Fetal Sleep Research Articles

Continuity and change in neural plasticity through embryonic morphogenesis, fetal activity-dependent synaptogenesis, and infant memory consolidation.

There is an apparent continuity in human neural development that can be traced to venerable themes of vertebrate morphogenesis that have shaped the evolution of the reptilian telencephalon (including both primitive three-layered cortex and basal ganglia) and then the subsequent evolution of the mammalian six-layered neocortex. In this theoretical analysis, we propose that an evolutionary-developmental analysis of these general morphogenetic themes can help to explain the embryonic development of the dual divisions of the limbic system that control the dorsal and ventral networks of the human neocortex. These include the archicortical (dorsal limbic) Papez circuits regulated by the hippocampus that organize spatial, contextual memory, as well as the paleocortical (ventral limbic) circuits that organize object memory. We review evidence that these dorsal and ventral limbic divisions are controlled by the differential actions of brainstem lemnothalamic and midbrain collothalamic arousal control systems, respectively, thereby traversing the vertebrate subcortical neuraxis. These dual control systems are first seen shaping the phyletic morphogenesis of the archicortical and paleocortical foundations of the forebrain in embryogenesis. They then provide dual modes of activity-dependent synaptic organization in the active (lemnothalamic) and quiet (collothalamic) stages of fetal sleep. Finally, these regulatory systems mature to form the major systems of memory consolidation of postnatal development, including the rapid eye movement (lemnothalamic) consolidation of implicit memory and social attachment in the first year, and then-in a subsequent stage-the non-REM (collothalamic) consolidation of explicit memory that is integral to the autonomy and individuation of the second year of life.

Evaluation of parameters for fetal behavioural state classification

Fetal behavioural states (fBS) describe periods of fetal wakefulness and sleep and are commonly defined by features such as body and eye movements and heart rate. Automatic state detection through algorithms relies on different parameters and thresholds derived from both the heart rate variability (HRV) and the actogram, which are highly dependent on the specific datasets and are prone to artefacts. Furthermore, the development of the fetal states is dynamic over the gestational period and the evaluation usually only separated into early and late gestation (before and after 32 weeks). In the current work, fBS detection was consistent between the classification algorithm and visual inspection in 87 fetal magnetocardiographic data segments between 27 and 39 weeks of gestational age. To identify how automated fBS detection could be improved, we first identified commonly used parameters for fBS classification in both the HRV and the actogram, and investigated their distribution across the different fBS. Then, we calculated a receiver operating characteristics (ROC) curve to determine the performance of each parameter in the fBS classification. Finally, we investigated the development of parameters over gestation through linear regression. As a result, the parameters derived from the HRV have a higher classification accuracy compared to those derived from the body movement as defined by the actogram. However, the overlapping distributions of several parameters across states limit a clear separation of states based on these parameters. The changes over gestation of the HRV parameters reflect the maturation of the fetal autonomic nervous system. Given the higher classification accuracy of the HRV in comparison to the actogram, we suggest to focus further research on the HRV. Furthermore, we propose to develop probabilistic fBS classification approaches to improve classification in less prototypical datasets.

Analgesia for fetal pain during prenatal surgery: 10 years of progress.

Some doubts on the necessity and safety of providing analgesia to the fetus during prenatal surgery were raised 10 years ago. They were related to four matters: fetal sleep due to neuroinhibitors in fetal blood, the immaturity of the cerebral cortex, safety, and the need for fetal direct analgesia. These objections now seem obsolete. This review shows that neuroinhibitors give fetuses at most some transient sedation, but not a complete analgesia, that the cerebral cortex is not indispensable to feel pain, when subcortical structures for pain perception are present, and that maternal anesthesia seems not sufficient to anesthetize the fetus. Current drugs used for maternal analgesia pass through the placenta only partially so that they cannot guarantee a sufficient analgesia to the fetus. Extraction indices, that is, how much each analgesic drug crosses the placenta, are provided here. We here report safety guidelines for fetal direct analgesia. In conclusion, the human fetus can feel pain when it undergoes surgical interventions and direct analgesia must be provided to it. IMPACT: Fetal pain is evident in the second half of pregnancy. Progress in the physiology of fetal pain, which is reviewed in this report, supports the notion that the fetus reacts to painful interventions during fetal surgery. Evidence here reported shows that it is an error to believe that the fetus is in a continuous and unchanging state of sedation and analgesia. Data are given that disclose that drugs used for maternal analgesia cross the placenta only partially, so that they cannot guarantee a sufficient analgesia to the fetus. Safety guidelines are given for fetal direct analgesia.

