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1.  Maternal Perception of Reduced Fetal Movements Is Associated with Altered Placental Structure and Function 
PLoS ONE  2012;7(4):e34851.
Background
Maternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). DFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency. To date there have been no studies of placental structure in cases of DFM.
Objective
To determine whether maternal perception of reduced fetal movements (RFM) is associated with abnormalities in placental structure and function.
Design
Placentas were collected from women with RFM after 28 weeks gestation if delivery occurred within 1 week. Women with normal movements served as a control group. Placentas were weighed and photographs taken. Microscopic structure was evaluated by immunohistochemical staining and image analysis. System A amino acid transporter activity was measured as a marker of placental function.
Placentas from all pregnancies with RFM (irrespective of outcome) had greater area with signs of infarction (3.5% vs. 0.6%; p<0.01), a higher density of syncytial knots (p<0.001) and greater proliferation index (p<0.01). Villous vascularity (p<0.001), trophoblast area (p<0.01) and system A activity (p<0.01) were decreased in placentas from RFM compared to controls irrespective of outcome of pregnancy.
Conclusions
This study provides evidence of abnormal placental morphology and function in women with RFM and supports the proposition of a causal association between placental insufficiency and RFM. This suggests that women presenting with RFM require further investigation to identify those with placental insufficiency.
doi:10.1371/journal.pone.0034851
PMCID: PMC3327709  PMID: 22523561
2.  Predictors of Poor Perinatal Outcome following Maternal Perception of Reduced Fetal Movements – A Prospective Cohort Study 
PLoS ONE  2012;7(7):e39784.
Background
Maternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). RFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency.
Objective
To identify predictors of poor perinatal outcome after maternal perception of reduced fetal movements (RFM).
Design
Prospective cohort study.
Methods
305 women presenting with RFM after 28 weeks of gestation were recruited. Demographic factors and clinical history were recorded and ultrasound performed to assess fetal biometry, liquor volume and umbilical artery Doppler. A maternal serum sample was obtained for measurement of placentally-derived or modified proteins including: alpha fetoprotein (AFP), human chorionic gonadotrophin (hCG), human placental lactogen (hPL), ischaemia-modified albumin (IMA), pregnancy associated plasma protein A (PAPP-A) and progesterone. Factors related to poor perinatal outcome were determined by logistic regression.
Results
22.1% of pregnancies ended in a poor perinatal outcome after RFM. The most common complication was small-for-gestational age infants. Pregnancy outcome after maternal perception of RFM was related to amount of fetal activity while being monitored, abnormal fetal heart rate trace, diastolic blood pressure, estimated fetal weight, liquor volume, serum hCG and hPL. Following multiple logistic regression abnormal fetal heart rate trace (Odds ratio 7.08, 95% Confidence Interval 1.31–38.18), (OR) diastolic blood pressure (OR 1.04 (95% CI 1.01–1.09), estimated fetal weight centile (OR 0.95, 95% CI 0.94–0.97) and log maternal serum hPL (OR 0.13, 95% CI 0.02–0.99) were independently related to pregnancy outcome. hPL was related to placental mass.
Conclusion
Poor perinatal outcome after maternal perception of RFM is closely related to factors which are connected to placental dysfunction. Novel tests of placental function and associated fetal response may provide improved means to detect fetuses at greatest risk of poor perinatal outcome after RFM.
doi:10.1371/journal.pone.0039784
PMCID: PMC3394759  PMID: 22808059
3.  Maternal perception of fetal motor activity. 
British Medical Journal  1979;2(6199):1183-1185.
A technique using real-time ultrasound for comprehensive recording of fetal motor activity was used in 20 subjects in the third trimester of pregnancy. Maternal awareness of fetal movement correlated with the number of fetal parts contributing to the movement but not with maternal parity or obesity, gestational age, placental site, or duration of the fetal movement. Some subjects recorded fetal breathing, passive fetal displacement, and Braxton Hicks's contractions as fetal movement. Most of our subjects were consistent and accurate in their perception of major fetal movements, but a few were inconsistent and one was completely unaware of major fetal movements. These results suggest that kick counts kept by most mothers will be accurate. Low counts of fetal movement should be an indication for fetal monitoring by other means and not, unconfirmed, for intervention.
