Reduction In Fetal Growth Research Articles

Early pregnancy phthalates and replacements in relation to fetal growth: The human placenta and phthalates study

BackgroundPregnant persons are exposed ubiquitously to phthalates and increasingly to chemicals introduced to replace phthalates. In early pregnancy, exposure to these chemicals may disrupt fetal formation and development, manifesting adverse fetal growth. Previous studies examining the consequences of early pregnancy exposure relied on single spot urine measures and did not investigate replacement chemicals. ObjectiveCharacterize associations between urinary phthalate and replacement biomarkers in early pregnancy and fetal growth outcomes. MethodsAnalyses were conducted among 254 pregnancies in the Human Placenta and Phthalates Study, a prospective cohort with recruitment 2017–2020. Exposures were geometric mean concentrations of phthalate and replacement biomarkers quantified in two spot urine samples collected around 12- and 14-weeks of gestation. Outcomes were fetal ultrasound biometry (head and abdominal circumferences, femur length, estimated fetal weight) collected in each trimester and converted to z-scores. Adjusted linear mixed effects (single-pollutant) and quantile g-computation (mixture) models with participant-specific random effects estimated the difference, on average, in longitudinal fetal growth for a one-interquartile range (IQR) increase in individual (single-pollutant) or all (mixture) early pregnancy phthalate and replacement biomarkers. ResultsMono carboxyisononyl phthalate and the sums of metabolites of di-n-butyl, di-iso-butyl, and di-2-ethylhexyl phthalate were inversely associated with fetal head and abdominal circumference z-scores. A one-IQR increase in the phthalate and replacement biomarker mixture was inversely associated with fetal head circumference (β: -0.36 [95% confidence interval: -0.56, −0.15]) and abdominal circumference (−0.31 [-0.49, −0.12]) z-scores. This association was mainly driven by phthalate biomarkers. ConclusionsUrine concentrations of phthalate biomarkers, but not replacement biomarkers, in early pregnancy were associated with reductions in fetal growth. Though the clinical implications of these differences are unclear, reduced fetal growth contributes to excess morbidity and mortality across the lifecourse. Given widespread global exposure to phthalates, findings suggest a substantial population health burden resulting from early pregnancy phthalate exposure.

Exposure-response analysis of the association of maternal smoking and use of electronic cigarettes (vaping) in relation to preterm birth and small-for-gestational-age in a national US sample, 2016-2018.

The US experienced a surge in use of e-cigarettes. Smoking women may consider e-cigarettes during pregnancy as an alternative to smoking. E-cigarettes typically contain nicotine, an established cause of reduction in fetal growth in animal studies. This cohort study included 99,201 mothers who delivered live singletons in 2016-2018 from the Pregnancy Risk Assessment Monitoring System. We created exposure categories based on self-reported number of cigarettes smoked per day and vaping frequency and evaluated their associations with preterm birth and small-for-gestational-age (SGA) birth (two established cigarette smoking-related risks). Dual users in late pregnancy were a heterogeneous group: 29% lightly smoked and occasionally vaped; 19% lightly smoked and frequently vaped; 36% heavily smoked and occasionally vaped; and 15% heavily smoked and frequently vaped. While dual users who heavily smoked and occasionally vaped had the highest adjusted OR for SGA (3.4, 95% CI 2.0, 5.7), all the dual users had, on average, about twice the odds of having SGA than non-users. While the risks of preterm birth were higher among sole light smokers (adjusted OR 1.3, 95% CI 1.1, 1.5) and sole heavy smokers (adjusted OR 1.5. 95% CI 1.2, 1.8) than non-users, the adjusted odds of preterm birth for dual users were not noticeably higher than those of non-users. Relative to non-users, both smoking and vaping during pregnancy appear to increase risk of SGA, but excess risk of preterm birth appears to be primarily attributable to smoking alone. Higher levels of exposure tended to confer more risk.

