Risk factors associated with congenital central nervous system abnormalities in the National Hospital of Zinder, Niger.

INTRODUCTION: Congenital malformations of the central nervous system (CNS) are morphological abnormalities of the brain and spinal cord that occur during fetal development. They constitute the second most common congenital disability, after congenital cardiac defects. Many risk factors have been identified; however, these studies included various types of congenital abnormality. Furthermore, there is a lack of information on risk factors for congenital CNS malformation, and notably in the Zinder region of Niger. OBJECTIVE: This study aimed to identify the risk factors associated with congenital CNS malformations in the Zinder region. METHODS: In a case-control design, patients with congenital CNS malformation were enrolled between June 2022 and April 2023 in the Department of Neurosurgery of the National Hospital of Zinder. RESULTS: Family history of malformation (aOR:3.31, 95% CI:1.25-8.78) and consanguine marriage (aOR:2.28, 95% CI:1.23-4.20) were significantly associated with congenital CNS malformation. In contrast, folic acid supplementation (aOR:0.34, 95% CI:0.13, 0.89), multiparity (aOR:0.34, 95% CI:0.13, 0.89), and grand multiparity (aOR, 0.47; 95% CI:0.23, 0.97) had a protective effect. CONCLUSION: Risk factors such as family malformation history and consanguine marriage increased the risk of developing congenital malformations of the central nervous system. In contrast, folic acid supplementation in the index period and multiparity had a significant protective effect.

Epidemiological trends of isolated and non-isolated central nervous system congenital malformations in live births in a middle-income setting.

OBJECTIVES: This study aimed to analyze, in the São Paulo state of Brazil, time trends in prevalence, neonatal mortality, and neonatal lethality of central nervous system congenital malformations (CNS-CM) between 2004 and 2015. METHODS: Population-based study of all live births with gestational age ≥22 weeks and/or birthweight ≥400 g from mothers living in São Paulo State, during 2004-2015. CNS-CM was defined by the presence of International Classification Disease 10th edition codes Q00-Q07 in the death and/or live birth certificates. CNS-CM was classified as isolated (only Q00-Q07 codes), and non-isolated (with congenital anomalies codes nonrelated to CNS-CM). CNS-CM associated neonatal death was defined as death between 0 and 27 days after birth in infants with CNS-CM. CNS-CM prevalence, neonatal mortality, and lethality rates were calculated, and their annual trends were analyzed by Prais-Winsten Model. The annual percent change (APC) with 95% confidence interval (95%CI) was obtained. RESULTS: 7,237,628 live births were included in the study and CNS-CM were reported in 7526 (0.1%). CNS-CM associated neonatal deaths occurred in 2935 (39.0%). Isolated CNS-CM and non-isolated CNS-CM were found respectively in 5475 and 2051 livebirths, with 1525 (28%) and 1410 (69%) neonatal deaths. CNS-CM prevalence and neonatal lethality were stationary, however neonatal mortality decreased (APC -1.66; 95%CI -3.09 to -0.21) during the study. For isolated CNS-CM, prevalence, neonatal mortality, and lethality decreased over the period. For non-isolated CNS-CM, the prevalence increased, neonatal mortality was stationary, and lethality decreased during the period. The median time of CNS-CM associated neonatal deaths was 18 h after birth. CONCLUSIONS: During a 12-year period in São Paulo State, Brazil, neonatal mortality of infants with CNS-CM in general and with isolated CNS-CM showed a decreasing pattern. Nevertheless CNS-CM mortality remained elevated, mostly in the first day after birth.

Patterns of multiple congenital anomalies in the National Birth Defect Prevention Study: Challenges and insights.