PMCID: PMC1597230  PMID: 519353
4.  Fetal Movement Counting Improved Identification of Fetal Growth Restriction and Perinatal Outcomes – a Multi-Centre, Randomized, Controlled Trial 
PLoS ONE  2011;6(12):e28482.
Background
Fetal movement counting is a method used by the mother to quantify her baby's movements, and may prevent adverse pregnancy outcome by a timely evaluation of fetal health when the woman reports decreased fetal movements. We aimed to assess effects of fetal movement counting on identification of fetal pathology and pregnancy outcome.
Methodology
In a multicentre, randomized, controlled trial, 1076 pregnant women with singleton pregnancies from an unselected population were assigned to either perform fetal movement counting from gestational week 28, or to receive standard antenatal care not including fetal movement counting (controls). Women were recruited from nine Norwegian hospitals during September 2007 through November 2009. Main outcome was a compound measure of fetal pathology and adverse pregnancy outcomes. Analysis was performed by intention-to-treat.
Principal Findings
The frequency of the main outcome was equal in the groups; 63 of 433 (11.6%) in the intervention group, versus 53 of 532 (10.7%) in the control group [RR: 1.1 95% CI 0.7–1.5)]. The growth-restricted fetuses were more often identified prior to birth in the intervention group than in the control group; 20 of 23 fetuses (87.0%) versus 12 of 20 fetuses (60.0%), respectively, [RR: 1.5 (95% CI 1.0–2.1)]. In the intervention group two babies (0.4%) had Apgar scores <4 at 1 minute, versus 12 (2.3%) in the control group [RR: 0.2 (95% CI 0.04–0.7)]. The frequency of consultations for decreased fetal movement was 71 (13.1%) and 57 (10.7%) in the intervention and control groups, respectively [RR: 1.2 (95% CI 0.9–1.7)]. The frequency of interventions was similar in the groups.
Conclusions
Maternal ability to detect clinically important changes in fetal activity seemed to be improved by fetal movement counting; there was an increased identification of fetal growth restriction and improved perinatal outcome, without inducing more consultations or obstetric interventions.
Trial Registration
ClinicalTrials.gov NCT00513942
doi:10.1371/journal.pone.0028482
PMCID: PMC3244397  PMID: 22205952
5.  A cross-sectional study of maternal perception of fetal movements and antenatal advice in a general pregnant population, using a qualitative framework 
Background
Maternal perception of fetal movements has been used as a measure of fetal well-being. Yet a Cochrane review does not recommend formal fetal movement counting compared to discretional fetal movement counting. There is some evidence that suggests that the quality of fetal movements can precede quantitative changes however there has been almost no assessment of how women describe movements and whether these descriptions may be useful in a clinical setting. Therefore we aimed to examine maternal perception of fetal movements using a qualitative framework.
Methods
Using a cross-sectional design we identified women during routine antenatal care at a tertiary referral hospital, in Sydney, Australia. Eligible women were pregnant ≥ 28 weeks, carrying a single child, > 18 years old, and with sufficient English literacy to self-complete a questionnaire. Post-natally the medical records were reviewed and demographic, pregnancy and fetal outcome data were extracted. Text responses to questions regarding maternal descriptions of fetal movements throughout pregnancy, were analysed using thematic analysis in an explicit process.
Results
156 women participated. There was a general pattern to fetal movement descriptions with increasing gestation, beginning with words such as “gentle”, to descriptions of “strong” and “limb” movements, and finally to “whole body” movements. Women perceived and described qualitative changes to fetal movements that changed throughout gestation. The majority (83%) reported that they were asked to assess fetal movements in an implicit qualitative method during their antenatal care. In contrast, only 16% regularly counted fetal movements and many described counting as confusing and reported that the advice they had received on counting differed.
Conclusions
This is the first study to use qualitative analysis to identify that pregnant women perceive fetal movements and can describe them in a relatively homogenous way throughout pregnancy that follow a general pattern of fetal growth and development. These findings suggest that women’s perception of fetal wellbeing based on their own assessment of fetal movement is used in an ad hoc method in antenatal care by clinicians.
doi:10.1186/1471-2393-13-32
PMCID: PMC3572429  PMID: 23383737
Pregnancy; Fetal movement; Qualitative analysis; Cross-sectional study
6.  The Role of 4D Ultrasound in the Assessment of Fetal Behaviour 
Mædica  2011;6(2):120-127.
