In-utero Development Research Articles

Physiological Conditions Leading to Maternal Subclinical Ketosis in Holstein Dairy Cows Can Impair the Offspring's Postnatal Growth and Gut Microbiome Development.

Maternal metabolic disruptions, such as ketosis, can have adverse effects on fetal development and influence postnatal factors. Twelve Holstein calves were randomly enrolled in this study at birth and monitored until 8 weeks of age. The study was conducted from fall 2018 until spring 2019. After completing the data collection period, calves were classified according to their respective dams ketotic condition after parturition. This classification was based on dam blood β-hydroxybutyrate < 1.4 mmol/L nonketotic (NONKET; n = 6 calves) or ≥1.4 mmol/L subclinical-ketotic (SK; n = 6 calves). SK calves had greater birth body weight (p = 0.05) but exhibited a slower growth rate compared to NONKET calves from 1 to 8 weeks (p = 0.02). At birth, SK calves had lower (p < 0.01) levels of non-esterified fatty acids and bilirubin compared to NONKET calves. Analysis of feces alpha diversity indicates that by 3 weeks, NONKET calves had greater diversity, richness, and evenness. Butyricicoccus pullicaecorum and Gallibacterium anatis were more abundant in SK calves (p < 0.05) at 3 weeks. In contrast, NONKET calves had a greater (p < 0.05) abundance of Sharpae azabuensis at 3 weeks. These findings suggest that subclinical ketosis in cows can impact the in-utero development, postnatal growth, and maturing gut microbiome of their offspring.

Nutrition paves the way to environmental toxicants and influences fetal development during pregnancy.

Nutrition plays a major role in the healthy pregnancy and development of the fetus. In addition, nutrition can expose humans to a wide range of potentially hazardous environmental constituents, such as organic pollutants and heavy metals from marine or agricultural food products while processing, producing, and packaging. Humans constantly face these constituents through air, water, soil, food, and domestic products. During pregnancy, the rate of cellular division and differentiation is higher; exposure to any of these environmental toxicants can lead to developmental defects as they cross the placental barrier and, in some cases, can harm the successive generation too, as some contaminants can act on the reproductive cells of the fetus (Diethylstilbestrol). Pregnant women are considered a vulnerable population to food contaminant exposure and require a proper dietary chart and conscious food choices. Food is a source of both essential nutrients and environmental toxicants. Here, we have researched the possible toxicants of the food industry and their influence on the fetus's in-utero development, along with the importance of dietary interventions and the need to balance a healthy diet to overcome the harms. The cumulative exposure to environmental toxicants can influence the mother's prenatal environment and affect the fetus's development.

Fetal development of functional thalamocortical and cortico-cortical connectivity.

Measuring and understanding functional fetal brain development in utero is critical for the study of the developmental foundations of our cognitive abilities, possible early detection of disorders, and their prevention. Thalamocortical connections are an intricate component of shaping the cortical layout, but so far, only ex-vivo studies provide evidence of how axons enter the sub-plate and cortex during this highly dynamic phase. Evidence for normal in-utero development of the functional thalamocortical connectome in humans is missing. Here, we modeled fetal functional thalamocortical connectome development using in-utero functional magnetic resonance imaging in fetuses observed from 19th to 40th weeks of gestation (GW). We observed a peak increase of thalamocortical functional connectivity strength between 29th and 31st GW, right before axons establish synapses in the cortex. The cortico-cortical connectivity increases in a similar time window, and exhibits significant functional laterality in temporal-superior, -medial, and -inferior areas. Homologous regions exhibit overall similar mirrored connectivity profiles, but this similarity decreases during gestation giving way to a more diverse cortical interconnectedness. Our results complement the understanding of structural development of the human connectome and may serve as the basis for the investigation of disease and deviations from a normal developmental trajectory of connectivity development.

Association between maternal infections during pregnancy and congenital defects in their offspring: a population-based case-control study in Bogota and Cali, Colombia 2001–2018