BACKGROUND: About 20%-30% of children with birth defects have multiple major birth defects in more than one organ system, often referred to as multiple congenital anomalies (MCAs). Evaluating the patterns of MCAs can provide clues to the underlying causes, pathogenic mechanisms, and developmental pathways. We sought to explore selected patterns of MCAs within the National Birth Defects Prevention Study (NBDPS), a population-based, case-control study that excluded cases attributed to known chromosomal or single-gene abnormalities. METHODS: We defined MCAs as having two or more NBDPS-eligible birth defects and calculated the adjusted observed-to-expected ratio for all observed MCA patterns using co-occurring defect analysis. RESULTS: Of the 50,186 case infants eligible for NBDPS, 2,734 (3.7%) had at least two eligible birth defects. We observed 209 distinct 2-way combinations of birth defects, 297 distinct 3-way combinations, 179 distinct 4-way combinations, and 69 distinct 5-way combinations. Sacral agenesis had the largest proportion of cases with MCAs (70%), whereas gastroschisis had the lowest (3%). Among the cases with MCAs, 63% had a heart defect, 23% had an oral cleft, and 21% had anorectal atresia/stenosis. Of the patterns with adjusted observed-to-expected ratios in the top 20%, most were consistent with the known associations or syndromes, including VATER/VACTERL association and CHARGE syndrome. CONCLUSIONS: Most but not all patterns that had the highest adjusted observed-to-expected ratios were instances of known syndromes or associations. These findings highlight the importance of considering birth defect combinations that suggest syndromic patterns in the absence of a formal syndromic diagnosis. New approaches for screening for sequences and associations, and VATER/VACTERL in particular, in surveillance systems with limited resources for manual review may be valuable for improving surveillance system quality. The observed MCA patterns within NBDPS may help focus future genetic studies by generating case groups of higher yield.

Evaluation of prenatal central nervous system anomalies: obstetric management, fetal outcomes and chromosome abnormalities.

OBJECTIVE: To study the outcomes of fetuses who were diagnosed with central nervous system (CNS) anomalies during prenatal period and to describe the obstetric management of those pregnancies. METHODS: In this retrospective study, fetuses who were detected to have central nervous system anomalies by prenatal ultrasound from January 2010 to December 2019 were recruited. Data regarding prenatal diagnosis and obstetric outcomes were retrieved from maternal and paediatric records. The prognosis of fetuses who were born alive was classified based on their neurodevelopmental outcome within two years of life. RESULTS: There were a total of 365 fetuses with CNS anomalies within the 10-year study period, with a mean gestational age of 24.65±7.37 weeks at diagnosis. Ventriculomegaly (23.36%) was the commonest CNS anomalies seen. 198 (54.20%) of these fetuses had associated extra-CNS anomalies, with cardiovascular being the most common system involved. Fetal karyotyping was performed in 111 pregnancies, with chromosomal aberrations detected in 53 (49.07%) cases and culture failure in 3 cases. Majority of the chromosomal abnormalities were Edward syndrome (trisomy 18) and Patau syndrome (trisomy 13). Fetuses with congenital CNS anomalies and abnormal chromosomal karyotyping were more likely to be diagnosed earlier by prenatal ultrasound and tend to have poorer obstetric and neurocognitive prognosis. Prenatally, 86 (23.56%) of the cases were lost to follow up and likely to deliver elsewhere. Among the 279 cases whom their pregnancy outcomes were available, 139 (49.82%) pregnancies resulted in live births, 105 (37.63%) pregnancies were electively terminated, while the remaining 35 (12.54%) pregnancies ended in spontaneous loss. The decision of termination of pregnancy largely depends on mean diagnostic gestational age, presence of chromosomal aberrations and abnormal amniotic fluid volume in those fetuses. Two years after delivery, only 75 (53.96%) children out of 139 live births were still alive, 43 (30.93%) died and 21 (15.11%) cases were lost to follow-up. 32 (23.02%) children with prenatally diagnosed CNS anomalies had normal neurodevelopmental outcome. The presence of multiple CNS anomalies and involvement of extra-CNS anomalies indicated a poorer neurodevelopmental prognosis. CONCLUSION: Less than 50% of fetuses with prenatally diagnosed CNS anomalies resulted in live births. Even if they survive till delivery, 36.45% of them passed away within 2 years and 62.79% of children who survived till 2 years old had neurodevelopmental disability.

Disorders of Neuronal Migration/Organization Convey the Highest Risk of Neonatal Onset Epilepsy Compared With Other Congenital Brain Malformations.