Mixtures of phthalates and phthalate replacements in relation to size-for-gestational age in the LIFECODES Fetal Growth Study

BACKGROUND AND AIM: Phthalate exposure has been previously associated with reductions in fetal growth, including small-for-gestational age (SGA) births. Little is known about how phthalate replacements may be associated with adverse growth outcomes, including changes at both the small and large ends of the growth spectrum. Thus, we estimated joint associations between phthalates and their replacements with size-for-gestational age, including both SGA and large-for-gestational age (LGA) births. METHODS: Using the LIFECODES Fetal Growth Study, a case-cohort of 249 SGA, 411 appropriate-for-gestational age (AGA), and 241 LGA births, we measured concentrations of metabolites for 13 phthalates and 4 phthalate replacements at three timepoints during pregnancy. We used quantile g-computation as a multipollutant approach to estimate the joint association between phthalates or phthalate replacements and the odds ratios (OR) (95% confidence intervals [CI]) of an SGA or LGA birth. RESULTS: Of the metabolites analyzed, 12 phthalate and 2 phthalate replacements were detected frequently (> 70% of participants). The highest correlations were observed within chemical classes. Phthalate replacement metabolites were negatively correlated with phthalate metabolites. A simultaneous one-quartile increase in the concentrations of all phthalate replacement metabolites was associated with higher odds of an SGA birth (OR: 1.33, 95% CI: 1.13, 1.57) and inverse, though null, associations were observed for phthalate metabolites (OR: 0.82, 95% CI: 0.64, 1.07). Associations with LGA births were generally inverse or null. Single-pollutant models were consistent with our mixtures results. For example, an interquartile range-increase in concentrations of the phthalate replacement metabolite mono-2-ethyl 5-carboxypentyl terephthalate (OR: 1.64, 95% CI: 1.25, 2.15) was associated with higher odds of an SGA birth. CONCLUSIONS: Phthalate replacements were associated with higher odds of an SGA birth. Given the increasing prevalence of exposure to phthalate replacements, further research should continue to examine their health impacts. KEYWORDS: phthalates, phthalate replacements, fetal growth, mixtures

An application of group-based trajectory modeling to define fetal growth phenotypes among small-for-gestational-age births in the LIFECODES Fetal Growth Study

Reductions in fetal growth are associated with adverse outcomes at birth and later in life. However, identifying fetuses with pathologically small growth remains challenging. Definitions of small-for-gestational age are often used as a proxy to identify those experiencing pathologic growth (ie, fetal growth restriction). However, this approach is subject to limitation as most newborns labeled small-for-gestational age are constitutionally, not pathologically, small. Incorporating repeated ultrasound measures to examine fetal growth trajectories may help distinguish pathologic deviations in growth from normal variability, beyond a simple definition of small-for-gestational age. This study aimed to characterize phenotypes of growth using ultrasound trajectories of fetal growth among small-for-gestational-age births. This study identified and described trajectories of fetal growth among small-for-gestational-age births (<10th percentile weight for gestational age; n=245) in the LIFECODES Fetal Growth Study using univariate and multivariate trajectory modeling approaches. Available ultrasound measures of fetal growth (estimated fetal weight, head circumference, abdominal circumference, and femur length) from health records were abstracted. First, univariate group-based trajectory modeling was used to define trajectories of estimated fetal weight z scores during gestation. Second, group-based multi-trajectory modeling was used to identify trajectories based on concurrent measures of head circumference, abdominal circumference, and femur length z scores. Last, how these trajectories were related to patient demographics, pregnancy characteristics, and birth outcomes compared with those observed among appropriate-for-gestational-age controls was described. Of note, 3 univariate trajectories of estimated fetal weight and 4 multivariate trajectories of fetal growth among small-for-gestational-age births were identified. In our univariate approach, infants with the smallest estimated fetal weight trajectory throughout pregnancy had poorer outcomes, including the highest risk of neonatal intensive care unit admission. The remaining univariate trajectory groups did not have an elevated risk of adverse birth outcomes relative to appropriate-for-gestational-age controls. In our multivariate approach, 2 groups at increased or moderately increased risk of neonatal intensive care unit admission were identified, including infants that remained extremely small for all parameters throughout pregnancy and those who had disproportionately smaller femur length and abdominal circumference compared with head circumference. The remaining multivariate trajectory groups did not have an elevated risk of adverse birth outcome relative to appropriate-for-gestational-age controls. Latent class group-based trajectory modeling applied to ultrasound measures of fetal growth may help distinguish pathologic vs constitutional growth profiles among newborns born small-for-gestational age. Although trajectories cannot be fully characterized until delivery, limiting the direct clinical application of these methods, they may still contribute to the development of approaches for separating growth restriction from constitutional smallness.