ABSTRACT
Fetal behavior is defined as any fetal action seen by the mother or fetus diagnosed by objective methods such as cardiotocography (CTG) or ultrasound. Analysis of the dynamics of the fetal behavior with morphological studies has lead to the conclusion that fetal behavior patterns are directly reflecting development and maturation of the central nervous system. The assessment of fetal behavior by 4D ultrasound could allow distinction between normal and abnormal fetal behavior patterns which might make possible the early recognition of fetal brain impairment.
Aim: Assessment of fetal movements throughout the pregnancy using 4D ultrasound.
Material and Method: The study group included 144 healthy pregnant women with single pregnancies between 7-38 weeks of gestation. For the first trimester of pregnancy we assessed eight types of fetal movements and for the second and third trimesters 14 types of fetal movements and facial expressions. The analyzed parameters for each trimester of pregnancy can be used for performing antenatal neurodevelopment test, used the first time by Professor Kurjak.
Results: After 15-20 minutes 4D ultrasound examination, we found a pattern of fetal behavior for each trimester of pregnancy.
Conclusions: Dynamic evaluation of fetal behavior reflects directly the processes of maturation and development of the central nervous system. This can make the difference between normal and abnormal brain development and may be used for early diagnosis of neurological disorders that become manifest in perinatal and postnatal periods.
PMCID: PMC3239390  PMID: 22205894
fetal behavior; 4D ultrasound; fetal movements
7.  Temporal patterns in count-to-ten fetal movement charts and their associations with pregnancy characteristics: a prospective cohort study 
Background
Fetal movement counting has long been suggested as a screening tool to identify impaired placental function. However, quantitative limits for decreased fetal movement perform poorly for screening purposes, indicating the need for methodological refinement. We aimed to identify the main individual temporal patterns in fetal movement counting charts, and explore their associations with pregnancy characteristics.
Methods
In a population-based prospective cohort in Norway, 2009–2011, women with singleton pregnancies counted fetal movements daily from pregnancy week 24 until delivery using a modified "count-to-ten” procedure. To account for intra-woman correlation of observations, we used functional data analysis and corresponding functional principal component analysis to identify the main individual temporal patterns in fetal movement count data. The temporal patterns are described by continuous functional principal component (FPC) curves, with an individual score on each FPC for each woman. These scores were later used as outcome variables in multivariable linear regression analyses, with pregnancy characteristics as explanatory variables.
Results
Fetal movement charts from 1086 pregnancies were included. Three FPC curves explained almost 99% of the variation in the temporal data, with the first FPC, representing the individual overall counting time, accounting for 91% alone. There were several statistically significant associations between the FPCs and various pregnancy characteristics. However, the effects were small and of limited clinical value.
Conclusions
This statistical approach for analyzing fetal movement counting data successfully captured clinically meaningful individual temporal patterns and how these patterns vary between women. Maternal body mass index, gestational age and placental site explained little of the variation in the temporal fetal movement counting patterns. Thus, a perceived decrease in fetal movement should not be attributed to a woman’s basic pregnancy characteristics, but assessed as a potential marker of risk.
doi:10.1186/1471-2393-12-124
PMCID: PMC3542088  PMID: 23126608
Fetal movement; Kick counting; Decreased fetal movement; Functional data analysis; Principal components; Temporal pattern
8.  Acetylcholine receptor δ subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita 
Journal of Clinical Investigation  2001;108(1):125-130.
Limitation of movement during fetal development may lead to multiple joint contractures in the neonate, termed arthrogryposis multiplex congenita. Neuromuscular disorders are among the many different causes of reduced fetal movement. Many congenital myasthenic syndromes (CMSs) are due to mutations of the adult-specific ε subunit of the acetylcholine receptor (AChR), and, thus, functional deficits do not arise until late in gestation. However, an earlier effect on the fetus might be predicted with some defects of other AChR subunits. We studied a child who presented at birth with joint contractures and was subsequently found to have a CMS. Mutational screening revealed heteroallelic mutation within the AChR δ subunit gene, δ756ins2 and δE59K. Expression studies demonstrate that δ756ins2 is a null mutation. By contrast, both fetal and adult AChR containing δE59K have shorter than normal channel activations that predict fast decay of endplate currents. Thus, δE59K causes dysfunction of fetal as well as the adult AChR and would explain the presence of joint contractures on the basis of reduced fetal movement. This is the first report of the association of AChR gene mutations with arthrogryposis multiplex congenita. It is probable that mutations that severely disrupt function of fetal AChR will underlie additional cases.
