Association of maternal cancer with congenital anomalies in offspring.

BACKGROUND: Congenital anomalies are common, but the possibility that maternal cancer increases the chance of having a child with a birth defect is not fully understood. OBJECTIVES: To examine the association between maternal cancer before or during pregnancy and the risk of birth defects in offspring. METHODS: We conducted a retrospective cohort study of live births in Quebec, Canada, between 1989 and 2022 using hospital data. The main exposure measure was maternal cancer before or during pregnancy. The outcome included birth defects detected in offspring during gestation or at birth. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association of maternal cancer with birth defects using log-binomial regression models adjusted for potential confounders. RESULTS: In this study of 2,568,120 newborns, birth defects were present in 6.0% and 6.7% of infants whose mothers had cancer before or during pregnancy, respectively, compared with 5.7% of infants whose mothers never had cancer. Cancer during pregnancy was associated with heart (RR 1.58, 95% CI 1.03, 2.44), nervous system (RR 4.05, 95% CI 2.20, 7.46) and urinary defects (RR 1.72, 95% CI 1.01, 2.95). Among specific types of malignancies during pregnancy, breast cancer was the most prominent risk factor for birth defects (RR 1.55, 95% CI 1.02, 2.37). Cancer before pregnancy was not associated with any type of birth defect or with defects overall (RR 1.01, 95% CI 0.92, 1.11). Moreover, no specific type of cancer before pregnancy was associated with an increased risk of birth defects. CONCLUSIONS: Maternal cancer during pregnancy is associated with the risk of congenital anomalies in offspring, however, cancer before pregnancy is not associated with this outcome.

Características de la descendencia de gestantes diabéticas atendidas en el Hospital "Comandante Ciro Redondo García", Artemisa / Characteristics of the Offspring of Pregnant Women Who Received Attention in the Hospital Comandante Ciro Redondo García, of Artemisa

Introducción: Múltiples investigaciones demuestran el efecto teratogénico de la diabetes mellitus durante el embarazo, considerada causa frecuente de morbilidad fetal. Objetivo: Describir las características del producto de la concepción de mujeres con diabetes pregestacional o gestacional, atendidas en el Hospital Provincial Comandante Ciro Redondo García, de Artemisa. Métodos: Se realizó un estudio observacional, descriptivo, transversal, en la Provincia Artemisa, Cuba, en el período de febrero 2016 a febrero 2018, en 316 mujeres con diabetes mellitus durante su gestación. La información se obtuvo mediante revisión documental y entrevista, conservando los datos en hoja de cálculo Excel. Resultados: El 69,9 por ciento de las pacientes diabéticas estudiadas presentaron morbilidades en su descendencia, entre las que predominaron los defectos congénitos en 139 casos; 34 neonatos macrosómicos; 21 pretérminos; 9 con retardo del crecimiento intrauterino y 5 fallecidos antes del año de vida. La diabetes, tanto pregestacional como gestacional, se relacionó con afecciones en la descendencia; sin embargo, un control preconcepcional adecuado de la enfermedad redujo el riesgo de tener hijos afectados. Los defectos congénitos fueron la alteración más frecuente cuando la madre padecía diabetes pregestacional. Si la diabetes materna era gestacional los hijos presentaron con frecuencia macrosomía y otras anomalías asociadas. Conclusiones: Alrededor de 70 de cada 100 mujeres diabéticas presentan morbilidades en su descendencia. Si la diabetes materna no es controlada antes de la concepción, estas morbilidades en sus hijos son predominantemente defectos congénitos con posible origen disruptivo, mientras que la diabetes gestacional se relaciona más con recién nacidos macrosómicos(AU)

Introduction: Multiple investigations show the teratogenic effect of diabetes mellitus during pregnancy, being considered a frequent cause of fetal morbidity. Objective: To describe the characteristics of the offspring of women with pregestacional or gestational diabetes who received attention at the Hospital Provincial Comandante Ciro Redondo García of Artemisa. Methods: An observational, descriptive, cross-sectional and descriptive study was conducted in Artemisa Province, Cuba, in the period from February 2016 to February 2018, with 316 pregnant women with diabetes mellitus. The information was obtained through documentary review and interview; the data were kept in an Excel spreadsheet. Results: 69.9 percent of the studied diabetic patients presented morbidities in their offspring, among which congenital defects predominated, accounting for 139 cases; 34 were macrosomic neonates; 21 were preterm; 9 presented intrauterine growth retardation; and 5 died within one year of life. Diabetes, both pregestational and gestational, was associated with conditions in the offspring; however, adequate preconception control of the disease reduced the risk for having affected children. Congenital defects were the most frequent alteration when the mother had pregestational diabetes. If maternal diabetes was gestational, the offspring frequently presented macrosomia and other associated anomalies. Conclusions: About 70 out of 100 diabetic women present morbidities in their offspring. If maternal diabetes is not controlled before conception, these morbidities in their offspring are predominantly congenital defects with a possible disruptive origin, while gestational diabetes is more related to macrosomic newborns(AU)

