Treatment of opioid-dependent pregnant women with buprenorphine

Aims: To assess the maternal and fetal acceptability of buprenorphine and neonatal abstinence syndrome (NAS) in children born to buprenorphine-maintained mothers. Design and setting: Open-label, flexible dosing, inpatient induction with outpatient maintenance, conducted at the University of Vienna within the existing pregnancy and drug addiction program. Participants: Fifteen opioid-dependent pregnant women. Intervention. Sublingual buprenorphine tablets (1-10 mg/day). Measurements: Mothers: withdrawal symptoms (Wang Scale), nicotine dependence (Fagerstrom Scale: FTQ) and urinalysis. Neonates: birth outcome and NAS (Finnegan Scale). Findings: All subjects were opioid-, nicotine- and cannabis-dependent. Buprenorphine was well tolerated during induction (Wang Score \< = 4) and illicit opioid use was negligible (91% opioid-negative). All maternal, fetal and neonatal safety laboratory measures were within normal limits or not of clinical significance. Mean birth outcome measures including gestational age at delivery (39.6 ± 1.5 weeks), Apgar scores (1 min = 8.9; 5 min = 9.9; and 10 min = 10), birth weight (3049 ± 346 g), length (49.8 ± 1.9 cm) and head circumference (34.1 ± 1.8 cm) were within normal limits. The NAS was absent, mild (without treatment) and moderate (with treatment) in eight, four and three neonates, respectively. The mean duration of NAS was 1.1 days. Conclusions: Buprenorphine appears to be well accepted by mother and fetus, and associated with a low incidence of NAS. Further investigation of buprenorphine as a maintenance agent for opioid-dependent pregnant women is needed.     

Transitioning from methadone to buprenorphine maintenance in management of opioid use disorder during pregnancy

Background: Opioid use disorder during pregnancy is a growing health concern. Methadone maintenance is the treatment of choice but emerging data indicate buprenorphine is a viable alternative. Due to costs and limited accessibility of methadone, pregnant women may require transition from methadone to buprenorphine for maintenance treatment. Objectives: To assess safety and effectiveness of transitioning from methadone to buprenorphine when necessary during pregnancy. Methods: A standardized protocol using low buprenorphine doses to minimize emergent withdrawal symptoms under careful obstetric and psychiatric monitoring was implemented in 20 pregnant women. Outpatient maternal and neonatal outcomes were assessed. Results: Women maintained on an average methadone dose of 44 ± 4.77 (20–100) mg/day (mean±standard error mean (SEM); range) were successfully transitioned to 12.60 ± 0.8 (8–16) mg/day (mean±SEM; range) of buprenorphine. Within 4 weeks of transition, 15% had illicit drugs detected in urine drug screens. Ninety percent of women maintained outpatient follow-up until delivery. At delivery, 38.9% of mothers were exclusively adherent to buprenorphine (without use of illicit substances and/or other psychotropic medications); this resulted in significantly lower rates of neonatal abstinence syndrome (NAS) and shorter hospital stays. Discussion: Pregnant women transitioned from methadone to buprenorphine maintenance showed maternal and neonatal outcomes comparable to studies of women on buprenorphine throughout pregnancy. Infants born to buprenorphine-maintained women who abstained from illicit substances and other prescribed psychotropic medications experienced less severe NAS and shorter hospitalizations compared with women with illicit substance use and other psychotropic medications. These findings suggest women can safely be transitioned from methadone to buprenorphine during pregnancy.     

Comparison of methadone and slow-release morphine maintenance in pregnant addicts