Aberrant inflammation in rat pregnancy leads to cardiometabolic alterations in the offspring and intrauterine growth restriction in the F2 generation.

Children of women with pre-eclampsia have increased risk of cardiovascular (CV) and metabolic disease in adult life. Furthermore, the risk of pregnancy complications is higher in daughters born to women affected by pre-eclampsia than in daughters born after uncomplicated pregnancies. While aberrant inflammation contributes to the pathophysiology of pregnancy complications, including pre-eclampsia, the contribution of maternal inflammation to subsequent risk of CV and metabolic disease as well as pregnancy complications in the offspring remains unclear. Here, we demonstrate that 24-week-old female rats (F1) born to dams (F0) exposed to lipopolysaccharide (LPS) during pregnancy (to induce inflammation) exhibited mild systolic dysfunction, increased cardiac growth-related gene expression, altered glucose tolerance, and coagulopathy; whereas male F1 offspring exhibited altered glucose tolerance and increased visceral fat accumulation compared with F1 sex-matched offspring born to saline-treated dams. Both male and female F1 offspring born to LPS-treated dams had evidence of anemia. Fetuses (F2) from F1 females born to LPS-treated dams were growth restricted, and this reduction in fetal growth was associated with increased CD68 positivity (indicative of macrophage presence) and decreased expression of glucose transporter-1 in their utero-placental units. These results indicate that abnormal maternal inflammation can contribute to increased risk of CV and metabolic disease in the offspring, and that the effects of inflammation may cross generations. Our findings provide evidence in support of early screening for CV and metabolic disease, as well as pregnancy complications in offspring affected by pre-eclampsia or other pregnancy complications associated with aberrant inflammation.

Prenatal PFAS and psychosocial stress exposures in relation to fetal growth in two pregnancy cohorts: Applying environmental mixture methods to chemical and non-chemical stressors

BackgroundPrenatal exposure to individual per‑ and poly‑fluoroalkyl substances (PFAS) and psychosocial stressors have been associated with reductions in fetal growth. Studies suggest cumulative or joint effects of chemical and non-chemical stressors on fetal growth. However, few studies have examined PFAS and non-chemical stressors together as a mixture, which better reflects real life exposure patterns. We examined joint associations between PFAS, perceived stress, and depression, and fetal growth using two approaches developed for exposure mixtures. MethodsPregnant participants were enrolled in the Chemicals in Our Bodies cohort and Illinois Kids Development Study, which together make up the ECHO.CA.IL cohort. Seven PFAS were previously measured in 2nd trimester maternal serum samples and were natural log transformed for analyses. Perceived stress and depression were assessed using self-reported validated questionnaires, which were converted to t-scores using validated methods. Quantile g-computation and Bayesian kernel machine regression (BKMR) were used to assess joint associations between PFAS, perceived stress and depression t-scores and birthweight z-scores (N = 876). ResultsIndividual PFAS, depression and perceived stress t-scores were negatively correlated with birthweight z-scores. Using quantile g-computation, a simultaneous one quartile increase in all PFAS, perceived stress and depression t-scores was associated with a slight reduction in birthweight z-scores (mean change per quartile increase = -0.09, 95% confidence interval = -0.21,0.03). BKMR similarly indicated that cumulative PFAS and stress t-scores were modestly associated with lower birthweight z-scores. Across both methods, the joint association appeared to be distributed across multiple exposures rather than due to a single exposure. ConclusionsOur study is one of the first to examine the joint effects of chemical and non-chemical stressors on fetal growth using mixture methods. We found that PFAS, perceived stress, and depression in combination were modestly associated were lower birthweight z-scores, which supports prior studies indicating that chemical and non-chemical stressors are jointly associated with adverse health outcomes.

