis of GDM who delivered during the years 1988–1999 with a follow-up period until 2010. Interventions A comparison of the incidence of cardiovascular morbidity. Results Of 47 909 deliveries that met the inclusion criteria, 4928 (10.3%) occurred in patients who were diagnosed with GDM. During a follow-up period of more than 10 years, compared with women who gave birth at the same time period, after adjustment for age and ethnicity, patients with GDM had higher rates of cardiovascular morbidity including non-invasive cardiac diagnostic procedures (OR=1.8; 95% CI 1.4 to 2.2), simple cardiovascular events (OR=2.7; 95% CI 2.4 to 3.1) and total cardiovascular hospitalisations (OR=2.3; 95% CI 2.0 to 2.5). In a Cox proportional hazards model, adjusted for comorbidities such as pre-eclampsia and obesity, GDM was independently associated with cardiovascular hospitalisations (adjusted HR 2.6, 95% CI 2.3 to 3). Conclusions GDM is an independent risk factor for long-term cardiovascular morbidity in a follow-up period of more than a decade.

Objective To investigate whether severe and recurrent pre-eclampsia increase the risk for long-term maternal atherosclerotic disease. Study design A population-based study compared the incidence of long-term atherosclerotic morbidity in a cohort of women who delivered in the years 1988–2012. The exposure variable was pre-eclampsia. Mean follow-up duration was 11.2 years. Kaplan–Meier survival curves were used to estimate cumulative incidence of simple, complex (ie, angina pectoris and congestive heart failure, respectively) cardiovascular-related and renal-related hospitalisations. Cox proportional hazards models were used to estimate the adjusted HRs for cardiovascular and renal morbidity. Results During the study, 96 370 patients met the inclusion criteria; 7824 (8.1%) in patients who were diagnosed at least once with pre-eclampsia. Patients with pre-eclampsia had higher rates of cardiovascular morbidity including cardiac non-invasive (OR 1.4; 95% CI 1.1 to 1.7; p=0.005) and invasive diagnostic procedures (OR 1.7; 95% CI 1.2 to 2.3; p=0.001), simple (OR 1.5; 95% CI 1.2 to 1.8; p=0.001), as well as complex cardiovascular events (OR 2.4; 95% CI 2.2 to 2.8; p=0.001) and renal (OR 3.7; 95% CI 2.2 to 6.0; p=0.001) hospitalisations. A significant linear association was noted between the severity of pre-eclampsia (no pre-eclampsia, mild pre-eclampsia, severe pre-eclampsia and eclampsia) and cardiovascular (2.7% vs 4.5% vs 5.2% vs 5.7%, respectively; p=0.001), as well as renal disease (0.1% vs 0.2% vs 0.5% vs 1.1%, respectively; p=0.001). Likewise, a linear association was found between the number of previous pregnancies with pre-eclampsia (no pre-eclampsia, one event and ≥2 events of pre-eclampsia) and risk for future simple cardiovascular disease (1.2% vs 1.6% vs 2.2%, respectively; p=0.001), complex cardiovascular disease (1.3% vs 2.7% vs 4.6%, respectively; p=0.001) and total cardiovascular hospitalisations (2.7% vs 4.4% vs 6.0%, respectively; p=0.001). Using a Kaplan–Meier survival curve, patients with pre-eclampsia had significantly higher cumulative incidence of atherosclerotic-related hospitalisations. In a Cox proportional hazards model, adjusted for confounders such as maternal age, parity, diabetes mellitus and obesity, pre-eclampsia remained independently associated with atherosclerotic hospitalisations. Conclusions Previous pregnancy with pre-eclampsia is an independent risk factor for long-term maternal atherosclerotic morbidity. The risk is more substantial for patients with severe and recurrent episodes of pre-eclampsia.

The aim of the current study was to assess the risk for post-partum depression among women delivering during the COVID-19 pandemic as compared to the risk among women delivering before the COVID-19 pandemic. A cohort study was performed among women delivering singletons at term which were recruited in the maternity wards of the Soroka University Medical Center. Recruitment was done during the COVID-19 strict isolation period (March 18 and April 29, 2020). Women delivering during the COVID-19 pandemic completed the Edinburgh Postnatal Depression Scale (EPDS), and the results were compared to women delivering at the same medical center before the COVID-19 pandemic. Multivariable logistic regression models were constructed to control for potential confounders. A total of 223 women who delivered during the COVID-19 strict isolation period were recruited. Women delivering during the COVID-19 pandemic had lower risk of having a high (> 10) or very high (≥ 13) EPDS score as compared with women delivering before the COVID-19 pandemic (16.7% vs 31.3%, p = 0.002, and 6.8% vs 15.2%, p = 0.014, for EPDS ≥ 10 and EPDS ≥ 13, respectively). These results remained similar in the multivariable logistic regression models, for both EPDS score ≥ 10 and EPDS score ≥ 13, while controlling for maternal age, ethnicity, marital status, and adverse pregnancy outcomes (adjusted OR 0.4, 95% CI 0.23–0.70, p = 0.001 and adjusted OR 0.3, 95% CI 0.15–0.74, p = 0.007 for EPDS score > 10 and > 13, respectively). In our population, delivering during the COVID-19 pandemic was independently associated with lower risk of post-partum depression.