Aims. To investigate whether the neonatal abstinence syndrome (NAS) is different in children born to women maintained on slow-release morphine, compared with those maintained on methadone, and to compare additional drug consumption in these groups of women . Design, Setting and Participants. An open, randomized trial was conducted in an established clinic. Forty-eight pregnant women who presented to the clinic as opiate or polysubstance abusers were enrolled and maintained on either methadone (24 women) or slow-release morphine (24 women) up to and following delivery. The programme included psychosocial therapy and support for their opiate-addicted partners . Measurements. Standard urinalysis methods were used to measure consumption of cocaine and benzodiazepines during pregnancy. Injection sites were monitored to indicate additional opiate use. NAS was measured according to Finnegan score and the amount of phenobarbiturates prescribed to alleviate the symptoms . Findings. No difference was found in the number of days that NAS was experienced by neonates born to methadone or morphine maintained mothers (mean = 16 and 21 days, respectively). All children were born healthy and no serious complications arose. Fewer benzodiazepines ( p 0.05) and fewer additional opiates ( p 0.05) were consumed by the morphinemaintained women compared with those who took methadone, but no difference was seen in cocaine consumption. Nicotine consumption was reduced significantly in both groups during pregnancy ( p 0.02) . Conclusions. Both methadone and morphine are suitable maintenance agents for pregnant opiate addicts. Maintenance agents that result in a less prolonged NAS should be studied in further trials.     

Buprenorphine withdrawal syndrome in newborns: a report of 13 cases

Aims To assess neonatal abstinence syndrome (NAS) and neurodevelopmental outcome in infants born to addicted mothers under buprenorphine substitution therapy. Setting District general hospital, Angoulême, France. Methods Retrospective case records study of infants admitted to the neonatal intensive care unit (NICU) and/or special care baby unit (SCBU) from January 1994 to December 2000 for surveillance and/or treatment of buprenorphine NAS. Results Thirteen infants were born to addicted mothers under buprenorphine maintenance therapy during the study period. Eight were male and five were female; mean birth term and weight were 39 weeks gestation and 3000 g, respectively. Apgar scores were within normal limits; four infants were small for gestational age, none was dysmorphologic and none was extracted for fetal distress. NAS occurred in 11 cases (85%) and required treatment in 10 cases. Morphine chlorhydrate 0.5 mg/kg/day was administered in divided doses to seven children and gave better results than paregoric alone or in combination with diazepam. Upon follow‐up, seven children presented transient lower limbs hypertonia, jerky movements and jitteriness that lasted 3–9 months. The overall milestones acquisitions were within normal limits. Conclusion Buprenorphine substitution seems to be safe during pregnancy, and has had no teratogenic effects reported to date. It induces NAS of variable intensity that is less prolonged in comparison to methadone; the neurodevelopmental outcome of exposed children is normal in the majority of cases, although some presented with transient motor abnormalities that resolved completely in 85% of those recruited to our study.     

Methadone in pregnancy: treatment retention and neonatal outcomes

AIM: To examine the association between retention in methadone treatment during pregnancy and key neonatal outcomes. DESIGN: Client data from the New South Wales Pharmaceutical Drugs of Addiction System was linked to birth information from the NSW Midwives Data Collection and the NSW Inpatient Statistics Collection from 1992 to 2002. MEASUREMENTS: Obstetric and perinatal characteristics of women who were retained continuously on methadone maintenance throughout their pregnancy were compared to those who entered late in their pregnancies (less than 6 months prior to birth) and those whose last treatment episode ended at least 1 year prior to birth. FINDINGS: There were 2993 births to women recorded as being on methadone at delivery, increasing from 62 in 1992 to 459 births in 2002. Compared to mothers who were maintained continuously on methadone throughout their pregnancy, those who entered treatment late also presented later to antenatal services, were more likely to arrive at hospital for delivery unbooked, were more often unmarried, indigenous and smoked more heavily. A higher proportion of neonates born to late entrants were born at less than 37 weeks gestation and were admitted to special care nursery more often. CONCLUSION: Continuous methadone treatment during pregnancy is associated with earlier antenatal care and improved neonatal outcomes. Innovative techniques for early engagement in methadone treatment by pregnant heroin using women or those planning to become pregnant should be identified and implemented.     

