Hypertensive disorders in pregnancy are a leading cause of maternal mortality worldwide. The incidence of hypertension in pregnancy continues to increase. Currently, we are unable to determine which patient will develop superimposed preeclampsia or identify subsets of preeclampsia syndrome. Opportunities for research in this area exist to better define treatment aimed at improving maternal outcomes.

Zika virus (ZIKV) infection during pregnancy leads to an increased risk of fetal growth restriction and fetal central nervous system malformations, which are outcomes broadly referred to as the Congenital Zika Syndrome (CZS). Here we infect pregnant rhesus macaques and investigate the impact of persistent ZIKV infection on uteroplacental pathology, blood flow, and fetal growth and development. Despite seemingly normal fetal growth and persistent fetal-placenta-maternal infection, advanced non-invasive in vivo imaging studies reveal dramatic effects on placental oxygen reserve accompanied by significantly decreased oxygen permeability of the placental villi. The observation of abnormal oxygen transport within the placenta appears to be a consequence of uterine vasculitis and placental villous damage in ZIKV cases. In addition, we demonstrate a robust maternal-placental-fetal inflammatory response following ZIKV infection. This animal model reveals a potential relationship between ZIKV infection and uteroplacental pathology that appears to affect oxygen delivery to the fetus during development.

This project was supported by the Oregon Health and Science University Knight Cardiovascular Institute, Center for Developmental Health and the Struble Foundation. There are no competing interests.

Importance: Marijuana is the most commonly used dependent substance in pregnancy. The main active chemical of marijuana ) readily crosses the placenta, and cannabinoid receptors have been identified in fetal brain and placenta. As a result, prenatal marijuana use could potentially have detrimental impact on fetal development.Objective: This review aims to summarize the existing literature and current recommendations for marijuana use while pregnant or lactating. Evidence Acquisition: A PubMed literature search using the following terms was performed to gather relevant data: "cannabis," "cannabinoids," "marijuana," "fetal outcomes," "perinatal outcomes," "pregnancy," "lactation."Results: Available studies on marijuana exposure in pregnancy were reviewed and support some degree of developmental disruption, including an increased risk of fetal growth restriction and adverse neurodevelopmental consequences. However, much of the existing prenatal marijuana research was performed in the 1980s, when quantities of THC were lower and the frequency of use was less. Additionally, most human studies are also limited and conflicting as most studies have been observational or retrospective, relying primarily on patient self-report and confounded by polysubstance abuse and small sample sizes, precluding determination of a causal effect specific for marijuana. Given the paucity of evidence, it is currently recommended to avoid using marijuana while pregnant or when breastfeeding. Conclusion and Relevance:There is a critical need for research on effects in pregnancy using present-day THC doses. Once the adverse perinatal effects of marijuana exposure are identified and well characterized, patient education and antenatal surveillance can be developed to predict and mitigate its impact on maternal and fetal health.

Purpose To characterize spatial patterns of T2∗ in the rhesus macaque placenta, to correlate these patterns with placental perfusion determined using dynamic contrast enhanced (DCE)-MRI, and to evaluate the potential for using the blood oxygen level-dependent (BOLD) effect to quantify placental perfusion without the use of exogenous contrast reagent. Methods Magnetic resonance imaging was performed on three pregnant rhesus macaques at gestational day 110. Multi-echo spoiled gradient echo measurements were used to compute maps of T2∗. Spatial maxima in these maps were compared with foci of early enhancement determined by DCE-MRI. Results Local maxima in T2∗ maps are strongly correlated with spiral arteries identified by DCE-MRI, with mean spatial separations ranging from 2.34 to 6.11 mm in the three animals studied. Spatial patterns of R2∗(=1∕T2∗) within individual placental lobules can be quantitatively analyzed using a simple model to estimate fetal arterial oxyhemoglobin concentration [Hbo,f] and a parameter viPS/Φ, reflecting oxygen transport to the fetus. Estimated mean values of [Hbo,f] ranged from 4.25 mM to 4.46 mM, while viPS/Φ ranged from 2.80×105 cm−3 to 1.61×106 cm−3. Conclusions Maternal spiral arteries show strong spatial correlation with foci of extended T2∗ observed in the primate placenta. A simple model of oxygen transport accurately describes the spatial dependence of R2∗ within placental lobules and enables assessment of placental function and oxygenation without requiring administration of an exogenous contrast reagent.

