Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical (EDC), is increasingly hypothesized to be a factor contributing to changes in fetal growth velocity. BPA exposure may be environmental, occupational, and/or dietary, with canned foods and plastic bottles contributing significantly. Our systematic review aims to evaluate the current literature and to investigate the role of BPA in abnormal fetal growth patterns. A search was conducted in the PubMed and Cochrane databases. A total of 25 articles met the eligibility criteria and were included in this systematic review. Eleven of them failed to show a clear relationship between BPA and abnormal fetal growth. The majority of the remaining studies (9/14) found an inverse association of BPA with indicators of fetal growth, whereas three studies suggested increased fetal growth, and two studies produced contradictory findings. Of note, both of the studies that collected a sample (amniotic fluid) directly reflecting BPA concentration in the fetus during the first half of pregnancy revealed an inverse association with birth weight. In conclusion, there is mounting evidence that combined exposure to BPA from dietary and non-dietary sources during pregnancy may contribute to abnormal fetal growth; a tendency towards fetal growth restriction was shown, especially when exposure occurs during the first half.

Background and Objectives: Fetal growth abnormalities increase the risk of negative perinatal and long-term outcomes. Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical to which humans may be exposed in a number of ways, such as from the environment, via various consumer products, and through the individual’s diet. Since the compound possesses estrogen-mimicking properties and exerts epigenetic and genotoxic effects, it has been associated with harmful effects impacting the entire spectrum of human life, including, vitally, the intrauterine period. We investigated the role of maternal exposure to BPA in abnormal fetal growth velocity, both impaired and excessive. Materials and Methods: Amniotic fluid samples were collected from 35 women who underwent amniocentesis early in the second trimester due to medical reasons. Pregnancies were followed until delivery, and birth weights were recorded. The amniotic fluid samples were subsequently divided into three groups based on fetal birth weight, as follows: AGA (appropriate for gestational age), SGA (small for gestational age), and LGA (large for gestational age). Amniotic fluid BPA levels were determined by gas chromatography coupled with mass spectrometry. Results: BPA was detected in 80% (28/35) of our amniotic fluid samples. Median concentration was 281.495 pg/mL and ranged from 108.82 pg/mL to 1605.36 pg/mL. No significant association was observed between the study groups regarding BPA concentration. A significant positive correlation between amniotic fluid BPA concentration and birth weight centile (r = 0.351, p-value = 0.039) was identified. BPA levels were also inversely associated with gestational age in pregnancies at term (between 37 and 41 weeks) (r = −0.365, p-value = 0.031). Conclusions: Our findings suggest that maternal exposure to BPA during the early second trimester of pregnancy can potentially contribute to increased birthweight percentiles and to decreased gestational age in pregnancies at term.

Placental insufficiency and gestational diabetes, which are both serious pregnancy complications, are linked to altered fetal growth, whether restricted or excessive, and result in metabolic dysfunction, hypoxic/oxidative injury, and adverse perinatal outcomes. Although much research has been carried out in this field, the underlying pathogenetic mechanisms have not as yet been fully elucidated. Particularly because of the role it plays in cardiovascular performance, glucose metabolism, inflammation, and oxidative stress, the adipokine apelin was recently shown to be a potential regulator of fetal growth and metabolic programming. This review investigated the numerous biological actions of apelin in utero and aimed to shed more light on its role in fetal growth and metabolic programming. The expression of the apelinergic system in a number of tissues indicates its involvement in many physiological mechanisms, including angiogenesis, cell proliferation, energy metabolism, inflammation, and oxidative stress. Moreover, it appears that apelin has a major function in disorders such as diabetes mellitus, fetal growth abnormalities, fetal hypoxia, and preeclampsia. We herein describe in detail the regulatory effects exerted by the adipokine apelin on fetal growth and metabolic programming while stressing the necessity for additional research into the therapeutic potential of apelin and its mechanisms of action in pregnancy-related disorders.

Introduction: Fetal growth disturbances place fetuses at increased risk for perinatal morbidity and mortality. As yet, little is known about the basic pathogenetic mechanisms underlying deranged fetal growth. Apelin is an adipokine with several biological activities. Over the past decade, it has been investigated for its possible role in fetal growth restriction. Most studies have examined apelin concentrations in maternal serum and amniotic fluid in the third trimester or during neonatal life. In this study, apelin concentrations were examined for the first time in early second-trimester fetuses. Another major regulator of tissue growth and metabolism is insulin. Materials and Methods: This was a prospective observational cohort study. We measured apelin and insulin concentrations in the amniotic fluid of 80 pregnant women who underwent amniocentesis in the early second trimester. Amniotic fluid samples were stored in appropriate conditions until delivery. The study groups were then defined, i.e., gestations with different fetal growth patterns (SGA, AGA, and LGA). Measurements were made using ELISA kits. Results: Apelin and insulin levels were measured in all 80 samples. The analysis revealed statistically significant differences in apelin concentrations among groups (p = 0.007). Apelin concentrations in large for gestational age (LGA) fetuses were significantly lower compared to those in AGA and SGA fetuses. Insulin concentrations did not differ significantly among groups. Conclusions: A clear trend towards decreasing apelin concentrations as birthweight progressively increased was identified. Amniotic fluid apelin concentrations in the early second trimester may be useful as a predictive factor for determining the risk of a fetus being born LGA. Future studies are expected/needed to corroborate the present findings and should ideally focus on the potential interplay of apelin with other known intrauterine metabolic factors.

