Fetal genital anomalies: an aid to diagnosis

OBJECTIVE: To report our experience with the prenatal diagnosis of fetal genital anomalies and suggest a protocol for management. METHODS: A retrospective review of all the cases with fetal genital anomalies or phenotype and genotype discrepancy identified by prenatal ultrasound. RESULTS: Twenty cases with abnormal fetal genitalia and four with a phenotype and genotype discrepancy were diagnosed prenatally. Genital anomalies were rarely found in isolation, most were found in combination with renal or multiple structural anomalies. The etiology of abnormal genitalia was broad and included metabolic, chromosomal and genetic syndromes. CONCLUSION: Prenatal detection of genital anomalies should stimulate a detailed ultrasound examination and determination of genotypic sex. Measurement of 17-OHP and Delta(4)-androstenedione or metabolites of the cholesterol pathway in the amniotic fluid and/or maternal urine may be helpful in making a definitive diagnosis. Identification of genital anomalies in fetuses with renal or multiple abnormalities can aid prenatal diagnosis, thereby facilitating accurate counseling of parents who are then in a better position to make informed choices.     

Mortality and morbidity of neonates born at <26 weeks of gestation (1998-2003). A population-based study

OBJECTIVE: To describe mortality and morbidity of neonates born at <26 weeks' gestation in a contemporary population-based cohort. METHODS: We analyzed data of neonates born at <26 weeks between 1998 and 2003 in the Federal State of Hesse, Germany. Survival was calculated at 28 days and at discharge from hospital. RESULTS: Out of a total of 800 births, 572 infants were liveborn. Among those admitted for neonatal intensive care, 62.3% survived until day 28. Among the neonates followed until death or discharge, 59.6% were discharged home. Logistic regression analyses showed the following variables to be associated with an increased risk of death: Twins (Odds Ratio (OR) 3.7; 95% Confidence Interval (CI) 1.34-10.26), multiple birth >or=3 (OR 8.14; CI 1.23-53.86), intraventricular hemorrhage (IVH) >or=grade III (OR 4.79; CI 1.89-12.14), clinical risk index for babies score >15 (OR 2.9; CI 1.09-7.76), and a gestational age or=grade III and/or periventricular leukomalacia in 15%, and severe retinopathy of prematurity in 29.8%. CONCLUSIONS: This study provides outcome data derived from a contemporary population-based cohort. Mortality and complication rates remain high.     

Promotion of BRCA1-associated triple-negative breast cancer by ovarian hormones

PURPOSE OF REVIEW: Mammary epithelial proliferation is controlled by the ovarian hormones estrogen and progesterone. Although BRCA1 (breast cancer 1, early onset) is ubiquitously expressed, women with BRCA1 mutations have a propensity to develop tumors in tissues sensitive to ovarian hormone. An understanding of the tissue-specific function of the BRCA1-encoded protein (BRCA1) provides additional insight that may improve cancer risk reduction in BRCA1 mutation carriers. RECENT FINDINGS: Studies using mouse models have shown that BRCA1 regulates the abundance of progesterone receptor. The half-life of progesterone receptor is extended in cells harboring mutations in BRCA1. Reduced ubiquitination of progesterone receptor contributes to its stabilization and is correlated with increased cell proliferation in response to progesterone. Treatment of mutant mice with antiprogesterone prevents/delays tumor development. In vitro, BRCA1 and its interacting protein BARD1 (BRCA1-associated RING domain) serve as an ubiquitin ligase for the monoubiquitination of estrogen receptor-alpha, which may lead to alterations in estrogen receptor-alpha activity. Furthermore, the ubiquitin ligase activities of BRCA1/BARD1 may be determined by the ubiquitin-conjugating enzyme E2. SUMMARY: BRCA1 exerts its tissue-specific function through the regulation of progesterone receptor and estrogen receptor-alpha. Interference with progesterone receptor, in addition to estrogen receptor-alpha, may be effective in reducing cancer risk in BRCA1 mutation carriers.     

