Prenatal diagnosis of acrania/exencephaly/anencephaly sequence (AEAS): additional structural and genetic anomalies.

OBJECTIVES: To analyse additional structural and genetic anomalies in fetuses with acrania/exencephaly/anencephaly sequence (AEAS). METHODS: A retrospective analysis of 139 fetuses with AEAS diagnosed between 2006 and 2020 in a single tertiary referral ultrasound department. RESULTS: The median gestational age at diagnosis decreased from 15 weeks in 2006 to 13 weeks in 2020 (- 0.21 per each year; p = 0.009). In 103 fetuses, the defects were limited to the neural tube (NTD) (74.1%), in 36 fetuses (25.9%), there were additional structural non-NTD anomalies. The most common were ventral body wall defects present in 17.8% (23/139), followed by anomalies of the limbs (7.2%; 10/139), face (6.5%; 9/139) and heart (6.5%; 9/139). Genetic anomalies were diagnosed in 7 of the 74 conclusive results (9.5%; 7/74; trisomy 18, n = 5; triploidy, n = 1; duplication of Xq, n = 1). In univariate logistic regression models, male sex, limb anomalies and ventral body wall defects significantly increased the risk of genetic anomalies (OR 12.3; p = 0.024; OR 16.5; p = 0.002 and OR 10.4; p = 0.009, respectively). CONCLUSIONS: A significant number of fetuses with AEAS have additional structural non-NTD anomalies, which are mostly consistent with limb body wall complex. Genetic abnormalities are diagnosed in almost 10% of affected fetuses and trisomy 18 is the most common aberration. Factors that significantly increased the odds of genetic anomalies in fetuses with AEAS comprise male sex, limb anomalies and ventral body wall defects.

Craniorachischisis with Exencephaly.

BACKGROUND: Neural tube defects can be as mild as spina bifida, to as severe as anencephaly, with only a fraction of these cases presenting as both craniorachischisis and exencephaly. Case report: The G3, P1011 mother was 25-years old, who at an estimated fetal gestational age of 17 weeks had a fetal diagnosis of anencephaly based on a sonogram, resulting in elective pregnancy termination. The female fetus had an open neural tube defect, consisting of craniorachischisis and exencephaly. No abnormalities were noted in any other organs. Conclusion: Although mostly associated with anencephaly, craniorachischisis can also be associated with exencephaly in early pregnancy.

Prenatal diagnosis of fetal microhydranencephaly: a case report and literature review.

BACKGROUND: The prenatal diagnosis of microhydranencephaly is important and needs to be distinguished from anencephaly, because unlike anencephaly, fetuses with microhydranencephaly can survive after birth. Herein, we report a case of microhydranencephaly that was diagnosed and distinguished from anencephaly prenatally. CASE PRESENTATION: The patient was an 18-year-old woman, 2 gravida nullipara, who presented at 15 weeks of gestation. Ultrasonography showed a normal biparietal diameter (BPD) and no major anomalies. At 23 weeks of gestation, an ultrasound examination revealed a BPD of 40 mm (-5.3 standard deviation, SD). At 29 weeks, anencephaly was suspected despite difficulty in visually examining the fetal head above the orbit. At 34 weeks, insertion of a metreurynter made it possible to observe the skull. Three-dimensional computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of the fetal skull, a prominent occipital bone, sloping forehead, marked microcephaly, cerebral loss, and excess cerebrospinal fluid. This allowed differentiation between microhydranencephaly and anencephaly. She delivered vaginally at 37 weeks, and the child had a birth weight of 2342 g and a head circumference of 24 cm (-5.4 SD). The baby's head was flat above the forehead, with a suspected partial head defect. The baby received desmopressin acetate due to central diabetes insipidus 6 months after birth. CONCLUSIONS: The use of multiple imaging modalities and physical manipulation of the fetal head are required to accurately differentiate between microhydranencephaly and anencephaly.

An Unusual First-Trimester Ultrasound Presentation of the Acrania-Anencephaly Sequence: The "Turkish Turban" Sign.

A previously unrecognized first-trimester presentation of the acrania-anencephaly sequence is described. Ultrasound features included a constriction ring around the external base of the developing skull and an enlarged globular head, resembling a Turkish turban, with large cystic spaces replacing the brain. This constellation of findings was noted in 3 first-trimester fetuses. In 2 of them, it was possible to identify the amniotic membrane attached to the constriction ring. One case presented with anencephaly and fetal demise at 16 weeks. The other 2 women terminated the pregnancies and aborted anencephalic fetuses. This subtype of the acrania-anencephaly sequence could represent an earlier segmental rupture of the amnion, which subsequently entraps the developing fetal skull.

