Neonatal Outcomes after Combined Opioid and Nicotine Exposure in Utero: A Scoping Review.
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ABSTRACT: Background
The majority of women who are pregnant with opioid use disorder (OUD) also smoke tobacco but are rarely offered tobacco cessation counseling. While the effects of exposure to opioids and nicotine in utero are well-understood separately, understanding the impact of the combined exposure to these substances on neonatal outcomes is lacking.Methods
A scoping review was conducted using PubMed and Scopus databases for studies addressing the combined exposure to opioids and nicotine during pregnancy published between 1 January 1980 and 9 July 2019. A total of 29 papers met the eligibility criteria for inclusion, with nine being identified as clinical trials (three from the MOTHER study) and two as secondary data analysis of clinical trial data.Results
Neonatal outcomes for infants who had a combined exposure to opioids and nicotine in utero indicated a reduction in birth weight and birth length. Findings in infants exposed to both nicotine and opioids were mixed with regard to the duration of neonatal abstinence syndrome (NAS), the likelihood of treatment for NAS, doses of medicine used to treat NAS, and NAS scores when compared with infants who had opioid exposure without nicotine.Conclusions
The combined exposure to nicotine and opioids during pregnancy may lead to a reduction in neonatal birth weight and birth length and more severe NAS signs, compared with opioid use alone, but more research is necessary to identify the minimum dosage and length of nicotine exposure to accurately predict these outcomes.
SUBMITTER: Isaacs KR
PROVIDER: S-EPMC8508043 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAlthough medication is generally avoided wherever possible during pregnancy, pharmacotherapy is required for the treatment of pregnancy associated hypertension, which remains a leading cause of maternal and fetal morbidity and mortality. The long-term effects to the child of in-utero exposure to antihypertensive agents remains largely unknown.ObjectiveThe aim of this study was to systematically review published studies on adverse outcomes to the child associated with in-utero exposure to antihypertensive medications.MethodsOVID, Scopus, EBSCO Collections, the Cochrane Library, and Web of Science databases were searched for relevant publications published between January 1950 and October 2016 and a total of 688 potentially eligible studies were identified.ResultsFollowing review, 47 primary studies were eligible for inclusion. The Critical Appraisal Skills Programme checklist was used to assess study quality. Five studies were of excellent quality; the remainder were either mediocre or poor. Increased risk of low birth weight, low size for gestational age, preterm birth, and congenital defects following in-utero exposure to all antihypertensive agents were identified. Two studies reported an increased risk of attention deficit hyperactivity disorder following exposure to labetalol, and an increased risk of sleep disorders following exposure to methyldopa and clonidine.ConclusionThe current systematic review demonstrates a paucity of relevant published high-quality studies. A small number of studies suggest possible increased risk of adverse child health outcomes; however, most published studies have methodological weaknesses and/or lacked statistical power thus preventing any firm conclusions being drawn.
| S-EPMC5625961 | biostudies-literature
Project description:The health of women and children affected by opioid use disorder is a priority for state Medicaid programs. Little is known about longer-term outcomes among Medicaid-enrolled children exposed to opioids in utero. We examined well-child visit use and diagnoses of pediatric complex chronic conditions in the first five years of life among children with opioid exposure, tobacco exposure, or neither exposure in utero. The sample consisted of 82,329 maternal-child dyads in the Pennsylvania Medicaid program in which the children were born in the period 2008-11 and followed up for five years. Children with in utero opioid exposure had a lower predicted probability of recommended well-child visit use at age fifteen months (42.1 percent) compared to those with tobacco exposure (54.1 percent) and those with neither exposure (55.7 percent). Children with in utero opioid exposure had a predicted probability of being diagnosed with a pediatric complex chronic condition similar to that among children with tobacco exposure and those with neither exposure (20.4 percent, 18.7 percent, and 20.2 percent, respectively). Our findings were consistent when we examined a subgroup of opioid-exposed children identified as having neonatal opioid withdrawal symptoms.
