Long Term Effects of Babies Born Addicted to Methadone

Neuroimage Clin. 2018; 18: 9–14.

Prenatal methadone exposure is associated with altered neonatal brain development

Victoria J. Monnelly,^a Devasuda Anblagan,^b Alan Quigley,^c Manuel Blesa Cabez,^a E. Sarah Cooper,^d Helen Mactier,^e Scott I. Semple,^f Marker E. Bastin,^b and James P. Boardman^{a, b, ⁎}

Victoria J. Monnelly

^aMRC Centre for Reproductive Health, University of Edinburgh, Britain

Devasuda Anblagan

^bMiddle for Clinical Brain Sciences, University of Edinburgh, UK

Alan Quigley

^cSection of Paediatric Radiology, Royal Hospital for Ill Children, NHS Lothian, Edinburgh, UK

Manuel Blesa Cabez

^aMRC Center for Reproductive Health, Academy of Edinburgh, UK

E. Sarah Cooper

^dDepartment of Obstetrics, Royal Infirmary of Edinburgh, NHS Lothian, UK

Helen Mactier

^ePrincess Royal Maternity and the University of Glasgow, UK

Scott I. Semple

^fBritish Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, UK

Marking E. Bastin

^bCentre for Clinical Brain Sciences, University of Edinburgh, UK

James P. Boardman

^aMRC Centre for Reproductive Health, Academy of Edinburgh, Uk

^bMiddle for Clinical Encephalon Sciences, University of Edinburgh, United kingdom of great britain and northern ireland

Received 2017 November 16; Revised 2017 Dec 15; Accepted 2017 Dec 22.

Abstruse

Methadone is used for medication-assisted treatment of heroin addiction during pregnancy. The neurodevelopmental consequence of children with prenatal methadone exposure can be sub-optimal. We tested the hypothesis that brain evolution is altered amid newborn infants whose mothers were prescribed methadone.

20 methadone-exposed neonates born after 37 weeks' postmenstrual historic period (PMA) and 20 non-exposed controls underwent diffusion MRI at hateful PMA of 39^+ two and 41^+ one weeks, respectively. An age-optimized Tract-based Spatial Statistics (TBSS) pipeline was used to perform voxel-wise statistical comparison of fractional anisotropy (FA) data between exposed and non-exposed neonates.

Methadone-exposed neonates had decreased FA within the centrum semiovale, inferior longitudinal fasciculi (ILF) and the internal and external capsules afterward aligning for GA at MRI (p < 0.05, TFCE corrected). Median FA across the white thing skeleton was 12% lower amid methadone-exposed infants. Mean caput circumference (HC) z-scores were lower in the methadone-exposed grouping (− 0.52 (0.99) vs 1.15 (0.84), p < 0.001); later on adjustment for HC z-scores, differences in FA remained in the anterior and posterior limbs of the internal capsule and the ILF. Polydrug apply among cases was common.

Prenatal methadone exposure is associated with microstructural amending in major white matter tracts, which is present at nativity and is independent of head growth. Although the findings cannot be attributed to methadone per se, the data indicate that further research to determine optimal management of opioid utilize disorder during pregnancy is required. Future studies should evaluate childhood outcomes including infant brain development and long-term neurocognitive function.

Keywords: Prenatal, Methadone, Encephalon, Neonate, MRI, Opioid

one. Introduction

Globally, in 2015 in that location were estimated to exist 17.7million by-year users of heroin or opium, and increased heroin use is a major driver of the current opioid epidemic (World Drug Report, 2017). Pregnant women with opioid utilize disorder (OUD) due to heroin are recommended medication-assisted treatment (MAT) with an alternative opioid (normally methadone or buprenorphine) because treatment is associated with improved use of antenatal services, reduced utilise of heroin during pregnancy and reduced preterm delivery. Fetal benefits of MAT include improved growth and lower risk of intrauterine death (American College of Obstetricians and Gynecologists, 2017).

Methadone is a synthetic long acting μ-opioid agonist, which crosses the placenta freely, thereby exposing the developing fetus to exogenous opioid at a disquisitional menses of brain development. Pre-clinical studies suggest that prenatal methadone exposure may modify developing dopaminergic, cholinergic and serotonergic systems, and change myelination. Antenatal exposure to the drug has behavioral consequences including depression, anxiety, and impaired learning, memory and social function (Chen et al., 2015, Robinson et al., 1996, Vestal-Laborde et al., 2014, Wong et al., 2014). In humans, prenatal methadone exposure is associated with increased incidence and severity of neonatal abstinence syndrome (NAS) (Wilson et al., 1981, Zelson et al., 1973) compared with heroin exposure, and with altered visual maturation in childhood (McGlone et al., 2013a, McGlone et al., 2008, Whitham et al., 2010). These observations heighten the possibility that prenatal methadone exposure may change early brain development; withal, the possible role of confounding by postnatal events, including pharmacotherapy with opioid for NAS and environmental factors, leaves uncertainty almost the impact of prenatal methadone exposure on the developing brain.

