Primary Care Provider Management of Congenital Hypothyroidism Identified Through Newborn Screening.

OBJECTIVE: To assess Primary Congenital Hypothyroidism (CH) management patterns and feasibility of providing long-term care for patients with CH identified through newborn screening by Primary Care Providers (PCPs) in California and Hawaii. STUDY DESIGN: A survey was mailed to all physicians (N=823) listed as the referral doctor for confirmed patients with CH identified through newborn screening programs in both states between 01/01/2009-12/31/2013. Information was collected on CH management patterns, barriers to providing care, and knowledge on CH treatment. Descriptive statistics and bivariate logistic regression results were reported. RESULTS: 206 PCPs completed the survey. Among these, 78% currently have patients with CH and 91% indicated willingness to provide long-term care to new patients with CH. Among PCPs currently caring for patients with CH, 17% managed CH by themselves with limited assistance from endocrinologists; 63% were involved in managing CH but endocrinologists played a larger role than PCPs; 19% were not involved in CH care. Only 49% of PCPs correctly answered questions regarding recommended follow-up frequencies and 23% knew the correct age for a trial off levothyroxine for suspected transient CH. Top two perceived barriers to providing long-term care included "need guidance or support from endocrinologists" (61%) and "not familiar with CH treatment guidelines" (28%). CONCLUSION: The majority of PCPs surveyed are willing to provide long-term care to patients with CH, but need support from endocrinologists and increased knowledge about current treatment guidelines.

Biochemical characteristics of newborns with carnitine transporter defect identified by newborn screening in California.

Carnitine transporter defect (CTD; also known as systemic primary carnitine deficiency; MIM 212140) is due to mutations in the SLC22A5 gene and leads to extremely low carnitine levels in blood and tissues. Affected individuals may develop early onset cardiomyopathy, weakness, or encephalopathy, which may be serious or even fatal. The disorder can be suggested by newborn screening. However, markedly low newborn carnitine levels can also be caused by conditions unrelated to CTD, such as the low carnitine levels often associated with normal pregnancies and some metabolic disorders occurring in the mother. In order to clarify the biochemical characteristics most useful for identification of CTD in newborns, we examined California Department of Public Health newborn screening data for CTD from 2005 to 12 and performed detailed chart reviews at six metabolic centers in California. The reviews covered 14 cases of newborn CTD, 14 cases of maternal disorders (CTD, 6 cases; glutaric aciduria, type 1, 5; medium-chain acyl CoA dehydrogenase deficiency, 2; and cobalamin C deficiency, 1), and 154 false-positive cases identified by newborn screening. Our results show that newborns with CTD identified by NBS exhibit different biochemical characteristics, compared to individuals ascertained clinically. Newborns with CTD may have NBS dried blood spot free carnitine near the lower cutoff and confirmatory plasma total and free carnitine levels near the normal lower limit, particularly if obtained within two weeks after birth. These findings raise the concern that true cases of CTD may exist that could have been missed by newborn screening. CTD should be considered as a possible diagnosis in cases with suggestive clinical features, even if CTD was thought to be excluded in the newborn period. Maternal plasma total carnitine and newborn urine total carnitine values are the most important predictors of true CTD in newborns. However, biochemical testing alone does not yield a discriminant rule to distinguish true CTD from low carnitine in newborns due to other causes. Because of this biochemical variability and overlap, molecular genetic testing is imperative to confirm CTD in newborns. Additionally, functional testing of fibroblast carnitine uptake remains necessary for cases in which other confirmatory testing is inconclusive. Even with utilization of all available diagnostic testing methods, confirmation of CTD ascertained by NBS remains lengthy and challenging. Incorporation of molecular analysis as a second tier step in NBS for CTD may be beneficial and should be investigated.

Extremely high phenylalanine levels in a newborn on parenteral nutrition: phenylketonuria in the neonatal intensive care unit.