| S-EPMC7328447 | biostudies-literature
Project description:Hypertensive disorders during pregnancy are an important risk to mother and fetus, frequently necessitating antihypertensive treatment. Data describing the safety of in utero exposure to antihypertensive treatment is conflicting, with many studies suffering from significant methodological issues, such as inappropriate study design, small sample sizes, and no untreated control group. We conducted a retrospective cohort study using linked routinely collected healthcare records for 268 711 children born 2010-2014 in Scotland to assess outcomes following in utero exposure to antihypertensive medication. We identified a cohort of 265 488 eligible children born over the study period; of which, 2350 were exposed to in utero antihypertensive medication, 4391 exposed to treated late-onset hypertension, and 7971 exposed to untreated hypertension during pregnancy. Untreated hypertension was associated with increased risk of preterm birth (adjusted risk ratio [aRR], 1.15 [99% CI, 1.01-1.30]), low birth weight (aRR, 2.01 [99% CI, 1.72-2.36]) and being small for gestational age (aRR, 1.50 [99% CI, 1.35-1.66]), while in utero antihypertensive exposure was also associated with preterm birth (aRR, 3.12 [99% CI, 2.68-3.64]), low birth weight (aRR, 2.23 [99% CI, 1.79-2.78]), and being small for gestational age (aRR, 2.13 [99% CI, 1.81-2.52]). Late-onset hypertension was also associated with preterm birth (aRR, 2.21 [99% CI, 1.86-2.62]), low birth weight (aRR, 2.06 [99% CI, 1.74-2.43]), and being small for gestational age (aRR, 1.90 [99% CI, 1.68-2.16]). Our results suggest that hypertension is a key risk factor for low birth weight and preterm birth. Although preterm birth may be associated with antihypertensive medication exposure during pregnancy, these associations may reflect increasing hypertension severity necessitating treatment.
| S-EPMC8032216 | biostudies-literature
Project description:ObjectiveTo provide absolute and relative risk estimates of neonatal abstinence syndrome (NAS) based on duration and timing of prescription opioid use during pregnancy in the presence or absence of additional NAS risk factors of history of opioid misuse or dependence, misuse of other substances, non-opioid psychotropic drug use, and smoking.DesignObservational cohort study.SettingMedicaid data from 46 US states.ParticipantsPregnant women filling at least one prescription for an opioid analgesic at any time during pregnancy for whom opioid exposure characteristics including duration of therapy: short term (<30 days) or long term (≥ 30 days); timing of use: early use (only in the first two trimesters) or late use (extending into the third trimester); and cumulative dose (in morphine equivalent milligrams) were assessed.Main outcome measureDiagnosis of NAS in liveborn infants.Results1705 cases of NAS were identified among 290,605 pregnant women filling opioid prescriptions, corresponding to an absolute risk of 5.9 per 1000 deliveries (95% confidence interval 5.6 to 6.2). Long term opioid use during pregnancy resulted in higher absolute risk of NAS per 1000 deliveries in the presence of additional risk factors of known opioid misuse (220.2 (200.8 to 241.0)), alcohol or other drug misuse (30.8 (26.1 to 36.0)), exposure to other psychotropic medications (13.1 (10.6 to 16.1)), and smoking (6.6 (4.3 to 9.6)) than in the absence of any of these risk factors (4.2 (3.3 to 5.4)). The corresponding risk estimates for short term use were 192.0 (175.8 to 209.3), 7.0 (6.0 to 8.2), 2.0 (1.5 to 2.6), 1.5 (1.0 to 2.0), and 0.7 (0.6 to 0.8) per 1000 deliveries, respectively. In propensity score matched analyses, long term prescription opioid use compared with short term use and late use compared with early use in pregnancy demonstrated greater risk of NAS (risk ratios 2.05 (95% confidence interval 1.81 to 2.33) and 1.24 (1.12 to 1.38), respectively).ConclusionsUse of prescription opioids during pregnancy is associated with a low absolute risk of NAS in the absence of additional risk factors. Long term use compared with short term use and late use compared with early use of prescription opioids are associated with increased NAS risk independent of additional risk factors.
