Characteristics and outcomes of SARS-CoV-2 positivity in neonates born to mothers with COVID-19 in Klang Valley, Malaysia: a retrospective observational study.

Objective: The aim of this study was to analyze the clinical characteristics of neonates born to mothers with coronavirus disease 2019 (COVID-19), along with the incidence and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) positivity in Klang Valley, Malaysia. Methods: The clinical records of all neonates born to mothers with COVID-19 who were admitted to Sungai Buloh Hospital, Selangor, Malaysia from October 1, 2020 to September 30, 2021 were reviewed retrospectively. Data collected included demographic details and the incidence, risk factors, and clinical outcomes of neonates with SARS-CoV-2 positivity. Results: A total of 766 neonates from 753 mothers with COVID-19 were included. Overall, 23 (3%) neonates tested positive by nasopharyngeal swab SARS-CoV-2 PCR taken within the first 8 days of life. There were three (0.4%) confirmed and four (0.5%) probable neonatal infections acquired intrapartum, seven (0.9%) confirmed neonatal infections acquired postpartum, and nine (1.2%) cases that did not fit within the classification. The rate of preterm delivery was 25% among all neonates born to mothers with COVID-19 and 39.1% among SARS-CoV-2-positive neonates. Of the SARS-CoV-2-positive neonates, 43.5% required ventilatory support. Factors identified to have a significant association with neonate SARS-CoV-2 positivity included maternal antepartum hemorrhage (odds ratio (OR) 7.33, P = 0.014), place of delivery in a non-designated COVID-19 center (OR 7.64, P < 0.001), exposure to the mother post-delivery (OR 4.13, P = 0.014), and a higher 5-minute Apgar score (score 6-10; OR 0.20, P = 0.0037). Conclusions: This study identified a risk of SARS-CoV-2 transmission from mothers with COVID-19 to their offspring, with infection acquired predominantly postpartum. A higher incidence of preterm delivery and ventilatory support were observed among SARS-CoV-2-positive neonates.

The association of maternal gestational hyperglycemia with breastfeeding duration and markers of milk production.

BACKGROUND: Previous studies focusing on the association between gestational diabetes and breastfeeding duration have been inconclusive. OBJECTIVES: We aimed to determine whether maternal gestational hyperglycemia is associated with the duration of breastfeeding and the concentrations of markers linked to breastmilk production. METHODS: Data from the prospective, multiethnic Growing Up in Singapore Towards Healthy Outcomes study were used to assess the association of fasting plasma glucose (FPG) and 2-h postglucose challenge (2hPG) measured at 26-28 wk of gestation with duration of breastfeeding and concentrations of protein, lactose, citrate, sodium, potassium, and zinc in breastmilk 3 wk postpartum. RESULTS: Of the 1035 participants, 5.2% and 9.5% had elevated FPG and 2hPG, respectively, consistent with a diagnosis of gestational diabetes mellitus based on International Association of Diabetes and Pregnancy Study Groups criteria. FPG ≥5.1 mmol/L was associated with a crude reduction in median breastfeeding duration of 2.3 mo. In a model adjusted for maternal prepregnancy BMI and intention to breastfeed, FPG ≥5.1 mmol/L predicted earlier termination of any breastfeeding (adjusted HR: 1.47; 95% CI: 1.04, 2.08) but not full breastfeeding (adjusted HR: 1.08; 0.76, 1.55). 2hPG ≥8.5 mmol/L was not significantly associated with the durations of any (adjusted HR: 0.86; 95% CI: 0.62, 1.19) or full (adjusted HR: 0.85; 95% CI: 0.62, 1.18) breastfeeding. Maternal FPG was significantly and positively associated with breastmilk sodium (adjusted coefficient: 1.28; 95% CI: 1.08, 1.51) and sodium-to-potassium ratio (adjusted coefficient: 1.29; 95% CI: 1.08, 1.54) but not with other measured breastmilk components. CONCLUSIONS: Women with FPG ≥5.1 mmol/L during pregnancy breastfeed for a shorter duration. Future work involving measurement of milk production is needed to determine whether low milk production predicts breastfeeding duration among women with elevated FPG. This trial was registered at www.clinicaltrials.gov as NCT01174875.

