Substance misuse problems during pregnancy with special emphasis on buprenorphine

Maternal drug abuse during pregnancy endangers the future health and wellbeing of the infant and growing child. On the other hand, via maternal abstinence, these problems would never occur; so the problems would be totally preventable. Buprenorphine is widely used in opioid maintenance treatment as a substitute medication. In Finland, during 2000 s buprenorphine misuse has steadily increased. In 2009 almost one third of clientele of substance treatment units were in treatment because of buprenorphine dependence. At Helsinki Women s Clinic the first child with prenatal buprenorphine exposure was born in 2001. During 1992-2001 in the three capital area maternity hospitals (Women s clinic, Maternity hospital, Jorvi hospital) 524 women were followed at special antenatal clinics due to substance abuse problems. Three control women were drawn from birth register to each case woman and matched for parity and same place and date of the index birth. According to register data mortality rate was 38-fold higher among cases than controls within 6-15 years after index birth. Especially, the risk for violent or accidental death was increased. The women with substance misuse problems had also elevated risk for viral hepatitis and psychiatric morbidity. They were more often reimbursed for psychopharmaceuticals. Disability pensions and rehabilitation allowances were more often granted to cases than controls. In total 626 children were born from these pregnancies. According to register data 38% of these children were placed in out-of-home care as part of child protection services by the age of two years, and half of them by the age of 12 years, the median follow-up time was 5.8 years. The risk for out-of-home care was associated with factors identifiable during the pre- and perinatal period. In 2002-2005 67 pregnant women with buprenorphine dependence were followed up at the Helsinki University Hospital, Department of Obstetrics and Gynecology. Their pregnancies were uneventful. The prematurity rate was similar and there were no more major anomalies compared to the national statistics. The neonates were lighter compared to the national statistics. They were also born in good condition, with no perinatal hypoxia as defined by standard clinical parameters or certain biochemical markers in the cord blood: erythropoietin, S100 and cardiac troponin-t. Almost 80% of newborns developed neonatal abstinence syndrome (NAS) and two third of them needed morphine medication for it. Maternal smoking over ten cigarettes per day aggravated and benzodiazepine use attenuated NAS. An infant s highest urinary norbuprenorphine concentration during their first 3 days of life correlated with the duration of morphine treatment. The average length of infant s hospital stay was 25 days.Äidin raskaudenaikainen päihteidenkäyttö vaarantaa syntyvän lapsen terveyden ja hyvinvoinnin. Samalla se on myös suurin yksittäinen täysin estettävissä oleva uhkatekijä näille ongelmille. Suomessa on 2000-luvun alusta alkaen yleistynyt buprenorfiinin, opioidikorvaushoidossa käytetyn lääkeaineen väärinkäyttö. Vuonna 2009 jo kolmasosaa päihdehoidossa olevista henkilöistä hoidettiin buprenorfiinin väärinkäytön vuoksi. Helsingin Naistenklinikalla syntyi ensimmäinen buprenorfiinille raskaudenaikana altistunut lapsi vuonna 2001. Rekisteritietojen perusteella raskauden aikana vuosina 1992 2001 päihdeongelman vuoksi pääkaupunkiseudun synnytyssairaaloissa (Naistenklinikka, Kätilöopisto, Jorvi) erityisäitiyspoliklinikoilla seurattujen 524 naisten kuolleisuus oli 38-kertainen 6 15 vuoden seurannassa verrattuna naisiin, joilla ei kyseistä ongelmaa ollut. Erityisesti väkivaltaisen tai onnettomuuden seurauksena tapahtuvan kuoleman riski oli suurentunut. Päihdeongelmaisilla naisilla oli enemmän virusmaksatulehduksia ja psyykkisiä sairauksia ja heille maksettiin useammin korvauksia psyykenlääkkeiden ostosta. He saivat myös useammin korvauksia työttömyyden ja työkyvyttömyyden vuoksi kuin verrokkinaiset. Rekisteritietojen perusteella näistä raskauksista syntyneistä 626 lapsista 38 % otettiin huostaan kahden vuoden ikään mennessä ja 50 % 12 vuoden ikään mennessä seuranta-ajan ollessa 2 12 vuotta (keskiseuranta-aika 5,8 vuotta). Jo raskausaikana oli tunnistettavissa huostaanotolle altistavia tekijöitä. Vuosina 2002 2005 Helsingin Naistenklinikalla seurattiin 67 buprenorfiinia käyttävän naisen raskauden ja synnytyksen kulkua. Raskaudet sujuivat säännöllisesti ja jatkuivat yhtä usein täysiaikaisiksi eikä heillä esiintynyt synnynnäisiä epämuodostumia useammin kuin väestössä keskimäärin. Vauvojen syntymäpaino oli kuitenkin pienempi kuin väestössä keskimäärin. Vastasyntyneet olivat syntyessään hyväkuntoisia eikä heillä ollut hapenpuutteeseen viittaavia löydöksiä tutkittaessa hapenpuutteeseen liittyviä merkkiaineita napaverestä. Sen sijaan lähes 80 % buprenorfiinille altistuneista vastasyntyneistä kärsi vieroitusoireista, ja kaksi kolmasosaa tarvitsi niiden hoidoksi morfiinilääkitystä. Äidin runsas tupakointi (yli kymmenen savuketta päivässä) pahensi vastasyntyneen vieroitusoireita, sen sijaan äidin raskaudenaikainen bentsodiatsepiinilääkitys lievensi niitä. Buprenorfiinin aineenvaihduntatuotteen, norbuprenorfiinin pitoisuus vastasyntyneen virtsassa kolmen ensimmäisen elinpäivän aikana ennusti vastasyntyneen tarvitseman morfiinihoidon kestoa. Vastasyntyneet viettivät sairaalahoidossa keskimäärin 25 päivää