The role of the "beret" sign and other markers in ultrasound diagnostic of the acrania-exencephaly-anencephaly sequence stages.

INTRODUCTION: Neural tube defects (NTDs) are a group of heterogeneous congenital anomalies of the central nervous system (CNS). Acrania is a non-NTD congenital disorder related to the CNS. It can transform into anencephaly through the acrania-exencephaly-anencephaly sequence (AEAS). In AEAS, the cerebral tissue is not protected and is gradually destroyed due to exposure to the harmful effect of amniotic fluid and mechanical injuries. These lead to exencephaly and then into anencephaly. In contrast to primary anencephaly (NTDs), this type of anencephaly authors suggests calling secondary anencephaly. OBJECTIVE: Analysis of the known prenatal ultrasonography (US) signs associated with AEAS. Simultaneously, the authors propose a new sign in the differentiation of acrania from exencephaly and anencephaly, called the "beret" sign. METHODS: It is a two-centre retrospective observational study. As part of the study, 4060 US scans were analyzed. RESULTS: In 10 cases, the absence of calvarium was diagnosed, allowing recognition of either AEAS stages or primary anencephaly. In 5 cases, cerebral structures were enclosed by an inertial rippled thin membrane, with a smooth outer contour. Between the described membrane and the brain structures, a thin anechoic space corresponding to cerebrospinal fluid was observed. This sign was defined as the "beret" sign. In these cases, acrania was diagnosed. In three cases calvarium was missing. The brain structures had an irregular appearance, did not wave and remained motionless. The outer contour was unequal as if divided into lobes. Amniotic fluid was anechoic. Exencephaly was diagnosed in these cases. In two cases calvarium, brain structures, and meninges were missing. The "frog eyes" sign and slightly echogenic amniotic fluid were visible. In this case, anencephaly was diagnosed. CONCLUSIONS: The "beret" sign seems to be a promising tool in the diagnosis of acrania. Furthermore, echogenicity of amniotic fluid could be useful during differentiation between primary and secondary anencephaly.

Prenatal diagnosis of holoprosencephaly.

Holoprosencephaly is a spectrum of congenital defects of forebrain development characterized by incomplete separation of the cerebral hemispheres. In vivo diagnosis can be established with prenatal brain imaging and disease severity correlates with extent of abnormally developed brain tissue. Advances in magnetic resonance imaging (MRI) over the past 25 years and their application to the fetus have enabled diagnosis of holoprosencephaly in utero. Here, we report on the prenatal diagnosis of holoprosencephaly using MRI as part of a diagnostic and management evaluation at a tertiary and quaternary referral center. Using an advanced MRI protocol and a 1.5-Tesla magnet, we show radiographic data diagnostic for the holoprosencephaly spectrum, including alobar, semilobar, lobar, middle interhemispheric, and septopreoptic variant. Accurate prenatal evaluation is important because the severity of imaging findings correlates with postnatal morbidity and mortality in holoprosencephaly. Therefore, this work has implications for the evaluation, diagnosis, management, and genetic counseling that families can receive during a pregnancy.

Absence of an anatomical origin for altered ductus venosus flow velocity waveforms in first-trimester human fetuses with increased nuchal translucency.

OBJECTIVE: To perform a morphological evaluation of the ductus venosus, heart and jugular lymphatic sac (JLS) in first-trimester human fetuses with normal and abnormal ductus venosus flow velocity waveforms (DV-FVWs) and normal and increased nuchal translucency (NT). METHOD: Postmortem examination was performed on fetuses with increased NT or structural malformations with previous NT and DV-FVW measurements. Ductus venosus morphology was examined using markers for endothelium, smooth muscle actin (SMA), nerves and elastic fibers. Fetal hearts were studied by microscopy. The nuchal region was analyzed using markers for lymphatic vessels, endothelium, SMA and nerves. RESULTS: Two trisomy 21 and two trisomy 18 fetuses with increased NT and abnormal DV-FVWs were analyzed. As a control, one euploid anencephalic fetus with normal NT, cardiac anatomy and DV-FVWs was examined. Similar endothelial and SMA expression was observed in the ductus venosus in all fetuses. Nerve and elastic fiber expression were not detected. Three trisomic fetuses showed cardiac defects, one trisomic fetus demonstrated normal cardiac anatomy. The JLS was abnormally enlarged or contained red blood cells in all trisomic fetuses. The control fetus showed a normal JLS. CONCLUSION: Abnormal DV-FVWs are not justified by alterations in ductus venosus morphology. DV-FVWs most probably reflect intracardiac pressure. © 2016 John Wiley & Sons, Ltd.