PMCID: PMC209343  PMID: 11435464
9.  Maternal Counting of Fetal Movements. Part II: Case Presentations 
Canadian Family Physician  1988;34:567-569.
The use of daily maternal counting of fetal movements as an antenatal screening test is illustrated in three case studies. The cases described carry both high and low risks, and illustrate the technique of counting fetal movements. The author suggests that performing this antenatal screening test on all patients may reduce perinatal mortality.
PMCID: PMC2219039  PMID: 21253143
fetal movement; antenatal screening; still birth
10.  Fetal activity and fetal wellbeing: an evaluation. 
British Medical Journal  1976;1(6021):1305-1307.
The clinical value of the 12-hour daily fetal movement count (DFMC) as a test of antepartum fetal wellbeing was assessed. The lowest 2-5% of 1654 DFMCs recorded by 61 women who subsequently delivered healthy infants fell below 10 movements per 12 hours. This level was taken as the lower limit of normal for clinical purposes. A normal DFMC in a population at risk was associated with a satisfactory fetal outcome. A low DFMC was associated with a high incidence of fetal asphyxia, and when fetal death occurred fetal movements rapidly diminished and stopped 12 to 48 hours before death. The DFMC is a generally applicable method of monitoring fetal welfare during pregnancy which provides an inexpensive adjunct or even an alternative to the more expensive placental function tests in current use.
PMCID: PMC1640347  PMID: 1268677
11.  Fetal breathing movements and other tests of fetal wellbeing: a comparative evaluation. 
British Medical Journal  1979;2(6190):577-579.
Sixty pregnant women whose fetuses were considered to be at high risk were intensively studied with fetal and placental function tests. Fetal breathing movements were studied with real-time ultrasound and the amount of time spent breathing and the variability of the breath-to-breath interval were measured. A reduction in the amount of time the fetus spent making breathing movements and decreased variability were indicative of fetal compromise. When these results were compared with those of other tests of fetal wellbeing measurement of fetal breathing movements and ultrasound assessment of growth were more sensitive tests of fetal wellbeing than the biochemical measures (urinary oestrogen, human placental lactogen, pregnancy-specific beta-1-glycoprotein, and unconjugated oestriol concentrations) or fetal heart rate. The predictive value was highest with serum unconjugated oestriol but the results of other tests were similar. Study of fetal breathing movements or an ultrasonic assessment of growth may provide a better screening test for fetal compromise than biochemical estimations.
PMCID: PMC1596521  PMID: 315254
12.  Behavioural states in normal mature human fetuses. 
Archives of Disease in Childhood  1990;65(1 Spec No):39-43.
Behaviour was studied by real time ultrasound in a group of 80 low risk fetuses between 36 and 42 weeks' gestation. There was close linkage of fetal eye movements, somatic movements and heart rate pattern reflecting three different states. Quiescence (state 1F) was characterised by no eye movements, no somatic movements except for the occasional startle, and a fetal heart rate pattern with little baseline variability. There were two active states: state 2F characterised by continuous eye movements, frequent bursts of somatic movements, and wide baseline variability with accelerations with movement, and state 4F characterised by continuous eye movements with almost continuous somatic movements and a sustained tachycardia. These fulfilled criteria for three of four behavioural states previously described in human fetuses. Cycling of quiescent and active states occurred in 77 (96%) of the fetuses within 100 minutes of starting the recording. 2F was the commonest behavioural state, being seen 58% of the time. 1F was seen 30% of the time, and 4F 9% of the time. During the remaining 3% of observation time the behavioural state was indeterminate.
PMCID: PMC1590168  PMID: 2306133
13.  Characterization of the Fetal Diaphragmatic Magnetomyogram and the Effect of Breathing Movements on Cardiac Metrics of Rate and Variability 
Early human development  2011;87(7):467-475.
