Reduced Fetal Movements and Perinatal Mortality

Bekiou, Aikaterini; Gourounti, Kleanthi

doi:10.5455/msm.2020.32.227-234

Cited by 14 publications

(9 citation statements)

References 42 publications

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“…In utero, congenital hand anomalies in which tendons are underdeveloped, are detected as early as the end of the first trimester. However, other tendonrelated syndromes, such as clubfoot, are typically detected later in the second and third trimesters (Browne, 1937;Quintero et al, 1999;Lee et al, 2002;Krakow et al, 2009;Kowalczyk and Felus, 2016;Bogers et al, 2019;Bekiou and Gourounti, 2020). Thus, the ability to treat tendon abnormalities at varying stages of tissue development is important.…”

Section: Discussionmentioning

confidence: 99%

Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment

Nguyen

Jana

Huang

et al. 2022

Front. Bioeng. Biotechnol.

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Tendon mechanical properties are significantly compromised in adult tendon injuries, tendon-related birth defects, and connective tissue disorders. Unfortunately, there currently is no effective treatment to restore native tendon mechanical properties after postnatal tendon injury or abnormal fetal development. Approaches to promote crosslinking of extracellular matrix components in tendon have been proposed to enhance insufficient mechanical properties of fibrotic tendon after healing. However, these crosslinking agents, which are not naturally present in the body, are associated with toxicity and significant reductions in metabolic activity at concentrations that enhance tendon mechanical properties. In contrast, we propose that an effective method to restore tendon mechanical properties would be to promote lysyl oxidase (LOX)-mediated collagen crosslinking in tendon during adult tissue healing or fetal tissue development. LOX is naturally occurring in the body, and we previously demonstrated LOX-mediated collagen crosslinking to be a critical regulator of tendon mechanical properties during new tissue formation. In this study, we examined the effects of recombinant LOX treatment on tendon at different stages of development. We found that recombinant LOX treatment significantly enhanced tensile and nanoscale tendon mechanical properties without affecting cell viability or collagen content, density, and maturity. Interestingly, both tendon elastic modulus and LOX-mediated collagen crosslink density plateaued at higher recombinant LOX concentrations, which may have been due to limited availability of adjacent lysine residues that are near enough to be crosslinked together. The plateau in crosslink density at higher concentrations of recombinant LOX treatments may have implications for preventing over-stiffening of tendon, though this requires further investigation. These findings demonstrate the exciting potential for a LOX-based therapeutic to enhance tendon mechanical properties via a naturally occurring crosslinking mechanism, which could have tremendous implications for an estimated 32 million acute and chronic tendon and ligament injuries each year in the U.S.

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Section: Discussionmentioning

confidence: 99%

Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment

Nguyen

Jana

Huang

et al. 2022

Front. Bioeng. Biotechnol.

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“…Decreased fetal movements (FM) may precede an abnormal fetal heart rate (FHR) or in utero fetal death by a few days or weeks [ 8 , 9 , 10 ], but pregnant women are poorly informed about what to do when they experience it, and some encounter a significant delay in accessing care or do not even contact health care [ 11 , 12 , 13 ]. Several studies have analyzed the effect of implementing a FM awareness campaign to reduce neonatal morbidity and mortality, but the outcomes are discordant.…”

Section: Introductionmentioning

confidence: 99%

Fetal Movement Counting in Prolonged Pregnancies: The COMPTAMAF Prospective Randomized Trial

et al. 2022

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In prolonged pregnancies, the risks of neonatal morbidity and mortality are increased. The aim of this trial was to assess the benefits of maternal information about fetal movement (FM) counting on neonatal outcomes in prolonged pregnancy. It was a prospective, single center, randomized, open-label study conducted from October 2019 to March 2022. Intention-to-treat analyses were performed on 278 patients randomized into two 1:1 groups (control group and FM counting group). The primary outcome was a composite score of neonatal morbidity (presence of two of the following items: fetal heart rate abnormality at delivery, Apgar score of <7 at 5 min, umbilical cord arterial pH of <7.20, and acute respiratory distress with mutation in neonatal intensive care unit). There was no significant difference between the two groups in the rate of neonatal morbidity (14.0% in the FM counting group versus 22.9% in the standard information group; p = 0.063; OR 0.55, 95% CI 0.29–1.0). In this study, fetal movement counting for women in prolonged pregnancy failed to demonstrate a significant reduction in adverse neonatal outcomes.

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“…RFM in utero is associated with a number of conditions and syndromes including Fetal Akinesia Deformation Sequence (FADS) which represents a spectrum of defects in bone and joint formation including hypomineralised, brittle bones prone to fracture (Temporary Brittle Bone Disease), and contracture of joints (reviewed in Shea et al, 2015); joint dysplasia, particularly of the hip (reviewed in Nowlan, 2015); and arthrogryposis, defined as multiple joint contractures, affecting approximately 1 in 3000 live births (Skaria et al, 2019;Hall, 2014). RFM can occur for a variety of reasons both intrinsic to the embryo, such as musculoskeletal disorders, and extrinsic factors including low amniotic fluid volume or restricted uterine space, placental abnormalities, or maternal drug use or illness (reviewed in Bekiou and Gourounti, 2020;Hall, 2009;Rodriguez et al, 1988a;Rodriguez et al, 1988b). Effects of RFM are variable and can range from mild to severe depending on the developmental window in which movement is interrupted (Filges et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Joint development recovery on resumption of embryonic movement following paralysis

Rolfe

O'Callaghan

Murphy

2021

Disease Models &Amp; Mechanisms

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Fetal activity in utero is a normal part of pregnancy and reduced or absent movement can lead to long-term skeletal defects such as Fetal Akinesia Deformation Sequence (FADS), joint dysplasia and arthrogryposis. A variety of animal models with decreased or absent embryonic movements show a consistent set of developmental defects providing insight into the aetiology of congenital skeletal abnormalities. At developing joints defects include reduced joint interzones with frequent fusion of cartilaginous skeletal rudiments across the joint. At the spine defects include shortening and a spectrum of curvature deformations. An important question, with relevance to possible therapeutic interventions for human conditions, is the capacity for recovery with resumption of movement following short term immobilisation. Here we use the well-established chick model to compare the effects of sustained immobilisation from embryonic day (E) 4-10 to two different recovery scenarios: (i) natural recovery from E6 until E10 and (ii) the addition of hyperactive movement stimulation during the recovery period. We demonstrate partial recovery of movement and partial recovery of joint development under both recovery conditions, but no improvement in spine defects. The joints examined (elbow, hip and knee) showed better recovery in hindlimb than forelimb, with hyperactive mobility leading to greater recovery in the knee and hip. The hip joint showed the best recovery with improved rudiment separation, tissue organisation and commencement of cavitation. This work demonstrates that movement post paralysis can partially-recover specific aspects of joint development which could inform therapeutic approaches to ameliorate the effects of human fetal immobility.

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Reduced Fetal Movements and Perinatal Mortality

Cited by 14 publications

References 42 publications

Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment

Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment

Fetal Movement Counting in Prolonged Pregnancies: The COMPTAMAF Prospective Randomized Trial

Joint development recovery on resumption of embryonic movement following paralysis

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