BACKGROUND: Although seizures in neonates are common and often due to acute brain injury, 10-15% are unprovoked from congenital brain malformations. A better understanding of the risk of neonatal-onset epilepsy by the type of brain malformation is essential for counseling and monitoring. METHODS: In this retrospective cohort study, we evaluated 132 neonates with congenital brain malformations and their risk of neonatal-onset epilepsy. Malformations were classified into one of five categories based on imaging patterns on prenatal or postnatal imaging. Infants were monitored with continuous video EEG (cEEG) for encephalopathy and paroxysmal events in addition to abnormal neuroimaging. RESULTS: Seventy-four of 132 (56%) neonates underwent EEG monitoring, and 18 of 132 (14%) were diagnosed with neonatal-onset epilepsy. The highest prevalence of epilepsy was in neonates with disorders of neuronal migration/organization (9/34, 26%; 95% confidence interval [CI] = 13-44%), followed by disorders of early prosencephalic development (6/38, 16%; 95% CI = 6-31%), complex total brain malformations (2/16, 13%; 95% CI = 2-38%), and disorders of midbrain/hindbrain malformations (1/30, 3%; 95% CI = 0-17%). Of neonates with epilepsy, 5 of 18 (28%) had only electrographic seizures, 13 of 18 (72%) required treatment with two or more antiseizure medicines (ASMs), and 7 of 18 (39%) died within the neonatal period. CONCLUSION: Our results demonstrate that disorders of neuronal migration/organization represent the highest-risk group for early-onset epilepsy. Seizures are frequently electrographic only, require treatment with multiple ASMs, and portend a high mortality rate. These results support American Clinical Neurophysiology Society recommendations for EEG monitoring during the neonatal period for infants with congenital brain malformations.

Prevalence of supratentorial anomalies assessed by magnetic resonance imaging in fetuses with open spina bifida.

OBJECTIVES: To determine the prevalence of brain anomalies at the time of preoperative magnetic resonance imaging (MRI) assessment in fetuses eligible for prenatal open spina bifida (OSB) repair, and to explore the relationship between brain abnormalities and features of the spinal defect. METHODS: This was a retrospective cross-sectional study, conducted in three fetal medicine centers, of fetuses eligible for OSB fetal surgery repair between January 2009 and December 2019. MRI images obtained as part of the presurgical assessment were re-evaluated by two independent observers, blinded to perinatal results, to assess: (1) the type and area of the defect and its anatomical level; (2) the presence of any structural central nervous system (CNS) anomaly and abnormal ventricular wall; and (3) fetal head and brain biometry. Binary regression analyses were performed and data were adjusted for type of defect, upper level of the lesion (ULL), gestational age (GA) at MRI and fetal medicine center. Multiple logistic regression analysis was performed in order to identify lesion characteristics and brain anomalies associated with a higher risk of presence of abnormal corpus callosum (CC) and/or heterotopia. RESULTS: Of 115 fetuses included, 91 had myelomeningocele and 24 had myeloschisis. Anatomical level of the lesion was thoracic in seven fetuses, L1-L2 in 13, L3-L5 in 68 and sacral in 27. Median GA at MRI was 24.7 (interquartile range, 23.0-25.7) weeks. Overall, 52.7% of cases had at least one additional brain anomaly. Specifically, abnormal CC was observed in 50.4% of cases and abnormality of the ventricular wall in 19.1%, of which 4.3% had nodular heterotopia. Factors associated independently with higher risk of abnormal CC and/or heterotopia were non-sacral ULL (odds ratio (OR), 0.51 (95% CI, 0.26-0.97); P = 0.043), larger ventricular width (per mm) (OR, 1.23 (95% CI, 1.07-1.43); P = 0.005) and presence of abnormal cavum septi pellucidi (OR, 3.76 (95% CI, 1.13-12.48); P = 0.031). CONCLUSIONS: Half of the fetuses assessed for OSB repair had an abnormal CC and/or an abnormal ventricular wall prior to prenatal repair. The likelihood of brain abnormalities was increased in cases with a non-sacral lesion and wider lateral ventricles. These findings highlight the importance of a detailed preoperative CNS evaluation of fetuses with OSB. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Phenotypic variability of a TREX1 variant in Aicardi-Goutieres type 1 patients from the Indian subcontinent.

Aicardi-Goutieres Syndrome (AGS) is a heterogeneous genetic syndrome, manifesting early as encephalopathy and is associated with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, thrombocytopenia and intracranial calcification. The most severe neonatal type, AGS1, is caused by biallelic disease-causing variants in TREX1. In this study, we describe four patients with TREX1-related AGS1 whose phenotype overlaps with intra-uterine infections and neonatal lupus. Exome sequencing identified a previously reported TREX1 variant, c.223dup (NM_016381.5; p. Glu75GlyfsTer82) in all the four patients belonging to the Indian subcontinent. The functional consequence of the disease-causing variant was predicted by using a new combination of bioinformatics softwares. The recurrence of this pathogenic variant indicates a possible founder effect in TREX1 for AGS1 in this population. The phenotypic variability in those with this founder mutation can mimic intrauterine infections and neonatal lupus, thereby leading to misdiagnosis warranting a targeted genetic testing approach to be a part of the diagnostic workup to obtain a definite, early and cost-effective diagnosis in patients from Indian subcontinent with early onset encephalopathy.

