First Three Years' Experience of Mucopolysaccharidosis Type-I Newborn Screening in California.

OBJECTIVE: To report on the first 3 years of mucopolysaccharidosis type I (MPS I) newborn screening (NBS) in the large and diverse state of California. STUDY DESIGN: The California Genetic Disease Screening Program began universal NBS for MPS I on August 29, 2018. The screening uses a 2-tiered approach: an α-L-iduronidase (IDUA) enzyme activity assay followed by DNA sequencing for variants in the IDUA gene. RESULTS: As of August 29, 2021, 1 295 515 California newborns were screened for MPS I. In tier 1 of screening, 329 (0.025%) had an IDUA enzyme measurement below the cutoff and underwent tier-2 IDUA DNA sequencing. After tier 2, 146 (0.011%) newborns were screen positive, all of whom were referred to a metabolic Special Care Center for follow-up. After long-term follow-up, 7 cases were resolved as severe MPS I (Hurler syndrome) and 2 cases as attenuated MPS I for an MPS I birth prevalence of 1/143 946. DNA sequencing identified 107 unique IDUA variants among a total of 524 variants; 65% were known pseudodeficiency alleles, 25% were variants of uncertain significance, and 10% were pathogenic variants. CONCLUSIONS: As a result of a 2-tiered NBS approach, 7 newborns diagnosed with Hurler syndrome had received early treatment for MPS I. Continuation of California's long-term follow-up program will be crucial for further understanding the complex genotype-phenotype relationships of MPS I.

Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal.

BACKGROUND: Cadmium and arsenic are ubiquitous metals commonly found in the environment which can harm human health. A growing body of research shows telomere length as a potential biomarker of future disease risk. Few studies have examined the effects of metals on telomere length and none have focused on adolescents. OBJECTIVES: In this study, the impact of cadmium and arsenic on salivary telomere length was studied in adolescents in Terai, Nepal. METHODS: Adolescents aged 12-16 years old (n=351)were recruited where questionnaire interviews and both saliva and urine collection took place. Telomere length was determined by quantitative polymerase chain reaction using DNA extracted from saliva. Urinary cadmium and arsenic concentration were measured by inductively coupled plasma mass spectrometry. Multivariable linear regression was used to examine associations between urinary metals and salivary telomere length. RESULTS: The geometric means and standard deviations of cadmium and arsenic were 0.33±0.33µg/g creatinine and 196.0±301.1µg/g creatinine, respectively. Urinary cadmium concentration was negatively associated with salivary telomere length after adjustment for confounders (ß=-0.24, 95% CI -0.42,-0.07). Arsenic showed positive associations with telomere length but did not reach statistical significance. CONCLUSIONS: This is the first study to demonstrate that cadmium may shorten adolescent telomeres, even at exposure levels that may be considered low. These results agree with prior experimental and adult epidemiological studies, and also help identify the mechanism of DNA damage by cadmium. This study expanded current evidence on the harmful effects of cadmium exposure on telomere length even to adolescents.

Shadow of a Pandemic: Persistence of Prenatal SARS-CoV-2 Antibodies in Newborn Blood Spots.

To investigate COVID-19 surveillance among pregnant women, the California Genetic Disease Screening Program conducted a screening performance and seroprevalence evaluation of maternal SARS-CoV-2 antibodies detected in banked newborn dried blood spots (DBS). We obtained seropositive results for 2890 newborn DBS from cohorts in 2020 and 2021 using Enable Bioscience's Antibody Detection by Agglutination-PCR (ADAP) assay for SARS-CoV-2 antibodies. To infer maternal infection, we linked 312 women with a known laboratory-confirmed COVID-19 episode with their newborn's DBS SARS-CoV02 antibody result. Among 2890 newborns, we detected 453 (15.7%) with SARS-CoV-2 antibodies in their DBS. Monthly snapshot statewide seroprevalence among neonates was 12.2% (95% CI 10.3-14.1%, n =1156) in December 2020 and 33.3% (95% CI 29.1-37.4%, n = 26) in March 2021. The longest time recorded from COVID-19 infection to a seropositive neonatal result was 11.7 months among the 312 mothers who had an available SARS-CoV-2 PCR test result. Approximately 94% (153/163) of DBS were seropositive when a known maternal infection occurred earlier than 19 days before birth. The estimated relative sensitivity of DBS to identify prevalent maternal infection was 85.1%, specificity 98.5% and PPV 99.2% (n = 312); the sensitivity was lowest during the December 2021 surge when many infections occurred within 19 days of birth. Fifty pre-pandemic specimens (100% seronegative) and 23 twin-pair results (100% concordant) support an intrinsic specificity and PPV of ADAP approaching 100%. Maternal infection surveillance is limited by a time lag prior to delivery, especially during pandemic surges.

