The view of Hong Kong parents on secondary use of dried blood spots in newborn screening program.

BACKGROUND: Residual dried blood spots (rDBS) from newborn screening programmes represent a valuable resource for medical research, from basic sciences, through clinical to public health. In Hong Kong, there is no legislation for biobanking. Parents' view on the retention and use of residual newborn blood samples could be cultural-specific and is important to consider for biobanking of rDBS. OBJECTIVE: To study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents. METHODS: A mixed-method approach was used to study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents of children 0-3 years or expecting parents through focus groups (8 groups; 33 participants) and a survey (n = 1012, 85% mothers) designed with insights obtained from the focus groups. We used framework analysis to summarise the themes as supportive factors, concerns and critical arguments for retention and secondary use of rDBS from focus group discussion. We used multiple logistic regression to assess factors associated with support for retention and secondary use of rDBS in the survey. RESULTS: Both in focus groups and survey, majority of parents were not aware of the potential secondary use of rDBS. Overall secondary use of rDBS in medical research was well accepted by a large proportion of Hong Kong parents, even if all potential future research could not be specified in a broad consent. However parents were concerned about potential risks of biobanking rDBS including leaking of data and mis-use of genetic information. Parents wanted to be asked for permission before rDBS are stored and mainly did not accept an "opt-out" approach. The survey showed that parents born in mainland China, compared to Hong Kong born parents, had lower awareness of newborn screening but higher support in biobanking rDBS. Higher education was associated with support in rDBS biobanking only among fathers. CONCLUSION: Long-term storage and secondary use of rDBS from newborn screening for biomedical research and a broad consent for biobanking of rDBS are generally acceptable to Hong Kong parents given their autonomy is respected and their privacy is protected, highlighting the importance of an accountable governance and a transparent access policy for rDBS biobanks.

Effectiveness of a childbirth massage programme for labour pain relief in nulliparous pregnant women at term: a randomised controlled trial.

INTRODUCTION: The effect of massage for pain relief during labour has been controversial. This study investigated the efficacy of a programme combining intrapartum massage, controlled breathing, and visualisation for non-pharmacological pain relief during labour. METHODS: This randomised controlled trial was conducted in two public hospitals in Hong Kong. Participants were healthy low-risk nulliparous Chinese women ≥18 years old whose partners were available to learn massage technique. Recruitment was performed at 32 to 36 weeks of gestation; women were randomised to attend a 2-hour childbirth massage class at 36 weeks of gestation or to receive usual care. The primary outcome variable was the intrapartum use of epidural analgesia or intramuscular pethidine injection. RESULTS: In total, 233 and 246 women were randomised to the massage and control groups, respectively. The use of epidural analgesia or pethidine did not differ between the massage and control groups (12.0% vs 15.9%; P=0.226). Linear-by-linear analysis demonstrated a trend whereby fewer women used strong pharmacological pain relief in the massage group, and a greater proportion of women had analgesic-free labour (29.2% vs 21.5%; P=0.041). Cervical dilatation at the time of pethidine/epidural analgesia request was significantly greater in the massage group (3.8 ± 1.7 cm vs 2.3 ± 1.0 cm; P<0.001). CONCLUSION: The use of a massage programme appeared to modulate pain perception in labouring women, such that fewer women requested epidural analgesia and a shift was observed towards the use of weaker pain relief modalities; in particular, more women in the massage group were analgesic-free during labour.

The predictive value of cervical shear wave elastography in the outcome of labor induction.