Clinical and genetic spectrum of 104 Indian families with central nervous system white matter abnormalities.

Genetic disorders with predominant central nervous system white matter abnormalities (CNS WMAs), also called leukodystrophies, are heterogeneous entities. We ascertained 117 individuals with CNS WMAs from 104 unrelated families. Targeted genetic testing was carried out in 16 families and 13 of them received a diagnosis. Chromosomal microarray (CMA) was performed for three families and one received a diagnosis. Mendeliome sequencing was used for testing 11 families and all received a diagnosis. Whole exome sequencing (WES) was performed in 80 families and was diagnostic in 52 (65%). Singleton WES was diagnostic for 50/75 (66.67%) families. Overall, genetic diagnoses were obtained in 77 families (74.03%). Twenty-two of 47 distinct disorders observed in this cohort have not been reported in Indian individuals previously. Notably, disorders of nuclear mitochondrial pathology were most frequent (9 disorders in 20 families). Thirty-seven of 75 (49.33%) disease-causing variants are novel. To sum up, the present cohort describes the phenotypic and genotypic spectrum of genetic disorders with CNS WMAs in our population. It demonstrates WES, especially singleton WES, as an efficient tool in the diagnosis of these heterogeneous entities. It also highlights possible founder events and recurrent disease-causing variants in our population and their implications on the testing strategy.

Association between confirmed congenital Zika infection at birth and outcomes up to 3 years of life.

Little is known about the long-term neurological development of children diagnosed with congenital Zika infection at birth. Here, we report the imaging and clinical outcomes up to three years of life of a cohort of 129 children exposed to Zika virus in utero. Eighteen of them (14%) had a laboratory confirmed congenital Zika infection at birth. Infected neonates have a higher risk of adverse neonatal and early infantile outcomes (death, structural brain anomalies or neurologic symptoms) than those who tested negative: 8/18 (44%) vs 4/111 (4%), aRR 10.1 [3.5-29.0]. Neurological impairment, neurosensory alterations or delays in motor acquisition are more common in infants with a congenital Zika infection at birth: 6/15 (40%) vs 5/96 (5%), aRR 6.7 [2.2-20.0]. Finally, infected children also have an increased risk of subspecialty referral for suspected neurodevelopmental delay by three years of life: 7/11 (64%) vs 7/51 (14%), aRR 4.4 [1.9-10.1]. Infected infants without structural brain anomalies also appear to have an increased risk, although to a lesser extent, of neurological abnormalities. It seems paramount to offer systematic testing for congenital ZIKV infection in cases of in utero exposure and adapt counseling based on these results.

Developmental malformations in Huntington disease: neuropathologic evidence of focal neuronal migration defects in a subset of adult brains.

Neuropathologic hallmarks of Huntington Disease (HD) include the progressive neurodegeneration of the striatum and the presence of Huntingtin (HTT) aggregates that result from abnormal polyQ expansion of the HTT gene. Whether the pathogenic trinucleotide repeat expansion of the HTT gene causes neurodevelopmental abnormalities has garnered attention in both murine and human studies; however, documentation of discrete malformations in autopsy brains of HD individuals has yet to be described. We retrospectively searched the New York Brain Bank (discovery cohort) and an independent cohort (validation cohort) to determine whether developmental malformations are more frequently detected in HD versus non-HD brains and to document their neuropathologic features. One-hundred and thirty HD and 1600 non-HD whole brains were included in the discovery cohort and 720 HD and 1989 non-HD half brains were assessed in the validation cohort. Cases with developmental malformations were found at 6.4-8.2 times greater frequency in HD than in non-HD brains (discovery cohort: OR 8.68, 95% CI 3.48-21.63, P=4.8 × 10-5; validation cohort: OR 6.50, 95% CI 1.83-23.17, P=0.0050). Periventricular nodular heterotopias (PNH) were the most frequent malformations and contained HTT and p62 aggregates analogous to the cortex, whereas cortical malformations with immature neuronal populations did not harbor such inclusions. HD individuals with malformations had heterozygous HTT CAG expansions between 40 and 52 repeats, were more frequently women, and all were asymmetric and focal, aside from one midline hypothalamic hamartoma. Using two independent brain bank cohorts, this large neuropathologic series demonstrates an increased occurrence of developmental malformations in HD brains. Since pathogenic HTT gene expansion is associated with genomic instability, one possible explanation is that neuronal precursors are more susceptible to somatic mutation of genes involved in cortical migration. Our findings further support emerging evidence that pathogenic trinucleotide repeat expansions of the HTT gene may impact neurodevelopment.

