Implications of prenatal ultrasound screening in the incidence of major genitourinary malformations.

PURPOSE: During the last 3 decades infant mortality has decreased nearly 50%. While neonatal intensive care deserves much of the credit, the recent increase in prenatal ultrasound from 33% of pregnancies in 1980 to 78% in 1987 has improved early detection. We evaluate the impact of prenatal ultrasound on major genitourinary malformations. MATERIALS AND METHODS: Data obtained from the Malformations Surveillance Program at Brigham and Women's Hospital between 1974 and 1994 tracked 163,431 pregnancies and termination rates of fetuses with spina bifida, bladder exstrophy, the prune belly syndrome and posterior urethral valves. RESULTS: Hospital data revealed that pregnancy was electively terminated due to spina bifida in 65% of cases, posterior urethral valves in 46%, the prune belly syndrome in 31% and exstrophy in 25%. CONCLUSIONS: Clearly, surveillance programs and improved accuracy of prenatal ultrasound have allowed early diagnosis of major genitourinary malformations. Many factors influence decision making in these affected fetal cases, including the financial and emotional impact of these major anomalies during lifetime. Future societal decisions and reduction in these anomalies may influence our training programs, manpower needs, medical facility requirements and character of our practices. These findings may have significant implications in the field of pediatric urology.

Heterotaxy: associated conditions and hospital-based prevalence in newborns.

PURPOSE: To provide insight into the possible etiology and prevalence of heterotaxy, we studied conditions associated with heterotaxy in a consecutive hospital population of newborns. METHODS: From 1972 to March, 1999 (except February 16, 1972 to December 31, 1978), 58 cases of heterotaxy were ascertained from a cohort of 201,084 births in the ongoing Active Malformation Surveillance Program at the Brigham and Women's Hospital. This registry includes livebirths, stillbirths, and elective abortions. Prevalence among nontransfers (i.e., patients whose mothers had planned delivery at this hospital) was calculated as approximately 1 per 10,000 total births (20 of 201,084). RESULTS: We analyzed a total of 58 patients consisting of 20 (34%) nontransfers and 38 (66%) transfers. Patients were categorized by spleen status as having asplenia (7 nontransfers, 25 total), polysplenia (8, 20), right spleen (4, 11), normal left (0, 1), and unknown (1, 0). Among the 20 nontransfer and 59 total heterotaxy patients, the following associated medical conditions were present: chromosome abnormality (1 nontransfer, 2 total), suspected Mendelian or chromosome microdeletion disorder (1 nontransfer, 6 total), and maternal insulin-dependent diabetes mellitus (1 nontransfer, 2 total). There were 6 twins (1 member each from 6 twin pairs including 1 dizygous, 4 monozygous, 1 conjoined; 2 were nontransfers). An associated condition occurred in 5 (25%) nontransfer and 16 (28%) total patients, or among 10 of 53 singleton births (19%). CONCLUSIONS: Although most cases of heterotaxy in this series were sporadic events, an associated condition was present in about one-fourth of the cases. Not all of these conditions would be considered causative etiologies. Based on this small series alone, maternal insulin-dependent diabetes cannot be viewed as a risk factor for heterotaxy. However, the specific association of diabetes with polysplenia with/without left atrial isomerism is noteworthy, and adds weight to animal and epidemiologic case-control data.

Synthesis of propionate motifs: diastereoselective tandem reactions involving anionic and free radical based processes.

Reported herein is a strategy employing a Mukaiyama reaction in tandem with a hydrogen transfer reaction for the elaboration of propionate motifs. The nature of the protecting groups on the chiral beta-alkoxy aldehyde and the type of Lewis acid used are varied to modulate the stereochemical outcome of the tandem reactions. The mode of complexation is thus controlled (monodentate or chelate) for the Mukaiyama reaction to give access to either syn or anti aldol products, precursors of the free radical reduction reaction. The endocyclic effect is subsequently capitalized upon to control the hydrogen transfer step so that the syn-reduced product may be achieved. Proceeding with excellent yield and diastereoselectivity, the synthetic sequence proposed gives access to syn-syn and syn-anti propionate motifs. Also considered is a complementary approach using a chelation-controlled Mukaiyama reaction in tandem with a free radical allylation reaction under the control of the endocyclic effect that leads to the anti-anti product.