A 1890-g newborn on total parenteral nutrition (TPN) had phenylalanine levels reaching 4164 µM indicating phenylketonuria (PKU). Review of 64 PKU cases from the California Newborn Screening Program disclosed another newborn diagnosed while on TPN. Phenylalanine levels rose five times faster with TPN, as estimated from rates in these infants. Thus, TPN use is associated with very high phenylalanine levels in newborns with PKU. When starting TPN soon after birth (for example, on day 1), early detection of PKU-by newborn screening 12 to 24 h after infusions are begun-should be helpful in limiting exposures to toxic levels of phenylalanine.

Prenatal ultrasound findings in affected and unaffected pregnancies that are screen-positive for trisomy 18: the California experience.

This study investigated whether significant differences in ultrasound findings exist between trisomy 18 affected and unaffected pregnancies positive by serum screening. Ultrasound reports were reviewed for 335 screen-positive women. This represented 65% of all trisomy 18 screen-positive patients who had follow-up services at any of 117 Californian state-approved Prenatal Diagnosis Centers during a six-month period from November 1, 1995 to April 30, 1996. Ultrasound reports were available for 100% of trisomy 18 fetuses diagnosed during the six month period (n=23). Ultrasound findings were reported as normal in 35% of the fetuses affected with trisomy 18. The number and type of abnormalities observed in the affected and unaffected groups are described. When compared to unaffected cases, the trisomy 18 affected fetuses had a greater re-dating discrepancy on follow-up ultrasound evaluation and significantly lower femur length to biparietal diameter (FL/BPD) ratio measurements. We recommend that all women who are screen positive for trisomy 18 be encouraged to have amniocentesis, regardless of ultrasound findings, since affected fetuses may not be detected otherwise.

Neural tube defect prevalence in California (1990-1994): eliciting patterns by type of defect and maternal race/ethnicity.

This study presents race/ethnicity-specific prevalence estimates of neural tube defects (NTDs) in California using 5 years of population-based data. NTD prevalence estimates include prenatally diagnosed cases, as well as cases diagnosed at birth. The California NTD Registry contains NTD case reports identified through the California Maternal Serum Alpha-Feto Protein (AFP) Screening Program, the California Birth Defects Monitoring Program, and additional reports from clinicians and clinics throughout the state. These data were used to estimate NTD prevalence in a large population-based study (n = 1,618,279). The overall NTD prevalence among White, Black, Hispanic, and Asian women are reported, as well as race/ethnic prevalence, for anencephaly, spina bifida, and encephalocele. Rates are expressed as the number of cases per 1,000 women screened between 1990 and 1994. Among 1,457 women with an NTD-affected pregnancy, the overall rate for anencephaly, spina bifida, and encephalocele was 0.49 (95% CI 0.46-0.53), 0.42 (95% CI 0.38-0.45), and 0.08 (95% CI 0.07-0.09), respectively. When these types of NTDs are combined, Hispanic women had the highest overall rate (1.12, 95% CI 1.04-1.21), followed by Whites (0.96, 95% CI 0.89-1.04), Blacks (0.75, 95% CI 0.59-0.91), and Asians (0.75, 95% CI 0.60-0.90). Hispanic women were 45% more likely than White women to have a pregnancy affected with anencephaly (odds ratio = 1.45, 95% CI 1.24-1.70), while Asian women were over two times less likely to have a pregnancy affected with spina bifida (odds ratio = 0.44, 95% CI 0.29-0.65). Considerable variation exists in the prevalence of NTDs by race/ethnicity and by type of NTD, with Hispanic women exhibiting the highest overall NTD rate.

The association between maternal serum alpha-fetoprotein and preterm birth, small for gestational age infants, preeclampsia, and placental complications.