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Project description:Health outcomes of in utero Ramadan exposure have been reported in a systematic literature review; however, the available literature on long-term effects were not fully covered. Our study aims to specifically review the long-term outcomes of in utero Ramadan exposure. We searched for original research articles analyzing any long-term outcome of in utero Ramadan exposure, excluding maternal and perinatal outcomes. Sixteen studies from 8304 non-duplicate search results were included. Most studies suggest negative consequences from in utero Ramadan exposure on health, as well as on economic outcomes later in adulthood. Higher under-five mortality rate, higher mortality under three months, and under one year, shorter stature, lower body mass index, increased incidence of vision, hearing and learning disabilities, lower mathematics, writing and reading scores, as well as a lower probability to own a home were associated with Ramadan exposure during conception or the first trimester of pregnancy. Furthermore, age and sex seem to play a pivotal role on the association. Existing studies suggest that in utero Ramadan exposure may adversely impact long-term health and economic well-being. However, evidence is limited. Meanwhile, increasing awareness of the potential risks of Ramadan fasting during pregnancy should be raised among pregnant women and clinicians and other antenatal care workers should promote better maternal healthcare.
| S-EPMC8704584 | biostudies-literature
Project description:It is well established that maternal lifestyle during pregnancy and lactation affects the intrauterine programming of F1 offspring. However, despite the co-use of alcohol and nicotine is a common habit, the effects of exposure to both substances on the reproductive system of F1 male offspring and the underlying mechanisms of developmental programming have not been investigated. The present study aimed to examine pre- and postnatal concurrent exposure to these substances on genetic and epigenetic alterations of sperm cells as well as testis properties of F1 offspring compared with exposure to each substance alone. Pregnant dams in the F0 generation randomly received normal saline, nicotine, ethanol, and combinations throughout full gestation and lactation periods. Sperm cells and testes of F1 male offspring were collected at postnatal day 90 for further experiments. High levels of sperm DNA fragmentation were observed in all exposed offspring. Regarding epigenetic alterations, there was a significant increase in the relative transcript abundance of histone deacetylase 1 and 2 in all exposed sperm cells. Moreover, despite a decrease in the expression level of DNA methyltransferase (DNMT) 3A, no marked differences were found in the expression levels of DNMT1 and 3B in any of the exposed sperm cells compared to non-exposed ones. Interestingly, combined exposure had less prominent effects relative to exposure to each substance alone. The changes in the testicular and sperm parameters were compatible with genetic and epigenetic alterations. However, MDA level as an oxidative stress indicator increased in all exposed pups, which may be responsible for such outputs. In conclusion, maternal co-exposure to these substances exhibited epigenotoxicity effects on germline cells of F1 male offspring, although these effects were less marked relative to exposure to each substance alone. These counteracting effects may be explained by cross-tolerance and probably less impairment of the antioxidant defense system.
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Project description:IntroductionMany countries recommend Nicotine Replacement Therapy (NRT) for smoking cessation in pregnancy. Preclinical studies of nicotine exposure to pregnant mammals could indicate how nicotine may adversely affect the developing fetus. As a first step towards summarising this literature, we undertook a systematic scoping review to determine the number and nature of offspring outcomes studied.MethodsWe searched MEDLINE and EMBASE databases for papers reporting empirical data on offspring outcomes following nicotine exposure to pregnant non-human mammals. We excluded studies that investigated exposure to only smoking, e-cigarettes, nicotine vaccines, or studies with no 'nicotine only' group. We developed a draft taxonomy and using this, described and quantified outcomes reported.ResultsWe identified 476 studies, which reported 729 offspring outcomes. The draft taxonomy classified outcomes as being measured in i) whole animals, ii) body systems and iii) 'other'. Body system outcomes were further categorised as being functional changes, or changes at macroscopic or cellular levels. The most frequently used outcomes were those detecting changes in the brain (n = 265), physical parameters measured in whole animals (n = 122) and any respiratory system changes (n = 97).ConclusionsThis scoping review quantifies the nature and frequency of outcomes used in preclinical studies investigating the potential impacts of nicotine administration in pregnancy on offspring. Systematic reviews of studies investigating outcomes involving animal brains, respiratory system, or 'whole animal' outcomes may have greatest potential for further advancing knowledge regarding impacts of gestational nicotine exposure on offspring.Protocol and registrationProtocol for this review can be found on Open Science Framework (https://osf.io/ptmzc/).
