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  1. Teoh AN, Kaur S, Shafie SR, Mohd Shukri NH, Ahmad Bustami N, Takahashi M, et al.
    Front Nutr, 2022;9:1078086.
    PMID: 36687684 DOI: 10.3389/fnut.2022.1078086
    Chrononutrition has been suggested to have an entrainment effect on circadian rhythm which is crucial for metabolic health. Investigating how chrononutrition affects maternal circadian rhythm can shed light on its role during pregnancy. This study aims to determine chrononutrition characteristics of healthy primigravida during pregnancy and its association with melatonin and cortisol rhythm across gestation. A total of 70 healthy primigravidas were recruited from ten randomly selected government maternal and child clinics in Kuala Lumpur, Malaysia. During the second and third trimesters, chrononutrition characteristics including meal timing, frequency, eating window, breakfast skipping, and late-night eating were determined using a 3-day food record. Pregnant women provided salivary samples at five time-points over a 24 h period for melatonin and cortisol assay. Consistently across the second and third trimesters, both melatonin and cortisol showed a rhythmic change over the day. Melatonin levels displayed an increment toward the night whilst cortisol levels declined over the day. Majority observed a shorter eating window (≤12 h) during the second and third trimesters (66 and 55%, respectively). Results showed 23 and 28% skipped breakfast whereas 45 and 37% ate within 2 h pre-bedtime. During the third trimester, a longer eating window was associated with lower melatonin mean (β = -0.40, p = 0.006), peak (β = -0.42, p = 0.006), and AUCG (β = -0.44, p = 0.003). During both trimesters, a lower awakening cortisol level was observed in pregnant women who skipped breakfast (β = -0.33, p = 0.029; β = -0.29, p = 0.044). Only during the second trimester, breakfast-skipping was significantly associated with a greater cortisol amplitude (β = 0.43, p = 0.003). Findings suggest that certain chrononutrition components, particularly eating window and breakfast skipping have a significant influence on maternal melatonin and cortisol rhythm. Dietary intervention targeting these characteristics may be useful in maintaining maternal circadian rhythm.
  2. Ng CM, Kaur S, Kok EY, Chew WL, Takahashi M, Shibata S
    BMC Public Health, 2023 Sep 16;23(1):1803.
    PMID: 37716989 DOI: 10.1186/s12889-023-16655-y
    BACKGROUND: Psychological wellbeing during pregnancy is imperative for optimal maternal outcomes. The present study aimed to determine the association between sleep quality, light exposure at night, and psychological wellbeing in the 2nd and 3rd trimesters of pregnancy.

    METHODS: This prospective study was conducted in 9 randomly selected government maternity clinics in Kuala Lumpur, Malaysia. Healthy women aged 20-48 years old with single pregnancy were recruited using convenience sampling (n = 169). Sleep quality, light exposure at night, and psychological wellbeing were self-reported using the Pittsburgh Sleep Quality Index (PSQI), Harvard Light Exposure Assessment (H-LEA), and Depression, Anxiety, and Stress Scale (DASS-21) in the 2nd trimester and followed-up at the 3rd trimester.

    RESULTS: During the 2nd and 3rd trimesters of pregnancy, mild to severe symptoms of stress (10.7 and 11.3%), anxiety (42 and 44.3%), and depression (9.6 and 16.6%) were observed among the participants. Adjusted multiple linear regression revealed that poor sleep quality and higher light exposure at night were attributed to greater stress and depression symptoms in the 3rd trimester. Higher lux level exposed from 10 pm to 

