Review

Authors: Hirobumi Asakura

The metabolic rate of the fetus per tissue weight is relatively high when compared to that of an adult. Moreover, heat is transferred to the fetus via the placenta and the uterus, resulting in a 0.3 degrees C to 0.5 degrees C higher temperature than that of the mother. Therefore, fetal temperature is maternally dependent until birth. At birth, the neonate rapidly cools in response to the relatively cold extrauterine environment. Thus, the neonatal temperature rapidly drops soon after birth. In order to survive, the neonate must accelerate heat production via nonshivering thermogenesis (NST), which is coupled to lypolysis in brown adipose tissue. Heat is produced by uncoupling ATP synthesis via the oxidation of fatty acids in the mitochondria, utilizing uncoupled protein. Thermogenesis must begin shortly after birth and continue for several hours. Since thermogenesis requires adequate oxygenation, a distressed neonate with hypoxemia cannot produce an adequate amount of heat to increase its temperature. In contrast to the neonate, the fetus cannot produce extra heat production. This is because the fetus is exposed to inhibitors to NST, which are produced in the placenta and then enter the fetal circulation. The important inhibitors include adenosine and prostaglandin E2, both of which have strong anti-lypolytic actions. The inhibitors play an important role in the metabolic adaptation of a physiological hypoxic fetus because NST requires adequate oxygenation. Furthermore, the presence of NST inhibitors allows the fetus to accumulate an adequate amount of brown adipose tissue before birth. The umbilical circulation transfers 85% of the heat produced by the fetus to the maternal circulation. The remaining 15% is dissipated through the fetal skin to the amnion, and is then transferred through the uterine wall to the maternal abdomen. As long as fetal heat production and loss are appropriately balanced, the temperature differential between the fetus and the mother remains constant (heat clump). However, when the umbilical circulation is occluded for any reason, the fetal temperature will rise in relation to the extent of the occlusion. The fetal temperature may elevate to the hyperthermic range in cases of acute cord occlusion; if this occurs, fetal growth, including brain development, may be impacted. Experimentally induced cord occlusion, which is recognized as a significant cause of brain damage, results in a rapid elevation of body temperature; however, the brain temperature tends to remain constant. This is considered to be a cerebral thermoregulatory adaptation to hypoxemia, which has the physiologic advantage of protecting the fetus from hyperthermia, a condition that predisposes the fetus to hypoxic injury (cerebral hypometabolism). A number of thermoregularatory mechanisms are in place to maintain normal fetal and neonatal growth. Data has primarily been collected from animal studies; aside from the strict thermal control provided in the newborn nursery, little information exists concerning these mechanisms in the human fetus and neonate. Probably further information on thermoregulation is necessary specially to improve perinatal management for hypoxic fetuses.

Topics: Body Temperature Regulation; Fetus; Humans; Infant, Newborn

PubMed: 15673956
DOI: 10.1272/jnms.71.360

Authors: Yayun Qin, Yanyi Yao, Nian Liu...

BACKGROUND

Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of prenatal WES and to investigate the pathogenic variants in structurally abnormal fetuses.

METHODS

We recruited 144 fetuses with structural anomalies between 14 and 2020 and 15 December 2021 in the study. Genetic screening was performed by WES combined with karyotyping and chromosomal microarray analysis. The molecular diagnostic yield of prenatal WES for each type of fetal structural anomaly and the identified pathogenic genes and mutations were reported.

RESULTS

In this study, we retrospectively analyzed the clinical and genetic data of 145 structurally anomalous fetuses. These cases were classified into 9 phenotypic classes based on antenatal ultrasound findings. Thirty-eight pathogenic variants in 24 genes were identified in 35 of the 145 cases, including 14 novel variants in 13 genes (EP300, MYH3, TSC2, MMP9, CPLANE1, INVS, COL1A1, EYA1, TTC21B, MKS1, COL11A2, PDHA1 and L1CAM). Five additional pathogenic variants were classified as incidental findings. Our study showed that the overall diagnosis rate of WES was 28.1% (27/96) in the parent-fetus trio cases and 16.3% (8/49) in the proband-only cases. Fetuses with musculoskeletal anomalies had the highest diagnostic yield (51.4%, 19/37). In addition, FGFR3 and COL1A1 were the most common pathogenic genes.