Urinary phthalate metabolite mixtures in pregnancy and fetal growth: Findings from the infant development and the environment study

BackgroundPrenatal phthalate exposure has been linked to reductions in fetal growth in animal and laboratory studies, but epidemiologic evidence is equivocal. ObjectiveExamine the association between prenatal phthalate metabolite mixtures and fetal growth and evaluate whether that association is modified by fetal sex or omega-3 intake during pregnancy. MethodsAnalyses included 604 singleton pregnancies from TIDES, a prospective pregnancy cohort with spot urine samples and questionnaires collected in each trimester. Pregnancy-averaged phthalate exposure estimates were calculated as the geometric means of specific-gravity corrected phthalate metabolites. Fetal growth outcomes included birthweight and length, and ultrasound-derived size and velocity of estimated fetal weight, femur length, abdominal and head circumferences in the second and third trimesters. We used a novel application of quantile g-computation to estimate the joint association between pregnancy-averaged phthalate exposure and fetal growth, and to examine effect modification of that association by infant sex or omega-3 intake during pregnancy. ResultsThere were few statistically significant differences in birth size and fetal growth by exposure. A one-quartile increase in the phthalate mixture was modestly associated with reduced birthweight(β [95% confidence interval)]: −54.6 [−128.9, 19.7] grams; p = 0.15) and length (−0.2 [−0.6, 0.2] centimeters; p = 0.40). A one-quartile increase in the phthalate mixture was associated with reduced birth length in males (−0.5 [−1.0, 0.0] centimeters) but not for females (0.1 [−0.2, 0.3] centimeters); interaction p = 0.05. The phthalate metabolite mixture was inversely associated with ultrasound-derived fetal growth among those with adequate omega-3 intake. For example, a one-quartile increase in the phthalate mixture was associated with reduced abdominal circumference in the third trimesters in those with adequate omega-3 intake (−3.3 [−6.8, 0.1] millimeters) but not those with inadequate omega-3 intake (1.8 [−0.8, 4.5] millimeters); interaction p = 0.01. ConclusionPrenatal phthalate exposure was not significantly associated with fetal growth outcomes, with some exceptions for certain subgroups.

Dose–response relationships between maternal urinary cotinine and placental weight and ratio of placental weight to birth weight: The Japan Environment and Children's Study

IntroductionStudies on the relationship between maternal self-reported smoking status and placental weight report inconsistent results. This study examined the relationships between maternal urinary cotinine concentration and placental weight and the ratio of placental weight to birth weight (PW/BW ratio). The study also examined the relationship between maternal smoking status, as determined by cotinine concentration, with placental weight and with PW/BW ratio, stratified by sex of offspring. MethodsOur analysis used information of 91,049 mother–child pairs enrolled in the Japan Environment and Children's Study. Maternal urinary cotinine concentration was quantified (during the second or third trimester) with high-performance liquid chromatography-tandem mass spectrometry. Using restricted cubic splines, placental weight and PW/BW ratio were plotted against natural log-transformed cotinine concentration. Taking cotinine levels of <0.17 ng/mL, 0.17 to <21.5 ng/mL (natural log-transformed values, −1.77 to 3.07), and ≥21.5 ng/mL as indicative of non-smokers, passive smokers, and active smokers, respectively, the relationships between maternal smoking status and placental weight and PW/BW ratio were examined, adjusting for confounders. ResultsPlacental weight and PW/BW ratio increased with increasing cotinine concentration. After cotinine reached a certain concentration, the placental weight decreased in male offspring whereas it plateaued in female offspring. Compared with not smoking, active smoking during pregnancy significantly increased placental weight and PW/BW ratio. ConclusionPlacental weight responded as an inverted U-shape whereas the PW/BW ratio followed a J-shape with increasing maternal urinary cotinine concentration measured during pregnancy, suggesting exposure to tobacco smoke induces a disproportionate reduction in fetal growth. The effect of tobacco smoke on placental growth varied by sex of offspring.

How hypoxia slows fetal growth: insights from high altitude.

