Maternal risk associated with the VACTERL association: A case-control study.

BACKGROUND: The VACTERL association (VACTERL) includes at least three of these congenital anomalies: vertebral, anal, cardiac, trachea-esophageal, renal, and limb anomalies. Assisted reproductive techniques (ART), pregestational diabetes mellitus, and chronic lower obstructive pulmonary disorders (CLOPD) have been associated with VACTERL. We aimed to replicate these findings and were interested in additional maternal risk factors. METHODS: A case-control study using self-administered questionnaires was performed including 142 VACTERL cases and 2,135 population-based healthy controls. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). RESULTS: Parents who used invasive ART had an increased risk of VACTERL in offspring (aOR 4.4 [95%CI 2.1-8.8]), whereas the increased risk for mothers with CLOPD could not be replicated. None of the case mothers had pregestational diabetes mellitus. Primiparity (1.5 [1.1-2.1]) and maternal pregestational overweight and obesity (1.8 [1.2-2.8] and 1.8 [1.0-3.4]) were associated with VACTERL. Consistent folic acid supplement use during the advised periconceptional period may reduce the risk of VACTERL (0.5 [0.3-1.0]). Maternal smoking resulted in an almost twofold increased risk of VACTERL. CONCLUSION: We identified invasive ART, primiparity, pregestational overweight and obesity, lack of folic acid supplement use, and smoking as risk factors for VACTERL.

No major role for periconceptional folic acid use and its interaction with the MTHFR C677T polymorphism in the etiology of congenital anorectal malformations.

BACKGROUND: Both genetic and nongenetic factors are suggested to be involved in the etiology of congenital anorectal malformations (ARM). Maternal periconceptional use of folic acid supplements were inconsistently suggested to play a role in the prevention of ARM. Therefore, we investigated independent associations and interactions of maternal periconceptional folic acid supplement use and the infant and maternal MTHFR (methylenetetrahydrofolate reductase) C677T polymorphisms with the risk of ARM and subgroups of ARM. METHODS: A case-control study was conducted among 371 nonsyndromic ARM cases and 714 population-based controls born between 1990 and 2012 using maternal questionnaires and DNA samples from mother and child. Cases were treated for ARM at departments of Pediatric Surgery of the Radboud university medical center, Sophia Children's Hospital-Erasmus MC Rotterdam, and the University Medical Center Groningen in The Netherlands and hospitals throughout Germany. RESULTS: No association with folic acid use was present (odds ratio = 1.1; 95% confidence interval: 0.8-1.4) for ARM as a group. Infant and maternal MTHFR C677T polymorphisms were weakly associated with isolated ARM in particular. Lack of folic acid supplement use in combination with infants or mothers carrying the MTHFR C677T polymorphism did not seem to increase the risk of ARM or subgroups of ARM. The relative excess risks due to interaction did not clearly indicate interaction on an additive scale either. CONCLUSION: This first study investigating interactions between periconceptional folic acid supplement use and infant and maternal MTHFR C677T polymorphisms in the etiology of ARM did not provide evidence for a role of this gene-environment interaction.

Fecal continence revisited: the anal external sphincter continence reflex.

BACKGROUND: None of the current theories on fecal incontinence can explain fecal continence adequately. OBJECTIVE: This study aims to evaluate the mechanism controlling fecal continence. DESIGN: Anal electrosensitivity, anorectal pressures, and rectal pressure volumetry tests were performed in 17 controls before and after superficial local anal anesthesia and in 6 controls before and after spinal anesthesia. The same tests were performed in 1 patient before and after injected local anal anesthesia and in 3 patients with spinal cord lesions at levels Th3 to L3. RESULTS: After superficial local anal anesthesia, anal electrosensitivity decreased, but basal anal pressure remained unaltered. Squeeze pressure decreased and rectal filling sensation levels remained. Local anesthesia reduced anal pressure recorded in the distal anal canal during progressive rectal filling. This was also the case, albeit more explicit, after the local anal anesthetic was injected. After spinal anesthesia, the anal canal became insensitive to electric stimulation, but basal and squeeze pressure values decreased substantially, and the increase in anal pressure during the balloon-retaining test disappeared completely. In the patients with spinal cord lesions, the external sphincter could not be squeezed on command, but during the balloon-retaining test, the anal sphincter did squeeze autonomously at more than 300 mmHg. LIMITATIONS: These were partially experimental measurements. The relevance of the found model in the daily clinical practice will have to be studied in a following study. CONCLUSIONS: Our results support the hypothesis that the component of fecal continence mediated by contraction of the external sphincter depends on a anal external sphincter continence reflex without involving the brain. Presumably, the afferent receptors of this reflex are contact receptors located superficially in the mucosa or submucosa of the distal anal canal. A nonfunctioning anal external sphincter continence reflex would, therefore, result in fecal incontinence (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A116).