Diffusion MRI (dMRI) is an established technique for studying brain development in early life. It provides objective measures of white matter microstructure that are sensitive to atypical developmental and injurious processes in the perinatal period, and which correlate with neurodevelopmental outcome in childhood (Counsell et al., 2014). Specifically, fractional anisotropy (FA) is a voxel-wise measure of the directional dependence of h2o molecule diffusion in tissue which is influenced past fiber density, axonal diameter and myelination, thereby enabling inference about underlying tissue microstructure. Tract-based Spatial Statistics (TBSS) enables unbiased group-wise analysis of FA volumes derived from dMRI data (Brawl et al., 2010, Smith et al., 2006). It has been applied to neonatal dMRI to map microstructural modify in white thing tracts of preterm infants at term equivalent age (Anjari et al., 2007), to place clinical risk factors for contradistinct brain development (Anblagan et al., 2016, Ball et al., 2010, Boardman et al., 2014), and to investigate neuroprotective treatment strategies in randomized clinical trials (Azzopardi et al., 2016, O'Gorman et al., 2015, Porter et al., 2010).

Based on the harmful effects of prenatal methadone exposure on neural systems and abnormal behavioral outcomes in pre-clinical models; and on human studies which suggest a modifying effect of prenatal methadone on postnatal behavior and development, we hypothesized that white matter development of neonates would be altered in neonates exposed to methadone in utero. We used TBSS to examine risks associated with prenatal methadone exposure, while minimizing the role of confounding past postnatal events and drug exposures.

ii. Methods and materials

two.1. Participants

The study was conducted according to the principles of the Declaration of Helsinki and ethical approval was obtained from the United kingdom National Ideals Service (Southward Eastward Scotland Research Ideals Committee 02, 14/SS/1106). Written informed parental consent was obtained for all participants. The written report group consisted of infants > 37 weeks' postmenstrual age (PMA) whose mothers had been prescribed methadone during pregnancy for the treatment of OUD (cases) and a comparator group of healthy infants born at > 37 weeks' PMA whose mothers did not use opioids (controls).

Mothers of cases were identified through a specialist antenatal dispensary for meaning women with substance misuse. All cases were born at the Royal Hospital of Edinburgh between Feb 2015 and April 2017 and underwent MRI brain scanning at the Clinical Research Imaging Centre, University of Edinburgh. The controls were selected, based on age matching, from a previously described group of healthy term neonates recruited as part of a study of typical brain evolution (Blesa et al., 2016) (South East Scotland Research Ethics Committee 02, 13/SS/0143). For cases and controls, exclusion criteria were congenital infection or chromosomal abnormalities, or whatsoever implanted medical device.

Clinical and demographic data was extracted from the mother and infant clinical records. Birth weight and head circumference (HC) were described in terms of z-score for calendar week of gestational historic period, calculated using INTERGROWTH-21st reference standards (Villar et al., 2014). The Scottish Alphabetize of Multiple Deprivation (SIMD) was used to narrate deprivation. The SIMD is the official Government tool used to place areas of impecuniousness: information technology divides Scotland into effectually 6505 areas each containing around 350 households and assigns an index to each area based on multiple measures of deprivation. The information are ranked from most to least deprived and are presented as deciles.

2.2. Ascertainment of maternal drug apply

Details of methadone use, tobacco smoking, alcohol intake, and apply of not-prescribed drugs were ascertained from medical records (including prescription charts), biological screening samples when these were performed as part of clinical care, and maternal interview at the time of delivery (V.M.)

two.iii. MRI acquisition

MRI was performed on a Siemens Magnetom Verio 3T arrangement (Siemens Healthcare Gmbh, Erlangen, Germany) using a 12-channel matrix phased array head coil. All infants were scanned axially to acquire: 3D T1-weighted MPRAGE volume (1 mm³ resolution), T2-weighted STIR (0.9 mm^three resolution), T2-weighted FLAIR (1 mm^three resolution), and diffusion MRI (dMRI) (eleven T2- and 64 diffusion encoding management (b = 750 s/mm²) unmarried-shot spin-echo echo planar imaging (EPI) volumes with 2 mm isotropic voxels, TE = 106 ms and TR = 7300 ms. Images were reported past a pediatric radiologist with experience in neonatal MRI (AQ), co-ordinate to the system described by Woodward et al. (Woodward et al., 2006), with the modification for grey matter scores proposed by Leuchter et al. (Leuchter et al., 2014).