A continuous oxygen supply is vital for fueling fetal growth, yet we know surprisingly little as to the precise mechanisms by which hypoxia reduces fetal growth. Animal models, while important, are limited by the enormous variability in mammalian physiologic responses to pregnancy. One of the earliest models for understanding hypoxia-induced reductions in fetal growth came from studies at high altitude that showed high altitude to have one of the strongest depressant effects on fetal growth. But all populations are not equally affected. Dolma et al., have added valuable information now showing that that Ladakhis, like Tibetans and Andeans, have a lower-than-expected frequency of small-for-gestational age (SGA) infants. Consistent with previous reports, these authors also found that uterine artery diameters at mid pregnancy (week 26–28) were larger in women giving birth to appropriate-for-gestational-age (AGA) than SGA infants at high but, interestingly, not at low altitude. Much remains to be learned about the physiologic pathways by which hypoxia impairs fetal growth. The variability among high-altitude populations and increasing sophistication of tools for investigating causal mechanisms have the potential to expand our presently limited means for identifying new treatments for hypoxia-related complications of pregnancy and fetal life.

Potential of NRF2 Pathway in Preventing Developmental and Reproductive Toxicity of Fine Particles.

Air pollution is associated with significant adverse health effects. Recent studies support the idea that inhalation of fine particles can instigate extrapulmonary effects on the cardiovascular system through several pathways. The systemic transfer of ultrafine particles (UFPs) or soluble particle components (organic compounds and metals) is of particular concern. An integral role of reactive oxygen species (ROS)-dependent pathways has been suggested in systemic inflammatory responses and vascular dysfunction at the molecular level. Accumulating lines of evidence suggest that fine particles affect fetal development, giving rise to low birth weight and a reduction in fetal growth, and also affect the immune, cardiovascular, and central nervous systems. Oxidative stress plays an important role in fine particles toxicity; pre-treatment with antioxidants partially suppresses the developmental toxicity of fine particles. On the other hand, Nuclear factor erythroid-derived 2-like 2 (Nfe2l2), also known as NRF2, is a transcription factor essential for inducible and/or constitutive expression of phase II and antioxidant enzymes. Studies using Nrf2-knockout mice revealed that NRF2 dysfunction is intimately involved in the pathogenesis of various human diseases. Multiple single nucleotide polymorphisms (SNPs) have been detected in human NRF2 locus. An NRF2 gene SNP (−617C > A; rs6721961), located in the upstream promoter region, affects the transcriptional level of NRF2 and thereby the protein level and downstream gene expression. It has been reported that the SNP-617 is associated with various diseases. The onset and exacerbation of the diseases are regulated by genetic predisposition and environmental factors; some people live in the air-polluted environment but are not affected and remain healthy, suggesting the presence of individual differences in the susceptibility to air pollutants. NRF2 polymorphisms may also be associated with the fetal effects of fine particles exposure. Screening high-risk pregnant women genetically susceptible to oxidative stress and prevention by antioxidant interventions to protect fetal development in air-polluted areas should be considered. This article reviews the recent advances in our understanding of the fetal health effects of fine particles and describes potential chemoprevention via the NRF2 pathway to prevent the developmental and reproductive toxicity of fine particles.

Evaluation of Perinatal Outcome in Women with Impaired Glucose Homeostasis During Pregnancy