Alcohol exposure during pregnancy results in impaired growth, stillbirth, and fetal alcohol spectrum disorder. Fetal alcohol deficits are lifelong issues with no current treatment or established diagnostic or therapeutic tools to prevent and/or ameliorate some of these adverse outcomes. Despite the recommendation to abstain, almost half of the women consume alcohol in pregnancy in the United States. This review focuses on the trends in prenatal alcohol exposure, implications for maternal and fetal health, and evidence suggesting that preconception and the prenatal period provide a window of opportunity to intervene, mitigate, and ideally curtail the lifetime effects of fetal alcohol spectrum disorder.

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy on the developing fetal brain is poorly understood. Other antenatal infections such as influenza have been associated with adverse neurodevelopmental outcomes in offspring. Although vertical transmission has been rarely observed in SARS-CoV-2 to date, given the potential for profound maternal immune activation, impact on the developing fetal brain is likely. Here we review evidence that SARS-CoV-2 and other viral infections during pregnancy can result in maternal, placental and fetal immune activation, and ultimately in offspring neurodevelopmental morbidity. Finally, we highlight the need for cellular models of fetal brain development to better understand potential short- and long-term impacts of maternal SARS-CoV-2 infection on the next generation.

Objective Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol linking altered placental function to impaired fetal development remain areas of active research. Recently, we developed MRI techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T2*, and perfusion using dynamic contrast-enhanced (DCE) MRI. The objective of this study was to evaluate the effects of first trimester alcohol exposure on macaque placental function and to characterize fetal brain development, in vivo. Study Design Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to orally self-administer either 1.5g/kg/day of a 4% ethanol solution (equivalent to 6 drinks/day) or an isocaloric control fluid from pre-conception until gestational day 60 (G60, term is G168). All underwent Doppler ultrasound (D-US) followed by MRI consisting of T2* and DCE measurements. D-US was used to measure uterine artery (Uta) and umbilical vein velocimetry and diameter to calculate Uta volume blood flow (cQuta) and placental volume blood flow (cQuv). After non-invasive imaging, animals underwent C-section delivery for placenta collection and fetal necropsy at G110 (n=6) or G135 (n=6). Results Fetal weight and biparietal diameter were significantly smaller in ethanol exposed compared to controls at G110. By D-US, cQuta was decreased (p=0.1) and cQuv was significantly lower (p=0.04) at both G110 and G135 in ethanol exposed versus control animals. A significant reduction in placental blood flow was evident by DCE-MRI. As we demonstrated recently, T2* values vary throughout the placenta, and reveal gradients in blood deoxyhemoglobin concentration ranging from highly oxygenated blood (long T2*) proximal to spiral arteries to highly deoxygenated blood (short T2*). Distributions of T2* throughout the placenta show significant global reduction in T2* (and hence high blood deoxyhemoglobin concentration) in ethanol exposed vs. control at G110 (p=0.02). Fetal brain measurements indicated impaired growth and development at G110, but less so at G135 in ethanol exposed vs. control. Conclusion Chronic first trimester ethanol exposure significantly reduces placental perfusion and oxygen supply to the fetal vasculature later in pregnancy. These perturbations of placental function are associated with fetal growth impairments. However, differences between ethanol-exposed and control animals in placental function and fetal developmental outcomes were smaller at G135 than at G110. These findings are consistent with placental adaptation to early perturbations allowing for compensated placental function and maintenance of fetal growth.