Infections are frequent during pregnancy and their teratogenic role is well documented in Toxoplasmosis, other infections, Rubella, Cytomegalovirus, and Herpes simplex (TORCH). However, the in-utero development effects of the rest of the infections that affect pregnant women are unknown. We described a cohort of patients with major Birth Defects (BD) and the exposure to infections during pregnancy from the information of Congenital Defects Surveillance Programs of two Colombian cities (Bogota and Cali) between 2001 and 2018. We evaluated associations between groups of maternal infections and BD among 3096 cases and 7446 controls that were registered. BD presentation was more frequent as isolated (64.3%), polymalformed (23.2%), and syndromic (12.4%). Infections during pregnancy were present in 52.5% of cases and 44.6% of controls. The most common single infection between cases and controls was vaginal infection. The most common polyinfection was vaginal and urinary tract infection. We found an association between BD and vaginal infections with an odds ratio (OR) 1.18 (CI 1.08–1.30), urinary tract infections OR 1.16 (CI 1.05–1.28), gastrointestinal infections OR 2.06 (IC 1.18–3.59), respiratory infections OR 1.56 (IC 1.28–1.9) and viral infections OR 1.88 (IC 1.18–3.0). Knowing the teratogenic effect of infections is important to extend prevention, screening, timely diagnosis, and appropriate treatment to pregnant women.

The Hallmarks of Environmental Insults and early childhood development

BACKGROUND AND AIM: Aging is a complex physiological phenomenon. The question why some subjects grow old while remaining free from disease whereas others prematurely die remains largely unanswered. We focus here on the role of air pollution and other environmental factors in biological aging from early life onwards. METHODS: Some of the hallmarks of aging are overlapping with the hallmarks of environmental insults including three main categories: genomic instability, telomere attrition, and epigenetic alterations leading to altered mitochondrial function and cellular senescence. RESULTS:During in-utero development, the fetus is susceptible to transplacental exposure to carcinogenic air particles. We proved translocation of black carbon from mother to fetus. Even below European Union air pollution thresholds, exposure to particulate matter is associated with an increased placental mutation rate. This increased mutation rate occurred in concert with epigenetic alterations in key DNA repair and tumor suppressor genes in the placenta. Moreover, at birth, the initial telomere length of the newborn is largely determined by environmental factors including prenatal air pollution, green space exposure, pre-pregnancy BMI as well as by maternal socio-economic factors. Telomere length at birth is a major predictor of later life telomere length and predicts telomere change in the transition from birth to child- and adulthood. Therefore, telomere length related health and disease later in life may be programmed at birth. Understanding the setting of initial telomere length and its environmental determinants may further gain insights in the developmental origins of health and disease. CONCLUSIONS:The telomere length – mitochondrial axis is a hallmark of environmental insults during gestation. Improved air quality may promote molecular longevity from birth onward. KEYWORDS: Ageing, telomeres, mitochondria, exposome, DOHaD

Relationship between finger print patterns with blood group and genotype among basic medical science, students of Bayero University, Kano

Fingerprint patterns and the blood genotypes of individuals are chiefly determined by genetic factors during in-utero development. Evaluating genotypes requires expertise and facilities which could relatively be difficult to obtain and operate in some setting. The aim of the current study was to determine the correlation between hand finger print patterns and the common blood typing phenotype (genotype and blood group) among agroup of consenting adult population in Nigeria. Four hundred students (217 males and 183 females) of the Faculty of Basic Medical Sciences in Bayero University Kano had their total hand fingerprints captured using a scanner / computer set up. Data regarding common blood phenotypes was also determined for all participants from the blood phenotype information on their University identification cards. The mean age of theparticipants was 21.86±3.37 years. Loop finger prints patternwas the most common identified in the participants (58.4%), followed by whorls (27.9%), and then the least was arches (13.7%). There was a significant association between the finger print patternon the left thumb (p=0.012) as well as right thumb (p=0.013) withblood groups, while the print in the right index (p=0.042) and left little finger (p= 0.024) were associated with genotypes in the participants respectively. There was a relationship between the finger prints patterns the thumb, index finger and little finger with the common blood typing phenotypes. Thus, finger print patterns on the right index and left little fingercorrelates with blood genotypes.

A proof of concept \u2018phase zero\u2019 study of neurodevelopment using brain organoid models with Vis/near-infrared spectroscopy and electrophysiology