Sikiöaikainen alkoholialtistus ja FASD: tunnistaminen, hoito ja haittojen ehkäisy

• Raskaudenaikainen alkoholinkäyttö voi aiheuttaa sikiölle useaan elinjärjestelmään pysyviä vaurioita, ¬joiden vaikeusaste vaihtelee. • Tunnistamista olisi mahdollista tehostaa tutkimalla odottajilta alkoholin käyttöä mittaava veren fosfatidyyli¬etanoli (B-PEth) äitiysneuvoloissa. • Alkoholista on turvallisinta pidättäytyä koko raskauden ajan ja jo raskautta suunniteltaessa. • Sikiöaikana päihteille altistuneen lapsen epäedulliset elinolosuhteet saattavat lisätä kehityksen ongelmia. • Välittävä ja oikea-aikaisia virikkeitä tarjoava kasvuympäristö voi lieventää altistuksen haitallisia vaikutuksia.Peer reviewe

Huumeet ja raskaus

English summaryPeer reviewe

18q12.3-q21.1 microdeletion detected in the prenatally alcohol-exposed dizygotic twin with discordant fetal alcohol syndrome phenotype

Abstract Background A pair of dizygotic twins discordantly affected by heavy prenatal alcohol exposure (PAE) was reported previously by Riikonen, suggesting the role of genetic risk or protective factors in the etiology of alcohol-induced developmental disorders. Now, we have re-examined these 25-year-old twins and explored genetic origin of the phenotypic discordancy reminiscent with fetal alcohol syndrome (FAS). Furthermore, we explored alterations in DNA methylation profile of imprinting control region at growth-related insulin-like growth factor 2 (IGF2)/H19 locus in twins' white blood cells (WBC), which have been associated earlier with alcohol-induced genotype-specific changes in placental tissue. Methods Microarray-based comparative genomic hybridization (aCGH) was used to detect potential submicroscopic chromosomal abnormalities, and developmental as well as phenotypic information about twins were collected. Traditional bisulfite sequencing was used for DNA methylation analysis. Results Microarray-based comparative genomic hybridization revealed a microdeletion 18q12.3-q21.1. in affected twin, residing in a known 18q deletion syndrome region. This syndrome has been associated with growth restriction, developmental delay or intellectual deficiency, and abnormal facial features in previous studies, and thus likely explains the phenotypic discordancy between the twins. We did not observe association between WBCs? DNA methylation profile and PAE, but interestingly, a trend of decreased DNA methylation at the imprinting control region was seen in the twin with prenatal growth retardation at birth. Conclusions The microdeletion emphasizes the importance of adequate chromosomal testing in examining the etiology of complex alcohol-induced developmental disorders. Furthermore, the genotype-specific decreased DNA methylation at the IGF2/H19 locus cannot be considered as a biological mark for PAE in adult WBCs.Peer reviewe

Cohort profile: ADEF Helsinki – a longitudinal register-based study on exposure to alcohol and drugs during foetal life

