BACKGROUND: An increased prevalence of cleft lip and/or palate (CL/P), a major congenital anomaly, has been observed in the offspring of women with elevated body mass index (BMI) before pregnancy. Likewise, gestational comorbidities, such as hypertension and diabetes mellitus, also increase the risk of CL/P; however, the risk linked to the coexistence of these conditions in women with higher BMI on birth prevalence of CL/P remains unclear. This study focused on the combined effects of a high BMI before pregnancy and gestational comorbidities on the birth prevalence of CL/P. METHODS: Among 98,373 live births from the Japan Environment and Children's Study (JECS), a nationwide birth cohort, 255 mothers of infants with CL/P (74, 112, and 69 infants born with cleft lip, cleft lip and palate, and isolated cleft palate, respectively) were included in the analyses. The association of CL/P birth prevalence with pre-pregnancy BMI and gestational comorbidities (hypertension and diabetes) was examined using multivariate logistic regression analyses after multiple imputations, with adjustments for several maternal (age at delivery, smoking habits, and alcohol intake) and child-related (sex and prevalence of other congenital diseases) variables, obtained through medical record transcriptions and self-reports on JECS transcription forms. RESULTS: Higher prevalence rates of overweight, gestational hypertension, and gestational diabetes mellitus were found in mothers of infants with CL/P (16.1%, 6.3%, and 4.7%, respectively) than in the control group (10.4%, 3.1%, and 3.1%, respectively). The odds ratio [95% confidence interval] for childbirth with CL/P was increased in mothers with high BMI before pregnancy (1.58 [1.11-2.24]). Furthermore, gestational hypertension and diabetes coexisting with high BMI additionally increased the odds ratios for childbirth with CL/P (2.91 [1.28-6.61] and 2.12 [0.87-5.19], respectively). CONCLUSION High maternal BMI, particularly when accompanied by gestational hypertension, was significantly associated with an increased prevalence of childbirth with CL/P.
Humans ; Female ; Cleft Lip/etiology* ; Cleft Palate/etiology* ; Pregnancy ; Japan/epidemiology* ; Prevalence ; Body Mass Index ; Adult ; Male ; Infant, Newborn ; Comorbidity ; Diabetes, Gestational/epidemiology* ; Risk Factors ; Young Adult ; Birth Cohort

The purpose of the present study was to investigate how the effects of high-fat diet feeding on the skeletal muscle persisted during aging using mice. Post-weaned male mice were fed a high-fat diet between 1- and 3-mo-old followed by return to supply a normal diet until 13-mo-old. Monthly physical tests demonstrated that age-related glucose intolerance that was generally developed after 10-mo-old in the control mice was significantly improved in mice fed a high-fat diet. Interestingly, mRNA expressions of Pdk4 , Ucp3, and Zmynd17 were up-regulated by high-fat feeding and persisted in the tibialis anterior muscle until 13-mo-old. At Pdk4 and Ucp3 loci, enhanced distributions of active histone modifications were noted in the high-fat-fed mice at 13-mo-old. In contrast, age-related accumulation of histone variant H3.3 at these loci was suppressed. These results indicated that epigenetic modifications caused by early nutrition mediated the changes in skeletal muscle gene expression during aging.