INTRODUCTION: Bishop score, the traditional method to assess cervical condition, is not a promising predictive tool of the outcome of labor induction. As an objective assessment tool, many cervical ultrasound measurements have been proposed to represent the individual components of the Bishop score, but none of them can measure the cervical stiffness. Cervical shear wave elastography is a novel tool to assess the cervical stiffness quantitatively. MATERIAL AND METHODS: A total of 475 women who required labor induction were studied prospectively. Prior to routine digital assessment of the Bishop score, transvaginal sonographic measurement of cervical length, posterior cervical angle, angle of progression and shear wave elastography was performed. Shear wave elastography measurement was made at the inner, middle and outer regions of the cervix to assess homogeneity. Association of labor induction outcomes including the overall cesarean section and subgroups of cesarean section for failure to enter active phase, with cervical sonographic parameters and the Bishop score, were assessed using multivariate regression analyses. The predictive accuracy of the outcomes using models based on ultrasound measurement and the Bishop score was compared using the area under the receiver-operating characteristics curves. RESULTS: Among 475 women, 82 (17.3%) required cesarean section. Shear wave elasticity was significantly higher in the inner cervical region than in other regions, indicating a greater stiffness (P < 0.001). Both inner cervical shear wave elasticity and cervical length were independent predictors of overall cesarean section (respective adjusted odds ratio [95% CI] 1.338 [1.001-1.598] and 1.717 [1.077-1.663]) and cesarean section for failure to enter active phase (respective adjusted odds ratio [95% CI] 1.689 [1.234-2.311] and 2.556 [1.462-4.467]), after adjusting for other covariates. Outcome prediction models using inner cervical shear wave elasticity and cervical length, had increased area under curve compared with models using the Bishop score (0.888 vs 0.819, P = 0.009). CONCLUSIONS: The cervix is not a homogenous structure, with the inner cervix having the highest stiffness, which is an independent predictor of overall cesarean section, and specifically for those indicated because of failure to enter active phase. Models based on shear wave elastography and cervical length had higher predictive accuracy than models based on the Bishop score.

Correction to: In utero exposure to gestational diabetes and adiposity: does breastfeeding make a difference?

In the original version of this article, the Publisher incorrectly listed the affiliation of the author, G.M. Leung. The correct affiliation for this author should be: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

In utero exposure to gestational diabetes and adiposity: does breastfeeding make a difference?

BACKGROUND/OBJECTIVES: Short-term breastfeeding from mothers with gestational diabetes (GDM) may programme metabolism and increase offspring diabetes risk. We examined the association of in utero GDM exposure with adiposity from infancy to adolescence, and whether any association was modified by breastfeeding during early infancy. METHODS: In the prospective Chinese birth cohort "Children of 1997" (n = 7342, 88% follow-up rate), generalised estimate equations with multiple imputation were used to assess associations of in utero GDM exposure with age- and sex-specific body mass index (BMI) z-score during infancy (3 and 9 months), childhood (2- < 8 years) and adolescence (8-16 years), adjusted for sex, parity, maternal age, birth place, preeclampisa, smoking, and family socio-economic position. We also tested whether the associations differed by mode of infant feeding (always formula-fed, mixed, always breastfed) during the first three months of life. RESULTS: In utero GDM exposure (7.5%) was associated with a lower BMI z-score during infancy (-0.13, 95% confidence interval (CI) -0.22, -0.05) but higher BMI z-scores during childhood (0.14, 95% CI 0.03, 0.25) and adolescence (0.25 95% CI 0.11, 0.38). Breastfeeding for the first three months did not modify the association of in utero GDM status with subsequent BMI (all p values for interaction >0.4). CONCLUSIONS: In utero GDM exposure was associated with greater adiposity during childhood and adolescence. Breastfeeding in early infancy from mothers with GDM was not associated with greater adiposity in children and thus should still be encouraged.

Duration of puberty in preterm girls.

OBJECTIVES: Preterm birth is associated with altered pubertal timing, but the effect on pubertal duration has rarely been assessed. Here, we tested the hypothesis that preterm birth is associated with shorter duration of puberty among girls in Hong Kong where preterm birth has little social patterning. METHODS: In the population-representative Chinese birth cohort "Children of 1997", we used multivariable linear regression to assess the association of preterm status (≤36 completed gestational weeks, n = 170; term birth 37-42 gestational weeks, n = 3476) with duration of puberty, adjusted for parent's highest education, mother's place of birth, maternal smoking during pregnancy, gestational diabetes, preeclampsia, and mother's age of menarche. RESULTS: The mean duration from thelarche to menarche was 2.53 years. Preterm girls had a shorter duration from thelarche to menarche by 2.6 months, 95% confidence interval 0.5-4.7 months. Age of menarche did not differ by preterm status but preterm girls had later thelarche. Preterm birth was not associated with a shorter duration from pubarche to menarche. CONCLUSIONS: Preterm births may be associated with shorter duration of puberty from thelarche to menarche, possibly through effects of in utero estrogen exposure, the drivers of thelarche, or the drivers of pubertal duration/progression, with potential implications for subsequent risk of cardiovascular disease and hormonal cancers.

The Association of Infant Growth Patterns with Adiposity in Adolescence: Prospective Observations from Hong Kong's 'Children of 1997' Birth Cohort.

