Identifying placental dysfunction in women with reduced fetal movements can be used to predict patients at increased risk of pregnancy complications
Introduction
Stillbirth remains a significant problem in both the developed and developing world. In the UK, stillbirth affects approximately 1 in 200 pregnancies after 24 weeks gestation [1]. The most common single cause of stillbirth is fetal growth restriction (FGR), which describes a failure of fetal growth in utero [2]. Despite significant advances in obstetric care, including widespread use of ultrasound imaging, the incidence of stillbirth has not declined significantly in the UK in the last two decades [3]. This is in part due to the lack of sufficiently sensitive and specific tests to identify pregnancies at risk of stillbirth to promote timely intervention. One screening tool to identify pregnancies at risk of stillbirth that has shown varying popularity throughout the last 40 years is maternal awareness of reduced fetal movements (RFM).
Maternal perception of fetal movements has been used as an indicator of fetal wellbeing for at least 500 years, being described in “The Byrth of Mankynde” by Thomas Raynalde in 1545. In contrast, a reduction in these perceived movements is associated with both pathological and non-pathological conditions [4]. Some of the most frequent and important adverse outcomes preceded by a period of RFM include fetal growth restriction (FGR) and stillbirth [5], [6]. Studies from 1973–2006 described the incidence of small for gestational age infants or FGR in 1.5–45% of women presenting with RFM [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]. The risk of stillbirth in these studies is reported to be 2.4–50% of those presenting with RFM [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]. A more recent study in 2009 using customised birthweight centiles corrected for gestational age, ethnicity and parity found that 24% of infants were small for gestational age, defined as a birthweight <10th centile, and the risk of stillbirth was 1.5%; all of the stillbirths in this cohort study had severe FGR (birthweight <0.4th centile) [16]. Importantly, 72% of the cases of FGR were not identified before presentation for RFM. Therefore, RFM may be a clinical sign that can alert clinicians to pregnancy at increased risk of complications.
Given the increased risk of stillbirth and FGR, women presenting with RFM require further assessment to identify any potential risk to their pregnancy. In a detailed investigation of antepartum stillbirths, the UK Confidential Enquiry into Stillbirths and Deaths in Infancy (CESDI) found that 1 in 6 stillbirths were associated with a period of RFM [17], proposing that correct identification of RFM may provide a window of opportunity in which intervention could prevent stillbirth. However, a lack of guidelines in the UK to instruct the identification and management of women presenting with RFM has led to a wide variation in practice [18]. This study also found that clinicians’ knowledge of associations with RFM was variable, with over 30% of clinicians being unaware of the link between RFM, FGR, fetal hypoxia and stillbirth [18]. Currently, there is a lack of an accepted and coherent hypothesis to link maternal perception of RFM to increased FGR and stillbirth. The absence of such a premise leads to inappropriate investigations which have insufficient sensitivity and specificity to predict and prevent stillbirth in this high risk group [19].
Here we present a hypothesis that links RFM to FGR and stillbirth through placental dysfunction. This understanding may also lead to the development of a reliable method of identifying women who are at an increased risk of adverse outcome, potentially in the form of ultrasound scanning or novel blood tests for placentally-derived factors.
Section snippets
Hypothesis
It is hypothesised that RFM is a sign of underlying placental insufficiency and that pregnancies at greatest risk of complications may be detected by investigation of altered placental structure or function.
Proposed pathophysiology of RFM
Fetal movements are generally noted from around 20 weeks gestation, although they diminish in magnitude but not frequency during the third trimester as the fetus increases in size [20]. A pathological reduction in the frequency of movement is thought to be a late reaction of the fetus to chronic hypoxia (described in Fig. 1). Initially, the fetus adapts to nutrient and oxygen deprivation by reducing growth rate, conserving cerebral development at the expense of subcutaneous fat deposition, the
RFM, placental insufficiency and stillbirth
Stillbirth can be attributed to a range of causes, including congenital abnormality to maternal infection [37] and feto-maternal haemorrhage [38]. However, the single largest cause relates to abnormal placental function, particularly in currently “unexplained” stillbirths, where over half have been shown to have FGR or have chronic fetal vascular insufficiency [39]. This suggests that FGR and placental insufficiency are key risk factors for stillbirth. Therefore, stillbirth is likely to share
Current tests after RFM
International guidelines recommend that women experiencing RFM are assessed by measurement of symphysiofundal height and assessment of the fetal heart rate by cardiotocography (CTG). Further investigations are usually based on the results of these tests, but can include ultrasound biophysical profile (incorporating assessment of fetal movements, breathing and tone, heart rate reactivity and amniotic fluid volume) or umbilical artery Doppler [6], [18], [21]. These investigations aim to exclude
Novel tests for placental dysfunction after RFM
Direct tests for placental dysfunction could involve the measurement of placenta-derived factors in maternal blood. As placental dysfunction originates in early pregnancy, investigators have measured placental factors such as pregnancy-associated plasma protein A (PAPP-A) and placental protein-13 (PP-13) to identify women who are at increased risk of adverse pregnancy outcome [42], [43], [44], [45]. Low levels of pregnancy-associated plasma protein A (PAPP-A) during the first trimester are
Testing this hypothesis
To address this hypothesis placental insufficiency needs to be proven in RFM, and similar pathology to that seen in FGR and stillbirth identified. Placental dysfunction could also be detected by measuring placentally-derived hormones and metabolites in maternal blood. To correlate changes in hormones and metabolites in maternal serum to changes occurring in the placenta, the transcription and translation of placental hormones should be analysed in the same patients as those giving serum
Conclusion
Awareness of RFM could be used to decrease perinatal mortality, particularly in cases of stillbirth secondary to placental dysfunction. This hypothesis merits further investigation for a number of reasons. Firstly, it will determine whether RFM is associated with placental abnormalities and this would indicate if women experiencing RFM should be identified as high risk. Secondly, it may reveal a placental marker that could be used in the subsequent management of these women to ascertain who is
Conflicts of interest statement
None declared.
