Assessing the relationship between maternal opiate use and neonatal mortality

We undertook a number of meta-analyses to estimate more precisely the relationship between neonatal mortality and use of opiates in three groups of women. First, women who continued to use illicit heroin throughout pregnancy; secondly, women stabilized on methadone at the time of conception or shortly after and thirdly, women who use heroin well into pregnancy with late entry into methadone treatment, or who continued to use illicit heroin during pregnancy while receiving methadone. FINDINGS: The pooled estimates of the relative risks of neonatal mortality for separate heroin and methadone use were both near unity: 1.47 (95% CI 0.88-2.33) and 1.75 (95% CI 0.60-4.59), respectively. The result for heroin may be due to the inclusion in the meta-analysis of a particularly large study, which, unlike the two other smaller studies included found a relative risk near unity. When this study was excluded from the meta-analysis the pooled estimate of the relative risk of neonatal mortality for heroin use was 3.27 (95% CI 0.95-9.60). In contrast to the results for use of methadone only, the pooled relative risk associated with heroin and methadone use was 6.37 (95% CI 2.57-14.68). CONCLUSIONS: The increased relative risk for neonatal mortality associated with women using heroin and methadone during pregnancy, compared to those stabilized on methadone, is probably due to the chaotic and high-risk life-style associated with illicit heroin use and not solely to the use of heroin and methadone per se. It is recommended tht women who use heroin well into pregnancy with late entry into methadone treatment, or who continue to use illicit heroin during pregnancy while receiving methadone, receive special attention over and above that provided to women stabilized on methadone.     

Heroin craving and drug use in opioid-maintained volunteers: Effects of methadone dose variations.

Recent data indicate that opioid agonist and antagonist challenges decrease and increase (respectively) heroin craving in physically dependent individuals. This study investigated effects of methadone dose variations on craving and new drug use in 18 outpatients who were given money contingencies. In Phase 1, volunteers were told in different test sessions that methadone dose would increase, decrease, or stay the same; drug-abstinence contingencies were suspended for 24 hr. Craving significantly increased and new heroin use marginally increased (relative to maintenance dose) only when a dose reduction was paired with a dose decrease instruction. In Phase 2 (detoxification), craving and heroin use significantly increased as methadone dose decreased. Thus, loss of μ-receptor agonist effect increased craving and risk of relapse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association between air pollution and low birth weight: a community-based study

The relationship between maternal exposure to air pollution during periods of pregnancy (entire and specific periods) and birth weight was investigated in a well-defined cohort. Between 1988 and 1991, all pregnant women living in four residential areas of Beijing were registered and followed from early pregnancy until delivery. Information on individual mothers and infants was collected. Daily air pollution data were obtained independently. The sample for analysis included 74,671 first-parity live births were gestational age 37-44 weeks. Multiple linear regression and logistic regression were used to estimate the effects of air pollution on birth weight and low birth weight (< 2,500 g), adjusting for gestational age, residence, year of birth, maternal age, and infant gender. There was a significant exposure-response relationship between maternal exposures to sulfur dioxide (SO2) and total suspended particles (TSP) during the third trimester of pregnancy and infant birth weight. The adjusted odds ratio for low birth weight was 1.11 (95% CI, 1.06-1.16) for each 100 micrograms/m3 increase in SO2 and 1.10 (95% CI, 1.05-1.14) for each 100 micrograms/m3 increase in TSP. The estimated reduction in birth weight was 7.3 g and 6.9 g for each 100 micrograms/m3 increase in SO2 and in TSP, respectively. The birth weight distribution of the high-exposure group was more skewed toward the left tail (i.e., with higher proportion of births < 2,500 g) than that of the low-exposure group. Although the effects of other unmeasured risk factors cannot be excluded with certainty, our data suggests that TSP and SO2, or a more complex pollution mixture associated with these pollutants, contribute to an excess risk of low birth weight in the Beijing population.     

