Intrauterine growth restriction (IUGR) is found in 1-10% of all pregnancies, and among women with risk factors even twice often. It is connected to worse obstetric results, and its complications can arise long time after delivery. In the paper we described etiology, diagnostics and monitoring of IUGR and its consequences for the child and for the course of neonatal periode.

Intrauterine growth restriction

Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development.

The steroid hormones progestagens, estrogens, androgens, and glucocorticoids as well as their precursor cholesterol are required for successful establishment and maintenance of pregnancy and proper development of the fetus The human placenta forms at the interface of maternal and fetal circulation It participates in biosynthesis and metabolism of steroids as well as their regulated exchange between maternal and fetal compartment This review outlines the mechanisms of human placental handling of steroid compounds Cholesterol is transported from mother to offspring involving lipoprotein receptors such as low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SRB1) as well as ATP-binding cassette (ABC)-transporters, ABCA1 and ABCG1 Additionally, cholesterol is also a precursor for placental progesterone and estrogen synthesis Hormone synthesis is predominantly performed by members of the cytochrome P-450 (CYP) enzyme family including CYP11A1 or CYP19A1 and hydroxysteroid dehydrogenases (HSDs) such as 3β-HSD and 17β-HSD Placental estrogen synthesis requires delivery of sulfate-conjugated precursor molecules from fetal and maternal serum Placental uptake of these precursors is mediated by members of the solute carrier (SLC) family including sodium-dependent organic anion transporter (SOAT), organic anion transporter 4 (OAT4), and organic anion transporting polypeptide 2B1 (OATP2B1) Maternal-fetal glucocorticoid transport has to be tightly regulated in order to ensure healthy fetal growth and development For that purpose, the placenta expresses the enzymes 11β-HSD 1 and 2 as well as the transporter ABCB1 This article also summarizes the impact of diverse compounds and diseases on the expression level and activity of the involved transporters, receptors, and metabolizing enzymes and concludes that the regulatory mechanisms changing the physiological to a pathophysiological state are barely explored The structure and the cellular composition of the human placental barrier are introduced While steroid production, metabolism and transport in the placental syncytiotrophoblast have been explored for decades, few information is available for the role of placental-fetal endothelial cells in these processes With regard to placental structure and function, significant differences exist between species To further decipher physiologic pathways and their pathologic alterations in placental steroid handling, proper model systems are mandatory

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Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

Fetal growth restriction (FGR) continues to be a leading cause of preventable stillbirth and poor neurodevelopmental outcomes in offspring, and furthermore is strongly associated with the obstetrical complications of iatrogenic preterm birth and pre-eclampsia. The terms small for gestational age (SGA) and FGR have, for too long, been considered equivalent and therefore used interchangeably. However, the delivery of improved clinical outcomes requires that clinicians effectively distinguish fetuses that are pathologically growth-restricted from those that are constitutively small. A greater understanding of the multifactorial pathogenesis of both early- and late-onset FGR, especially the role of underlying placental pathologies, may offer insight into targeted treatment strategies that preserve placental function. The new maternal blood biomarker placenta growth factor offers much potential in this context. This review highlights new approaches to effective screening for FGR based on a comprehensive review of: etiology, diagnosis, antenatal surveillance and management. Recent advances in novel imaging methods provide the basis for stepwise multi-parametric testing that may deliver cost-effective screening within existing antenatal care systems.

Screening for fetal growth restriction and placental insufficiency.