Vírus e fissuras orofaciais: um histórico isolado e de associação / Viruses and orofacial clefts: an isolated and associational history / Virus y fisuras orofaciales: una historia aislada y asociativa

Os vírus são microrganismos comumente associados as doenças e infectam todos os seres vivos. Atuam de forma direta e indireta levando a pressão seletiva, com papel significativo e ainda em exploração no planeta. As fissuras orofaciais são anomalias congênitas de etiologia complexa e multifatorial, sendo as infecções virais durante a gestação um dos possíveis fatores etiológicos. A história da humanidade frente aos vírus e fissuras orofaciais de forma isolada é vasta, remontando a períodos antes de Cristo, seja por meio de leis para o controle de pragas e/ou por lendas de míticas criaturas deificadas e/ou demonizadas, cuja criação está fundamentada na Teoria Alegórica do surgimento das mitologias, demonstrando assim o interesse do ser humano e sua curiosidade em inovação e explicação destes assuntos. Considerando a relevância histórica, bem como a possível relação etiológica destes dois elementos, uma revisão da literatura foi realizada para apresentar a história mitológica e científica dos vírus e fissuras orofaciais, de forma isolada e associadas para fins de comparação. Para isso, foram utilizadas as bases PubMed/Medline, SciElo, LILACS e Portal Periódicos (CAPES) com os descritores: Virus, Anomalias/Anomalies, Virus and Anomalias/Virus and Anomalies, A History of viruses/História dos vírus, Virus and History/História and Virus, Virus and Myth/Virus and Mito, Anomalias and Mitos/Anomalies and Myths, Vampires and Virus/Vampiros and Virus. Enquanto o histórico mitológico é cheio de teorias contraditórias, o histórico cientifico acadêmico se revela coerente, porém resistente as novas áreas de atuação, não ponderando novas possibilidades e limitando a exploração científica, que só pôde ser alcançada nos séculos atuais. Quanto a associação, a linha de pesquisa relacionando vírus e fissuras orofaciais não possui nem meio século de existência, propiciando um grande campo a ser explorado e na mesma medida limitando os benefícios em prevenção que poderiam ser obtidos através destes estudos.

Viruses are microorganisms commonly associated with diseases that infect all living beings, they act directly and indirectly leading to selective pressure, their role on the planet is significant and still under exploration. Orofacial clefts are congenital anomalies that have a complex multifactorial etiology, with viral infections during pregnancy being one of the possible etiological factors. The history of humanity in the face of viruses and orofacial clefts in isolation is vast, dating back to periods before Christ, whether through laws for pest control and/or legends of mythical deified and/or demonized creatures, whose creation is fundamentalized in the Allegorical Theory of the emergence of mythologies, thus demonstrating the interest of human beings and their curiosity in innovation and explanation of these subjects. Considering the historical relevance, as well as the possible etiology relationship of these two elements, we carried out a literature review to present the mythological and scientific history of viruses and orofacial clefts, isolated and associated for comparison purposes. For this intent, the bases PubMed/Medline, SciElo, LILACS and Portal Periódicos (CAPES) were selected with the descriptors: A History of viruses/História dos vírus, Virus and History/História and Virus, Virus and Myth/Virus and Mito, Anomalias and Mitos/Anomalies and Myths, Vampires and Virus/Vampiros and Virus. While the mythological history is full of contradictory theories, the academic, scientific history proves to be consistent, but resistant to new areas of action, not considering new possibilities and limiting scientific exploration, which can only be achieved in the present centuries. As for the association, the line of research relating viruses and orofacial clefts does not even have half a century of existence, providing a large field to be explored and at the same time limiting the benefits of prevention that could be obtained through these studies.