Impact of prenatal heavy metal exposure on newborn leucocyte telomere length: A birth-cohort study.

Arsenic, cadmium and lead are toxic environmental contaminants. They were shown to be associated with telomere length (TL) in adults. Although they can cross the placental barrier, the effect of prenatal exposure of these metals on newborn TL is unknown. The aim of this study was to examine whether prenatal exposure to heavy metals has an impact on newborn leucocyte TL. A birth-cohort study was conducted with 409 pregnant women and their newborns in Myanmar. During the first visit, face-to-face interviews were conducted, and maternal spot urine sampling was performed. Cord blood samples were collected during follow-up. Urinary heavy metal concentration was measured by ICP-MS and adjusted for creatinine. Relative TL was measured by quantitative real-time polymerase chain reaction. The extent of prenatal arsenic, cadmium and lead exposure and their associations with newborn leucocyte TL were assessed using multivariate linear regression. The median values of maternal urinary arsenic, cadmium, and lead concentrations were 73.9, 0.9, and 1.8 µg/g creatinine, respectively. Prenatal arsenic and cadmium exposure was significantly associated with newborn TL shortening (lowest vs highest quartile, coefficient = - 0.13, 95% CI: - 0.22, - 0.03, p = 0.002, and coefficient = - 0.17, 95% CI: - 0.27, - 0.07, p = 0.001, respectively), and the associations remained robust after adjusting for confounders. There was no significant association between prenatal lead exposure and newborn TL. The present study identified the effect of arsenic and cadmium exposure on TL shortening, even in utero exposure at a lower concentration.

Are Husbands Involving in Their Spouses' Utilization of Maternal Care Services?: A Cross-Sectional Study in Yangon, Myanmar.

INTRODUCTION: Husbands can play a crucial role in pregnancy and childbirth, especially in patriarchal societies of developing countries. In Myanmar, despite the critical influence of husbands on the health of mothers and newborns, their roles in maternal health have not been well explored. Therefore, the aim of this study was to identify the factors associated with husbands' involvement in maternal health in Myanmar. This study also examined the associations between husbands' involvement and their spouses' utilization of maternal care services during antenatal, delivery and postnatal periods. METHODS: A community-based, cross sectional study was conducted with 426 husbands in Thingangyun Township, Yangon, Myanmar. Participants were husbands aged 18 years or older who had at least one child within two years at the time of interview. Face to face interviews were conducted using a pretested structured questionnaire. Factors associated with the characteristics of husband's involvement as well as their spouses' utilization of maternal care services were analyzed by multivariable logistic regression models. RESULTS: Of 426 husbands, 64.8% accompanied their spouses for an antenatal visit more than once while 51.6% accompanied them for a postnatal visit. Husbands were major financial supporters for both antenatal (95.8%) and postnatal care (68.5%). Overall, 69.7% were involved in decision making about the place of delivery. Regarding birth preparedness, the majority of husbands prepared for skilled birth attendance (91.1%), delivery place (83.6%), and money saving (81.7%) before their spouses gave birth. In contrast, fewer planned for a potential blood donor (15.5%) and a safe delivery kit (21.1%). In the context of maternal health, predictors of husband's involvement were parity, educational level, type of marriage, decision making level in family, exposure to maternal health education and perception of risk during pregnancy and childbirth. Increased utilization of maternal health services was found among spouses of husbands who accompanied them to antenatal visits (AOR 5.82, 95% CI, 3.34-10.15) and those who had a well birth plan (AOR 2.42, 95% CI, 1.34-4.39 for antenatal visit and AOR 2.88, 95% CI, 1.52-5.47 for postnatal visit). CONCLUSION: The majority of husbands supported their spouses' maternal care services use financially; however, they were less involved in birth preparedness and postnatal care. Exposure to maternal health education and their maternal health knowledge were main predictors of their involvement. Women were more likely to use maternal care services when their husbands company them for ANC visits and had a well-birth plan in advance.