A Point Process Framework for the Characterization of Fetal Sleep States.

In the fetal period, the progressive coordination among several subsystems promotes the emergence of sleep states. For this reason, the characterization of fetal behavioral states plays a crucial role in assessing fetal wellbeing. Nevertheless, current methodologies aimed at assessing fetal sleep states over limited time intervals require visual observation of the traces. In this work, we validate a point process approach for a continuous in time characterization of fetal behavioral states. We compare traditional heart rate variability (HRV) parameters and the corresponding point process-extracted sets of time and frequency measures in a population of 39 fetuses whose fetal ECG was recorded overnight during the third trimester of gestation.Clinical Relevance- Our results provide evidence for the proposed point process framework to capture fetal HRV dynamics with a high degree of reliability, suggesting its potential application for instantaneous estimates of fetal sleep states.

A study on the association between eye movements and regular mouthing movements (RMMs) in normal fetuses between 24 to 39 weeks of gestation.

Regular Mouthing Movements (RMMs) are movements in which lips and lower jaw movements occur regularly and can be observed in the fetus using transabdominal ultrasonic tomography. In near term infants, it is known that RMMs form clusters during the quiet sleep period. The notation of RMMs is not uniform, and is described as spontaneous sucking movement or non-nutritive sucking in newborns. Non-nutritive sucking is used to evaluate neurological function after birth, but there are no fetal indicators. The purpose of this study was to clarify the changes in the RMM clusters in fetuses at 24-39 weeks of gestation, and to investigate the relationship with the non-eye movement (NEM) period, which corresponds to the quiet sleep period after birth. Subjects included 83 normal single pregnancy cases. Fetal RMMs and eye movement (EM) were observed for 60 minutes using ultrasonic tomography and recorded as moving image files. We created time series data of eye movements and mouth movements from video recordings, and calculated RMM clusters per minute within effective observation time, RMM clusters per minute in EM period, RMM clusters per minute in NEM period, mouthing movements per cluster and ratio of number of RMM clusters per minute between NEM and EM periods and analyzed using linear regression analysis. As a result, critical points were detected in at two time points, at 32-33 weeks and 36-37 weeks of gestation, in RMM clusters per minute within the effective observation time and RMM clusters per minute in NEM period, respectively. RMM clusters in human fetuses increased from 32-33 to 36-37 weeks. This change is thought to represent fetal sleep development and central nervous system development.

The comorbidity of fetal alcohol syndrome and sleep apnea/hypopnea syndrome in a 7‑year-old girl (a clinical case)

Fetal alcohol syndrome is the result of prenatal effect of alcohol on the fetus and manifests as disorders of neural and mental development and various congenital developmental disorders leading to comorbid diseases. Among congenital developmental disorders for the pathology, adenotonsillar pathology was described. Narrowing of the nasopharyngeal opening, faciomaxillary dysmorphias and muscle hypotony can lead to sleep apnea syndrome. The article presents a clinical case of fetal alcohol syndrome and sleep apnea in a 7‑year-old girl with multiple developmental disorders born form alcohol-abusing mother. Breathing abnormalities during sleep must be differentiated per character and cause. Cardiorespiratory monitoring is used to diagnose respiratory abnormalities, the results determine patient management tactics. Interdisciplinary approach to observation and treatment of a child with fetal alcohol syndrome is necessary to increase the effectiveness of rehabilitation measures and patient’s quality of life.

Advanced automatic detection of fetal body movements from multichannel magnetocardiographic signals