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Project description:In utero smoke exposure has been shown to have detrimental effects on lung function and to be associated with persistent wheezing and asthma in children. One potential mechanism of IUS effects could be alterations in DNA methylation, which may have life-long implications. The goal of this study was to examine the association between DNA methylation and nicotine exposure in fetal lung and placental tissue in early development; nicotine exposure in this analysis represents a likely surrogate for in-utero smoke. We performed an epigenome-wide analysis of DNA methylation in fetal lung tissue (n = 85, 41 smoke exposed (48%), 44 controls) and the corresponding placental tissue samples (n = 80, 39 smoke exposed (49%), 41 controls) using the Illumina HumanMethylation450 BeadChip array. Differential methylation analyses were conducted to evaluate the variation associated with nicotine exposure. The most significant CpG sites in the fetal lung analysis mapped to the PKP3 (P = 2.94 × 10(-03)), ANKRD33B (P = 3.12 × 10(-03)), CNTD2 (P = 4.9 × 10(-03)) and DPP10 (P = 5.43 × 10(-03)) genes. In the placental methylome, the most significant CpG sites mapped to the GTF2H2C and GTF2H2D genes (P = 2.87 × 10(-06) - 3.48 × 10(-05)). One hundred and one unique CpG sites with P-values < 0.05 were concordant between lung and placental tissue analyses. Gene Set Enrichment Analysis demonstrated enrichment of specific disorders, such as asthma and immune disorders. Our findings demonstrate an association between in utero nicotine exposure and variable DNA methylation in fetal lung and placental tissues, suggesting a role for DNA methylation variation in the fetal origins of chronic diseases.
| S-EPMC4623268 | biostudies-literature
Project description:BACKGROUND:While use of prescription opioids and medication assisted therapy (MAT) for opioid use disorder in pregnancy, as well as the incidence of neonatal opioid withdrawal syndrome (NOWS) continue to rise, little is known about outcomes for children with NOWS beyond the newborn period. METHODS:We examined 1) prenatal MAT exposure vs. unexposed healthy controls [HC]; and 2) treatment for NOWS and NOWS severity on infant neurodevelopmental and behavioral outcomes at 5-8?months of age in 78 maternal-infant pairs from the ENRICH prospective cohort study. Data were obtained from 3 study visits: prenatal, delivery, and neurodevelopmental evaluation at 5-8?months of age. Neurodevelopmental outcomes included the Bayley Scales of Infant Development [BSID-III], caregiver questionnaires (Parenting Stress Index [PSI-SF], Infant Behavior Questionnaire [IBQ-R], Sensory Profile), and the experimental Still-Face Paradigm (SFP). RESULTS:No differences in the BSID-III, PSI-SF, or IBQ-R scores were observed between MAT and HC groups; however, MAT-exposed and HC infants differed with respect to SFP self-regulation (??=?-18.9; p?=?0.01) and Sensory Profile sensation seeking (OR?=?4.87; 95% CI: 1.55; 15.30) after adjusting for covariates. No significant differences between Treated-for-NOWS vs. not-Treated-for-NOWS were observed. Shorter timing to NOWS treatment initiation was associated with higher Total Stress (??=?-9.08; p?=?0.035), while longer hospitalization was associated with higher Parent-child dysfunctional interaction (p?=?0.018) on PSI-SF. CONCLUSIONS:Our results provide additional evidence of little-to-no effect of MAT and pharmacological treatment of NOWS on infant neurodevelopmental and behavioral outcomes at 5-8?months of age. However, prolonged hospitalization might increase family psychosocial stress and requires further examination.
| S-EPMC6348117 | biostudies-literature
Project description:BackgroundAdolescent pregnancy is a public health issue with well-defined causes and health risks with social and economic implications. Aim of this review was to examine adverse pregnancy outcomes and risk factors associated with adolescent pregnancy in Africa.MethodPubMed Central, Science Direct and JSTOR were the main databases for the literature review. Other online sources and experts were consulted for relevant studies. In all, 11,574 records were identified and 122 were considered as full-text studies for evaluation after thorough screening and removal of duplicates. Finally, 53 studies were included in this review for thematic synthesis.ResultsThe 53 studies sampled 263,580 pregnant women, including 46,202 adolescents (< 20 years) and 217,378 adults (> 20 years). Adolescent pregnancy was associated with higher risks of adverse pregnancy outcomes. Factors of poor pregnancy outcomes included low socioeconomic and educational status, poor utilization of antenatal care, risky lifestyles such as alcohol consumption, and unattractive health care factors. Maternal health care utilization was identified as an important factor to improve pregnancy outcomes among adolescents in Africa.ConclusionTo prevent adolescent pregnancy, stakeholders need to help lower socioeconomic inequalities, poor utilization of antenatal care, alcohol consumption, and improve adolescents' health care and their educational status. Issues such as child marriage, abortion, poor health care infrastructure and non-adolescent friendly health facilities need to be addressed.
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