CONCLUSIONS

Our work expands the mutation spectrum of the genes associated with fetal structural anomalies and provides valuable information for future parental genetic counselling and pregnancy management of the structurally anomalous fetuses.

Topics: Female; Humans; Pregnancy; East Asian People; Exome Sequencing; Fetus; Pregnancy Trimester, First; Prenatal Diagnosis; Retrospective Studies; Ultrasonography, Prenatal; Congenital Abnormalities

PubMed: 37880672
DOI: 10.1186/s12920-023-01697-3

Authors: R Hagege, K Krajden Haratz, G Malinger...

OBJECTIVE

To report on a large cohort of fetuses with mild forms of tubulinopathy and to define prenatal ultrasound and magnetic resonance imaging (MRI) features that can facilitate prenatal diagnosis.

METHODS

This was a retrospective multicenter study of fetuses diagnosed between January 2007 and February 2022 with a mild tubulinopathy (without lissencephaly or microlissencephaly). We collected and reviewed brain imaging and genetic data, and defined major criteria as findings observed in ≥ 70% of the patients and minor criteria as those observed in ≥ 50% but < 70% of the patients.

RESULTS

Our cohort included 34 fetuses. The mean gestational age at ultrasound screening, when suspicion of a central nervous system anomaly was first raised, was 24.2 (range, 17-33) weeks. Callosal anomalies (n = 19 (56%)) and abnormal ventricles (n = 18 (53%)) were the main reasons for referral. The mean gestational age at neurosonography was 28.3 (range, 23-34) weeks and that at MRI was 30.2 (range, 24-35) weeks. Major ultrasound criteria were midline distortion, ventricular asymmetry, dysmorphic and/or dilated frontal horn(s) and abnormal sulcation. Minor ultrasound criteria were distortion of the cavum septi pellucidi, abnormal corpus callosum, absent or asymmetric olfactory sulci, ventriculomegaly and basal ganglia dysmorphism. Major MRI criteria were midline distortion, distortion of the cavum septi pellucidi, ventricular asymmetry, dilatation (generally unilateral) and/or distortion, dysmorphic and/or dilated frontal horn(s) and abnormal sulcation (mainly dysgyria). Minor MRI criteria were absent or asymmetric olfactory sulci, abnormal bulge of the pons, anteroposterior diameter of the pons ≤ 5 centile and brainstem asymmetry. A mutation was found in TUBB3 (44.1% of cases), TUBB (23.5%), TUBB2B (14.7%) or TUBA1A (17.6%). The mutation was inherited from a parent in 18/34 cases. The pregnancy was terminated in 23/34 cases.

CONCLUSIONS

Prenatal diagnosis of mild forms of tubulinopathy is possible but challenging. We have defined, in this large series of fetuses, major and minor criteria that can help identify this entity in utero. Most findings can be visualized on ultrasound. This evaluation is also important for prenatal counseling. Once a prenatal diagnosis of mild tubulinopathy is suspected, the family members should be referred for exome sequencing and MRI. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Topics: Pregnancy; Female; Humans; Infant; Ultrasonography, Prenatal; Nervous System Malformations; Brain; Prenatal Diagnosis; Fetus; Gestational Age; Retrospective Studies; Magnetic Resonance Imaging