Objective: Both heart rate (HR) monitoring and detection and description of fetal movements provide essential information of the integrity of in utero development and fetal wellbeing. Our previously described method to identify movements from multichannel magnetocardiographic (MCG) recordings lacks of reliability in some cases. This work is aimed at the improvement of fetal movement detection by means of an advanced signal processing and validation strategy. Approach: The previously proposed methodology of fetal body movement detection from MCG recordings using single space angle (SSA), min–max amplitude (MMA) and a measure of the overall signal strength across (RSS) was extended by moving correlation coefficient (MCC). The methodology was developed with respect to the discrimination between active and quiet sleep, validated by testing its coupling with HR accelerations in a total of 137 recordings lasting 30 min from 98 fetuses aged 34–38 weeks of gestation (WGA) of normal pregnancy. Main results: The developed algorithm improves the reliable automatic detection of fetal body movements independent of the fetal sleep states and their changes in the individual MCG recordings. In the fetuses aged 34–38 WGA 94% of 15 × 15 HR accelerations were coupled with detected movements. The visual inspection of the movement graphs of 30 fetuses aged 20–32 WGA supports the transferability of the movement detector to this age. In four subjects MCG-based movement detection and maternal report on percepted fetal movements were consistent. Significance: The presented methodology allows the parallel automatic acquisition of precise fetal heart rate variability (HRV) indices based on subsequent beat intervals and of fetal body movements from MCG recordings during late 2nd and 3rd trimester. Potential advantages of parallel monitoring of fetal HRV and movements using MCG compared to established ultrasound technology should be investigated in subsequent studies with respect to the identification of fetuses at risk.

The Impact of "Mom/Dad of the Day" Cards, Newborn Heart Auscultation, and Father Skin-to-Skin Care on Parent-Newborn Bonding.

Texas Tech Pediatrics at Northwest Texas Hospital System in Amarillo, Texas, currently practices giving "Mom/Dad of the Day" cards to all new parents, offering the opportunity for fathers to auscultate the newborn heart sound, and encouraging maternal and paternal skin-to-skin contact. New parents were asked to fill out 2 anonymous surveys regarding these practices. Survey results showed statistically significant positive responses by the parents for subjective improvement in fetal sleep and feeding as well as parental confidence and preparedness for taking care of their newborn. Additionally, these practices are desired by parents, with 96% fathers recommending that the hospital routinely offering opportunities for heart auscultation and 94% parents recommending "Mom/Dad of the Day" cards for all future parents in the hospital. Small, nonmedical initiatives such as these are well received and can be feasibly adopted in more hospitals to improve patient quality of care.

Non Stress Test – An Update

Non stress test is a time tested, convenient and reliable test of antenatal fetal surveillance. It accurately predicts those fetus that do not require acute or premature obstetric intervention and thereby prevents pregnancies from being subjected to unnecessary iatrogenic risks and avoids unnecessary medical, financial and emotional burden. The principle of non stress test is that the heart rate of a fetus with adequate oxygenation and normal neurological response will temporarily accelerate with fetal movement. Loss of reactivity is commonly associated with a fetal sleep cycle but may result from any cause of central nervous system depression, fetal acidosis or maternal drug intake and requires further evaluation for an extended period or evaluation with other techniques like biophysical profile or amniotic fluid testing or umbilical artery Doppler study as per the overall clinical scenario. A correctly performed NST, using standard technique with proper interpretation may be of great value in planning further management.

A Prospective Study on Impact of Non Stress Test in Prediction of Pregnancy Outcome

This prospective study was done at Department of Obstetrics and Gynecology, Manipal College of Medical Sciences, Pokhara, Nepal to identify effectiveness of NST in detecting high risk fetus thus preventing perinatal morbidity and mortality. The cohort of 125 pregnant mothers from 37 completed weeks to 42 weeks irrespective of risk factors, were subjected to NST for 20 minutes and extended to 40 minutes to avoid fetal sleep cycle. NST was categorized into Cat I, II and III according to NICHD. Fetal distress, meconium stained liquor was higher in Cat III group. There was more intervention in Cat II and Cat III group. Total number of patients who underwent LSCS was 51. Most common indication for LSCS (53%) was for fetal distress out of which 85% had NST of Cat II (37%) and Cat III (48%). For detecting high risk fetus, NST is a simple screening procedure and is helpful in decreasing perinatal morbidity and mortality.