Breastfeeding Duration and Development of Dysglycemia in Women Who Had Gestational Diabetes Mellitus: Evidence from the GUSTO Cohort Study.

(1) Background: Breastfeeding has been shown to support glucose homeostasis in women after a pregnancy complicated by gestational diabetes mellitus (GDM) and is potentially effective at reducing long-term diabetes risk. (2) Methods: Data from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study were analyzed to understand the influence of breastfeeding duration on long-term dysglycemia (prediabetes and diabetes) risk in women who had GDM in the index pregnancy. GDM and dysglycemia four to seven years postpartum were determined by the oral glucose tolerance test (OGTT). A Poisson regression model with a robust error variance was used to estimate incidence rate ratios (IRRs) for dysglycemia four to seven years post-delivery according to groupings of the duration of any breastfeeding (<1, ≥1 to <6, and ≥6 months). (3) Results: Women who had GDM during the index pregnancy and complete breastfeeding information and OGTT four to seven years postpartum were included in this study (n = 116). Fifty-one women (44%) had postpartum dysglycemia. Unadjusted IRRs showed an inverse association between dysglycemia risk and ≥1 month to <6 months (IRR 0.91; 95% confidence interval [CI] 0.57, 1.43; p = 0.68) and ≥6 months (IRR 0.50; 95% CI 0.27, 0.91; p = 0.02) breastfeeding compared to <1 month of any breastfeeding. After adjusting for key confounders, the IRR for the ≥6 months group remained significant (IRR 0.42; 95% CI 0.22, 0.80; p = 0.008). (4) Conclusions: Our results suggest that any breastfeeding of six months or longer may reduce long-term dysglycemia risk in women with a history of GDM in an Asian setting. Breastfeeding has benefits for mothers beyond weight loss, particularly for those with GDM.

Evaluation of the Ages and Stages Questionnaire (ASQ 3) as a developmental screener at 9, 18, and 24 months.

BACKGROUND: Without the use of standardized screening tools, only 30% of the estimated 5-15% of children with developmental delay can be identified, potentially delaying intervention. AIM: 1)To evaluate the ASQ-3's reliability and validity at 9, 18, and 24 months and to compare the results with normative USA data. 2)To determine the risk factors for a screen positive result, which requires further evaluation. METHODS: Study of 649 low-risk children was part of a larger longitudinal cohort study, the GUSTO project. Socio-demographic and ASQ3 data were analyzed to estimate reliability, validity, mean ASQ scores, and cut-off scores. RESULTS: ASQ-3 showed an acceptable to good internal consistency (0.49-0.83) and a medium level of correlations (0.22-0.59) between the five domains but differed significantly compared to normative USA data. Using local cut-off scores, 12.6-13.6% of the cohort had a positive screen in ≥ 1 domain at 9, 18, or 24 months. ASQ-3 screening categorization was consistent, with only 3-11% of children showing change in categorization longitudinally. On regression, lower family income (OR 3.3-9.42) and maternal education (OR2.65-3.03) were predictive of a positive screen across domains and age intervals. INTERPRETATION: ASQ-3 is a useful, valid screening tool in Singapore. Further research is needed to investigate item functioning and to assess its concurrent validity with a criterion standard tool for culturally sensitive developmental screening.

Is breastfeeding associated with later child eating behaviours?