Homeostatic control of neuronal excitability by modulation of synaptic inhibition (I) and excitation (E) of the principal neurons is important during brain maturation. The fundamental features of in-utero brain development, including local synaptic E–I ratio and bioenergetics, can be modeled by cerebral organoids (CO) that have exhibited highly regular nested oscillatory network events. Therefore, we evaluated a 'Phase Zero' clinical study platform combining broadband Vis/near-infrared(NIR) spectroscopy and electrophysiology with studying E–I ratio based on the spectral exponent of local field potentials and bioenergetics based on the activity of mitochondrial Cytochrome-C Oxidase (CCO). We found a significant effect of the age of the healthy controls iPSC CO from 23 days to 3 months on the CCO activity (chi-square (2, N = 10) = 20, p = 4.5400e−05), and spectral exponent between 30–50 Hz (chi-square (2, N = 16) = 13.88, p = 0.001). Also, a significant effect of drugs, choline (CHO), idebenone (IDB), R-alpha-lipoic acid plus acetyl-l-carnitine (LCLA), was found on the CCO activity (chi-square (3, N = 10) = 25.44, p = 1.2492e−05), spectral exponent between 1 and 20 Hz (chi-square (3, N = 16) = 43.5, p = 1.9273e−09) and 30–50 Hz (chi-square (3, N = 16) = 23.47, p = 3.2148e−05) in 34 days old CO from schizophrenia (SCZ) patients iPSC. We present the feasibility of a multimodal approach, combining electrophysiology and broadband Vis–NIR spectroscopy, to monitor neurodevelopment in brain organoid models that can complement traditional drug design approaches to test clinically meaningful hypotheses.

Cellular and molecular events in early and mid gestation porcine implantation sites: a review

Commercial, North American pork breeds (Sus sada) experience significant loss of genetically-normal conceptuses during the peri-implantation (attachment) period and at mid-gestation (day 50 to 90 of the 114 day porcine gestation interval). Although exact causes for these losses are not defined, asynchronous in-utero development and deficits in vascularization of the endometrium and placenta appear to be involved. Understanding of normal maternal-fetal dialogue is critical to develop breeding or therapeutic strategies that improve fetal health and overall litter size in commercial pigs. The non-invasive, epitheliochorial porcine placenta permits investigation of maternal or fetal compartments without cross contaminating cells. We developed and use protocols to capture single, homogenous populations of porcine cells (endometrial lymphocytes, dendritic or endothelial cells) from histological sections using laser capture microdissection (LCM), a powerful tool for study of gene expression that reflects the in vivo environment. These data are compared with gene expression in biopsies of endometrium and of trophoblast from the same, attachment sites. Here we review justifications for selection of the genes we have studied and our published and in progress work. These data provide new insights into the roles of the endometrial immune environment in the regulation of the success and failure of porcine conceptuses.

Maternal gestational exposure to di-butyl phthalate (DBP) from medications and birthweight of progeny

TPS 742: Adverse birth outcomes 1, Exhibition Hall, Ground floor, August 27, 2019, 3:00 PM - 4:30 PM Background: Birthweight, an important predictor of long-term morbidity, is affected by several environmental factors. Thus, birthweight can be used as an early indicator for adverse health conditions that are linked with suboptimal in-utero development, including those possibly caused by gestational exposures to environmental toxicants. Di-butyl phthalate (DBP) is used as an excipient in some mesalamine medications prescribed for treatment of inflammatory bowel disease (IBD), leading to extremely high exposures among patients. DBP is an endocrine disruptor, yet its effects on birthweight have not been conclusively elucidated. We evaluated whether maternal gestational use of DBP-containing medications is linked with alterations in birthweight of progeny. Methods: We conducted a population-based analysis of 546,432 singletons born in 1999-2015 in a large Israeli health fund. Medication dispensing, birthweight, and demographic data were abstracted from electronic medical records. Analyses were performed using generalized estimating equation (GEE) and generalized additive linear regression models. Results: 2,276 singletons were exposed to mesalamine medications during gestation, of which 162 were exposed to a mesalamine formulation with DBP. In models adjusted for sociodemographic factors and other known predictors of birthweight, maternal gestational use of DBP-containing mesalamine formulation was associated with a reduction of 132.0g [95% C.I.:-240.8,-23.1] in birthweight, whereas use of non-DBP mesalamine formulations was associated with a decrease of 77.8g [95% C.I.:-104.7,-51.0] as compared to singletons from mothers not treated with mesalamine. Additional adjustment for gestational age did not alter results. Conclusions: Maternal gestational use of DBP-containing mesalamine medications was associated with a reduction in birthweight, although some of the effect is likely attributed to the underlying IBD. Subsequent analyses will examine longer-term adverse developmental outcomes possibly associated with gestational pharmaceutical exposure to DBP and other phthalate congeners. Future studies should evaluate whether similar findings are observed with less extreme exposures that more closely reflect background environmental levels.