Hepatic Involvement in Aicardi-Goutières Syndrome.

Aicardi-Goutières syndrome (AGS) is a monogenic type-I interferonopathy that results in neurologic injury. The systemic impact of sustained interferon activation is less well characterized. Liver inflammation is known to be associated with the neonatal form of AGS, but the incidence of AGS-related hepatitis across lifespan is unknown.We compared natural history data including liver enzyme levels with markers of inflammation, (liver-specific autoantibodies and interferon signaling gene expression[ISG] scores). Liver enzymes were classified as normal or elevated by the fold increase over the upper limit of normal (ULN). The highest increases were designated as hepatitis, defined as aspartate-aminotransferase or alanine-aminotransferase threefold ULN, or gamma-glutamyl transferase 2.5-fold ULN. A larger cohort was used to further characterize the longitudinal incidence of liver abnormalities and the association with age and genotype.Across the AGS cohort (n = 102), elevated liver enzymes were identified in 76 individuals (74.5%) with abnormalities at a level consistent with hepatitis in 29 individuals (28.4%). SAMHD1 mutations were less likely to be associated with hepatitis (log-rank test; p = 0.011). Hepatitis was associated with early-onset disease and microcephaly (log-rank test; microcephaly p = 0.0401, age onset p = 0.0355). While most subjects (n = 20/33) were found to have liver-specific autoantibodies, there was no association between the presence of autoantibodies or ISG scores with hepatitis-level enzyme elevations.In conclusion, all genotypes of AGS are associated with transient elevations of liver enzymes and the presence of liver-associated autoantibodies. This adds to our growing understanding of the systemic pathology AGS.

Early maternal Zika infection predicts severe neonatal neurological damage: results from the prospective Natural History of Zika Virus Infection in Gestation cohort study.

OBJECTIVE: To define the prevalence of adverse outcomes of maternal infection in a large cohort of ZIKV-infected Brazilian women and their infants. DESIGN: Prospective population-based cohort study. SETTING: Ribeirão Preto's region's private and public health facilities. POPULATION: Symptomatic ZIKV-infected mothers and their infants. METHODS: Prenatal/early neonatal data were obtained for all mother-child pairs. A subgroup of infants had cranial ultrasonography, eye fundoscopy, hearing and neurological examinations and Bayley III screening tests within 3 months of age. MAIN OUTCOME MEASURES: Prevalence of pregnancy losses and anomalies detected at birth or within 3 months according to the gestational age of infection. RESULTS: Overall, 511 ZIKV-infected women were identified from a total of 1116 symptomatic women; as there were two twins, there were a total of 513 fetuses included. Of these, 13 (2.5%; 95% CI 1.5-4.3) presented with major signs of congenital Zika syndrome (CZS). Of the 511 women, there were 489 livebirths and 24 (4.7%) pregnancy losses (20 miscarriages and four stillbirths). ZIKV-related anomalies occurred in the offspring of 42/511 (8.2%) mothers. Microcephaly or other CNS malformations were diagnosed in 1/4 (25.0%) stillbirths and in 19/489 (3.9%; 95% CI 2.5-5.9) of the liveborn infants. Fetal abnormalities were 14.0 (95% CI 7.6-26.0) times more likely with gestational infection occurring in ≤11 weeks. On follow up of 280 asymptomatic infants, 2/155 (1.3%) had eye abnormalities, 1/207 (0.5%) had CNS imaging findings and 16/199 (8%) presented neurological alert signs. CONCLUSIONS: This prospective population-based study represents the largest Brazilian cohort study of ZIKV in pregnancy. Congenital anomalies potentially associated with CZS are less frequent than previously thought. There is a strong association between the gestational age of infection (≤11 weeks) and a poorer early infant prognosis. A notable proportion of apparently asymptomatic newborns can present with subclinical findings within 3 months of age. TWEETABLE ABSTRACT: ZIKV and pregnancy: adverse outcomes are less common, more prevalent for first-trimester infections, and potentially subclinical.

Cancer risk in individuals with major birth defects: large Nordic population based case-control study among children, adolescents, and adults.

