BackgroundIt remains unclear to what extent midgut rotation determines human intestinal topography and pathology. We reinvestigated the midgut during its looping and herniation phases of development, using novel 3D visualization techniques.ResultsWe distinguished 3 generations of midgut loops. The topography of primary and secondary loops was constant, but that of tertiary loops not. The orientation of the primary loop changed from sagittal to transverse due to the descent of ventral structures in a body with a still helical body axis. The 1st secondary loop (duodenum, proximal jejunum) developed intraabdominally towards a left-sided position. The 2nd secondary loop (distal jejunum) assumed a left-sided position inside the hernia before returning, while the 3rd and 4th secondary loops retained near-midline positions. Intestinal return into the abdomen resembled a backward sliding movement. Only after return, the 4th secondary loop (distal ileum, cecum) rapidly “slid” into the right lower abdomen. The seemingly random position of the tertiary small-intestinal loops may have a biomechanical origin.ConclusionsThe interpretation of “intestinal rotation” as a mechanistic rather than a descriptive concept underlies much of the confusion accompanying the physiological herniation. We argue, instead, that the concept of “en-bloc rotation” of the developing midgut is a fallacy of schematic drawings. Primary, secondary and tertiary loops arise in a hierarchical fashion. The predictable position and growth of secondary loops is pre-patterned and determines adult intestinal topography. We hypothesize based on published accounts that malrotations result from stunted development of secondary loops.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-015-0081-x) contains supplementary material, which is available to authorized users.

Migratory failure of somitic cells is the commonest explanation for ventral body wall defects. However, the embryo increases ~ 25-fold in volume in the period that the ventral body wall forms, so that differential growth may, instead, account for the observed changes in topography. Human embryos between 4 and 10 weeks of development were studied, using amira reconstruction and cinema 4D remodeling software for visualization. Initially, vertebrae and ribs had formed medially, and primordia of sternum and hypaxial flank muscle primordium laterally in the body wall at Carnegie Stage (CS)15 (5.5 weeks). The next week, ribs and muscle primordium expanded in ventrolateral direction only. At CS18 (6.5 weeks), separate intercostal and abdominal wall muscles differentiated, and ribs, sterna, and muscles began to expand ventromedially and caudally, with the bilateral sternal bars fusing in the midline after CS20 (7 weeks) and the rectus muscles reaching the umbilicus at CS23 (8 weeks). The near-constant absolute distance between both rectus muscles and approximately fivefold decline of this distance relative to body circumference between 6 and 10 weeks identified dorsoventral growth in the dorsal body wall as determinant of the 'closure' of the ventral body wall. Concomitant with the straightening of the embryonic body axis after the 6th week, the abdominal muscles expanded ventrally and caudally to form the infraumbilical body wall. Our data, therefore, show that the ventral body wall is formed by differential dorsoventral growth in the dorsal part of the body.

BackgroundStudies on birth weight and congenital anomalies in sub-Saharan regions are scarce.MethodsData on child variables (gestational age, birth weight, sex, and congenital malformations) and maternal variables (gravidity, parity, antenatal care, previous abortions, maternal illness, age, medication, and malformation history) were collected for all neonates delivered at Ayder referral and Mekelle hospitals (Northern Ehthiopia) in a prospective study between 01-12-2011 and 01-05-2012.ResultsThe total number of deliveries was 1516. More female (54%) than male neonates were born. Birth weights were 700-1,000 grams between 26 and 36 weeks of pregnancy and then increased linearly to 3,500-4,000 grams at 40 weeks. Thirty-five and 54% of neonates were very-low and low birth weight, respectively, without sex difference. Very-low birth-weight prevalence was not affected by parity. Male and female neonates from parity-2 and parity-2-4 mothers, respectively, were least frequently under weight. Sixty percent of newborns to parity -3 mothers weighed less than 2,500 grams, without sex difference. The percentage male neonates dropped from ~50% in parity-1-3 mothers to ~20% in parity-6 mothers. Diagnosed congenital malformations (~2%) were 2-fold more frequent in boys than girls. The commonest malformations were in the central nervous system (CNS; ~1.5% of newborns). Parity, low birth weight, gestational age less than 35 weeks, male sex, and lack of antenatal care were the most significant risk factors for congenital anomalies.ConclusionThe high prevalence of neonates with low birth weight and CNS anomalies in Northern Ethiopia was very high. The findings may reflect the harsh conditions in the past 2 decades and suggest environmental and/or nutritional causes. Male sex and parity affected the outcome of pregnancy negatively.