Effects of altered maternal folate and vitamin B12 on neurobehavioral outcomes in F1 male mice

Maternal folate and vitamin B12 status during pregnancy may influence development of central nervous system (CNS) in the offspring. Very little attention has been paid to understand the combined effects of both the vitamins during pregnancy. The present study was designed to evaluate the biochemical and behavioral outcomes following alterations in folate and vitamin B12 levels in C57BL/6 mice. The female mice were fed with different combinations of folate and vitamin B12 whereas; males were fed with normal diet for 4 weeks. The mice were mated and the pregnant mice received the same diets as before pregnancy. The F1 male mice were further continued on maternal diet for 6 weeks following neurobehavioral and biochemical assessment. The body weight of the F1 male mice was significantly decreased in the mice that received folate and vitamin B12 deficient diet. Altered cognitive functions were observed in the folate and B12 deficient F1 male mice as assessed by Morris water maze and novel object recognition tests. Spontaneous locomotor activity was decreased in F1 male mice fed with folate and B12 deficient diets. Elevated homocysteine levels and decreased hydrogen sulfide levels were also observed in the brain of F1 male mice on folate and B12 deficient diets. However, GSH and GSSG levels were increased in the brain of the animals supplemented with folate deficient diet with different combinations of B12. The study suggests that exposure of female mice to folate and vitamin B12 deficiency during pregnancy effects in-utero development of fetus, which further leads to behavioral anomalies in adult life and is sufficient to cause impaired cognitive behavior in the subsequent generation. Thus, elucidating the role and importance of maternal dietary folate and B12 ratio during pregnancy.

Ultrasound Imaging Reveals Accelerated In-utero Development of a Sensory Apparatus in Echolocating Bats

Organ development, both in-utero and after birth, follows a different path for every organ depending upon how early the newborn will use it. Perception of the environment using echolocation occurs very early in the life of neonatal bats. In nostril-emitting echolocating bats of the families Hipposideridae and Rhinolophidae, the shape and area of the nasal-horseshoe is crucial for echolocation emission. We therefore hypothesized that most of this organ’s ontogeny will be completed in-utero while skull and wings will develop slower and continue their growth after birth. We used intrauterine ultrasonography of pregnant females, and measured newborn Asellia tridens (Hipposideridae) to test our hypothesis at different stages of ontogeny. We found that horseshoe development is completed in-utero and neonates begin emitting precursor echolocation calls already two days after birth. In contrast, skull and forearm only develop to 70% and 40% of adult size (respectively), and continue development after birth.

Ventricular remodeling in preterm infants: computational cardiac magnetic resonance atlasing shows significant early remodeling of the left ventricle.

Premature birth is associated with ventricular remodeling, early heart failure, and altered left ventricular (LV) response to physiological stress. Using computational cardiac magnetic resonance (CMR) imaging, we aimed to quantify preterm ventricular remodeling in the neonatal period, and explore contributory clinical factors. Seventy-three CMR scans (34 preterm infants, 10 term controls) were performed to assess in-utero development and preterm ex-utero growth. End-diastolic computational atlases were created for both cardiac ventricles; t statistics, linear regression modeling, and principal component analysis (PCA) were used to describe the impact of prematurity and perinatal factors on ventricular volumetrics, ventricular geometry, myocardial mass, and wall thickness. All preterm neonates demonstrated greater weight-indexed LV mass and higher weight-indexed end-diastolic volume at term-corrected age (P < 0.05 for all preterm gestations). Independent associations of increased term-corrected age LV myocardial wall thickness were (false discovery rate <0.05): degree of prematurity, antenatal glucocorticoid administration, and requirement for >48 h postnatal respiratory support. PCA of LV geometry showed statistical differences between all preterm infants at term-corrected age and term controls. Computational CMR demonstrates that significant LV remodeling occurs soon after preterm delivery and is associated with definable clinical situations. This suggests that neonatal interventions could reduce long-term cardiac dysfunction.

Pre-implantation alcohol exposure and developmental programming of FASD: an epigenetic perspective.

Exposure to alcohol during in-utero development can permanently change the developmental programming of physiological responses, thereby increasing the risk of neurological illnesses during childhood and later adverse health outcomes associated with fetal alcohol spectrum disorder (FASD). There is an increasing body of evidence indicating that exposure to alcohol during gestation triggers lasting epigenetic alterations in offspring, long after the initial insult; together, these studies support the role of epigenetics in FASD etiology. However, we still have little information about how ethanol interferes with the fundamental epigenetic reprogramming wave (e.g., erasure and re-establishment of DNA methylation marks) that characterizes pre-implantation embryo development. This review examines key epigenetic processes that occur during pre-implantation development and especially focus on the current knowledge regarding how prenatal exposure to alcohol during this period could affect the developmental programming of the early stage pre-implantation embryo. We will also outline the current limitations of studies examining the in-vivo and in-vitro effects of alcohol exposure on embryos and underline the next critical steps to be taken if we want to better understand the implicated mechanisms to strengthen the translational potential for epigenetic markers for non-invasive early detection, and the treatment of newborns that have higher risk of developing FASD.

