, on behalf of the California Cystic Fibrosis Newborn Screening Consortium abstract OBJECTIVES: This article describes the methods used and the program performance results for the first 5 years of newborn screening for cystic fibrosis (CF) in California.METHODS: From July 16, 2007, to June 30, 2012, a total of 2 573 293 newborns were screened for CF by using a 3-step model: (1) measuring immunoreactive trypsinogen in all dried blood spot specimens; (2) testing 28 to 40 selected cystic fibrosis transmembrane conductance regulator (CFTR) mutations in specimens with immunoreactive trypsinogen values $62 ng/mL (top 1.6%); and (3) performing DNA sequencing on specimens found to have only 1 mutation in step 2. Infants with $2 mutations/variants were referred to CF care centers for diagnostic evaluation and follow-up. Infants with 1 mutation were considered carriers and their parents offered telephone genetic counseling.RESULTS: Overall, 345 CF cases, 533 CFTR-related metabolic syndrome cases, and 1617 carriers were detected; 28 cases of CF were missed. Of the 345 CF cases, 20 (5.8%) infants were initially assessed as having CFTR-related metabolic syndrome, and their CF diagnosis occurred after age 6 months (median follow-up: 4.5 years). Program sensitivity was 92%, and the positive predictive value was 34%. CF prevalence was 1 in 6899 births. A total of 303 CFTR mutations were identified, including 78 novel variants. The median age at referral to a CF care center was 34 days (18 and 37 days for step 2 and 3 screening test-positive infants, respectively). CONCLUSIONS:The 3-step model had high detection and low false-positive levels in this diverse population. WHAT'S KNOWN ON THIS SUBJECT:Several newborn screening models for cystic fibrosis (CF) exist, including DNA-based models that use mutation panels. There is limited experience with models (such as used in California) that include comprehensive DNA sequence testing methods as part of newborn screening.WHAT THIS STUDY ADDS: California' s 3-step newborn screening model for CF showed high efficiency, sensitivity, and positive predictive value. More than 300 mutations were found, reflecting the state' s diverse population. Some CF transmembrane conductance regulator-related metabolic syndrome cases converted to CF over time.

This study investigated the relation between self-reported vaginal bleeding during pregnancy and preterm birth in a prospective cohort of 2,829 pregnant women enrolled from prenatal clinics between 1995 and 2000 in central North Carolina. The overall association between vaginal bleeding and preterm birth was modest (risk ratio (RR) = 1.3, 95% confidence interval (CI): 1.1, 1.6). Bleeding in the first trimester only was associated with earlier preterm birth (< or =34 weeks' gestation) (RR = 1.6, 95% CI: 1.1, 2.4) and preterm birth due to preterm premature rupture of the membranes (PPROM) (RR = 1.9, 95% CI: 1.1, 3.3). Bleeding in both trimesters was associated with preterm birth due to preterm labor (RR = 3.6, 95% CI: 1.9, 6.8). Bleeding of multiple episodes, on multiple days, and with more total blood loss was associated with an approximate twofold increased risk of earlier preterm birth, PPROM, and preterm labor. In contrast, bleeding in the second trimester only, of a single episode, on a single day, and with less total blood loss was not associated with any category of preterm birth. Vaginal bleeding was not associated with preterm birth among African Amercians (RR = 1.2, 95% CI: 0.9, 1.7). This study indicates that more intense but not less intense bleeding is associated with earlier preterm birth and spontaneous preterm birth presenting as PPROM or preterm labor, and it suggests that bleeding is less predictive of preterm birth among African-American compared with White women.

BackgroundLarge-scale analysis of the transmission, mutation characteristics and the relationship between the reading frame and phenotype of the DMD gene has previously been performed in several countries, however, analogous studies have yet to be performed in Chinese populations.MethodsClinical data from 1053 Chinese patients with DMD/BMD were collected, and the DMD gene was tested by MLPA in all patients and 400 proband mothers. In 20 patients with negative MLPA, sequencing was also performed.ResultsWe found that 27.50% of cases had a family medical history of DMD/BMD, and large rearrangements were identified in 70.56% of the probands, of which 59.35% and 11.21% were deletions or duplications, respectively. The carrier status of the mothers in the study was determined to be 50.75%, and it was established that the DMD mutation was inherited from the mother in 51.72% of the probands. Exons 45–54 and 3–22 were the most frequently deleted regions, and exons 3–11 and 21–37 were the most prevalently duplicated regions of the gene. Breakpoints mainly occurred in introns 43–55 for deletion mutations and in introns 2 and 7 for duplication mutations. No breakpoints were found at the 5′ or 3′ end of introns 31, 35, 36, 40, 65, 68, and 74–78 in any of the deletion or duplication mutations. The reading frame rule held true for 86.4% of the DMD patients and 74.55% of the BMD patients.ConclusionIt is essential to increase physicians’ understanding of DMD/BMD, to promote scientific information, and to increase awareness in regards to genetic counseling and prenatal diagnosis in pedigrees with a family history of the disease, particularly in families with small DMD lesions in China. In addition, such a large-scale analysis will prove to be instructive for leading translational studies between basic science and clinical medicine.

OBJECTIVE To examine recurrent preterm birth and early term birth in women’s initial and immediately subsequent pregnancies. METHODS This retrospective cohort study included 163,889 women who delivered their first and second liveborn singleton neonates between 20 and 44 weeks of gestation in California from 2005 through 2011. Data from hospital discharge records and birth certificates were used for analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models adjusted for risk factors. RESULTS Shorter gestational duration in the first pregnancy increased the risk of subsequent preterm birth (both early, before 32 weeks of gestation, and later, from 32 to 36 weeks of gestation) as well as early term birth (37–38 weeks of gestation). Compared with women with a prior term birth, women with a prior early preterm birth (before 32 weeks of gestation) were at the highest risk for a subsequent early preterm birth (58/935 [6.2%] compared with 367/118,505 [0.3%], adjusted OR 23.3, 95% CI 17.2–31.7). Women with a prior early term birth had more than a twofold increased risk for subsequent preterm birth (before 32 weeks of gestation: 171/36,017 [0.5%], adjusted OR 2.0, 95% CI 1.6–2.3; from 32 to 36 weeks of gestation: 2,086/36,017 [6.8%], adjusted OR 3.0, 95% CI 2.9–3.2) or early term birth (13,582/36,017 [37.7%], adjusted OR 2.2, 95% CI 2.2–2.3). CONCLUSION Both preterm birth and early term birth are associated with these outcomes in a subsequent pregnancy. Increased clinical attention and research efforts may benefit from a focus on women with a prior early term birth as well as those with prior preterm birth.