Proceedings of 2011 Stillbirth Summit

The previous Stillbirth Summit presented by the Star Legacy Foundation and supported by various organisations was held in October 2011 in Minneapolis to discuss emerging ideas in the field of stillbirth research and management. In particular the focus was on the placenta, cord, infection and inflammation, reduced fetal movements and maternal sleep. Attendees were invited researchers, stillbirth advocates and parents. One of the strengths of the meeting was the robust debate amongst the researchers, alongside the energy and passion of the parents. Unlike some scientific meetings which are talkfest, the Summit in 2011 had tangible outcomes. The first of which was that the majority of the researchers summarised their presentations, which were published in the BMC Pregnancy and Childbirth, which is an open access journal allowing anyone to access the content online [1]. Several important collaborations developed. Jane Warland and Ed Mitchell had independently developed conceptual models for the mechanism of stillbirths, which were adapted from the SIDS triple risk model. These authors collaborated in developing their ideas further and this has been recently published [2]. In 2011 Tomasina Stacey summarised the findings from The Auckland Stillbirth Study, a case-control study, which identified maternal non-left position on going to sleep was associated with a two fold increase risk of late stillbirths. The researchers urged caution and identified the need for robust, peer reviewed supporting evidence before recommending change or public health campaigns. Alex Heazell took up the challenge and with the support of the Auckland group has developed the Midland and North of England Stillbirth Study (MiNESS), which is funded by Action Medical Research and Cure Kids [3]. The most notable outcome was the development of the STARS Study, led by Louise O’Brien and Jane Warland, and supported by the Star Legacy Foundation. In essence this is an internet survey of women who had lost a baby in late pregnancy (28+ weeks gestation). There were two components, the first was women who had lost their baby more than 3 weeks prior to completing the survey. “The experiences of 1310 mothers of late stillbirths” was presented at the Stillbirth Summit 2014 by Jane Warland. The second component was a case-control study. The cases are mothers who had a late stillbirth less than 3 weeks prior to completing the interview. They are compared with women who had live ongoing pregnancies also at 28+ weeks gestation. The survey was extensive covering a wide range of issues. Recruitment has been difficult and the expected number of cases and controls are less than expected. Ed Mitchell presented interim findings from 132 cases and 283 controls. As these analyses were interim, the results are not presented here.

Ontogeny and control of the heart rate power spectrum in the last third of gestation in fetal sheep

Power spectral analysis of fetal heart rate variability has been proposed to provide a non-invasive estimate of autonomic balance. However, there are few systematic data before birth. We therefore examined developmental changes in the frequency power spectrum at very low (0-0.04 Hz), low (0.04-0.15 Hz) and high frequencies (0.15-0.4 Hz), as well as the ratio of low- to high-frequency power (LF/HF), in chronically catheterized, healthy fetal sheep at 0.6 (n = 8), 0.7 (n = 7) and 0.8 gestational age (ga; n = 11). In a second study, 0.8 ga fetuses received either atropine (4.8 mg bolus, then 4.8 mg h(-1) for 30 min, n = 6) or 6-hydroxydopamine (20 mg ml(-1) at 2.5 ml h(-1) for 3 h; n = 9). Data were analysed by sleep state, defined by low-voltage-high-frequency (LV) or high-voltage-low-frequency (HV) EEG. Total spectral power increased with gestational age (P < 0.05), while LF/HF decreased from 0.6 to 0.7 ga. At 0.8 ga, heart rate and LF/HF were significantly higher during HV than LV sleep (P < 0.05). Consistent with this, although total spectral power was not significantly greater during HV sleep, there was a significant interaction between sleep state and frequency band (P = 0.02). Both atropine (P = 0.05) and 6-hydroxydopamine (P < 0.05) were associated with an overall reduction in spectral power but no significant effect on the LF/HF ratio. This study does not support substantial, consistent differences between the frequencies of sympathetic and parasympathetic activity in late-gestation fetal sheep.

Emerging ideas to better understand and prevent stillbirths

It is estimated that over 3.6 million babies are stillborn each year [1]. Although the majority of these occur in low-income countries, stillbirth continues to place a significant burden on maternity services in high-income settings where approximately 1 in 200 infants born after 24 weeks gestation is stillborn [1]. Despite advances in ultrasound detection of lethal fetal anomalies and widespread access to antenatal care, the stillbirth rate in many high-income countries has not decreased in over two decades. Stillbirth remains an enigma, in part due to lack of research investigation, but also due to a failure to accurately identify causes and understand how they lead to stillbirth. Recent meta-analyses resulting from international collaborations have highlighted the need to expand the understanding of stillbirth. To this end, a meeting, the Stillbirth Summit, presented by the Star Legacy Foundation and supported by various organizations, was held in October 2011, Minneapolis, MN (USA) to discuss emerging ideas in the field of stillbirth research and management. In particular the focus was on the placenta, cord, infection and inflammation, reduced fetal movements and maternal sleep. Attendees were invited researchers, stillbirth advocates and parents. The aim of this supplement is to briefly summarise the scientific aspects of the meeting.

Fetal sleep organization: A biological precursor of self-regulation in childhood and adolescence?