Fetal Myelomeningocele After Maternal Methotrexate Administration: A Case Report.

Background: Folate supplementation in women of reproductive age has a well-established role in the prevention of neural tube defects. Methotrexate is a commonly used drug which functions by inhibiting normal folate metabolism in active cells. An association between fetal methotrexate exposure and myelomeningocele might be expected, considering this relationship. However, to our knowledge, no cases of myelomeningocele secondary to in utero methotrexate exposure have been reported. Case: We present the case of a gravid patient who, having received methotrexate for management of an ectopic pregnancy, was lost to follow-up and returned several weeks later carrying an intrauterine pregnancy. The fetus was found prenatally to be suffering from multiple congenital anomalies. At birth the infant demonstrated many of the abnormalities commonly associated with fetal methotrexate syndrome, including craniosynostosis and talipes equinovarus. Most interestingly, the newborn was also diagnosed with a lumbar myelomeningocele and concomitant type II Chiari malformation, as is often associated with such a neural tube defect. Conclusion: Methotrexate exposure may impact the fetal risk of myelomeningocele. Patients should be counseled thoroughly on the importance of follow-up care.

Timing of detection of anencephaly in The Netherlands.

OBJECTIVE: The objective of this study is to assess the gestational age at detection and prevalence of anencephaly in the North of The Netherlands over a 5-year period. METHODS: A case list of all cases of anencephaly from two fetal medicine units was compiled. Cases were included if the estimated due date was between 1 August 2008 and 31 July 2013. RESULTS: Overall prevalence of anencephaly was 5.4 per 10.000 pregnancies (n = 110). The majority of cases (69%) was detected before 18 weeks' gestation. Factors determining successful early diagnosis were competence level of the sonographers, with a significantly higher detection rate when scans were performed by a sonographer licensed by the Fetal Medicine Foundation (FMF) for nuchal translucency measurement (p = 0.001), and gestational age at or beyond 11 weeks of gestation (p = 0.024). CONCLUSION: Improving detection of anencephaly in the first trimester requires ultrasound screening at or after 11 weeks of gestation, performed by experienced sonographers trained in recognizing fetal anomalies. Sonographers should be instructed that the goal of the first trimester scan is not only to measure nuchal translucency thickness but also to exclude major anomalies.

Acardius acephalus fetus--report of distinctive anatomical anomalies with regards to pathophysiology of TRAP sequence.

Acardiac fetuses are consequences of twin reversed arterial perfusion (TRAP). Here the authors present a case of 40-year-old gravida IX who gave birth to a healthy, 2,900 g female child by a cesarean section. Additionally amorphic 1,020 g maldeveloped fetus was removed. There was a diamnion monochorionic type of twin placenta with incorrect single umbilical arteries (SUA) both in umbilical cord of healthy fetus and in atrophic second umbilical cord. A malformed fetus developed a rather well formed lower leg with four digital foot and oval shape amorphous body mass with omphalocele and eventration of the intestines. X-ray picture showed well visible metatarsal and femur bone and anatomically undefined bones cluster in the central part. A cavity of fetal body contained intestines--the only one well-formed organ, nests of heterotopic pilosebaceous residues, remnants of adrenal glands, well-formed ganglia, and nests of neural tissue covered by neuroepithelium.

Maternal reporting of prenatal ultrasounds among women in the National Birth Defects Prevention Study.