Individual differences in children's eating behaviours emerge early. We examined the relationship between breastfeeding exposure and subsequent eating behaviours among children from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Children (n = 970) were grouped according to their breastfeeding exposure: high (full breastfeeding ≥ 4 months with continued breastfeeding ≥ 6 months), low (any breastfeeding < 3 months or no breastfeeding) and intermediate (between low and high breastfeeding categories). Aspects of eating behaviour from ages 15 months to 6 years were captured using a combination of maternal reports (Child Eating Behaviour Questionnaire; Infant Feeding Questionnaire; Preschooler Feeding Questionnaire) and laboratory-based measures of meal size, oral processing behaviours (e.g. average eating speed and bite size) and tendency to eat in the absence of hunger. Most children had low (44%) or intermediate (44%) breastfeeding exposure; only 12% had high exposure. After adjusting for confounders, multivariable linear regression analyses indicated the high (but not intermediate) breastfeeding group was associated with significantly lower reported food fussiness at 3 years compared to low breastfeeding group (-0.38 [-0.70, -0.06]), with similar but non-significant trends observed at 6 years (-0.27 [-0.66, 0.11]). At 3 years, mothers in the high breastfeeding group also reported the least difficulty in child feeding compared to low breastfeeding group (-0.22 [-0.43, -0.01]). However, high breastfeeding was not associated with any other maternal-reports of child feeding or eating behaviours, and no significant associations were observed between breastfeeding exposure and any of the laboratory measures of eating behaviour at any of the time points. These results do not strongly support the view that increased breastfeeding exposure alone has lasting and consistent associations with eating behaviours in early childhood.

Direct vs. Expressed Breast Milk Feeding: Relation to Duration of Breastfeeding.

BACKGROUND: Studies examining direct vs. expressed breast milk feeding are scarce. We explored the predictors of mode of breastfeeding and its association with breastfeeding duration in a multi-ethnic Asian population. METHODS: We included 541 breastfeeding mother-infant pairs from the Growing Up in Singapore Toward healthy Outcomes cohort. Mode of breastfeeding (feeding directly at the breast, expressed breast milk (EBM) feeding only, or mixed feeding (a combination of the former 2 modes)) was ascertained at three months postpartum. Ordinal logistic regression analyses identified predictors of breast milk expression. Cox regression models examined the association between mode of breastfeeding and duration of any and of full breastfeeding. RESULTS: Maternal factors independently associated with a greater likelihood of breast milk expression instead of direct breastfeeding were Chinese (vs. Indian) ethnicity, (adjusted odds ratio, 95% CI; 3.41, 1.97-5.91), tertiary education (vs. secondary education or lower) (2.22, 1.22-4.04), primiparity (1.54, 1.04-2.26) and employment during pregnancy (2.53, 1.60-4.02). Relative to those who fed their infants directly at the breast, mothers who fed their infants EBM only had a higher likelihood of early weaning among all mothers who were breastfeeding (adjusted hazard ratio, 95% CI; 2.20, 1.61-3.02), and among those who were fully breastfeeding (2.39, 1.05-5.41). Mothers who practiced mixed feeding, however, were not at higher risk of earlier termination of any or of full breastfeeding. CONCLUSIONS: Mothers who fed their infants EBM exclusively, but not those who practiced mixed feeding, were at a higher risk of terminating breastfeeding earlier than those who fed their infants directly at the breast. More education and support are required for women who feed their infants EBM only.

A Comparison of Practices During the Confinement Period among Chinese, Malay, and Indian Mothers in Singapore.

BACKGROUND: Confinement (restrictions placed on diet and practices during the month right after delivery) represents a key feature of Asian populations. Few studies, however, have focused specifically on ethnic differences in confinement practices. This study assesses the confinement practices of three ethnic groups in a multi-ethnic Asian population. METHODS: Participants were part of a prospective birth cohort study that recruited 1,247 pregnant women (57.2% Chinese, 25.5% Malay, and 17.3% Indian) during their first trimester. The 1,220 participants were followed up 3 weeks postpartum at home when questionnaires were administered to ascertain the frequency of adherence to the following confinement practices: showering; confinement-specific meals; going out with or without the baby; choice of caregiver assistance; and the use of massage therapy. RESULTS: Most participants reported that they followed confinement practices during the first 3 weeks postpartum (Chinese: 96.4%, Malay: 92.4%, Indian: 85.6%). Chinese and Indian mothers tended to eat more special confinement diets than Malay mothers (p < 0.001), and Chinese mothers showered less and were more likely to depend on confinement nannies during this period than mothers from the two other ethnic groups (p < 0.001 for all). Malay mothers tended to make greater use of massage therapy (p < 0.001), whilst Indian mothers tended to have their mothers or mothers-in-law as assistant caregivers (p < 0.001). CONCLUSION: Most Singapore mothers follow confinement practices, but the three Asian ethnic groups differed in specific confinement practices. Future studies should examine whether ethnic differences persist in later childrearing practices.