Los virus son microorganismos comúnmente asociados a enfermedades que infectan a todos los seres vivos, actúan directa e indirectamente provocando presión selectiva, su papel en el planeta es significativo y aún en exploración. Las hendiduras orofaciales son anomalías congénitas que tienen una compleja etiología multifactorial, siendo las infecciones virales durante el embarazo uno de los posibles factores etiológicos. La historia de la humanidad frente a los virus y las hendiduras orofaciales de forma aislada es vasta, remontándose a períodos anteriores a Cristo, ya sea a través de leyes para el control de plagas y/o leyendas de criaturas míticas deificadas y/o demonizadas, cuya creación se fundamentaliza en la Teoría Alegórica del surgimiento de las mitologías, demostrando así el interés del ser humano y su curiosidad en la innovación y explicación de estos temas. Considerando la relevancia histórica, así como la posible relación etiológica de estos dos elementos, realizamos una revisión bibliográfica para presentar la historia mitológica y científica de los virus y las hendiduras orofaciales, aislados y asociados para fines de comparación. Para ello, se seleccionaron las bases PubMed/Medline, SciElo, LILACS y Portal Periódicos (CAPES) con los descriptores: A History of viruses/História dos vírus, Virus and History/História and Virus, Virus and Myth/Virus and Mito, Anomalias and Mitos/Anomalías y Mitos, Vampiros and Virus/Vampiros y Virus. Mientras que la historia mitológica está llena de teorías contradictorias, la historia académica, científica, se muestra coherente, pero resistente a nuevos campos de actuación, no considerando nuevas posibilidades y limitando la exploración científica, que sólo puede alcanzarse en los siglos actuales. En cuanto a la asociación, la línea de investigación que relaciona virus y hendiduras orofaciales no tiene ni medio siglo de existencia, proporcionando un gran campo a ser explorado y al mismo tiempo limitando los beneficios de prevención que podrían ser obtenidos a través de estos estudios.

Influenza vaccination during pregnancy and risk of selected major structural noncardiac birth defects, National Birth Defects Prevention Study 2006-2011.

PURPOSE: To assess associations between influenza vaccination during etiologically-relevant windows and selected major structural non-cardiac birth defects. STUDY DESIGN: We analyzed data from the National Birth Defects Prevention Study, a multisite, population-based case-control study, for 8233 case children diagnosed with a birth defect and 4937 control children without a birth defect with delivery dates during 2006-2011. For all analyses except for neural tube defects (NTDs), we classified mothers who reported influenza vaccination 1 month before through the third pregnancy month as exposed; the exposure window for NTDs was 1 month before through the first pregnancy month. For defects with five or more exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; maternal age, race/ethnicity, smoking and alcohol use, low folate intake; and, for NTDs, folate antagonist medications. RESULTS: There were 334 (4.1%) case and 197 (4.0%) control mothers who reported influenza vaccination from 1 month before through the third pregnancy month. Adjusted ORs ranged from 0.53 for omphalocele to 1.74 for duodenal atresia/stenosis. Most aORs (11 of 19) were ≤1 and all adjusted CIs included the null. The unadjusted CIs for two defects, hypospadias and craniosynostosis, excluded the null. These estimates were attenuated upon covariate adjustment (hypospadias aOR: 1.25 (95% CI 0.89, 1.76); craniosynostosis aOR: 1.23 (95% CI: 0.88, 1.74)). CONCLUSIONS: Results for several non-cardiac major birth defects add to the existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. Under-reporting of vaccination may have biased estimates downward.

Correlation between Exposure to Fine Particulate Matter (PM2.5) during Pregnancy and Congenital Anomalies: Its Surgical Perspectives.