Buprenorphine in pregnant opioid-dependent women: first results of a prospective study

Aim To report results on the prospective follow‐up of 34 pregnant women exposed to buprenorphine maintenance for opiate dependence. Design and setting Prospective multicentre study: all pregnant women receiving buprenorphine as maintenance therapy were included as early as possible during their pregnancy. Participants The pregnant women were recruited from opiate maintenance therapy centres, general practitioner‐networks involved in addiction, maternity hospitals and centres for drug information during pregnancy. Measurements Women: drugs and medications consumed, medical and obstetrical events; offspring: withdrawal syndrome, malformation, neonatal disease. Findings The buprenorphine‐exposed pregnancies resulted in 31 live births, one stillbirth, one spontaneous abortion and one voluntary termination. A neonatal withdrawal syndrome was observed in 13 cases (41.9%) and eight of these babies required opiate treatment. Two neonates had a malformation: a premature ductus arteriosus stricture and a tragus appendix. Conclusion Taken together with other prospective studies, no alarming results were observed concerning pregnancy outcomes. However, further data from the comparative prospective study are required to determine whether buprenorphine can be considered as a good alternative to methadone treatment in pregnant women.     

Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy comparison study

AIMS: To evaluate the efficacy and safety of methadone versus buprenorphine treatment in pregnant opioid-dependent women. DESIGN: Randomized, double-dummy, double-blind, flexible-dosing comparison study. SETTING: Addiction Clinic at the Medical University of Vienna, Austria. PARTICIPANTS: Eighteen women were assigned randomly to receive either methadone (n = 9) or buprenorphine (n = 9) during weeks 24-29 of pregnancy. After dropouts, data were available from 14 cases (six in the methadone and eight in the buprenorphine group). INTERVENTION: Sublingual buprenorphine tablets (8-24 mg/day) or oral methadone solution (40-100 mg/day), with matched placebos. MEASUREMENTS: Mothers: retention in treatment, urine toxicology and nicotine use. Neonates: Routine birth data, neonatal abstinence syndrome (NAS) in severity and duration. FINDINGS: There was somewhat greater retention in the buprenorphine group but significantly lowered use of additional opioids in the methadone group (P = 0.047).Neonates: There was earlier onset of NAS in neonates born to the methadone (mean 60 hours) than to the buprenorphine groups (mean 72 hours after last medication); 43% did not require NAS-treatment with short treatment duration in both groups (mean 5 days). CONCLUSION: This preliminary study had limited power to detect differences but the trends observed suggest this kind of research is practicable and that further studies are warranted.     

ALT异常对HBsAg阳性孕妇妊娠过程与结局的影响

目的探讨孕期异常的ALT对HBsAg阳性的孕妇妊娠并发症及妊娠结局的影响。方法将327例HB-sAg阳性孕妇根据孕期ALT水平分为ALT正常组（n=251）和ALT异常组（n=76）,比较两组的妊娠期并发症和最终的妊娠结局。结果与ALT正常组比较,ALT异常组早产、胎儿窘迫和产后出血发生率明显升高（P均〈0.05）;ALT异常组低体重儿发生率高于ALT正常组（P〈0.05）;ALT异常组所分娩新生儿体质量、胎龄、出生后1 min Ap-gar评分均低于ALT正常组（P均〈0.01）。结论 HBsAg阳性的孕妇若妊娠期出现ALT异常,更易增加妊娠期并发症并影响妊娠结局。     

Factors predictive of neonatal thrombocytopenia in pregnant women with immune thrombocytopenia

To determine predictive factors for neonatal thrombocytopenia in deliveries with immune thrombocytopenia (ITP), we conducted a retrospective study at a tertiary hospital between 1997 and 2013. During this period, 30 women with ITP delivered 44 children. Neonatal thrombocytopenia (<100 × 10⁹/L) at birth was observed in seven neonates; four of these cases were severe (<50 × 10⁹/L). No cases were complicated by intracranial hemorrhage, and there was no neonatal mortality. Platelet counts at birth of neonates born to mothers, who had first been diagnosed with ITP during pregnancy were significantly higher than those born to mothers diagnosed with ITP before pregnancy. There were significant correlations between neonatal platelet counts in the first and second siblings at birth (P = 0.015) and at nadir (P = 0.035). Platelet counts of neonates born vaginally were significantly more likely to decline after birth than those delivered by cesarean section (13/16 vs. 10/23, P = 0.024). In conclusion, diagnosis of ITP before pregnancy was significantly associated with neonatal thrombocytopenia, and the platelet count of an older sibling is a strong predictor for that of the next baby. The delivery mode may be an indicator of the timing of platelet count nadir after birth.     