MRI was performed in the neonatal menstruum during natural sleep, without sedation. A neonatologist was present for the duration of each MRI browse, and the babe had continuous oxygen saturation and heart rate monitoring. For acoustic protection, flexible earplugs and neonatal earmuffs (MiniMuffs, Nat's Medical Inc., CA) were used.

2.iv. Tract-based spatial statistics

DMRI data were preprocessed using FSL tools (FMRIB, Oxford, UK; http://www.ndcn.ox.ac.united kingdom/divisions/fmrib). This included brain extraction, and removal of majority infant movement and eddy current induced artefacts by registering the diffusion-weighted volumes to the first T2-weighted EPI volume for each field of study. Using DTIFIT, FA volumes were generated for every subject field. Diffusion volumes were assessed visually and were excluded if there was move corruption.

TBSS assay was performed using a pipeline optimized for neonatal dMRI data (Ball et al., 2010). An average FA book and hateful FA skeleton (thresholded at FA > 0.15) were created from the aligned data. Statistical comparison between groups with and without exposure to methadone during pregnancy was performed with FSL's Randomise using a general linear univariate model, with GA at paradigm acquisition and HC z-score at image acquisition listed every bit covariates. All FA data were subject to family-wise error correction for multiple comparisons following threshold-free cluster enhancement (TFCE) and are shown at p < 0.05 (Smith and Nichols, 2009).

2.5. Statistics

Educatee's t-test or the Isle of man-Whitney test was used to investigate differences in clinical and demographic variables between infants exposed to methadone (north = 20) and those not exposed (n = 20) and chi-squared or Fisher's verbal exam was used to compare proportions. Statistical assay was performed using SPSS v22.0 (SPSS Inc., Chicago, IL).

3. Results

three.1. Participants

Conventional structural and dMRI data amenable to TBSS analysis were acquired from 40 neonates: xx cases (10 female), who were exposed to prenatal methadone, and 20 unexposed controls (vii female). Table one summarizes maternal and baby characteristics.

Tabular array i

Maternal and infant characteristics of participants. BMI, torso mass index; SIMD, Scottish Alphabetize of Multiple Impecuniousness; PMA, postmenstrual age; HC, head circumference.

	Methadone	Command	p value
	n = twenty	northward = xx
Maternal characteristics
Hateful age (range)/years	30 (23–41)	30.9 (19–39)	0.56
Hateful BMI (range)	25.8 (21–41)	23.2 (19–39)	0.08
Median SIMD decile (Interquartile range)	3 (two–5)	8 (6–10)	0.012
Infant characteristics
Hateful PMA at birth (range)/weeks	38+ 5 (37+ ane–41+ 0)	39+ 1 (37+ 2–41+ iii)	0.32
Gender (One thousand:F)	10:x	13:7	0.52
Mean birth weight (range)/yard	2721 (2150–3440)	3349 (2346–4550)	< 0.01
Hateful birth weight z-score (sd)	− 1.062 (0.68)	0.443 (0.86)	< 0.01
Median (range) postnatal age at scan/days	3 (one to 21)	13 (5 to 29)	0.005
Mean PMA at scan (range)/weeks	39+ two (37+ 2–41+ 4)	41+ i (39+ 0–42+ 2)	0.004
Hateful HC at scan (range)/cm	33.one (31.ii–35.0)	35.9 (32.half-dozen–37.4)	< 0.01
Mean HC z-score (sd)	− 0.523 (0.986)	1.146 (0.837)	< 0.01

The mean methadone dose prescribed at pregnancy booking was 55 mg/twenty-four hours (range 0–160) and the mean dose at delivery was 70 mg/twenty-four hour period (range 8–160). Nineteen (95%) of the women prescribed methadone smoked tobacco, one reported drinking excessive booze (4 units/day at booking), and nineteen women had illicit or prescribed polydrug use (Fig. one). Boosted prescribed medications included paroxetine (n = one), mirtazapine (n = 1), gabapentin (n = 2), and pregabalin (n = 1).

Euler diagram indicating prenatal drug exposures. Stimulant includes cocaine and amphetamine; *codeine phosphate and tramadol.

None of the cases had neonatal encephalopathy, seizures or hypoglycemia. The mean arterial string pH of the grouping was vii.26 (range 7.xvi–7.36). Three cases had minor congenital anomalies (1 hypospadias, 1 scissure lip, 1 fixed bilateral talipes). I methadone exposed baby required admission to the Neonatal Unit for treatment of transient tachypnoea of the newborn.

No baby had received pharmacological treatment for NAS at the fourth dimension of epitome conquering and none of the control group was exposed prenatally to opioid drugs.

