Genome-wide DNA methylation and gene expression in human placentas derived from assisted reproductive technology.

Background: Assisted reproductive technology (ART) has been associated with increased risks for growth disturbance, disrupted imprinting as well as cardiovascular and metabolic disorders. However, the molecular mechanisms and whether they are a result of the ART procedures or the underlying subfertility are unknown.

Methods: We performed genome-wide DNA methylation (EPIC Illumina microarrays) and gene expression (mRNA sequencing) analyses for a total of 80 ART and 77 control placentas.

Cumulative risk factors for injuries and poisoning requiring hospital care in youth with prenatal substance exposure: A longitudinal controlled cohort study.

To investigate whether the youth with prenatal substance exposure (PSE) (aged 15-24 years,  = 615) had been in hospital care more often due to injuries and poisoning in comparison with unexposed matched controls ( = 1787). Data from medical records (exposure) and national health and social welfare registers (outcome and confounders) were combined and youths were monitored from birth until either outpatient or inpatient hospital care for injury or poisoning, death or the end of the study period (December 2016). Cox regression models were used in the analyses accounting for associated child and maternal risk factors.

Extended-release versus oral buprenorphine as opioid maintenance treatment during pregnancy-maternal and neonatal outcomes.

Objective: To get information on subcutaneous extended-release buprenorphine as opioid maintenance treatment during pregnancy, we compared it to orally administered buprenorphine and buprenorphine-naloxone treatments. We hypothesized that maternal and neonatal outcomes do not differ between the treatment groups. Study design In this population-based cohort study, 60 pregnant individuals receiving non-changed opioid maintenance treatment for opioid use disorder with a buprenorphine product from the time before conception to the time after delivery and their newborns were included.

Intrauterine exposure to maternal opioid maintenance treatment and associated risk factors may impair child growth.

Aim: How maternal opioid maintenance treatment (OMT) affects children is under-researched. This population-based registry study investigated child growth and somatic health following intrauterine exposure to this treatment.

Methods: Children born between 1 March 2011 and 30 May 2021 to mothers who used buprenorphine, buprenorphine-naloxone, or methadone throughout their pregnancies were followed for 2 years at the Helsinki University Hospital, Finland.

Rapid urine screening for ethyl glucuronide from pregnant women as a tool for detecting prenatal alcohol exposure.

Background: An increasing prevalence of alcohol consumption is a major public health problem, which has also led to an increasing number of children who have been prenatally exposed to the toxic effects of ethanol. However, obtaining reliable information on prenatal alcohol exposure through maternal self-reports has proved difficult.

Aims: Our aim was to evaluate the potential for rapid screening test for measuring ethyl glucuronide (EtG), a specific alcohol metabolite, from urine samples of pregnant women.

Adverse childhood experiences and neurodevelopmental disorders among youth with and without prenatal substance exposure: A longitudinal matched register-based cohort study.

Previous research has shown an association between adverse childhood experiences (ACEs) and secondary mental health problems in youth with prenatal substance exposure (PSE), but the association between ACEs and neurodevelopmental disorders is less clear. This longitudinal register-based cohort study investigated relationships between health at birth, ACEs (out-of-home care (OHC) and maternal adversities), and neurodevelopmental disorders among youth with PSE (alcohol/drugs,  = 615) and matched unexposed controls ( = 1787). Hospital medical records and register data were merged and analysed using Cox regression models.

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

Introduction: Current 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.

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

Background: 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.

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.

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.

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.

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

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.

In vitro fertilization does not increase the incidence of de novo copy number alterations in fetal and placental lineages.

Although chromosomal instability (CIN) is a common phenomenon in cleavage-stage embryogenesis following in vitro fertilization (IVF), its rate in naturally conceived human embryos is unknown. CIN leads to mosaic embryos that contain a combination of genetically normal and abnormal cells, and is significantly higher in in vitro-produced preimplantation embryos as compared to in vivo-conceived preimplantation embryos. Even though embryos with CIN-derived complex aneuploidies may arrest between the cleavage and blastocyst stages of embryogenesis, a high number of embryos containing abnormal cells can pass this strong selection barrier.

rs10732516 polymorphism at the locus associates with genotype-specific effects on placental DNA methylation and birth weight of newborns conceived by assisted reproductive technology.