Importance The magnitude of the association of intrauterine growth restriction (IUGR) and small for gestational age (SGA) status with cognitive outcomes in preterm and term-born children has not been established. Objective To examine cognitive outcomes of preterm and term-born children who had IUGR and were SGA compared with children who were appropriate for gestational age (AGA) during the first 12 years of life. Data Sources For this systematic review and meta-analysis, the Scopus, PubMed, Web of Science, Science Direct, PsycInfo, and ERIC databases were searched for English-language, peer-reviewed literature published between January 1, 2000, and February 20, 2020. The following Medical Subject Heading terms for IUGR and SGA and cognitive outcomes were used:intrauterine growth restriction,intrauterine growth retardation,small for gestational ageANDneurodevelopment,neurodevelopmental outcome,developmental outcomes, andcognitive development. Study Selection Inclusion criteria were assessment of cognitive outcomes (full-scale IQ or a cognitive subscale), inclusion of an AGA group as comparison group, and inclusion of gestational age at birth and completion of cognitive assessment up to 12 years of age. Data Extraction and Synthesis The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed. Data were double screened for full-text articles, and a subset were independently coded by 2 authors. Standardized mean differences (SMDs) and odd ratios from individual studies were pooled by applying random-effects models. Main Outcomes and Measures Cognitive outcomes, defined as mental, cognitive, or IQ scores, estimated with standardized practitioner-based cognitive tests or as borderline intellectual impairment (BII), defined as mental, cognitive, or IQ scores at least 1 SD below the mean cognitive score. Results In this study of 89 samples from 60 studies including 52 822 children, children who had IUGR and were SGA had significantly poorer cognitive outcomes (eg, cognitive scores and BII) than children with AGA in childhood. For cognitive scores, associations are consistent for preterm (SMD, −0.27; 95% CI, −0.38 to −0.17) and term-born children (SMD, −0.39; 95% CI, −0.50 to −0.28), with higher effect sizes reported for term-born IUGR and AGA group comparisons (SMD, –0.58; 95% CI, –0.82 to –0.35). Analyses on BII revealed a significantly increased risk in the preterm children who had IUGR and were SGA (odds ratio, 1.57; 95% CI, 1.40-1.77) compared with the children with AGA. Conclusions and Relevance Growth vulnerabilities assessed antenatally (IUGR) and at the time of birth (SGA) are significantly associated with lower childhood cognitive outcomes in preterm and term-born children compared with children with AGA. These findings highlight the need to develop interventions that boost cognitive functions in these high-risk groups.

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Association of Intrauterine Growth Restriction and Small for Gestational Age Status With Childhood Cognitive Outcomes: A Systematic Review and Meta-analysis

Fetal growth restriction (FGR) is a condition that affects 5–10% of pregnancies and is the second most common cause of perinatal mortality. This review presents the most recent knowledge on FGR and focuses on the etiology, classification, prediction, diagnosis, and management of the condition, as well as on its neurological complications. The Pubmed, SCOPUS, and Embase databases were searched using the term “fetal growth restriction”. Fetal growth restriction (FGR) may be classified as early or late depending on the time of diagnosis. Early FGR (<32 weeks) is associated with substantial alterations in placental implantation with elevated hypoxia, which requires cardiovascular adaptation. Perinatal morbidity and mortality rates are high. Late FGR (≥32 weeks) presents with slight deficiencies in placentation, which leads to mild hypoxia and requires little cardiovascular adaptation. Perinatal morbidity and mortality rates are lower. The diagnosis of FGR may be clinical; however, an arterial and venous Doppler ultrasound examination is essential for diagnosis and follow-up. There are currently no treatments to control FGR; the time at which pregnancy is interrupted is of vital importance for protecting both the mother and fetus. Early diagnosis of FGR is very important, because it enables the identification of the etiology of the condition and adequate monitoring of the fetal status, thereby minimizing risks of premature birth and intrauterine hypoxia.

Fetal growth restriction: current knowledge.

Maternal Blood Fatty Acid Levels in Small and Adequate for Gestational Age Pregnancies

Abstract Objective:  To assess the maternal blood levels of fatty acids (FAs) in pregnancies with fetal growth restriction (FGR). Methods:  This prospective cross-sectional study included pregnant women with gestational age between 26 and 37 + 6 weeks with FGR and appropriate for gestational age (AGA) fetuses. The levels of saturated, trans, monounsaturated, and polyunsaturated FAs were measured using centrifugation and liquid chromatography. The Student's t - test, Mann–Whitney test, and general linear model, with gestational age and maternal weight as covariants, were used to compare FA levels and the FGR and AGA groups. The Chi-square was used to evaluate the association between groups and studied variables. Results:  Maternal blood sample was collected from 64 pregnant women, being 24 FGR and 40 AGA. A weak positive correlation was found between the palmitoleic acid level and maternal weight (r = 0.285, p  = 0.036). A weak negative correlation was found between the gamma-linoleic acid level and gestational age (r = − 0.277, p  = 0.026). The median of the elaidic acid level (2.3 vs. 4.7 ng/ml, p  = 0.045) and gamma-linoleic acid (6.3 vs. 6.6 ng/ml, p  = 0.024) was significantly lower in the FGR than the AGA group. The palmitoleic acid level was significantly higher in the FGR than AGA group (50.5 vs. 47.6 ng/ml, p  = 0.033). Conclusion:  Pregnant women with FGR had lower elaidic acid and gamma-linoleic acid levels and higher palmitoleic acid levels than AGA fetuses.

Vivian Macedo Gomes Marçal

Papers

Fetal growth restriction: current knowledge.

Maternal Blood Fatty Acid Levels in Small and Adequate for Gestational Age Pregnancies

Maternal Blood Fatty Acid Levels in Fetal Growth Restriction