O-32 Prenatal exposure to acetamin-ophen and risk for attention defi-cit disorder (adhd): a systematic review and meta analysis

Background Acetaminophen is the most commonly used analgesic and antipyretic medication during preg-nancy. Recent epidemiological studies have suggested a possible association between acetaminophen exposure in-utero and impaired paediatric neurological develop-ment, including hyperactive attention deficit (ADHD) and related disorders. Methods We conducted a systematic-review and me-ta-analysis to evaluate the risk for ADHD in children of women exposed to acetaminophen during pregnancy. We searched MEDLINE and EMBASE up to January 2017. We used meta-regression analysis to evaluate factors that may moderate this association. Reports of cohorts were pooled using random-effects models. Results Six cohort studies met our inclusion criteria. Among 76 146 mothers who reported acetaminophen use during pregnancy, acetaminophen was associated with an increased risk for ADHD (RR=1.33, 95% CI: 1.19–1.47, I2=77%), hyperactivity symptoms (RR=1.24, 95% CI: 1.02–1.46, I2=95%), and conduct disorders (RR=1.28; 95% CI, 1.05–1.52, I2=93%). Using meta-regression, we found that the association was greater and heterogeneity re-duced as child’s age at diagnosis increased (β=0.045, p=0.035, heterogeneity accounted for (R2)=65.98%). Conclusion This meta-analysis suggests that maternal acetaminophen use during pregnancy is associated with a higher risk for ADHD or related disorders. However, there is evidence of significant heterogeneity in the observed effect, and many of the studies suffer from significant lim-itations. These findings, together with additional recent evidence on teratogenicity of acetaminophen, warrants further investigation and consideration of public health actions. PROSPERO registry-CRD42017055827

Maternal epigenetics and fetal and neonatal growth.

The article provides an update on new insights of factors altering inherited maternal epigenome that ultimately affect fetal and neonatal growth. A number of new publications have identified mechanisms through which maternal nutrition, environmental exposures such as stress and toxic substances altering expression of imprinted genes during pregnancy can influence fetal and neonatal phenotype and susceptibility to disease development later in life. The possible causes of metabolic syndrome by in-utero epigenetic alterations of genes involved in energy metabolism (PPARγ and PPARα), microRNAs, arginine methyltransferases, lysine demethylases, and histone deacetylaces have been elucidated. Moreover associations between methylation of key genes (NRC31, HSD11β1/2, GFI1) involved in the hypothalamic-pituitary-adrenal axis have been identified. Alcohol exposure during pregnancy was found to alter methylation patterns of several imprinted genes (H19, SLC22A18, SLC6A3, DRD4). Finally alterations in vulnerable epigenetic marks of imprinted genes such as H19/IGF2, during early stages of embryonic development result in intrauterine growth restriction. All these investigations continue to provide new insights for improved clinical management of in-utero development.

Anogenital distance of women in relation to their mother’s gynaecological characteristics before or during pregnancy

Animal models suggest that anogenital distance (AGD) at birth reflects androgen concentrations during in-utero development and predicts adult AGD. Several human observational studies show an association between menstrual cycle irregularities and a hyperandrogenic environment and that may result in a potential alteration of the female reproductive tract during in-utero development. This study examined associations between AGD of young women and their mother’s gynaecological characteristics before or during pregnancy. This is cross-sectional study of 100 college-age volunteers in southern Spain. Physical and gynaecological examinations were conducted on the young women and they and their mothers completed epidemiological questionnaires on lifestyles and gynaecological history. Linear regression analysis was used to examine the association between AGD measurements (anus–fourchette (AGDAF) and anus–clitoris (AGDAC)) of women and their mother’s gynaecological characteristics. Longer AGDAF was associated with the presence of mother’s menstrual cycle irregularities before pregnancy (P=0.03). Longer female AGD has been related to excess androgen exposure in utero in toxicological studies. The current findings may be consistent with studies in which an association between menstrual cycle irregularities and an hyperandrogenic environment has been reported, which therefore may result in a potential modification of the female offspring’s reproductive tract during in-utero development, including AGD.Rodent models suggest that perineal length at birth reflects male hormone concentrations (androgens) during in-utero development and predicts adult perineal length. Several human studies show a relationship between menstrual cycle irregularities and an excessive androgen environment. We hypothesize that androgen excess may result in a potential alteration of the female reproductive tract during in-utero development. Our aim was to examine associations between perineal length of young women and their mother’s gynaecological characteristics before or during pregnancy. This is a study of 100 college-age volunteers in Southern Spain. Physical and gynaecological examinations were conducted on the young women and they and their mothers completed epidemiological questionnaires on lifestyles and gynaecological history. We used multivariate analyses to assess the association between perineal length of women and their mother’s gynaecological characteristics. Longer perineal length was associated with the presence of mother’s menstrual cycle irregularities before pregnancy. Longer female perineal length has been related to excess androgen exposure in utero in rodent studies. Our findings may be consistent with previous studies in which an association between menstrual cycle irregularities and an excess of androgen has been reported, which therefore may result in a potential modification of the female offspring’s reproductive tract during in-utero development, including perineal length.