Role of maintenance treatment in opioid dependence

Methadone maintenance treatment (MMT) involves the daily administration of the oral opioid agonist methadone as a treatment for opioid dependence-a persistent disorder with a substantial risk of premature death. MMT improves health and reduces illicit heroin use, infectious-disease transmission, and overdose death. However, its effectiveness is compromised if low maintenance doses of methadone (<60 mg) are used and patients are pressured to become prematurely abstinent from methadone. Pregnancy and psychiatric comorbidity are not contraindications for MMT. As an alternative to MMT, other oral opioid agents (eg, naltrexone, buprenorphine) may increase patient choice and avoid some of the more unpleasant aspects of MMT. The public-health challenge for the future is to develop and continue to deliver safe and effective forms of opioid maintenance treatment to as many opioid-dependent individuals as can benefit from them.     

First-trimester growth and the risk of low birth weight

BACKGROUND: Previous studies have demonstrated a correlation between first-trimester size and birth weight. It is not known, however, whether low birth weight is related to first-trimester growth. We sought to determine whether the risk of low birth weight and birth weight that was low for gestational age is related to the size of the embryo or the fetus in the first trimester. METHODS: From a data base of ultrasound records of more than 30,000 pregnancies, we identified women who had no important medical problems, a normal menstrual history, and a first-trimester ultrasound scan in which the crown-rump length of the embryo or fetus had been measured. We examined the relation between the outcome of 4229 pregnancies and the difference between the measured and the expected crown-rump length in the first trimester, expressed as equivalent days of growth. RESULTS: A first-trimester crown-rump length that was two to six days smaller than expected was associated with an increased risk (as compared with a normal or slightly larger than expected crown-rump length) of a birth weight below 2500 g (relative risk, 1.8; 95 percent confidence interval, 1.3 to 2.4), a birth weight below 2500 g at term (relative risk, 2.3; 95 percent confidence interval, 1.4 to 3.8), a birth weight below the fifth percentile for gestational age (relative risk, 3.0; 95 percent confidence interval, 2.0 to 4.4), and delivery between 24 and 32 weeks of gestation (relative risk, 2.1; 95 percent confidence interval, 1.1 to 4.0), but not with delivery between 33 and 36 weeks (relative risk, 1.0; 95 percent confidence interval, 0.7 to 1.5). CONCLUSIONS: Suboptimal first-trimester growth may be associated with low birth weight, low birth-weight percentile, and premature delivery.     

Buprenorphine versus methadone maintenance for opioid dependence

Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification of multiprotein complexes containing DNA replication factors by native immunoblotting of HeLa cell protein preparations with T-antigen-dependent SV40 DNA replication activity

Adequate prenatal care has been linked to improved birth outcomes in general populations but has not been assessed in HIV-infected women. We examined longitudinal claims files and vital statistics records for women in the New York State Medicaid HIV/AIDS data base delivering a singleton from 1985 through 1990. Adequacy of the self-reported number of prenatal visits was assessed by the Kessner index. In logistics models, we estimated the association of prenatal care, illicit drug use, and other maternal characteristics with three outcomes; low birth weight, preterm birth, and small-for-gestational-age. Of 2,254 singletons delivered by this HIV-infected cohort, 28% were low birth weight, 23% were preterm birth, and 20% were small for gestational age. Two-thirds had inadequate prenatal care. Non-drug users had 57 and 26% lower adjusted odds of low birth weight and preterm delivery than drug users. The adjusted odds of low birth weight and preterm birth for women with an adequate number of prenatal visits were, respectively, 48 and 21% lower than for women with inadequate care. Adequate prenatal care was also associated with a 43% reduction in the odds of small-for-gestational-age. An adequate number of prenatal visits by women in this HIV cohort was associated with a significant reduction in all three adverse birth outcomes, but most had inadequate prenatal care. These data support strengthening efforts to bring pregnant, HIV-infected women into care.     

Effectiveness of methadone maintenance for heroin addiction

Methadone maintenance programs have effectively reduced heroin dependency and are available in most countries affected by heroin addiction. Methadone, developed in Germany during World War II as a pain killer, does not have the euphoric effects of heroin and the goal of treatment is to substitute methadone for heroin use. Recidivism is probably a life-long risk. Methadone maintenance programs began in the 1960s in the United States in New York City. Once tolerance is developed, it may be used continually without harmful side effects. Dosage is important for effectiveness as are counseling, rehabilitation services, and employment support. Reduction in criminality and AIDS has been associated with methadone maintenance programs.     