Determinants of Breastfeeding Practices and Success in a Multi-Ethnic Asian Population.

BACKGROUND: Many countries in Asia report low breastfeeding rates and the risk factors for early weaning are not well studied. We assessed the prevalence, duration, and mode of breastfeeding (direct or expressed) among mothers of three Asian ethnic groups. METHODS: Participants were 1,030 Singaporean women recruited during early pregnancy. Data collected included early breastfeeding experiences, breastfeeding duration, and mode of breastfeeding. Full breastfeeding was defined as the intake of breast milk, with or without water. Cox regression models were used to identify factors associated with discontinuation of any and full breastfeeding. Logistic regression analyses assessed the association of ethnicity with mode of breastfeeding. RESULTS: At 6 months postpartum, the prevalence of any breastfeeding was 46 percent for Chinese mothers, 22 percent for Malay mothers, and 41 percent for Indian mothers; prevalence of full breastfeeding was 11, 2, and 5 percent, respectively. More Chinese mothers fed their infants expressed breast milk, instead of directly breastfeeding them, compared with the other two ethnic groups. Duration of any and full breastfeeding were positively associated with breastfeeding a few hours after birth, higher maternal age and education, and negatively associated with irregular breastfeeding frequency and being shown how to breastfeed. Adjusting for maternal education, breastfeeding duration was similar in the three ethnic groups, but ethnicity remained a significant predictor of mode of breastfeeding. CONCLUSIONS: The low rates and duration of breastfeeding in this population may be improved with breastfeeding education and support, especially in mothers with lower education. Further work is needed to understand the cultural differences in mode of feeding and its implications for maternal and infant health.

Hearing Loss in Newborns with Cleft Lip and/or Palate.

INTRODUCTION: This study aims to review the results of hearing screens in newborns with cleft deformities. MATERIALS AND METHODS: A retrospective audit of 123 newborns with cleft deformities, born between 1 April 2002 and 1 December 2008, was conducted. Data on the results of universal newborn hearing screens (UNHS) and high-risk hearing screens, age at diagnosis, severity/type of hearing loss and mode of intervention were obtained from a prospectively maintained hearing database. RESULTS: Thirty-one of 123 newborns (25.2%) failed the first automated auditory brainstem response (AABR). Seventy percent of infants (56 out of 80) who passed the UNHS failed the high-risk hearing screens which was conducted at 3 to 6 months of age. Otolaryngology referral rate was 67.5% (83/123); 90.3% of 31 newborns who failed the first AABR eventually required otolaryngology referrals. Incidence of hearing loss was 24.4% (30/123; 25 conductive, 2 mixed and 3 sensorineural), significantly higher than the hospital incidence of 0.3% (OR: 124.9, 95% CI, 81.1 to 192.4, P <0.01). In terms of severity, 8 were mild, 15 moderate, 5 severe, 2 profound. Eighteen out of 30 infants (60%) were detected from the high-risk hearing screens after passing the first AABR. CONCLUSION: These newborns had a higher risk of failing the UNHS and high-risk hearing screen. There was a higher incidence of hearing loss which was mainly conductive. Failure of the first AABR was an accurate predictor of an eventual otolaryngology referral, suggesting that a second AABR may be unnecessary. High-risk hearing screens helped to identify hearing loss which might have been missed out early on in life or which might have evolved later in infancy.