Background: Glucose tolerance testing in pregnancy identifies many women with glycaemic responses that exceed normal range but that do not meet the threshold required to diagnose Gestational Diabetes Mellitus. It is controversial whether maternal hyperglycemia less severe than in diabetes is associated with increased risk of adverse pregnancy outcome or not. Materials and methods: All women were subjected to Glucose Challenge Test(GCT) with 50 gram glucose either at first visit or between 24-28 weeks on the basis of risk profile. High risk cases were screened at first visit and the rest between 24-28 weeks. Patients with a GCT value ≥200mg/dl were not subjected for GTT and were diagnosed as GDM.Value of GCT &lt;140 mg/dl was taken as normal. Irrespective of GCT result, women were subjected to Oral Glucose Tolerance Test (OGTT) as recommended by WHO with 75 gram glucose using WHO criteria. Study group was identified with 4 categories with abnormal glucose homoeostasis as defined by the following criteria: 1. Abnormal GCT (&gt;140 mg/dl) with normal OGTT; 2. Normal GCT with only Impaired Fasting Glucose(IFG) in OGTT; 3. Normal GCT with Gestational Glucose Intolerance(GGI); 4. Patients diagnosed as GDM: a. If fasting is &gt;126mg/dl; b. If 2hr OGTT ≥ 140mg/dl &amp; ≤ 199 mg/dl; c. If value of either GCT or OGTT &gt;200 mg/dl. The control group comprised of women with normal GCT and normal OGTT. In all the above groups, adverse prenatal outcome and maternal outcomes were evaluated by the primary and secondary outcome measures. Results: There were 10 cases (15.3%) of hypertensive disorder of pregnancy in the study group (3 cases of gestational hypertension in abnormal GCT, 3 cases of pre eclampsia in each GGI and GDM and 1 antepartum eclampsia in GGI category) and 2 cases in control group (3%) (p=0.03). There were 2 cases of Fetal Growth Reduction (FGR) and 5 cases of Premature Rupture Of Membranes(PROM) in both study and control group. There was 1 case of cholestasis of pregnancy in study group. Term inductions were 11 and 13 in the study and control group respectively.Within the study group number of cases induced were more in GGI(n=7) and GDM(n=4) category. There were 14 caesarean sections (21.5%) and 2 (3%) instrumental deliveries among the study group. However there were 6 caesarean sections (9.2%) and no instrumental deliveries among control groups. The rate of elective LSCS is more in GDM (n=5) vs other 3 categories and the difference is significant (p=0.04) The overall number of LSCS (14 cases) was significantly higher in GDM. Conclusion: Cases with abnormal glucose homeostasis of lesser degree than GDM, like only abnormal GCT, IFG and GGI also were observed to have adverse maternal outcomes than controls, in form of hypertensive disorders of pregnancy, significantly higher LSCS rates, and increased risk of macrosomia. Instead of 2 step procedure, single step screening cum diagnostic test with 75 gm OGTT for diagnosing GDM could be an option to be universally practiced.

Deletion of the Imprinted Phlda2 Gene Increases Placental Passive Permeability in the Mouse.

Genomic imprinting, an epigenetic phenomenon that causes the expression of a small set of genes in a parent-of-origin-specific manner, is thought to have co-evolved with placentation. Many imprinted genes are expressed in the placenta, where they play diverse roles related to development and nutrient supply function. However, only a small number of imprinted genes have been functionally tested for a role in nutrient transfer capacity in relation to the structural characteristics of the exchange labyrinthine zone. Here, we examine the transfer capacity in a mouse model deficient for the maternally expressed Phlda2 gene, which results in placental overgrowth and a transient reduction in fetal growth. Using stereology, we show that the morphology of the labyrinthine zone in Phlda2−/+ mutants is normal at E16 and E19. In vivo placental transfer of radiolabeled solutes 14C-methyl-D-glucose and 14C-MeAIB remains unaffected at both gestational time points. However, placental passive permeability, as measured using two inert hydrophilic solutes (14C-mannitol; 14C-inulin), is significantly higher in mutants. Importantly, this increase in passive permeability is associated with fetal catch-up growth. Our findings uncover a key role played by the imprinted Phlda2 gene in modifying placental passive permeability that may be important for determining fetal growth.

In utero exposure to dexamethasone causes a persistent and age-dependent exacerbation of the neurotoxic effects and glia activation induced by MDMA in dopaminergic brain regions of C57BL/6J mice

Clinical and preclinical evidence indicates that prenatal exposure to glucocorticoids may induce detrimental effects in the offspring, including reduction in fetal growth and alterations in the CNS. On this basis, the present study investigated whether in utero exposure to high levels of glucocorticoids is a risk factor that may lead to an exacerbation of the central noxious effects induced by psychoactive drugs consumed later in life. To this end, pregnant C57BL6/J dams were treated with dexamethasone (DEX, 0.05 mg/kg per day) from gestational day 14 until delivery. Thereafter, the male offspring were evaluated to ascertain the magnitude of dopaminergic damage, astrogliosis and microgliosis elicited in the nigrostriatal tract by the amphetamine-related drug 3,4-­methylenedioxymethamphetamine (MDMA, 4 × 20 mg/kg, 2 h apart, sacrificed 48 h later) administered at either adolescence or adulthood. Immunohistochemistry was performed in the substantia nigra pars compacta (SNc) and striatum, to evaluate dopaminergic degeneration by measuring tyrosine hydroxylase (TH), as well as astrogliosis and microgliosis by measuring glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1), respectively. Moreover, immunohistochemistry was used to ascertain the co-localization of IBA-1 with either the pro-inflammatory interleukin (IL) IL-1β or the anti-inflammatory IL IL-10, in order to determine the microglial phenotype. In utero administration of DEX induced dopaminergic damage by decreasing the density of TH-positive fibers in the striatum, although only in adult mice. MDMA administration induced dopaminergic damage and glia activation in the nigrostriatal tract of adolescent and adult mice. Mice exposed to DEX in utero and treated with MDMA later in life showed a more pronounced loss of dopaminergic neurons (adolescent mice) and astrogliosis (adolescent and adult mice) in the SNc, compared with control mice. These results suggest that prenatal exposure to glucocorticoids may induce an age-dependent and persistent increase in the susceptibility to central toxicity of amphetamine-related drugs used later in life.