3.2. Magnetic Resonance Imaging

None of the cases or controls had features consequent with injury to white matter or grey matter on conventional structural T1- or T2-weighted structural MRI. 4 cases had mild enlargement of the lateral ventricular organisation; 1 case had asymmetric myelination of the posterior limb of the internal sheathing (but had developed symmetric myelination on repeat MRI four weeks later); and no case had abnormalities in brainstem, cerebellum, deep or cortical grey affair, or extracerebral infinite. 2 (10%) methadone exposed infants had developmental venous anomalies: one consisted of an surface area of low T2-weighted indicate in the left peritrigonal white matter (most likely haemosiderin), with a curvilinear vessel extending peripherally and draining into the superior anastamotic vein of Trolland, which continues up to the superior sagittal sinus; and the 2nd was characterized by an area of depression T2-weighted point in the right peritrigonal white matter with a depression T2-weighted signal vessel that drains toward the choroid plexus.

3.3. White matter correlates of prenatal methadone exposure

Methadone-exposed neonates had decreased FA within the centrum semiovale, inferior longitudinal fasciculi (ILF), and the internal and external capsules later on adjustment for PMA at MRI (p < 0.05, TCFE corrected) (Fig. 2A). Mean HC z-scores were lower in the methadone exposed group (− 0.52 (0.99) vs ane.xv (0.84), p < 0.001). After adjustment for HC z-scores, differences in FA remained in the anterior and posterior limbs of the internal capsule and the ILF (Fig. 2B). Radial diffusivity was increased in internal sheathing and junior longitudinal fasciculus in neonates with prenatal methadone exposure (Fig. three). At that place were no differences in hateful or axial diffusivities between groups.

Mean FA map of the subjects in transverse, coronal and sagittal planes. Voxels with significantly lower FA in neonates with prenatal methadone exposure are shown in xanthous-ruby-red color scale. Fig. 2A shows results adjusted for PMA at scan, and Fig. iiB shows results adapted for PMA at scan and head circumference z-score. FA, fractional anisotropy.

Mean RD map of the subjects in transverse, coronal and sagittal planes. Voxels with significantly college RD in neonates with prenatal methadone exposure are shown in yellowish-blood-red color scale. Fig. 3A shows results adapted for PMA at scan, and Fig. 3B shows results adapted for PMA at scan and caput circumference z-score. RD, radial diffusivity.

Median FA beyond the white thing skeleton was 12% lower among methadone-exposed infants (Fig. four).

Mean FA across the white matter skeleton of neonates with prenatal methadone exposure compared with unexposed controls. FA, fractional anisotropy.

4. Discussion

These information show that prenatal exposure to methadone is associated with altered microstructure in major white thing tracts of the newborn brain, independent of head growth. Children whose mothers take methadone during pregnancy are at increased risk of neurodevelopmental harm, behavioral difficulties, and visual issues, merely study designs accept left uncertainty nearly the office of confounding past prematurity, postnatal opioid exposure for handling of NAS, and environmental factors, in mediating adverse outcomes(Hans and Jeremy, 2001, Hunt et al., 2008, Konijnenberg and Melinder, 2015, McGlone et al., 2014, McGlone and Mactier, 2015, Rosen and Johnson, 1985, van Baar, 1990, Wilson, 1989). An association between prenatal methadone exposure and reduced somatic and head growth is documented (Mactier et al., 2014) just to our knowledge, this is first study to demonstrate brain tissue furnishings present around the time of nascency after methadone exposure in utero.

We used TBSS to investigate encephalon evolution because of its sensitivity to grouping-wise differences in FA when used to survey the unabridged white matter skeleton (Ball et al., 2013). FA is a robust marker of tract microstructure that reflects fiber density, axonal diameter, wrapping by pre-myelinating oligodendrocytes and myelination. Therefore, these data advise that neonates exposed to methadone in utero have less coherently organized and more immature fiber tracts compared to controls. Furthermore, correspondent increases in radial diffusivity without changes in axial diffusivity imply that abnormal myelination may contribute to altered FA among the cases. Since neonatal FA values in major white matter tracts correlate with later neurodevelopment, the findings may explain the prevalence of neurobehavioral problems seen in children with prenatal methadone exposure.

Quantitative MRI techniques have identified specific vulnerabilities of the developing brain to psychoactive drugs. Midazolam exposure during neonatal intensive care of preterm infants is associated with attenuated hippocampal growth (Duerden et al., 2016), and functional connectivity of the amygdala–frontal and thalamic networks is altered in neonates with prenatal cocaine exposure (Salzwedel et al., 2016, Salzwedel et al., 2015). In a preliminary study, Walhovd and colleagues reported college mean diffusivity in the superior longitudinal fasciculus of 13 methadone-exposed cases compared to 7 controls, but infants were scanned at mean age of 3 weeks after nascency and 85% of the cases had been treated with morphine for NAS, which limits inference about the effects of prenatal opioid exposure (Walhovd et al., 2012). Two (ten%) cases had developmental venous anomalies (DVA), which was higher than expected based on estimated prevalence of one.5% in neonates (Brinjikji et al., 2017). These did not occur in the cases exposed to cocaine, which is known to be associated with central nervous system vascular anomalies (Frank et al., 1999); therefore the possibility that prenatal methadone exposure is associated with CNS vascular malformation warrants further study.