  3. Teoh AN, Kaur S, Shafie SR, Shukri NHM, Bustami NA, Takahashi M, et al.
    BMC Pregnancy Childbirth, 2023 Jul 04;23(1):491.
    PMID: 37403031 DOI: 10.1186/s12884-023-05796-y
    Chrononutrition emerges as a novel approach to promote circadian alignment and metabolic health by means of time-of-the-day dietary intake. However, the relationship between maternal circadian rhythm and temporal dietary intake during pregnancy remains understudied. This study aimed to determine the change in melatonin levels in pregnant women across gestation and its association with temporal energy and macronutrient intake. This was a prospective cohort involving 70 healthy primigravidas. During the second and third trimesters, pregnant women provided salivary samples collected at 9:00, 15:00, 21:00, and 3:00 h over a 24 h day for melatonin assay. Data on chrononutrition characteristics were collected using a 3-day food record. Parameters derived from melatonin measurements including mean, amplitude, maximal level, area under the curve with respect to increase (AUCI), and area under the curve with respect to ground (AUCG) were computed. A rhythmic melatonin secretion over the day that remained stable across trimesters was observed among the pregnant women. There was no significant elevation in salivary melatonin levels as pregnancy advanced. In the second trimester, higher energy intake during 12:00-15:59 h and 19:00-06:59 h predicted a steeper melatonin AUCI (β=-0.32, p = 0.034) and higher AUCG (β = 0.26, p = 0.042), respectively. Macronutrient intake within 12:00-15:59 h was negatively associated with mean melatonin (Fat: β=-0.28, p = 0.041) and AUCG (Carbohydrate: β=-0.37, p = 0.003; Protein: β=-0.27, p = 0.036; Fat: β=-0.32, p = 0.014). As pregnant women progressed from the second to the third trimester, a flatter AUCI was associated with a reduced carbohydrate intake during 12:00-15:59 h (β=-0.40, p = 0.026). No significant association was detected during the third trimester. Our findings show that higher energy and macronutrient intakes particularly during 12:00-15:59 h and 19:00-06:59 h are associated with the disparities in maternal melatonin levels. Findings suggest the potential of time-based dietary approaches to entrain circadian rhythm in pregnant women.
  4. Lim SY, Ishiura H, Ramli N, Shibata S, Almansour MA, Tan AH, et al.
    Parkinsonism Relat Disord, 2020 05;74:25-27.
    PMID: 32289521 DOI: 10.1016/j.parkreldis.2020.03.025
    Two ethnic Chinese men with clinico-radiologic features of Fragile X-associated tremor-ataxia syndrome (FXTAS) were found on genetic testing to have neuronal intranuclear inclusion disease (NIID), highlighting that NIID should be considered in the differential diagnosis of FXTAS. NIID may also be much more common than FXTAS in certain Asian populations.
  5. Teoh AN, Kaur S, Mohd Shukri NH, Shafie SR, Ahmad Bustami N, Takahashi M, et al.
    Chronobiol Int, 2021 07;38(7):959-970.
    PMID: 33779445 DOI: 10.1080/07420528.2021.1902338
    Psychological distress during pregnancy may increase the risk of adverse maternal and infant outcomes. Past studies have demonstrated the association between circadian disturbances with psychological health. However, the roles of chronotype and social jetlag on psychological state during pregnancy are yet to be identified. We aimed to examine the psychological state in pregnant women and its relations to chronotype, social jetlag (SJL), sleep quality and cortisol rhythm. The current study included a subsample of participants from an ongoing cohort study. A total of 179 primigravidas (mean age 28.4 ± 4.0 years) were recruited. Chronotype and sleep quality during the second trimester were assessed using the Morning-Eveningness Questionnaire (MEQ) and Pittsburgh Sleep Quality Index (PSQI), respectively. SJL was calculated based on the difference between mid-sleep on workdays and free days. Psychological state of participants was evaluated using the Depression, Anxiety, and Stress Scale-21 (DASS-21). Subsamples (n = 70) provided salivary samples at 5 time points over a 24 h period during the second trimester for cortisol assay. A higher proportion of pregnant women experienced moderate to severe anxiety symptoms (n = 77, 43.0%), followed by depressive (n = 17, 9.5%) and stress (n = 14, 7.8%) symptoms. No association was observed between chronotype and psychological distress during pregnancy. There was no significant difference in cortisol rhythms in relation to psychological distress. SJL and sleep quality were significantly associated with stress symptoms among pregnant women in the second trimester. Poor sleep quality, particularly daytime dysfunction (β = 0.37, p = .006) and sleep disturbances (β = 0.23, p = .047), were significantly associated with psychological distress (depressive, anxiety and stress symptoms) during the second trimester. The findings suggest that sleep is a potential modifiable lifestyle factor that can be targeted to improve psychological health among pregnant women.
  6. Kaur S, Teoh AN, Shukri NHM, Shafie SR, Bustami NA, Takahashi M, et al.
    BMC Pregnancy Childbirth, 2020 Feb 11;20(1):96.
    PMID: 32046676 DOI: 10.1186/s12884-020-2797-2
    BACKGROUND: Circadian rhythm plays an important role as our internal body's clock that synchronizes behavior and physiology according to the external 24-h light-dark cycle. Past studies have associated disrupted circadian rhythm with higher risk of miscarriages, preterm birth and low birth weights. This paper described the protocol of a prospective cohort study which aims to determine the circadian rhythm in pregnant women, identify its association with maternal factors during pregnancy, gestational weight gain, birth and infant outcomes.

    METHODS: Ten government maternal and child health clinics in Kuala Lumpur, Malaysia will be randomly selected. Sample size of 438 first-trimester pregnant women will be followed-up until the birth of their infant. Salivary melatonin and cortisol concentration among subsample will be determined using enzyme-linked immunosorbent assay. Data on sleep quality, psychological distress and morningness/eveningness chronotype of pregnant women will be collected using validated questionnaires. Pedometer will be used to measure 5-day physical activity data. Total gestational weight gain will be determined at the end of pregnancy. Utilization of 3-day food record is to capture meal timing and nutrient intake. All measurements will be done in 2nd and 3rd trimester. Birth outcomes will be collected through clinic records and Centers for Disease Control and Prevention (CDC) Neonatal questionnaire. Infants will be followed-up at 6 and 12 months old to obtain anthropometric measurements.

    DISCUSSION: There is a growing recognition of the role of maternal circadian rhythm, which entrains fetal circadian rhythms that may subsequently have long-term health consequences. The present study will identify the effect of circadian rhythm on pregnancy outcomes and infant growth in the first year of life.

  7. Ishiura H, Shibata S, Yoshimura J, Suzuki Y, Qu W, Doi K, et al.
    Nat Genet, 2019 08;51(8):1222-1232.
    PMID: 31332380 DOI: 10.1038/s41588-019-0458-z
    Noncoding repeat expansions cause various neuromuscular diseases, including myotonic dystrophies, fragile X tremor/ataxia syndrome, some spinocerebellar ataxias, amyotrophic lateral sclerosis and benign adult familial myoclonic epilepsies. Inspired by the striking similarities in the clinical and neuroimaging findings between neuronal intranuclear inclusion disease (NIID) and fragile X tremor/ataxia syndrome caused by noncoding CGG repeat expansions in FMR1, we directly searched for repeat expansion mutations and identified noncoding CGG repeat expansions in NBPF19 (NOTCH2NLC) as the causative mutations for NIID. Further prompted by the similarities in the clinical and neuroimaging findings with NIID, we identified similar noncoding CGG repeat expansions in two other diseases: oculopharyngeal myopathy with leukoencephalopathy and oculopharyngodistal myopathy, in LOC642361/NUTM2B-AS1 and LRP12, respectively. These findings expand our knowledge of the clinical spectra of diseases caused by expansions of the same repeat motif, and further highlight how directly searching for expanded repeats can help identify mutations underlying diseases.
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