Assessing the relationship between maternal opiate use and antepartum haemorrhage

AIMS/DESIGN: Assessment of the association between the regular use of opiates by women during pregnancy and antepartum haemorrhage has been made difficult by the low prevalence of these conditions observed in clinical settings. As a consequence, most published studies lack statistical power due to the small number of cases. We combined all suitable published data in a meta-analysis to assess the association more accurately. FINDINGS: Meta-analysis produced a pooled estimate of the crude odds ratio for antepartum haemorrhage in relation to maternal opiate use of 2.33 (95% CI 1.32-4.30). CONCLUSIONS: This odds ratio estimate is consistent with a moderately strong association. Studies included did not adjust for possible confounders (e.g. prenatal care, cocaine or tobacco), so confounding is likely to account for at least some of the observed effect. The relative consistency of results from studies included in the meta-analysis that were conducted in different countries and at different times adds to the strength of the evidence for an association between opiate use and antepartum haemorrhage. Well designed studies are urgently required to assess the independent effects of different types and patterns of maternal opiate use and confounders such as cigarette smoking, illicit cocaine use and antenatal care on antepartum haemorrhage.     

Birth characteristics and asthma symptoms in young adults: results from a population-based cohort study in Norway

There is evidence that the origin of obstructive lung disease may be traced back to foetal life. The associations between birth characteristics and asthma symptoms were studied in a random population sample of young Norwegian adults. Respiratory symptoms were recorded in a population-based questionnaire survey. The records of all subjects aged 20-24 yrs were linked with the Medical Birth Registry of Norway. Of 868 subjects born in Norway, there were 690 (79%) responders. The associations between asthma symptoms and birth characteristics were analysed by logistic regression, adjusted for possible confounding factors. Asthma symptoms in young adults were inversely associated with birth weight (odds ratio (OR)wheeze=0.82; 95% confidence interval (CI)=0.69-0.96x500 g increase in birth weight(-1))), and after adjustment for gestational age, birth length, parity and maternal age (ORwheeze=0.69; 95% CI=0.50-0.95x500 g increase in birth weight(-1)). The association did not vary according to adult smoking habits or atopic status and remained when premature and low weight births were excluded (ORwheeze=0.73; 95% CI=0.60-0.90x500 g increase in birth weight(-1)). The association was consistent for all asthma symptoms. Adjusted for birth weight, asthma symptoms were further associated with low gestational age, high birth length and low maternal age. In a random sample of young adults, asthma symptoms were strongly associated with low birth weight, an association driven by the full-term births within the normal birth weight range. The findings show that the risk for adult asthma is partly established early in life and suggest that poor intrauterine growth is involved in the aetiology of asthma.     

Hemodynamic performance of four mechanical bileaflet prosthetic valves in the mitral position: an echocardiographic study

Plasma methadone concentrations and its main metabolite D,L-2-ethylidiene-1,5-dimethyl-3,5-diphenylpyrrolidine (EDDP) were determined in 93 patients under methadone maintenance treatment to assess their relationship with heroin use and opioid withdrawal symptoms. Neither plasma concentrations of methadone nor EDDP were significantly different when patients that used heroin in last 3 months were compared with those testing negative for this drug (methadone, 355 +/- 217 versus 369 +/- 216 ng/ml, t = 0.29, P = NS; EDDP, 49 +/- 28 versus 54 +/- 40 ng/ml, t = 0.51, P = NS). No correlation between opioid withdrawal scale scores and plasma concentrations of methadone (r = 0.02, P = NS) and EDDP (r = -0.14, P = NS) was found. Therapeutic drug monitoring during methadone maintenance seems to be useful for assessing compliance with treatment but not for predicting heroin use and subjective withdrawal symptoms.     

Infant birth weight among women with or at high risk for HIV infection: The impact of clinical, behavioral, psychosocial, and demographic factors.