Methadone dose and neonatal abstinence syndrome—systematic review and meta‐analysis

Aim To determine if there is a relationship between maternal methadone dose in pregnancy and the diagnosis or medical treatment of neonatal abstinence syndrome (NAS). Methods PubMed, EMBASE, the Cochrane Library and PsychINFO were searched for studies reporting on methadone use in pregnancy and NAS (1966–2009). The relative risk (RR) of NAS was compared for methadone doses above versus below a range of cut‐off points. Summary RRs and 95% confidence intervals (CI) were estimated using random effects meta‐analysis. Sensitivity analyses explored the impact of limiting meta‐analyses to prospective studies or studies using an objective scoring system to diagnose NAS. Results A total of 67 studies met inclusion criteria for the systematic review; 29 were included in the meta‐analysis. Any differences in the incidence of NAS in infants of women on higher compared with lower doses were statistically non‐significant in analyses restricted to prospective studies or to those using an objective scoring system to diagnose NAS. Conclusions Severity of the neonatal abstinence syndrome does not appear to differ according to whether mothers are on high‐ or low‐dose methadone maintenance therapy.     

Pregnancy-associated malaria affects toll-like receptor ligand-induced cytokine responses in cord blood

BACKGROUND: Pregnancy-associated malaria is known to modify fetal immunity. Most previous studies have been cross-sectional in nature and have focused on the priming of acquired immune responses in utero. In this context, the influence of the timing and/or duration of placental infection with Plasmodium falciparum are unknown, and changes to innate immune responses have not been studied extensively. METHODS: Pregnant women in Gabon, where P. falciparum infection is endemic, were followed up through monthly clinical and parasitological examinations from the second trimester to delivery. Cells of neonates born to mothers who had acquired P. falciparum infection 相似文献   

Goitrogenesis during pregnancy and neonatal hypothyroxinaemia in a borderline iodine sufficient area

OBJECTIVE: Severe iodine deficiency disorders (IDDs) may have been eradicated in many parts of the world, but milder forms still exist and may escape detection. We evaluated the impact of pregnancy on the maternal and fetal thyroid axis in Hong Kong, a coastal city in southern China with borderline iodine intake. DESIGN: A prospective study performed in a maternity hospital. PATIENTS: Two hundred and thirty pregnant women were prospectively studied and their neonates assessed at birth. MEASUREMENTS: Urine iodine concentration, thyroid function tests and thyroid volume (TV) by ultrasound were determined in the mothers during pregnancy and up to 3 months postpartum and in the neonates. RESULTS: Increased urinary iodine concentration was seen from first trimester onwards and the proportion of women having urine iodine concentration of < 0.4 micromol/l decreased from 11.3% in the first trimester to 4.7% in the third trimester. There was progressive reduction in circulating fT4 and fT3 concentrations and free thyroxine index (FTI) with increasing gestation and the percentage of women having subnormal levels at term were 53.2%, 61.1% and 4.8%, respectively. The serum TSH concentration during pregnancy doubled towards term. In the first trimester, multiparous women had significantly larger TV than the nulliparous women (P < 0.001). By the third trimester, TV had increased by 30% (range 3-230%) so that the goitre incidence was 14.1%, 21.8%, 25.9% during the three trimesters of pregnancy, and 24.3% and 21.9% at 6 weeks and 3 months postpartum (ANOVA, P < 0.05). The change in thyroid volume during pregnancy correlated positively with the change in thyroglobulin (r = 0.225, P < 0.002) and negatively with urinary iodine concentration (r = - 0.149, P < 0.02). Fourteen women with excessive thyroidal stimulation in the second trimester (defined as those with thyroglobulin (Tg) concentrations in the highest tertile and FTI in the lowest tertile) were found to have lower urine iodine concentrations and larger TV (both P < 0.005) throughout pregnancy, and their neonates had higher cord TSH (P < 0.05), Tg (P < 0.05) and slightly larger TV (P = 0.06) as compared to the findings in 216 pregnant women without evidence of thyroid stimulation. Seven neonates (50%) born to these women had subnormal fT4 levels at birth. CONCLUSION: In a borderline iodine sufficient area, pregnancy posed an important stress resulting in higher rates of maternal goitrogenesis as well as neonatal hypothyroxinaemia and hyperthyro- trophinaemia. An adequate iodization program is necessary to eliminate iodine deficiency disorders during pregnancy.     