Breathing movements are one of the earliest fetal motor behaviors to emerge andare ahallmark of fetal well-being. Fetal respiratory sinus arrhythmia (RSA) has been documented but efforts to quantify the influence of breathing on heart rate (HR) and heart rate variability (HRV) are difficult due to the episodic nature of fetal breathing activity. We used a dedicated fetal biomagnetometer to acquire the magnetocardiogram (MCG) between 36-38 weeks gestational age (GA). We identified and characterized a waveform observed in the raw data and independent component decomposition that we attribute to fetal diaphragmatic movements during breathing episodes. RSA and increased high frequency power in a time-frequency analysis of the IBI time-series was observed during fetal breathing periods. Using the diaphragmatic magnetomyogram (dMMG) as a marker, we compared time and frequency domain metrics of heartrate and heart rate variability between breathing and non-breathing epochs. Fetal breathing activity resulted in significantly lower HR, increased high frequency power, greater sympathovagal balance, increased short-term HRV andgreater parasympathetic input relative to non-breathing episodesconfirming the specificity of fetal breathing movements on parasympathetic cardiac influence. No significant differences between breathing and non-breathing epochs were found in two metrics reflecting total HRVor very low, low and intermediate frequency bands. Using the fetal dMMG as a marker, biomagnetometry can help to elucidate the electrophysiologic mechanisms associated with diaphragmatic motor function and may be used to study the longitudinal development of human fetal cardiac autonomic control and breathing activity.
doi:10.1016/j.earlhumdev.2011.03.012
PMCID: PMC3114157  PMID: 21497027
Autonomic Nervous System; Magnetocardiogram; Fetal Biomagnetometry; Diaphragm Activation
14.  Placental mesenchymal dysplasia, a case of intrauterine sudden death of fetus with rupture of cirsoid periumbilical chorionic vessels 
Diagnostic Pathology  2011;6:38.
We report a 32-year-old woman (1-gravid, 1-para) with a vesicular lesion in her uterus that was pointed out on ultrasound at 8 weeks' gestation. Amniocentesis at 15 weeks' gestation showed a normal female karyotype, 46XX. As the pregnancy advanced, the mole-like lesion became relatively reduced. Throughout gestation, the maternal human chorionic gonadotropin level was normal, but the serum alpha fetoprotein level rose as her pregnancy progressed. Her fetus did not exhibit any remarkable anomalies. The patient visited our hospital complaining of a diminished feeling of fetal movements at 36 weeks 5 days' gestation, and intrauterine fetal death (IUFD) was confirmed. She delivered a 2336-g female without any definite anomalies. A pathological examination led to a diagnosis of placental mesenchymal dysplasia, and androgenetic/biparental mosaicism in the placenta was identified using p57kip2 immunohistochemical staining. And it also revealed that the rupture of the cirsoid chorionic vessels had led to IUFD.
doi:10.1186/1746-1596-6-38
PMCID: PMC3094260  PMID: 21513565
15.  Screening and triage of intrauterine growth restriction (IUGR) in general population and high risk pregnancies: a systematic review with a focus on reduction of IUGR related stillbirths 
BMC Public Health  2011;11(Suppl 3):S1.
Background
There is a strong association between stillbirth and fetal growth restriction. Early detection and management of IUGR can lead to reduce related morbidity and mortality. In this paper we have reviewed effectiveness of fetal movement monitoring and Doppler velocimetry for the detection and surveillance of high risk pregnancies and the effect of this on prevention of stillbirths. We have also reviewed effect of maternal body mass index (BMI) screening, symphysial-fundal height measurement and targeted ultrasound in detection and triage of IUGR in the community.
Methods
We systematically reviewed all published literature to identify studies related to our interventions. We searched PubMed, Cochrane Library, and all World Health Organization Regional Databases and included publications in any language. Quality of available evidence was assessed using GRADE criteria. Recommendations were made for the Lives Saved Tool (LiST) based on rules developed by the Child Health Epidemiology Group. Given the paucity of evidence related to the effect of detection and management of IUGR on stillbirths, we undertook Delphi based evaluation from experts in the field.
Results
There was insufficient evidence to recommend against or in favor of routine use of fetal movement monitoring for fetal well being. (1) Detection and triage of IUGR with the help of (1a) maternal BMI screening, (1b) symphysial-fundal height measurement and (1c) targeted ultrasound can be an effective method of reducing IUGR related perinatal morbidity and mortality. Pooled results from sixteen studies shows that Doppler velocimetry of umbilical and fetal arteries in ‘high risk’ pregnancies, coupled with the appropriate intervention, can reduce perinatal mortality by 29 % [RR 0.71, 95 % CI 0.52-0.98]. Pooled results for impact on stillbirth showed a reduction of 35 % [RR 0.65, 95 % CI 0.41-1.04]; however, the results did not reach the conventional limits of statistical significance. This intervention could be potentially recommended for high income settings or middle income countries with improving rates and standards of facility based care. Based on the Delphi, a combination of screening with maternal BMI, Symphysis fundal height and targeted ultrasound followed by the appropriate management could potentially reduce antepartum and intrapartum stillbirth by 20% respectively. This estimate is presently being recommended for inclusion in the LiST.
