Fetal Growth Restriction: Mechanisms, Epidemiology, and Management

Kamphof, Hester D.; Posthuma, Selina; Gordijn, Sanne J.; Ganzevoort, Wessel

doi:10.1097/fm9.0000000000000161

Cited by 20 publications

(12 citation statements)

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“…The umbilical artery connects the maternal and fetal circulatory systems, and the blood ow status of the umbilical artery can indicate pathological alterations in the placenta. Reference values of the UA-PI gradually decrease during pregnancy, and an increased mean UA PI indicates abnormally high resistance which is a proxy for placental insu ciency [44]. The signi cant decrease in UA-PI indicates that successful prevention of placental insu ciency is possible.…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of phosphodiesterase-5 (PDE-5) inhibitors in fetal growth restriction: a systematic literature review and meta-analysis

Liu

Bai

et al. 2023

Preprint

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Background The efficacy and safety of phosphodiesterase-5(PDE-5) inhibitors in the management of fetal growth restriction (FGR) remains inconclusive and new evidence continues to emerge. This study aimed to evaluate the most recent evidence about the clinical outcomes and safety profiles of PDE-5 inhibitors used to manage FGR. Methods Eight databases were searched for articles published in English and Chinese from the database inception to 30th September 2022. Randomized controlled trials (RCTs) reporting the use of PDE-5 inhibitors in FGR were included. Odds ratio (OR) and mean difference (MD) (95% confidence intervals) were pooled for analysis. Results From 229 citations identified, 16 studies involving 1492 pregnant women met the inclusion criteria. Only sildenafil (15 RCTs) and tadalafil (1 RCT) were investigated for their use in FGR. Sildenafil use was associated with an increase in birth weight (MD:164.07, 95%CI:61.55-266.59), pregnancy prolongation (MD:6.09,95%CI:2.15–10.03) and umbilical artery pulsatility indices (MD: -0.24, 95%CI: -0.32 - -0.15). However, sildenafil also had an increased risk of pulmonary hypertension in newborns (OR:4.37, 95%CI:1.49–12.80), as well as headache (OR:5.57, 95%CI:2.89–10.72) and flushing/rash in mothers (OR:5.11, 95%CI:2.08–12.53). No clinical differences in gestation age, perinatal mortality or major neonatal morbidity, stillbirth, neonate death, infants admitted to neonatal intensive care unit, intraventricular hemorrhage and necrotizing enterocolitis in infants were reported with the use of sildenafil. There was no evidence of any increase in the risk of pregnancy hypertension and gastrointestinal side effects in mothers. Subgroup analyses by age showed similar significant effects of sildenafil on birth weight for mothers younger than 30 years old (MD:198.6, 95%CI:19.95-377.25) and those aged 30 years or older (MD:82.73, 95%CI:7.14-158.32). However, no significant effect was observed for pregnancy prolongation. Conclusions The evidence from this review indicates that PDE-5 inhibitors improve birth weight and duration of pregnancy without causing severe maternal side effects. However, it has been shown that sildenafil can also increase the risk of neonatal pulmonary hypertension. It remains uncertain whether the benefits of PDE-5 inhibitors in FGR outweighs the risks and further investigation with larger studies is warranted.

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Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of phosphodiesterase-5 (PDE-5) inhibitors in fetal growth restriction: a systematic literature review and meta-analysis

Liu

Bai

et al. 2023

Preprint

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“…A placental syndrome develops on the basis of impairment onset, intensity, and association with other dysfunctions, e.g., dysbiosis. Our research is focused on alterations in the diversity and structure of the microbiome in preeclampsia and FGR, as important problems in obstetrics, affecting 5–10% of pregnancies worldwide [ 58 , 59 ]. However, the incidence of FGR in women with severe preeclampsia can exceed 22% [ 60 ].…”

Section: Placenta-related Syndromesmentioning

confidence: 99%

Evaluating Current Molecular Techniques and Evidence in Assessing Microbiome in Placenta-Related Health and Disorders in Pregnancy

