Elsevier

Medical Hypotheses

Volume 76, Issue 1, January 2011, Pages 17-20
Medical Hypotheses

Identifying placental dysfunction in women with reduced fetal movements can be used to predict patients at increased risk of pregnancy complications

https://doi.org/10.1016/j.mehy.2010.08.020Get rights and content

Summary

Maternal perception of fetal movements has historically been used to indicate fetal wellbeing, and has been used with varying success in recent years to identify those pregnancies at increased risk of stillbirth, and other placental pathologies. We present a hypothesis that links reduced fetal movements (RFM) to fetal growth restriction (FGR) and stillbirth through placental dysfunction, and suggests the possibility that this can allow development of a reliable method to identify those women experiencing RFM who are at increased risk of adverse outcome. Reduced fetal movement is thought to represent fetal compensation in a chronic hypoxic environment due to inadequacies in the placental supply of oxygen and nutrients. Placental analysis in FGR and in stillbirth has revealed a number of structural abnormalities and an imbalance in cell turnover, and in terms of function, FGR is also associated with reduced nutrient transport. Both FGR and stillbirth are linked to changes in maternal levels of placental hormones. However, no such studies have been performed in samples from pregnancies affected by RFM. Currently, there are no formal guidelines to direct the management of such women, although it is recommended they undergo measurement of symphysis-fundal height and cardiotocography, and possibly Doppler ultrasound and biophysical profiling. Novel tests could involve the measurement of placental-derived hormones in maternal serum. To address this hypothesis, macroscopic and microscopic analysis of placental samples from both normal pregnancies and those affected by RFM is needed to detect any changes in structure. Placental function could be evaluated by levels of placental hormones in maternal blood. If placental dysfunction can be linked to RFM, and a robust method of identifying those women with placental insufficiency can be developed; screening patients with RFM could lead to a reduction in perinatal morbidity and mortality.

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)

  • C.-P. Chen et al.

    Decreased vascularization and cell proliferation in placentas of intrauterine growth-restricted fetuses with abnormal umbilical artery flow velocity waveforms

    Am J Obstet Gynecol

    (2002)
  • D. Kidron et al.

    Placental findings contributing to fetal death, a study of 120 stillbirths between 23 and 40 weeks gestation

    Placenta

    (2009)
  • M.M. Parast et al.

    Placental histologic criteria for umbilical blood flow restriction in unexplained stillbirth

    Hum Pathol

    (2008)
  • J.M. Dicke et al.

    Placental amino acid uptake in normal and complicated pregnancies

    Am J Med Sci

    (1988)
  • G.C. Smith et al.

    Stillbirth

    Lancet

    (2007)
  • P.F. Chamberlain

    Ultrasound evaluation of amniotic fluid volume. I. The relationship of marginal and decreased amniotic fluid volumes to perinatal outcome

    Am J Obstet Gynecol

    (1984)
  • A.E. Heazell

    Effects of oxygen on cell turnover and expression of regulators of apoptosis in human placental trophoblast

    Placenta

    (2008)
  • Confidential Enquiry into Maternal and Child Health, Perinatal Mortality 2007: England, Wales and Northern Ireland....
  • J. Gardosi

    Classification of stillbirth by relevant condition at death (ReCoDe): population based cohort study

    BMJ

    (2005)
  • CEMACH. Confidential Enquiry into Maternal and Child Health (CEMACH) Perinatal Mortality 2007. London: CEMACH;...
  • A.E. Heazell et al.

    Methods of fetal movement counting and the detection of fetal compromise

    J Obstet Gynaecol

    (2008)
  • E. Sadovsky et al.

    Daily fetal movement recording and fetal prognosis

    Obstet Gynecol

    (1973)
  • A.E. Heazell et al.

    What investigation is appropriate following maternal perception of reduced fetal movements?

    J Obstet Gynaecol

    (2005)
  • Cited by (31)

    • Cerebroplacental ratio and neonatal outcome in low-risk pregnancies with reduced fetal movement: A prospective study

      2022, European Journal of Obstetrics and Gynecology and Reproductive Biology: X
      Citation 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 Hypotheses
      Citation 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].

    • Management of reduced fetal movements

      2013, Fetal and Maternal Medicine Review
    • Low Fetal Resistance to Hypoxia as a Cause of Stillbirth and Neonatal Encephalopathy

      2024, Clinical and Experimental Obstetrics and Gynecology
    View all citing articles on Scopus
    View full text