Fetal sleep states emerge during the third trimester of pregnancy and involve multiple interconnected neuronal networks. We examined whether fetal sleep characteristics predict child and adolescent self-regulation in a non-clinical sample (study group, n=25; reference group, n=48). Combined recordings of three sleep variables (fetal heart rate, body movements and rapid eye movements) were made for 2h at 36–38 weeks’ gestation. Fetuses showing synchronous change of sleep variables (i.e. within 3min) at transition from quiet into active sleep reached a higher level of effortful control, both at 8–9 and 14–15 years, than fetuses not making synchronous transitions and compared with the reference group. Results are discussed from a Developmental Origins of Behavior, Health and Disease (DOBHaD) point of view. It is concluded that studying sleep ontogeny offers the possibility to gain insight into brain maturational processes and/or environmental adaptive processes that may have long term behavioral developmental consequences.

Maternal dexamethasone and EEG hyperactivity in preterm fetal sheep

Maternal treatment with synthetic corticosteroids such as dexamethasone (DEX)significantly reduces neonatal morbidity and mortality, but its effects on the fetal brain remain unclear. In this study we evaluated the effects of DEX on EEG activity in preterm fetal sheep. Ewes at 103 days gestation received two intramuscular injections of DEX (12 mg, n = 8) or saline vehicle (n = 7) 24 h apart. Fetal EEG activity was recorded from 6 h before until 120 h after the first injection (DEX-1). DEX-1 was associated with a marked transient rise in total EEG power, maximal at 12 h (P < 0.001), with a relative increase in delta and reduced theta, alpha and beta activity, resolving by 24 h. Continuous EEG records showed a shift to larger but less frequent transient waveforms (P < 0.001). Unexpectedly, evolving epileptiform activity, consistent with electrographic and clinical seizures, developed from 178 ± 44 min after DEX-1.Similar but smaller changes were seen after the second injection. Following the injections, total power returned to control values, but the proportion of alpha activity progressively increased vs. controls (P < 0.001), with reduced interburst interval duration and number (P < 0.001). No histological neural injury or microglial activation was seen. In summary, exposure to maternal dexamethasone was associated with dramatic, evolving low-frequency hyperactivity on fetal cortical EEG recordings, followed by sustained changes consistent with maturation of fetal sleep architecture. We postulate that these effects may contribute to improved neonatal outcomes.

Poor Fetal Heart Rate Variability in a Pregnant Woman with Acute Appendicitis

Fetal heart rate (FHR) variability indicates autonomic nervous system response. Absence of variability may be due to various causes, including fetal metabolic acidosis, neurologic abnormality, marked prematurity, cardiac arrhythmia, effects of drugs, fetal sleep or inactivity. We present the case of a pregnant woman with acute appendicitis whose fetus demonstrated poor variability in heart rate, and we explore the possible reasons that caused poor variability in FHR in this patient. A pregnant woman at 40+1 weeks of gestation was admitted because of acute right lateral subcostal tenderness and rebounding pain. Under the impression of acute appendicitis, emergency appendectomy was arranged. Epidural combined with general anesthesia were offered to the patient. Absent variability of FHR on fetal monitoring was noted immediately after laparotomy, and did not reappear until 5 hours after the operation. Emergency cesarean section with spinal anesthesia was arranged due to prolonged active phase in cervical dilatation. The fetus was born with Apgar scores of 6 and 8 at 1 and 5 minutes, respectively. Abdominal sepsis due to acute appendicitis that subsequently caused chorioamnionitis and fetal infection was the most probable reason for the poor FHR variability. When sources of infection are eradicated from a pregnant patient, whether by surgical or medical methods, FHR variability will gradually return. Seldom is cesarean section indicated at the time of appendectomy. We suggest that the choice of delivery should depend on the obstetric indications, and not on the event of acute appendicitis.

Sinusoidal heart rate pattern: Reappraisal of its definition and clinical significance.