Conclusion
There is insufficient evidence to recommend in favor or against fetal movement counting for routine use for testing fetal well being. Doppler velocimetry of umbilical and fetal arteries and appropriate intervention is associated with 29 % (95 % CI 2% to 48 %) reduction in perinatal mortality. Expert opinion suggests that detection and management of IUGR with the help of maternal BMI, symphysial-fundal height measurement and targeted ultrasound could be effective in reducing IUGR related stillbirths by 20%.
doi:10.1186/1471-2458-11-S3-S1
PMCID: PMC3231882  PMID: 21501426
16.  Diagnosing Arthrogryposis Multiplex Congenita: A Review 
ISRN Obstetrics and Gynecology  2012;2012:264918.
Arthrogryposis multiplex congenita (AMC) refers either to a syndromic or to a nonsyndromic group of conditions with varied etiology and complex clinical features, including multiple congenital contractures in different body areas. Its etiology still remains unclear but generally any cause that leads to reduced fetal movement may lead to congenital contractures and in severe cases to fetal akinesia deformation sequence (FADS). It affects approximately 1 in 2-3000 live births with an approximately equal gender ratio. There are many known subgroups of AMC differing in signs, symptoms, and causes. The primary diagnosis is made when a lack of mobility and an abnormal position is noted in routine ultrasound scanning. Early diagnosis, prenatal evaluation, and further surveillance via image scanning (ultrasound and MRI) give the opportunity for family counseling concerning neonatal morbidity and mortality and labor or delivery planning. Better understanding of the ultrasound findings and the etiology of this clinical situation offers the opportunity for careful prenatal assessment.
doi:10.5402/2012/264918
PMCID: PMC3461621  PMID: 23050160
17.  Do Facial Expressions Develop before Birth? 
PLoS ONE  2011;6(8):e24081.
Background
Fetal facial development is essential not only for postnatal bonding between parents and child, but also theoretically for the study of the origins of affect. However, how such movements become coordinated is poorly understood. 4-D ultrasound visualisation allows an objective coding of fetal facial movements.
Methodology/Findings
Based on research using facial muscle movements to code recognisable facial expressions in adults and adapted for infants, we defined two distinct fetal facial movements, namely “cry-face-gestalt” and “laughter- gestalt,” both made up of up to 7 distinct facial movements. In this conceptual study, two healthy fetuses were then scanned at different gestational ages in the second and third trimester. We observed that the number and complexity of simultaneous movements increased with gestational age. Thus, between 24 and 35 weeks the mean number of co-occurrences of 3 or more facial movements increased from 7% to 69%. Recognisable facial expressions were also observed to develop. Between 24 and 35 weeks the number of co-occurrences of 3 or more movements making up a “cry-face gestalt” facial movement increased from 0% to 42%. Similarly the number of co-occurrences of 3 or more facial movements combining to a “laughter-face gestalt” increased from 0% to 35%. These changes over age were all highly significant.
Significance
This research provides the first evidence of developmental progression from individual unrelated facial movements toward fetal facial gestalts. We propose that there is considerable potential of this method for assessing fetal development: Subsequent discrimination of normal and abnormal fetal facial development might identify health problems in utero.