BACKGROUND: Fine particulate matter (PM2.5) can easily penetrate blood vessels and tissues through the human respiratory tract and cause various health problems. Some studies reported that particular matter (PM) exposure during pregnancy is associated with low birth weight or congenital cardiovascular anomalies. This study aimed to investigate the correlation between the degree of exposure to PM ≤ 2.5 µm (PM2.5) during pregnancy and congenital anomalies relevant to the field of pediatric surgery. METHODS: Mother-infant dyads with registered addresses in the Metropolitan City were selected during 3 years. The electronic medical records of mothers and neonates were retrospectively analyzed, with a focus on maternal age at delivery, date of delivery, gestation week, presence of diabetes mellitus (DM) or hypertension, parity, the residence of the mother and infant, infant sex, birth weight, Apgar score, and presence of congenital anomaly. The monthly PM2.5 concentration from the first month of pregnancy to the delivery was computed based on the mothers' residences. RESULTS: PM2.5 exposure concentration in the second trimester was higher in the congenital anomaly group than in the non-congenital anomaly group (24.82 ± 4.78 µg/m3, P = 0.023). PM2.5 exposure concentration did not affect the incidence of nervous, cardiovascular, and gastrointestinal anomalies. While statistically insignificant, the groups with nervous, cardiovascular, gastrointestinal, musculoskeletal, and other congenital anomalies were exposed to higher PM2.5 concentrations in the first trimester compared with their respective counterparts. The effect of PM2.5 concentration on the incidence of congenital anomalies was significant even after adjusting for the mother's age, presence of DM, hypertension, and parity. The incidence of congenital anomalies increased by 26.0% (95% confidence interval of 4.3% and 49.2%) per 7.23 µg/m3 elevation of PM2.5 interquartile range in the second trimester. CONCLUSIONS: The congenital anomaly group was exposed to a higher PM2.5 concentration in the second trimester than the non-congenital anomaly group. The PM2.5 exposure concentration level in the first trimester tended to be higher in groups with anomalies than those without anomalies. This suggests that continuous exposure to a high PM2.5 concentration during pregnancy influences the incidence of neonatal anomalies in surgical respects.

Diagnosis and Management of Infertility: A Review.

IMPORTANCE: In the US, approximately 12.7% of reproductive age women seek treatment for infertility each year. This review summarizes current evidence regarding diagnosis and treatment of infertility. OBSERVATIONS: Infertility is defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse. Approximately 85% of infertile couples have an identifiable cause. The most common causes of infertility are ovulatory dysfunction, male factor infertility, and tubal disease. The remaining 15% of infertile couples have "unexplained infertility." Lifestyle and environmental factors, such as smoking and obesity, can adversely affect fertility. Ovulatory disorders account for approximately 25% of infertility diagnoses; 70% of women with anovulation have polycystic ovary syndrome. Infertility can also be a marker of an underlying chronic disease associated with infertility. Clomiphene citrate, aromatase inhibitors such as letrozole, and gonadotropins are used to induce ovulation or for ovarian stimulation during in vitro fertilization (IVF) cycles. Adverse effects of gonadotropins include multiple pregnancy (up to 36% of cycles, depending on specific therapy) and ovarian hyperstimulation syndrome (1%-5% of cycles), consisting of ascites, electrolyte imbalance, and hypercoagulability. For individuals presenting with anovulation, ovulation induction with timed intercourse is often the appropriate initial treatment choice. For couples with unexplained infertility, endometriosis, or mild male factor infertility, an initial 3 to 4 cycles of ovarian stimulation may be pursued; IVF should be considered if these approaches do not result in pregnancy. Because female fecundity declines with age, this factor should guide decision-making. Immediate IVF may be considered as a first-line treatment strategy in women older than 38 to 40 years. IVF is also indicated in cases of severe male factor infertility or untreated bilateral tubal factor. CONCLUSIONS AND RELEVANCE: Approximately 1 in 8 women aged 15 to 49 years receive infertility services. Although success rates vary by age and diagnosis, accurate diagnosis and effective therapy along with shared decision-making can facilitate achievement of fertility goals in many couples treated for infertility.

Hypoxia: A teratogen underlying a range of congenital disruptions, dysplasias, and malformations.

In this review, we explore evidence that hypoxia in the developing human fetus can lead not only to the more commonly accepted disruptive-type defects, but also patterns of anomalies that suggest that hypoxia can exert a more classic teratogenic effect, using the brain as one example. We review neuropathology in the context of intrauterine hypoxia, particularly as it relates to carbon monoxide poisoning, in utero strokes, and homozygous alpha-thalassemia. In general, the associated brain injuries resemble those seen with other causes of hypoxic-ischemic injury. Fetal strokes during development usually lead to loss of brain tissue in areas that do not follow a typical embryologic pattern, and therefore are considered disruptions. However, there is also evidence that fetal brain ischemia can cause more classically recognized patterns of abnormal embryonic neuronal migration and organization such as polymicrogyria, cortical dysplasia, or dysgenesis, including select types of focal cortical dysplasia. This study summarizes available literature and evidence to raise clinicians' awareness regarding the association between hypoxia and congenital anomalies, including brain malformations.