BACKGROUND: Increased availability and usage of ultrasound screening have led to improved identification of fetal structural abnormalities prenatally. Few population-based studies have been published on prenatal detection for structural birth defects in the United States. The aim of this study is to determine the frequency of maternal reporting of abnormal prenatal ultrasounds for selected birth defects and to investigate associated maternal characteristics. METHODS: Participants included 4013 mothers enrolled in the National Birth Defects Prevention Study who carried a fetus with at least one of 14 structural birth defects between 1997 and 2004. Frequencies of abnormal prenatal ultrasounds were based on maternal report and computed for isolated and multiple defects. Associations between maternal characteristics and abnormal prenatal ultrasounds were assessed using logistic regression. RESULTS: Overall, 46% of participants reported an abnormal ultrasound. Infants with omphalocele, anencephaly, gastroschisis, and renal agenesis were more likely to have abnormal prenatal ultrasounds than those with cleft and limb abnormalities. Hispanic women were less likely to report abnormal prenatal ultrasounds of birth defects than Caucasians, as were women who had a body mass index ≥ 30 kg/m(2) compared with those with a normal body mass index. CONCLUSION: Of the 14 selected birth defects in this study, less than half were reported by mothers of affected infants to have had an abnormal ultrasound during pregnancy. The frequency of reporting abnormal prenatal ultrasounds varies by type of defect, maternal race/ethnicity, and maternal body mass index status.

Dichorionic twin pregnancy discordant for anencephaly: two cases with different management.

BACKGROUND: Prevalence ofanencephaly in dichorionic twins is higher than in singleton pregnancies. The authors report two cases with two different management strategies. CASE 1: Spontaneous dichorionic diamniotic twin pregnancy with the second twin diagnosed with anencephaly at 12 weeks gestation. Selective feticide was performed at the age of 13.2 weeks. Vaginal delivery occurred at 39 weeks, and birth weight was 2,850 g. CASE 2: Dichorionic diamniotic twin pregnancy discordant for anencephaly in the second twin was diagnosed at 13 weeks gestation. An expectant management was decided. Preterm delivery occurred at 35 weeks due to hydramnios of the affected fetus, delivering a healthy newborn weighing 2,300 g and an anencephalic neonate who died immediately after delivery. CONCLUSION: Anencephaly should be diagnosed as soon as possible, idealistically at 11-13+6 weeks ultrasound (US) scan, in order to offer the most appropriate counselling to the parents, ranging from selective feticide or expectant management. This short series suggests that selective early feticide may increase gestational age and birth weight.

Neonatal liver cell donation: a case report.

Traditional organ transplant options for newborns have been rare. There continues to be an increasing need for organs for transplant and a limited number of available organs, especially for small children. Liver cell transplantation is a promising alternative to orthotopic liver transplantation to treat liver-based inborn errors of metabolism.1 The procedure is minimally invasive and can be performed repeatedly. The safety of the procedure has been well established, and the clinical results are encouraging.1 The liver cell donation process is an option for families who experience the loss of a newborn and offers them a legacy for their child by providing life for others. The purpose of this article is to discuss the neonatal liver cell donation process and present a case report of an anencephalic infant whose parents chose to participate in this unique program.

Concordant fatal congenital anomaly in twin pregnancy: a case report and review of the literature.

BACKGROUND: When a pregnant mother finds out she has a fetus with a congenital defect, the parents feel profound worry, anxiety, and melancholy. Anomalies can happen in singleton or twin pregnancies, though they are more common in twin pregnancies. In twins, several congenital defects are typically discordant. We present a rare case of concordant fatal anomaly in twin pregnancy in a 22-year-old African patient primigravida mother from Western Ethiopia who presented for routine antenatal care. An obstetric ultrasound scan showed anencephaly, meningomyelocele, and severe ventriculomegaly. After receiving the counseling, the patient was admitted to the ward, and the pregnancy was terminated with the medical option. Following a successful in-patient stay, she was given folic acid supplements and instructed to get preconception counseling before getting pregnant again. CONCLUSION: The case demonstrates the importance of early obstetric ultrasound examination and detailed anatomic scanning, in twin pregnancies in particular. This case also calls for routine preconceptional care.

Chromosomal anomalies and additional sonographic findings in fetuses with open neural tube defects.