Coffee intake during pregnancy and neonatal low birth weight: data from a multicenter Italian cross sectional study

Aim: Coffee intake is common during pregnancy. However, the influence of coffee and caffeine on pregnancy has not yet been fully determined. Some studies show that high coffee intake could cause miscarriage, preterm birth or reduction of fetal growth, but other studies do not support these findings. The aim of the present study was to analyze data collected from a database focusing on coffee intake during pregnancy, which was specifically created for multicenter studies carried out in the maternity units of Italian general hospitals. Principal outcomes of pregnancy during pregnancy were considered. Methods: Data of 5405 pregnancies were collected by a direct questionnaire supplemented with data from patients’clinical records during the survey named PHYTO.VIG.GEST. Results: We observed that 42.3% of the total sample had consumed at least one coffee a day during pregnancy. Analysis of a dose–response relationship showed that, in pregnant women starting from the consumption of three coffees a day (6% of pregnant women consuming coffee), there is a statistically significant association between number of coffees and reduction of babies birth weight (< 2500 g). Coclusion: Even though high coffee intake is known to influence negatively birth weight, our results indicate that a significant percentage of pregnant women maintain this habit.

VP06.09: Procedure‐related risk of premature delivery and fetal growth reduction following amniocentesis, transcervical and transabdominal chorionic villus sampling: a retrospective study

VP06.09: Procedure‐related risk of premature delivery and fetal growth reduction following amniocentesis, transcervical and transabdominal chorionic villus sampling: a retrospective study

Increased creatine demand during pregnancy in Arginine: Glycine Amidino-Transferase deficiency: a case report

BackgroundCreatine (Cr), an amino acid derivative, is one of the most important sources of energy acting as both a spatial and temporal energy buffer through its phosphorylated analogue phosphocreatine (PCr) and creatine kinase (CK). Maternal Cr biosynthesis and metabolism seem to play an important role in pregnancy, as shown in preclinical and in healthy human pregnancy studies. Patients with Arginine:Glycine Amidino-Transferase deficiency (AGAT-d), due to the deficit of the first enzyme involved in Cr synthesis, are at a disadvantage due to their failure to synthesize Cr and their dependence on external intake, in contrast to normal subjects, where changes in Cr biosynthesis supply their needs.We report the outcomes of a pregnancy in an AGAT-d woman, and the challenge we faced in managing her treatment with oral Cr to ensure optimal conditions for her fetus.Case presentationA 22-year-old AGAT-d woman referred to our Institute for the management of her first conception at 11 weeks of fetal gestational age. Sonographic monitoring at 20 w GA indicated a reduction of fetal growth, in particular of the head circumference that was below the 3rd centile. Biochemical monitoring of Cr in biological fluids of the mother revealed a decline of the Cr concentrations, in particular in the urine sample, requiring prompt correction of the Cr dose. At 35 weeks of gestation the patient delivered a male infant, heterozygous for GATM mutation, with normal brain Cr levels; at one year the baby achieved typical developmental milestones.ConclusionsThis rare pregnancy demonstrates that Cr levels in the blood and urine of the mother with AGAT-d decreased since the first months of gestation. The increase of the Cr daily dose administered to the mother seems to have produced beneficial effects also on the fetus.