All of our cases had been exposed to one time daily dosing with methadone. Although the benefits of MAT with an opioid substitute during pregnancy are unequivocal (ACOG, 2017), there is no consensus regarding the optimal dosing regimen for methadone, or the function of buprenorphine as an alternative substitute. A single daily dose of methadone is commonly prescribed, but some authors suggest that accelerated metabolism of methadone past physiological induction of CYP450 enzymes during pregnancy might predispose women and fetuses to daily withdrawal stress and risk of relapse to illicit drugs (Bogen et al., 2013, McCarthy et al., 2017, McCarthy et al., 2015). Studies that support the employ of divided dosing to minimize fluctuations in serum concentration report favorable furnishings on maternal symptoms of withdrawal, and on fetal neurobehavior and NAS prevalence (Jansson et al., 2009, McCarthy et al., 2015, Wittmann and Segal, 1991), just no study has evaluated the touch on of dosing regimen on fetal/neonatal encephalon development or long-term outcome. Monitoring of maternal plasma methadone concentration during the peripartum catamenia with dose titration to keep levels inside the maternal therapeutic range has been suggested, only this is not skilful widely (McCarthy et al., 2017). Buprenorphine is a partial mu-opioid agonist and kappa-opioid antagonist that is an adequate substitute to pregnant women and is associated with lower hazard of preterm birth, improved growth parameters at birth and less NAS, without apparent harm, when compared with methadone (Jones et al., 2010, Zedler et al., 2016). These neonatal outcomes suggest that buprenorphine may have a more than favorable safe profile for the child, although long-term consequence studies are required.

Polydrug use, both illicit and prescribed, was very common among women prescribed methadone in our study. This is consequent with observations from other cohorts of methadone using pregnant women (McGlone et al., 2013b, Rosen and Johnson, 1985, van Baar, 1990). In our study population, heroin and oral benzodiazepines were used by xi (55%) and 12 (60%) of cases respectively, and so it is possible that either drug could take confounded the observed clan. No other drug class (anti-depressant, anti-epileptic, stimulant) was taken past > 15% of the cases and so it is unlikely that exposure to these classes of drug explained the findings. The enquiry implication of highly prevalent polydrug utilize in the target population is that future studies into optimal management of OUD in pregnancy are likely to require businesslike designs that define case definition based on prescribed substitute, with mail hoc aligning for other drug exposures if they are shown to differ between groups.

The strengths of the report are that: dMRI acquisition took place soon after birth earlier exposure to postnatal opioids or other pharmacological handling for NAS; preterm birth, which is an of import source of confounding for neurodevelopmental effect was excluded; and detailed information nigh methadone dose and exposure to other drugs was available. Our study was limited by reliance on maternal report for drug exposures amongst control women; yet, none of the control participants were prescribed opioids during pregnancy, and the likelihood of undisclosed heroin apply or non-prescription opioids was depression. A limitation of this report is that we could non evaluate causation, and therefore cannot exclude potential mediating or interacting factors such timing and dose furnishings of methadone and the function of other prenatal drug exposures. Yet, our data support pre-clinical studies, objective studies of visuo-cortical function in the newborn period and afterward infancy, and neurodevelopmental and behavioral studies, which strongly suggest an adverse event of prenatal methadone upon the developing fetal brain and upon long-term childhood outcomes.

In conclusion, prenatal methadone exposure is associated with altered white affair microstructure that is apparent before long later on nativity. The information focus inquiry attention on determining optimal management of pregnant women with OUD, including a pressing need to evaluate methadone dose regimens and culling substitutes; hereafter written report designs should evaluate fetal or neonatal brain development and long-term neurocognitive outcome.

Acknowledgements

Nosotros give thanks the families that participated in this research; the specialist substance misuse midwives (LC and SC); and the radiographers at the Clinical Enquiry Imaging Middle, Edinburgh, United kingdom of great britain and northern ireland. We thank Thorsten Feiweier at Siemens Healthcare for collaborating with dMRI acquisitions (Works-in-Progress Package for Avant-garde EPI Improvidence Imaging). This work was supported by Theirworld (www.theirworld.org) and was undertaken in the MRC Eye for Reproductive Health, which is funded by MRC Centre Grant (MRC G1002033). The report was sponsored by the Academy of Edinburgh.

Financial disclosures

None of the authors report biomedical fiscal interests or potential conflicts of interest.