Paternal Exposure to Immunosuppressive and/or Biologic Agents and Birth Outcomes in Patients With Immune-Mediated Inflammatory Diseases.

BACKGROUND & AIMS: We conducted a retrospective cohort study to inform the safety of exposure to immunosuppressive and/or biologic agents around conception in expectant fathers with immune-mediated inflammatory diseases (IMIDs) on birth outcomes. METHODS: Using a deidentified administrative claims database (OptumLabs Data Warehouse), we identified 7453 expectant fathers with IMIDs (inflammatory bowel diseases, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis) linked to newborns with periconception medication exposure between 38 and 60 weeks before the newborn birth date (34-58 weeks prior for preterm newborns) and neonatal follow-up for 3 months after the birth date. Through logistic regression adjusting for paternal age and race (and, in a subset, for maternal age, race, presence of IMIDs, and nonsingleton births), we compared the risk of major congenital malformations (primary outcome) and preterm birth and low birth weight in fathers exposed to thiopurines (n = 461), methotrexate (n = 171), tumor necrosis factor (TNF) α antagonists (n = 1082), or non-TNF-targeting biologic agents (n = 132) vs fathers not exposed to any of these medications (n = 5607). RESULTS: As compared to unexposed fathers (3.4% prevalence of major congenital malformations), exposure to thiopurines (relative risk [RR], 1.12; 95% confidence interval [CI], 0.66-1.76), methotrexate (RR, 0.67; 95% CI, 0.21-1.55), TNF-α antagonists (RR, 1.14; 95% CI, 0.81-1.57), and non-TNF-targeting biologic agents (RR, 1.75; 95% CI, 0.80-3.24) was not associated with increased risk of major congenital malformations. No association was observed between paternal medication exposure and risk of preterm birth or low birth weight. Results were stable on subanalyses of linked father-mother-newborn triads. CONCLUSIONS: In a large cohort study of 7453 expectant fathers with IMIDs, exposure to immunosuppressive or biologic agents around conception was not associated with increased risk of adverse birth outcomes.

Risk factors associated with congenital anomalies among newborns in southwestern Ethiopia: A case-control study.

INTRODUCTION: Human embryo is well protected in the uterus by the embryonic membrane, although teratogens may cause developmental disruptions after maternal exposure to them during early pregnancy. Most of the risk factors contributing to the development of congenital anomalies are uncertain; however, genetic factors, environmental factors and multifactorial inheritance are found to be risk factors. Regardless of their clinical importance, there are little/no studies conducted directly related to predisposing risk factors in southwestern Ethiopia. OBJECTIVE: The study aimed to determine the associated risk factors with congenital anomalies among newborns in southwestern Ethiopia. METHODS: Case-control study was conducted on newborns and their mothers in six purposively selected hospitals in southwestern Ethiopia from May 2016 to May 2018. Data was collected after evaluation of the neonates for the presence of congenital anomalies using the standard pretested checklist. The data was analyzed using SPSS version 25.0. P <0.01 was set as statistically significant. RESULTS: Risk factors such as unidentified medicinal usage in the first three months of pregnancy (AOR = 3.435; 99% CI: 2.012-5.863), exposure to pesticide (AOR = 3.926; 99% CI: 1.266-12.176), passive smoking (AOR = 4.104; 99% CI: 1.892-8.901), surface water as sources of drinking (AOR = 2.073; 99% CI: 1.221-3.519), folic acid supplementation during the early pregnancy (AOR = 0.428; 99% CI: 0.247-0.740) were significantly associated with the congenital anomalies. CONCLUSIONS: In this study, risk factors such as passive smoking, exposure to pesticides, chemicals and use of surface water as a source of drinking during early pregnancy had a significant association with congenital anomalies. There is a need to continuously provide health information for the community on how to prevent and control predisposing risk factors.

Chornobyl radiation-congenital anomalies: A persisting dilemma.