Borderline viability--neonatal outcomes of infants in Singapore over a period of 18 years (1990 - 2007).

INTRODUCTION: This study assesses the trends and predictors of mortality and morbidity in infants of gestational age (GA) <27 weeks from 1990 to 2007. MATERIALS AND METHODS: This is a retrospective cross-sectional cohort study of infant deliveries between 1990 and 2007 in the largest perinatal centre in Singapore. This is a study of infants born at <27 weeks in 2 Epochs (Epoch 1 (E1):1990 to 1998, Epoch 2 (E2):1999 to 2007) using logistic regression models to identify factors associated with mortality and composite morbidity. The main outcomes that were measured were the trends and predictors of mortality and morbidity. RESULTS: Four hundred and eight out of 615 (66.3%) live born infants at 22 to 26 weeks survived to discharge. Survival improved with increasing GA from 22% (13/59) at 23 weeks to 87% (192/221) at 26 weeks (P <0.01). Survival rates were not different between E1 and E2, (61.5% vs 68.8%). In logistic regression analysis, higher survival was independently associated with increasing GA and birthweight, while airleaks, severe intraventricular haemorrhage (IVH) and necrotizing enterocolitis (NEC) contributed to increased mortality. Rates of major neonatal morbidities were bronchopulmonary dysplasia (BPD) (45%), sepsis (35%), severe retinopathy of prematurity (ROP) (31%), severe IVH/ periventricular leucomalacie (PVL) (19%) and NEC (10%). Although composite morbidity comprising any of the above was not significantly different between the 2 Epochs (75% vs 73%) a decreasing trend was seen with increasing GA (P <0.001). Composite morbidity/ mortality was significantly lower at 26 weeks (58%) compared to earlier gestations (P <0.001, OR 0.37, 95% CI, 0.28 to 0.48) and independently associated with decreasing GA and birth weight, male sex, hypotension, presence of patent ductus arteriosus (PDA) and airleaks. CONCLUSION: Increasing survival and decreasing composite morbidity was seen with each increasing week in gestation with marked improvement seen at 26 weeks. Current data enables perinatal care decisions and parental counselling.

Improvement of drug safety by the use of lipid-based nanocarriers.

Drug toxicity is an important factor that contributes significantly to adverse drug events in current healthcare practice. Application of lipid-based nanocarriers in drug formulation is one approach to improve drug safety. Lipid-based delivery systems include micelles, liposomes, solid lipid nanoparticles, nanoemulsions and nanosuspensions. These carriers are generally composed of physiological lipids well tolerated by human body. Delivery of water-insoluble drugs in these formulations increases their solubility and stability in aqueous media and eliminates the need for toxic co-solvents or pH adjustment to solubilize hydrophobic drugs. Association or encapsulation of peptides/proteins within lipid-based carriers protects the labile biologics against enzymatic degradation, hence reducing the therapeutic dose required and risk of dose-dependent toxicity. Most importantly, lipid-based nanocarriers alter the pharmacokinetics and biodistribution of drugs through passive and active targeting, leading to increased drug accumulation at target sites while significantly decreasing non-specific distribution to other tissues. Furthermore, surface modification of these nanocarriers reduces immunogenicity of drug-carrier complexes, imparts stealth by preventing opsonization and removal by phagocytes and minimizes interaction with circulating blood components. In view of heightening attention on drug safety in patient treatment, lipid-based nanocarrier is therefore an important and promising option for formulation of pharmaceutical products to improve treatment safety and efficacy.

High prevalence of hearing loss in Down syndrome at first year of life.