OBJECTIVE: To determine whether high levels of serum alpha-fetoprotein (AFP) predict increased risk of adverse pregnancy outcomes, including preterm birth (before 37 weeks), preterm birth occurring at or before 28 weeks, small for gestational age (SGA) infant, preeclampsia, and placental abnormalities, and to determine whether low levels of serum AFP predict increased or decreased risk of these outcomes. METHODS: Using the mother's first name, last name, and zip code, we linked the records of 51,008 women who participated in the California Alpha-Fetoprotein Screening Program between June 15, 1986, and October 31, 1987, with California birth certificates for singleton infants born in 1987. The accuracy of the data linkage was confirmed by manually examining complete names, mother's ethnicity, and mother's age for a sample of 500 of the mother-infant linkages. Blood samples were obtained at 15-19 weeks. RESULTS: A strong gradient of increasing risk of preterm birth with increasing levels of serum AFP was observed (test for trend, P < .01). Among women with high levels of serum AFP (at least 2.5 multiples of the median [MoM]), 24.3% had preterm births, compared with 3.8% of women with low levels of serum AFP (0.81 MoM or less), odds ratio 8.7, 95% confidence interval 7.1-10.7). This gradient persisted when preterm infants of 28 weeks or less were examined separately. Similar gradients were observed for the risk of preeclampsia and placental abnormalities. There was a weaker U-shaped relation between serum AFP level and the risk of an SGA infant. CONCLUSION: Low levels of second-trimester maternal serum AFP are associated with a very low risk of preterm birth, preeclampsia, and placental complications. High levels of serum AFP are strongly associated with preterm birth, preeclampsia, and placental abnormalities. There is a modest association between AFP levels (both low and high) and SGA birth.

Fetal karyotyping for chromosome abnormalities after an unexplained elevated maternal serum alpha-fetoprotein screening.

OBJECTIVE: To study the chromosome abnormality rate among women with elevated levels of maternal serum alpha-fetoprotein (MSAFP) and the types of chromosome abnormalities in this population, and to compare this rate with reports in the literature and the rate observed in the general population. METHODS: We studied 8097 women who chose to undergo amniocentesis and fetal karyotyping after having an elevated MSAFP test of 2.5 multiples of the median (MOM) or higher. All abnormal karyotypes were reviewed and grouped according to whether the elevated MSAFP value could be explained by a ventral wall or neural tube defect. RESULTS: The overall chromosome abnormality rate was 13.83 per 1000 amniocenteses. The rate in the "unexplained" group was 10.92 per 1000 amniocenteses. Just over half (53%) of the abnormal karyotypes were autosomal anomalies, and 47% were sex chromosome abnormalities. The autosomal aneuploidies observed most frequently were triploidy and trisomy 13. The sex chromosome abnormalities observed most frequently were the XXY and XYY karyotypes. CONCLUSION: Women who have unexplained elevated MSAFP values of 2.5 MOM or greater have a twofold increase in the rate of chromosome abnormalities in their fetuses compared with the general population (P < or = .001). This rate is consistent with other studies that used a 2.5 MOM cutoff. Studies that used a 2.0 MOM cutoff have reported chromosome abnormality rates that do not vary from general population estimates.

The California Maternal Serum alpha-Fetoprotein Screening Program: the role of ultrasonography in the detection of spina bifida.

Between January 1988 and June 1990, 161 cases of open spina bifida were identified by the California Maternal Serum alpha-Fetoprotein Screening Program. Eight percent of these cases were not diagnosed by an initial ultrasonographic evaluation. Three defects were not recognized until birth. Ultrasonography is inadequate to identify all cases of open spina bifida.

Prevention: the cost-effectiveness of the California Diabetes and Pregnancy Program.

BACKGROUND: The California Diabetes and Pregnancy Program is a new preventive approach to improving pregnancy outcomes through intensive diabetes management preconception and early in pregnancy. METHODS: Hospital charges and length of stay data were collected on 102 program enrollees and 218 control cases. Ninety program enrollees and 90 control cases were matched on mother's age. White's classification, and race. Regression models controlled for these variables in addition to MediCal status, birth weight, and enrollment in the program. RESULTS: Hospital charges were about 30% less for program participants and days in the hospital were roughly 25% less. The program effects were larger for women that enrolled before 8 weeks gestation. More serious diabetics were also found to have larger reductions in charges and days. CONCLUSION: After adjusting for inflation and differences in charges across hospitals, $5.19 is saved for every dollar spent on the program.