Cord blood iodothyronine and thyrotropin concentrations in newborns of mothers exposed to povidone iodine in the last trimester

In the present study, we have evaluated thyroid function in neonates at delivery and in their mothers who used vaginal povidone-iodine (PVP-I) during the last trimester of pregnancy. Newborns and their mothers without a history of iodine exposure, admitted to the same department and residing in the same geographical area served as controls. Maternal serum thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and thyrotropin (TSH) concentrations at delivery were not significantly different between the two groups of pregnant women. Cord blood thyroid hormone concentrations in the newborns of iodine exposed mothers were not significantly different from those in control newborns. In contrast, cord blood TSH concentrations in the neonates of mothers exposed to PVP-I during the last trimester of pregnancy were significantly higher than values in control neonates (p less than 0.05). These data confirm that the fetal thyroid gland, even in the last trimester of pregnancy, does not adapt completely to the inhibitory action of iodine on thyroid hormone synthesis and/or release.     

A longterm follow-up study of children born to women with contagious diseases at delivery

Data are presented from a long-term follow-up study of 308 live born children to women admitted post partum to the Department of Infectious Diseases (DID), Danderyd Hospital, Sweden, during a 10-year period (1975-1984) for avoiding nosocomial transmission of infections in the obstetrical wards. The rate of stillbirths (1/309 deliveries) was not higher than reported for all births in Stockholm. 20% of the live born children were transferred within 24 h after birth to the pediatric department for observation, but half of them could return to their mothers at the DID within 6 days (generally 3 days). Four newborns were treated at an intensive care unit. Only 3 fatalities occurred, all of them among newborns to mothers with an overt infection at delivery. The fatality rate (1.8%) was significantly higher among the newborns of these mothers than normally (0.3%) noted among all children born in Stockholm county during the period studied. Two of the 3 newborns, who all died within 3 days of life, had a low birth weight (600 and 1,000 g). The total number of newborns with low birth weights (less than 2,500 g) was, however, not higher in the above-mentioned group of newborns than for all children born in Stockholm county 1980. None of the 3 fatalities was caused by infection transmitted from the mother. No further deaths occurred. Infections in pregnancy at term, at birth or post partum were transmitted from the women to 41 (13%) of their newborns.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of smoking on neonatal and maternal serum and breast milk leptin levels

Maternal smoking is considered to be a risk factor for low birth weight. It is hypothesized that alteration in leptin concentration may be associated with reduced fetal growth. In this study, we assess the effect of smoking during pregnancy on maternal and neonatal serum leptin concentrations, and also on breast milk leptin levels. When the infants were brought to routine physical examination at 7 days old, blood samples and breast milk specimens were taken for leptin measurement from mothers who smoked during pregnancy and their newborns. Nonsmoking mothers and their infants were recruited randomly over the same period as a control group. Maternal age, number of pregnancy, weight of the mothers, birth weight, and gestational age of the infants were similar in both groups (p > 0.05). There was no significant difference between groups in maternal serum and breast milk leptin levels (p = 0.14 and p = 0.96, respectively). However, serum leptin levels were found significantly lower in neonates born to smoking mothers compared with infants born to nonsmoking mothers (p = 0.02). Our findings suggest that maternal smoking dose not have an effect on maternal serum and breast milk leptin levels but decreases neonatal serum leptin concentration independent of birth weight.     