OBJECTIVE: To examine associations between birth defects and cancer from birth into adulthood. DESIGN: Population based nested case-control study. SETTING: Nationwide health registries in Denmark, Finland, Norway, and Sweden. PARTICIPANTS: 62 295 cancer cases (0-46 years) and 724 542 frequency matched controls (matched on country and birth year), born between 1967 and 2014. MAIN OUTCOME MEASURES: Relative risk of cancer in relation to major birth defects, estimated as odds ratios with 99% confidence intervals from logistic regression models. RESULTS: Altogether, 3.5% (2160/62 295) of cases and 2.2% (15 826/724 542) of controls were born with major birth defects. The odds ratio of cancer for people with major birth defects compared with those without was 1.74 (99% confidence interval 1.63 to 1.84). For individuals with non-chromosomal birth defects, the odds ratio of cancer was 1.54 (1.44 to 1.64); for those with chromosomal anomalies, the odds ratio was 5.53 (4.67 to 6.54). Many structural birth defects were associated with later cancer in the same organ system or anatomical location, such as defects of the eye, nervous system, and urinary organs. The odds ratio of cancer increased with number of defects and decreased with age, for both non-chromosomal and chromosomal anomalies. The odds ratio of cancer in people with any non-chromosomal birth defect was lower in adults (≥20 years: 1.21, 1.09 to 1.33) than in adolescents (15-19 years: 1.58, 1.31 to 1.90) and children (0-14 years: 2.03, 1.85 to 2.23). The relative overall cancer risk among adults with chromosomal anomalies was markedly reduced from 11.3 (9.35 to 13.8) in children to 1.50 (1.01 to 2.24). Among adults, skeletal dysplasia (odds ratio 3.54, 1.54 to 8.15), nervous system defects (1.76, 1.16 to 2.65), chromosomal anomalies (1.50, 1.01 to 2.24), genital organs defects (1.43, 1.14 to 1.78), and congenital heart defects (1.28, 1.02 to 1.59) were associated with overall cancer risk. CONCLUSIONS: The increased risk of cancer in individuals with birth defects persisted into adulthood, both for non-chromosomal and chromosomal anomalies. Further studies on the molecular mechanisms involved are warranted.

Lessons Learned from CNV Analysis of Major Birth Defects.

The treatment of major birth defects are key concerns for child health. Hitherto, for the majority of birth defects, the underlying cause remains unknown, likely to be heterogeneous. The implicated mortality and/or reduced fecundity in major birth defects suggest a significant fraction of mutational de novo events among the affected individuals. With the advent of systematic array-based molecular karyotyping, larger cohorts of affected individuals have been screened over the past decade. This review discusses the identification of disease-causing copy-number variations (CNVs) among individuals with different congenital malformations. It highlights the differences in findings depending on the respective congenital malformation. It looks at the differences in findings of CNV analysis in non-isolated complex congenital malformations, associated with central nervous system malformations or intellectual disabilities, compared to isolated single organ-system malformations. We propose that the more complex an organ system is, and the more genes involved during embryonic development, the more likely it is that mutational de novo events, comprising CNVs, will confer to the expression of birth defects of this organ system.

Tendencia de los Defectos de Tubo Neural en el Estado de Hidalgo México del 2013-2018 / Trend of Neural Tube Defects in Hidalgo Mexico from 2013-2018

INTRODUCCIÓN: los Defectos de Tubo Neural (DTN) son defectos congénitos del sistema nervioso central resultado del cierre inadecuado en alguna zona del tubo neural, siendo los más frecuentes Anencefalia y Espina Bífida en sus diferentes variantes. En Latinoamérica y México se encuentran dentro de las principales causas de morbilidad y mortalidad infantil. MATERIAL Y MÉTODOS: Análisis de series de tiempo de casos y defunciones de DTN en Hidalgo del 2013-2018 generado a partir de la base de datos de la Dirección General de Vigilancia Epidemiológica de los Defectos del Tubo Neural y Craneofaciales proporcionada por la Secretaria de Salud del Estado de Hidalgo, se incluyeron 187 casos con DTN que nacieron y radican en el Estado. Se calcularon las tasas de mortalidad infantil específicas por DTN con el objetivo de identificar probables factores que incidan o incrementen dichas tendencias. RESULTADOS: la incidencia de DTN fue de 58.7 en el periodo estudiado, la Anencefalia es el más incidente 45% (84), seguido del Mielomeningocele 33% (62) él cual muestra una incidencia creciente. El 84% de la población estaba afiliada al Seguro Popular. Solo el 7.5% (14) de las madres de los casos consumieron ácido fólico tres meses previos al embarazo y el 55% (103) acudieron a 3 consultas prenatales o menos. CONCLUSIONES: Los DTN requieren de estudio y vigilancia permanente pues representan una causa importante de morbilidad y mortalidad en la infancia que afecta a los individuos que los padecen, sus familias, la sociedad y el sistema de salud, con esto se evitarían resultados negativos