References

• American College of Obstetricians and Gynecologists Committee opinion no. 711: opioid use and opioid utilise disorder in pregnancy. Obstet. Gynecol. 2017;130:e81–e94. [PubMed] [Google Scholar]
• Anblagan D., Pataky R., Evans M.J., Telford E.J., Serag A., Sparrow Southward., Piyasena C., Semple S.I., Wilkinson A.G., Bastin Grand.E., Boardman J.P. Association between preterm brain injury and exposure to chorioamnionitis during fetal life. Sci. Rep. 2016;6 [PMC gratis article] [PubMed] [Google Scholar]
• Anjari M., Srinivasan L., Allsop J.Grand., Hajnal J.Five., Rutherford Thou.A., Edwards A.D., Counsell S.J. Diffusion tensor imaging with tract-based spatial statistics reveals local white matter abnormalities in preterm infants. NeuroImage. 2007;35:1021–1027. [PubMed] [Google Scholar]
• Azzopardi D., Robertson N.J., Bainbridge A., Cady East., Charles-Edwards K., Deierl A., Fagiolo One thousand., Franks North.P., Griffiths J., Hajnal J., Juszczak Due east., Kapetanakis B., Linsell L., Maze M., Omar O., Strohm B., Tusor N., Edwards A.D. Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia lonely after birth asphyxia (TOBY-Xe): a proof-of-concept, open up-label, randomised controlled trial. Lancet Neurol. 2016;15:145–153. [PMC gratis article] [PubMed] [Google Scholar]
• van Baar A. Development of infants of drug dependent mothers. J. Kid Psychol. Psychiatry. 1990;31:911–920. [PubMed] [Google Scholar]
• Brawl G., Counsell S.J., Anjari M., Merchant Due north., Arichi T., Doria Five., Rutherford M.A., Edwards A.D., Rueckert D., Boardman J.P. An optimised tract-based spatial statistics protocol for neonates: applications to prematurity and chronic lung disease. NeuroImage. 2010;53:94–102. [PubMed] [Google Scholar]
• Ball Grand., Boardman J.P., Arichi T., Merchant N., Rueckert D., Edwards A.D., Counsell S.J. Testing the sensitivity of tract-based spatial statistics to false treatment effects in preterm neonates. PLoS One. 2013;8:e67706. [PMC gratis article] [PubMed] [Google Scholar]
• Blesa Thousand., Serag A., Wilkinson A.G., Anblagan D., Telford E.J., Pataky R., Sparrow S.A., Macnaught M., Semple S.I., Bastin M.E., Boardman J.P. Parcellation of the healthy neonatal brain into 107 regions using atlas propagation through intermediate time points in babyhood. Front. Neurosci. 2016;10:220. [PMC free article] [PubMed] [Google Scholar]
• Boardman J.P., Walley A., Ball G., Takousis P., Krishnan M.50., Hughes-Carre L., Aljabar P., Serag A., King C., Merchant N., Srinivasan L., Froguel P., Hajnal J., Rueckert D., Counsell S., Edwards A.D. Mutual genetic variants and risk of encephalon injury after preterm birth. Pediatrics. 2014;133:e1655–1663. [PubMed] [Google Scholar]
• Bogen D.L., Perel J.M., Helsel J.C., Hanusa B.H., Romkes One thousand., Nukui T., Friedman C.R., Wisner K.L. Pharmacologic evidence to support clinical decision making for peripartum methadone handling. Psychopharmacology. 2013;225:441–451. [PMC free article] [PubMed] [Google Scholar]
• Brinjikji West., El-Rida El-Masri A., Wald J.T., Lanzino K. Prevalence of developmental venous anomalies increases with age. Stroke. 2017;48:1997–1999. [PubMed] [Google Scholar]
• Chen H.H., Chiang Y.C., Yuan Z.F., Kuo C.C., Lai M.D., Hung T.W., Ho I.One thousand., Chen S.T. Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats. Neuropsychiatr. Dis. Treat. 2015;11:609–618. [PMC free article] [PubMed] [Google Scholar]
• Counsell S.J., Ball G., Edwards A.D. New imaging approaches to evaluate newborn brain injury and their office in predicting developmental disorders. Curr. Opin. Neurol. 2014;27:168–175. [PubMed] [Google Scholar]
• Duerden E.Thousand., Guo T., Dodbiba L., Chakravarty Chiliad.M., Chau V., Poskitt K.J., Synnes A., Grunau R.Eastward., Miller S.P. Midazolam dose correlates with abnormal hippocampal growth and neurodevelopmental upshot in preterm infants. Ann. Neurol. 2016;79:548–559. [PubMed] [Google Scholar]
• Frank D.A., McCarten K.M., Robson C.D., Mirochnick M., Cabral H., Park H., Zuckerman B. Level of in utero cocaine exposure and neonatal ultrasound findings. Pediatrics. 1999;104:1101–1105. [PMC free commodity] [PubMed] [Google Scholar]