The Effects of Prenatal Exposure to Marijuana on Early Childhood Development: A Systematic Literature Review

To assess the effect of prenatal marijuana exposure (PME) on the newborn, infant and early childhood development through review of current literature. A systematic literature review was conducted in the electronic database from 1996 to 2017 for the effects of PME and their fetal and early childhood outcomes. 7% of pregnant women self-reported using marijuana in the last year, while 16% of them reported near-daily use. Marijuana use has been reported to: a) interfere with normal placentation leading to miscarriage, preeclampsia and preterm labor through imbalance in Cannabinoid receptor type 1 (CBR1) stimulation; b) could lead to reduction of fetal growth and head circumference due to increased plasticity and resistance of uterine artery; c) be associated with impaired memory function, decreased verbal scores, increased aggression and hyperactivity, impaired abstract and visual reasoning; and d) could alter sleep patterns. Finally, there is no consensus regarding the effects of marijuana through breastfeeding exposure and no postpartum withdrawal effects in the newborn were reported. Research on the effects of PME on offspring has been limited by several confounding factors including self-reporting bias, concomitant use of other illicit drugs and psychosocial factors. Overall, PME may lead to negative consequences on the developing offspring. Public health messages to health care providers and pregnant women regarding the harmfulness of PME should become a high priority. Further research is needed to reinforce the existing data and examine additional potential negative effects on the developing child.

EP19.02: Increased uterine artery diameter protects from altitude associated reduction in fetal growth

EP19.02: Increased uterine artery diameter protects from altitude associated reduction in fetal growth

Procedure related risk of premature delivery and fetal growth reduction following amniocentesis, transcervical and transabdominal chorionic villus sampling: a retrospective study.

Background The aim of this study was to compare transabdominal and transcervical chorionic villus sampling (CVS) as well as amniocentesis (AC) with respect to their rates of premature delivery and fetal growth restriction. Methods We retrospectively evaluated the mentioned procedures of invasive prenatal testing performed in a single center between 2001 and 2016. Seven hundred and ninety-nine cases of AC and 719 cases of CVS were included, of which 400 were performed transvaginally. Only singleton pregnancies with a normal karyotype and delivery after 24 + 0 weeks of gestation were included. Fetal growth restriction was defined as birth weight below the 10th percentile. Premature delivery was defined as delivery before 37 + 0 weeks of gestation. Data were compared to a control group without an invasive procedure. Results The frequency of premature delivery was 8.5% after transabdominal CVS, 6.3% after transcervical CVS and 10.5% after AC as compared to 10.8% in the control group. The frequency of fetal growth restriction was 8.2% after transabdominal CVS 6.8% after transcervical CVS and 8.4% after AC as compared to 9.7% in the control group. Conclusion Our study supports that the three different methods of invasive prenatal testing do not lead to a higher risk of either premature delivery or fetal growth restriction when compared to controls. We found no difference in risk profile among the three techniques.

Major flood related strains and pregnancy outcomes.

To assess the impact of experiencing a major flood during pregnancy on fetal growth and length of gestation, and to consider how flood-related strains might contribute to these effects. The Red River Pregnancy Project was a prospective study carried out for 3 months immediately after the historic 2009 crest of the Red River in Fargo, North Dakota. Pregnant community residents who were at least 18 years old with a singleton, intrauterine pregnancy participated in the study (N = 169). Analyses examined if birth weight and length of gestation were associated with residential distance from flooding and gestational age at time of the flood crest. For pregnancies earlier in gestation during the crest (-1 SD = 12 weeks), birth weight decreased as distance from flooding decreased (-42.29 g/mi, p < .01). For pregnancies later in gestation at crest (+1 SD = 26 weeks), distance was not associated with birth weight (p > .10). Biparietal growth trajectories showed a decrease in growth after the crest of the flood but only for women early in pregnancy. However, various measures of flood related and general stress or strain did not explain these effects. Length of gestation was not associated with distance from or the timing of the flood. Pregnant women in the first trimester who experience a major flood near their homes are at risk of having lower birth weight neonates due to a reduction in fetal growth. The mechanisms of this effect deserve further attention in rapidly mounted investigations after disaster. (PsycINFO Database Record