INTRODUCTION: Neural Tube Defects (DTN) are congenital defects of the central nervous system resulting from an inadequate closure in some area of ​​the neural tube, the most frequent being Anencephaly and Spina Bifida in their different variants. In Latin America and Mexico, they are among the main causes of infant morbidity and mortality. MATERIAL AND METHODS: Analysis of time series of cases and deaths of DTN in Hidalgo from 2013-2018 generated from the database of the General Directorate of Epidemiological Surveillance of Neural Tube and Craniofacial Defects directly by the Ministry of Health of the State of Hidalgo, included 187 cases with DTN that were born and reside in the State. DTN specific infant mortality rates will be calculated in order to identify probable factors that influence or increase various trends. RESULTS: the incidence of DTN was 58.7 in the period studied, Anencephaly is the most incident 45% (84), followed by Myelomeningocele 33% (62), which shows an increasing incidence. 84% of the population was affiliated at the Seguro Popular. Only 7.5% (14) of the mothers of the cases consumed folic acid three months before the pregnancy and 55% (103) attended 3 or less prenatal visits. CONCLUSIONS: DTN are problems of study and permanent surveillance, since they represent an important cause of morbidity and mortality in childhood that affect the individuals who suffer, their families, society and the health system, this would avoid negative results

The incidence, maternal, fetal and neonatal consequences of single intrauterine fetal death in monochorionic twins: A prospective observational UKOSS study.

OBJECTIVE: Report maternal, fetal and neonatal complications associated with single intrauterine fetal death (sIUFD) in monochorionic twin pregnancies. DESIGN: Prospective observational study. SETTING: UK. POPULATION: 81 monochorionic twin pregnancies with sIUFD after 14 weeks gestation, irrespective of cause. METHODS: UKOSS reporters submitted data collection forms using data from hospital records. MAIN OUTCOME MEASURES: Aetiology of sIUFD; surviving co-twin outcomes: perinatal mortality, central nervous system (CNS) imaging, gestation and mode of delivery, neonatal outcomes; post-mortem findings; maternal outcomes. RESULTS: The commonest aetiology was twin-twin transfusion syndrome (38/81, 47%), "spontaneous" sIUFD (22/81, 27%) was second commonest. Death of the co-twin was common (10/70, 14%). Preterm birth (<37 weeks gestation) was the commonest adverse outcome (77%): half were spontaneous and half iatrogenic. Only 46/75 (61%) cases had antenatal CNS imaging, of which 33 cases had known results of which 7/33 (21%) had radiological findings suggestive of neurological damage. Postnatal CNS imaging revealed an additional 7 babies with CNS abnormalities, all born at <36 weeks, including all 4 babies exhibiting abnormal CNS signs. Major maternal morbidity was relatively common, with 6% requiring ITU admission, all related to infection. CONCLUSIONS: Monochorionic twin pregnancies with single IUD are complex and require specialist care. Further research is required regarding optimal gestation at delivery of the surviving co-twin, preterm birth prevention, and classifying the cause of death in twin pregnancies. Awareness of the importance of CNS imaging, and follow-up, needs improvement.

Prevalence of MRI abnormalities in people with epilepsy in rural China.

OBJECTIVE: To assess the prevalence of brain MRI abnormalities in people with epilepsy in rural China and to compare it with that of individuals in the United Kingdom. METHODS: Brain MRI scans were obtained in people with epilepsy who participated in a rural community-based program in China between July 2010 and December 2012. Individual epileptogenic lesion types were reviewed and their associations with seizure control examined. The MRI findings were compared with 2 previous similar studies in the United Kingdom. RESULTS: Among the 597 individuals (58% male, median age 38 years) with MRI scans analyzed, 488 (82%) had active epilepsy. The MRI was abnormal in 389 individuals (65%), with potentially epileptogenic lesion in 224 (38%) and nonspecific abnormalities in 165 (28%), and 108 (18%) were potentially resectable. The potentially epileptogenic lesions were less frequently detected in children (<18 years old, 12 of 68, 18%) than in adults (212 of 529, 40%; p < 0.001). In people with potentially epileptogenic lesions, 67% (150 of 224) had failed ≥2 antiseizure medications. They had higher risk of uncontrolled epilepsy than those with normal MRI (risk ratio [RR] 1.25; p < 0.001) and those with nonspecific abnormality (RR 1.15; p = 0.002) after adjustment for age and sex. The diagnostic yield of MRI was similar to that reported in community- and hospital-based studies in the United Kingdom. CONCLUSIONS: More than one-third of people with chronic epilepsy in rural China have potentially epileptogenic lesions identifiable on brain MRI, with two-thirds fulfilling the definition of pharmacoresistance. These findings highlight the magnitude of the unmet needs for epilepsy surgery in China.