INTRODUCTION: Infants with Down syndrome (DS) are at higher risk of hearing loss (HL). Normal hearing at one year of age plays an important part in language development. An audit was conducted to determine the impact of the newborn hearing screening program on the incidence, type and timing of diagnosis of HL during first year of life. MATERIALS AND METHODS: Infants with DS were scheduled for Universal Newborn Hearing Screening (UNHS) within 4 weeks of life. If they passed, they had a high-risk screen at 3 to 6 months. They were referred to the otolaryngology department if they did not pass the UNHS or the high-risk screen. Information was obtained from the computerised data tracking system and case notes. Infants born from April 2002 to January 2005 and referred to the DS clinic of our hospital were analysed. RESULTS: Thirty-seven (82.2%) of 45 infants underwent UNHS, of which 12 (32.4%) infants did not pass. Of remaining 33 infants, 27 had high-risk screen done of which 14 (51.8%) did not pass. Twenty-eight infants were referred to the ear, nose, throat (ENT) clinic: 12 from UNHS, 14 from high-risk screens and 2 from the DS clinic. Eleven (39.2%) defaulted follow-up. Fourteen (82.3%) of 17 infants who attended the ENT Clinic had HL. Twelve (85.7%) were conductive, and 2 (14.2%) mixed. Nine (64.2%) had mild-moderate HL and 3 (21%) had severe HL. The mean age of diagnosis was 6.6 ± 3.3 months. All were treated medically, plus surgically if indicated. By 12 months of age, the hearing had normalised in 4 (28.6%) infants and remained the same in 3 (21.4%). Five (35.7%) defaulted follow-up. Thirty-five out of 45 (77.8%) underwent complete hearing screen in the first year of life (UNHS & High-risk screen). Six out of 45 (13.3%) had incomplete screening. Fourteen out of 41 (34.1%) had HL of varying degrees. Four out of 45 (8.8%) did not have any audiological assessment in first year of life. CONCLUSION: The incidence of HL in the first year of life was high (34.1%). Eighty-five percent were conductive with 64.2% in mild-moderate range. One third of infants hearing normalized after treatment, one third remained unaltered and one third of infants did not attend follow-up. An aggressive approach involving early screening after birth and continued surveillance and early referral to appropriate agencies are essential for establishing timely diagnosis and treatment. Measures to reduce the high default rate during long-term follow-up are needed. Parent education and integrated multidisciplinary follow-up clinic may be useful.

Handling request for non-disclosure of clinical information in paediatrics.

Non-disclosure in Paediatric Practice is a controversial issue. There was a time when the care of children was solely the responsibility of parents and any decision with respect to treatment or non-treatment would have been the joint responsibility of the parents and of the attending medical professionals. This practice, viewed as adopting a more paternalistic approach, has been challenged in many parts of the world. In essence what is being challenged is the notion that the sole responsibility of decision-making rests with parents.

Micellar nanomedicine of human neuropeptide Y.

Human neuropeptide Y (NPY) is an important biologics that regulates a multitude of physiological functions and could be amenable to therapeutic manipulations in certain disease states. However, rapid (within minutes) enzymatic degradation and inactivation of NPY precludes its development as a drug. Accordingly, we determined whether self-association of NPY with biocompatible and biodegradable sterically stabilized phospholipid micelles (SSM) improves its stability and bioactivity. We found that in saline NPY spontaneously aggregates; however, in the presence of SSM it self-associates with the micelles as monomers. Three NPY molecules self-associate with 1 SSM at saturation. This process stabilizes the peptide in α-helix conformation, abrogates its degradation by dipeptidyl peptidase-4 and potentiates NPY-induced inhibition of cAMP elaboration in SK-N-MC cells. Collectively, these data indicate that self-association of NPY with SSM stabilizes and protects the peptide in active monomeric conformation, thereby amplifying its bioactivity in vitro. We propose further development of NPY in SSM as a novel, long-acting nanomedicine. FROM THE CLINICAL EDITOR: Human neuropeptide Y (NPY) regulates a multitude of physiological functions and could be amenable to therapeutic manipulations, which is currently limited by its short half life. Self-association of NPY with spherically stabilized micelles (SSM) protects and stabilizes the peptide in active monomeric conformation, thereby amplifying its bioactivity in vitro, enabling future therapeutic considerations.