Purpose:The need for longitudinal studies on prenatal substance exposure (PSE) extending into adulthood is widely recognised. In particular, studies on the dual effect of exposure to substances and adverse childhood experiences are needed. This register-based matched cohort study investigates the effect of this dual exposure on the health and development of youth with PSE. The follow-up is from birth to young adulthood.Participants:The exposed youth were born in 1992?2001 to mothers with a significant substance misuse problem during pregnancy. The mothers were identified in primary care maternity clinics in the Helsinki metropolitan area and referred for intensified pregnancy follow-up in a tertiary care setting (HAL-clinics). Data from hospital medical records were collected for the mothers during the pregnancy follow-up and linked with register data from multiple national health and social welfare registers obtained for each mother?child dyad from birth until the end of 2015?2018. Similar register data were gathered for three matched mother?child dyads without any evidence of the mother?s substance misuse in national health and social welfare registers. The study consists of 615 exposed and 1787 unexposed youth aged 15?24 years.Findings to date:A majority of the exposed youth (64%) had been in out-of-home care at least once compared with 8% among the unexposed. Outpatient and inpatient hospital care due to mental or behavioural disorders were two to three times more common among the exposed than among the unexposed. The exposed had less often completed secondary school education and had more often needed social assistance.Future plans:The data comprise a wide range of information on infant health, youth?s mental and somatic health and development, out-of-home care history, and mother?s life situation at the delivery and later health. Risk and protective factors for different long-term developmental outcomes in adolescence or in young adulthood will be studied.Peer reviewe

Prenatal substance exposure, adverse childhood experiences and diagnosed mental and behavioral disorders - A longitudinal register-based matched cohort study in Finland

Both prenatal substance exposure (PSE, alcohol/drugs) and experiences during the first years of life have powerful effects on brain development. However, only a few studies have investigated the combined effect of PSE and adverse childhood experiences (ACEs) on mental and behavioral disorders among exposed adolescents and adults. This longitudinal register-based cohort study 1) compared the nature and extent of diagnosed mental and behavioral disorders among youth with PSE and matched unexposed controls, and 2) investigated the influence of PSE, health in infancy and ACEs (maternal risk factors and out-of-home care, OHC) on diagnoses of mental and behavioral disorders. The data consisted of 615 exposed youth aged 15-24 years and 1787 matched unexposed controls. Data from hospital medical records and nine registers were merged for the analysis. Descriptive analysis methods and Cox regression were used. The results showed that the prevalence of mental and behavioral disorders was twice as high among exposed compared with controls. The highest levels of mental and behavioral disorders and ACEs were found among exposed with at least one OHC episode. The difference in the risk of mental and behavioral disorders between exposed and controls diminished after controlling for the effect of ACEs. Low birth weight, maternal risk factors, and OHC were the strongest predictors of mental and behavioral disorders. The results suggest that PSE alone does not explain poorer mental health among exposed youth. Risk factors accumulate, and low birth weight and ACEs are strongly associated with increased risk of mental and behavioral disorders.Peer reviewe

Buprenorphine-naloxone, buprenorphine, and methadone throughout pregnancy in maternal opioid use disorder

IntroductionCurrent WHO guidelines recommend using methadone or buprenorphine as maintenance treatments for maternal opioid use disorder. However, buprenorphine-naloxone, with a lower abuse risk than buprenorphine monotherapy or methadone, offers a potentially beneficial alternative, but scientific evidence on its effects on pregnancies, fetuses, and newborns is scarce. This paper compares the outcomes of the pregnancies, deliveries, and newborns of women on buprenorphine-naloxone, buprenorphine, or methadone maintenance treatments. According to the hypothesis, as a maintenance treatment, buprenorphine-naloxone does not have more adverse effects than buprenorphine, whereas methadone is more complicated. Material and methodsIn this population-based study, 172 pregnant women on medical-assisted treatments were followed-up at Helsinki University Women's Hospital (Finland). Women receiving the same opioid maintenance treatment from conception to delivery and their newborns were included. Consequently, 67 mother-child dyads met the final inclusion criteria. They were divided into three groups based on their opioid pharmacotherapy. The outcomes were compared among the groups and, where applicable, with the Finnish population. ResultsThe buprenorphine-naloxone and buprenorphine groups showed similar outcomes and did not significantly differ from each other in terms of maternal health during pregnancies, deliveries, or newborns. Illicit drug use during the pregnancy was common in all groups, but in the methadone group it was most common (p = 0.001). Most neonates (96%) were born full-term with good Apgar scores. They were of relatively small birth size, with those in the methadone group tending to be the smallest. Of the neonates 63% needed pharmacological treatment for neonatal opioid withdrawal syndrome. The need was lower in the buprenorphine-based groups than in the methadone group (p = 0.029). ConclusionsBuprenorphine-naloxone seems to be as safe for pharmacotherapy for maternal opioid use disorder as buprenorphine monotherapy for both mother and newborn. Hence it could be a choice for oral opioid maintenance treatment during pregnancy, but larger studies are needed before changing the official recommendations. Women on methadone treatment carry multifactorial risks and require particularly cautious follow up. Furthermore, illicit drug use is common in all treatment groups and needs to be considered for all patients with opioid use disorder.Peer reviewe