To address the clinical significance of sinusoidal heart rate (SHR) pattern and review its occurrence, define its characteristics, and explain its physiopathology. In 1972, Manseau et al. and Kubli et al. described an undulating wave form alternating with a flat or smooth baseline fetal heart rate (FHR) in severely affected, Rh-sensitized and dying fetuses. This FHR pattern was called 'sinusoidal' because of its sine waveform. Subsequently, Modanlou et al. described SHR pattern associated with fetal to maternal hemorrhage causing severe fetal anemia and hydrops fetalis. Both Manseau et al. and Kubli et al. stated that this particular FHR pattern, whatever its pathogenesis, was an extremely significant finding that implied severe fetal jeopardy and impending fetal death. UNDULATING FHR PATTERN: Undulating FHR pattern may be due to the following: (1) true SHR pattern; (2) drugs; (3) pre-mortem FHR pattern; (4) pseudo-SHR pattern; and (5) equivocal FHR patterns. FETAL CONDITIONS ASSOCIATED WITH SHR PATTERN: SHR pattern has been reported with the following fetal conditions: (1) severe fetal anemia of several etiologies; (2) effects of drugs, particularly narcotics; (3) fetal asphyxia/hypoxia; (4) fetal infection; (5) fetal cardiac anomalies; (6) fetal sleep cycles; and (7) sucking and rhythmic movements of fetal mouth. DEFINITION OF TRUE SHR PATTERN: Modanlou and Freeman proposed the following definition for the interpretation of true SHR pattern: (a) stable baseline FHR of 120-160 bpm; (b) amplitude of 5-15 bpm, rarely greater; (c) frequency of 2-5 cycles per minute; (d) fixed or flat short-term variability; (e) oscillation of the sinusoidal wave from above and below a baseline; and (f) no areas of normal FHR variability or reactivity. Since its early recognition, the physiopathology of SHR became a matter of debate. Murata et al. noted a rise of arginine vasopressin levels in the blood of posthemorrhagic/anemic fetal lamb. Further works by the same authors revealed that with chemical or surgical vagotomy, arginine vasopressin infusion produced SHR pattern, thus providing the role of autonomic nervous system dysfunction combined with the increase in arginine vasopressin as the etiology. SHR is a rare occurrence. A true SHR is an ominous sign of fetal jeopardy needing immediate intervention. The correct diagnosis of true SHR pattern should also include fetal biophysical profile and the absence of drugs such as narcotics.

Role of Adenosine in Regulating Fetal Sleep States and Breathing Activity

A review of: Koos BJ, Maeda T, and Jan C 2001 Adenosine A1 and A2A receptors modulate sleep state and breathing in fetal sheep. J Appl Physiol 91:343–350; and Koos BJ, Maeda T 2001 Adenosine A2A receptors mediate cardiovascular responses to hypoxia in fetal sheep. Am J Physiol Heart Circ Physiol 280:H83–H89

The association between fetal and maternal sleep patterns in third-trimester pregnancies

Objective: We sought to investigate the association between fetal heart rate and maternal electroencephalogram patterns during overnight sleep. Study Design: Data were collected prospectively between December 1, 1999, and June 30, 2001. Initially, the participating patients were asked to complete a 66-question survey for the assessment of maternal perception of sleep quality that was referred to as the sleep disturbance score: a continuous score from 0 (no evidence of sleep disturbance) to 110 (extreme sleep disturbance). Second, a subgroup of patients was monitored overnight by concomitant fetal heart rate and maternal electroencephalogram tracings. Statistical analysis included the Student t test, χ2 test, logistic regression, and Cramer's V contingency correlation. Results: One hundred two singleton pregnancies formed the study population. The mean sleep disturbance score was 26.7 ± 9.9. Maternal age was the only variable that correlated with sleep disturbance score. A subgroup of 11 patients was studied overnight. A significant correlation between active fetal sleep and maternal wakefulness was demonstrated in 6 patients. The mean sleep disturbance score for these patients was significantly higher than for patients without such correlation (P =.04). Conclusion: This study establishes an association between fetal activity and maternal wakefulness, which explains many of the maternal awakenings during sleep in the third trimester. (Am J Obstet Gynecol 2002;186:924-5.)

Fetal urine production and micturition and fetal behavioral state.

The rate of fetal urine production and the incidence of fetal micturition was compared in periods of fetal sleep and awakeness. Sonography and fetal heart rate monitoring were concomitantly performed on 12 normal term pregnancies. Fetal bladder volumes were serially calculated, and the rate of urine production and micturition were compared between the periods of fetal sleep and awakeness. Fetal micturition occurred almost exclusively during periods of fetal awakeness (p = 0.001). There were no demonstrable differences in the rates of urine production during periods of fetal sleep and awakeness. Fetal micturition is behavioral-state dependent. Nevertheless, the fetal behavioral state is not a necessary consideration when applying urine production measurements as a test of fetal well-being.