• Hans S.L., Jeremy R.J. Postneonatal mental and motor development of infants exposed in utero to opioid drugs. Infant Mental Wellness Journal. 2001;22:15. [Google Scholar]
• Chase R.W., Tzioumi D., Collins E., Jeffery H.Eastward. Adverse neurodevelopmental consequence of infants exposed to opiate in-utero. Early Hum. Dev. 2008;84:29–35. [PubMed] [Google Scholar]
• Jansson L.M., Dipietro J.A., Velez M., Elko A., Knauer H., Kivlighan K.T. Maternal methadone dosing schedule and fetal neurobehaviour. J. Matern. Fetal Neonatal Med. 2009;22:29–35. [PMC gratuitous article] [PubMed] [Google Scholar]
• Jones H.E., Kaltenbach K., Heil S.H., Stine S.K., Coyle M.One thousand., Arria A.M., O'Grady K.E., Selby P., Martin P.R., Fischer G. Neonatal abstinence syndrome later on methadone or buprenorphine exposure. Northward. Engl. J. Med. 2010;363:2320–2331. [PMC free article] [PubMed] [Google Scholar]
• Konijnenberg C., Melinder A. Visual selective attention is impaired in children prenatally exposed to opioid agonist medication. Eur. Addict. Res. 2015;21:63–70. [PubMed] [Google Scholar]
• Leuchter R.H., Gui L., Poncet A., Hagmann C., Lodygensky M.A., Martin Due east., Koller B., Darque A., Bucher H.U., Huppi P.Due south. Association between early on assistants of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age. JAMA. 2014;312:817–824. [PubMed] [Google Scholar]
• Mactier H., Shipton D., Dryden C., Tappin D.M. Reduced fetal growth in methadone-maintained pregnancies is non fully explained by smoking or socio-economic deprivation. Addiction. 2014;109:482–488. [PubMed] [Google Scholar]
• McCarthy J.J., Leamon 1000.H., Willits N.H., Salo R. The outcome of methadone dose regimen on neonatal forbearance syndrome. J. Addict. Med. 2015;9:105–110. [PubMed] [Google Scholar]
• McCarthy J.J., Leamon M.H., Finnegan L.P., Fassbender C. Opioid dependence and pregnancy: minimizing stress on the fetal brain. Am. J. Obstet. Gynecol. 2017;216:226–231. [PubMed] [Google Scholar]
• McGlone L., Mactier H. Infants of opioid-dependent mothers: neurodevelopment at vi months. Early Hum. Dev. 2015;91:xix–21. [PubMed] [Google Scholar]
• McGlone L., Mactier H., Hamilton R., Bradnam K.S., Boulton R., Borland W., Hepburn 1000., McCulloch D.50. Visual evoked potentials in infants exposed to methadone in utero. Arch. Dis. Child. 2008;93:784–786. [PubMed] [Google Scholar]
• McGlone L., Hamilton R., McCulloch D.L., Boulton R., Bradnam M.S., Weaver L.T., Mactier H. Neonatal visual evoked potentials in infants built-in to mothers prescribed methadone. Pediatrics. 2013;131:e857–863. [PubMed] [Google Scholar]
• McGlone L., Mactier H., Hassan H., Cooper G. In utero drug and alcohol exposure in infants born to mothers prescribed maintenance methadone. Arch Dis Child Fetal Neonatal Ed. 2013;98:F542–544. [PubMed] [Google Scholar]
• McGlone L., Hamilton R., McCulloch D.Fifty., MacKinnon J.R., Bradnam Thousand., Mactier H. Visual result in infants born to drug-misusing mothers prescribed methadone in pregnancy. Br. J. Ophthalmol. 2014;98:238–245. [PubMed] [Google Scholar]
• O'Gorman R.L., Bucher H.U., Held U., Koller B.M., Huppi P.S., Hagmann C.F. Tract-based spatial statistics to appraise the neuroprotective effect of early erythropoietin on white thing development in preterm infants. Brain. 2015;138:388–397. [PubMed] [Google Scholar]
• Porter East.J., Counsell Due south.J., Edwards A.D., Allsop J., Azzopardi D. Tract-based spatial statistics of magnetic resonance images to appraise affliction and handling furnishings in perinatal asphyxial encephalopathy. Pediatr. Res. 2010;68:205–209. [PubMed] [Google Scholar]
• Robinson South.E., Guo H., Maher J.R., McDowell K.P., Kunko P.M. Postnatal methadone exposure doe non prevent prenatal methadone-induced changes in striatal cholinergic neurons. Brain Res. Dev. Brain Res. 1996;95:118–121. [PubMed] [Google Scholar]
• Rosen T.S., Johnson H.L. Long-term effects of prenatal methadone maintenance. NIDA Res. Monogr. 1985;59:73–83. [PubMed] [Google Scholar]