BACKGROUND: The role of infant growth in adiposity remains unclear. METHODS: We used multivariable linear regression, with inverse probability weighting and multiple imputation to account for loss to follow-up, in a population-representative Chinese birth cohort, 'Children of 1997' in Hong Kong, to examine, in terms births, the adjusted association of infant (birth to 12 months) weight growth trajectories with body mass index (BMI) (n = 6861, 88% follow-up), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) (n = 5398, 69% follow-up) at ∼ 14 years. RESULTS: Infant weight growth trajectories had graded associations with adolescent BMI and WHtR but not with WHR, such that compared with adolescents born light with slow infant growth, adolescents born heavy with fast infant growth had higher BMI z-score [0.60, 95% confidence interval (CI) 0.49, 0.70], higher WHtR z-score (0.17, 95% CI 0.08, 0.26) but similar WHR z-score (-0.02, 95% CI -0.11, 0.08), adjusted for sex, gestational age, parental education, parental BMI, parental height, and parental place of birth. CONCLUSIONS: Varying associations of infant growth with different adiposity measures suggest a complex role of infant growth in long-term health, perhaps because infant growth, or its underlying drivers, influences build and body composition as well as adiposity.

Are the 2006 World Health Organization standards for infant growth applicable to Hong Kong Chinese? Universalistic standards or epidemiological transition stage-specific norms.

1. Parental socio-economic status was positively associated with length and body mass index of Hong Kong Chinese infants at 9 months. 2. Maternal smoking in pregnancy was negatively associated with infant length at 9 months. 3. Some of the World Health Organization (WHO) criteria for an optimal nurturing environment contributed positively to growth. At 36 months, Hong Kong Chinese infants were generally shorter and fatter than the WHO growth references.

Small for gestational age and age at puberty: evidence from Hong Kong's "Children of 1997" birth cohort.

The predictive-adaptive response paradigm postulates that slow fetal growth advances puberty as a life-history strategy for reproductive success, when constraints on postnatal growth are minimal. The authors examined the association of birth weight for gestational age and small for gestational age (SGA) status (birth weight for gestational age <10th percentile, 6.9%) with clinically assessed age at onset of Tanner stage II in a non-Western developed population using interval-censored regression in 7,366 children (89% follow-up) from a population-representative Chinese birth cohort, "Children of 1997" in Hong Kong. Neither SGA status nor birth weight z score for gestational age was associated with age at onset of puberty, adjusted for sex, mother's place of birth, parental height, income, and parental education. Greater childhood height and linear growth were associated with younger age at onset of puberty. SGA status was associated with earlier puberty after adjustment for childhood height (time ratio = 0.984, 95% confidence interval: 0.972, 0.995) but later puberty after adjustment for linear growth (time ratio = 1.017, 95% confidence interval: 1.005, 1.030). In this developed city of China, SGA status was not associated with timing of puberty. However, the observation may be contextually specific depending on how other attributes, such as childhood growth, differ between SGA and other children.

The role of vitamin C in pneumonia and COVID-19 infection in adults with European ancestry: a Mendelian randomisation study.

BACKGROUND: High dose vitamin C infusion has been proposed to treat critically ill patients, including patients with pneumonia and severe COVID-19. However, trials have shown mixed findings. Here we assessed the unconfounded associations of vitamin C with COVID-19 and pneumonia using the Mendelian randomisation approach. METHODS: This is a separate-sample Mendelian randomisation study using publicly available data. We applied single nucleotide polymorphisms (SNPs) that were associated with plasma vitamin C, in a recent genome-wide association study (GWAS) as genetic instruments to the GWAS of severe COVID-19, COVID-19 hospitalisation and any infection in the COVID-19 host genetics initiative and the GWAS of pneumonia in the UK Biobank, to assess whether people with genetically predicted higher levels of plasma vitamin C had lower risk of severe COVID-19 and pneumonia. RESULTS: Genetically predicted circulating levels of vitamin C was not associated with susceptibility to severe COVID-19, COVID-19 hospitalisation, any COVID-19 infection nor pneumonia. Similar results were obtained when a weighted median and MR-Egger methods were used. CONCLUSIONS: Mendelian randomisation analysis provided little evidence for an association of genetically predicted circulating levels of vitamin C with COVID-19 or pneumonia and thus our findings provided little support to the use of vitamin C in prevention and treatment in these patients, unless high dose vitamin C infusion has therapeutic effects via different biological pathways.

Methylenetetrahydrofolate reductase genotypes and haplotypes associated with susceptibility to colorectal cancer in an eastern Chinese Han population.