Relationships between severe neonatal thrombocytopenia and maternal characteristics in pregnancies associated with autoimmune thrombocytopenia

In pregnant women with antecedents of autoimmune thrombocytopenia (AITP), no predictive factor for severe fetal thrombocytopenia has been identified. We evaluated the relationships between the course of the maternal disease before and during pregnancy and the risk of severe fetal thrombocytopenia, in 64 pregnant women with known chronic AITP antecedents, over a 12-year period. 28 pregnant women had undergone splenectomy before pregnancy and 17 experienced severe thrombocytopenia (< 50 × 10⁹/l) during pregnancy (monthly determination). Eight infants presented with severe thrombocytopenia at birth (12.5%), and four in the following days (6.25%). No severe haemorrhage was observed. Severe thrombocytopenia at birth was present in 57% (CI 95% 18–90%) of the infants born to mothers with severe pregnancy-associated thrombocytopenia and splenectomy antecedents, and in 0% (CI 95% 0–15%) of the infants born to mothers who presented none of these antecedents ( P  = 0.001). In thrombocytopenic mothers the infant platelet counts at birth were positively correlated to the nadir maternal platelet count during the index pregnancy ( r  = 0.42, P  = 0.0075).
These results suggest that severe autoimmune disease is a risk factor for severe fetal thrombocytopenia, and that pregnant women with no antecedent of splenectomy nor severe thrombocytopenia during pregnancy have a very low risk of severe fetal thrombocytopenia.     

Methadone and perinatal outcomes: a prospective cohort study

Aims Methadone use in pregnancy has been associated with adverse perinatal outcomes and neonatal abstinence syndrome (NAS). This study aimed to examine perinatal outcomes and NAS in relation to (i) concomitant drug use and (ii) methadone dose. Design Prospective cohort study. Setting Two tertiary care maternity hospitals. Participants A total of 117 pregnant women on methadone maintenance treatment recruited between July 2009 and July 2010. Measurements Information on concomitant drug use was recorded with the Addiction Severity Index. Perinatal outcomes included pre‐term birth (<37 weeks' gestation), small‐for‐gestational‐age (<10th centile) and neonatal unit admission. NAS outcomes included: incidence of medically treated NAS, peak Finnegan score, cumulative dose of NAS treatment and duration of hospitalization. Findings Of the 114 liveborn infants 11 (9.6%) were born pre‐term, 49 (42.9%) were small‐for‐gestational‐age, 56 (49.1%) had a neonatal unit admission and 29 (25.4%) were treated medically for NAS. Neonates exposed to methadone‐only had a shorter hospitalization than those exposed to methadone and concomitant drugs (median 5.0 days versus 6.0 days, P = 0.03). Neonates exposed to methadone doses ≥80 mg required higher cumulative doses of morphine treatment for NAS (median 13.2 mg versus 19.3 mg, P = 0.03). The incidence and duration of NAS did not differ between the two dosage groups. Conclusions The incidence and duration of the neonatal abstinence syndrome is not associated with maternal methadone dose, but maternal opiate, benzodiazepine or cocaine use is associated with longer neonatal hospitalization.     

A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura

Numerous studies have examined the outcomes of infants born to mothers with idiopathic thrombocytopenic purpura (ITP). Fewer studies have discussed the morbidity of obstetric patients with ITP. We describe a retrospective study of 92 women with ITP during 119 pregnancies over an 11-year period. Most women had thrombocytopenia during pregnancy. At delivery, women in 98 pregnancies (89%) had platelet counts lower than 150 x 109/L; most had mild to moderate thrombocytopenia. For many, the pregnancy was uneventful; however, women had moderate to severe bleeding in 25 pregnancies (21.5%). Women in 37 pregnancies (31.1%) required treatment to increase platelet counts. During delivery, 44 women (37.3%) received epidural analgesia without complications, with most having a platelet count between 50 and 149 x 109/L. Most deliveries (82.4%) were vaginal. Bleeding was uncommon at delivery. Infant platelet counts at birth ranged from 12 to 436 x 109/L; 25.2% of infants had platelet counts lower than 150 x 109/L, and 9% had platelet counts lower than 50 x 109/L. Eighteen infants (14.6%) required treatment for hemostatic impairment. Two fetal deaths occurred. One was caused by hemorrhage. ITP in pregnancy carries a low risk, but mothers and infants may require therapy to raise their platelet counts.