Differences in opinion regarding the development of the infrahepatic inferior caval and azygos venous systems in mammals centre on the contributions of 'caudal cardinal', 'subcardinal', 'supracardinal', 'medial and lateral sympathetic line' and 'sacrocardinal' veins. The disagreements appear to arise from the use of topographical position rather than developmental origin as criterion to define separate venous systems. We reinvestigated the issue in a closely spaced series of human embryos between 4 and 10 weeks of development. Structures were visualized with the Amira â reconstruction and Cinema4D â remodelling software. The vertebral level and neighbouring structures were used as topographic landmarks. The main results were that the caudal cardinal veins extended caudally from the common cardinal vein between CS11 and CS15, followed by the development of the subcardinal veins as a plexus sprouting ventrally from the caudal cardinal veins. The caudal cardinal veins adapted their course from lateral to medial relative to the laterally expanding lungs, adrenal glands, definitive kidneys, sympathetic trunk and umbilical arteries between CS15 and CS18, and then became interrupted in the part overlaying the regressing mesonephroi (Th12-L3). The caudal part of the left caudal cardinal vein then also regressed. The infrarenal part of the inferior caval vein originated from the right caudal cardinal vein, while the renal part originated from subcardinal veins. The azygos veins developed from the remaining cranial part of the caudal cardinal veins. Our data show that all parts of the inferior caval and azygos venous systems developed directly from the caudal cardinal veins or from a plexus sprouting from these veins.

Subdivision of cloaca into urogenital and anorectal passages has remained controversial because of disagreements about the identity and role of the septum developing between both passages. This study aimed to clarify the development of the cloaca using a quantitative 3D morphological approach in human embryos of 4–10 post‐fertilisation weeks. Embryos were visualised with Amira 3D‐reconstruction and Cinema 4D‐remodelling software. Distances between landmarks were computed with Amira3D software. Our main finding was a pronounced difference in growth between rapidly expanding central and ventral parts, and slowly or non‐growing cranial and dorsal parts. The entrance of the Wolffian duct into the cloaca proved a stable landmark that remained linked to the position of vertebra S3. Suppressed growth in the cranial cloaca resulted in an apparent craniodorsal migration of the entrance of the Wolffian duct, while suppressed growth in the dorsal cloaca changed the entrance of the hindgut from cranial to dorsal on the cloaca. Transformation of this ‘end‐to‐end’ into an ‘end‐to‐side’ junction produced temporary ‘lateral (Rathke's) folds’. The persistent difference in dorsoventral growth straightened the embryonic caudal body axis and concomitantly extended the frontally oriented ‘urorectal (Tourneux's) septum’ caudally between the ventral urogenital and dorsal anorectal parts of the cloaca. The dorsoventral growth difference also divided the cloacal membrane into a well‐developed ventral urethral plate and a thin dorsal cloacal membrane proper, which ruptured at 6.5 weeks. The expansion of the pericloacal mesenchyme followed the dorsoventral growth difference and produced the genital tubercle. Dysregulation of dorsal cloacal development is probably an important cause of anorectal malformations: too little regressive development may result in anorectal agenesis, and too much regression in stenosis or atresia of the remaining part of the dorsal cloaca.

Differentiation of endodermal cells into hepatoblasts is well studied, but the remodeling of the vitelline and umbilical veins during liver development is less well understood. We compared human embryos between 3 and 10 weeks of development with pig and mouse embryos at comparable stages, and used Amira 3D reconstruction and Cinema 4D remodeling software for visualization. The vitelline and umbilical veins enter the systemic venous sinus on each side via a common entrance, the hepatocardiac channel. During expansion into the transverse septum at Carnegie Stage (CS)12 the liver bud develops as two dorsolateral lobes or 'wings' and a single ventromedial lobe, with the liver hilum at the intersection of these lobes. The dorsolateral lobes each engulf a vitelline vein during CS13 and the ventromedial lobe both umbilical veins during CS14, but both venous systems remain temporarily identifiable inside the liver. The dominance of the left-sided umbilical vein and the rightward repositioning of the sinuatrial junction cause de novo development of left-to-right shunts between the left umbilical vein in the liver hilum and the right hepatocardiac channel (venous duct) and the right vitelline vein (portal sinus), respectively. Once these shunts have formed, portal branches develop from the intrahepatic portions of the portal vein on the right side and the umbilical vein on the left side. The gall bladder is a reliable marker for this hepatic vascular midline. We found no evidence for large-scale fragmentation of embryonic veins as claimed by the 'vestigial' theory. Instead and in agreement with the 'lineage' theory, the vitelline and umbilical veins remained temporally identifiable inside the liver after being engulfed by hepatoblasts. In agreement with the 'hemodynamic' theory, the left-right shunts develop de novo.