Background: During the early stages of human fetal development, the fetal skeleton system is chiefly made up of cartilage, which is gradually replaced by bone. Fetal bone development is mainly regulated by the parathyroid hormone parathormone (PTH) and PTH-related protein, with specific calprotectin playing a substantial role in cell adhesion and chemotaxis while exhibiting antimicrobial activity during the inflammatory osteogenesis process. The aim of our study was to measure the levels of PTH and calprotectin in early second trimester amniotic fluid and to carry out a comparison between the levels observed among normal full-term pregnancies (control group) and those of the groups of embryos exhibiting impaired or enhanced growth. Methods: For the present prospective study, we collected amniotic fluid samples from pregnancies that underwent amniocentesis at 15 to 22 weeks of gestational age during the period 2021–2023. Subsequently, we followed up on all pregnancies closely until delivery. Having recorded fetal birthweights, we then divided the neonates into three groups: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Results: In total, 64 pregnancies, including 14 SGA, 10 LGA, and 40 AGA fetuses, were included in our study. Both substances were detected in early second trimester amniotic fluid in both groups. Concentrations of calprotectin differed significantly among the three groups (p = 0.033). AGA fetuses had a lower mean value of 4.195 (2.415–6.425) IU/mL, whereas LGA fetuses had a higher mean value of 6.055 (4.887–13.950) IU/mL, while SGA fetuses had a mean value of 5.475 (3.400–9.177) IU/mL. Further analysis revealed that only LGA fetuses had significantly higher calprotectin concentrations compared to AGA fetuses (p = 0.018). PTH concentration was similar between the groups, with LGA fetuses having a mean value of 13.18 (9.51–15.52) IU/mL, while SGA fetuses had a mean value of 14.18 (9.02–16.00) IU/mL, and AGA fetuses had similar concentrations of 13.35 (9.05–15.81) IU/mL. The differences in PTH concentration among the three groups were not statistically significant (p = 0.513). Conclusions: Calprotectin values in the amniotic fluid in the early second trimester were higher in LGA fetuses compared to those in the SGA and AGA categories. LGA fetuses can possibly be in a state of low-grade chronic inflammation due to excessive fat deposition, causing oxidative stress in LGA fetuses and, eventually, the release of calprotectin. Moreover, PTH concentrations in the amniotic fluid of early second trimester pregnancies were not found to be statistically correlated with fetal growth abnormalities in either LGA or SGA fetuses. However, the early time of collection and the small number of patients in our study should be taken into account.

Introduction: Acrylamide, an organic compound, is, chemically speaking, a vinyl-substituted primary amide. It is produced industrially, principally as a precursor to polyacrylamides, for use in such products as plastics and cosmetics. This same compound, however, forms naturally in certain foods, both home-cooked and packaged, especially when prepared at high temperatures. We developed and validated a novel reliable technique for the determination of acrylamide in amniotic fluid. Multiple reaction monitoring (MRM) is a targeted mass spectrometry (MS) technique which enables the detection and quantification of particular molecules in a complex mixture. Thanks to its throughput, selectivity, and sensitivity, MRM-MS has been identified as offering an alternative to antibody-based studies for the purpose of biomarker verification. Our aim was to investigate the presence of acrylamide in amniotic fluid and, via the MRM-MS technique, to determine whether there is any correlation between maternal exposure to acrylamide, through a woman’s diet, and fetal growth. Methods: Our amniotic fluid bank included 40 samples from various fetal growth rates, as objectively denoted by the neonatal weight centile at delivery, while our analytical detection method was based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Acrylamide was determined with reversed phase chromatography and monitoring of two multiple reaction monitoring (MRM) transitions. Quantification was performed using the matrix-matched calibration curve. Results: Acrylamide was detected at concentrations between 7.1 and 1468 ng/mL in six out of the total of 40 amniotic fluid samples that were used. Our method limit of detection and quantification was 1.4 ng/mL and 4.6 ng/mL, respectively. The repeatability of our method ranged between 11 and 14%, expressed as relative standard deviation levels between 5 and 100 ng/mL. Conclusions: Detection of acrylamide in early second trimester amniotic fluid, for the first time in the literature to our knowledge, raises concerns about fetal health, given that published data on animal studies have attributed a number of birth defects to acrylamide. Our novel LC-MS/MS method for the determination of acrylamide in amniotic fluid proved to be effective and its performance in practice was very accurate, simple, and fast. Validation of the method revealed that the use of a matrix-matched curve is necessary for the quantification.