Gonadotropin-releasing hormone (GnRH)-I regulation of interleukin (IL)-1b and IL-1 receptor antagonist expression in cultured human endometrial stromal cells

Aim:  Human endometrium is an active site of cytokine production and action. Among these cytokines, the interleukin-1 (IL-1) system seems to be relevant to the embryonic implantation process. We have previously reported the production of GnRH-I by human blastocyst, as well as the presence of GnRH-I receptor in human endometrium. This suggests a close interaction between the immune and endocrine systems through these cytokine mediators in embryonic implantation.
Methods:  To test the relevance of this interaction during embryonic implantation, we investigated GnRH-I regulation of IL-1b and IL-1ra mRNA and protein expression in human endometrial stromal cells using quantitative competitive polymerase chain reaction and ELISA.
Results:  IL-1b mRNA and protein expression in cultured human endometrial stromal cells was significantly enhanced by GnRH-agonist in comparison to control groups. IL-1ra mRNA and protein was significantly decreased by GnRH-agonist in comparison to control groups. In contrast, the GnRH-antagonist ablated the regulatory effects of GnRH agonist in 1b and IL-1ra mRNA and protein levels in a dose-dependent manner.
Conclusions:  In conclusion, these results suggest a possible close interaction between the immune and endocrine systems in human embryonic implantation through the classical neuropeptide hormone GnRH and its receptor.     

Self-administered measurement of symphysis-fundus heights

BACKGROUND: Antenatal identification of infants small for gestational age (SGA) improves their perinatal outcome. Repeated measurement of symphysis-fundus (SF) heights performed by midwives is the most widespread screening method for detection of SGA. However, the inefficiency of this method necessitates improved practices. Earlier start and more frequent SF measurements, which could be accomplished by self-administered measurements, might improve the ability to detect deviant growth. The present study was set up to evaluate whether pregnant women can reliably perform SF measurements by themselves. METHOD: Forty healthy women with singleton and ultrasound-dated pregnancies from 2 antenatal clinics in Uppsala, Sweden, were asked to perform 4 consecutive SF measurements once every week, from 20 to 25 weeks of gestation until delivery. The self-administered SF measurements were recorded and systematically compared with midwives' SF measurements. RESULTS: Thirty-three pregnant women performed self-administered SF measurements over a 14-week period (range: 1-21). The SF curves constructed from self-administered SF measurements had the same shape as previously constructed population-based reference curves. The variance for self-administered SF measurements was higher than that of the midwives. CONCLUSIONS: Pregnant women are capable of measuring SF heights by themselves, but with higher individual variance than midwives. Repeated measurements at each occasion can compensate for the higher variance. The main advantage of self-administered SF measurements is the opportunity to follow fetal growth earlier and more frequently.     

Avoidant/restrictive food intake disorder symptoms in children: Associations with child and family variables

This study sought to determine the frequency of possible cases of avoidant/restrictive food intake disorder (ARFID) in a Portuguese sample of school-aged children and to assess the associations with child’s internalizing problems, BMI z-score and body dissatisfaction, and parents’ eating habits, attitudes and practices. We assessed 330 children through child’s and parents’measures. Fifty-one (15.5%) children were possible cases of ARFID based on their symptom’s presentation. There were no association between sex and possible cases of ARFID, and no significant differences between possible cases of ARFID and nonpossible cases of ARFID regarding age. Lower BMI z-score and anxiety/depression were associated with possible cases of ARFID.     

Mutational spectrum of ATRX aberrations in neuroblastoma and associated patient and tumor characteristics

Neuroblastoma is the most common extracranial solid tumor in children. The chromatin remodeler ATRX is frequently mutated in high‐risk patients with a poor prognosis. Although many studies have reported ATRX aberrations and the associated clinical characteristics in neuroblastoma, a comprehensive overview is currently lacking. In this study, we extensively characterize the mutational spectrum of ATRX aberrations in neuroblastoma tumors reported in previous studies and present an overview of patient and tumor characteristics. We collected the data of a total of 127 neuroblastoma patients and three cell lines with ATRX aberrations originating from 20 papers. We subdivide the ATRX aberrations into nonsense, missense, and multiexon deletions (MEDs) and show that 68% of them are MEDs. Of these MEDs, 75% are predicted to be in‐frame. Furthermore, we identify a missense mutational hotspot region in the helicase domain. We also confirm that all three ATRX mutation types are more often identified in patients diagnosed at an older age, but still approximately 40% of the patients are aged 5 years or younger at diagnosis. Surprisingly, we found that 11q deletions are enriched in neuroblastomas with ATRX deletions compared to a reference cohort, but not in neuroblastomas with ATRX point mutations. Taken together, our data emphasizes a distinct ATRX mutation spectrum in neuroblastoma, which should be considered when studying molecular phenotypes and therapeutic strategies.