doi:10.1371/journal.pone.0024081
PMCID: PMC3164123  PMID: 21904607
18.  Development of Fetal Movement between 26 and 36-Weeks’ Gestation in Response to Vibro-Acoustic Stimulation 
Background: Ultrasound observation of fetal movement has documented general trends in motor development and fetal age when motor response to stimulation is observed. Evaluation of fetal movement quality, in addition to specific motor activity, may improve documentation of motor development and highlight specific motor responses to stimulation. Aim: The aim of this investigation was to assess fetal movement at 26 and 36-weeks gestation during three conditions (baseline, immediate response to vibro-acoustic stimulation (VAS), and post-response). Design: A prospective, longitudinal design was utilized. Subjects: Twelve normally developing fetuses, eight females and four males, were examined with continuous ultrasound imaging. Outcome Measures: The fetal neurobehavioral coding system (FENS) was used to evaluate the quality of motor activity during 10-s epochs over the three conditions. Results: Seventy-five percent of the fetuses at the 26-week assessment and 100% of the fetuses at the 36-week assessment responded with movement immediately following stimulation. Significant differences in head, fetal breathing, general, limb, and mouthing movements were detected between the 26 and 36-week assessments. Movement differences between conditions were detected in head, fetal breathing, limb, and mouthing movements. Conclusion: Smoother and more complex movement was observed with fetal maturation. Following VAS stimulation, an immediate increase of large, jerky movements suggests instability in fetal capabilities. Fetal movement quality changes over gestation may reflect sensorimotor synaptogenesis in the central nervous system, while observation of immature movement patterns following VAS stimulation may reflect movement pattern instability.
doi:10.3389/fpsyg.2011.00350
PMCID: PMC3245669  PMID: 22207855
motor development; fetal programming; prenatal; pregnancy; fetal movement
19.  A Novel Approach to Track Fetal Movement Using Multi-sensor Magnetocardiographic Recordings 
Annals of biomedical engineering  2010;39(3):964-972.
Changes in fetal magnetocardiographic (fMCG) signals are indicators for fetal body movement. We propose a novel approach to reliably extract fetal body movements based on the field strength of the fMCG signal independent of its frequency. After attenuating the maternal MCG, we use a Hilbert transform approach to identify the R-wave. At each R-wave, we compute the center-of-gravity (cog) of the coordinate positions of MCG sensors, each weighted by the magnitude of the R-wave amplitude recorded at the corresponding sensor. We then define actogram as the distance between the cog computed at each R-wave and the average of the cog from all the R-waves in a 3-min duration. By applying a linear de-trending approach to the actogram we identify the fetal body movement and compare this with the synchronous occurrence of the acceleration in the fetal heart rate. Finally, we apply this approach to the fMCG recorded simultaneously with ultrasound from a single subject and show its improved performance over the QRS-amplitude based approach in the visually verified movements. This technique could be applied to transform the detection of fetal body movement into an objective measure of fetal health and enhance the predictive value of prevalent clinical testing for fetal wellbeing.
doi:10.1007/s10439-010-0231-z
PMCID: PMC3037432  PMID: 21140290
Center-of-gravity; Hilbert transform; Fetal magenetocardiogram; Fetal body movement; Ultrasound
20.  Professional and patient perspectives of NICE guidelines to abandon maternal monitoring of fetal movements 
Over the past 30 years, fetal movement counts have been recommended to women in the second half of pregnancy as a way of monitoring fetal wellbeing and providing an early warning of fetal distress. However, guidance from the National Institute of Clinical Excellence (NICE) recommends abandoning this. Evidence is reviewed to show that the chance of preventing physical damage to the fetus is indeed low. The activity of monitoring movements has been favoured by the majority of women. The new NICE guidance is useful to clarify professional understanding of the limitation of counting fetal movements, but women who notice decreased movements will still need referral for human factors.
PMCID: PMC1324922  PMID: 15527614
fetal movement; maternal welfare; perinatal care
21.  Bio-magnetic signatures of fetal breathing movement 
Physiological measurement  2011;32(2):263-273.
The purpose of fetal magnetoencephalography (fMEG) is to record and analyze fetal brain activity. Unavoidably, these recordings consist of a complex mixture of bio-magnetic signals from both mother and fetus. The acquired data include biological signals that are related to maternal and fetal heart function as well as fetal gross body and breathing movements. Since fetal breathing generates a significant source of bio-magnetic interference during these recordings, the goal of this study was to identify and quantify the signatures pertaining to fetal breathing movements (FBM). The fMEG signals were captured using superconducting quantum interference devices (SQUIDs) The existence of FBM was verified and recorded concurrently by an ultrasound-based video technique. This simultaneous recording is challenging since SQUIDs are extremely sensitive to magnetic signals and highly susceptible to interference from electronic equipment. For each recording, an ultrasound-FBM (UFBM) signal was extracted by tracing the displacement of the boundary defined by the fetal thorax frame by frame. The start of each FBM was identified by using the peak points of the UFBM signal. The bio-magnetic signals associated with FBM were obtained by averaging the bio-magnetic signals time locked to the FBMs. The results showed the existence of a distinctive sinusoidal signal pattern of FBM in fMEG data.
doi:10.1088/0967-3334/32/2/009
PMCID: PMC3102004  PMID: 21252416
fetal breathing movement; bio-magnetic signal; fetal magnetoencephalography; ultrasound
22.  Fetal Eye Movements on Magnetic Resonance Imaging 
PLoS ONE  2013;8(10):e77439.