Background: Assisted reproductive technology (ART) has been associated with low birth weight of fresh embryo transfer (FRESH) derived and increased birth weight of frozen embryo transfer (FET)-derived newborns. Owing to that, we focused on imprinted insulin-like growth factor 2 ()/ locus known to be important for normal growth. This locus is regulated by imprinting control region (ICR) with seven binding sites for the methylation-sensitive zinc finger regulatory protein (CTCF).

rs10732516 polymorphism at the locus associates with a genotype-specific trend in placental DNA methylation and head circumference of prenatally alcohol-exposed newborns.

Study Question: Does prenatal alcohol exposure (PAE) affect regulation of the locus in placenta and the growth-restricted phenotype of newborns?

Summary Answer: PAE results in genotype-specific trends in both placental DNA methylation at the locus and head circumference (HC) of newborns.

What Is Known Already: PAE can disturb development of the nervous system and lead to restricted growth of the head, even microcephaly. To clarify the etiology of alcohol-induced growth restriction, we focused on the imprinted locus known to be important for normal placental and embryonic growth.

Alcohol and substance abuse identified during pregnancy: maternal morbidity, child morbidity and welfare interventions.

Aim: To study the relations between postnatal maternal morbidity, child morbidity and welfare interventions in families with prenatal alcohol or substance abuse.

Methods: A register-based longitudinal retrospective cohort study. The exposed cohort included 638 children born to 524 women followed-up during pregnancy for alcohol or substance abuse 1992-2001.

Early healthcare utilization and welfare interventions among children of mothers with alcohol and substance abuse: a retrospective cohort study.

Aim: Early childhood healthcare utilization, mortality and welfare interventions were studied among children of mothers with identified gestational alcohol and/or substance abuse.

Methods: Register-based retrospective cohort study. The exposed cohort consisted of 638 children born to 524 women followed up antenatally 1992-2001 at special outpatient clinics in the capital area of Finland.

Maternal welfare, morbidity and mortality 6-15 years after a pregnancy complicated by alcohol and substance abuse: a register-based case-control follow-up study of 524 women.

Background: A register-based retrospective case-control study to investigate the long-term morbidity, mortality, and welfare among women with alcohol and/or substance misuse identified during pregnancy.

Methods: Cohort of 524 women followed-up ante- and perinatally 1992-2001 at special out-patient clinics of maternity hospitals in the capital area of Finland. The control group of 1792 women with no evidence of alcohol or substance misuse was matched for maternal age, parity, date of birth and hospital of index delivery.

Prenatal buprenorphine exposure: effects on biochemical markers of hypoxia and early neonatal outcome.

Objective: To evaluate the possible association between prenatal buprenorphine exposure and compromised early neonatal outcome in view of markers of perinatal hypoxia. DESIGN, SETTING AND SAMPLE: The study group consisted of 27 full-term neonates exposed to buprenorphine prenatally and prospectively followed up at a special tertiary outpatient clinic for pregnant drug abusers. Serving as controls were 27 full-term neonates exposed prenatally to illicit substances other than opioids and 38 full-term neonates from uncomplicated pregnancies of healthy parturients.

Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero.

Aim: To study the neonatal outcome of infants exposed to buprenorphine in utero.

Methods: We prospectively followed 54 buprenorphine-using pregnant women and their 58 infants. Urinary buprenorphine and norbuprenorphine concentrations in the mothers were measured prior to delivery, and in the infants during the first 3 days of life.

Risk factors for out-of-home custody child care among families with alcohol and substance abuse problems.

Aim: To study the risk of children to mothers with alcohol and/or substance abuse related problems for early childhood out-of-home care in Finland.

Methods: A population-based cross-sectional retrospective analysis of 526 pregnant women attending special outpatient clinics during 1992-2001 and their 626 offspring, with out-of-home care data until 2003 provided by the National Child Welfare Register.

Results: Fifty percent (95% confidence interval 46-54%) were at some point and 38% (34-42%) by the age of two years, in out-of-home care.

A prospective study on buprenorphine use during pregnancy: effects on maternal and neonatal outcome.

Background: Exposure to illicit drugs in utero is associated with low birth weight and premature birth. Therefore, maintenance therapy for opioid dependence during pregnancy has been recommended to help withdrawal from street drugs, in order to improve maternal health and decrease risks to the fetus.

Methods: In 2002-2005, 67 pregnancies of 66 buprenorphine users were followed prospectively in an outpatient multidisciplinary antenatal setting by an obstetrician, a midwife, a psychiatric nurse and a social worker.