Methylenetetrahydrofolate reductase (MTHFR) plays an important role in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, C677T and A1298C have been associated with several diseases, including cancer. We made a case-control study to analyze a possible association of MTHFR gene polymorphisms C677T and A1298C with risk for colorectal cancer in an eastern Chinese Han population of 137 patients with a confirmed histopathological diagnosis of CRC and 145 age- and gender-matched controls with no history of cancer. DNA was isolated from peripheral blood samples and the genotypes were determined by PCR-RFLP. The concentrations of folate in plasma were measured by chemiluminescence immunoassay. The MTHFR 677TT genotype had a protective effect against colorectal cancer, with an odds ratio (OR) = 0.467 (95% confidence interval (CI) = 0.225-0.966). The 1298CC genotype was significantly correlated with a reduced risk of colorectal cancer (OR = 0.192; 95%CI = 0.040-0.916). Compared with the MTHFR 677CC and MTHFR 1298 AA genotypes, for individuals who carried both MTHFR 677CC and 1298CC genotypes, the OR of colorectal cancer was 0.103 (95%CI = 0.012-0.900); among individuals who carried both MTHFR 677TT and 1298AC genotypes, the OR for risk of colorectal cancer was 0.169 (95%CI = 0.044-0.654). MTHFR 677TT+CT genotypes had a significantly lower plasma folate concentration than those with the MTHFR 677CC genotype. MTHFR 1298AC+CC genotypes had a lower plasma folate concentration than those with the MTHFR 1298AA genotype (P < 0.05). In conclusion, subjects with the MTHFR 677TT and MTHFR 1298CC genotypes appeared to have a significantly lower risk for colorectal cancer. MTHFR haplotypes 677CC/1298CC and 677TT/1298AC were less common in cases than in controls. These haplotypes, when compared to the most common haplotype 677CC/1298AA, were associated with a decreased risk for colorectal cancer. We conclude that plasma folate level is influenced by MTHFR genotypes.

Infant growth during the first year of life and subsequent hospitalization to 8 years of age.

BACKGROUND: There is accumulating evidence that rapid infant growth is associated with subsequent metabolic risk, but less investigation of potential benefits. We tested the life history trade-off hypothesis that rapid infant growth is associated with lower risk of serious childhood morbidity (in particular, infection) proxied by hospital admission. METHODS: We studied term births (n = 7833, 94% follow-up) from a Chinese birth cohort, "Children of 1997," comprising 88% of births in Hong Kong in April and May 1997. We used multivariable negative binomial regression to examine the association of growth trajectory (5 categories) from birth to 12 months with subsequent hospital admissions until the child's 8th birthday. Potential confounders included sex, gestational age, parental education, type of birth hospital, infant feeding, and the presence of congenital disease. RESULTS: Infants with the slowest growth trajectory (smallest birth weight and slowest weight gain) were more likely to be hospitalized between 1 and 8 years of age-particularly for noninfectious illnesses. Infants in the 4 faster growth trajectories differed little in their risk of hospitalization. Adjusted incident rate ratios of hospitalization for infectious diseases were 0.93 (95% confidence interval = 0.81-1.06), 0.97 (0.85-1.12), 0.91 (0.78-1.06), and 0.92 (0.79-1.08) for the 4 faster growth trajectories compared with the slowest. Results were similar when growth was assessed as change in weight-for-age z-score. CONCLUSION: Fast infant growth does not protect against serious infectious morbidity, but low birth weight infants born with slow growth are more vulnerable to serious morbidity, either as a consequence of poor growth or as a parallel marker of underlying health state. Whether maximum growth rates are ideal should be considered, as should the effects of infant over-nutrition.

Short- and medium-term outcomes of accelerated infant growth in a Hong Kong Chinese birth cohort.

1. In a large, population representative,Chinese birth cohort, higher birth weight and rapid growth, particularly at 0-3 months, were associated with higher body mass index (BMI) at 7 years. 2. Boys born heavy who had grown fast had the highest BMI, but rapid growth had the largest impact in lighter-born boys. 3. Rapid growth at 0-3 months or 3-12 months was not associated with a compensatory lower risk of serious infectious morbidity. 4. The ability to grow fast may be an embodiment of good health status, rather than fast growth being causally protective.

How OSA Evolves From Childhood to Young Adulthood: Natural History From a 10-Year Follow-up Study.