OBJECTIVE: To evaluate the results and the necessity of chromosome analysis in fetuses prenatally detected with a neural tube defect and to determine the significance of ultrasonographic evaluation for the identification of underlying or accompanying chromosomal anomalies. METHODS: Ninety fetuses that underwent prenatal and/or postnatal chromosome analysis after being diagnosed with open neural tube defects (NTD) between the years 2006 and 2010 in the Department of Obstetrics and Gynecology at Ondokuz Mayis University School of Medicine were included in this study. Detailed fetal ultrasonography was performed in all cases in order to investigate any additional anomalies. Karyotype was determined in the prenatal period by amniocentesis in 72 (80%) of the 90 fetuses, and by cordocentesis in 5 (5.5%). In 13 (13.3%) fetuses, karyotype was determined in the postnatal period by blood sampling. RESULTS: Fourteen (15.5%) of the 90 fetuses were diagnosed with acrania/anencephaly, 14 (15.5%) with encephalocele, 2 (2.2%) with iniencephaly, 60 (66.6%) with open spina bifida. None of the 90 fetuses with open NTD who had undergone chromosome analysis was diagnosed with chromosomal anomalies. None of the 19 (21.1%) fetuses diagnosed with additional ultrasound findings had a chromosomal abnormality, either. Seventy-one (78.9%) fetuses having sonograhically isolated NTD were also isolated in postmortem examination. CONCLUSION: In fetuses with open NTD, we could not find the chromosomal anomaly rate as high as reported in previous literature. The necessity of fetal karyotyping should be questioned especially in isolated cases.

Prenatal diagnosis of craniorachischisis totalis.

Craniorachischisis totalis (anencephaly with total open spina bifida) is the most severe form of neural tube defects. The exact aetiology of neural tube defects remains poorly understood. We report a case of a primigravida in her 20s with a fetus in which craniorachischisis totalis was diagnosed during the first-trimester ultrasound at 11 weeks of gestation. The parents opted for pregnancy termination and the diagnosis was confirmed postnatally. Besides the lack of folic acid supplementation during preconception, no other risk factor was found. This case highlights the importance of the first-trimester ultrasound in the diagnosis of severe malformations. The right diagnosis is crucial for future prenatal counselling, yet investigation is still required to better understand the aetiology behind neural tube defects and assess the possibility of underlying genetic features, thus enabling better counselling.

Do assisted conception twins have an increased risk for anencephaly?

BACKGROUND: The incidence rates of anterior neural tube defects, anencephaly and encephalocele appear increased among twins compared with singletons. The current study aimed to evaluate whether the etiology of this phenomenon is related to twinning, assisted reproductive technology (ART), or both. METHODS: The study cohort consisted of parturient women who were referred to our ultrasonography unit between January 1998 and December 2009 due to suspicion of severe fetal abnormality. The study cohort was divided into two subgroups based on mode of conception: spontaneous and ART (including IVF and ICSI). The subgroups were further subdivided into singleton and multiple pregnancies. We also compared pregnancies diagnosed with anencephaly in the study group to all live births in the Department of Obstetrics and Gynecology. RESULTS: Anencephaly was diagnosed in 43 fetuses out of 1154 (3.7%) pregnancies diagnosed with severe fetal anomaly. Anencephaly was diagnosed in 9 out of 78 twin pregnancies (11.5%); of these, 8 of 45 (17.8%) were ART conceived and 1 of 33 (3%) spontaneously conceived. A significant correlation was found between twinning and anencephaly, with an odds ratio (OR) of 3.4 [confidence interval (CI) = 1.3-8.9, P= 0.011], while no significant correlation was found between ART and anencephaly. A significant correlation was found between anencephaly and the combination of ART conception and twinning (OR of 6.6, CI = 2.8-15.3, P< 0.01). Analyzing the distribution of pregnancies diagnosed with anencephaly in the study group compared with the total number of live births in the department revealed a significant correlation between twinning and anencephaly, with an OR of 11.4 (CI = 4.9-26.5, P< 0.01), with no significant correlation between ART and anencephaly. Among all live births, a significant correlation was found between anencephaly and the combination of ART conception and twinning (OR of 24.6, CI = 11.4-53.2, P< 0.01). CONCLUSIONS: Our data suggest that twin pregnancies conceived by ART constitute a high-risk group for anencephaly, due to a possible synergistic effect of twinning and ART.

Monoamniotic twins with one fetal anencephaly and cord entanglement diagnosed with three dimensional ultrasound at 14 weeks of gestation.

A 29-year-old pregnant woman with parity 0-0-0-0 was diagnosed with monoamniotic twin pregnancy discordant for anencephaly at 14 weeks gestation. Umbilical cord entanglement, which is an important cause of fetal death in monoamniotic twins, was confirmed by three-dimensional ultrasound. Cesarean section was performed at 34 weeks of gestation, and the normal newborn infant was discharged without any complications. We report a case of monoamniotic twin pregnancy discordant for anencephaly and diagnosed with cord entanglement by three-dimensional ultrasound at 14 weeks of gestation, and now report it along with a literature review.