PubMed: 36484554
DOI: 10.1002/uog.26140

Review

Authors: Kiho Im, P Ellen Grant

Spatial distribution and specific geometric and topological patterning of early sulcal folds have been hypothesized to be under stronger genetic control and are more associated with optimal organization of cortical functional areas and their white matter connections, compared to later developing sulci. Several previous studies of sulcal pit (putative first sulcal fold) distribution and sulcal pattern analyses using graph structures have provided evidence of the importance of sulcal pits and patterns as remarkable anatomical features closely related to human brain function, suggesting additional insights concerning the anatomical and functional development of the human brain. Recently, early sulcal folding patterns have been observed in healthy fetuses and fetuses with brain abnormalities such as polymicrogyria and agenesis of corpus callosum. Graph-based quantitative sulcal pattern analysis has shown high sensitivity in detecting emerging subtle abnormalities in cerebral cortical growth in early fetal stages that are difficult to detect via qualitative visual assessment or using traditional cortical measures such as gyrification index and curvature. It has proven effective for characterizing genetically influenced early cortical folding development. Future studies will be aimed at better understanding a comprehensive map of spatio-temporal dynamics of fetal cortical folding in a large longitudinal cohort in order to examine individual clinical fetal MRIs and predict postnatal neurodevelopmental outcomes from early fetal life.

Topics: Brain; Fetus; Humans

PubMed: 29601953
DOI: 10.1016/j.neuroimage.2018.03.057

Authors: Sarah A Strand, Janette F Strasburger, Ronald T Wakai...

BACKGROUND

Fetal magnetocardiography (fMCG) is the most direct and precise method of assessing fetal rhythm and conduction. Although the utility of fMCG for evaluation of fetuses with serious arrhythmia is generally acknowledged, many aspects of fetal rhythm and conduction are relatively unstudied.

OBJECTIVE

To record fMCG in a large group of normal fetuses in order to provide a more comprehensive evaluation of fMCG waveform characteristics, including waveform intervals, amplitudes, and morphology.

METHODS

The subjects were 132 healthy women with uncomplicated singleton pregnancies, studied at 15.7-39.9 (mean 28.9) weeks' gestation in 259 sessions. The P, PR, QRS, QT, QTc, and RR intervals and the P/QRS and T/QRS amplitude ratios were measured.

MAIN RESULTS

The P, PR, QRS, and RR intervals increased with gestational age, but QT and QTc did not. U-waves were seen in 11% of fetuses. The T-waves were often flat with low T/QRS amplitude ratios. Equiphasic QRS complexes were associated with tall P-waves. The PR, QRS, and QT intervals showed a power law dependence on RR interval with power law exponents 0.445, 0.363, and 0.381, respectively.

SIGNIFICANCE

The data establish prediction intervals for fMCG waveform intervals and amplitudes in normal fetuses. This is critical for identification of fetuses with abnormal rhythm. Our study is the first to document the incidence of U-waves and flat T-waves in the fetus, both of which are uncommon postnatally. The association of tall P-waves with equiphasic QRS complexes provides a useful means of improving the resolution of fetal P-waves.

Topics: Adult; Female; Fetus; Gestational Age; Healthy Volunteers; Humans; Magnetocardiography; Pregnancy; Signal Processing, Computer-Assisted

PubMed: 30802886
DOI: 10.1088/1361-6579/ab0a2c

Review

Authors: Vassilios Fanos, Luigi Atzori, Karina Makarenko...

Metabolomics in maternal-fetal medicine is still an "embryonic" science. However, there is already an increasing interest in metabolome of normal and complicated pregnancies, and neonatal outcomes. Tissues used for metabolomics interrogations of pregnant women, fetuses and newborns are amniotic fluid, blood, plasma, cord blood, placenta, urine, and vaginal secretions. All published papers highlight the strong correlation between biomarkers found in these tissues and fetal malformations, preterm delivery, premature rupture of membranes, gestational diabetes mellitus, preeclampsia, neonatal asphyxia, and hypoxic-ischemic encephalopathy. The aim of this review is to summarize and comment on original data available in relevant published works in order to emphasize the clinical potential of metabolomics in obstetrics in the immediate future.

Topics: Amniotic Fluid; Female; Fetal Blood; Fetus; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Maternal-Fetal Relations; Metabolomics; Obstetric Labor, Premature; Placenta; Pregnancy; Pregnancy Complications

PubMed: 23841090
DOI: 10.1155/2013/720514

Authors: Andre L Lima Diniz, Francisco J B Sampaio, Luciano A Favorito...