Acknowledgements
Dr. Alexander Heazell holds a grant from the Manchester Wellcome Trust Clinical Research Facility to recruit patients to a cohort study investigating tests to predict poor pregnancy outcome in women presenting with reduced fetal movements. The sponsors of the research had no input in the production of this manuscript. LW is supported by a studentship from Wolfson foundation.
References (47)
- et al.
Fetal movement and fetal outcome in a low-risk population
J Nurse Midwifery
(1981) Clinical implications from monitoring fetal activity
Am J Obstet Gynecol
(1982)- et al.
Fetal movement in the third trimester of normal pregnancy
Early Hum Dev
(1986) - et al.
Maternal perception of decreased fetal movement as an indication for antepartum testing in a low-risk population
Am J Obstet Gynecol
(1991) Decreased fetal movements in the third trimester: what to do?
Gynecol Obstet Fertil
(2005)Management of decreased fetal movements
Semin Perinatol
(2008)Relationship between fetal biophysical activities and umbilical cord blood gas values
Am J Obstet Gynecol
(1991)Structural analysis of placental terminal villi from growth-restricted pregnancies with abnormal umbilical artery Doppler waveforms
Placenta
(1996)- et al.
Increased placental apoptosis in intrauterine growth restriction
Am J Obstet Gynecol
(1997) Trophoblast apoptosis from pregnancies complicated by fetal growth restriction is associated with enhanced p53 expression
Am J Obstet Gynecol
(2002)
Decreased vascularization and cell proliferation in placentas of intrauterine growth-restricted fetuses with abnormal umbilical artery flow velocity waveforms
Am J Obstet Gynecol
Placental findings contributing to fetal death, a study of 120 stillbirths between 23 and 40 weeks gestation
Placenta
Placental histologic criteria for umbilical blood flow restriction in unexplained stillbirth
Hum Pathol
Placental amino acid uptake in normal and complicated pregnancies
Am J Med Sci
Stillbirth
Lancet
Ultrasound evaluation of amniotic fluid volume. I. The relationship of marginal and decreased amniotic fluid volumes to perinatal outcome
Am J Obstet Gynecol
Effects of oxygen on cell turnover and expression of regulators of apoptosis in human placental trophoblast
Placenta
Classification of stillbirth by relevant condition at death (ReCoDe): population based cohort study
BMJ
Methods of fetal movement counting and the detection of fetal compromise
J Obstet Gynaecol
Daily fetal movement recording and fetal prognosis
Obstet Gynecol
What investigation is appropriate following maternal perception of reduced fetal movements?
J Obstet Gynaecol
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2022, European Journal of Obstetrics and Gynecology and Reproductive Biology: XCitation Excerpt :Out of these, while there is only one transient episode in most cases, approximately 4–15% of women are referred to prenatal clinics due to recurrence of reduction in fetal movement [2–4]. It has been reported in previous studies that pregnancies complicated with RFM are associated with higher rates of poor neonatal outcomes and increased prenatal morbidity and mortality [5–9]. In addition, other studies have shown that RFM combined with intrauterine growth restriction (IUGR) can predict abnormal pregnancy outcomes [10,11].
Excessive fetal movements are a sign of fetal compromise which merits further examination
2018, Medical HypothesesCitation Excerpt :The mostly commonly studied maternal symptom to date is maternal perception of reduced fetal movements (RFM) [3]. RFM is hypothesised to be associated with adverse pregnancy outcome through placental dysfunction [4]. In combination with findings from confidential enquiries into antepartum stillbirths [5,6], this observed association has led to the development of guidelines to improve information for women and standardise care following maternal perception of RFM [7].
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