We report population prevalence rates of neural tube defects (NDT) and microcephaly (MIC) as well as levels of incorporated Cs137 by pregnant women in two areas of the Rivne Province of Ukraine, a northern half (Polissia) polluted by Chornobyl radiation and not-Polissia areas. Monitoring of congenital malformations was conducted with adherence to methods adopted by a European surveillance network (EUROCAT). Incorporated Cs137 (Bq/kg) by pregnant women residing in the Polissia and not-Polissia areas were obtained concurrently with prenatal ultrasound examinations. In Polissia, the incorporated Cs137 levels by pregnant women as well as the prevalence rates of NDTs and MIC are significantly higher than in not-Polissia. In Polissia, the prevalence rates of NDTs and MIC are among the highest in Europe. The debate concerning the teratogenic impact of chronic exposures to low levels of ionizing radiation was re-ignited by our 2010 report. Health agencies uphold the notion that exposure to Chornobyl radiation levels are too low to be teratogenic, which is inconsistent with our observations. Further investigations in Rivne by international teams can, we believe, contribute facts to the ongoing debate. Our monitoring system, experience and data can facilitate concurrent investigations of teratogenic risks from exposures to other sources of ionizing radiation, alcohol, folate, and zinc deficiencies, among other risk factors. Study of genomic impacts can likewise be undertaken.

Dolutegravir in pregnant mice is associated with increased rates of fetal defects at therapeutic but not at supratherapeutic levels.

BACKGROUND: Dolutegravir (DTG) is a preferred regimen for all people with HIV including pregnant women, but its effects on the fetus are not fully understood. Periconceptional exposure to DTG has been associated with increased rates of neural tube defects (NTDs), although it is unknown whether this is a causal relationship. This has led to uncertainty around the use of DTG in women of reproductive potential. METHODS: Pregnant C57BL/6J mice were randomly allocated to control (water), 1x-DTG (2.5 mg/kg-peak plasma concentration ~3000 ng/ml - therapeutic level), or 5x-DTG (12.5 mg/kg-peak plasma concentration ~12,000 ng/ml - supratherapeutic level), once daily from gestational day 0.5 until sacrifice. DTG was administered with 50 mg/kg tenofovir+33.3 mg/kg emtricitabine. Fetal phenotypes were determined, and maternal and fetal folate levels were quantified by mass-spectrometry. FINDINGS: 352 litters (91 control, 150 1x-DTG, 111 5x-DTG) yielding 2776 fetuses (747 control, 1174 1x-DTG, 855 5x-DTG) were assessed. Litter size and viability rates were similar between groups. Fetal and placenta weights were lower in the 1x-DTG vs. control. Placental weight was higher in the 5x-DTG vs. control. Five NTDs were observed, all in the 1x-DTG group. Fetal defects, including microphthalmia, severe edema, and vascular/bleeding defects were more frequent in the 1x-DTG group. In contrast, defect rates in the 5x-DTG were similar to control. Fetal folate levels were similar between control and 1x-DTG, but were significantly higher in the 5x-DTG group. INTERPRETATION: Our findings support a causal relationship of DTG at therapeutic doses with increased risk for fetal defects, including NTDs at a rate that is similar that reported in the Tsepamo study for women exposed to DTG-based ART from conception. The non-monotonic dose-response relationship between DTG and fetal anomalies could explain the previous lack of fetal toxicity findings from pre-clinical DTG studies. The fetal folate levels suggest that DTG is unlikely to be an inhibitor of folate uptake. FUNDING: This project has been funded with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN275201800001I.

Increasing serum alkaline phosphatase is associated with bone deformity progression for patients with polyostotic fibrous dysplasia.

BACKGROUND: Fibrous dysplasia (FD) is a rare bone disorder in which normal intramedullary bone is replaced by fibro-osseous tissue, which is complicated by the progression of Shepherd's crook deformity. How to predict the progression of Shepherd's crook deformity is still a challenging for the orthopedic surgeon. METHODS: A total of 159 cases were reviewed in the retrospective study between January 2000 and September 2016. Clinical and monitoring data were collected. We analyzed the correlationship between the bone turnover markers and other parameters (age, gender, FD type, deformity, BMI, and lesion location). RESULTS: Age, gender, lesion location, lesion type, and shepherd's crook deformity had a close relationship with preoperative ALP level in the univariate analysis, and the multivariate analysis showed age, gender, lesion type, and shepherd's crook deformity had the significant relationship with the preoperative serum ALP level. The surgery could remove the bone lesion and suppressed the abnormal bone metabolism. Furthermore, the preoperative ALP level of FD patients with the shepherd's crook deformity was obviously higher than that without deformity, and the preoperative calcium and phosphorus levels of FD patients with deformity were significantly lower than that without deformity. Notably, for some patients with progression of the shepherd's crook deformity during the follow-up, ALP increased to the high level and at that time X-ray showed the shepherd's crook deformity severely progressing. CONCLUSIONS: PFD with higher serum ALP level has obvious tendency to progress severely, and risk factors of progression to the deformity are the condition of bony metabolism and FD type. The deformity of PFD may be related to high speed of bone turnover, which is exactly reflected by the levels of serum ALP and calcium. Evaluation of patients with FD should include a thorough evaluation of calcium/phosphate metabolism and bone turnover.

