The ex vivo human placenta perfusion model has proven to be clinically relevant to study transfer- and fetal exposure of various drugs. Although the method has existed for a long period, the setup of the perfusion model has not been generalized yet. This review aims to summarize the setups of ex vivo placental perfusion models used to examine drug transfer across the placenta to identify generalized properties and differences across setups. A literature search was carried out in PubMed September 26, 2022. Studies were labeled as relevant when information was reported, between 2000 and 2022, on the setups of ex vivo placental perfusion models used to study drug transfer across the placenta. The placenta perfusion process, and the data extraction, was divided into phases of preparation, control, drug, and experimental reflecting the chronological timeline of the different phases during the entire placental perfusion process. 135 studies describing an ex vivo human placental perfusion experiment were included. Among included studies, the majority (78.5%) analyzed drug perfusion in maternal to fetal direction, 18% evaluated bi-directional drug perfusion, 3% under equilibrium conditions, and one study investigated drug perfusion in fetal to maternal direction. This literature review facilitates the comparison of studies that employ similar placenta perfusion protocols for drug transfer studies and reveals significant disparities in the setup of these ex vivo placental perfusion models. Due to interlaboratory variability, perfusion studies are not readily comparable or interchangeable. Therefore, a stepwise protocol with multiple checkpoints for validating placental perfusion is needed.

Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disruptors.
The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity.
The search was performed on the bibliographic databases PubMed and Embase with text strings containing terms related to prenatal, breastfeeding, childhood, overweight, obesity, and PFASs. Only papers describing a biomonitoring study in pregnant women or in children up to 18 years that assessed body mass index (BMI), waist circumference (WC), or fat mass in children were included. When the estimates of the association between a PFAS and an outcome were reported from at least 3 studies, a meta-analysis was conducted; moreover, to correctly compare the studies, we developed a method to convert the different effect estimates and made them comparable each other. Meta-analyses were performed also stratifying by sex and age, and sensitivity analyses were also performed.
In total, 484 and 779 articles were retrieved from PubMed and Embase, respectively, resulting in a total of 826 articles after merging duplicates. The papers included in this systematic review were 49: 26 evaluating prenatal exposure to PFASs, 17 childhood exposure, and 6 both. Considering a qualitative evaluation, results were conflicting, with positive, negative, and null associations. 30 papers were included in meta-analyses (19 prenatal, 7 children, and 4 both). Positive associations were evidenced between prenatal PFNA and BMI, between PFOA and BMI in children who were more than 3 years, and between prenatal PFNA and WC. Negative associations were found between prenatal PFOS and BMI in children who were 3 or less years, and between PFHxS and risk of overweight. Relatively more consistent negative associations were evidenced between childhood exposure to three PFASs (PFOA, PFOS, and PFNA) and BMI, in particular PFOS in boys. However, heterogeneity among studies was high.
Even though heterogeneous across studies, the pooled evidence suggests possible associations, mostly positive, between prenatal exposure to some PFASs and childhood BMI/WC; and relatively stronger evidence for negative associations between childhood exposure to PFASs and childhood BMI.

OBJECTIVE: To investigate the occupational and environmental factors in the etiology of infantile hypertrophic pyloric stenosis (IHPS).
METHODS: Protocol was drafted according to the PRISMA guidelines and registered on PROSPERO (CRD42020152460). A search for a combination of terms related to IHPS, fetus and neonates, and environmental exposure was performed for studies published between 2000 and 2020 in the EMBASE, Pubmed, and MEDLINE databases.
RESULTS: Overall, 2203 abstracts were identified and 829 were screened. The full text of the selected articles (N = 98) was assessed for eligibility. Fifteen studies were included in quantitative synthesis. IHPS risk was significantly lower in black and Hispanic mothers than in white mothers [OR 0.47 (95% CI 0.44-0.51, p < 0.001), OR 0.85 (95% CI 0.77-0.94, p = 0.002), respectively]. Lower maternal education level and maternal smoking were risk factor for IHPS. We further observed a non-significant association between maternal folic acid usage and IHPS risk. Data were insufficient to evaluate occupational exposure.
CONCLUSIONS: This review provides an understanding of the role of environmental exposures in IHPS etiology. Lower maternal educational level, maternal smoking, and white ethnicity are associated with a significantly increased risk of IHPS, while folic acid use seems non-significantly associated with IHPS risk.
METHODS: III.

Physiologically-based pharmacokinetic (PBPK) modeling has emerged as a useful tool to study pharmacokinetics (PK) in special populations, such as pregnant women, fetuses, and newborns, where practical hurdles severely limit the study of drug behavior. PK in pregnant women is variable and everchanging, differing greatly from that in their nonpregnant female and male counterparts typically enrolled in clinical trials. PBPK models can accommodate pregnancy-induced physiological and metabolic changes, thereby providing mechanistic insights into maternal drug disposition and fetal exposure. Fueled by the soaring opioid epidemic in the United States, opioid use during pregnancy continues to rise, leading to an increased incidence of neonatal opioid withdrawal syndrome (NOWS). The severity of NOWS is influenced by a complex interplay of extrinsic and intrinsic factors, and varies substantially between newborns, but the extent of prenatal opioid exposure is likely the primary driver. Fetomaternal PBPK modeling is an attractive approach to predict in utero opioid exposure. To facilitate the development of fetomaternal PBPK models of opioids, this review provides a detailed overview of pregnancy-induced changes affecting the PK of commonly used opioids during gestation. Moreover, the placental transfer of these opioids is described, along with their disposition in the fetus. Lastly, the implementation of these factors into PBPK models is discussed. Fetomaternal PBPK modeling of opioids is expected to provide improved insights in fetal opioid exposure, which allows for prediction of postnatal NOWS severity, thereby opening the way for precision postnatal treatment of these vulnerable infants.

This paper surveys the existing scientific literature on metals concentrations in meconium. We examine some 32 papers that analyzed meconium for aluminum, arsenic, barium, calcium, chromium, copper, iron, lithium, magnesium, manganese, zinc, lead, mercury, manganese, molybdenum, nickel, phosphorus, lead, antimony, selenium, tin, vanadium, and zinc. Because of the lack of detail in the statistics it is not possible to do a rigorous meta-analysis. What stands out is that almost every study had subjects with seemingly large amounts of at least one of the metals. The significance of metals in meconium is not clear beyond an indication of exposure although some studies have correlated metals in meconium to a number of adverse outcomes. A number of outstanding questions have been identified that, if resolved, would greatly increase the utility of meconium analysis for assessment of long-term gestational metals exposures. Among these are questions of the developmental and long-term significance of metals detected in meconium, the kinetics and interactions among metals in maternal and fetal compartments and questions on best methods for meconium analyses.