Stupak

Kwaśniewski

2023

Biomolecules

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The microbiome is of great interest due to its potential influence on the occurrence and treatment of some human illnesses. It may be regarded as disruptions to the delicate equilibrium that humans ordinarily maintain with their microorganisms or the microbiota in their environment. The focus of this review is on the methodologies and current understanding of the functional microbiome in pregnancy outcomes. We present how novel techniques bring new insights to the contemporary field of maternal–fetal medicine with a critical analysis. The maternal microbiome in late pregnancy has been extensively studied, although data on maternal microbial changes during the first trimester are rare. Research has demonstrated that, in healthy pregnancies, the origin of the placental microbiota is oral (gut) rather than vaginal. Implantation, placental development, and maternal adaptation to pregnancy are complex processes in which fetal and maternal cells interact. Microbiome dysbiosis or microbial metabolites are rising as potential moderators of antenatal illnesses related to the placenta, such as fetal growth restriction, preeclampsia, and others, including gestational diabetes and preterm deliveries. However, because of the presence of antimicrobial components, it is likely that the bacteria identified in placental tissue are (fragments of) bacteria that have been destroyed by the placenta’s immune cells. Using genomic techniques (metagenomics, metatranscriptomics, and metaproteomics), it may be possible to predict some properties of a microorganism’s genome and the biochemical (epigenetic DNA modification) and physical components of the placenta as its environment. Despite the results described in this review, this subject needs further research on some major and crucial aspects. The phases of an in utero translocation of the maternal gut microbiota to the fetus should be explored. With a predictive knowledge of the impacts of the disturbance on microbial communities that influence human health and the environment, genomics may hold the answer to the development of novel therapies for the health of pregnant women.

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“…Although easy to measure, birth weight has limitations as a proxy for fetal adversity. It does not distinguish between normal growth in constitutionally small but healthy newborns and fetal growth restriction, the condition in which a fetus does not reach its growth potential (13,14). A key player in fetal growth restriction is the placenta.…”

Section: Introductionmentioning

confidence: 99%

Exploring the causal effect of placental physiology in susceptibility to mental and addictive disorders: a Mendelian randomization study

Jácome-Ferrer,

Costas

2024

Preprint

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Background: Epidemiological studies have linked low birth weight to psychiatric disorders, including substance use disorders. Genomic analyses suggest a role of placental physiology on psychiatric risk. We investigated whether this association is causally related to impaired trophoblast function. Methods: We conducted a two-sample summary-data Mendelian randomization study using as instrumental variables genetic variants strongly associated with birth weight, whose effect is exerted through the fetal genome, and are located near genes with differential expression in trophoblasts. Eight psychiatric and substance use disorders with > 10,000 samples were included as outcomes. The inverse variance weighted method was used as the main analysis and several sensitivity analyses were performed for those significant results. Results: The inverse variance weighted estimate, based on 14 instrumental variables, revealed an association, after correction for multiple tests, between birth weight and broadly-defined depression (beta=-0.165, 95% CI=-0.282 to -0.047, P=0.0059). Sensitivity analyses revealed absence of heterogeneity in the effect of instrumental variables, confirmed by leave-one-out analysis, MR_Egger intercept and MR_PRESSO. The effect was consistent using robust methods. Reverse causality was not detected. The effect was specifically linked to genetic variants near genes involved in trophoblast physiology instead of genes with fetal effect on birth weight or involved in placenta development. Conclusion: Impaired trophoblast functioning, probably leading to reduced fetal brain oxygen and nutrient supply, is causally related to broadly-defined depression. Considering the therapeutic potential of some agents to treat fetal growth restriction, further research on the effect of trophoblast physiology on mental disorders may have future implications in prevention.

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Fetal Growth Restriction: Mechanisms, Epidemiology, and Management

Cited by 20 publications

References 100 publications

Safety and Efficacy of phosphodiesterase-5 (PDE-5) inhibitors in fetal growth restriction: a systematic literature review and meta-analysis

Safety and Efficacy of phosphodiesterase-5 (PDE-5) inhibitors in fetal growth restriction: a systematic literature review and meta-analysis

Evaluating Current Molecular Techniques and Evidence in Assessing Microbiome in Placenta-Related Health and Disorders in Pregnancy

Exploring the causal effect of placental physiology in susceptibility to mental and addictive disorders: a Mendelian randomization study

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