Fatty-acid composition of maternal and umbilical cord plasma and early childhood atopic eczema in a Spanish cohort

Fatty-acid status during in-utero development might influence the risk of atopic diseases in early childhood. The aim of this work was to identify the relationship between maternal plasma and cord blood fatty acid (FA) composition and the risk of atopic eczema in the offspring at 14 months of age. Two hundred and eleven non-atopic mothers and their children were studied. Mothers were recruited in their first trimester of gestation and children were monitored until 14 months of age. Samples of maternal plasma and cord blood plasma were analyzed to determine the FA profile of total lipids. Presence of atopic eczema in the infants was documented through questionnaires at 6 and 14 months of age. Higher concentrations of total long-chain polyunsaturated FA (LC-PUFA) were found in maternal plasma of non-atopic children in relation to atopic group. Moreover, this maternal plasma LC-PUFA content was negatively correlated with the atopic eczema (odds ratios (OR)=0.83, P=0.04) in infants. Regarding cord blood samples, docosahexaenoic acid (DHA C22:6n3) and the sum of total n-3 and of LC-PUFA n-3 showed a negative correlation with the prevalence of the disease (OR=0.50, 0.49 and 0.49, respectively). Our results show that the fatty-acid status of the fetus during pregnancy has an important role in the development of atopic eczema in early childhood. The prevalence of this atopic disorder is related to lower cord blood plasma levels of FA belonging to n-3 series, especially DHA.

Maternal B vitamin supplementation from preconception through weaning suppresses intestinal tumorigenesis in Apc1638N mouse offspring

ObjectiveVariations in the intake of folate are capable of modulating colorectal tumorigenesis; however, the outcome appears to be dependent on timing. This study sought to determine the effect of altering...

Fetal and neonatal liver tumours

Liver tumours are rare in children and account for about 5% of all tumours in the fetus and newborn. The most frequently occurring are benign vascular tumours and mesenchymal hamartomas although malignancy in the form of hepatoblastoma is a possibility. While the diagnosis can be suspected antenatally (by ultrasound and MR scan), a precise diagnosis is often difficult due to the complexity of the tumours. Inutero development of such tumours may be associated with polyhydramnios, fetal hydrops and extreme cases the maternal mirror syndrome. Postnatal symptoms may include abdominal distension, cardiac failure, consumptive coagulopathy and bleeding due to tumour rupture, but is dependent on the nature of the actual tumour. Treatment options may include watchful waiting, surgical resection, hepatic artery embolisation/ligation and chemotherapy.

In‐utero development of the fetal anal sphincter

To investigate the in-utero development of the fetal anal sphincter using transabdominal ultrasound. This was a cross-sectional study in which the diameter of the fetal anal sphincter was measured sonographically once in 631 well-dated, non-anomalous fetuses scanned between 19 and 38 weeks of gestation. Visualization rates were determined. Regression analysis was used to assess the relationship between the diameter of the fetal anal sphincter and gestational age (GA), and reference values including the mean and 95% reference interval were calculated for each GA. The sonographic visualization rate of the fetal anal sphincter increased with gestational age, plateauing at 90-100% between 23-34 weeks of gestation. There was a significant positive relationship between fetal anal sphincter diameter and GA, which was best described by the equation: anal sphincter diameter (mm) = - 0.014 x GA(2) + 1.107 x GA - 11.664 (R(2) = 0.62). We have provided reference values for the in-utero development of the fetal anal sphincter throughout gestation.