A novel peptide nanomedicine against acute lung injury: GLP-1 in phospholipid micelles.

PURPOSE: Treatment of acute lung injury (ALI) observed in Gram-negative sepsis represents an unmet medical need due to a high mortality rate and lack of effective treatment. Accordingly, we developed and characterized a novel nanomedicine against ALI. We showed that when human glucagon-like peptide 1(7-36) (GLP-1) self-associated with PEGylated phospholipid micelles (SSM), the resulting GLP1-SSM (hydrodynamic size, ~15 nm) exerted effective anti-inflammatory protection against lipopolysaccharide (LPS)-induced ALI in mice. METHODS: GLP1-SSM was prepared by incubating GLP-1 with SSM dispersion in saline and characterized using fluorescence spectroscopy and circular dichroism. Bioactivity was tested by in vitro cAMP induction, while in vivo anti-inflammatory effects were determined by lung neutrophil cell count, myeloperoxidase activity and pro-inflammatory cytokine levels in LPS-induced ALI mice. RESULTS: Amphipathic GLP-1 interacted spontaneously with SSM as indicated by increased α-helicity and fluorescence emission. This association elicited increased bioactivity as determined by in vitro cAMP production. Correspondingly, subcutaneous GLP1-SSM (5-30 nmol/mouse) manifested dose-dependent decrease in lung neutrophil influx, myeloperoxidase activity and interleukin-6 in ALI mice. By contrast, GLP-1 in saline showed no significant anti-inflammatory effects against LPS-induced lung hyper-inflammatory responses. CONCLUSIONS: GLP1-SSM is a promising novel anti-inflammatory nanomedicine against ALI and should be further developed for its transition to clinics.

Freeze drying of peptide drugs self-associated with long-circulating, biocompatible and biodegradable sterically stabilized phospholipid nanomicelles.

The purpose of this study was to determine optimal lipid concentration range for lyophilization of sterically stabilized phospholipid nanomicelles (SSM) and the freeze drying feasibility of self-associated therapeutic peptide-SSM assemblies. SSM at 5-20 mM 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000) (DSPE-PEG(2000)) were analyzed for particle size and viscosity before and after freeze drying which showed no significant changes (p>0.05). However, a steep increase in viscosity was seen for SSM above 15 mM phospholipid implying micelle-micelle interaction. Greater shrinkage of lyophilized cakes was observed below 10 mM phospholipid while they were more fibrous above 15 mM. Therefore, 10-15 mM DSPE-PEG(2000) was chosen as the optimal phospholipid concentration for lyophilized SSM. When vasoactive intestinal peptide (VIP), glucagon-like peptide 1 (GLP-1) or gastric inhibitory peptide (GIP) (each, 67 microM) was added to SSM (10mM), formulations showed no significant change in particle size, peptide fluorescence and peptide alpha-helicity before and after lyophilization. In conclusion, we found that peptide drug-SSM interactions are conserved during lyophilization.

Establishing a universal newborn hearing screening programme.

As congenital hearing impairment has a worldwide incidence of 4 to 5 per 1000 babies and is thus one of the most common congenital problems seen today, universal newborn screening has a crucial role to play in its early detection and intervention. It provides the opportunity for better outcomes and normal language development. Prior to embarking on a screening programme, the newborn population and the current health care system should be analysed to select the best method of coverage. The screening tool and protocol, communication of results, as well as the follow-up measures should be clearly determined and tested. The multidisciplinary team required should be provided with the necessary information. Parents need to be educated about the importance of early hearing screening. Data management and surveillance should be established in a systematic manner. The costs of the programme should be carefully anticipated and funding sources determined. Finally, support for the programme should be sought from governmental or public health bodies, to ensure the success of the programme. Legislation can be considered if necessary.

The effect of the phytoestrogens genistein, daidzein, and equol on the growth of tamoxifen-resistant T47D/PKC alpha.

