Pharmacologic evidence to support clinical decision making for peripartum methadone treatment.

RATIONALE: Limited pharmacological data are available to guide methadone treatment during pregnancy and postpartum. OBJECTIVES: Study goals were to (1) characterize changes in methadone dose across childbearing, (2) determine enantiomer-specific methadone withdrawal kinetics from steady state during late pregnancy, (3) assess enantiomer-specific changes in methadone level/dose (L/D) ratios across childbearing, and (4) explore relationships between CYP2B6, CYP2C19, and CYP3A4 single-nucleotide polymorphisms and maternal dose, plasma concentration, and L/D. METHODS: Methadone dose changes and timed plasma samples were obtained for women on methadone (n = 25) followed prospectively from third trimester of pregnancy to 3 months postpartum. RESULTS: Participants were primarily white, Medicaid insured, and multiparous. All women increased their dose from first to end of second trimester (mean peak increase = 23 mg/day); 71 % of women increased from second trimester to delivery (mean peak increase = 19 mg/day). Half took a higher dose 3 months postpartum than at delivery despite significantly larger clearance during late pregnancy. Third trimester enantiomer-specific methadone half-lives (range R-methadone 14.7-24.9 h; S-methadone, 8.02-18.9 h) were about half of those reported in non-pregnant populations. In three women with weekly 24-h methadone levels after delivery, L/D increased within 1-2 weeks after delivery. Women with the CYP2B6 Q172 variant GT genotype have consistently higher L/D values for S-methadone across both pregnancy and postpartum. CONCLUSIONS: Most women require increases in methadone dose across pregnancy. Given the shorter half-life and larger clearances during pregnancy, many pregnant women may benefit from split methadone dosing. L/D increases quickly after delivery and doses should be lowered rapidly after delivery.

Outcome of children identified as anemic by routine screening in an inner-city clinic.

BACKGROUND: Children found to be anemic on routine screening by HemoCue, a rapid and relatively inexpensive method of screening for hemoglobin (Hb), are often prescribed iron as a diagnostic tool and potential treatment for presumed iron deficiency anemia (IDA). We questioned this approach given the declining prevalence of IDA and the concomitant relative increase in other causes of anemia. OBJECTIVE: To evaluate the practice of Hb screening for IDA by determining the prevalence of anemia by HemoCue; the proportion of anemic patients treated with iron and followed up; the frequency of repeated Hb testing, additional iron studies, and iron prescriptions; and the 6-month outcomes of treated and untreated anemia. DESIGN: Retrospective cohort study. RESULTS: Of 1358 children aged 9 to 36 months who underwent screening, 343 (25%) had anemia, defined as a Hb level of less than 110 g/L. Outpatient medical records of 334 of the anemic children revealed that 239 (72%) were prescribed iron while 95 (28%) were not prescribed iron at the first visit for anemia. Anemia follow-up rates were low for the prescribed and not prescribed groups: 7% vs 5% returned within 1 month, while 37% vs 42% did not return within 6 months for follow-up. Of the children who were prescribed iron, 107 (71%) of 150 responded to treatment or anemia resolved within 6 months compared with 27 (68%) of 40 not prescribed iron. Children underwent repeated blood testing for measurement of Hb and complete blood cell count, but underwent few iron-specific studies. CONCLUSIONS: Routine screening for IDA by HemoCue followed by a therapeutic trial of iron was problematic because of a high rate of anemia in this predominantly African American population, low follow-up rates, and a high spontaneous resolution rate. Prospective studies are needed to evaluate other screening methods to differentiate IDA from other forms of anemia and to improve compliance and outcome in inner-city children.

Screening for iron deficiency anemia by dietary history in a high-risk population.

BACKGROUND: Iron deficiency anemia (IDA) in young children is important to identify because of its adverse effects on behavior and development. Because of costs and inconvenience associated with blood test screening and the decline in prevalence of IDA, the Institute of Medicine and the Centers for Disease Control and Prevention recommend that blood test screening for IDA be targeted to children first identified by dietary and health history. OBJECTIVE: To evaluate a parent-completed dietary and health history as the first stage of 2-stage screening for IDA. DESIGN AND METHODS: A cross-sectional study was conducted in inner-city clinics in children 9 to 30 months old having routine anemia screening as part of a scheduled visit. Parents completed a questionnaire and children had venous blood sampling for complete blood count and ferritin. Anemia was defined as Hb <11.0 g/dL. Iron deficiency (ID) was defined as ferritin <10 microg/L or mean corpuscular volume <70 fL and red cell distribution width >14.5%. Children were categorized into 1 of 4 groups: iron-sufficient, not anemic (ISNA); iron-sufficient, anemic (ISA); iron-deficient, not anemic (IDNA); and iron-deficient anemic (IDA). The questionnaire consisted of 15 dietary items in domains of infant diet, intake of solid food, intake of beverages, and participation in the Special Supplemental Nutrition Program for Women, Infants, and Children together with 14 historical items in domains of birth history, recent illness, chronic medical conditions, history of anemia, and maternal history. Analysis was performed on individual items, domains, and combinations of selected items. RESULTS: In the 282 study subjects, the prevalence of anemia (35%), IDNA (7%), and IDA (8%) did not vary significantly by age. Among individual historical and dietary questions, maternal history of anemia and drinking >2 glasses of juice per day identified the highest proportion of children with IDA: 50% sensitivity (95% confidence interval [CI]: 16,81) and 77% sensitivity (95% CI: 54,89), respectively. However, specificities for these questions were 60% (95% CI: 55,65) and 22% (95% CI: 17,27), respectively. Domains of questions with the highest sensitivity for IDA were beverage intake (91%; 95% CI: 68,99) and intake of solid food (91%; 95% CI: 68,99). However, specificities of the domains were only 14% (95% CI: 10,18) and 29% (95% CI: 24,35), respectively. The dietary items used by Boutry and Needlman were 95% (95% CI: 77, 99) sensitive but only 15% (95% CI: 11,19) specific for IDA. The recommendations of the Centers for Disease Control and Prevention for health and dietary screening were 73% (95% CI: 56,92) sensitive and 29% (95% CI: 24,35) specific for IDA. The individual questions, domains of questions, and interdomain groups of questions had similar sensitivity and specificity for anemia and ID (IDA + IDNA). CONCLUSION: In this high-risk population, neither individual nor combinations of parental answers to dietary and health questions were able to predict IDA, anemia, or ID well enough to serve as a first-stage screening test.