BACKGROUND: Understanding the natural history of childhood OSA can help to determine disease prognosis and to guide risk stratification and management strategies. METHODS: To evaluate the natural history of childhood OSA and factors associated with spontaneous remission and persistent and incident OSA from childhood to late adolescence/early adulthood, a longitudinal analysis of a prospective community-based cohort was designed. Subjects from a cohort established for an OSA prevalence study were invited to participate in this 10-year follow-up study. RESULTS: Two hundred and forty-three participants (59% male) took part, and their mean age was 9.8 (SD, ± 1.8) and 20.2 (SD, ± 1.9) years at baseline and follow-up, respectively. The mean follow-up duration was 10.4 (SD, ± 1.1) years. Associations between baseline and follow-up log-transformed obstructive apnea-hypopnea index (OAHI) differed by age; a significant positive association was observed only among participants aged 10 years or older at baseline. Overall polysomnographic remission rate (with OAHI < 1 event/h at follow-up) of childhood OSA was 30%, and 69% had an OAHI < 5 events/h at follow-up. Complete remission of OSA was associated with female sex. Incidence of adolescent/adult OSA with an OAHI ≥ 5 events/h at follow-up was 22%. Male sex and higher baseline BMI z score were associated with incident OSA. CONCLUSIONS: A proportion of children with OSA, particularly female children, had complete resolution during transition to late adolescence or early adulthood. Childhood and adolescent OSA are distinct entities, with the latter more likely to persist into adulthood. Obesity and male sex are consistent key risk factors for incident OSA.

Breastfeeding in Infancy and Lipid Profile in Adolescence.

OBJECTIVES: Breast milk has higher cholesterol than formula. Infants who are breastfed have different cholesterol synthesis and metabolism in infancy than infants who are formula fed. Little is known as to whether breastfeeding is associated with subsequent lipid profile, independent of adiposity. We assessed the association of breastfeeding in early infancy with lipid profile and adiposity at ∼17.5 years in a setting where exclusive breastfeeding is not associated with higher socioeconomic position. METHODS: We used multivariable linear regression with multiple imputation and inverse probability weighting to examine the associations of contemporaneously reported feeding in the first 3 months of life (exclusive breastfeeding [7.5%], mixed feeding [40%], or always formula feeding [52%]) with lipids and adiposity at ∼17.5 years in 3261 participants in the Hong Kong Chinese birth cohort Children of 1997, adjusting for sex, birth weight, gestational weeks, parity, pregnancy characteristics, parents' highest education, mother's place of birth, and age at follow-up. RESULTS: Exclusive breastfeeding, but not mixed feeding at 0 to 3 months, compared with formula feeding was associated with lower total cholesterol and low-density lipoprotein cholesterol but not with high-density lipoprotein cholesterol at ∼17.5 years. BMI and fat percentage measured by bioimpedance did not differ by type of infant feeding. CONCLUSIONS: Exclusive breastfeeding in early infancy may promote a healthier lipid profile in late adolescence through mechanisms unrelated to adiposity, implicating its potential long-term benefits for cardiovascular health.

New approaches to obtaining individual peak height velocity and age at peak height velocity from the SITAR model.

OBJECTIVE: We compared three methods for estimating the individual peak height velocity (PHV) and age at peak height velocity (APHV) from the SuperImposition by Translation and Rotation (SITAR) model. METHODS: We fitted the SITAR model using simulated data and heights of 12 girls from the Chard Growth Study and obtained individual PHVs and APHVs from three methods: the model method, the quadratic function method and the numerical method, which are available in our newly developed R package"iapvbs". The mean, interquartile range, range of biases in estimated APHV and PHV as well as the rates of warning and unreasonable cases, i.e. estimated APHVs being outside the range of age measurements, from the three methods were presented and compared. RESULTS: When the growth curves of all individuals were well fitted by the SITAR model, all three methods estimated individual APHVs with similarly small biases, with a few unreasonable cases (0.16%) observed when the model method was used while more computation time required for the numerical method. When the growth curves of some individuals were not very well fitted, the model method generated more unreasonable individual APHV (8.15%) and more bias in PHV and APHV, compared to those estimated by the numerical method and quadratic function method. In line with the observations from the simulated data, the real data analysis demonstrated that the numerical method generated more reliable PHV and APHV for individuals with growth curve not well fitted by the SITAR model. CONCLUSION: The performance of different methods estimating individual APHV depends largely on how well the growth curves are fitted by the SITAR model. The quadratic function method is more superior when growth curves of all individuals are well fitted by the SITAR model; otherwise, the numerical method should be adopted for getting most robust estimates of PHV and APHV. The model method generates unreasonable APHV estimates, particularly when the growth curves are not well fitted.