Objectives
Eye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed.
Methods
Dynamic SSFP sequences were acquired in 72 singleton fetuses (17–40 GW, three age groups [17–23 GW, 24–32 GW, 33–40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid.
Results
In 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded.
Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3–45%.
Conclusions
In human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations.
doi:10.1371/journal.pone.0077439
PMCID: PMC3806733  PMID: 24194885
23.  Prenatal Antecedents of Newborn Neurological Maturation 
Child development  2010;81(1):115-130.
Fetal neurobehavioral development was modeled longitudinally using data collected at weekly intervals from 24- to -38 weeks gestation in a sample of 112 healthy pregnancies. Predictive associations between 3 measures of fetal neurobehavioral functioning and their developmental trajectories to neurological maturation in the 1st weeks after birth were examined. Prenatal measures included fetal heart rate variability, fetal movement, and coupling between fetal motor activity and heart rate patterning; neonatal outcomes include a standard neurologic examination (n = 97) and brainstem auditory evoked potential (BAEP; n = 47). Optimality in newborn motor activity and reflexes was predicted by fetal motor activity; fetal heart rate variability and somatic-cardiac coupling predicted BAEP parameters. Maternal pregnancy-specific psychological stress was associated with accelerated neurologic maturation.
doi:10.1111/j.1467-8624.2009.01384.x
PMCID: PMC2846092  PMID: 20331657
24.  Fetal Cardiac Autonomic Control during Breathing and Non-Breathing Epochs: The Effect of Maternal Exercise 
Early human development  2012;88(7):539-546.
We explored whether maternal exercise during pregnancy moderates the effect of fetal breathing movements on fetal cardiac autonomic control assessed by metrics of heart rate (HR) and heart rate variability (HRV). Thirty women were assigned to Exercise or Control group (n=15/group) based on the modifiable physical activity questionnaire (MPAQ). Magnetocardiograms (MCG) were recorded using a dedicated fetal biomagnetometer. Periods of fetal breathing activity and apnea were identified using the fetal diaphragmatic magnetomyogram (dMMG) as a marker. MCG R-waves were marked. Metrics of fetal HR and HRV were compared using 1 breathing and1 apneic epoch/fetus. The main effects of group (Exercise vs. Control) and condition (Apnea vs. Breathing) and their interactions were explored. Fetal breathing resulted in significantly lower fetal HR and higher vagally-mediated HRV. Maternal exercise resulted in significantly lower fetal HR, higher total HRV and vagally-mediated HRV with no difference in frequency band ratios. Significant interactions between maternal exercise and fetal breathing were found for metrics summarizing total HRV and a parasympathetic metric. Post hoc comparison showed no group difference during fetal apnea. Fetal breathing was associated with a loss of Total HRV in the Control group and no difference in the Exercise group. Both groups show enhanced vagal function during fetal breathing; greater in the Exercise group. During in utero breathing movements, the fetus of the exercising mother has enhanced cardiac autonomic function that may give the offspring an adaptive advantage.
doi:10.1016/j.earlhumdev.2011.12.017
PMCID: PMC3753784  PMID: 22264436
Exercise; Autonomic Nervous System; Magnetocardiogram; Fetal Biomagnetometry; Diaphragm Activation
25.  Combined one- and two-dimensional ultrasound system for monitoring fetal breathing movements. 
British Medical Journal  1976;2(6042):975-976.
A combined one- and two-dimensional ultrasonic system for monitoring respiratory movements in the human fetus has been developed. A real-time cross-sectional image of the fetal chest at the level of the fetal heart can be obtained, and a time motion recording of fetal respiratory movements can then be written on a strip-chart recorder. Combining the features of one-dimensional and two-dimensional systems produces an accurate means of investigating fetal breathing movements.
Images
PMCID: PMC1689269  PMID: 987828

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