Timing of primary maternal cytomegalovirus infection and rates of vertical transmission and fetal consequences.

OBJECTIVE: Cytomegalovirus infection is the most frequent congenital infection and a major cause of long-term neurologic morbidity. The aim of this meta-analysis was to calculate the pooled rates of vertical transmission and fetal impairments according to the timing of primary maternal infection. DATA SOURCES: From inception to January 2020, MEDLINE, Scopus, Cochrane Library, and gray literature sources were used to search for related studies. STUDY ELIGIBILITY CRITERIA: Cohort and observational studies reporting the timing of maternal cytomegalovirus infections and rate of vertical transmission or fetal impairments were included. The primary outcomes were vertical transmission and fetal insult, defined as either prenatal findings from the central nervous system leading to termination of pregnancy or the presence of neurologic symptoms at birth. The secondary outcomes included sensorineural hearing loss or neurodevelopmental delay at follow-up and prenatal central nervous system ultrasonography findings. STUDY APPRAISAL AND SYNTHESIS METHODS: The pooled rates of the outcomes of interest with their 95% confidence intervals (CI) were calculated for primary maternal infection at the preconception period, periconception period, first trimester, second trimester, and third trimester. RESULTS: A total of 17 studies were included. The pooled rates of vertical transmission (10 studies, 2942 fetuses) at the preconception period, periconception period, first trimester, second trimester, and third trimester were 5.5% (95% CI, 0.1-10.8), 21.0% (95% CI, 8.4-33.6), 36.8% (95% CI, 31.9-41.6), 40.3% (95% CI, 35.5-45.1), and 66.2% (95% CI, 58.2-74.1), respectively. The pooled rates of fetal insult in case of transmission (10 studies, 796 fetuses) were 28.8% (95% CI, 2.4-55.1), 19.3% (95% CI, 12.2-26.4), 0.9% (95% CI, 0-2.4%), and 0.4% (95% CI, 0-1.5), for maternal infection at the periconception period, first trimester, second trimester, and third trimester, respectively. The pooled rates of sensorineural hearing loss for maternal infection at the first, second, and third trimester were 22.8% (95% CI, 15.4-30.2), 0.1% (95% CI, 0-0.8), and 0% (95% CI, 0-0.1), respectively. CONCLUSION: Vertical transmission after maternal primary cytomegalovirus infection increases with advancing pregnancy, starting from the preconception period. However, severe fetal impairments are rare after infection in the first trimester of pregnancy.

Periventricular pseudocysts of noninfectious origin: Prenatal associated findings and prognostic factors.

OBJECTIVE: The purpose of this study was to establish prognostic factors in fetuses diagnosed with periventricular pseudocysts (PVPCs) without known congenital infection, between 28 and 37 weeks of gestation. METHODS: This retrospective study included cases of fetal PVPC from 2008 to 2018. PVPCs were classified according to location, number, extension, morphology, and size. Additional findings, MRI and genetic studies were recorded. Pregnancy outcome, postnatal, or postmortem results were obtained. Images from patients with normal (Group 1) and abnormal postnatal development (Group 2) were compared for analysis of factors predictive of outcome. RESULTS: One-hundred and fifteen pseudocysts were observed in 59 patients. In 34 fetuses (57%), the PVPC was an isolated finding. Thirty-nine patients delivered live newborns, 27% opted for termination of pregnancy, and 4 patients were lost to follow-up. Eighty-four percent of the liveborns had normal development. When assessing for the influence of pseudocyst characteristics, a wide CSP, or large head circumference, neither of these affected the outcome. The presence of additional anomalies was the only positive predictor for abnormal development regradless of specific PVPC characteristics (P = .002). CONCLUSIONS: In fetuses with PVPCs, the presence of additional anomalies was the only predictor for adverse postnatal outcome. No association between cystic characteristics and adverse outcome was observed.