Síndrome Nance-Horan, cataratas congénitas y anomalías dentales / Nance-Horan syndrome, congenital cataracts and dental anomalies

RESUMEN Introducción: La presencia de estructuras dentofaciales atípicas puede ser el primer indicador de otros defectos congénitos relacionados con síndromes también de origen genético. El síndrome Nance-Horan es un trastorno monogénico ligado al cromosoma X, caracterizado fenotípicamente por alteraciones dismorfológicas dentales y craneofaciales distintivas, cataratas congénitas y déficit cognitivo. Objetivo: Describir un caso inusual de anomalías dentarias en el curso del síndrome Nance-Horan. Presentación de caso: Paciente de 13 años de edad, masculino, de piel blanca. Al examen clínico se constató un patrón dismórfico dado por facies alargada y estrecha, orejas prominentes con anteversión de la aurícula, nariz grande con puente nasal alto, diastema generalizado en ambas arcadas, todos los dientes con anomalías de forma y microdónticos. En el estudio radiológico periapical se constataron raíces cortas y cámaras pulpares amplias. Los antecedentes patológicos personales de nuestro paciente, el patrón dismórfico cráneo facial y las radiografías coinciden con características de otros casos de síndrome Nance-Horan reportados en la literatura. La mutación del gen síndrome Nance-Horan se expresa completamente solo en los varones. Como los varones son hemicigóticos para los genes ligados al cromosoma X, basta con una copia del alelo mutado para que aparezca una enfermedad de herencia recesiva ligada al sexo. Conclusiones: Se evidenció que es de crucial importancia realizar un cuidadoso examen, tanto clínico como radiográfico, de los pacientes con anomalías dentales. Se insiste en el trabajo mancomunado entre diferentes disciplinas y especialidades, tanto médicas como estomatológicas(AU)

ABSTRACT Introduction: The presence of atypical dentofacial structures may be the first indicator of other congenital defects related to syndromes of likewise genetic origin. Nance-Horan syndrome is a monogenic X linked disorder phenotypically characterized by distinctive dysmorphic dental and craniofacial alterations, congenital cataracts and cognitive deficit. Objective: Describe an unusual case of dental anomalies in the course of Nance-Horan syndrome. Case presentation: A case is presented of a white male 13-year-old patient. Clinical examination revealed a dysmorphic pattern characterized by long narrow facies, prominent ears with auricular anteversion, a big nose with a high nasal bridge, generalized diastema in both arches, and all the teeth microdontic and abnormally shaped. Periapical radiological examination found short roots and broad pulp chambers. The personal pathological antecedents of the patient, the dysmorphic craniofacial pattern and the radiographs correspond to characteristics of other cases of Nance-Horan syndrome reported in the literature. Mutation of the Nance-Horan syndrome gene is completely expressed only in males. Since males are hemizygous for X linked genes, one copy of the mutated allele is sufficient for the appearance of a sex-linked recessive inheritance disease. Conclusions: Evidence was found of the crucial importance of conducting careful examination, both clinical and radiographic, of patients with dental anomalies. Emphasis is placed on the joint work of various disciplines and specialties, both medical and dental(AU)

Neonatal and Maternal Outcomes among Women with Glomerulonephritis.