Completed secondary education among youth with prenatal substance exposure : A longitudinal register-based matched cohort study

Introduction: The dual impact of prenatal substance exposure (i.e. alcohol/drugs) and adverse postnatal caregiving environment on offspring secondary education completion is an understudied research area. The aim was to investigate the influence of childhood adversities, out-of home care, and offspring's mental and/or behavioural disorders on secondary education completion among prenatally exposed offspring in comparison to matched unexposed offspring. Methods: This is a longitudinal register-based matched cohort study in Finland including offspring with a history of prenatal substance exposure and a matched unexposed cohort. The study sample included 283 exposed and 820 unexposed offspring aged 18-23 years. Results: The results showed a time lag in secondary education completion and lower educational attainment overall among exposed compared with unexposed (37.8% vs. 51.0%, respectively). The results from the multivariate logistic regression models showed that the differences in the secondary education completion between exposed and unexposed were diminished in the presence of covariates. A cumulative childhood adversity score and out-of-home care were not associated with secondary education completion in the multivariate models, whereas the different domains of offspring's mental and/or behavioural disorders including psychiatric disorders (AOR 0.65, 95% CI 0.45-0.96), neuropsychological disorders (AOR 0.35, 95% CI 0.23-0.54) and dual psychiatric and neuropsychological disorder (AOR 0.29, 95% CI 0.18-0.48) showed an independent negative effect on secondary education completion. Conclusions: Inferior educational outcomes may not be directly linked with prenatal substance exposure but may rather reflect the extent of evolving offspring's mental and/or behavioural disorders over time influenced by childhood adversities.Peer reviewe

Out-of-home care and diagnosed mental and behavioral disorders among youth with and without prenatal substance exposure – a longitudinal register-based cohort study

A majority of youths with prenatal substance exposure (PSE) have experienced out-of-home care (OHC), but there is a lack of studies on its association with mental health in adolescence and adulthood. The main aim of this retrospective longitudinal cohort study was to explore whether type of OHC (family/institutional) and number of OHC placements are associated with mental and behavioral disorders among youth with PSE (n=393) and unexposed controls (n=147) after controlling for the effect of important confounding factors. Before these anal-yses, characteristics of OHC and factors associated with the age at entry to care were ana-lyzed separately in both groups. Data from hospital medical records and nine registers were merged and analyzed using descriptive statistics, Pearson correlations and multivariate Cox regression models. Exposed youths entered OHC earlier in life, and the lifetime duration of OHC was longer with more placements and a higher proportion of family-type OHC. Despite these differences in OHC history, a high number of placements was associated with behav-ioral and emotional disorders with onset in childhood and adolescence (International Statisti-cal Classification of Diseases ICD-10, F90-F98) among both the exposed and controls. Among the exposed, the number of placements and institutional care were also associated with later appearing mental and behavioral disorders (F10-F69). The results suggest that in-terventions to support placement stability and favor family-type care could be beneficial in the promotion of mental health among children and youth entering OHC.Peer reviewe

Mood and neurotic disorders among youth with prenatal substance exposure : A longitudinal register-based cohort study

Publisher Copyright: © 2022 The AuthorsBackground: Prenatal substance exposure is associated with mood and neurotic disorders but this association is complex and understudied. This study investigated the recorded use of specialised healthcare services for mood and neurotic disorders among youth with prenatal substance exposure in comparison with an unexposed matched cohort. Furthermore, the influence of adverse maternal characteristics and out-of-home care (OHC) is investigated. Methods: This longitudinal register-based matched cohort study included 594 exposed and 1735 unexposed youth. Cox proportional hazard regression models were applied to study the first episode of mood and neurotic disorders in specialised healthcare from 13 years of age, and the influence of adverse maternal characteristics and OHC. Mediation analysis was applied to study the mediating effect of OHC on the association between prenatal substance exposure and the disorders. Results: The exposed cohort had a two-fold higher likelihood of being treated at specialised healthcare for mood and neurotic disorders compared with the unexposed cohort (HR 2.34, 95% CI 1.86–2.95), but this difference was attenuated to non-significant levels (AHR 1.29, 95% CI 0.92–1.81) following adjustments with adverse maternal characteristics and OHC. OHC mediated 61% (95% CI 0.41–0.94) of the association between prenatal substance exposure and youth's mood and neurotic disorders. Limitations: Register data likely include more severe cases of disorders, and as an observational study, causality cannot be assessed. Conclusion: Mood and neurotic disorders are more common following prenatal exposure to substances and interlinked with significant adversities in the postnatal caregiving environment and OHC.Peer reviewe