The SLC26A4 c.706C>G (p.Leu236Val) Variant is a Frequent Cause of Hearing Impairment in Filipino Cochlear Implantees.

HYPOTHESIS: Variants in SLC26A4 are an important cause of congenital hearing impairment in the Philippines. BACKGROUND: Cochlear implantation is a standard rehabilitation option for congenital hearing impairment worldwide, but places a huge cost burden in lower-income countries. The study of risk factors such as genetic variants that may help determine genetic etiology of hearing loss and also predict cochlear implant outcomes is therefore beneficial. METHODS: DNA samples from 29 GJB2-negative Filipino cochlear implantees were Sanger-sequenced for the coding exons of SLC26A4. Exome sequencing was performed to confirm results. RESULTS: Four cochlear implantees with bilaterally enlarged vestibular aqueducts (EVA) were homozygous for the pathogenic SLC26A4 c.706C>G (p.Leu236Val) variant, which has a minor allele frequency of 0.0015 in Filipino controls. In patients with the SLC26A4 variant there was no association between cochlear implant outcome and age at implantation or duration of implant. There was also no association between the occurrence of the SLC26A4 variant and postsurgical audiometric thresholds and parents' evaluation of aural/oral performance of children (PEACH) scores. On the other hand, the SLC26A4 variant increased presurgical median audiometric thresholds (p = 0.01), particularly at 500 to 2000 Hz. CONCLUSION: The SLC26A4 c.706C>G (p.Leu236Val) variant is a frequent cause of congenital hearing impairment in Filipinos and is associated with bilateral EVA and increased presurgical audiometric thresholds, but does not adversely affect post-implant outcomes.

Maternal metabolic adaptations to pregnancy among young women in Cebu, Philippines.

OBJECTIVES: Evidence that fetal development has long-term impacts on health has increased interest in maternal-fetal nutrient exchange. Although maternal metabolism is known to change during gestation to accommodate fetal nutrient demands, little is known about these modifications outside of a Western, clinical context. This study characterizes maternal metabolic adaptations to pregnancy, and their associations with offspring birth weight (BW), among women living in the Philippines. METHODS: Fasting glucose, triglycerides, insulin, leptin, and adiponectin were assessed in 808 participants in the Cebu Longitudinal Health and Nutrition Survey (Metropolitan Cebu, Philippines). Cross-sectional relationships between metabolites and hormones and gestational and lactational status were evaluated. Among the subset of currently pregnant women, associations between maternal glucose and triglycerides and offspring BW were also examined. RESULTS: Women in their second and third trimesters had significantly lower fasting glucose and adiponectin compared to nulliparous women, and leptin levels and triglyceride levels were notably higher late in pregnancy (all P < .05). Among pregnant women, fasting glucose was a positive predictor of offspring BW, but only in males (P = .012, R2 = .28). Hormones and metabolites in post-partum women trend back toward levels found in nulliparous women, with some differences by breastfeeding status. CONCLUSIONS: We find evidence for marked changes in maternal lipid and carbohydrate metabolism during pregnancy, consistent with known adaptations to support fetal growth. The finding of sex-specific relationships between maternal glucose and offspring BW adds to evidence for greater impacts of the maternal-gestational environment on biology and health in male offspring.

Functional limitation trajectories and their determinants among women in the Philippines.

BACKGROUND: Limited evidence exists regarding how functional limitation patterns of women in developing countries unfold through midlife and into old age, a critical period during which the tendency to develop severe problems is fomented. OBJECTIVE: Functional limitation prevalence and patterns through midlife into early old age, and their determinants, are examined among women in the Philippines. METHODS: Data from the Cebu Longitudinal Health and Nutrition Study are monitored from 1994 to 2015. Patterns are categorized using group-based trajectory modeling. Predictors of group membership are modeled. RESULTS: About half responding to all survey waves report functional limitation at least once over the study period. Movements in and out of functional limitation states are common. Between age 30 and 70, trajectories are categorized into four groups: 1) robust, 2) late onset, 3) early onset, and 4) recovery. Being married, living in a nuclear household, higher successful birth ratio, and higher education associate with favorable trajectories. More births, higher age at first birth, wealth, and urbanicity associate with less favorable trajectories. CONCLUSION: Many possible routes into and out of functional limitation exist. The manifold patterns can be grouped into common trajectories. A number of earlier life characteristics associate with these trajectories. CONTRIBUTION: This is the first analysis to ascertain common functional limitation trajectories and earlier life predictors among women as they age in a high fertility developing country setting. Recognizing these is an important step toward understanding global health given aging of the population and the likelihood of functional problems developing in women as they move into old age.