Although the intrinsic muscles of the back are defined by their embryological origin and innervation pattern, no detailed study on their development is available. Human embryos (5-10 weeks development) were studied, using Amira3D® reconstruction and Cinema4D® remodeling software for visualization. At Carnegie Stage (CS)15, the epaxial portions of the myotomes became identifiable laterally to the developing vertebrae. At CS16, these portions fused starting cranially to form a longitudinal muscle column, which became innervated by the dorsal branches of the spinal nerves. At CS17, the longitudinal muscle mass segregated into medial and lateral columns (completed at CS18). At CS18, the medial column segregated again into intermediate and medial columns (completed at CS20). The lateral and intermediate columns did not separate in the lower lumbar and sacral regions. Between CS20 and CS23, the cervical portions of the three columns segregated again from lateral to medial resulting ventrolaterally in rod-like continuations of the caudal portions of the columns and dorsomedially in spade-like portions. The observed topography identifies the iliocostalis and splenius as belonging to the lateral column, the longissimus to the intermediate column, and the (semi-)spinalis to the medial column. The medial (multifidus) group acquired its transversospinal course during closure of the vertebral arches in the early fetal period. Hence, the anatomical ontology of the epaxial muscles is determined by craniocaudal and lateromedial gradients in development. Three longitudinal muscle columns, commonly referred to as the erector spinae, form the basic architectural design of the intrinsic muscles of the back. Clin. Anat. 29:1031-1045, 2016. © 2016 Wiley Periodicals, Inc.

Congenital malformations are defects of the morphogenesis of organs or body during the pregnancy period and are identifiable at pre- or postnatal. They are identified as the major cause of child mortality worldwide. There is a need to understand the prevalence of congenital malformations in Tigray and Ethiopia in general as surveillance data are lacking. Hence, this study was designed to investigate the burden of major congenital malformations in the Tigray Region, Northern Ethiopia. Hospital-based cross-sectional study was conducted to identify neonates with major congenital anomalies in the labor ward admitted at six major public hospitals of Tigray region, Ethiopia between January 2018 and 2019. All newborns/neonates delivered in all study hospitals during the study period were considered as the study population. The prevalence of major congenital anomalies and the distribution of each type of major congenital anomalies within total birth were calculated. Data on maternal, and newborn demographic characteristics was collected. Statistical analysis was done using SPSS and p value < 0.05 was considered significant. A total of 12,225 births and terminations were recorded in the six hospitals during the study period. Of total 12,225 births and terminations examined, 383 births had major congenital malformations and the overall prevalence of congenital malformations was 3.13% of the total births examined. Congenital anomalies (CAs) of the central nervous system specifically neural tube defects (NTDs) were the commonest anomalies in this study, found in 68.7% (263NTDs/383 CAs) of the neonates with CAs. The overall prevalence of NTDs was 2.15% (263/12,225 births) of the total births examined. Maternal factors such as women 20 years of age or younger (p < 0.0001) and women older than 35 years of age (p < 0.0001), abortion history (p < 0.0001), gravidity above 4 (p = 0.005), were more likely associated with an increased risk of babies with congenital anomalies. Fetal factors including gestational ages below 28 weeks (p < 0.0001) and above 40 weeks (p < 0.0001) were strongly associated with an increased risk of babies with congenital anomalies. However, these associated factors were not resulted from multivariable logistic regression analysis. Thus, the result might be affected by possible confounding factors. This study has shown a high prevalence of major congenital anomalies in the study community. Of the total congenital anomalies observed, most of neonates are affected with neural tube defects, a birth defect with well–established evidence having folic acid deficiency or insufficiency is the predominant cause of spina bifida and anencephaly. This just screams urgency to implement effective/mandatory/ programs to get all women of reproductive age an adequate folic acid to prevent spina bifida and anencephaly.