Topics: Anencephaly; Fetus; Humans; Kidney

PubMed: 32822134
DOI: 10.1590/S1677-5538.IBJU.2020.06.02

Authors: M I Sharifah, M Noryati, C D Che Zubaidah...

Foetus-in-fetu is a rare condition in which a calcified mass is in the abdomen of its host, a newborn or an infant. We report a case of a newborn in whom abdominal radiograph and ultrasonography revealed a mass in which the contents favour a foetus-in-fetu. Diagnosis was confirmed by macroscopic examination that showed a soft tissue mass resembling a foetus, attached to the membranous sac. It was covered entirely with intact skin. There were two malformed lower limbs with a rudimentary digit and one malformed upper limb.

Topics: Abdomen; Fetus; Humans; Upper Extremity

PubMed: 23756803
DOI: No ID Found

Authors: Dustin F Kapraun, John F Wambaugh, R Woodrow Setzer...

Many parameters treated as constants in traditional physiologically based pharmacokinetic models must be formulated as time-varying quantities when modeling pregnancy and gestation due to the dramatic physiological and anatomical changes that occur during this period. While several collections of empirical models for such parameters have been published, each has shortcomings. We sought to create a repository of empirical models for tissue volumes, blood flow rates, and other quantities that undergo substantial changes in a human mother and her fetus during the time between conception and birth, and to address deficiencies with similar, previously published repositories. We used maximum likelihood estimation to calibrate various models for the time-varying quantities of interest, and then used the Akaike information criterion to select an optimal model for each quantity. For quantities of interest for which time-course data were not available, we constructed composite models using percentages and/or models describing related quantities. In this way, we developed a comprehensive collection of formulae describing parameters essential for constructing a PBPK model of a human mother and her fetus throughout the approximately 40 weeks of pregnancy and gestation. We included models describing blood flow rates through various fetal blood routes that have no counterparts in adults. Our repository of mathematical models for anatomical and physiological quantities of interest provides a basis for PBPK models of human pregnancy and gestation, and as such, it can ultimately be used to support decision-making with respect to optimal pharmacological dosing and risk assessment for pregnant women and their developing fetuses. The views expressed in this article are those of the authors and do not necessarily represent the views or policies of the U.S. Environmental Protection Agency.

Topics: Blood Circulation; Female; Fetus; Hematocrit; Humans; Models, Anatomic; Models, Biological; Mothers; Pregnancy; Tissue Distribution

PubMed: 31048866
DOI: 10.1371/journal.pone.0215906

Authors: A Karykowska, Z A Domagała, B Gworys...

BACKGROUND

The lateral compartment of the leg, due to its distal and concurrent superficial positioning, is a multiple trauma site. Detailed knowledge of compartimentum lateralis cruris (CLC) structure is crucial for physicians. Musculus peroneus longus (MPL) is located within the structures of the CLC most superficially. There is a lot of data on the morphology of the MPL but there is no publication analysing in detail its anatomy in the foetal period. The aim of the study was to determine the variability of metric and morphological parameters of MPL in a studied period of prenatal ontogenesis.

MATERIALS AND METHODS

The analysis included 207 human foetuses (101 males and 106 females) at calendar age from 113 to 222 days. The analysed material comes from the local anatomy collection. Foetuses were stored in typical preservation solutions. Access to the muscle was obtained on the basis of standard preparation techniques. The authors evaluated the metric parameters of the muscle showing the presence of variable dynamics of metric increments of the examined muscle in particular age classes.

RESULTS

In the studied period of prenatal ontogenesis, MPLs of the foetuses increased by about 60% in the length and width dimension and by about 100% in the thickness dimension. The topography of the initial and final muscle attachment was also evaluated. Statistically significant dimorphic differences were found in some aspects of muscle attachment topography.

CONCLUSIONS

The analysis of the place of the origin and insertion of MPL showed a relatively large variety of these features.

Topics: Female; Fetus; Humans; Leg; Male; Muscle, Skeletal; Pregnancy

PubMed: 33124032
DOI: 10.5603/FM.a2020.0129