Soy supplements are often consumed by women for alleviating menopausal symptoms or for the perceived protective effects against breast cancer. More concerning is the concurrent consumption of soy isoflavones with tamoxifen (TAM) for prevention or treatment of breast cancer. We previously described a T47D:A18/protein kinase C (PKC)alpha TAM-resistant tumor model that exhibits autonomous growth and estradiol-induced tumor regression. We compared the estrogenicity of the isoflavones genistein, daidzein, and the daidzein metabolite equol in the parental T47D:A18 and T47D:A18/PKC alpha cell lines in vitro and in vivo. Whereas equol exerts estrogenic effects on T47D:A18 cells in vitro, none of the isoflavones stimulated T47D:A18 tumor growth. T47D:A18/PKC alpha tumor growth was partially stimulated by genistein, yet partially inhibited by daidzein. Interestingly, coadministration of TAM with either daidzein or genistein produced tumors of greater size than with TAM alone. These findings suggest that simultaneous consumption of isoflavone supplements with TAM may not be safe.

Auditory neuropathy/auditory dys-synchrony detected by universal newborn hearing screening.

The implementation of neonatal hearing screening has enabled early detection and intervention in hearing loss. The use of otoacoustic emissions (OAE) and auditory brainstem response testing in universal screening has led to the recognition of this recently described disorder called auditory neuropathy/auditory dys-synchrony (AN/AD). This diagnosis indicates that the infant has significant hearing loss despite having normal outer hair cells in the cochlea. We reviewed the characteristics and natural history of nine infants detected to have AN/AD from universal newborn hearing screening in a national pediatric hospital. Fifty-two cases of hearing loss were detected from 14,807 consecutively screened cases. Of the 52 cases, 9 had electrophysiological test results consistent with AN/AD. They include both premature infants who had major neonatal complications and term infants with no perinatal complications. Six cases had bilateral and three cases had unilateral findings. We suggest that AN/AD can occur in low-risk infants and hence screening of high-risk cases alone is insufficient. Our findings are discussed with reference to the current literature.

Two-year neurodevelopmental outcome in children conceived by intracytoplasmic sperm injection: prospective cohort study.

OBJECTIVE: Primary outcome was to compare neurodevelopmental outcome at two years in intracytoplasmic sperm injection (ICSI) conceived children versus matched controls. Secondary outcome was to determine incidence of major congenital malformations and study perinatal outcome. DESIGN: Prospective cohort study. SETTING: Tertiary care perinatal centre over a period of 13 months. POPULATION: Seventy-six ICSI conceived children and 261 matched controls selected by matching for maternal age, sex, date of delivery, race, plurality and parity. METHODS: Mental Development Index (MDI) and Psychometric Development Index (PDI) of the Bayley's Scale of Development (BSID-II) and Vineland Adaptive Behaviour Scale (VABS) were used to assess the neurodevelopmental and functional outcome. The congenital malformations were classified according to ICD-9 code. MAIN OUTCOME MEASURES: Primary outcome measure--neurodevelopmental and functional outcomes. Secondary outcome measure--congenital malformations and perinatal outcomes. RESULTS: Neurodevelopmental and functional outcome were comparable in both groups. The mean MDI score was 92 [16] versus 90 [14] in the study and control groups respectively. Fourteen (18.4%) in the ICSI group had MDI <85 compared with 87 (33%) controls (P= 0.002). On linear regression the MDI was independently affected by plurality (P= 0.001), maternal education and socio-economic status (P= 0.01). The study group had a lower gestation (36 [3] vs 37.1 [2] weeks; P= 0.005) and a higher incidence of prematurity <34 weeks [19 (25%)] vs [31 (12%)] P= 0.012]. Six (7.9%) of the ICSI babies and seven (2.7%) of the controls had a major congenital malformation (P= 0.05). CONCLUSIONS: Children born by ICSI pregnancies did not have an adverse neurodevelopmental outcome. The incidence of major congenital malformations in ICSI needs further evaluation.