The purpose of these analyses was to provide a prospective examination of the impact of HIV on birth weight using clinical, behavioral, psychosocial, and demographic correlates. 319 HIV-positive and 220 HIV-negative pregnant women matched for HIV risk factors (i.e., drug use and sexual risk behaviors) were interviewed during the 3rd trimester of pregnancy and 6 weeks postpartum. Medical chart reviews were also conducted for the HIV-seropositive pregnant women to verify pregnancy-related and birth outcome data. In a logistic regression analysis, controlling for parity and gestational age, women who were HIV seropositive were 2.6 times more likely to have an infant with low birth weight. Black women and those who did not live with their partners were more than 2 times as likely to have infants with low birth weight, and those who smoked were 3.2 times more likely to have infants with low birth weight. Knowing that women with HIV, those who are Black, and those not living with a partner are at highest risk for adverse birth outcomes can help those in prenatal clinics and HIV specialty clinics to target resources and develop prevention interventions. This is particularly important for women with HIV because birth weight is associated with risk of HIV transmission from mother to child. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence for an association between environmental tobacco smoke exposure and birthweight: a meta-analysis and new data

Because of the strong association of active smoking with fetal growth retardation, increasing interest has focused on whether there is also an association with exposure to environmental tobacco smoke (ETS). We examined this issue in a retrospective study and by conducting a review of the literature and data pooling. In our study, nonsmoking women with singleton livebirths born in 1986-87 (n = 992) provided information on exposure to ETS for 1 h or more per day and paternal smoking. The risk of low birthweight (LBW, < 2500 g) was not increased in infants of ETS-exposed women, but there was a somewhat increased risk for LBW at term (adjusted odds ratio [OR] 1.8, 95% confidence interval [CI] 0.6, 4.8) and small-for-gestational-age (< 10th percentile of weight; OR = 1.4, 95% CI = 0.8, 2.5). These results were in the range of 16 other studies in the literature that had odds ratios from 1.0 to 2.2. A weighted average of the results of all studies on LBW at term or small-for-gestational-age yielded a pooled estimate of 1.2 [95% CI = 1.1, 1.3] in nonsmoking women. The pooled estimate of mean birthweight indicated a decrement of 28 g with ETS exposure of nonsmoking women [95% CI = -41, -16], with a greater decrement (about 40 g) seen among more homogeneous studies.     

Self-efficacy and illicit opioid use in a 180-day methadone detoxification treatment.

Self-efficacy ratings coincided with illicit opioid use across the 3 phases of a 180-day methadone detoxification treatment. Efficacy ratings increased after patients received their first dose of methadone, did not change while they were maintained on a stable dose of methadone, and declined during the taper as they attempted to face high-risk situations without the full benefit of methadone. Efficacy ratings measured at a point before a phase of treatment predicted illicit opioid use across that phase. For clarification of the relation between self-efficacy and illicit opioid use, 3 conceptual models proposed by J. S. Baer, C. S. Holt, and E. Lichtenstein (see record 1987-13846-001) were tested. Self-efficacy influenced subsequent drug use in parallel with previous behavior, but this influence was found only at the start of the stabilization phase and immediately before the start of the taper phase. These findings highlight the usefulness of the self-efficacy concept for the treatment of opioid addiction (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of maternal heroin and methadone use on birthweight

An analysis of birthweights of 337 neonates in relation to history of maternal narcotic usage was undertaken. Mean birthweight of infants born to mothers abusing heroin during the pregnancy was 2,490 gm, an effect primarily of intrauterine growth retardation. Low mean birthweight (2,615 gm) was also seen in infants born to mothers who had abused heroin only prior to this pregnancy, and mothers who had used both heroin and methadone during the pregnancy (2,535 gm). Infants born to mothers on methadone maintenance during the pregnancy had significantly higher mean birthweights (2.961 gm), but lower than the control group (3,176 gm). A highly significant relationship was observed between maternal methadone dosage in the first trimester and birthweight, i.e., the higher the dosage, the larger the infant. Heroin causes fetal growth retardation, an effect which may persist beyond the period of addiction. Methadone may promote fetal growth in a dose-related fashion after maternal use of heroin.     

Motivational Enhancement Therapy for Nicotine Dependence in Methadone-Maintained Pregnant Women.