• Salzwedel A.P., Grewen K.One thousand., Vachet C., Gerig G., Lin W., Gao W. Prenatal drug exposure affects neonatal encephalon functional connectivity. J. Neurosci. 2015;35:5860–5869. [PMC complimentary article] [PubMed] [Google Scholar]
• Salzwedel A.P., Grewen G.G., Goldman B.D., Gao W. Thalamocortical functional connectivity and behavioral disruptions in neonates with prenatal cocaine exposure. Neurotoxicol. Teratol. 2016;56:16–25. [PMC free article] [PubMed] [Google Scholar]
• Smith Due south.Thou., Nichols T.E. Threshold-gratis cluster enhancement: addressing issues of smoothing, threshold dependence and localisation in cluster inference. NeuroImage. 2009;44:83–98. [PubMed] [Google Scholar]
• Smith South.M., Jenkinson K., Johansen-Berg H., Rueckert D., Nichols T.E., Mackay C.Due east., Watkins Yard.E., Ciccarelli O., Cader Grand.Z., Matthews P.M., Behrens T.E. Tract-based spatial statistics: voxelwise analysis of multi-field of study improvidence data. NeuroImage. 2006;31:1487–1505. [PubMed] [Google Scholar]
• United Nations Office of Drugs and Crime . United nations; 2017. World Drug Study 2017. United Nations publication, Sales No. East.17.Eleven.half dozen. [Google Scholar]
• Vestal-Laborde A.A., Eschenroeder A.C., Bigbee J.Westward., Robinson S.East., Sato-Bigbee C. The opioid organization and brain development: effects of methadone on the oligodendrocyte lineage and the early stages of myelination. Dev. Neurosci. 2014;36:409–421. [PMC complimentary article] [PubMed] [Google Scholar]
• Villar J., Cheikh Ismail L., Victora C.1000., Ohuma E.O., Bertino E., Altman D.Thousand., Lambert A., Papageorghiou A.T., Carvalho One thousand., Jaffer Y.A., Gravett M.K., Purwar M., Frederick I.O., Noble A.J., Pang R., Barros F.C., Chumlea C., Bhutta Z.A., Kennedy S.H. International standards for newborn weight, length, and head circumference past gestational age and sex: the Newborn Cross-sectional Written report of the INTERGROWTH-21st Project. Lancet. 2014;384:857–868. [PubMed] [Google Scholar]
• Walhovd K.B., Watts R., Amlien I., Woodward 50.J. Neural tract evolution of infants born to methadone-maintained mothers. Pediatr. Neurol. 2012;47:one–6. [PubMed] [Google Scholar]
• Whitham J.N., Spurrier N.J., Sawyer Chiliad.Chiliad., Baghurst P.A., Taplin J.E., White J.M., Gordon A.L. The effects of prenatal exposure to buprenorphine or methadone on infant visual evoked potentials. Neurotoxicol. Teratol. 2010;32:280–288. [PubMed] [Google Scholar]
• Wilson G.S. Clinical studies of infants and children exposed prenatally to heroin. Ann. N. Y. Acad. Sci. 1989;562:183–194. [PubMed] [Google Scholar]
• Wilson One thousand.S., Desmond Thou.One thousand., Wait R.B. Follow-up of methadone-treated and untreated narcotic-dependent women and their infants: health, developmental, and social implications. J. Pediatr. 1981;98:716–722. [PubMed] [Google Scholar]
• Wittmann B.1000., Segal S. A comparison of the effects of single- and split-dose methadone administration on the fetus: ultrasound evaluation. Int. J. Addict. 1991;26:213–218. [PubMed] [Google Scholar]
• Wong C.Due south., Lee Y.J., Chiang Y.C., Fan L.W., Ho I.K., Tien L.T. Upshot of prenatal methadone on reinstated behavioral sensitization induced by methamphetamine in adolescent rats. Behav. Encephalon Res. 2014;258:160–165. [PubMed] [Google Scholar]
• Woodward Fifty.J., Anderson P.J., Austin Northward.C., Howard K., Inder T.Eastward. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N. Engl. J. Med. 2006;355:685–694. [PubMed] [Google Scholar]
• Zedler B.Yard., Mann A.50., Kim M.M., Amick H.R., Joyce A.R., Murrelle Due east.Fifty., Jones H.Due east. Buprenorphine compared with methadone to care for pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the female parent, fetus and child. Addiction. 2016;111:2115–2128. [PMC gratuitous article] [PubMed] [Google Scholar]
• Zelson C., Lee Due south.J., Casalino Thou. Neonatal narcotic addiction. Comparative effects of maternal intake of heroin and methadone. N. Engl. J. Med. 1973;289:1216–1220. [PubMed] [Google Scholar]

corbouldeaspost.blogspot.com

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760461/

Share this post