BACKGROUND: The outcomes of pregnancy in women with renal diseases remain controversial. The purpose of the study was to report fetal and maternal outcomes among women with glomerular disease in comparison with healthy pregnant women and a review of the current literature on this issue. METHODS: Retrospective analysis included 72 pregnancies in 62 women with biopsy-proven glomerulonephritis (GN) (in 65.3% of cases, immunoglobulin A nephropathy was found). The control group consisted of 315 healthy pregnant women. We assessed fetal (prematurity, low birth weight, hypotrophy, fetal malformation, or intrauterine death) and maternal (gestational hypertension, preeclampsia, deterioration in kidney function, and maternal death) outcomes. Descriptive data analysis, Fisher's exact test, unpaired Student's t test, and ANOVA were performed. RESULTS: Hypertension prevalence among the GN group and controls was 76.4 and 10.2%, respectively. Preeclampsia complicated 29.2% of pregnancies among women with GN and 2.9% of controls. In 8.3% of patients, at least a 50% decrease in GFR during pregnancy was observed. Preterm delivery prevalence in the GN group and controls was 74.7 and 12.7%, respectively. Hypotrophy was diagnosed in 12.5% of cases from the GN group and 5.4% of controls. The analysis showed that low estimated glomerular filtration rate, hypertension, and proteinuria were risk factors of adverse neonatal outcomes. CONCLUSION: Women with GN are a risk factor of adverse pregnancy outcomes. As pregnancy complications are more prevalent across all the CKD stages, even in patients with near-normal kidney function, they require specialized care. It might be advisable to screen pregnant women for the presence of CKD, as especially in the early stage, it is often asymptomatic. Both hypertension and proteinuria are risk factors for neonatal and maternal complications.

Pregnancy After Breast Cancer in Patients With Germline BRCA Mutations.

PURPOSE: Young women with germline BRCA mutations have unique reproductive challenges. Pregnancy after breast cancer does not increase the risk of recurrence; however, very limited data are available in patients with BRCA mutations. This study investigated the impact of pregnancy on breast cancer outcomes in patients with germline BRCA mutations. PATIENTS AND METHODS: This is an international, multicenter, hospital-based, retrospective cohort study. Eligible patients were diagnosed between January 2000 and December 2012 with invasive early breast cancer at age ≤ 40 years and harbored deleterious germline BRCA mutations. Primary end points were pregnancy rate, and disease-free survival (DFS) between patients with and without a pregnancy after breast cancer. Pregnancy outcomes and overall survival (OS) were secondary end points. Survival analyses were adjusted for guarantee-time bias controlling for known prognostic factors. RESULTS: Of 1,252 patients with germline BRCA mutations (BRCA1, 811 patients; BRCA2, 430 patients; BRCA1/2, 11 patients) included, 195 had at least 1 pregnancy after breast cancer (pregnancy rate at 10 years, 19%; 95% CI, 17% to 22%). Induced abortions and miscarriages occurred in 16 (8.2%) and 20 (10.3%) patients, respectively. Among the 150 patients who gave birth (76.9%; 170 babies), pregnancy complications and congenital anomalies occurred in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up from breast cancer diagnosis was 8.3 years. No differences in DFS (adjusted hazard ratio [HR], 0.87; 95% CI, 0.61 to 1.23; P = .41) or OS (adjusted HR, 0.88; 95% CI, 0.50 to 1.56; P = .66) were observed between the pregnancy and nonpregnancy cohorts. CONCLUSION: Pregnancy after breast cancer in patients with germline BRCA mutations is safe without apparent worsening of maternal prognosis and is associated with favorable fetal outcomes. These results provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility.

Approaches to studying the genomic architecture of complex birth defects.

Every year nearly 6 percent of children worldwide are born with a serious congenital malformation, resulting in death or lifelong disability. In the United States, birth defects remain one of the leading causes of infant mortality. Among the common structural congenital defects are conditions known as neural tube defects (NTDs). These are a class of malformation of the brain and spinal cord where the neural tube fails to close during the neurulation. Although NTDs remain among the most pervasive and debilitating of all human developmental anomalies, there is insufficient understanding of their etiology. Previous studies have proposed that complex birth defects like NTDs are likely omnigenic, involving interconnected gene regulatory networks with associated signals throughout the genome. Advances in technologies have allowed researchers to more critically investigate regulatory gene networks in ever increasing detail, informing our understanding of the genetic basis of NTDs. Employing a systematic analysis of these complex birth defects using massively parallel DNA sequencing with stringent bioinformatic algorithms, it is possible to approach a greater level of understanding of the genomic architecture underlying NTDs. Herein, we present a brief overview of different approaches undertaken in our laboratory to dissect out the genetics of susceptibility to NTDs. This involves the use of mouse models to identify candidate genes, as well as large scale whole genome/whole exome (WGS/WES) studies to interrogate the genomic landscape of NTDs. The goal of this research is to elucidate the gene-environment interactions contributing to NTDs, thus encouraging global research efforts in their prevention.