Pregnant women who are dependent on nicotine and illicit substances are at especially high risk for health complications and psychosocial problems. Motivational enhancement therapy (MET) for reducing smoking during pregnancy was compared with standard-care practitioner advice in a 2-group randomized design. Participants were 63 pregnant opioid-dependent smokers seeking substance abuse treatment, methadone maintenance, and prenatal care. At a 10-week follow-up, self-report and biological measures (i.e., CO, cotinine) indicated no differences in smoking between the MET and standard-care groups. However, MET participants were more likely to have moved forward on the stage of change continuum than those in standard care. Intensive treatment for nicotine dependence, environmental interventions, and innovative harm reduction strategies are recommended to address the barriers to quitting observed in this population of pregnant women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

BCG vaccination in low birth weight newborns: analysis of lymphocyte proliferation, IL-2 generation and intradermal reaction to PPD

OBJECTIVE: To study vaccinal scar formation and post-vaccinal immune response in newborns with birth weight ranging from 2000 to 2499 g vaccinated in the first week of life with intradermal bacille Calmette-Guérin (BCG) (Moreau-Rio de Janeiro strain). METHOD: Specific immune response to PPD was assessed in 30 low birth weight newborns (mean birth weight = 2311.7 +/- 122.1 g; mean gestational age = 38.1 +/- 1.8 weeks) in comparison to 56 control infants (mean birth weight = 3198.9 +/- 267.2 g; mean gestational age = 38.5 +/- 1.2 weeks. RESULTS: Low birth weight infants have an efficient immune response to vaccinal stimulus when compared to control infants as judged by specific in vitro lymphocyte proliferation (mean SI = 9.7 +/- 12.9 vs SI = 8.8 +/- 10.0, P = 0.72) and IL-2 production (mean SI = 3.1 +/- 3.4 vs SI = 2.6 +/- 2.0, P = 0.38). Intradermal reaction to PPD was also comparable in both groups (mean induration diameter = 9.5 +/- 5.1 mm vs 9.6 +/- 5.0 mm, P = 0.94). CONCLUSION: These data suggest that low birth weight newborns show a good immune response to BCG, thus reinforcing the inclusion of such infants in regular vaccination programs with intradermal BCG.     

Relation of hemoglobin measured at different times in pregnancy to preterm birth and low birth weight in Shanghai, China

This paper addresses two questions: 1) What is the relation of hemoglobin in the second gestational month to preterm birth and low birth weight? 2) How does the relation differ when hemoglobin in the fifth or eighth month or the lowest pregnancy hemoglobin are examined in place of first trimester values? These relations were examined prospectively in 829 women from Shanghai, China in 1991-1992. The population was nearly homogeneous by race, parity, antenatal care, and smoking. Rates of birth outcomes were compared between hemoglobin categories based on 10 g/liter groupings, with 110-119 g/liter as the reference group. Rates of low birth weight and preterm birth (but not small-for-gestational age) were related to early pregnancy hemoglobin concentration in a U-shaped manner. The relative risks (95% confidence intervals) for preterm birth in women by g/liter of hemoglobin were 2.52 (0.95-6.64) for > or = 130 g/liter, 1.11 (0.41-2.99) for 120-129 g/liter, 1.64 (0.77-3.47) for 100-109 g/liter, 2.63 (1.17-5.90) for 90-99 g/liter, and 3.73 (1.36-10.23) for 60-89 g/liter. Use of hemoglobin values in the fifth or eighth month attenuated the association with preterm birth. When lowest pregnancy hemoglobin values were used, the association of anemia with both outcomes was obscured, and risk of preterm birth at high hemoglobin values increased dramatically.     

Neonatal Candida parapsilosis outbreak with a high case fatality rate

A Candida parapsilosis outbreak of 58 cases in a neonatal intensive care unit lasted for 55 months. Patients infected by or colonized with C. parapsilosis were mainly very low birth weight infants (birth weight < 1500 g). Their mean birth weight was 817 g and their mean gestational age was 28 weeks. Statistical analysis including logistic regression confirmed that prematurity was the main risk factor. The analysis also suggested that C. parapsilosis infection (or colonization) was associated with a poor prognosis. In infants with gestational age < 29 weeks the risk for death in C. parapsilosis-infected patients was 16-fold greater than in those with no C. parapsilosis infection. The case fatality rate of C. parapsilosis patients was higher than that of the controls (9 of 23 vs. 1 of 40; P < 0.0001). The outbreak was most likely a result of cross-infection because C. parapsilosis could be isolated only from the patients and from the hands of four nurses immediately after they had cared for a colonized patient. Cessation of the outbreak was temporally associated with long term parenteral fluconazole (6 mg/kg/day) prophylaxis.